5BONE STRUCTUREAND FUNCTION INNORMAL ANDDISEASE STATESPhilip Sambrook

Chapter objectives

After studying this chapter you should be able to:

b Understand normal bone structure and function including bone remodelling andthe different hormones that affect calcium metabolism.

c Appreciate the aetiopathogenesis of the most common metabolic bone diseases.

d Understand the epidemiology of osteoporosis and its clinical importance.

e Assess the risk factors commonly associated with osteoporosis.

f Describe the essential anatomy of the hip joint relevant to femoral neck fracturesand other common diseases affecting the hip.

g Understand the general principles of management of osteoporosis.

h Understand the general principles of surgical treatment of hip fractures and theircomplications.

Introduction

The principal functions of the skeleton are mechanicalsupport, maintenance of calcium homeostasis andhaematopoiesis in the bone marrow. These can be dis-turbed in a variety of conditions encompassed by thegeneral term, metabolic bone disease. Osteoporosis isthe commonest metabolic bone disease. It is already an important public health problem in all developedcountries and is becoming one in most developingcountries. Osteoporosis means skeletal fragility lead-ing to an increased risk of fracture. Hip fractures are the most important type of osteoporotic fracture,both in terms of direct health costs and social effectson the patient. In western countries, up to 1 in 2women and 1 in 3 men will sustain an osteoporoticfracture during their lifetime. The cost of treating hipfractures alone has been estimated at 750 millionpounds in the UK in 1995. In the USA, the total costfor treating all types of fractures (not just hip fractures)was estimated at $14 billion in 1999. Early diagnosis isnow possible using precise methods of bone densitymeasurement.

This chapter will review normal bone structure and function as well as the major metabolic bone diseases. Since this topic will be illustrated by a casein which an osteoporotic hip fracture has occurred, thekey anatomy of the hip joint will also be reviewed.

Normal skeletal structure and function

Bones are extremely dense connective tissue that, invarious shapes, constitutes the skeleton. Although oneof the hardest structures in the body, bone maintains a degree of elasticity owing to its structure and composition. Bone is enclosed, except where it iscoated with articular cartilage, in a fibrous outer mem-brane called the periosteum. Periosteum is composedof two layers, an outer fibrous layer and a deeperelastic layer containing osteoblasts that are capable ofproliferating rapidly when a fracture occurs, as will bediscussed further in Chapter 10. In the interior of thelong bones is a cylindrical cavity (called the medullarycavity) filled with bone marrow and lined with a mem-brane composed of highly vascular tissue called theendosteum.

Types of bone: cortical and cancellous

There are two types of bone: (a) compact or corticalbone and (b) trabecular or cancellous bone. Corticalbone is found principally in the shafts (diaphyses) of long bones. It consists of a number of irregularly

SYSTEMS OF THE BODY

5BO

NE

STRU

CTU

RE A

ND

FU

NC

TIO

N IN

NO

RMA

L A

ND

DIS

EASE

STA

TES

68

Fig. 5.1X-ray showing fracture of left femoral neck.

Osteoporosis box 1

Case history

Mrs Jones, a 74-year-old woman living independentlyin the community, has suffered several recent falls.Today, whilst out walking, she fell backwards ontoher left hip. Her GP has been treating her for cardiacfailure, obstructive airways disease and intermittentlow back pain. Because of the back pain, she has beensleeping poorly and her GP recently commenced heron a sedative, to be taken before retiring. On admis-sion to hospital, it is found she is taking 10 differentmedications. Mrs Jones is uncertain of what thesewere all for, but is able to remember that she is on‘fluid tablets for her heart’, ‘a cortisone puffer for herlungs’ and ‘an anti-inflammatory for her back pain’.Her past medical history reveals several risk factorsfor osteoporosis. These include an early menopause,a family history of osteoporosis, and smoking andpoor nutrition.

On examination in hospital, her left leg is noted tobe shortened and externally rotated. Mrs Jones is alsotender over the lateral aspect of the right hip butwithout bruising there. X-rays reveal a fracturethrough the neck of her left femur (Fig. 5.1).

