basic anatomical and physiological data: the...

BASIC ANATOMICAL AND PHYSIOLOGICAL DATA: THE SKELETON

The primary tissues of the skeleton

(1) The skeletal system as defined here includes bone, bone marrow, periosteum, all cartilage of the body, teeth, and the blood vessels contained in those tissues. Estimated weights of skeletal tissues generally include blood vessels but only an amount of blood or other fluids that would not be lost when the tissue is dissected at autopsy and prepared for weighing. Periarticular tissue, a heavy, thick, connective tissue situated around joints such as knee and hip, is difficult to remove completely from dissected bones and is sometimes included, in part, in the estimated weight of the skeleton.

(2) In the ICRP’s Reference Man document published in 1975, periarticular tissue was considered as part of the skeleton and represented 900 g of the lo-kg skeleton of the reference adult male. In the present document, periarticular tissue is not considered as part of the skeleton.

Bone as a tissue

(3) The tissue bone is to be distinguished from bones, which are organs that contain red and yellow marrow, cartilage, periosteum, and blood, in addition to bone tissue.

(4) Bone consists largely of an organic matrix impregnated with inorganic salts and permeated by a complex cellular network (Fig. 1). The matrix of bone is composed of various proteins, carbohydrates, lipids, and other substances, but the bulk of the organic material is made up of a protein called collagen (Triffitt, 1980). The inorganic matter of bone consists mainly of submicroscopic deposits of forms of calcium phosphate (Neuman, 1980; Fawcett, 1986).

“INACTIVE” OSTEOBLASTS

OSTEOCLAST

BONE FLUID

MINERALISED MATRIX

MINERALIZATION ~STEOCYTES FRONT (LACUNAE 6 CANAllCULll

Fig. 1. Schematic representation of the lacunar-canalicular system of bone as it opens into the cellular space on the bone surface. From Jaworski (1976).

1

2 RADIOLOGICAL PROTECTION DATA: THE SKELETON

(5) In bone formation, bone-forming cells (osteoblasts) synthesise the organic matrix, and this pre-osseous tissue (osteoid) then undergoes mineralisation (Triffitt, 1980). This results in a hard, durable structure but not a permanent one. Throughout life there is a continual modification (remodelling) of bone by bone resorbing cells, called osteoclasts, and osteoblasts to maintain the mechanical competence of the structure and to accommodate conditioning forces that are applied through locomotion, lifting, and the maintenance of posture (Frost, 1980). Bone remodelling may also serve a role in calcium homeostasis (Frost, 1980).

(6) Two main types of bone structure can be distinguished by differences in hardness, porosity, and soft-tissue content: compact (cortical) bone and trabecular (cancellous, spongy) bone (Figs. 2 and 3). Compact bone is the hard, dense bone that forms the outer wall of all bones, but the bulk of compact bone is found in the shafts of the long bones. Trabecular bone is a soft, spongy bone composed of a lattice-work of fragile appearance and located at the interior of flat bones and ends of long bones. Trabecular bone has a much higher porosity or soft tissue content (consisting mainly of bone marrow) and consequently a much lower fractional volume than compact bone, that is, a much lower portion of volume remaining within external surfaces of bone after subtraction of volumes of all holes normally occupied by organic material (Frost, 1963a). Not all bone tissue is easily classified as either compact or trabecular, since there often is a zone between the two bone types that is intermediate in porosity and surface-to-volume ratio (Par&t, 1988).

(7) Some authors use the term “trabecular bone” to refer to the osseous tissue of the trabeculae plus the soft tissue filling the trabecular cavities. In this document, “trabecular bone” will refer only to the osseous tissue of the trabeculae, and trabecular bone plus its supported soft tissue will be referred to as “spongiosa”.

Fig. 2. Appearance of trabecular (spongy, cancellous) and cortical (compact) bone in proximal humerus and scapula. From Fawcett (1986).

RADIOLOGICAL PROTECTION DATA: THE SKELETON 3

Fig. 3. A closer view of compact bone and the lattice of trabeculae of the cancellous bone, from a section of the tibia. From Fawcett (1986).

(8) Throughout the interstitial substance of bone are nearly uniformly spaced cavities, called lacunae (Fig. 1). Each lacuna is filled by a bone cell or osteocyte, which is essentially an osteoblast that has become surrounded by bone matrix (Matthews, 1980; Fawcett, 1986). Radiating in all directions from each lacuna are slender, branching tubular passages, called canaliculi, that penetrate the interstitial substance and join with canaliculi of neighbouring lacunae. Thus, the lacunae form a continuous system of cavities connected by an extensive network of minute canals (Fawcett, 1986).

(9) The dominant microscopic structure of compact bone is the haversian system or osteon (Fig. 4). The typical osteon is a cylinder running parallel to the long axis of bone and is about 200 pm in diameter, but there is considerable variation in the shape, direction, and size of these structures (Par&t, 1983; Fawcett, 1986). Within the osteon is a central canal about 40 pm in diameter, containing blood vessels, lymphatics, nerves, and connective tissue. The walls of the osteon consist of concentric lamellae (layered bone) about 7 pm thick (Par&t, 1983). Between the haversian systems of compact bone are irregularly shaped systems of lamellar bone, called interstitial systems (Fig. 4), separated from the haversian systems by thin lines of dense connective tissue called cement lines.

(10) Haversian canals are connected with one another and communicate with the bone marrow and exterior surfaces of bone via supporting channels called Volkmann’s canals (Fig. 4). Volkmann’s canals are typically oblique or transverse and are structurally distinct from haversian canals in that they are not surrounded by concentrically arranged lamellae but traverse the lamellae around haversian systems (Fawcett, 1986). The haversian systems, together with Volkmann’s canals, serve to supply nutrients to the canalicular network, which in turn carries the nutrients to the cells in the interior of compact bone.


p&r@umferential

A

XelS

r’s

Fig. 4. Diagram of a sector of the shaft of a long bone illustrating the Haversian systems, Volkmann’s canals, intexstitial Iamellae, outer and inner circumferential lamellae, and attachment of periosteom to bone. From Fawcett

(1986).

(11) Cancellous bone has relatively few haversian systems and usually consists primarily of angular pieces of lamellar bone (Fawcett, 1986). The bone cells are generally nourished by diffusion from the endosteal surface via minute canaliculi that interconnect the lacunae and extend to the surface (Fawcett, 1986).

(12) Bones normally are covered in a fibrous sheath, called the periosteum. The periosteum consists of a variably thick layer of fibrous connective tissue and, during growth, a thin innet layer of bone-forming cells called osteoblasts. In the adult, these cells revert to a resting form (Fawcett, 1986).

(13) The periosteum is penetrated by blood vessels that communicate with Volkmarm’s canals, which in turn communicate with vessels of the haversian canals. The periosteum is abundantly supplied with nerves (Moss, 1966). Muscle tendons and ligaments may attach directly into the compact outer surface of a bone, or they may blend with outer layers of the periosteum (Moss, 1966). The numerous small blood vessels penetrating the periosteum may help keep the periosteum attached to the underlying bone (Fawcett, 1986). In addition, there are coarse bundles of collagenous fibres, called Sharpey’s fibres or perforating fibres (Fig. 4) that turn inward from the outer layer of the periosteum and penetrate the outer circumferential lamellae and interstitial systems of the bone (Fawcett, 1986).


(14) The endosteum is a layer of cells lining the wails of all cavities in bone that house the bone marrow. The endosteum resembles the periosteum in its bone-forming potential but is much thinner, usually being composed of a single layer of cells without associated connective tissue fibres. All cavities of bone, including the haversian canals and the marrow spaces within trabecular bone, are lined by endosteum (Fawcett, 1986).

(15) In the adult human, the typical long bone is composed of a central cylindrical shaft called a diaphysis; two roughly spherical, terminal articular regions, called epiphyses and two intermediate cone-like regions, called metaphyses, that connect the shaft and articular ends (Fig. 5). In growing children, the epiphysis is separated from the diaphysis by a cartilaginous epiphyseal plate (Fig. 6), which is united to the diaphysis by columns of trabecular bone in the metaphysis.

(16) The flat bones of the skull generally lack a central marrow cavity but consist of two plates of compact bone with an intervening trabecular region, called the diplo& (Moss, 1966; Fawcett, 1986). The outer surfaces of both plates are covered with a periosteum, and

trabecular

epiphysis

bone

g_ compact bone

diaphysis

Fig. 5. A section of the upper end of the mature human femur. Mod&d from Moss (1966).

6 RADIOLOGICAL PROTEKTION DATA: THE SKELETON

Fig. 6. Upper half of the tibia of a young girl, showing the epiphysis, the cartilaginous epiphyseal plate, and the shaft or diaphysis. From Fawcctt (19g6).

the diploic space is lined with an endosteum. In the case of the bones of the skull vault, the outer surface is lined by a connective tissue covering called the pericranium and the inner surface is lined by the dura mater of the brain; these linings do not differ greatly in structure or function from the periosteum and endosteum of long bones (Moss, 1966; Fawcett, 1986).

Bones of the body

(17) The major bones of the human body are shown in Fig. 7. In addition to the labelled bones in this figure, there are numerous small bones, particularly in the skull, hands, and feet.

(18) The total number of bones in the body varies slightly from person to person. Some initially independent bones unite to form a single bone during the maturation process, but even among mature adults there may be differences in the number of developed bones. For example, there are usually 12 ribs on each side, but this number may be increased by the development of a cervical or lumbar rib, or there may be only 11 ribs in some cases (Gray’s Anatomy, 1962). In middle life there are usually 206-208 distinct bones. These have been divided into the following general classes (Gray’s Anatomy, 1959):


Forearm

Swum --‘-

coccyx - I I -I-

Mctacarpun

p-6a ;z

Fig. 7. Larger bones of the human skeleton. From Dorlund’s Illustrated Medical Dictic (1965).


Axial skeleton (trunk with head) skull: 29, including the bones of the face and the auditory ossicles spine: 26 vertebrae ribs and sternum: 25-27

Appendicular skeleton (limbs) shoulders, arms, and hands: 64 pelvis, legs, and feet: 62

Total skeleton: 206-208.

Fresh weight of the skeleton

Adults

(19) Reported weights of dissected skeletons from adult male and female subjects are listed in Tables 1 and 2, respectively, and are summarised by study in Table 3. Data for emaciated subjects (defined as weighing < 50 kg for males or ~42 kg for females) or extremely old subjects (>95 years) were omitted, as were data for chemically treated skeletons (e.g. Muehlmann, 1927; Dempster, 1955).

(20) Borisov and Marei (1974) designed a study for the purpose of deriving reference values for the weights of the fresh and ashed skeleton and of certain fresh and ashed bones. They selected 10 males and 10 females who died in Moscow at ages between 37 and 50 years, with all cadavers having normal body build and no signs of either obesity or malnutrition, The male cadavers were selected “to match as closely as possible the height and weight of the so-called standard man (170 cm and 70 kg, respectively)“. Body weights and heights were in the range 66-79 kg and 168-183 cm, respectively, for males and 54-71 kg and 158-164 cm, respectively, for females. The fresh weight of each bone of each cadaver was determined immediately after dissection. According to Borisov (personal communication, 1988), “To prepare the fresh bones for weighing, I removed all soft and semi-soft tissues adjacent to bone: muscles, ligaments, and periosteum. I did not remove the cartilage from the articulation surfaces because of its negligible mass contribution to the total weight of a fresh bone, maybe except for the spinal column . . .” Borisov estimated that the mass of “intervertebral fibrosus semi-elastic plates” may account for about 5% of the total mass of column plus sacrum; for comparison, Woodard and White (1982) estimate that cartilage represents about 11% of the weight of the vertebral column in adult males. Thus, the skeletal weights reported by Borisov and Marei apparently represent more than bone and marrow but less than the total skeleton as defined here, since they would not include periosteum, costal cartilage, or cartilage from such areas as the external ear, walls of the external auditory and eustachian tubes, larynx, epiglottis, and tracheal rings.

(21) The results of Borisov and Marei are in reasonable agreement with those of an earlier postmortem study conducted in Leningrad by Mechanik (1926), who determined weights of all bones, including bone marrow, from at least eight adult males, aged 25-58 years, and eight adult females, aged 26-86 years (Tables l-3). It appears that most cartilage, as well as periarticular tissue, was removed from the bones (Mechanik, 1926; Bigler and Woodard, 1976). As with the data of Borisov and Marei, the reported weights appear to represent less tissue than does the skeleton as defined here. Several of Mechanik’s subjects had died of wasting diseases that may have caused considerable loss of body mass as well as bone mass.

(22) Higher relative skeletal weights than those of either Borisov and Marei or Mechanik are indicated by data of Mitchell, Forbes, and coworkers (Mitchell et al., 1945; Forbes et al.,

RADIOLOGICAL PROTECTION DATA: THE SKELETON

Table 1. Skeletal weights of adult males

9

Investigator Age weight Height W (kg) (a)

Skeletal weight

kg % of TB

Bischoff, 1863 Dursy, 1863 Dursy, 1863 Volkmann, 1873’ Volkmann, 1873’ Volkmann, 1874’ van Liebig, 1874 von Liebig, 1874 Me&an&, 1926 Me&an& 1926 Mechanik, 1926 Me&an&, 1926 Me&an&, 1926 Me&an&, 1926 Mechanik, 1926 Me&an& 1926 Mitchell et aZ., 1945 Forbes et al., 1953 Forbes et al., 1956 Forbes et al., 1956 Borisov and Marei, 1974 Borisov and Marei, 1974 Borisov and Marei, 1974 Borisov and Marei, 1974 Borisov and Marei, 1974 Borisov and Marei, 1974 Borisov and Marei, 1974 Borisov and Marei, 1974 Borisov and Marei, 1974 Borisov and Marei, 1974 Clarys et al., 1984 Clarys et al., 1984 Clarys et al., 1984 Clarys et al., 1984 Clarys et al., 1984 Clarys et al., 1984 Clarys et al., 1984 Clarys et al., 1984 Clarys et al., 1984 Clarys et ul., 1984 Clary-s et al., 1984 Clarys et al., 1984 McIuroy et al., 1985 McInroy et al., 1991

33 36 42 38 45

3u5 30-45

;: 32 50 50 51 55

:“5 46 48 60

37-50 37-50 37-U) 37-50 37-50 37-50 37-50 37-50 37-50 37-50

73 78 78 70 83 72 65 59 81 73 73 55 49 62

69.7 50.5 65.3 64.5 63.0 62.5 55.7 76.5

E 65:0 60.0 60.1 59.6 61.5 61.9 70.6 53.8 62.0 73.5 66 74 13 67 76 13 74 79 77

:;.8 70.4 71.5 58.5 51.7 65.1 54.8 16.8 61.0 85.1 57.7 88.9 64.9 75.0

168 163 172

183 169 169 172 168 174 172 170 174 174 177 183 178 181 156 163 167 159 168 166 166 173 177 172 164 187 182 173

11.1 15.9 1.6 15.0 9.8 15.0 1.9 12.2 1.5 11.9

10.2 16.3 11.5 20.6 13.9 18.2 8.1 13.5 9.3 14.7 9.3 14.3 8.3 13.8 9.2 15.3 8.0 13.4 8.4 13.7 6.9 11.1

10.5 14.8 9.5 17.6

10.3 16.7 11.0 15.0 8.3 12.6 8.9 12.0 9.6 13.2 9.1 14.5

10.1 13.3 10.1 13.9 10.4 14.1 10.9 13.8 12.7 16.4 13.4 17.0 1.4 13.9 8.9 12.7

11.7 16.4 7.9 13.5 9.8 19.0 9.6 14.8 8.8 16.1

10.1 13.1 8.7 14.3

10.3 12.1 7.3 12.7

11.1 12.5 9.0 13.9 8.1 11.6

* From Vierordt (1906), Mueblmam~ (1927), Clarys et al. (1984).

1953, 1956) for four adult male subjects studied in Illinois (three white subjects aged 35, 46, and 60 years and a black subject aged 48 years). The skeletal weights reported by these authors, when expressed as a percentage of total-body weight (%TBW), agree reasonably well with pre-1900 data for seven male subjects aged 30-45 years (Table 3). It is not evident whether the dissected skeletons of the pre-1900 subjects or those of Mitchell, Forbes, and coworkers were freed of substantial portions of cartilage, periosteum, and/or periarticular tissues, but Mitchell et al. (1945) indicate that their reported value of 14.8% of total-body


Table 2. Skeletal weights of adult females

Investigator Age Weight (Y) or&

Height (cm)

Skeletal weight

kg % OfTB

Schwann, 1843 21 50.0 Bischoff, 1863 22 55.4 Dursy, 1863 61 44 Mechanik, 1926 26 53.3 I&char& 1926 32 52.1 Mechanik, 1926 40 58.3 Mechanik, 1926 42 55.2 Me&a& 1926 60 47.6 Mcchanik, 1926 66 48.2 Mechanik, 1926 70 49.3 Me&an&, 1926 86 49.4 Moore et al., 1968 67 43.4 Borisov and Marei, 1974 37-50 54 Borisov and Marei, 1974 37-50 59 Borisov and Marei, 1974 37-50 59 Borisov and Marei, 1974 37-50 64 Borisov and Marei, 1974 37-50 61 Borisov and Marei, 1974 37-50 67 Borisov and Marei, 1974 37-50 62 Borisov and Marei, 1974 37-50 68 Borisov and Marei, 1974 37-50 71 Borisov and Marei, 1974 37-50 69 Clarys et al., 1984 83 61.6 Clarys et al., 1984 94 49.1 Clarys et al., 1984 79 48.3 Clarys et al., 1984 84 75.4 Clarys et al., 1984 69 62.9 Clarys et al., 1984 70 63.4 Clarys et al., 1984 79 58.9 Clarys et al., 1984 83 74.2 Clarys et al., 1984 82 48.2 Clarys et al., 1984 77 71.6 Clarys et a/., 1984 68 69.0 Clarys et al., 1984 86 61.2 Clarys et aZ., 1984 82 68.8

145 159 153

158 160 160 162 164 162 164 163 164 162 148 152 157 158 169 160 160 172 162 151 154 157 164

4.7 9.4 8.4 15.2 5.9 13.4 6.6 12.4 6.5 12.5 6.4 11.0 7.3 13.2 4.1 8.6 5.3 11.0 6.6 13.3 6.3 12.8 8.8 20.3 7.2 13.3 8.5 14.5 8.9 15.0 8.9 13.9 9.0 14.8 9.2 13.8 9.1 14.7 9.5 14.0 9.4 13.2

10.1 14.7 7.0 11.3 7.1 15.6 7.4 15.3 8.0 10.7

10.0 15.8 7.3 11.6 7.1 13.1 8.8 11.8 1.4 15.4 7.6 10.6 6.7 9.1 1.7 12.6 7.3 10.5

weight for one subject was “exclusive of ligaments”. Two of the subjects of Forbes and coworkers were underweight by current standards, as were most of the pre-1900 subjects.

(23) Clarys et al. (1984) determined skeletal weights of 25 Belgian subjects, 12 males aged 55-83 years and having mean weights of 71.7k8.5 kg and 13 females aged 68-94 years and having mean weights of 62.5 f 9.4 kg. The preparation of skeletons appears to be similar to that of Borisov and Marei (1974), in that bones were scraped free of muscle and adipose tissue, for example, and cartilage of articular surfaces was not removed.

(24) It appears, therefore, that most of the skeletal weights given in Tables l-3 include articular cartilage but exclude a substantial portion of the body’s cartilage. All of the cartilage in the adult human might represent about 1.5% of total-body weight (F. D. Moore, personal communication to authors of ICRP Publication 23,1975). The cartilage left with the skeleton in the studies of Borisov and Marei and of Clarys and coworkers, for example, probably would represent considerably less than half of that amount. Hence, cartilage representing 1% or more of the body’s weight could be excluded from most of the skeletal weights given in these tables. On the other hand, it is likely that even the most careful

RADIOLOGICAL PROTRCTION DATA: THE SKELETON

Table 3. Mean weights of skeletons, as percentage of total-body weight, from different studies

11

Skeletal weight as % body weight

Study Males Females

Borisov and Marei (1974) Ages 37-50 y

Mechanik (1926) Age 2-2 y Ages SO-58 y Ages 60-86 y

Mitchell, Forbes and coworkers (1945-1956) Ages 35-48 y Age6Oy

Clarys et al. (1984) Ages 55-94 y

McInroy and coworkers (1985, 1991) Age 49 y Age 62 y

Pre-1900 studies Ages 21-22 y Ages 33-45 y Age 61 y

a Number of subjects in parentheses.

14.1& 1.6 (IO)’ 14.2+0.6 (10)

14.2f0.6 (3) 12.3 f0.9 (4) 13.5* 1.5 (5)

11.4+2.1 (4)

16.4+ 1.5 (3) 15.0 (1)

14.3f2.0 (12) 12.6ziz2.2 (13)

13.9 (1) 11.6 (1)

12.3k4.1 (3) 15.6h3.1 (7)

13.4 (1)

investigators left a non-trivial amount of extraneous soft and semi-soft tissues with their dissected skeletons, since virtually complete removal of all such material from all types of bones from each of several skeletons may be prohibitive. In this regard, Alexander (1964) found that the weights of sternum plus costal cartilage dissected from human cadavers by standard techniques were reduced 817% by tedious removal of intercostal muscle and other hard-to-remove soft tissues. Thus, the underestimate expected to be derived from data in Tables 1 and 2 due to exclusion of most of the body’s cartilage will be at least partially offset by inclusion of extraneous material in the dissected skeletons.