We can see from the details of this case that MrsJones has suffered a hip fracture due to osteoporo-sis. In deciding what investigations are appropriate and how best to manage her, an understanding ofcalcium metabolism and bone structure and functionis necessary.

spaced overlapping cylindrical units termed Haversiansystems. Each consists of a central Haversian canal-surrounded by concentric lamellae of bony tissue (Fig. 5.2A). Trabecular bone is found principally at theends of long bones, and in vertebral bodies and flat bones. It is composed of a meshwork of trabeculaewithin which are intercommunicating spaces (Fig.5.2B).

The skeleton consists of approximately 80% corticalbone, largely in peripheral bones, and 20% trabecularbone, mainly in the axial skeleton. These amounts varyaccording to site and relate to the need for mechanicalsupport. While trabecular bone accounts for the minor-ity of total skeletal tissue, it is the site of greater boneturnover because its total surface area is greater thanthat of cortical bone.

Blood supply of bone

Bones are generally richly supplied with blood, viaperiosteal vessels, vessels that enter close to the artic-ular surfaces and nutrient arteries passing obliquelythrough the cortex before dividing into longitudinallydirected branches. Loss of the arterial supply to partsof a bone results in death of bone tissue, usually calledavascular necrosis or osteonecrosis. Certain bones inthe body are prone to this complication, usually afterinjury, including the head of the femur (discussed laterin this chapter), the scaphoid bone in the wrist, thenavicular in the foot and the tibial plateau. Nutrientarteries to the scaphoid bone are large and numerousat the distal end but become sparse and finer as theproximal pole is approached. Fractures of the sca-phoid, especially of the waist or proximal pole, may beassociated with inadequate blood supply resulting innecrosis and later secondary osteoarthritis. In the foot,the navicular bone is the last tarsal bone to ossify andits ossification centre may be dependent on a singlenutrient artery. Compressive forces on weight bearingare thought to be the cause of avascular necrosis of theossification centre, which usually presents as a painfullimp in a child. This condition is also known asKohler’s disease.

Calcium homeostasis and hormonal control

In addition to its role as a support structure, bone’sother primary function is calcium homeostasis. Morethan 99.9% of the total body calcium resides in the skeleton. The maintenance of normal serumcalcium depends on the interplay of intestinal calciumabsorption, renal excretion and skeletal mobilisation or uptake of calcium. Serum calcium represents lessthan 1% of total body calcium but the serum level

is extremely important for maintenance of normal cellular functions. Serum calcium regulates and is regulated by three major hormones: parathyroidhormone (PTH), 1,25-dihydroxyvitamin D and calcitonin (Fig. 5.3). Parathyroid hormone is an 84-amino acid peptide secreted by the four para-thyroid glands located adjacent to the thyroid gland inthe neck. Calcitonin is a 32-amino acid peptidesecreted by the parafollicular cells of the thyroid gland.Vitamin D, from dietary sources (D3) or synthesised inskin (D2), is converted to 25-hydroxyvitamin D in theliver and then to 1,25-dihydroxyvitamin D in thekidney.

PTH and 1,25-dihydroxyvitamin D are the majorregulators of calcium and bone homeostasis. Althoughcalcitonin can directly inhibit osteoclastic bone resorp-tion, it appears to play a relatively minor role incalcium homeostasis in normal adults. PTH acts on thekidney to increase calcium reabsorption, phosphateexcretion and 1,25-dihydroxyvitamin D production. Itacts on bone to increase bone resorption. 1,25-dihy-droxyvitamin D is a potent stimulator of bone resorp-tion and an even more potent stimulator of intestinalcalcium (and phosphate) absorption. It is also neces-sary for bone mineralisation. Intestinal calciumabsorption is probably the most important calciumhomeostatic pathway.