(25) Based on original and collected data of Clarys et al. (1984), skeletal weight as a percentage of adipose-free total body weight would appear to be reasonably constant, averaging about 20% i2% for 19 adult males and about 21% f2.5% for 15 adult females. Thus, it might be expected that the relative skeletal weight would decrease with increasing total body weight, insofar as additional body weight represents mainly an increase in adipose tissue. Such a decrease is indicated in Fig. 8, which is based on data from Tables 1 and 2. The least-square linear fits to the gender-specific data are

Males: SW= 18.6-0.062 x Z’BW(R= - 0.28), (1) Females: SW= 17.1-0.069 x TBW (R= - 0.27), (2)

where TB W is the total body weight in kg and SW is skeletal weight expressed as a percentage of TBW. The best-fitting curve for females is nearly parallel to, but lower than, that for males (Fig. 8). Variance with age in the collective data in Tables l-3 cannot be readily separated from variance with dissection technique, although the data arc suggestive of a decline in skeletal weights with increasing age, not only in absolute terms but also as a percentage of total-body weight.


.- Males o- - &males

Fig. 8. Skeletal weight versus total body weight in adult subjects. Data from Tables 1 and 2.

16 ??- Males

- o- - &males

Fig. 9. Skeletal weight versus height in adult subjects. Data from Tables 1 and 2.

(26) Skeletal weight may be more closely related to height than to total-body weight. Skeletal weight versus height based on data from Tables 1 and 2 is shown in Fig. 9. The least- square linear fits are

Males: SW= - 10.7+0.119x HT (R=OAO), (3) Females: SW= - 17.0-t-0.157x HT (R=0.76), (4)

where HT is body height in cm and SW is skeletal weight in kg. (27) Based either on eqn (1) or (3), the dissected skeleton of a 176-cm tall adult male

weighing 73 kg would represent about 14% of total body weight, compared with a value of 14.1% derived from the single best available study (Borisov and Marei, 1974). Considering the sources of error discussed above, the total weight of bone, bone marrow, and cartilage in this typical adult male might represent a slightly higher percentage, perhaps 14.5%, of the total body weight. Thus, as an average, the weight of the skeleton on a 73-kg adult male might be about 10.5 kg.


(28) Based on eqn (2), the dissected skeleton of a 60-kg, 163~cm-tall adult female would represent 13.0% of TB W. A value of 14.3% is predicted by eqn (4). Because skeletal weight as a percentage of adipose-free total body may be reasonably constant for adult males and females, the lower value of 13% seems consistent with the results for males, whose lean body mass typically represents a greater portion of total-body weight. Thus, as an average, the total skeleton of a 60-kg adult female might weigh about 7.8 kg.

Reference value for the weight of the matie skeleton: Adult male (age 35 years): 10,500 g Adult female (age 35 years): 7800 g.

Pre-adults

(29) Reported skeletal weights for the foetus, infant, child, and adolescent are summarised in Table 4. The values of Borisov (1973) and Swanson and Iob (1940) for the foetus and infant, which are considerably smaller than those of other investigators, apparently include most of the body’s cartilage but virtually no supportive tissue. According to Swanson and Iob (1940), the “freeing of bone and cartilage from the other body tissues becomes more difficult as the foetus approaches term.. . In the full-term foetus the supportive tissues had to be cut and scraped away.” The larger values obtained by other investigators may reflect

Table 4. Weight of skeleton in pre-adults

Investigator Age

Number, Total Sex body wt

(if known) (kg)

Skeletal weight

% of (g) total body wt

Prenatal: Borisov, 1972, 1973 Swanson and Iob, 1940 Borisov, 1972, 1973 Bischoff, 1863 Borisov, 1972, 1973 Swanson and Iob, 1940 Borisov, 1972, 1973 Muehhnann, 1927” Borisov, 1972, 1973 Swanson and Iob, 1940 Swanson and Iob, 1940 Swanson and Iob, 1940

Postnatal: Borisov, 1972, 1973 Klose, 1914 Bischoff. 1863 Bischoff; 1863 Wihner, 1940b Klose, 1914 Muehhnann. 1927a Muehhnann; 1927a Mechanik, 1926 Muehhnann, 1927’

<5mo 4.1 mo 5-6mo 6mo 6-7 mo

7-8 mo 8mo 8-9 mo 9.1 mo

10.0 mo

Newborn Newborn Newborn Newborn Newborn 33 d

2Y 10 Y 16 Y 16~

20

12 1

11

17 1

17

40 1, M 1, F 1, M

1, E 1

1, F 4 M

0.37 f0.08 0.039 * 0.009 0.53 0.064 0.64f0.10 0.076 f 0.013 0.49 0.101 1.07*0.10 0.116+0.011 1.10 0.121 1.41 f0.17 0.159+0.018 1.76 0.265 2.06f0.17 0.228 + 0.013 2.06 0.211 3.20 0.312 4.07 0.399

3.43 i 0.45 3.21 2.92 2.36 2.52 3.09

14.0 26.6 43.5 35.5

0.388 * 0.75 11.3 0.512 16.0 0.467 16.0 0.425 18.0 0.446 17.1 0.489 15.8 2.068 14.8 2.558 9.6 4.4 10.1 8.4 23.1

10.5 12.0 11.9 20.6 10.8 11.1 11.3 15.0 11.1 10.2 9.8 9.8

’ From Muehhnann’s smnmary of data of Schwann, Dursy, von Liebig, Bischoff, Volkmann and Theile. The specific investigator was not given.

b Summarizing “data collected in this laboratory as well as a series of records collated from the literature.” c oedemous.


inclusion of more periosteum and supportive tissue, including some tendon attachments. In this regard, Wilmer (1940) describes the summary values based on his data and that of others as representing the “fresh ligamentous skeleton”.

(30) There is a paucity of data for the postnatal period, particularly after the first few days of life. The few available data points for persons 2-16 years of age are of limited value because of their wide scatter and because some of the subjects may have died of wasting diseases.

(31) The reference value for the weight of the skeleton at birth was based on the assumption that the skeleton represents 10.5% (10-l 1%) of total-body weight at that time. Reference values for skeletal weight in children and adolescents were derived as the sum of values derived for individual skeletal components, as described in later sections.

Reference values for skeletal weight in infants, children, and adolescents: Newborn: 370 g

1 year: 1170 g 5 years: 2430 g

10 years: 4500 g 15 years (male): 7950 g 15 years (female): 7180 g.

Fresh weights of individual bones

(32) Fresh weights of individual bones including bone marrow were determined by Borisov and Marei (1974) for the 20 adult Russian subjects described earlier and by Borisov (1973) for up to 40 Russian newborns (Table 5). With regard to the percentage of total fresh skeletal weight contributed by the various bones, no substantial differences with gender are evident. There are, however, considerable differences between newborns and adults. The most

Table 5. Percentage of total fresh skeletal weigbt contributed by various bones, including bone marrow

Bone Adult male Adult female Newbotll

Head: Skull Mandible

Trunk: Vertebrae and sacrum Ribs Sternum

Limbs: Femora Tibiae and fibulae Pelvic bones Feet Humeri Radii and ulnae Scapulae Hands Clavicles Patellae

11.8f1.6 1.250.2

19.0* 1.6 7.050.4 1.2f0.2

15.3 f 1.5 11.3f 1.4 10.6f0.8 6.3f0.7 5.3io.s 3.61t0.6 3.6*0.2 2.3ztO.3 0.8zkO.l 0.7fO.l

11.9hO.8 32.1 1.2io.2 1.6

20.4 f 1.5 5.6kO.4 1.2f0.2

15.9io.7 11.9+0.7 10.5 f 1.0 6.8zkO.5 4.7 f 0.4 3.2ztO.3 2.9zto.2 2.4zkO.5 0.7*0.1 0.6-10.1

21.4 5.0

9.5 6.0 6.4 4.5 4.5 2.5 2.7 3.4 0.5

From Borisov (1973) and Borisov and Marei (1974).


striking difference is in the relative weight of the skull, which accounts for 32% of the skeletal weight in newborns but only about 12% in adults. Bones of the trunk have fairly similar relative weights in adults and newborns, while bones of the limbs (excluding the hands) are relatively smaller in newborns (Fig. 10).

DIAPXYSES A EPXPX_Y AVVEAR

SES ‘APPEAR FUSE

,

GROWTH OF .SiKELETON

I A NEWBoRN k 8 YEARS

c ADULT

Fig. 10. Growth and ossiCc.ation of the human skeleton. From Anson (1966).


(33) Fresh weights of individual bones, exclusive of bone marrow, were determined by Mechanik (1926) for the adult Russian subjects described earlier (Table 6). Presented for comparison in Table 6 are estimated relative weights of individual bones, apparently representing marrow-free bone, of adult Japanese subjects (Tanaka et al., 1981). These values are based on a collection of individual bones from a large number of modem-day subjects and are similar to those obtained from a review of earlier Japanese literature by Tanaka and coworkers, except that the skull represented a noticeably smaller portion and the femur a noticeably larger portion of the skeleton in the 1981 study. Also presented for comparison are data of Hudson (1965) on marrow-free bones of the head, trunk, and limbs in 16 infants and third-trimester foetuses studied in Great Britain. In the foetus and infant, the bones of the head represent more than 40% of the marrow-free skeleton, compared with 1420% in adults; the trunk represents fairly similar portions of the mineralised skeleton in the two groups; and the limbs represent nearly two-thirds of the mineralised skeleton in adults but only one-third in the foetus and newborn.

Table 6. Percentage of total fresh skeletal weight contributed by various bones (mineralized tissue only)

Bone

Adult male Adult female Newborn”

Mechanik Tanaka et al., Mechanik Tanaka et al., Hudson 1926b 1981’ 1926b 1981’ 1965

Head: 14.3 Skull 12.4zk 1.4 Mandible 1.9hO.3

16.5 16.5d

15.9 14.4h2.4 1.5hO.3

19.8 42.5zt3.1 19.8d 39.9*3.1

2.650.2

Trunk: 19.4 18.9 20.3 18.6 23.4 f 2.0 Vertebrae 9.4* 1.3 9.1 10.512.0 9.0 SacrUm 2.0+0.3 2.0 2.7 ztO.5 1.9 Ribs 7.4f 1.4 7.3 6.4-110.7 7.2 Sternum 0.650.1 0.5 0.7f0.3 0.5

Limbs: Femora Tibiae Fibulae Pelvic bones Feet Humeri Radii Ulnae Hands Patellae

66.4 64.6 64.1 18Szt 1.2 18.6 18.6i 1.0 10.9f 1.3 10.5 9.8*1.2 2.3 zt0.4 2.5 2.2f0.4 8.8-+ 1.2 8.4 10.3hO.8 6.4hO.4 7.1+0.4 2.2rto.2 2.8-+0.3 2.5+0.4 0.6jzO.l 3.2f0.3 1.1 izo.1

5.5 6.8 2.1 2.7 2.5 0.7 3.1 1.2

6.3 * 1.6 6.1 +0.4 1.8f0.2 2.2*0.2 2.5 kO.3 0.7fO.l 2.710.3 0.9fO.l

61.7 34.1 f 2.4 17.8 10.1 2.4 8.8 4.9zto.4 5.2 5.9 1.9 2.4 2.3 0.7 3.0 1.2

3.6rtO.2

Scapulae Clavicles Scapulae + clavicles

a Includes foetuses in third trimester. b Data for Russian subjects (6 males and 7 females), as reduced by Bigler and Woodard (1976). ’ Based on a collection of individual bones from a large number of modemday Japanese subjects. d Including mandible and teeth.

Weight of the “dry” or “dry, fat-free” skeleton

(34) The weight of the so-called “dry” or “dry, fat-free” human skeleton (or skeletal parts) has been studied from the early fetal period through old age (Ingalls, 1931; Trotter, 1954; Trotter and Peterson, 1955, 1968, 1969a,b, 1970; Merz et al., 1956; Baker and


Newman, 1957; Lowrance and Latimer, 1957; Hudson, 1965; Spiers, 1968; Trotter and Hixon, 1974; Nuti et al., 1988). Reported data actually represent only partially dried or defatted and dried skeletons, since drying and defatting processes have usually been applied to whole bones that would still contain considerable non-osseous, organic material at the end of treatment. The various data sets are not directly comparable for the most part because different investigators have applied considerably different processes. Ingalls (193 1) macerated, cleaned, and dried his skeletons but did not “degrease” them. Skeletons of Lowrance and Latimer (1957) were described as dried and “thoroughly degreased”. Data from Trotter (1954) and Merz et al. (1956) have usually been regarded as referring to dry, fat-free skeletons; these skeletons were dried and degreased, but the skeletons were “not dry and fat-free in the sense that chemists use those terms” (Trotter, 1954). Trotter and Hixon (1974) describe their material as the “dry, fat-free osseous human skeleton” and add that weights “are of dry, fat-free bones in contrast to weights of bones from the Terry Collection reported by Trotter (1954) and Men et al. (1956).” The difference seems to be that Trotter and Hixon first applied the timed drying and degreasing processes applied to the Terry Collection but then applied further drying and immersion in acetate until constant weight was attained. Trotter and Peterson (1955) pointed out, that “the term, dry fat-free bone in this study includes in addition to the osseous organic and inorganic constituents some remains of non-osseous organic material, since the bones were brought to the dry, fat-free state in the whole condition.” Data reported by Nuti et al. (1988) refer to skeletons that were dried but not “skimmed”; the authors multiplied measured weights by 0.68 to approximate fat-free weight.

(35) Mean weights of so-called “dry, fat-free” skeletons reported by Trotter and Hixon (1974) are listed in Table 7, according to age group, race, and gender. Trotter and Hixon found the skeletal weights to be substantially greater in black subjects than white subjects of the same gender after about age 3 years but noted that the small numbers of skeletons and

Table 7. Mean dry, fat-free (DFF) weight of the skeleton, according to race, sex, and age

Prenatal Postnatal (age in years)

374 wk O-O.5 OS-3 3-13 13-adult 45-64

white male: No. subjects Mean age (y) DFF weight (g)

White female: No. subjects Mean age (Y) DFF weight (g)

Black male: No. subjects Mean age Q DFF weight (g)

Black female: No. subjects Mean age (y) DFF weight (g)

4 7 5 7 9 11 40.8 wk 0.26 1.5 7.2 18.8 54.9

108.3 95.8 315.8 932.6 4004.4 3538.4

15 3 4 10 3 13 39.0 wk 0.26 2.0 8.2 17.7 56.0 85.1 71.0 268.4 1132.4 2724.3 2336.2

9 4 13 9 29 15 39.6 wk 0.22 1.3 7.8 18.2 53.9 82.5 110.0 260.2 1456.6 4228.5 3973.2

11 4 7 11 19 7 40.5 wk 0.11 1.9 8.2 18.1 57.3 89.3 102.3 382.3 1305.6 3256.2 3005.2

From Trotter and Hixon (1974).


dissimilar age distributions may give a distorted picture. Data from Baker and Newman (1957) for adult males dying in the Korean war also indicate that the dry weight of the skeleton per kg living body weight may be substantially greater in black subjects than in whites.

Weights of “w or “dry, fat-free” bones

(36) Dry or dry, fat-free weights of individual bones have been determined by several investigators (Ingalls, 1931; Trotter and Peterson, 1955; Merz et al., 1956; Baker and Newman, 1957; Lowrance and Latimer, 1957; Spiers, 1968; Horsman et al., 1970; Lloyd and Hodges, 1971; Trotter and Hixon, 1974; Nuti et al., 1988). Relative weights of dry or dry, fat-free bones (as a percentage of the weight of the total dry or dry, fat-free skeleton) as determined in four major studies are summarised in Table 8. Ingalls (1931) examined bones of 100 white, adult male subjects, probably from the Cleveland, Ohio area; Lowrance and Latimer (1957) studied 105 fully mature skeletons of Asiatic subjects of unknown age and gender; Trotter and Hixon (1974) summa&d their data for black male, black female, white male, and white female subjects (30 in each group) of mean age 60-66 years); and Nuti et al. (1988) summarised data of Galli and coworkers for 200

Table 8. Relative weights of dry bones of adults as a percentage of the total dry skeleton

Trotter and Hixon (1974) Lowrance and Illgalls Latimer Nuti et al.

White White. Black Black (1931) (1957) (1988) males females males females males both sexes males

Had: Cranium Mandible

Vertebrae: Cervical Thoracic Lumbar Sacrum

Ribs, sternum, shoulders: Sternum Ribs Scapula Clavicle

Pelvis:

Arms: Humerus Radius Ulna Hands

Legs: FerIlUr Patella Tibia Fibula Feet

17.3 22.3 17.4 22.4 14.8 20.4 15.5 15.7 20.7 15.4 20.3 13.1 18.0

1.6 1.6 2.0 2.1 1.7 2.4

10.4 11.4 10.8 11.4 11.6 10.1 11.0 1.5 1.7 1.5 1.7 1.5 3.8 4.2 4.0 4.1 4.4 3.2 3.5 3.4 3.6 3.5 1.9 2.0 1.9 2.0 2.2

10.6 10.0 11.3 10.4 11.5 10.7 10.9 0.5 0.4 0.5 0.4 0.7 0.5 6.0 5.8 6.5 6.1 6.6 6.4 3.1 2.8 3.2 2.9 3.1 2.8 1.0 1.0 1.1 1.0 1.1 1.0

8.3 8.6 7.8 8.0 11.3 7.8 10.0

14.6 12.5 15.1 13.0 14.9 13.8 14.3 6.8 5.8 6.9 5.9 7.2 6.4 2.3 1.9 2.4 2.1 2.2 2.2 2.9 2.4 3.1 2.6 2.7 2.7 2.6 2.4 2.7 2.4 2.8 2.5

38.6 35.2 37.6 34.8 36.6 37.2 38.3 19.0 17.6 18.3 17.0 18.4 17.7 0.6 0.6 0.6 0.5 0.6

11.1 9.7 11.0 10.1 10.8 10.6 2.3 2.1 2.3 2.2 1.2 2.5 5.6 5.2 5.4 5.0 6.2 5.8


Italian male subjects of mean age 37 years. Despite the different preparations of the bones (as described earlier), the relative weights are fairly similar from one study to another. Potential differences with gender are suggested for the skull and arms, but the data are inconclusive.

(37) Age-specific proportions of total skeletal weight contributed by various “dry, fat- free” bones, as reported by Trotter and Hixon (1974), are summarised in Table 9 according to age group, race, and gender. The skull contributes over 40% of the total weight of the dry skeleton of the foetus, infant, and young child, but only about 20% in adults. This difference is largely balanced by the percentage contribution of the lower limbs, which increases from about 20% in the foetus and infant to more than 40% in the adolescent and adult. Slight decreases with age in the relative contribution of the vertebral column, ribs, and sternum are nearly balanced by increases with age in the contribution of the upper limbs. These patterns are similar in all four race-gender groups.

Table 9. Means of percentages of the total weight of the dry, fat-free skeleton contributed by the four major divisions of the skeleton, according to race, sex, and age

Prenatal Postnatal (age in years)

37-44 wk O-O.5 0.53 3-13 13-adult 4564

Mean age Skull“ Postcrallialb Upper limbs’ Lower limbsd

Mean age Skull” Postcranialb Upper limbs” Lower limbsd

Mean age Skull Postcranialb Upper limbs” Lower limbsd

Mean age Skull’ Postcranialb Upper limbsC Lower limbs

(4) (7) (5) 40.8 0.26 1.5 41 50 46 24 20 23 14 12 11 22 18 20

(15) 39.0 42 23 13 21

(9) 39.6 43 23 14 20

(11) 49.5 42 23 14 21

(3) 0.26

42 23 14 21

(4) 0.22

45 22 14 19

(4) (7) 0.11 1.9

44 48 24 21 13 11 19 20

(4) 2.0

46 26 10 18

(13) 1.3

48 22 12 18

White male (7)

7.2 41 21 13 25

White female (10)

8.2 33 22 14 31

Black male (9)

7.8 34 18 14 34

Black female (11)

8.2 30 19 14 37

(9) (11) 18.8 54.9 19 17 19 17 17 19 45 47

(3) (13) 17.7 56.0 19 22 21 17 17 17 43 44

(29) (15) 18.2 53.9 17 17 18 18 19 20 46 45

(19) (7) 18.1 57.3 20 21 19 18 17 17 44 44

’ Cranium, mandible. b Vertebral cohmm, ribs, sternum. ’ Clavicles, scapulae, humeri, radii, ulnae, hands. d Hip bones, femora, tibiae, fibulae, feet. From Trotter and Hixon (1974). Number of subjects given in parentheses.


Relative amounts of compact and trabecular bone

(38) Typically, 7585% of the total bone mass in adults is compact bone and the remainder is trabecular bone (Par&t, 1988; Johnson, 1964, Frost, 1963a). The percentage of trabecular bone is usually higher in the axial than in the appendicular skeleton, but there are exceptions (Pa&t, 1988). Estimates of the fractions of compact and trabecular bone within individual bones, based on studies by Johnson (1964) and Spiers and Beddoe (1983), are

Table 10. Cortical and trabecular portions of different bones as percentage of mass of bone tissue

Bone

Johnson (1964) Spiers and Beddoe (1983)

Cortical Trabecular Cortical Trabecular

Femur Tibia Humerus Radius Ulna Fibula Vertebral column

cervical Thoracic Lumbar

Innominate Skull Hands Feet Chest cage

(clavicle, sternum, scapula, ribs)

61 33 17 23 14 26 83 17 80 20 90 10 84 16 87 13 87 13 87 13 76 24 89 11

25 15 25 15 34 66 75 25 90 10 95 5 95 5 65 5 94 6

given in Table 10. In contrast to estimates of Johnson (1964), Nottestad et al. (1987) estimated that only 3342% of the bone of human thoracic and lumbar vertebral bodies is trabecular. In beagles, cortical Ca was found to represent about 82%, 56%, and 66% of the total Ca in cervical, thoracic, and lumbar vertebrae, respectively, and the ratio of cortical to trabecular Ca in the whole skeleton was estimated as 79.6:20.4 (Parks et al., 1986).