A number of feedback loops operate to control thelevel of serum calcium and the two major calciumhomeostatic hormones. A calcium-sensing receptor,identified in parathyroid and kidney cells but alsofound in other tissues, that senses extracellularcalcium plays a critical role in calcium homeostasis.Low serum calcium levels stimulate 1,25-dihydroxyvi-tamin D synthesis directly through stimulation of PTHrelease (and synthesis). The physiological response toincreasing levels of PTH and 1,25-dihydroxyvitamin D is a gradual rise in serum calcium level. To preventan elevated level of serum calcium, a second set offeedback loops operate to decrease PTH and 1,25-dihydroxyvitamin D levels. These feedback loopsmaintain serum calcium within a narrow physiologi-cal range. Disturbances in these control mechanisms orover/underproduction of these three major hormonescan lead to various clinical states, discussed in moredetail below. More recently, a PTH-related peptide(PTHrP) has been identified as playing a role incalcium homeostasis, especially in the fetus and in thegrowing skeleton.

Cellular basis of bone remodelling

The structural components of bone consist of extracel-lular matrix (largely mineralised), collagen and cells.

THE MUSCULOSKELETAL SYSTEM

69

5

BON

E STRUC

TURE A

ND

FUN

CTIO

N IN

NO

RMA

L AN

D D

ISEASE STA

TES

SYSTEMS OF THE BODY

5BO

NE

STRU

CTU

RE A

ND

FU

NC

TIO

N IN

NO

RMA

L A

ND

DIS

EASE

STA

TES

70

Subperiosteal outercircumferential lamellae

Concentric lamellae ofosteon (Haversian system)

Concentriclamellae of osteon(haversian system)

Peripheral arteriolar branch of nutrientartery gives rise to capillaries that enter

Volkmann’s canals of cortical (compact) bone

Central arteriolar branchesof nutrient artery

Trabeculae projectinto central medullary

(marrow) cavity

Nutrient artery eventually anastomoseswith distal metaphyseal arteries

Nutrient artery eventuallyanastomoses with distal

metaphyseal arteries

Marrow meshworksurrounds sinusoids

(contains haematopoieticcells, fibroblasts,

and fat cells)

Periosteum

Interstitial lamellae

Capillaries inhaversian canals

Capillaries inVolkmann’s canals

Vein

Nutrientartery

On cut surfaces (as in sections),trabeculae may appear asdiscontinuous spicules

Osteoid(unmineralized matrix)

Active osteoblastsproduce osteoid

Inactive osteoblasts(lining cells)

Marrow spacescontain haematopoietic

cells and fat

Trabeculae

Osteocytes

Osteoclasts (in Howship's lacunae)

Fig. 5.2Structure of bone: (A) cortical (compact) bone; (B) trabecular bone.

A

B

The collagen fibres are of type I, comprise 90% of the total protein in bone and are oriented in a prefer-ential direction giving lamellar bone its structure.Spindle- or plate-shaped crystals of hydroxyapatite[3Ca3(PO4)2]·(OH)2 are found on the collagen fibres,within them, and in the ground substance. The groundsubstance is primarily composed of glycoproteins andproteoglycans. These highly anionic complexes have ahigh ion-binding capacity and are thought to play animportant role in the calcification process. Numerousnon-collagenous proteins have been identified in bonematrix, such as osteocalcin synthesised by theosteoblasts, but their role is unclear.

The principal cells in bone are the osteoclasts and osteoblasts (including bone-lining cells and

osteocytes). Osteoclasts, the cells responsible forresorption of bone, are derived from haematopoieticstem cells. Osteoblasts are derived from local mes-enchymal cells. They are the pivotal bone cell, respon-sible directly for bone formation and indirectly, viaparacrine factors, for regulating osteoclastic boneresorption.

Various cytokines control osteoclast recruitment andactivity, including interleukin-1b (IL-1b) and IL-6.Recently, a transmembrane protein belonging to thetumour necrosis factor superfamily, called osteoclastdifferentiating factor (or ODF), has been identified asplaying an important role in osteoclast differentiationand activity (Fig. 5.4A). Its receptor is called RANK(receptor activator of NFkB) since, after binding, atranscriptional factor known as NFkB translocates tothe nucleus and appears responsible for expression ofgenes that lead to the osteoclast phenotype. Thisprocess is inhibited by a soluble receptor, osteoprote-gerin (OPG), which competes for binding of ODF toproduce an inactive complex.