(39) In long bones, the proportion of trabecular bone generally is relatively high in the metaphyses and relatively low in the diaphyses. In a study of femurs from seven women and four men aged 37-95 years, Bohr and Schaadt (1985) determined that cortical ash represented 5366% (mean 57%) of the total ash from the neck and 91-98% (mean 95%) of the total ash from the shaft. In tibia specimens from 10 males and 10 females in the age range 32-99 years, bone within a few centimetres of the proximal tibia plateau was 55-75% trabecular, while that at the midshaft was less than 1% trabecular (Hu et al., 1989). Schlenker and VonSeggen (1976) found a large percentage of trabecular bone (sometimes as great as 80-90%) within the first 3 cm of the styloid tips and a small amount of trabecular bone (typically 0.5-10%) at 3-12 cm from the styloid tips of radii and ulnae from four women aged 21,43, 63 and 85 years. The percentage of trabecular bone in the most distal 10% of the length of the radius and ulna was judged to remain fairly constant with age, but the percentage in the segment lying 30-40% of the length as measured from the styloid process appeared to increase with age.

Reference values for adult male or female: 80% of the total bone mass is compact bone and 20% is trabecular bone.


Surface-to-volume ratios for compact and trabecular bone

21

(40) Each bone has four surfaces: periosteal, haversian (intracortical), cortical-endosteal (inner cortical), and trabecular endosteal, with the latter three being in continuity. The periosteal envelope (an envelope is a surface that divides space into an inside and an outside) encloses all tissues of a single bone. The endosteal envelope, which is subdivided into trabecular, inner cortical, and haversian surfaces, encloses all of the soft tissues within the bone except osteocytes and their processes. Thus, bone tissue lies inside the periosteal envelope and outside the endosteal envelope (Pa&t, 1983). The total volume of bone tissue (absolute bone volume) is the volume of the skeleton minus the volume of soft tissues within the endosteal envelope (Par&t, 1983). According to this definition, absolute bone volume includes the volume of the lacunar-canalicular system.

(41) If it is assumed that (1) the ash contents of hydrated cortical and trabecular bone are 1.18 g/cm3 and 1.08 g/cm3, respectively (Gong et al., 1964); (2) Ca represents 37.5% of bone ash by weight (as discussed later); (3) the Ca content of the skeleton of a typical adult male weighing 73 kg and standing 176 cm tall is 1180 g (discussed in a later section); (4) 80% of the Ca in the skeleton is in cortical bone and 20% is in trabecular bone; then it can be calculated that the volume of cortical bone in a typical adult male is about 2130 cm3 and that of trabecular bone is about 580 cm3, giving about 2710 cm3 for all bone tissue.

(42) Some reported surface-to-volume ratios for compact and trabecular bone are listed in Tables 11 and 12, respectively. A surface-to-volume ratio of 3 mm2/mm3, or 30 cm2/cm3, may be typical for compact bone of adults. This yields an estimate of 30 x 2130 cm2 or about 6.5 m2 for the surface area of all cortical bone in a typical adult male.

(43) The variation in reported values is greater for trabecular than cortical bone due to the relatively low ratios (3.8-7.8 mm2/mm3) measured in the parietal trabecular bone and the generally lower values given by Lloyd and coworkers (1968, 1971) than other investigators. A value of 18 rnm2/mm3 (180 cm2/cm3) may be a reasonable estimate of the mean surface-to- volume ratio of all trabecular bone of adults. This yields an estimate of 180 x 580 cm2 or about 10.5 m2 for the surface area of all trabecular bone and a total surface area of about 17 m2 for all bone tissue of an adult male with 1180 g of skeletal Ca.

Table 11. Surface-to-volume ratios (S/v) estimated for human cortical bone

Reference W

(mm%& Bone Surface Age of subject(s)

(Y)

Lloyd and Hodges (1971) 3.0

Sissons et al. ( 1967)b 3-4

femur c”

C

adults

20-50

Beddoe (1977) 1.9 tibia 2.3 humerus 2.9 femur 3.1 tibia 3.5 humerus 3.9 humerus 2.1 femur 3.5 femur

C C C c+pc c+p c+p C c+p

:: 50 50 50 50 9 9

’ Cavity surfaces, that is, wrfaces of Haversian and Volkmann canals and resorption cavities. b As reported by Beddoe (1977). ’ Periostcal surfaces.


Table 12. Surface-to-volume ratios (S/v) estimated for human trabecular bone

References Bonea

Ages of subjects

0

Amstutz and Sissons (1969)

Arnold and Wei (1972)

Beddoe et al. (1976)

Bromley et al. (1966)

Dyson et al. (1970)

Lloyd et al. (1968)

Lloyd and Hodges (1971)

Mea and Schenk (1970)

Schulz and Delling (1976c)

14.6 LV

23.0 LV

23.9 19.7 17.3 18.5 17.2 7.8

25.8 18.4 19.8 22.8

2% 23.0 23.7 29.6

3.8

K

: XC PB LV F R IC PB LV F R IC PB

14.0 LV

21.0 LV

11.4 LV 9.5 FH

11.5 R 11.5 cv

12.0 LV 12.0 TV 4.1 PB

10.0 FH 18.0 IC

17.4

20.2 18.6 20.9 18.4 20.2 21.4 18.6 21.6 21.0 17.5

IC

IC

Young adult ( l)b

39-50 (7)

39-55 (8) 44 (1)

9 (1)

1.7 (1)

30-60

Adult (1)

Adult (1)

Adult (1)

3060 (59)

O-l (4) l-10 (3)

1 l-20 (6) 21-30 (7) 31-40 (7) 41-50 (6) 51-60 (11) 61-70 (14) 71-80 (10) 81-90 (6)

’ LV, lumbar vertebrae; TV, thoracic vertebrae; F, femur (neck and head); FH, femur head; IC, iliac crest; R, rib; PB, parietal bone.

b Number of subjects in parentheses.

(44) Data of Beddoe and coworkers (1976) indicate that the surface-to-volume ratios may not vary substantially with age for most bones. An exception is the parietal bone, where thicker trabeculae and smaller cavities in children may give rise to a smaller ratio for children than for adults.


Reference values for volume and surface area of bone in the adult male: (1) Volume of bone tissue (i.e. inside the periosteal envelope and outside the endosteal

envelope) AU bone tissue, 2710 cm3 Cortical bone, 2130 cm3 Trabecular bone, 580 cm3

(2) Surface&-volume ratio: Cortical bone: 3 mm2/mm3 (30 cm’/cm”> Trabecular bone: 18 mm2/mm3 (180 cm2/cmq

(3) Total surface area: All bone: 17 m2 Cortical bone: 6.5 m* Trabecular bone: 10.5 m2.

Age- and gender-related changes in characteristics of compact bone

(45) The vascularity and porosity of compact bone change continually throughout life. In early development of the skeleton, compact bone is highly vascular and has numerous resorption cavities and developing osteons, and a large portion of the bone surface shows formation and destruction. By contrast, the compact bone of a young adult has a more uniform appearance and is relatively inert in terms of formation and destruction (Fig. 11). By the fifth decade, compact bone begins to become more porous due to an increasing number of incompletely developed osteons and increased resorption of bone. In the midshaft of the femur, the total volume represented by haversian canals may increase by more than 100% in males and more than 50% in females from the sixth to the ninth decade of life (Thompson, 1980). Compact bone tissue in the endosteal region may be replaced by trabecular bone or removed completely in older persons (Sissons, 1962).

(46) Gains and losses in compact (cortical) bone have been described in terms of the “combined cortical thickness” or “cortical area” (cross-sectional area) at the midshaft of the long bones, fingers, and toes. The combined cortical thickness is the outside diameter (0) minus the diameter of the endosteal envelope (d), and cortical area at the midshaft of a nearly circular bone may be approximated by 3.1416 x [(D/2)2-(d/2)2]. As indicated in Tables 13 and 14, the pattern of change with age of cortical thickness varies in different regions of the skeleton, but for most bones there is an increase in cortical thickness and cortical area until some time in the fourth decade of life and a gradual decrease beginning in the fifth decade or later. An apparent delay in loss of cortical thickness and/or cortical area in bones of the leg indicated in these tables could be an artifact stemming from the changing shapes of these bones in later years. For example, the mid-shaft of the femur becomes more triangular than circular in shape in later years, possibly causing measurements of cortical thickness and calculations of cortical area based on a circular shape to be misleading (Epker, 1976). Most of the loss in cortical thickness after the fourth decade appears to be due to bone loss in the endosteal region; in fact, the outside diameter apparently increases throughout life for most bones (Epker, 1976). The decrease with age in cortical thickness is greater in females than males for all bones. Cortical thickness in females may decrease an average of about 35% below the maximum value by age 80 years, compared with an average decrease of 20% in males. IW 25:*-c


Fig. 11. Top: microradiograph of a femoral cortex from a 2.5year-old male. Bottom: microradiograph of a femoral cortex from a 20-year-old female. From Sissons (1962).

RADIOLOGICAL PROTECTION DATA: THE SKELETON 25 Table 13. Cortical thickness of the midshaft of various bones, relative to the mean cortical thickness of these bones in

30-year-old males

Age (Y)

Proximal Neck of Second humerus radius metacarpal

m/f8 m/f m/f

Second proximal phalanx

m/f Femur

m/f Tibia m/f

Fibula m/f

1 2 3 4 5 6 7

: 10 11 12 13 14 15 16 17 18 19 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90

0.35/0.37 0.42/O& 0.25/0.23 0.3910.36 0.26/0.24 0.37/0.36 0.33/0.30 0.42/0.42 0.47/0.45 0.31/0.30 0.45/0.41 0.3210.29 0.42/0.40 0.39/0.36 0.4710.46 0.53/0.51 0.37/0.36 0.50/0.47 0.3710.35 0.47/0.44 O&/O.41 0.52/0.50 0.57/0.55 0.42/0.43 0.54/0.50 0.42/0.41 0.5210.48 0.49/0.45 0.5710.54 0.61/0.58 0.48/0.47 0.59/0.55 0.47/0.46 0.56/0.52 0.54/0.50 0.61/0.57 0.65/0.62 0.5310.52 0.63/0.60 0.51/0.49 0.59/0.55 0.58/0.53 0.65/0.60 0.69/0.66 0.58/0.56 0.67/0.64 0.5610.54 0.63/0.58 0.62/0.57 0.6910.63 0.7210.70 0.62/0.60 0.7010.67 0.59/0.58 0.66/0.60 0.65/0.61 0.7210.65 0.7510.73 0.65/0.63 0.7310.70 0.63/0.62 0.69/0.63 0.6910.63 0.7610.67 0.78/0.75 0.6910.67 0.7610.73 0.6610.65 0.7210.65 0.72/0.66 0.7810.69 0.81/0.78 0.72/0.70 0.7810.75 0.69/0.67 0.7510.67 0.7_5/0.69 0.81/0.71 0.84/0.80 0.75/0.73 0.80/0.78 0.72/0.70 0.77/0.69 0.77/0.71 0.8310.72 0.85/0.82 0.7710.75 0.83/0.79 0.7510.73 0.80/0.70 0.80/0.73 0.85/0.74 0.87/0.84 0.80/0.78 0.85/0.81 0.7710.75 0.8210.72 0.82/0.76 0.8710.76 0.89/0.86 0.82/0.79 0.8710.83 0.7910.77 0.8410.74 0.84/0.77 0.89/0.77 0.91/0.87 0.85/0.81 0.8910.85 0.82/0.80 0.85/0.75 0.86/0.78 0.9010.78 0.9210.88 0.86/0.83 0.91/0.86 0.84/0.81 0.8710.76 0.88/0.80 0.9210.79 0.93/0.90 0.88/0.85 0.92/0.88 0.85/0.83 0.89/0.78 0.89/0.81 0.93/0.80 0.94/0.91 0.90/0.86 0.93/0.89 0.87/0.85 0.9010.79 0.91/0.83 0.96/0.81 0.96/0.91 0.93/0.88 0.95/0.91 0.91/0.87 0.93/0.80 0.94/0.85 0.98/0.82 0.98/0.93 0.96/0.90 0.9710.93 0.95/0.91 0.96/0.83 0.9710.87 1.00/0.84 LOO/O.94 1.00/0.93 1.00/0.94 1.00/0.95 LOO/O.85 1.00/0.89 1.00/0.84 1.00/0.94 LOO/O.93 1.00/0.94 1.03/0.97 1.02/0.85 1.02/0.90 1.00/0.82 0.9910.92 LOO/O.92 1.00/0.92 1.05/0.98 l&4/0.85 1.03/0.88 0.98/0.81 0.97/0.90 LOO/O.89 1.00/0.89 1.05/0.98 l&4/0.85 1.03/0.87 0.96/0.77 0.9410.86 0.9910.86 0.98/0.85 1.0510.97 1.04/0.83 1.01/0.85 0.9210.75 0.91/0.82 0.96/0.83 0.9610.8 1 1.05/0.95 1.04/0.81 1.00/0.82 0.89/0.71 0.8710.77 0.94/0.78 0.9310.78 1.03/0.90 1.0210.79 0.9810.78 0.84/0.67 0.8210.73 0.90/0.73 0.8910.72 1.00/0.85 0.9910.76 0.9510.75 0.8010.63 0.7710.66 0.8610.68 0.86/0.67 0.98/0.83 0.98/0.73 0.92/0.70 0.7410.58 0.72/0.60 0.82/0.61 0.82/0.61 0.95/0.80 0.97/0.70 0.89/0.66 0.69/0.53 0.66/0.55 0.78/0.57 0.78/0.55 0.90/0.76 0.96/0.66 0.86/0.61 0.63/0.50 0.6110.49 0.72/0.49 0.7410.49 0.86/0.73 0.9410.63 0.83/0.56 0.5710.43 0.55/0.43 0.69/0.43 0.67/O&l 0.82/0.71 0.91/0.59 0.80/0.52

Typical values for combined cortical thickness in males, age 30 years (mm): 10 5.3 5.7 4.6 20 13 7.3

a Male/female. Baaed on data of Virtama and Helell (1969), Jowsey (1964, 1966), Garn (1970), Epker (1976), Plato and Norris

(1980), Thompson (1980), Meema and Meema (1981), and Fox et al. (1986). Data have been smoothed.

Age- and gender-related changes in characteristics of trabecular bone

(47) The structure of trabecular bone also undergoes continual changes throughout life. During growth there are rapid changes in trabeculae, particularly in the ends of long bones, where growth in the length of bone requires removal of some trabeculae and compaction of others to form a whorled arrangement of new cortical bone. Even after bone growth has slowed or ceased there are changes in the pattern and arrangement of trabecular bone in response to changes in tension and compression on the bone (Enlow, 1963).


Table 14. Cortical area of the midshaft of various bones, relative to the mean cortical area of these bones in 30-year- old males

Age Proximal (Y) humerus

Second metatarsal Mean Radius

Second metacarpal

0.22/0.18 0.16/0.18 0.28/0.25 0.22/0.20 0.32/0.31 0.2610.23 0.3510.34 0.2QjO.26 0.39/0.36 0.43/0.40

0.34/0.30 0.37/0.34

0.4810.42 0.4QjO.48

0.4210.37 0.42jO.39

0.52/0.51 0.45/0.42 0.55/0.55 0.49/0.48 0.60/0.55 0.55/0.52 0.66/0.63 0.70/0.70

0.61/0.56 0.65/0.57

0.7910.72 0.8QjO.75

0.72/0.61 0.77’10.65

1.01/0.76 1.02/0.83

0.83/0.70 0.85/0.74

0.9910.82 0.97jO.81

0.8810.75 0.9310.76

0.98/0.80 l.OojO.80

0.98/0.77 1 JJOjO.79

0.98/0.79 0.9410.74

0.9910.79 O.QQjO.77

0.8810.67 0.98/0.73 0.83/0.58 0.9610.67 0.7610.52 0.87/0.63 0.68/0.47 0.73/0.60

0.21/0.17 0.10/0.08 0.13/0.12 0.16/0.16 0.19/0.18 0.21/0.21

0.17/0.10 0.17/0.14 2 3 4 5 6 7 8 9

10 11 12 13 14

0.2310.23 0.2610.27

0.23/0.18 0.22/0.20 0.2810.25 0.2510.24

0.27jO.29 0.3210.29

0.31jO.28 0.38/0.33

0.28jO.27 0.32/0.30 0.37/0.33 0.41/0.36 o&l/o.41 0.48/0.44 0.52/0.49 0.571052

0.35iO.29 0.40/0.30

0.2zqo.22 0.4210.40 O-28/0.26 0.4710.47

0.4210.32 0.4qo.35 0.4710.37 0.51/0.41 0.55/0.46 0.55/0.53 0.6310.58 0.69/0.60 0.7510.62

0.32iO.32 0.52/0.55 0.36/0.36 0.61/0.58 0.42/0.41 0.68/0.64 0.48/0.45 0.71/0.68 0.4910.53 0.7810.77 0.50/0.61 0.81/0.78 0.57/0.56 0.87/0.79 0.65/0.49 0.90/0.81 0.7610.45 O.QS/O.SS

0.62/0.59 o&l/o.64 0.72/0.65 0.78/0.66 0.86/0.68 0.8710.72 0.88/0.73 0.92/0.75 0.96/0.77 1.00/0.80 0.99/0.81 0.99/0.79 0.97/0.75 0.93/0.68 0.85/0.62 0.7310.56

17 0.7710.63 18 0.7810.62

0.7610.52 0.97/0.87 0.8010.59 0.95/0.87

19 22 30 40 50 60

0.87jO.64 0.9310.67 1.00/0.71 0.9710.70

0.84jO.66 0.97jO.88 0.9310.73 0.98/0.90 1 JlOjO.82 1 .OC$OSO 1.0210.87 1.0010.90

0.9410.67 0.90/0.62 0.86/0.57 0.7310.48 0.5210.38

1.05jO.91 1 .OC$O.87 l.lO/O.Ql 0.99/0.81 1.0710.87 0.93/0.72 O.QQ/O.81 0.89/0.66 0.8610.74 0.86/0.62

70 80 90

Typical values for cortical areas in males, age 30 years (mm’) 320 105 59 750 58

Based on data of Virtama and Helelg (1969), but data have been smoothed.

(48) After the skeleton has matured there is a continual net loss in trabecular bone mass, amounting to 2545% of the peak trabecular mass in normal humans (Arnold et al., 1966; Bartley and Arnold, 1967; Epker, 1976). In the femur, there is considerably more bone loss with advancing age in trabecular than in cortical bone (Bohr and Schaadt, 1985).

(49) Estimated changes from birth to old age in trabecular bone volume (that is, the fraction of spongiosa occupied by trabeculae) of trabecular regions of different bones are summarised in Table 15. There apparently is a fairly rapid decrease in trabecular bone volume in the first few months of life and a continual but slower decrease thereafter. For example, Witmer (1969) found that the trabecular structure of vertebrae changed drastically during the first 3-4 months of life but only slowly thereafter (Fig. 12).

(50) Data of Melsen et al. (1978) indicate that trabecular bone volume in the iliac crest is substantially greater in females than males early in life but is fairly similar in the two genders after age 50 years. Measurements of Meunier and Courpron (1976) indicate that trabecular bone volume in the iliac crest may be greater in females than males throughout most of the adult life but that greater bone loss in females during the sixth and seventh decades results in a reversal of this relationship near age 60-65 years. A pattern similar to that found by Meunier and Courpron was observed by Genant et al. (1982) for the density of the spine. On the other hand, Aaron et al. (1987) found that loss of trabecular volume in the ilium was

RADIOLOGICAL PROTECTION DATA: THE SKELETON 27 Table 15. Reported percentages of trabccular bone volume (portion of spongiosa occupied by trabeculae) as a

function of age in trabecular regions of different bones. Data for males and females are combined.

Percent trabecular bone volume

Age Vertebrae” Iliac crestb Ferl.lurC Rib= Parietal bone’

O-1 Y O-l mo 2-3 mo 3-6 mo 0.5-l y

l-10 y l-7 y l-2 y 2+ Y 5-14 y 9Y

1 l-20 y 21-30 y 31-40 y 41-50 y

51-60 y 11.4 61-70 y 8.5 71-80 y 8.5 81-90 y 7.7

37.5 43 30 20.5 22

19.9 20.5 23

17.6

15.6 15.3 11.9

23.0 19.0 25.8 24.5

22.9 17.6 26.3 17.3

20.7 20.4 20.0 19.9 14.gd 10.4

30”

18.6 15.2 14.2

82.1

68.1

55.4

’ Adapted from data of Bcddoe et al. (1976) for children of age 1.7 and 9 y, Witmer (1969) for other infant and child ages, and Arnold and Wei (1972) for adults.

b From Schulz and Delling (1976c), except: values for ages 1.7 and 9 y are from Beddoe et al. (1976), and value for approximate age range 5-14 y is weighted average for French and American children, from Table 2 of Witmer et al. (1976).