Bone is continually undergoing renewal calledremodelling (Fig. 5.4B). In the normal adult skeleton,new bone laid down by osteoblasts exactly matchesosteoclastic bone resorption, i.e. formation and resorp-tion are closely ‘coupled’. Although there is a lesseramount of trabecular bone than cortical bone in theskeleton, because trabecular bone ‘turns over’ between3–10 times more rapidly than cortical bone, it is moresensitive to changes in bone resorption and formation.Most bone turnover occurs on bone surfaces, espe-cially at endosteal surfaces. Moreover, the rate ofremodelling differs in different locations according tophysical loading, proximity to a synovial joint or thepresence of haemopoietic rather than fatty tissue inadjacent marrow.

Bone remodelling follows an ordered sequence,referred to as the basic multicellular unit of boneturnover or bone remodelling unit (BMU). In thiscycle, bone resorption is initiated by the recruitment ofosteoclasts, which act on matrix exposed byproteinases derived from bone lining cells. Aresorptive pit (called a Howship’s lacuna) is created bythe osteoclasts. Osteoclasts have a convolutedmembrane called a ruffled border through whichlysosomal enzymes are released into pockets, causingmatrix resorption. This resorptive phase is thenfollowed by a bone formation phase where osteoblastsfill the lacuna with osteoid. The latter is subsequentlymineralised to form new bone matrix. This cycle ofcoupling of bone formation and resorption is vital tothe maintenance of the integrity of the skeleton.Uncoupling of the remodelling cycle, so that boneresorption or formation are in excess of each otherleads to net bone change (gain or loss).

THE MUSCULOSKELETAL SYSTEM

71

5

BON

E STRUC

TURE A

ND

FUN

CTIO

N IN

NO

RMA

L AN

D D

ISEASE STA

TES

Vitamin D

25-OH-D

25-OH-D-1αHydroxylase

Kidney

PTH

Parathyroidglands

High Ca++

Increasedabsorption

Boneresorption

Low Ca++

Stimulation

Inhibition

Bloodcalcium

Intestine

1, 25-(OH)2-D1, 25-(OH)2-D

Liver

Fig. 5.3Schematic diagram of the hormonal control loop forcalcium metabolism.

Skeletal development

Bones develop by one of two processes, either:

• from a preformed cartilaginous structure(endochondral ossification), or

• de novo at specific sites in the skeleton(intramembranous ossification).

Subsequent skeletal growth involves remodelling ofbone. In the growing skeleton, the long bones consistof a diaphysis (or shaft) separated from the ends of the

In clinical practice, it is possible to measure bio-chemical markers of bone remodelling (Table 5.1). For example, the matrix protein osteocalcin can bemeasured in serum, as can bone-specific alkaline phos-phatase (i.e. these are markers of bone formation).Pyridinium cross-links normally join up adjacent type1 collagen molecules in bone, and urinary pyridino-lines can be measured as a marker of collagen break-down (i.e. these are markers of bone resorption). Thesemarkers have been shown to be independent predic-tors of fracture risk.