’ From Beddoe ef al. (1976), except that value of 30% for femur is from Lloyd and Hodges (1971). d Neck and head of femur. ’ Femur head.

common to both genders and similar in extent, falling from about 25-30% in early adulthood to about 16% by the eighth decade. They concluded, however, that the histologic basis for the loss differed, with decreased formation being the principal factor in bone loss in men and increased resorption causing bone loss in women. Bone loss in women was attributable mainly to total removal of individual trabeculae, while in men there was generalised attenuation of trabecular bone.

(51) Widths, or “mean path-lengths”, of trabeculae and trahecular cavities as a function of age have been examined by Witmer (1969) for vertebrae and by Beddoe (1976) for various bones. Reported values are summarised in Table 16, along with bone volumes found by those authors. There appears to be a rapid increase in the size of trabecular cavities during infancy and a continued but more gradual increase during childhood. The data also indicate some increase in the size of trabeculae during infancy and childhood.

Bone remodelling

(52) In the following, bone remodelling refers to a process of bone turnover that replaces existing bone but changes the shape and total amount of bone very slowly or not at all. Bone


a b

Fig. 12. Microradiographs of cross sections of cervical vertebrae from infants and young children of age (a) 2 days, (b) 5 months, (c) 2.5 years (l/2 vertebra), and (d) 8 years (l/4 vertebra). From Witmer (1969).

modelling refers to local influences that alter the size and shape of growing bones. Bone growth refers to a process that increases the volume of bones (Frost, 1980).

(53) The remodelling process is carried out by certain cells on the bone surfaces, namely, osteoclasts, osteoblasts, and their precursors. Each surface is always in one of three functional states: forming, resorbing, or quiescent. Bone-resorbing surfaces are scalloped by Howship’s lacunae containing osteoclasts and poorly characterised mononuclear cells. Bone- forming surfaces are covered by osteoid seams and osteoblasts.

(54) As a result of continual remodelling, bones of adults are composed of many small elements of bone made at different times (Fig. 13). These elements are called bone structural units (BSU). The BSU are held together by dense connective tissue (so-called “cement” lines or surfaces).

(55) The characteristic structural unit of adult compact bone is the secondary osteon or haversian system, which is a cylinder about 200 pm in diameter, running roughly parallel to the long axis of the bone, with a central canal about 40 pm in diameter. Within the canal run blood vessels, lymphatics, nerves, and connective tissue, all continuous with those of the bone


Table 16. Change with age in trabecular bone volume, trabecular width, and trabecular cavity width in various bones

Age

Vertebrae:d o-4 d (5) O-l mo (12) 2-3 mo (7) 46 mo (9) 0.5-l (4) y l-2 (3) Y 2-8 (5) Y

Lumbar vertebrae:’ 1.7 y 9Y

44Y

Cervical vertebraexe 9Y

44Y

Rib? 1.7 y 9Y

44Y

Iliac crest:’ 1.7 y 9Y

44Y

Bone volume’

44.4 43 30 20.5 22 20.5 23

19.9 15.4 15.3

13.8 21.7

24.5 17.3 10.4

19.0 17.6 18.8

Mean trabecular

widthb

150 165 131 149 150 152 203

189 168 235

162 276

191 231 265

195 180 253

Mean cavity width=

203 232 344 654 611 672 755

696 857

1172

906 897

559 1133 1706

597

9’:

* Percentage of volume of spongiosa occupied by trabecular bone. b Mean distance in micrometres of the lengths of random straight lines

drawn through the trabeculae (i.e. osseous tissue). ’ Mean distance in micrometres of the lengths of random straight lines

drawn through the trabecular cavities. d Witmer (1969) and Cournot-Winner (1992, personal communication);

number of subjects in parentheses. ’ Beddoe (1976); one subject at each age.

marrow and the periosteum. The mean length of a human cortical BSU is about 2.5 mm and the mean volume is about 0.065 mm3 (Beddoe, 1977; Par&t, 1983).

(56) In trabecular bone the BSU are flattened and lie roughly parallel to the plane of the trabecular plates (Pa&t, 1983). The BSU forming the trabecular surface are shaped somewhat like shallow segments of a cylinder of radius about 600 pm, with each segment being about 50 pm in depth at the centre and about 1 mm in length (Pa&t, 1983). The mean volume of a trabecular surface BSU is about 0.025 mm3.

(57) Bone remodelling rates have been estimated by a variety of indirect methods, such as analysis of the rate of turnover of radionuclide labels (Bryant and Loutit, 1961; Rowland, 1964; Bauer, 1964; Leggett et al., 1982) or of the rate of change with age in the number of osteons in compact bone (Kerley, 1965; ZCRP 1973). Remodelling rates of relatively small regions of the skeleton, primarily from the rib and ilium, have been studied more directly by tetracycline-based histological analysis, a method pioneered by Frost (1961, 1963b, 1964, 1969); (see also Santoro and Frost, 1967, 1968; Villanueva et al., 1976; Melsen and Mosekilde, 1978; Vedi et al., 1983; Reeker et al., 1988; Pa&t, 1990; Agerbaek ef al., 1991). It


1 2 3

CL RC

HC

BS 1

CL

3 4 HL OS

Fig. 13. Evolution of bone structural units (BSU) in cortical and trabecular bone. The original BSU (stage 1) are demarcated by cement lines (CL). In cortical bone the resorptive process (stages 2 and 3) enlarges the haversian canal (HC) and in this illustration removes most of one and part of four other BSU to form a resorption cavity (RC). In trabecular bone the resorptive process erodes from the bone surface (BS) and in this illustration removes part of three BSU to form a Howship’s lacuna (I-IL). The formation process converts the resorption perimeter (dashed line) to a new cement line (stage 4) within which an osteoid seam (OS) is laid down and the new BSU is progressively

constructed (stages 5 and 6). IB is interstitial bone. From Par&t 1983.

was discovered that tetracycline antibiotics deposit in vivo in sites of bone formation and that the deposits can be observed by fluorescence microscopy (Milch et al., 1957). If tetracycline is administered continuously over several days or administered in two doses taken several days apart, then the rate of construction of BSUs that were forming during the period(s) of label administration can be estimated from consideration of the width or separation of labelled bands.

(58) The data in Table 17 are derived from tetracycline-based histological analysis of cortical remodelling in the middle third of the sixth human rib (Frost, 1969). These data describe remodelling in a typical cubic millimetre of compacta within the “haversian envelope”, that is, excluding periosteal and endosteal activity. It appears that the rate of remodelling of rib cortical bone is high in infants and young children, reaches a minimum in middle ages, and increases again in older persons. A similar qualitative pattern, but a consistently lower rate of remodelling, was determined for cortical-endosteal surfaces (marrow cavity wall) of the sixth human rib (Frost, 1969). The values for the “haversian envelope” should be more representative of the total formation rate of rib cortical bone than those determined for the relatively small surface area represented by the marrow cavity wall.

(59) Bone remodelling rates determined for rib cortical bone are compared in Table 18 with cruder estimates of remodelling rates for cortical bone of the clavicle and various long bones (femur, humerus, tibia, fibula) of human subjects. The estimates in Table 18 for bones other than ribs are based on data of Frost (1963) for a relatively small number of subjects, some of whom were seriously ill at the time of tetracycline administration. These data are broadly consistent with the more complete data on ribs, particularly with regard to the

Tabl

e 17

. Hav

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an r

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g da

ta f

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uman

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iddl

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ird

of 6

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Age

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0.33

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24

35

44

55

64

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9 40

49

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9 70

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No.

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43

20

49

52

53

63

37

23

Para

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er

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ts

Bon

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rmat

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rate

* m

m3/

mm

3/Y

0.

85

0.38

0.

21

0.06

7 0.

018

0.03

7 0.

036

0.04

0 (0

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(0.2

4)

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(EO

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0.80

0.

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(0.3

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(0.2

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(0.2

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ure

rate

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0.

53

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(0

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(E

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0.41

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(0.1

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(0.1

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(0.1

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0.22

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w

L


Table 18. Comparative formation rates (% y-‘) of compact bone of rib, clavicle, and various long bones (combined data for femur, humerus, tibia, and fibula)

Age range (y) O-t).9 l-9 lo-19 20-29 30-39 40-49 50-59 60-69 70-79

Rib No. subjects Standard deviation

Clavicle No. subjects Standard deviation

Long bones No. subjects Standard deviation

0.85 0.38 0.21 16 43 20 0.40 0.24 0.15

1.1 - 0.24 1 - 5

- 0.21

1.1 - 0.25 1 - 3

- 0.17

0.067 0.018 0.037 49 52 53 0.037 0.006 0.013

0.025 0.010 0.009 2 4 2 0.019 0.008 0.005

- 0.020 - - 3

0.015

0.036 0.040 0.044 63 37 23 0.012 0.013 0.015

0.038 0.045 0.022 I 13 3 0.032 0.041 0.018

0.068 -- 4 0.050

Estimates for rib are taken from Table 17. Estimates for other bones are based on data of Frost (1963b).

Table 19. Age-dependent parameters for formation and resorption in the mandible cortex’

Percentage surface Percentage surface involved in involved in

Age (Y) formation resorption

0.15 48 48 2 33 21 5 18 20 7 11 9

1 l-20 8 7 21-30 1 2 31-40 1 8 41-50 2 5 51-60 3 7 61-70 3 13 71-80 2 8 81-90 4 9

a Crude estimates based on Figs. 1 and 2 of Manson (1964).

pattern of change with age in the rate of cortical bone formation. A similar pattern of change with age is indicated by remodelling data for the mandible cortex (Table 19).

(60) Villanueva et al. (1977) concluded that cortical bone formation rates were roughly the same in the ilium and the eleventh rib in subjects with osteoporosis or osteomalacia. Recent data on healthy women of age less than 50 years indicate a rate of cortical bone formation in the ilium of about 6-7% y-l, assuming a surface-to-volume ratio of about 3 mm2/mm3 (Par&t, 1990).

(61) Indirect estimates of bone remodelling based on the rate of turnover of bone-seeking radionuclides from the skeleton suggest potentially large variation in cortical remodelling rates in different parts of the skeleton (Bryant and Loutit, 1961; Rowland, 1964; Bauer, 1964). Particularly slow remodelling rates (< 1% y -‘) have been estimated by this method for the shafts of certain long bones of persons exposed many years earlier to 226Ra (Rowland, 1964), but the data are complicated by the possibility that the bone tissues received relatively high radiation doses that may have slowed their remodelling.


(62) Par&t (1983) reviewed data on cortical remodelling rates in adults and concluded that an average value of about 3% y - ’ for all cortical bone is reasonably consistent with both direct and indirect information.

(63) Remodelling rates are less well established for trabecular bone than for compact bone. Indirect estimates based on turnover of bone-seeking radionuclides depend on the biokinetic model employed but are typically on the order of lO-25% y-l for adult trabecular bone (Leggett et al., 1982; Pa&t, 1983). Histological analysis of trabecular bone remodelling rates have been confined largely to the iliac crest of adult subjects (Melsen and Mosekilde, 1978; Vedi et al., 1983; Reeker et al., 1988; Parfltt 1983, 1990; Agerbaek et al., 1991). The remodelling rate of iliac trabecular bone appears to be in the range 2040% y-l (Reeker et al., 1988; Parfitt 1983, 1990, personal communication). There are indications of a substantial variation with age in the rate of iliac trabecular remodelling, at least in women (Melsen and Mosekilde, 1978; A. M. Pa&t, personal communication).

(64) The iliac crest is a standard site for trabecular bone biopsy in human subjects because of its accessibility, but the ilium is in many ways an atypical bone that may remodel at a higher rate than most other regions of the skeleton (Pa&t, 1983). The rate of remodelling of vertebral trabecular bone has not been measured directly, but indirect comparisons with iliac trabecular bone based on osteoid surface and volume and fractions of surfaces covered by osteoblasts and osteoclasts suggest a rate of remodelling in vertebral trabecular bone that is roughly one-half of that in the ilium (Par&t, 1983).

(65) In ICRP Publication 20 (1973), the average rate of bone remodelling during adulthood was estimated as 2.5% y - ’ for compact bone and 10% y- ’ for trabecular bone. The estimate for compact bone was derived mainly from (1) osteon counts and lamellar area in midshafts of long bones covering ages from birth to 95 years, (2) histological data based on tetracycline labelling, (3) microradiographic measurements of bone formation, and (4) estimated turnover rates of radionuclides in man. The estimate for trabecular bone was based on the assumption that the amount of bone formation per unit area of bone surface is the same in compact as in trabecular bone, together with the estimates that the surface-to-volume ratio is 3 mm2/mm3 for compact bone and four times larger, or 12 mm2/mm3, for trabecular bone. The estimated remodelling rate of 2.5% y-l for compact bone is reasonably consistent with newer information, but the estimate of trabecular remodelling and the corresponding surface-to-volume ratio of trabecular bone are both lower than indicated by much of the newer information.

(66) Typical values for bone remodelling and related processes in adult humans are summa&d in Table 20. A value of 3% y- ’ was selected as a typical value for the average rate of remodelling of compact bone in adult humans, based mainly on histological data and radionuclide turnover data. A value of 18% y -’ was selected as a reference value for the average rate of remodelling of trabecular bone in adult humans, based mainly on the limited histological data for trabecular bone, consideration of the rate of turnover of radionuclides in adult humans, and the estimate that the surface-to-volume ratio of trabecular bone is six times that of cortical bone as an average (as discussed earlier). It is emphasised that remodelling rates appear to vary substantially with age during adulthood, and that the indicated typical values are estimated averages covering the period from age 25 years through old age.

(67) Although the rate of remodelling of trabecular bone may be substantially higher than that of compact bone, at least in the adult, the qualitative pattern of change with age in remodelling rates appears to be similar for the two bone types. This is indicated, for example, by analysis of turnover of environmental WSr (Leggett et al., 1982) and by the surface extent of bone-forming and bone-resorbing cells at different ages (Table 21). The following


Table 20. Representative values for bone remodelling in the adult skeleton

Quantity Cortical Trabecular

Fractional volume (mm3/mm3) Surface to volume ratio (mmz/mm3) Total bone volume (mm31 Total tissue volume (mm ) Total internal surface (mm2) Total Ca (g) Mineral apposition rate @m/d) Duration of formation (d) Bone formation rate (mm3/mm3/y) Bone turnover rate (%/y) Total turnover (cm3/d) Total turnover (g Ca/d)

0.95 3 2.1 x 106 2.2 x 106 6.5 x lo6

944 1.0

94 0.03 3 0.18 0.08

0.20 18 0.6 x lo6 3.0 x 106

10.5 x 106 236

0.75 67 0.18

18 0.30 0.12

Resorbing surface Percent of total surface Per unit bone volume (mmz/mm3) Total (m2)

Forming surface Percent of total surface Per unit bone volume (mm2/mm3) Total (m’)

Inert surface Percent of total surface Per unit bone volume (mm2/mm3) Total (m’)

Osteoid volume Percent of total volume Total (cm3)

0.6 1.2 0.018 0.21 0.040 0.13

3.0 6.0 0.09 1.0 0.20 0.63

96.4 92.8 2.85 16.2 6.27 9.74

0.1 0.8 2.2 4.8

Modified from a summary by Par&t (1983).

Table 21. Agedependent parameters for trabecular bone formation and resorption

Age 01)

Surface extent Relative numbers of osteoid with of osteoclasts per osteoblasts (%) unit surface areab

O-l 22.5 13.4 l-10 7.0 6.1

1 l-20 5.0 6.2 21-30 4.5 3.0 31-40 2.0 1.5 41-50 2.0 2.0 51-60 2.0 2.4 61-70 2.0 1.5 71-80 1.0 2.5 81-90 2.5 1.2

’ Values read from graph and rounded to multiple of 0.5. b Normalized to 2.0 at ages 41-50 years for comparison. Based on Schulz and Delling (1976a,b).


estimates of bone remodelling rates at different ages were derived from radionuclide turnover data together with the histological data summarised in Tables 17-21 (Leggett et al., 1982; Leggett, 1992; ICRP Publication 1989). The estimates are crude, particularly for young children, but are indicative of the different magnitudes of the bone remodelling rates at different stages of life.

Reference values for bone remodellhg rates at different ages (% y - ‘): Age Cortical bone Trabecular bone

O-3 mo 300 300 1 year 105 105 5 years 56 66

10 years 33 48 15 years 19 35 22 years 9 27 35 years 2 10 60 years 4 20 average after age 25 years 3 18

Bone density

(68) Bone density is the mass of bone per unit volume, but there are several ways to view the volume to which mass is referred. For example, bone density may refer to: (1) the volume of mineralised bone tissue excluding voids associated with lacunae and canaliculi, (2) that volume including those voids, (3) mineralised bone with voids plus associated soft tissue (either bone marrow or contents of haversian canals), or (4) the whole bone. In practice, voids associated with lacunae and canaliculi are generally included in the volume referent. Some variation arises in reported bone densities because the density depends on the treatment of a bone sample (e.g. soaking, drying, defatting) before measurement. Reported values for the density of fresh bone with associated soft tissues may vary substantially, depending on the amount of bone marrow and other soft tissues present.

(69) The density of the whole fresh skeleton is on the order of 1.3 g/cm3 (Robinson, 1960). Dry, mineralised collagenous bone matrix has a density of about 2.3 g/cm3 (Robinson, 1960).

(70) Gong et al. (1964) compared the densities of vertebral trabecular bone, free of marrow, from 10 adult human subjects and cortical bone from three adult human subjects. In general, the ash content was slightly higher, while water and organic contents were slightly lower, in cortical bone than in trabecular bone. The mean density of trabecular bone was 1.92 g/cm3 and that of cortical bone was 1.99 g/cm3.

(71) Blanton and Biggs (1968) determined densities of fresh compact bone and fresh spongiosa (trabecular bone with marrow) taken from nine male and four female Caucasian subjects of age 35-79 years. Trabecular bone specimens were taken from thoracic and lumbar vertebrae and the calcaneus, and compact bone was obtained from shafts of tibiae and femora. The mean density of spongiosa was 1.08 g/cm3 and that of cortical bone was 1.85 g/cm3. The authors noted the wide variation in density of bone specimens taken from the same area of one bone. For example, the density of spongiosa from the thoracic vertebrae of one cadaver varied from 0.8 to 1.4 g/cm3, and that of samples of cortical bone from the midshaft of the tibia of a second cadaver varied from 1.5 to 2 g/cm3,

(72) The density of hydrated bone tissue varies with age (Woodard, 1962, 1964; Mueller et al., 1966; Arnold et al., 1966; Atkinson 1982). In the newborn the specific gravity of hydrated


cortical bone tissue is in the range 1.5-1.8 (Robinson, 1960) and may average about 1.65 (Steindler, 1936). The hydrated density of bone may rise by 5--25% or more, depending on the bone and bone site, from early childhood to early adulthood and perhaps may continue to rise gradually to about age 40 years (Figs. 14 and 15). The mean density of hydrated cortical bone from the diaphyses of apparently normal long bones was 1.80 g/cm3 in 4 children 2-5 years old, 1.83 in 10 children 6-13 years old, and 1.92 in 24 adults 20-74 years old (Woodard, 1962, 1964; Woodard and White, 1986). In view of the bone sites studied, these values might be expected to represent upper estimates for the average density of cortical bone at the given ages. The function

CD(A) = -0.000156 A2f0.0125 A+ 1.65, A<40 years, (5)

where A is age in years and CD(A) is cortical density in g/cm3, may provide a reasonable estimate of the increase with age, from birth through the fourth decade of life, in the average

l.4: r I I

0 20 40 60 au Age (Yl

Fig. 14. Change with age in bone density measured at posterior (P) and anterior (A) sites at the metaphysis of the human femur. The curves represent central estimates based on data of Atkinson (1982) for 80 posterior and 173

anterior samples.

2.10 -

2.05 -

2.00 -

E 1.95

tij I.90

z .

??------0-o*-00 :?f+ghai.7a .0# w . .

0 I.85 *+,o* - . ?? ?? w .

w l.Go 1 x m 1.75 -

y” I.70 - Q % 1.65 -

z I.60 , I I I I I I I I I IO 20 30 40 50 60 70 60 so

AGE (yrord ?? MALE

0 FEMALE

Fig. 15. Change with age in density (g/cm3) of hydrated trabecular bone from vertebrae. From Arnold et al. (1966).

RADIOLOGICAL PROTECMON DATA: THE SKELETON 37

density of human cortical bone. In the fifth or sixth decade there begins a decline in the hydrated density of bone that may be drastic in some regions of some bones (Fig. 14).

Reference values for density of skeletal components: whole skeleton, adults: 1.3 g/cm3 dry, mineral&& collagenous bone mat& adults: 2.3 g/cm3 hydrated cortical bone

infant: 1.65 g/cm3 1 year: 1.66 g/cm3 5 years: 1.70 g/cm3

10 years: 1.75 g/cm3 15 years: 1.80 g/cm3 20 years: 1.85 g/cm3 35 years: 1.90 g/cm3.

Composition of bone and bones

Organic and inorganic components of bone tissue (73) The interstitial substance of bone has two major components, an organic matrix and

inorganic salts. In bone formation, bone-forming cells (osteoblasts) synthesise an organic matrix (osteoid), and this pre-osseous tissue then undergoes mineralisation (Triffitt, 1980). The matrix of bone contains various proteins, carbohydrates, lipids, and other substances, but the bulk of the organic material is made up of a protein called collagen (Triffitt, 1980).

(74) Relative amounts of mineral and organic material in dry fat-free human femoral cortex, vertebra, and rib are given in Table 22 (Quelch et al., 1983). The organic contents were measured in two ways: as the weight lost during ashing, and as the weight of material left after demineralisation. The difference in estimates obtained by these two methods was roughly 5%, which was attributed to the carbonate and citrate content of bone. Bone from infants and juveniles contained less mineral and more organic material than did mature bone. Relative changes with age in organic material were consistent with earlier results of Rogers and coworkers (1952) for dry, fat-free human femurs.

(75) Estimated collagen contents and proportions of total bone nitrogen (N) accounted for by collagen in epiphyses and cortical bone of the human femur are summarised in Table 23 (Dickerson, 1962). During the first 5-7 months gestation there is a rapid increase in the proportion of N accounted for by collagen; thereafter, this proportion slowly but steadily increases into the teenage years and possibly into early adulthood (Table 23).

Table 22. Mineral and organic contents of dry, fat-free human bone

Bone

Adult Juvenile femoral femoral cortex cortex

Neonatal femoral cortex

Adult vertebra

Adult rib

Number 22 3 6 2 3 Age Q, mean f S.D. 37* 18 8f3 - 58 59zk 14 Age W, range 16-82 4-11 36-40 wk 47, 69 39-70 Mineral (%) 66.8 * 1.04 64.9 f 0.47 64.5* 1.14 66.3 66.4* 1.72 Organic by ashing (%) 33.1 ho.98 35.1* 0.47 35.6 f 1.07 33.7 33.6* 1.71 Organic by demineralization (%) 27.5 f 1.38 30.2*0.90 30.4* 1.95 29.6 28.7 (2)

From Quelch et al. (1983).


Table 23. Mean collagen contents and proportions of total nitrogen accounted for by collagen in epiphyses and cortices of human femurs

Age

% Fresh femur weight

Cortical bone, Whole epiphyses middle l/3 of shaft

Water as % Collagen in Collagen % Collagen in Collagen % fat-free dry fat-free Nas % dry fat-free Nas % fresh wt solids total N solids total N

12-14 wk (3)’ 15-16 wk (4) 20-24 wk (9) 25-28 wk (4) 30-34 wk (5) Newborn (6)

2-17 d (5) 2-4.5 mo (6) 5-9 mo (5)

12-24 mo (5) 11-12 y (2) 16 Y (2) 18-35 y (8)

73.0 85.6 15.5 31.9 61.7 89.2 21.9 42.2 61.4 84.7 29.7 51.6 51.4 85.1 34.2 56.9 53.1 83.7 40.3 64.1 50.4 19.2 42.2 67.1 51.0 81.2 41.5 61.5 48.5 19.2 48.8 70.8 41.1 77.3 48.0 74.6 42.9 72.5 52.9 81.7 31.3 50.1 41.4 90.7

16.2 20.8 22.5 23.3 22.4 23.3 22.9 24.4 23.7 24.3 25.4 24.0 23.0

49.0 65.5 71.6 86.0 80.6 83.0 82.5 83.4 80.6 83.2 93.4 96.4 87.5

* Number of subjects in parentheses. From Dickerson (1962).

(76) The inorganic matter of bone consists mainly of submicroscopic deposits of forms of calcium phosphate (Neuman, 1980; Fawcett, 1986). Bone mineral may represent a wide array of intermediates seen in the transition of solution Ca2’ and Pi to solid phase hydroxyapatite [Cai0(PO&(OH)2], with younger or more recently calcified structures predominating in dicalcium phosphate dihydrate [Ca(HP04)2H20], amorphous calcium phosphate [Ca#O&(var.)] and possibly octacalcium phosphate [Ca&I(PO&], and more mature structures being predominantly hydroxyapatite (Neuman, 1980).

(77) Reported percentage weights of Ca and P in bone ash are remarkably consistent (Table 24), usually being slightly less than theoretical values for hydroxyapatite. While the values in Table 24 represent a variety of mixtures of bone and soft tissue, the variable amount of soft tissues affects the proportions of Ca and P only to a small extent because of the low ash content of soft tissues. Reasonable central estimates for percentage weights of Ca and P in bone ash may be about 37.5% and 16.5%, respectively, for adults and about 36.5% and 18%, respectively, for young children.

(78) In addition to calcium, bone ash contains small amounts of Na, Mg, and other cations. Other than phosphate, the main anions of bone ash are carbonate and citrate, and there are small amounts of chloride and fluoride (Orten and Neuhaus, 1982).

Reference values for percentage weights of Ca and P in bone ash Adults Ca = 37.5%; P = 16.5% Infants and young children: Ca = 36.5%; P = 18%.

Water, fat, protein, and ash contents of bones and the whole skeleton (79) Reported water, fat, protein, and ash contents of bones and of the entire skeleton are

summarised in Tables 25 and 26, respectively. Some differences in values reported by different authors probably arise from differences in fat solvents applied and in temperatures and duration of heating in drying or ashing of bones (Dickerson, 1962; Miglio and Noveroske, 1988). In addition to studies listed in Table 25, there have been numerous studies in which the


Table 24. Concentrations of Ca and P in bone ash

39

Percentage by weight in ash

Reference Age/= Bone Ca P

Klose (1914)

Toverud and Toverud (1933)


Booher and Hansmann (193 1)

Borisov (1973) Dyson and Whitehouse (1970)

Mitchell et al. (1945)

Forbes et al. (1953)


Moore et al. (1968)

Gabriel (1894)’ Gassmalm (1910)’ Loll (1923)’ Funaoka and Shirakawa (1931)’ Klement (1938)’ Nelp et al. (1972)

Robinson (1975) Tanaka et al. (1981)

Obrant and Odselius (1986)

Kathren et al. (1987)

Newborn/M 33 d/F Infants’ Infants” Infantsb Infalltsb Infants/M Infants/F Infants 17 mo 20 mo 20mo 20 mo 20 mo

35 Y/M 35 Y/M 35 Y/M 35 Y/M 46 Y/M 46YFr 46 Y/M 46 Y/M

48 YIM 6OYFI 67 YIP

34 YIF 53 YIP 59 Y/M 59 Y/M 73 YIP

42 Y/M 36 Y/M 20-30 y/M

70-80 Y/M

49-62 YW

Total skeleton Total skeleton Parietal Rib

Parietal Rib Tibia Tibia

Total skeleton Vertebra/trab= Vertebra/trabc Femur/trab= Femur/trab’ Femur shaft

Tibia uhla Rib Total skeleton Tibia

Ea Total skeleton Total skeleton Total skeleton Total skeleton”

HUUXlW Rib Rib

HUfIWUs Various bones Total skeleton Total skeleton Total skeleton Total skeleton Total skeleton Various bones Ulna Hand Iliac/trab’

Iliac/trab’

Various bones

34.0 35.9 39.7 38.4 37.8 37.0 37.5hO.2 37.3*0.3 36.2jzO.01 34.2* 34.4* 35.9* 37.9 38.5 38.0 39.4 39.0 38.1 37.6 35.6 37.0 40.0 37.3 39.5 33.8

36.7 38.8 37.1 36.3 35.1 36.5 36.6 36.7 36.3 36.6 3g8 37.8 36.6 39.0* 1.4

(36.H2.3) 40.0* 1.4

(37.0-42.7)

37.3 f 6.9

20.9 17.6 17.6 17.4 17.3 17.4

18.2* 18.1* 18.3* 18.7 17.9

16.8 17.1 16.6 16.7 16.5 15.5 16.7 17.3 17.7 17.8 15.4

16.0 17.4 17.0 15.4 15.2 16.7 16.3 17.0 16.8 16.9 18’3

17.2+ 1.0 (15.7-19.7) 17.7rto.7

(15.9-20.4)

’ ‘kenty-six full-&m infants born of mothers with good diet during pregnancy. b Combined data for 48-49 premahue infants, twins, and full-term infants born to mothers with poor diet during

Pngnancy. a Trabecular bone. d Samples included bone marrow.

: E$zE$ Mitchell et al. (1945). g Typical values baaed on large number of samples.

40 RADIOLOGICAL PROTRCHON DATA: THR SKELETON

Table 25. Water, fat, protein, and ash coutent of bones or parts of bones

% of weight of wet tissue

Investigator/bone Age Number Water Fat Protein Ash”

Dickerson (1962)/ whole femur

Brubacher ( 1890)b/ whole femur femur shaft

Dickerson (1962)/ whole femur

Woodard (1964)/ cortical bone from diaphysm of long bones

Brubacher (1 890)b/ whole femur femur shaft

Gong e% al. (1964)/ trabecular bone from vertebrae compact bone from femur, tibia shafts

Mitchell et al. (1945)/ whole tibia whole ulna whole ninth rib

Forbes ef al. (1953)/ whole tibia whole ulna whole tenth rib

Forbes and Lewis (1956)/ whole tibia

12-14 wk 25-16 wk 20-24 wk 25-28 wk 30-34 wk

Foetua

Postnatah Newborn 2-11 d 2-4.5 mo 5-9mo 12-24 mo 11-12 y 18-35 y

2-19 y 20-74 y

4Y

38-75 y

35 Y/M

60 Y/M 1 13.7

3 77.8

d 78.4 72.9

4 68.4 5 63.4

1 69 37

; 63.8 64.3

6 63.7 5 57.9

: 52.1 27.0

8 15.6

16 15.4 26 12.2

1 45 26

10 14.0 3 11.9

1 16.3 12.5 26.3

1 11.9 15.8 26.3

Nil Nil Nil Nil 0.15

0.4 0.4

13 39

0.14 0.28 0.65 2.09 7.54

26.0 31.8

25.7 54.7 24.6 57.9

12 2

22 47

55.9 59.4

36.4 15.8 31.4 17.8 20.9 44.6 7.8 23.3 37.9

49.1 19.9 7.9

35.5

15.6 30.5 22.3 42.2 29.0 34.3

’ Extensive data are available on ash contents of individual bone-a (e.g. see Holtzman (1962), McInroy et al. (1991)).

b Reported by L.enz (1954).

ash content of bones or parts of bones was determined, but it is difhcult to reduce the results of the various studies to a common basis due to potential differences in the amount of bone marrow left in the samples and the amount of water lost during storage.

(80) Woodard (1962,1964) determined the water, ash, Ca, P, and protein contents, and the specific gravity of compact bone from which the periosteum and trabeculae had been scraped. The water, ash, and Ca contents were found to depend on age, as did the ratio Ca/p (Fig. 16). Ash as percent wet weight averaged 54.7% for subjects 2-19 years of age and 58% for adult

RADIOLOGICAL PROTlX!TION DATA: THE SKELETON

Table 26. Composition of whole skeleton as percentage water, fat, protein, and ash

41

% of weight of wet skeleton

Investigator Age No&x Water Fat PrOkill Ash

Swanson and Iob (1940)

Borisov (1973)

Borisov (1973)

Rlose (1914)

Bischoff (1863)

Volkmann (1874)c


Borisov and Marei (1974)



McInroy et al. (1985)

McInroy et of. (1991)

Moore et al. (1968) With soft tissue After beetling

Prenatal: 4.1 mo 9.1 mo 10 mo

1 72.3 1 62.3 1 56.0

<Smo 20/B’ 5-6mo 12p 6-7 mo 11/R. 7-8 mo 17/B. 8-9 mo 17/B’

Postnatal: Newborn

Newborn 33 d

33 Y

Adult

35 Y

37-50 y

46 Y

48 Y 6OY

49 Y

62 Y

67 Y

40/B.

l/M l/F

l/M

l/M

1Fr

l/F

l/M

l/M l/M

l/M

l/M

l/F

51.2 52.6 49.8 49.8

48.8

64 70b

22.0

31.8 17.2 18.9

28.2 25.0

39.5 10.1 30.2 22.0

40.3 18.2 19.4 21.2 12.2 1.8 31.3 55.7

0.4 1.1

2.6 17.3 0.6b 15.5b

19.7

20.8 19.7

15.3 15.4 16.6 18.3 18.1

19.4

15.0 13.3b

22.1

28.9

21.5

26.6

29.2 27.2

28.2

30.9

a Both sexes. b Subject was oedemous. ’ As reported by von Voit (1881).

subjects. The protein content varied little if any with age. The water content of compact bone as a percentage of wet weight may be about 15-20% at age 5 years and may gradually decrease by roughly one-third over the next 10-15 years.

(81) Currey and Butler (1975) determined the ash content of specimens of femoral cortical bone (midshaft) from 18 subjects between the ages of 2 and 48 years. The ash content averaged about 61% at ages 2-4 years, 63% at ages 6-17 years, and 65% at ages 2648 years.

(82) It appears from the data in Tables 25 and 26 that half or more of the skeleton of the foetus and infant, but a third or less of the adult skeleton, is water. The proportion of water in the femur shaft falls during development from about 35% in the foetus at 14 weeks gestation to about 12% in an adult (Widdowson and Dickerson, 1964). In the epiphyses of the femur, the water content falls from about 8085% in the foetus to about 50% by age 1 l- 12 years (Dickerson, 1962).

(83) There is little fat in the skeleton in early life, but the fat content increases substantially during maturation, largely because of the replacement of active bone marrow by fat. By early


L WATER i

. 0 .* . . i

Fig. 16. Left: Ca as percent of wet weight of bone and the molar ratio Ca/P in hydrated cortical bone, as related to age. Right: Relation of ash and water content of cortical bone to specific gravity. From Woodard (1962).

adulthood essentially all marrow in shafts of long bones and part of that in the spongiosa is inactive, fatty marrow. In adults, fat may represent as much as 20-25% of the weight of the skeleton.

(84) Several direct measurements of the ash content of the fetal, infant, or adult skeleton have been reported (Table 26). The results are highly variable, perhaps in large part because of technical differences in dissecting, storing, and ashing the skeletons.

(85) The data in Table 26 indicate that the ash content of the skeleton increases substantially from birth to adulthood. The ash content of the skeleton appears to represent less than 20% of total skeletal weight in the infant. Among modern determinations of the ash content of the adult skeleton, values for six males are 26.630.9% (mean 28.5% +_ 1.1%) and values for two female subjects (one of whom had been seriously ill for an extended period before her death at age 67 years) are 21.2% and 21.5% of the weight of the fresh skeleton (Table 26). The suggested difference with gender is inconsistent with results for individual bones or bone parts and probably is not real. For example, Dickerson (1962) determined water, fat, collagen, N, Ca, and P contents of femurs of 62 human subjects ranging in age from 12 weeks gestation to 35 years and found no difference in the composition of bones of the two genders at any age. Also, Quelch et al. (1983) found no difference with gender in the mineral or organic portions of femoral cortex from 22 adult subjects.

(86) Moreover, the relatively low values for the two female subjects are inconsistent with indirect but probably more reliable estimates based on data for total-body Ca, of which about 99% is found in the skeleton. The skeleton of a typical 35-year-old female is estimated to weigh 7.8 kg and (as described later) to contain 860 g Ca. Since the Ca content of bone ash is about 37.5% in the adult, the ash content of the skeleton is estimated as


[(860/0.375)/7800] x 100% =29.4%, which is about one-third higher than determined in the two female subjects. For males, the indirect estimate agrees closely with the direct measurements. Based on a skeletal weight of 10,500 g and Ca content of 1180 g, the ash content of the skeleton would be [(1180/0.375)/10,500] x 100% = 30%, compared with the mean value of 28.5% determined for the six male subjects. A lower ash content is expected for elderly persons, because the rate of loss of bone tissue at higher ages is expected to be greater than the rate of reduction in total skeletal mass.

(87) Indirect estimates of the ash content of the skeleton can also be made for children, based on gender- and age-specific estimates of total-body Ca given in a later section. The following reference values are based on consideration of both direct measurements and indirect estimates. The assumption is made that the ash content of the skeleton is independent of gender.

Reference values for ash content of skeleton (% by weight): Infant: 20%

1 year: 23% 5 years: 24%

10 years: 24% 15 years: 24% 35 years: 29%.

Elemental content of bone and bones (88) Woodard (1962, 1964) determined the elemental composition of hydrated cortical

bone of diaphyses of apparently normal long bones of four children 2-5 years old, ten children 6-13 years old, and 24 adults 20-74 years old (Table 27). The data indicate that, between early childhood and mature adulthood, there is an increase in the Ca content of cortical bone as a percentage of weight, a decrease in H, 0, and N, and no clear change with age in C, Mg, or P. The Na and S contents were determined only for adult bone.

(89) Yoshinaga et al. (1989) determined the concentrations of several elements, including Ca, Fe, K, Mg, Mn, Na, P, Zn, C, and N, in dried ribs from Japanese subjects aged 2 months to 82 years. They concluded that the Fe concentration was significantly higher and the P concentration significantly lower in males than females. Ca, P, Fe, Mg, Na, and Zn and some trace contaminants showed noticeable variation with age. Data for Na and Mg are shown in Fig. 17.

(90) When bones are dried and defatted, the remaining material is mainly bone mineral, of which Ca and P are measures, and collagen and other proteins, of which N is a measure. Absolute amounts of Ca and mass ratios Ca:N and Ca:P in various dried, defatted bones and

Table 27. The elemental composition of hydrated cortical bone

% by mass Age (Y) Number C Ca H Mg N Na 0 P s

2-5 4 15.7 20.1 4.0 0.2 4.5 45.4 10.1 6-13 10 15.8 20.9 3.9 0.2 4.4 45.0 9.8

20-74 24 15.5 22.5 3.4 0.2 4.2 0.1 43.5 10.3 0.3

From Woodard (1962, 1964); also see Woodard and White (1986).


, , . 0 FEMME UALE , ( , , , , 0 10 20 30 40 50 60 70 80

AGE (Y)

, 1

0 10 20 30 40 so 60 70 80

AGE (Y) Fig. 17. Changes with age in the Na and Mg contents of dried ribs from Japanese subjects. From Yoshinaga et al.

(1989).

bone parts are given in Table 28. Calcium typically represents about 24% of the weight of dry, fat-free bones. Much smaller values are found in the early fetal period, and somewhat smaller values are found for whole long bones from infants and children, due in part to a low Ca to ash ratio for the epiphyses. Also, during the suckling period there is a fall in the degree of calcification of the cancellous bone of the metaphyses (Dickerson, 1962). The ratio Ca:P appears to be fairly constant after early gestation, except in the epiphyses, where this ratio decreases continually throughout the growth period. The ratio CazN probably increases until birth, decreases with deminerahsation of the skeleton during the suckling period, and then increases again until the skeleton is mature.

(91) The mass percentage of Ca in whole bones and bone parts, including bone tissue, increases substantially from the prenatal period to adulthood as the water content falls (Table 29). The following reference values for the mass percentage of Ca in bone tissue of young children, adolescents, and adults are based mainly on data of Woodard (1962, 1964) for the diaphyses of long bones, but Woodard’s measured values have been decreased slightly because the organic and water contents of the sampled sites are probably lower than average for all mineral bone. Reference values for ages 0 and 1 year were reduced further to reflect relatively high organic and water contents of bone at those ages compared with age 5 years, say.


Table 28. Absolute amounts of Ca and runsa ratios Ca : N and Ca : P in dry, defatted bone

45

Bone: Reference No. Age Ca (% of

total mass)

Mass ratios

Ca:N Ca:P

1. Skull (parietal, frontal) MacDonald (1954)

2. Skull (parietal): Toverud and Toverud (1933)

3. Rib, without marrow: Baker et al. (1946)

Follis (1952)

Quelch et al. (1983)

Yoshinaga et al. (1989)

4. Rib, with marrow: Follis (1952)


Kramer et al. (1939)’

5. Tibia, whole: Booher and Hansmann (1931)

6. Femur, tram Baker et al. (1946)

7. Femur, compact: Baker et al. (1946)

Rogers et al. (1952)”

Dickerson (1962)

21 Foetus (28-43 wk)

24.4 2.26

1nfant~ 24.0 2.26 Infantb 21.6 2.18

!

:

2 1 1 6

2

6

2; 6

3-11 mo 1.1-1.8 y 15Y 25-75 y

2.5-3 y 11 Y 17 Y 21-66 y

39-70 y

0.17-19 y 2&39 y 40-59 y 60-82Y 0.17-82 y

24.3 24.6 26.8 25.4

25.6 24.1 25.1 26.1

26.9

22.5 24.7 24.1 23.6

4.52 4.66 5.09 5.03

2.13 2.23 2.18 2.21

2.24

1.88 1.96 1.96 1.95

4.86

2 1

:,

26 48

1 1 1 1 1

2.5-3 y 23.2 2.11 1lY 22.0 2.14 17 Y 23.0 2.13 2166 y 23.4 2.15

Infant’ 21.7 2.24 Infantb 20.4 2.13

17 wk foetusd 24.9 2.09 Newborn 22.4 2.02 Newborn 22.7 2.14 10 Y 22.0 2.14 29 Y 22.2 2.20

t Infant 16.7 Infant 16.5

6 32-69 y 25.2 5.5

6 32-69 y 25.6 5.8

7 6

2: 3

0.75-3 y &lo y 11-17 y 20-6lY 64-9oY

13 wk foetusd 15 wk foehud 22 wk foehud 26 wk foetuad 32 wk foetusd

4.4 5.1

:3 5:3

18.9

z.s 2417 24.7

3.22 2.07 4.22 2.22 4.46 2.22 5.05 2.32 4.90 2.26


Table 28--(eontinued)

Bone: Reference No. Age Ca(%of

total mass)

Mass ratios

Ca:N Ca:P

Quelch et al. (1983)

8. Femur, epiphyses: Dickerson (1962)

9. Femur, non-epiphysial parts:’ Dickerson (1962)

10. Femur, whole: Dickerson (1962)

Newborn 24.6 4.88 2.27 2-17 d 24.2 4.82 2.25 24.5 mo 23.1 4.52 2.21 5-9 mo 24.9 4.69 2.26 l-2 y 24.6 4.70 2.21 11-12 y 25.3 5.18 2.21 16~ 25.1 5.62 2.22 18-35 y 26.4 5.58 2.29

36-40 wk 24.4 2.04 4-11 y 26.2 2.15 16-82 y 25.9 2.24

13 wk foetusd 0.50 0.06 0.58 15 wk foetusd 1.29 0.14 1.09 22 wk foetus’ 1.08 0.12 1.36 26 wk foetus* 0.92 0.09 1.35 32 wk foetusd 0.69 0.06 1.37 Newborn 1.28 0.11 1.84 2-17 d 1.44 0.13 1.98 24.5 mo 1.56 0.13 1.91 5-9mo 2.97 0.27 2.22 l-2 y 4.42 0.39 2.29 11-12 y 15.45 1.88 2.17

12 wk foetus 16wkfoehu 20 wk foetus 26 wk foetus 32 wk foetus Newborn 2-17 d 2mo 4.5 mo 1Y 11-12 y

13 wk foetusd 10.9 15 wk foetus* 16.1 22 wk foetus* 16.0 26 wk foetusd 16.6 32 wk foehu* 15.6 Newborn 16.7 2-17 d 16.2 2-4.5 mo 14.8 5+mo 14.3 l-2 y 14.6 11-12 y 18.9 18-35 y 23.0

16

:i

23.5 21.5 21.5 19.5 18

ii.5

2.75 2.6

Es 317 4.0

::;5

:*;5 415

1.50 1.61 2.09 2.16 2.18 2.20

% 2.22

2124 2.17 2.13

2.25 2.17 1.78 2.03 1.81 2.19 2.04 2.14 3.62 2.21 4.82 2.34

’ Full-term infants born of mothers with good diet during pregnanq. b Combined data for prematore iofants, twins, and full-texm infants born to mothers with insu&ient diets during

P=.gnancy. ’ As reported by Follis (1952). * Approximate mean age of subjects. ’ Typical values for age ranges, as read from a graph. ’ Rounded values read from graphs.


Table 29. The calcium content as percent wet weight of different bones, bone types, and whole skeleton at different ages

Investigator Bone’ Age/sex Ca (% wet weight)

Dickerson (1962) Femur

Swanson and Iob (1940) Skeleton

Borisov (1973) Skeleton

Klose (1914)

Booher and Hansmann (1931)

Borisov (1973)

Dyson and Whitehouse (1970)

Dickerson (1962)




Agna et al. (1958)

Woodard and White (1986)

Moore et al. (1968)

Skeleton

Tibia

Skeleton Cranium Long bones Ribs Vertebrae/sacrum Vertebral trab.b Vertebral trabab Femur trab.b Femur mid&aft FenXU

Tibia

%a Skeleton Tibia Rib Ulna Skeleton Skeleton

Skull’ Rib’ Ilium’ Cortical bone from diaphyses of long bonesd

Skeleton’

Prenatal: 12-14 wk 15-16 wk 20-24 wk 25-28 wk 3@34 wk 4.1 mo 9.1 mo 10 mo <5mo 5-6 mo 6-7 mo 7-8 mo 8-9 mo

Postnatal: Newborn/M 33 d/F Newborns/M Newborns/F Newborns

17 mo 20 mo 20 mo 20 mo Newborns 2-17 d 2-4.5 mo 5-9 mo l-2 y 11-12 y 18-35 y

35 Y/M

46Y/M

48 YIM 60 Y/M 23-62 y (mean 35 y)

2-5 y 6-13 y 20-74 y

67 YIF

:4 413 5.3 5.6 4.1 6.9 8.3

5zto.4 6rtO.5 6kO.4 7*0.5 7zto.4

:I: 6.0 5.7

8+0.8 8.8 8.0

15.2 4.9 4.8 4.7 4.7

19.4 6.1 5.8

::;

1:; 13:4 11.9 14.8 17.6 11.0 11.4 12.7 15.0 10.7 11.5 10.2 19.7 17.0 14.6 20.1 20.9 22.5

7.0

a Whole bone or whole skeleton, unless otherwise indicated. b Trabecular bone with marrow. ’ Marrow-free. d Scraped free of soft tissues. ’ Including periarticular tissues.


Reference values for the Ca content of bone as % wet weight: Infant: 16.5%

1 year: 17% 5 years: 19%

10 years: 20% 15 years: 20.5% 35 years: 21.5%.

The Ca accretion rate during growth (92) The Ca content of the total body (TBCa) or of the skeleton, which contains about

99% of the body’s Ca, has been measured by chemical analysis in several cadavers (Tables 30 and 31). Also, numerous external measurements of TBCa in living subjects, mainly adults, are now available (Nelp et al., 1972; Cohn et al., 1974, 1976, 1980, 1986; Ellis and Cohn, 1975; Mazess et al., 1981a,b; Kennedy ef al., 1982; Horsman et al., 1983, Ott et al., 1983). Based on the chemical analyses summa&d in Table 3 1 and the external measurements cited above, the total mass of skeletal Ca is estimated at 1180 g in a healthy 35year-old male weighing 73 kg and standing 176 cm tall, and 860 g in a healthy 35-year-old female weighing 60 kg and standing 163 cm tall.

(93) TBCa in the near-term foetus and newborn is about 0.8% of total-body weight (Tables 30 and 31). There is a paucity of direct information on TBCa for the period between infancy and adulthood. Balance considerations, radiomorphometry, and chemical analysis of bones indicate that there is a kind of “osteoporosis” or decalcification of the skeleton during the first year or more of life that could result in a slight, temporary decline of TBCa/TBW, particularly in children receiving human milk (Stettner, 1931; Brock, 1932; Steams, 1939; Dickerson, 1962; Widdowson and Dickerson, 1964; Gam, 1970). The absolute values of TBCa listed in Table 31 for three reportedly well-nourished Jamaican infants (Garrow and Fletcher, 1964) are probably low for the given ages, considering their small body sixes. The 4.5-year-old subject, who died of tuberculous meningitis after two weeks illness, was described as “moderately nourished but rather thin” (Widdowson et al., 1951); the indicated TBCa might not be unusual for his age and height, but TBCa/TBW could be abnormally high in this case.

Table 30. Total body calcium in the foetus based on chemical analyses

gCaper Reference Age Sex Wt (kg) Ca (g) kg body wt

Swanson and Iob (1940) 4.1 mo 0.53 2.59 4.9

Borisov (1973) <5mo 0.37 f 0.08 1.76ztO.S 4.8 5-6mo 0.64*0.10 3.89hO.5 6.1 6-7 mo 1.07zlz0.10 6.44*0.7 6.0 7-8 mo 1.41f0.17 10.00* 1.5 7.1 8-9 mo 2.06f0.17 14.27kl.4 6.9

Swanson and Iob (1940) 9.1 mo 2.06 14.5 7.0 10.0 mo 3.20 26.0 8.1

(94) A model of TBCa accretion (g) in males that has been widely used is the curve of Mitchell et al. (1945):

TBCa(A) = 28 + 86.8284 - 16.5105/I’+ 1.5625A3 - 0.04114A4 (g),


Table 3 1. Total body calcium in newborns, children, and adults baaed on chemical analyses

49

Reference Age/sex

gcaperkg body wt/g Ca

Wt erg) Ht (a) Ca (g) percmht

Camerer (1900, 1902)

Widdowson and Spray (195 1)

Klose (1914)

Borisov (1973)

Garrow and Fletcher (1964)

Widdowson et al. (195 1)




Moore et al. (1968)

Widdowson er al. (1951)

Nelp et al. (1972)

Newborns Newborn/F Newborn/M

Newborns

2.8zt0.3 3.1 3.4

3.5 28.2 8.1lO.55

Newborn/M 33 d/F

Newborns

3.2 3.1

518 50 53

51a

518 51a

518

20.4 zt 4.4 7.310.40 23.2 7.510.46 25.0 7.410.47

25.8 8.1/0.51 23.6 7.610.46

3.4zko.4 27.3 + 5.9 8.010.54

9mo 7.5 65 54 7.510.83 10 mo 4.7 57 33 7.210.58 13 mo 7.7 71 69 9.410.97

4.5 y/M

35 Y/M

46 Y/M

48 YIM 60 Y/M

67 YIF

25 Y/M 42 YIF 48 Y/M

58 YIM 59 Y/M 53 Y/F 34 Y/F 73 YIF 59 YIM

14

71

54

62 74

107

183

169

169 172

228 16.312.13

1126 15.916.15

1026 19.0/6.07

1228 19.817.27 1139 15.416.62

60 - 628 lO.S/?

72 179 1304 18.117.28 45 169 856 19.0/5.07 64 - 1022 16.0/?

70 168 871 12.415.18 90 183 1039 11.515.68 45 155 792 17.615.11 63 161 767 12.214.76 56 163 741 13.214.55 92 173 1029 11.215.95

’ Assumed height; typical for Western newborns.

where A is age in years (4520). This equation was based on total-body growth data for boys from 5 to 17 years old, the assumptions that the Ca content at birth is 0.8% of body weight and in the adult is about 1.6% of body weight, and the assumption that “the change from the infantile to the adult percentage occurs progressively throughout growth, but more rapidly when growth is more rapid” (Mitchell et al., 1945). Mitchell’s estimates of TBCa/TBW in newborns and adults were based on chemical analyses and are reasonably consistent with current data (Table 31).

(95) Mitchell’s Ca accretion curve and various other measurements or models of TBCa accretion in males are summarised in Fig. 18. Measurements and models for females are summa&d in Fig. 19. Estimates for young children based on chemical analyses (Table 31) are assumed to apply equally to both genders.

(96) Values in Figs. 18 and 19 labelled as “extrapolated from femur” are based on the method of Mitchell but use relative calcification data of Dickerson (1962) for the femur (see Table 29). Specifically, the assumptions are made that TBCa/TBW is 0.008 for a newborn and 0.016 for a 20-year-old male, that relative calcification of the femur at a given age (meaning the percentage of the fresh femur weight at that age represented by Ca, divided by


0: , ( , , / , , , / 0 2 4 6 8 10 12 14 16 18 20

Age (Y)

Fig. 18. Increase with age in total-body Ca in males, as estimated by different methods.

m_ ..__.~_~~ /.... -.-I’:

--.CWtibi~l7X&i ,I’. __ P

x- *cbtst!mm * d. (SE) ,/’

NY- ,,,’ I

,_-- /” /,’ I

I A’ **

5OC- ,,I.

,z’ ’ ,‘*,

y x*

m- ,;’ ,Pd”X ,,,.,’ , ,

SOI- ,,..‘:d ‘A’ -’ p’*-X

200- /p;‘-6 ‘Y_ B;9S Females

I / I I I I / I / / 0 2 4 6 8 10 12 14 16 18 20

Fig. 19. Increase with age in total-body Ca in females, as estimated by different methods.

the corresponding value for young adults) is typical of the whole skeleton, and that the skeleton represents a fixed percentage of total-body weight at all ages.

(97) Values in Figs. 18 and 19 derived from the dry, fat-free skeletal weight are based on the estimate (discussed earlier) that Ca represents 24% of the weight of the dry, fat-free skeleton. Crude estimates for the weight of the dry, fat-free skeleton were obtained for some ages from data of Trotter et al. (1970, 1974) by restricting attention to a few selected age ranges covering no more than 2 years each, assigning the median of the skeletal weights in a selected age range to the median age in that range, assuming that there is no difference with gender in TBCa through age 12 years, and ignoring potential differences with race at all ages.

RADIOLOGICAL PROTJXTION DATA: THE SKELETON 51

(98) The “height-age” model is based on the observation that TBCa (g) is nearly proportional to the cube of height (Nelp et al., 1972; Harrison et al., 1980). More specifically, measurements of TBCa by chemical analysis or total- or partial-body counting of neutron- induced 4gCa can be predicted reasonably well by a function of the form 185Hz, where His height in m and 2 is a function of age that increases from about 2.8 during early childhood to about 2.9 by age 10-13 years and to 3.1-3.2 by sometime during young adulthood. A simple function that satisfies these conditions is Z = 2.75 + 0.013 A, where age A is in years.

(99) The “cortical area model” is an extension of a method of Gam (1970), who assumed that the weight of the dry, fat-free skeleton is proportional to metacarpal “cortical volume”, estimated as cortical area at the midpoint of the second metacarpal times the length of the bone as determined by radiographic morphometry. Gam determined the proportionality constant from typical adult metacarpal cortical volume and typical dry, fat-free weight of the adult skeleton. The cortical area model whose predictions are shown in Figs. 18 and 19 considers a larger portion of the skeleton, reduces the importance of random errors in measurements, and considers a larger number of factors contributing to TBCa. Spe&cally, it is assumed that TBCa is proportional to R(A) x height x C(A), where C(A) is an average of relative cortical areas at age A y determined from several “cylindrical” bones (see Table 14), and R(A) is the estimated average density of cortical bone at age A normalised to 1.0 at age 40 years. The proportionality constant derived from an assumed TBCa of 1180 g for a typical adult male is 676. Thus, the cortical area model is

TBCa (g)=676x R(A) x Hx C(A).

The function R(A) is taken to be CD(A)/I.9, where CD(A) is defined by eqn (S), paragraph (72).

(100) The different approaches to estimating Ca accretion during growth are reasonably consistent, with the exception of the method of Christiansen et al. (1975), which is based on photon absorptiometry measurements of bone mineral content (BMC) in the distal part of the forearm. The conversion factor from local BMC to TBCa derived for adult skeletons was applied by Christiansen and coworkers to all age groups, a problem that may lead to sizeable errors at some ages because of the considerable variation with age in the fraction of total bone mass represented by the limbs (e.g. see Trotter and Hixon, 1974).

(101) The following estimates of the Ca content of the infant and adult skeletons were based on direct measurements. Estimates for young children and adolescents were based mainly on the height-age model. The mass of total-body Ca is assumed to be independent of gender from birth to age 10 years. For present purposes, no distinction is made between skeletal Ca and TBCa.

Reference values for skeletal Ca: Infant: 28 g

1yearzlOOg 5years:UOg

10 years: 460 g Male, 15 years: SO g Female, 15 years: 760 g Male, 35 years: 1180 g Female, 35 years: 860 g

(102) Reference values for the weight of bone tissue are based on these reference values for skeletal Ca, together with reference values given earlier for the Ca content of wet bone.


Reference values for the weight of bone tissue: Infant: 170 g

lyesuz59og 5 years: 1260 g

10 years: 2300 g Male, 15 years: 4050 g Female, 15 years: 3700 g Male, 35 years: 5500 g Female, 35 years: 4000 g.

Cartilage

Function and composition of cartilage

(103) Cartilage is a pliable, resistant, dense connective tissue composed largely of collagen and noncollagenous proteins. Cartilage acts as a shock absorber and as a bearing surface that allows bones to move smoothly against one another while supporting great weight. It also serves to protect some tubular organs and makes possible the growth in length of bones (Fawcett, 1986). Most of the axial and appendicular skeleton is first formed as cartilage but is later replaced by bone.

(104) Cartilage consists of cells, called chondrocytes, embedded in a gel-like matrix. Unlike other connective tissues, cartilage has no blood vessels and no nerves. While bone cells must be near a vascular space because of the impermeability of bone, cartilage cells receive nutrients via a permeable matrix that is in direct contact with extracellular fluid (Marks and Popoff, 1988).

(105) Three kinds of cartilage, called hyaline, elastic, and fibro cartilage, are distinguish- able by the amount of gel-like matrix and the relative abundance of the collagenous and elastic fibres embedded in this matrix. Hyaline cartilage is found on the ventral ends of the ribs, in the tracheal rings and larynx, and on the joint surfaces of bones. Elastic cartilage is found primarily in the external ear, the walls of the external auditory and eustachian tubes, and the epiglottis. Fibrocartilage is associated with the intervertebral discs, certain articular cartilages, the symphysis pubis, the ligaments of joints, and sites of attachment of certain tendons to bones.

(106) Hyaline cartilage is the most abundant and most commonly studied type. The extracellular matrix of hyaline cartilage is composed principally of thin (10-20 nm) collagen fibrils forming a loose meshwork throughout the matrix and intertwined with proteoglycan aggregates (Fig. 20). Proteoglycans are molecules containing a core of protein to which carbohydrates, called glycosaminoglycans, are attached. The principal glycosaminoglycans of cartilage matrix are chondroitin sulphate and keratan sulphate (Fawcett, 1986).

(107) On the articular surfaces of the ends of long bones, the thin layer of cortical bone is covered by a layer of hyaline cartilage called articular cartilage. The proteoglycan of articular cartilage provides this tissue with extreme elasticity and allows it to recover quickly and completely from intermittent pressures (Roughley and White, 1980). Histochemical studies of human articular cartilage have demonstrated important changes with age in this tissue, particularly in the proteoglycan subunits (Elliott and Gardner, 1979; Roughley and White, 1980; Roughley et al., 1987). Changes between birth and mature adulthood apparently include a decrease in the proteoglycan content of cartilage, a decrease in the size of the proteoglycan subunit, an increase in keratan sulphate relative to chondroitin sulphate,


Hyaluronic acid

molecules

Collagen fibrils

Proteoglycan subunits

Glycosaminoglycan

Fig. 20. Schematic representation of the organization of the extracellular matrix of cartilage. The matrix is composed of collagen fibrils with intertwining proteoglycan aggregates occupying the interstices. From Fawcett

(1986).

changes in the nature of the chondroitin sulphate chains, an increase in protein relative to glycosaminoglycan, and a change in composition of the core protein of proteoglycan (Roughley and White, 1980). Measurements on articular cartilage of the femur (lateral femoral condyle) indicate that glycosaminoglycans may form about half of the dry weight of cartilage at birth but only about 15% of the dry weight of adult cartilage (Elliott and Gardner, 1979). Chondroitin sulphate accounts for almost all of the glycosaminoglycans at birth but with increasing age are replaced to some extent by keratan sulphate (Table 32). The data indicated in Table 32 are for superficial samples of articular cartilage, taken at depths of O-100 pm; samples taken at 900-1000 pm revealed similar changes with age from birth to early adulthood but indicated only a small decline in chondroitin sulphate between ages 20 years and 70 years (Elliott and Gardner, 1979). Measurements by Roughley et al. (1981) on knee and shoulder cartilage from human subjects of various ages indicate that changes with age are similar for high and low weight-bearing human articular cartilage.

(108) Articular cartilage varies in thickness in different joints and different regions of a given joint, with reported values ranging from 0.2 to 6 mm (Weinmann and Sicher, 1955; Anson, 1966). Roughley and White (1980) observed that the thickness of articular cartilage covering the subchondral bone of the distal femur decreased with increasing age in mature humans.

(109) The water content of cartilage is similar to that of the soft tissues and much higher than for bone. Water apparently represents about 80-85% of the weight of cartilage in the developing human foetus (Iob and Swanson, 1937) and perhaps 70%, as an average, in the mature adult (Vierordt, 1906; Manery, 1954; Eastoe, 1961a; ICRP 1975), but reported values for adult humans are sparse and variable. The ash content of dry cartilage tissue is roughly 4%, with reported values in the range 2.6-5.6% (Eastoe, 1961a, ICRP 1975). The specific gravity of fresh cartilage is about 1.1 (Vierordt, 1906; ICRP 1975).


Table 32. Changes with age in the composition of the matrix of human articular cartilage

Percentage of total glycosaminoglycan by weight

Age of subject Total Cbondroitin Keratan Hyaluronic

(Y) glycosaminoglycan” sulphate solphate acid

0 251 98.2 1.8 co.2 0 394 99.3 0.7 <O.l 0 417 94.6 5.4 <O.l 2 312 94.4 5.6 <0.2 4 239 96.7 2.6 0.7 8 177 91.2 8.8 <0.3

10 131 89.2 10.8 <0.4 12 82 90.8 9.2 <0.6 12 119 84.0 14.4 1.6 13 131 83.2 15.0 1.7 18 126 75.7 21.1 0.8 18 138 70.8 27.4 1.9 20 125 79.9 18.5 1.6 20 134 89.0 9.2 1.7 22 137 84.5 14.0 1.5 26 96 83.9 11.0 5.1 32 105 69.3 28.8 1.9 36 108 66.0 31.8 2.2 37 165 85.1 12.7 2.2 39 127 80.7 14.6 4.7 43 78 78.8 12.3 8.9 43 106 77.8 15.3 6.9 46 77 75.8 19.4 4.8 47 92 68.6 27.5 3.9 51 69 68.3 25.9 5.8 53 141 78.0 20.4 1.7 55 196 74.1 24.3 1.6 56 164 82.0 13.1 4.9 68 74 78.2 15.3 6.5 70 83 83.6 12.5 3.9

a &mg dry cartilage. Based on data of Elliott and Gardner (1979) for presumably normal cartilage obtained

post mortem from right femur (sampled at depths of less than 100 q).

(110) The potassium content of cartilage varies with cartilage type and appears to decrease substantially from birth to adulthood in conjunction with a decrease in cartilage cells (Manery, 1954; Johnson, 1966). The concentration of potassium in cartilage of the adult human is estimated as 0.1% of wet weight (Williams and Leggett, 1987). Anderson ef al. (1964) determined that dry, human articular cartilage powder is 14-15.4% nitrogen and 1.3- 1.4% sulphur by weight and found that these concentrations vary little between ages 10 years and 90 years. According to Eastoe (1961a), the sulphate content of human costal cartilage decreases substantially between early childhood and middle adulthood.

findochondral osszjication (111) Bones in the extremities, in the pelvis, in the vertebral column, and at the base of the

skull are called “cartilage bones” because they are first formed of hyaline cartilage, which is later replaced by bone in a process called endochondral ossification (Fig. 21). This process has been best characterised, both qualitatively and quantitatively, in long bones, where the following stages are evident between the early gestational period and the end of skeletal


m hypertrophied cartilage

@ fibrous tissue

m cancel lous bone

compact bone

D E F G

Fig. 21. Schematic representation of the maturation of a long bone in which the length of the bone has been kept constant. Approximate age scale: A, 6th prenatal week; B, 7th prenatal week, C, 12th prenatal week; D, 16th prenatal

week to 2 years; E, 2-6 years; F, 6-16 years; G, adulthood. From Roche (1980).

maturity: (1) the cartilage model is formed; (2) a periosteal bone collar appears; (3) cartilage begins to calcify, starting in the middle of the shaft of the hyaline cartilage model; (4) blood vessels penetrate into cavities created by degeneration of chondrocytes, dividing the calcified cartilage matrix into upper and lower zones of ossification and later entering the upper and lower zones and beginning ossifkation centres at those locations; (5) as the bone ceases to grow in length, the lower and upper epiphyseal plates disappear, and the bone marrow cavity becomes continuous throughout the bone, and blood vessels of the diaphysis, metaphyses, and epiphyses intercommunicate (Fawcett, 1986).

(112) During the growth in length of the cartilage model after the appearance of the diaphyseal center of ossification, the chondrocytes in the adjacent regions of the epiphyses are arranged in longitudinal columns (in contrast to the small groups of chondrocytes usually found in hyaline cartilage) (Fawcett, 1986). Along the lengths of these columns are several distinct zones of cells: farthest from the diaphyseo-epiphyseal junction is a zone of proliferation, where frequent division of the small flattened cells enables continuous elongation of the columns; this is followed by a zone of maturation, in which cells that have stopped dividing begin to enlarge; next is a zone of hypertrophy or provisional calcification, where the matrix becomes the site of Ca deposition; and at the diaphyseal end of the columns IW W&E


is a zone where the chondrocytes are degenerating (Fawcett, 1986). The number of cells per column and the proportion of proliferative cells vary with the stage of development and appear to correlate with growth velocity (Kember and Sissons, 1976; Gruber and Rimoin, 1989). In human rib cartilage, the number of cells per column and the proportion of proliferative cells per column were found to be significantly greater in 10 foetuses and newborns than in 15 subjects aged 0.3-16 years (12.6+_ 1.0 versus 8.4kO.4 cells per column, respectively, and 39.6% _+ 6.9% versus 24.4% + 2.5% proliferative cells, respectively) (Gruber and Rimoin, 1989). In human femur cartilage, the number of cells per column and number of proliferating cells is somewhat greater and there is a more gradual decrease in the number of cells after birth than has been observed in rib cartilage (Table 33). The “cycle time” for the cartilage cells of the proliferation zone of the plate has been estimated to be about 20 days for ages 2-8 years (Kember and Sissons, 1976).

(113) Observed rates of longitudinal growth of the distal plate of the femur of boys and girls are plotted in Fig. 22, which is based on data of Kember and Sissons (1976). Small differences with gender in measured means before the age of 8 years were assumed to be insignificant. The adolescent growth spurt begins and ends earlier in girls than in boys. After the growth spurt, the rate of growth falls sharply.

Table 33. Changes with age in the cells of cartilage from the human femur

Age (Y) Sex

Maturing and proliferating

cells

Hypertrophic Cells Width of Width of

inert zone columnar zone No. Height (lan) (mm) (mm)

0 M 0.9 M 1.3 F 2 M 2 M 3.5 M 5 M I M 8 M

13 M 14 M 28 6 39 14 F 21 2 25

62 43 46 49 48 54 36 36 34 21

12 35 8 38 8 34 6 30 8 35

38 33 31 29 30

0.X 0.6 0.9 0.8 1.1 1.0 1.2 0.6 0.5 0.5 0.8 0.5 0.1 0.5 0.1 0.4

0.9 0.7 0.8 0.7 0.7 0.8 0.6

From Kember and Sissons (1916).

Amount of cartilage in the body (114) In this document, all cartilage, including nasal cartilage and the auricle of the ear, is

considered as part of the skeleton. (115) Data of Swanson and Iob (1940) and Borisov (1973) indicate that the fraction of the

skeleton that is cartilaginous tissue decreases from about 4045% at four months’ gestation to about 25-35% at birth (Table 34). Since these values apparently exclude cartilage not considered as part of some bone, the upper values (45% and 35%, respectively) may be reasonable estimates for these ages.

(116) From the dissection of an adult female subject, a value of 3.6% of total-body weight was obtained for “cartilage, joints, and periarticular tissue” (Moore et al., 1968). The principal investigator in that study has suggested that cartilage might represent about 1.5% of total-body weight (personal communication to authors of ZCZiP Publication 23, 1975).


01 0 2 4 6 8 10 12 14 16 18

Ageinyears

0

Fig. 22. Rate of longitudinal growth of the distal plate of the femur in boys and girls, based on data of Kember and Sissons (1976).

Table 34. Amount of cartilage in fresh bones and skeleton of foetus and newborn, as percentage of total weight of bones or skeleton

Investigator Age Bones Total weight of bones (g)

Weight of cartilage

(% of total)

Swanson and Iob (1940) Prenatal: 4.1 mo ? 9.1 mo

10 mo ?

Borisov (1973) Postnatal: Newborn Newborn Newborn Newborn Newborn Newborn Newborn

Total skeleton 63.5 42.5 Total skeleton 121 41.7 Total skeleton 211 36.1 Total skeleton 312 30.3 Total skeleton 399 36.1

Femora 36.7 Tibiae + Fibulae 23.2 Humeri 17.4 Ulnae+Radii 9.7 Scapulae 10.5 Pelvis 24.9 Total skeleton 388

52.0 40.1 47.1 25.8 27.6 28.1 25’

’ Rough estimate, cartilage apparently was not measured in all bones.

(117) Reference values for the total mass of cartilage in newborns and adults are based on the few available reported measurements. The mass of cartilage in the newborn is assumed to represent 35% of the weight of the skeleton, or 130 g. For the adult, cartilage is assumed to represent 1.5% of total-body weight. No information was found on the total weight of cartilage in the body between early infancy and adulthood. A model of the rate of change with age of the cartilage content of the skeleton was based on consideration of established qualitative changes with age at different skeletal sites and the assumption that the decline in the cartilage content (as percentage weight) during growth parallels the decline in the water content of the skeleton (Tables 25 and 26).


Reference values for weight of cartilage: Infantz 130 g

1 year: 360 g 5 years: 600 g

10 years: 820 g Male, 15 years: 1140 g Female, 15 years: 920 g Male, 35 years: 1100 g Female, 35 years: 900 g.

Bone marrow

Structure and function of bone marrow

(118) Bone marrow is a soft, highly cellular tissue that occupies the cylindrical cavities of long bones and the cavities within the trabecular bone of the vertebrae, ribs, sternum, and the flat bones of the cranium and pelvis. Total bone marrow consists of a sponge-like, reticular, connective tissue framework called stroma; myeloid (blood-cell-forming) tissue; fat cells; small accumulations of lymphatic tissue; and numerous blood vessels and sinusoids (Weiss, 1966; Fawcett, 1986).

(119) There are two kinds of bone marrow, red and yellow. Red marrow is haemopoietically active and gets its colour from the large numbers of erythrocytes (red blood cells) being produced. Yellow marrow gets its colour from fat cells, which occupy most of the space within the stroma of the yellow bone marrow, although a few primitive blood cells also occur.

(120) In addition to erythrocytes, red marrow produces all granulocytes and monocytes (two types of white blood cells), platelets (subcellular structures involved in coagulation of the blood), and a substantial portion of lymphocytes (another type of white blood cell). Yellow marrow does not produce blood cells but may be converted to red marrow in response to unusual demands for blood cells (Brobeck, 1979; Kricun, 1985).

(121) Bone marrow first appears during the second or third lunar month in the developing bone. At this time it is not yet a haemopoietic tissue but is associated with formation, growth, and modelling of bone. It assumes major haemopoietic functions during the latter half of fetal development (Fig. 23) but also maintains some osteogenic functions throughout life. In addition to its haemopoietic and osteogenic functions, the marrow contains free macrophages as well as fixed reticular cells that are capable of phagocytosis, inactivation of toxins, and other functions of the reticuloendothelial system. The marrow destroys some imperfectly produced, aged, or damaged erythrocytes, a process called erythroclasia. It is also an immunologically capable tissue, although it is less powerful in this regard than the spleen and lymph nodes (Weiss, 1966).

Haemopoietic stem cells (122) A small number of cells in the bone marrow, called stem cells, have the capacity for

both self-duplication and differentiation. If their progeny are able to differentiate into several different types of mature blood cells, they are called pluripotential haemopoietic stem cells (PHSC). The immediate progeny of a pluripotent stem cell that retain the capacity for self- renewal but are able to differentiate only into a single end-cell type are called unipotential stem cells or committed stem cells.


(00 I /

00 . \

LIVER - ,/’

\ 1 ./BONE 60 __ " 1 MARROW -_

40 >i I

, ' ' SPLEEN

20 _-.-.

,J--7-- \

/ _..:'

/ .' ,/ 'b.... \

--._ n wO 50 (00 150 200 250 200

Gestational age (d)

Fig. 23. Stages of haemopoiesis as a function of gestational age. Modified from ICRP Publication 23 (1975).

(123) A diagram of the principal myelopoietic cell lineages is given in Fig. 24. The pluripotent stem cell giving rise to all blood cells is designated the colony-forming unit or colony-forming unit-spleen (CFU or CFU-S). Some of the progeny of this cell lose their pluripotentiality and become irreversibly committed to production of erythrocytes. Studies of these unipotential progenitor cells in cultures have revealed two successive stages of stem cells, called the erythroid burst-forming units (E-BFU or CFU-B) and erythroid colony- forming units (E-CFU or CFU-E). The CFU also gives rise to a progenitor stem cell committed to formation of granulocytes and monocytes (CFU-GM), as well as the committed stem cell of thrombopoiesis (platelet production), called the colony-forming unit- megakaryocyte (CFU-M).

Cell turnover times

Erythropoiesis (124) In normal persons the red cells are produced exclusively within the red bone marrow.

In the infant, all bone marrow actively produces these cells, but with maturation the red marrow retreats from the extremities and in adults is found mainly in the vertebrae, ribs, pelvis, cranium, scapulae, sternum, and upper ends of femora and humeri.

(125) In normal erythropoiesis there is a clearly defined flow of cells from the primitive, common stem cell to the mature red cell in the blood. Upon entering the erythropoietic compartment the stem cell rapidly assumes cytological characteristics of the differentiated line. As the cytological characteristics of the nucleus and cytoplasm change, the cells receive successively different names-proerythroblasts, large basophilic normoblasts (erythroblasts), small basophilic normoblasts, polychromatophilic normoblasts, late nondividing normoblasts, reticulocytes, and the erythrocyte. In the first four cells in this lineage there is mitosis and deoxyribonucleic acid (DNA) synthesis, but these phenomena are rarely if ever seen beyond the fourth cell level (Brobeck, 1979).

(126) The overall transit time from proerythroblast to reticulocyte has been estimated at about 72 hr. The following maturation times may be typical of specific cells in this series (Cronkite, 1960):


CFU-B I

PHSC I

0 CFU-S

CFU-GM

--- CFY-E ------------________---_-________ _______________________~~~~~~~~~~~~~ ______

Barophilic erythroblast

I

Polychromatophilic erythroblest

I

Reticulocyte

I

“0 * Erythrocytes

lvlyeloblast

, Prom yelocyte ,

@

I

@ @

I

Metafnyelocyte

Band, form

Barophil Neutrophil Eoeinophil

Megekaryocyto- blest

Megekeryocyte

Pletelete

Fig. 24. Diagram of tbe principal myelopoietic cell lineages. Above the dotted line are the stem cells: pluripotential baemopoietic stem cell (PHSC); colony-forming unit-spleen (CFU-S); colony-forming unit-burst (CFU-3); colony- foxming unit-erythrocyte (CFU-E); colony-forming unit-granulomonocyte (CFU-OM); and colony-Forming unit- megakaryocyte (CFU-M). Below the dotted line are tbe morphologically recognizable cell lines that difkrentiate

from these stem cells. From Fawcett (1986).


Proerythroblast: 30 (20-40) hr Basophilic normoblast: 15 hr Polychromatophilic normoblasts: 11 hr Late nondividing normoblasts: 16 hr

The time for marrow reticulocyte maturation is about 65 hr. Active haemoglobin synthesis occurs during the first day and a half when the marrow reticulocyte synthesises roughly one fourth of the haemoglobin of the cell and then declines to a rate of synthesis of < 5% during the final day, before release of the reticulocyte into the circulation. Reticulocytes appear to spend a further maturation time of about 25 hr in blood (Trubowitz and Davis, 1982b).

Granulopoiesis (127) The earliest morphologically recognizable cell of the granulocyte series is the

myeloblast, a small nucleated cell devoid of granules. This cell transforms after about one day into a larger nucleated, granulated cell called a promyelocyte. The granulocyte lineage then diverges along three separate paths of differentiation with the appearance in the myelocytes of specific granules with differing tinctorial properties and distinctive ultrastructure (Fawcett, 1986).

(128) The entire transit time from stem cell to mature granulocyte is estimated as 10-14 days (Wintrobe et al., 1981; Fawcett, 1986). The following turnover times have been estimated for the neutrophilic series (Wintrobe et al., 1981):

Myeloblasts: 15 hr Promyelocytes: 24 hr Myelocytes: 70-104 hr Metamyelocyte to mature neutrophil: 158-200 hr.

(129) The production rate of granulocytes in humans may be on the order of 1.6 x 104/kg/ day. The majority of end-cells produced in this series are neutrophils. A large reserve of metamyelocytes, band-forms, and mature neutrophils, perhaps amounting to as much as 10 times the daily production, is maintained in the marrow and can be mobilised to meet unusual demands. Mature neutrophils are preferentially released, but many band-forms and even metamyelocytes may enter the circulation during infections (Fawcett, 1986).

Monopoiesis (130) The monocyte-macrophage cell line shares with the granulocytes a common

committed stem cell (CFU-GM). This lineage includes, in order of appearance, the monoblast, promonocytes, and monocytes. About half of the promonocytes of the marrow rapidly proliferate to generate nonproliferating monocytes. The remainder constitute a reserve of slowly renewing progenitor cells that can be activated to meet unusual demands for tissue macrophages. The monocyte production rate may be on the order of 7 x 106/kg body weight per hr. The stem cell to monocyte transit time is about 55 hr. Monocytes probably remain in the circulation no more than about 12-16 hr before migrating to the tissues, where they differentiate into macrophages, the functional phase of this cell line. Maintenance of the macrophage population in tissues depends largely on the continuous inflow of monocytes from blood. Although macrophages are capable of cell division, their proliferation normally does not contribute substantially to renewal of the population in tissues (Wintrobe et al., 1981; Fawcett, 1986).

Thrombopoiesis (13 1) Thrombocytes and platelets are cellular elements of the blood of vertebrates that

protect against blood loss by promoting clotting at sites of injury. The term thrombopoiesis


refers to the development of thrombocytes and platelets in haemopoietic organs. The anucleate platelets of mammals are the functional equivalent of nucleated thrombocytes in lower vertebrates and are formed by fragmentation of the cytoplasm of huge polymorpho- nuclear cells called megakaryocytes, found among the other haemopoietic cells in bone marrow (Fawcett, 1986).

(132) The committed stem cell of mammalian thrombopoiesis (CFU-M), gives rise to the earliest morphologically identifiable cell of this lineage, the megakaryoblast. Subsequent cells in this lineage are the promegakaryocyte and megakaryocyte, which forms the platelet. The generation from stem cell to platelet-producing megakaryocyte is estimated at 10 days in humans (Fawcett, 1986). The maturation time of the megakaryocyte is estimated at 10-25 days (Schumacher and Erslev, 1965). A regulatory mechanism seems to ensure that production is responsive to needs for circulating platelets. Excessive bleeding is followed in several days by a three- to four-fold increase in megakaryocyte numbers in the marrow and a rebound in circulating platelets to 150-200% of the initial level (Fawcett, 1986).

Lymphopoiesis (133) Bone marrow is probably the major site of lymphopoiesis in mammals. In rodents,

the marrow has a high continuous rate of lymphocyte production throughout fetal and postnatal life, and lymphocytes constitute 30% of all nucleated marrow cells and exceed the number of erythroblasts at all ages. The dividing precursors of small lymphocytes are larger cells, called transitional cells, that are actively proliferating and constitute about one fifth of all marrow lymphocytes. The production rate of small lymphocytes in mouse marrow may be on the order of IO8 cells per day (Fawcett, 1986). The turnover time of lymphocytes has not been clearly established, but there appear to be both short-lived (days) and long-lived (weeks to months) lymphocytes in bone marrow of laboratory animals (Davis et al., 1982).

Number of haemopoietic cells in bone marrow (134) Estimates of the absolute number of bone marrow cells of any given type are crude

and variable. The total marrow may contain on the order of lo8 cells at the gestational age of 13 weeks, 10’ at 22 weeks, and 2 x 10” at birth (Trubowitz and Davis, 1982a). The following estimates have been given for the erythrocytic series in the adult human (Wintrobe et al., 1981):

Nucleated erythrocytes: 5 x log/kg (body weight) Marrow reticulocytes: 5 x log/kg Circulating reticulocytes: 3.3 x log/kg Circulating erythrocytes: 3.3 x lO”/kg

Typically, there may be about three non-erythroid cells to one erythroid cell in marrow (Table 35). Thus, there may be about 2 x 10” nucleated marrow cells per kg body weight in the adult.

(135) Differential counts of bone marrow aspirates from 12 healthy adult males are listed in Table 35, and changes with age in differential counts of major cell lineages are given in Table 36. The myeloid-to-erythroid ratio was de8ned by Wintrobe et al. (1981) as the ratio of neutrophils and neutrophil precursors to nucleated erythroid precursors.

Distributions and masses of active, inactive, and total bone marrow (136) During prenatal life all of the bone marrow is red except shortly before birth, when

small amounts of fat may appear (Emery and Follett, 1964). Thus, for the foetus and newborn, the weight of total bone marrow and of red marrow are essentially the same.


Table 35. Differential cell counts of bone marrow aspirates from 12 healthy adult males

63

Mean (%)

Observed 95% range confidence (%) (%)

Neutrophilic series (total) Myeloblast Promyelocyte Myelocyte Metamyelocyte ., Band Segmented

Eosinophilic series (total) Myelocyte Metamyelocyte Band Segmented

Basophilic and mast cells Erytbrocytic series (total)

Pronormoblasts Basophilic Polychromatophilic orthochromatic

Lymphocytes Plasma cells Monocytes Megakaryocytes Reticulum cells M:E ratio

53.6 49.2-65.0 0.9 0.2-1.5 3.3 2.1-4.1

12.7 8.2-15.7 15.9 9.6-24.6 12.4 9.5-15.3 7.4 6.0-12.0 3.1 1.2-5.3 0.8 0.2-1.3 1.2 0.4-2.2 0.9 0.2-2.4 0.5 (r1.3

co.1 O-O.2 25.6 18.4-33.8 0.6 0.2-1.3 1.4 0.5-2.4

21.6 17.9-29.2 2.0 044.6

16.2 11.1-23.2 1.3 0.4-3.9 0.3 O-O.8

<O.l O-O.4 0.3 (M.9 2.3 1.5-3.3

33.6-73.6 0.1-1.7 1.9-4.7 8.5-16.9 7.1-24.7 9.4-15.4 3.8-l 1.0 1.1-5.2 0.2-1.4 0.2-2.2

C-2.7 O-1.1

15.Ck36.2 0.1-1.1 0.42.4

13.1-30.1 0.3-3.7 8.6-23.8

O-3.5 0.6

0.8 1.1-3.5

M = myeloid, E = erytbroid. From Wintrobe et 01. (1981).

Table 36. Changes with age in di&rential counts of bone marrow cells

Birth lmo-ly 1-4Y 4-12 y Adult

Neutropbilic series 17% 60 33 50 95% limits 42-78 1747 32-68

Eosinophilic series 3% 3 3 6 95% limits l-5 l-5 2-10

Lymphocytes 3% 14 47 95% limits 3-25 34-63

Erythrocytic 2% 95% limits

M:E ratio R

14 8 2-28 2-16

4.3 4.0

22 8-36

19 11-27

2.6

52 35-69

3 l-5

18 12-28

21 11-31

2.5

57 39-79

3 1-5

17 lo-24

20 10-30

2.6

M = myeloid, E = erythroid. From Wintrobe et al. (1981).

(137) Hudson determined the volume of bone marrow in 16 foetuses (10 females and 6 males) ranging in age from 29 weeks to full term (Table 37). Of the total fetal bone marrow volume, 29.5% f 4.2% was found in the skull, 23.4% f 2.5% in the trunk, and 47.1% ) 3.1% in the limbs.


Table 37. Volume of bone marrow as a function of gestational age

Estimated gestational age

(d)

Volume of bone marrow

(cm3)

203 217 224 231 238 (n = 2) 245 252 (n=3) 259 266 273 280 287 (n = 2)

From Hudson (1965).

16.4 21.5 24.8 22.7

31.7; 32.8 36.0

29.8; 33.2; 36.3 43.9 38.3 41.0 36.9

42.7; 43.1

(138) In the infant, all bones contain dark red haemopoietically active marrow. During childhood there begins a transformation of haemopoietically active red marrow to relatively inactive yellow marrow. This transformation occurs over a period of decades in some bones and is much more rapid in others. In the toes, for example, the replacement of bone marrow by fat may begin before birth and may be mainly complete by age 1 year (Emery and Follett, 1964). By early adulthood essentially all marrow in shafts of long bones as well as part of the marrow in the spongiosa is inactive.

(139) In examinations of the bone marrow in iliac crest samples from subjects who died suddenly but were haematologically normal, Hartsock and coworkers (1965) determined that marrow fat increased steadily from about 20% of the total marrow at age 5 years to about 50% by age 35 years, remained fairly stable until age 65 years, and then rose to about 67% by age 75 years. These results are consistent with findings of Dunnill et al. (1967) for the second lumbar vertebra of normal subjects. Meunier et al. (1971) determined that the volume of marrow fat in samples from the ilium rose from 15% at age 20 years to 60% at age 65 years, while the trabecular bone volume decreased from 26% at age 20 years to 16% at age 65 years. They also observed that the less abundant marrow cell populations generally were found in areas with the least bone.

(140) Data of Mechanik (1926) for 13 adult subjects, some with wasting diseases, indicate that the total bone marrow may represent roughly 5% of total-body weight (see also Woodard and Holodny, 1960; Bigler and Woodard, 1976). Mean values were 4.7% (standard deviation, 0.9%) for all 13 cadavers, 5% for the six males, and 4.5% for the seven females.

(141) Wetzel(l926) reported weights of total bone marrow for three subjects: 2915 g for a 20-year-old person, 4192 g for a 55-year-old person, and 4050 g for an elderly person. Custer (1974) suggested that the skeleton of a typical 70-kg male might contain about 3500 g of bone marrow, but the basis for this estimate was not given.

(142) In the near-term foetus and newborn, the total bone marrow represents roughly 1.3% of total-body weight, with about 30% of the bone marrow residing in the skull, 20- 25% in the trunk, and 45-50% in the limbs (Toeppich, 1914; Hudson, 1965; Cuau ef al., 1968). Experimentally determined and calculated marrow contents of specific bones of the newborn are given in Table 38.

Tabl

e 38

. D

istr

ibut

ion

of a

ctiv

e m

arro

w i

n ne

wbo

rns,

as

mea

sure

d or

est

imat

ed b

y di

lfere

nt a

utho

rs

Bod

y re

gion

and

bon

e gr

oups

H

udso

n (1

965)

”

Exp

erim

enta

l va

lues

Cua

u et

al.

(196

8)b

Tiip

pich

(1

914)

c

Cal

cula

ted

valu

es

Atk

inso

n’s

(196

2)

Cri

sty’

s m

etho

d m

etho

d

Cri

sty’

s re

com

men

ded

valu

esd

Skul

l 29

.5&

4.2%

cr

aniu

m

27.0

f 4.

1 M

andi

ble

2.5f

0.2

Trun

k B

ibs

and

ster

num

B

ibs

Ster

num

V

erte

brae

C

ervi

cal

vert

ebra

e Th

orac

ic

vert

ebra

e Lu

mba

r ve

rteb

rae

Sacr

mn

23.4

zk2.

5

Upp

er l

imbs

and

sho

ulde

r gi

rdle

Sc

rapr

dae

and

clav

icle

s Sc

apul

ae

Cla

vicl

es

14.2

3.

5f0.

4

uppe

r lim

bs

Low

er l

imbs

and

hip

bon

es

OS

coxa

e

10.7

zko.

9

Low

er l

imbs

32.9

9.

2zkO

.6

23.7

zk 2

.2

26.5

%

33.0

f 1.

6%

7.0%

27

.8%

23

.4

6.3

25.3

3.

0 0.

6 2.

5

29.5

%

27.0

2.

5

20.6

24

.7zk

o.9

28.0

27

.0

23.4

8.

1 8.

7zkO

.3

8.8

8.4

9.2

8.1

7.3

7.0

9.2

0 1.

4 1.

4 0

12.5

16

.0f0

.8

19.3

18

.6

14.2

3.

0 1.

8 1.

7 3.

4 7.

3 7.

4 7.

1 8.

3 2.

1 5.

6 5.

4 2.

4 0.

1 4.

5 4.

3 0.

1

19.7

14

.oIt

o.4

14.5

13

.3

14.2

4.

2 3.

2 3.

0 3.

5 3.

4 2.

4 2.

3 2.

7 0.

8 0.

8 0.

7 0.

8 15

.6

11.3

10

.2

10.7

33.2

28

.3 f

0.4

50.6

7.

9 11

.6

25.3

38

.9

31.9

32

.9

11.2

9.

2 20

.7

23.7

a N

mnb

er o

f sk

elet

ons

anal

ysed

was

16.

b

One

ske

leto

n.

= Th

ree

skel

eton

s.

d H

udso

n’s

valu

es w

ere

used

whe

reve

r av

aila

ble;

the

Cua

u et

al.

valu

es w

ere

used

els

ewhe

re,

afte

r no

rmal

ixin

g.

From

C&

y (1

981)

.


(143) The percentage of total-body weight represented by active marrow may not change greatly during the maturation process (Table 39), although the distribution of active marrow changes substantially (Table 40, Fig. 25). By early adulthood, active marrow is located primarily in the ribs, vertebrae, and OS coxae, with the skull containing only about 8% and the limbs only about 10% of the total active marrow (Tables 40 and 41). The age-specific distribution of active marrow indicated in Table 40 is based on a collection of quantitative and qualitative age-specific marrow cellularity data for specific bones (Table 41), together with information on relative volumes of body regions at the indicated ages (Cristy, 1981).

Table 39. Estimated amounts of total marrow, active marrow, and inactive marrow (expressed as percentage of total-body weight) in humans

% total-body weight represented by:

Age (Y) Total marrow Active marrow Inactive marrow

Newborn 1.3 1.3 0.0 1 1.7 1.5 0.2 5 2.5 1.7 0.8

10 3.8 1.9 1.9 15 4.5 1.9 2.6 35, male 5.0 1.6 3.4 35, female 4.5 1.5 3.0

Estimates are based mainly on conclusions of Mechanik (1926), Woodard and Holodny (1960), Hudson (1965), Bigler and Woodard (1976), and Cristy (1980, 1981).

Table 40. Active marrow in a given bone expressed as a percentage of active marrow in the body

Percentage of active marrow at various ages (y)

Bone 0 1 5 10 15 25 40

Cranium 27.0 25.1 15.9 11.6 9.2 7.7 7.6 Mandible 2.5 2.4 1.6 1.1 0.9 0.8 0.8 Scapulae 2.1 2.1 2.7 2.9 3.3 2.9 2.8 Clavicles 0.8 0.8 0.9 0.9 1.0 0.8 0.8 Sternum 0 0.8 1.7 2.1 2.1 3.0 3.1 Ribs 9.2 8.9 8.8 10.9 13.6 15.2 16.1 Cervical vertebrae 3.4 2.8 2.2 2.7 3.3 3.1 3.9 Thoracic vertebrae 8.3 8.4 8.9 10.9 13.7 15.3 16.1 Lumbar vertebrae 2.4 4.3 6.8 8.4 10.5 11.7 12.3 sacrum 0.1 2.4 5.5 6.7 8.4 9.4 9.9 OS coxae 9.2 11.1 13.1 15.6 18.5 19.5 17.5 Femora, upper half 3.7 4.1 6.8 9.4 9.2 7.4 6.7 Femora, lower half 3.1 3.9 6.3 6.1 2.0 0 0 Tibiae, fibulae, patellae 8.0 8.1 9.0 5.5 0 0 0 Ankle and foot bones 8.3 4.1 2.5 0 0 0 0 Humeri, upper half 2.3 2.4 2.4 2.5 3.1 2.5 2.3 Humeri, lower half 2.3 2.3 2.2 1.6 0.7 0 0 Ulnae and radii 2.5 2.5 2.0 1.1 0 0 0 Wrist and hand bones 3.6 1.9 0.9 0 0 0 0

From Cristy (1981).


Figure 25. Sites of red marrow in adults and young children. Modified from Bierman (1961).

Reference values for weights of active and inactive bone marrow: active inactive

Infant: 50 g Og 1 year: 150 g 20 g

- 5 years: MOg 1~g 10 years: 630 g 63Og Male, 15 years: 1080 g 1mg Female, 15 years: 1OOOg 13gOg Male, 35 years: 1170 g mg Female, 35 years: 9oog 1WO g.

Tabl

e 41

. Age

-spe

cific

bo

ne m

arro

w

cellu

larit

y

Cel

lula

rity

fact

or

at v

ario

us

ages

(y)

Bon

e 0

1 5

10

15

25

40

Sour

ce o

f ce

llula

rity

valu

es

Ver

tebr

ae,

ster

num

, rib

s 1.

00

0.95

0.

85

0.80

0.

75

0.72

0.

70

Age

40

valu

es t

aken

fro

m H

ashi

mot

o an

d Y

amad

a (1

964)

; age

pat

tern

s ba

sed

on

Skul

l, sc

apul

ae

1.00

0.

95

0.80

0.

65

0.55

0.

42

0.38

sh

apes

of

cel

lula

rity

agai

nst

age

curv

es

for

verte

brae

, st

emum

an

d rib

s gi

ven

by

Cla

vicl

es

1.00

0.

95

0.79

0.

63

0.52

0.

31

0.33

C

uste

r (1

949,

197

4) a

nd f

or a

nter

ior

iliac

cre

st g

iven

by

Har

tsoc

k et

al.

(196

5)

Upp

er

half

of f

cmor

a an

d hu

mer

i 1.

00

0.95

0.

77

0.60

0.

45

0.30

0.

25

Low

er h

alf

of f

emor

a an

d hu

mer

i 1.

00

0.89

0.

71

0.39

0.

10

0 0

Fem

ur

shaf

t da

ta o

f C

uste

r (1

974)

Tibi

ae,

fibul

ae,

pate

llae,

uln

i, ra

dii

1.00

0.

89

0.57

0.

23

0 0

0 Ti

bia

shaf

t da

ta o

f C

uste

r (1

974)

Ank

le,

foot

, w

rist,

and

band

bon

es

1.00

0.

50

0.20

0

0 0

0 R

ough

es

timat

e,

base

d on

inf

orm

atio

n gi

ven

by E

mer

y an

d Fo

llett

(196

4)

0s c

oxae

an

d F’

iney

(192

2)

1.00

0.

95

0.79

0.

72

0.64

0.

58

0.48

A

nter

ior

iliac

cre

st d

ata

of H

arts

ock

et a

l. (1

965)

From

C

risty

(19

81)


Skeletal blood flow and blood content

69

(144) Estimates of blood flow rates to skeletal tissues or blood volumes of these tissues are sometimes required in the development of biokinetic or dose models for radionuclides, pharmaceuticals, or chemicals. For this reason, typical values for the percentage of cardiac output received by the skeleton and the volume of blood in skeletal tissues are estimated here, even though the skeletal system as defined in this document does not include blood.

(145) The problem of determining the percentage of cardiac output received by the skeleton is complicated by the complex vascular organisation of bones and the variation in flow rates to different parts of the skeleton. Reported values for the percentage of cardiac output received by the skeleton in adult human subjects or laboratory animals range from less than 1.0% to more than 25% of cardiac output (see reviews by Van Dyke et al., 1975; Brookes, 1971, 1974; Williams and Leggett, 1989). In a review of the literature on the distribution of cardiac output, Williams and Leggett (1989) concluded that the most strongly based estimates fall in the range 2.5-9.5% and derived a central estimate of 5% for the percentage of cardiac output received by the skeleton of a resting adult human.

(146) Frost (1963a) estimated that the vascular channel space represents about 6% of the total space enclosed by the periosteal envelope, which would yield about 40 ml blood kg-’ tissue for bone and bone marrow combined. This would represent about 67% of the total blood volume in the adult male.

(147) The volume of blood per unit mass of tissue is not uniform in the skeleton but is substantially higher in active marrow than fatty marrow and higher in total bone marrow than in total bone tissue. In a review of the literature on regional blood volumes in man, Leggett and Williams (1991) estimated that total bone marrow may contain about 5% of the total blood volume and the rest of the skeleton may contain another 2%. Assuming that the blood content of fatty marrow is the same as that of adipose tissue, they estimated that about 1% of the total blood volume of the adult human is associated with fatty marrow and 4% is associated with active marrow.

(148) Data on laboratory animals indicate that the percentage of cardiac output received by the skeleton as well as the percentage of the total blood volume contained in the skeleton may be 1 S-3 times greater in rapidly growing animals than in mature adults. Similar changes with age in the skeletal circulation probably also apply to man (Leggett and Williams, 1991).

Teeth

Tissues and composition of teeth (149) All teeth consist of a crown projecting above the gum and one or more roots that

occupy sockets on the bone of the maxilla or mandible (Fawcett, 1986). Incisors have a single root, lower molars have two roots, and upper molars have three roots. The hard portions of a tooth consist of dentine (or dentin), enamel, and cementum (Fig. 26), which have specific gravities of approximately 3.0, 2.14, and 2.03, respectively (Eastoe, 1961b). The bulk of the tooth consists of dentine. This tissue surrounds a central pulp chamber, which continues downward into each root as a narrow canal that communicates with the periodontal membrane. In the region of the crown the outer surface of the dentine is covered by a layer of enamel. The root is covered by a thin layer of cementum (Fawcett, 1986).

(150) The water content of enamel that can be removed by normal drying techniques is only about 3% by weight and that of dentine and cementum is about 10% by weight, but


Figure 26. Tissues of a tooth. A molar tooth is shown. After Eastoe (1961b).

some &mly bound water is also present. The water content of pulp, which is a soft tissue, is much higher than that of the hard tissues (Eastoe, 1961b).

(151) As much as 95.6% of the moist weight and 99.4% of the dry weight of enamel is inorganic material. Corresponding values for dentine are 71% and 80%, respectively. The principal inorganic constituents of both enamel and dentine are Ca, P, Mg, and C03. The relative amounts of these substances vary with age and physiological state but for moist enamel are typically about 35%, 16.5%, 0.4%, and 2.5%, respectively, and in moist dentine are typically about 24%, 11.5%, 0.9%, and 3.0%, respectively. The inorganic material occurs as crystallites. The ionic lattice is an apatite pattern, perhaps hydroxyapatite with adsorbed carbonate ions in the surface (Eastoe, 1961b).

(152) The organic matter of enamel is about 25% keratin, 5% insoluble collagen, 10% soluble collagen, 15 % “enamel protein”, 25% peptides, and 20% citrate. Collagen may represent as much as 85-90% of the organic matter of dentine (Eastoe, 1961b).

Primary teeth (or deciduous, temporary, or milk teeth) (153) There are 20 primary teeth. Symmetric sets of four teeth (left upper, right upper, left

lower, right lower) are often identified by capital letters A-E: A = central incisor, B = lateral incisor, C = canine, D = first molar, and E = second molar (Buckler, 1979). The full primary dentition may be depicted as follows:

Right Left Upper E D C B A A B C D E Lower E D C B A A B C D E

(154) The primary teeth begin to calcify at about 3-4 months intrauterine life (Buckler, 1979). Approximate weights of the developing teeth, based on the pattern of growth observed by Stack (1964), are given in Table 42.


(155) Eruption times of the deciduous teeth are influenced by racial and familial factors and body size and vary considerably from one person to another. The deciduous teeth usually begin to erupt at 6-8 months postnatal life and normally reach their full complement at age 6-8 years (Graber, 1966; Buckler, 1979; Fawcett, 1986). The normal sequence of eruption is A B D C E, with lower teeth usually appearing slightly ahead of upper teeth (Buckler, 1979). The roots of primary teeth usually continue to develop for 2 years after tooth eruption, and about 3 years after eruption the roots begin to be resorbed due to pressure from underlying secondary teeth (Buckler, 1979). When all of the root or roots of a tooth have been resorbed, the crown is shed and a secondary tooth takes its place. Primary teeth typically are shed in the order in which they erupt, with lowers being shed before uppers (Buckler, 1979). Mean ages for eruption and shedding of primary teeth are given in Table 43.

(156) Measurements of Bolk (1925) indicate a total weight of 9.5 g for the primary teeth at full maturity. Measured weights of specific teeth are given in Table 44.

Secondary teeth (permanent teeth)

(157) There are usually 32 secondary teeth. Symmetric sets of four teeth are often depicted by numbers l-8: 1 =central incisor, 2 = lateral incisor, 3 = canine, 4 =first premolar,

Table 42. Sum of weights of all developing teeth as a function of prenatal and postnatal age

Age (wk) Weight of teeth (mg)

Prenatal: 24 30 36 39

Postnatal: 0 5

10 20 30

25 150 450 650

650 950

1200 2100 3000

From Stack (1964).

Table 43. Mean ages at eruption and shedding of primary teeth

Teeth

Central incisors Lateral incisors First molars Canines Second molars

Age at which eruption occurs Age at which shedding begins (mo) (Y)

6-8 6-8 7-12 8-9

l&l5 lo-11 18-19 lo-11 20-24 11-12

From Scammon (1923). ICRP 25:2-F


Table 44. Mean weights for primary teeth

Teeth

Upper

Mean weight (g)

Lower

Mean weight (g)

Central incisors 0.30 0.14 Lateral incisors 0.22 0.20 Canines 0.39 0.39 First molars 0.58 0.57 Second molars 1.0 0.97

From Bolk (1925).

5 = second premolar, 6 = first molar, 7 = second molar, and 8 = third molar or wisdom tooth (Buckler, 1979). The full secondary dentition may be depicted as follows:

Bight Left Upper 87654321 12345678 Lower 87654321 12345678

Teeth l-5 replace primary teeth (1 replaces A, 2 replaces B, and so forth), but molar teeth, 6-8, do not succeed primary teeth.

(158) The normal order of eruption is 6, 1, 2, 3, 4, 5, 7, 8, with lowers usually erupting slightly ahead of uppers. The first molar (6) typically erupts at about 6 years of age. The wisdom teeth appear at about 18 years of age as an average, but their eruption age varies considerably. Approximate median ages for eruption of the various teeth are given in Table 45.

(159) The permanent dentition (all 32 teeth) weighs about 45-50 g in moist condition (Cheyne and Oba, 1943; Eastoe, 1961b). Typical fresh weights of individual permanent teeth at maturity are given in Table 46.

Reference value for weight of primary teeth: 10 g. Reference value for weight of permanent teeth:

Male: 50 g. Female: 40 g.

Table 45. Approximate median ages for eruption of permanent teeth

Tooth

Lower teeth Median age (y)

Males Females

Upper teeth Median age (y)

Males Females

First incisor 6.5 7 7 Second incisor 7.5 8.5 8 Canine 10 9.5 11.5 11 First premolar 11 10 10 10 Second premolar 11 11 11 11 Fist molar 6 6 6 6 Second molar 12 12 13 12

From Anson (1966), Buckler (1979), and ICRP (1975).

RADIOLOGICAL PROTECTION DATA: THE SKELETON 73 Table 46. Weights of human permanent teeth and content of enamel and dentine

Tooth

Moist weight (g)

Mean Range

Dcntine plus Dentine to Enamel cementum enamel

(%) (%) ratio

Upper jaw: 1st incisor 2nd incisor Canine 1 st premolar 2nd premolar 1st molar 2nd molar 3rd molar

Mean

Lower jaw: 1st incisor 2nd incisor Canine 1st premolar 2nd premolar 1st molar 2nd molar 3rd molar

Mean

1.19 0.87-1.62 22.02 77.98 3.54 0.82 0.52-1.17 21.30 78.70 3.70 1.28 0.85-1.84 22.01 77.99 3.54 1.23 0.90-1.76 22.67 77.33 3.41 1.13 0.87-1.38 19.43 80.57 4.15 2.48 1.98-3.18 23.79 76.21 3.20 2.18 1.41-2.91 20.48 79.52 3.88 1.73 1.07-2.44 23.30 76.70 3.29

22.06 77.94 3.53

0.55 0.30-0.78 12.67 87.33 6.89 0.63 0.44-0.93 18.83 81.17 4.31 1.09 0.75-1.62 12.44 87.56 7.04 0.97 0.73-1.39 16.96 83.04 4.90 1.09 0.79-1.51 29.58 70.42 2.38 2.32 1.78-3.18 21.87 78.13 3.57 2.27 1.51-2.90 26.10 73.90 2.83 1.99 1.51-2.81 26.15 73.85 2.82

22.28 77.72 3.49

From Eastoe (1961b).

Table 47. Reference masses (g) of skeletal tissues and skeletal calcium

Age (Y)

0 1 5 10 _------bo~sexes-__---- (n!Zle) (fztie) (Ze) (feiZle)

Skeleton” 370 1170 2430 4500 7950 7180 10500 7800 Bone 170 590 1260 2300 4050 3700 5500 4000 Active marrow 50 150 340 630 1080 1000 1170 900 Inactive marrow 0 20 160 630 1480 1380 2480 1800 Cartilage 130 360 600 820 1140 920 1100 900 Miscellaneousb 20 50 70 120 200 180 250 200

Skeletal Ca 28 100 240 460 830 760 1180 860

a As de&red here, the skeleton does not include periarticular tissue or blood. b Includes teeth, periosteum, and blood vessels.

Summary of reference weights of major skeletal components

(160) Reference weights of major skeletal components are summarised in Table 47. A small amount of miscellaneous tissue has been included to account for teeth, periosteum, and blood vessels.

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