SYSTEMS OF THE BODY

5BO

NE

STRU

CTU

RE A

ND

FU

NC

TIO

N IN

NO

RMA

L A

ND

DIS

EASE

STA

TES

72

New bone structural unit

Cement line

Cement line

Quiescence

Lining cells

Lining cells

New bone structural unit

Osteoclasts

Osteoblasts

Osteoid

Resorption

Reversal

Formation

Quiescence

Cement line

Cement line

A

Bone matrix

Bisphosphonates

Osteoblast/stromal cell

Bisphosphonates

Bone matrix

Ruffledborder

Mature osteoclast

ODFM-CSF

Osteoclast precursor

Ostrogen/SERMS-

OPG

InactiveOPG/RANK

complex

B

Fig. 5.4(A) Osteoblasts and stromal cells produce both macrophage colony-stimulating factor (M-CSF) and osteoclastdifferentiating factor (ODF). In the presence of permissive concentrations of cellular or soluble M-CSF, binding ofODF to its receptor (RANK) on osteoclast precursor cells results in their differentiation and activation. This process isregulated by an inhibitor of ODF, osteoprotegerin (OPG), which competes with RANK for binding of ODF to produce an inactive complex. The sites of action of various agents used for treating osteoporosis are also shown:SERMS = selective oestrogen-receptor modulators. (B) The bone remodelling sequence is initiated by osteoclasts.Subsequently, osteoblasts appear within the resorption bay and synthesise matrix, which is mineralised later.

bone (called the epiphyses) by cartilage. The part of thediaphysis immediately adjacent to the epiphysial car-tilage is the site of advancing ossification and is knownas the metaphysis. Endochondral ossification is acomplex process in which the growth plate cartilage is progressively replaced by bone. The growth plate(physis) and bone front steadily advance away fromthe bone centre, resulting in progressive elongation ofbone. Longitudinal growth continues while the growthplate remains open.

Growth plates start to close after puberty inresponse to the surge in circulating oestrogen. Severalhormones including growth hormone, insulin-likegrowth factor-1 (IGF-I) and PTHrP play a role in bone

growth. With growth throughout early childhood,bone size and mass gradually increase in a linearfashion. Then between the onset of puberty and youngadulthood, skeletal mass approximately doubles. Mostof the increase in bone mass in early puberty is due to increases in bone size. In cortical bone, both theinner (endocortical) and outer (periosteal) diametersincrease, owing to enhanced resorption and appositionon these surfaces respectively. Later in puberty, bone density increases again but this is less related to increase in bone size. Gains in bone mineral density during puberty are dependent on the pubertalstage.

Growth ceases when closure of the growth plateoccurs, but bone mass and density may continue toincrease beyond this time by a process called con-solidation. The maximum skeletal mass achieved is termed the peak bone mass. The age at which this is attained varies in different skeletal sites. Forexample, forearm peak bone mass in children occursaround age 25. However, in the lumbar spine andfemoral neck, peak bone mass may be achieved by age18.

The adult skeleton

In both men and women, bone mineral loss from theskeleton starts from age 40–50, again depending uponthe skeletal site. In addition, in women bone loss can be rapid immediately after the menopause. Bonesize also contributes to bone strength. Thus men have higher bone mineral density (and a lower frac-ture risk) than women, because they have biggerbones. In clinical practice, osteoporosis is usuallydefined in relation to the degree to which bone mineraldensity is reduced. Bone mineral density is usuallyexpressed as a T score (number of standard deviationsfrom the young normal mean) or Z score (number ofstandard deviations from the age-matched mean).Osteoporosis is usually defined as a T score below -2.5(Fig. 5.5).

THE MUSCULOSKELETAL SYSTEM

73

5

BON

E STRUC

TURE A

ND

FUN

CTIO

N IN

NO

RMA

L AN

D D

ISEASE STA

TES

+2

BM

D (

T-sc

ore)

Diagnostic categories based on bone densitometry

+1

0

Normal

Osteopenia

Osteoporosis

-1

-2

-3

20 40 60Age (years)

80

Fig. 5.5Diagnostic categories based upon bone densitometryaccording to the number of standard deviations fromthe young normal mean (a T score of zero). T scoresbetween -1 and -2.5 are called low bone mass orosteopenia. T scores below -2.5 are called osteoporosis.

Table 5.1Biochemical markers of bone turnover

Bone formation Bone resorption

Serum Osteocalcin Tartrate-resistant acid phosphataseBone-specific alkaline Cross-linked C telopeptide of type 1 collagen

phosphataseUrine – Pyridinolone, deoxypyridinoline

N telopeptide of collagen cross-linksC telopeptide of collagen cross-links

not matched by a concomitant increase in formation.The bone matrix is normally mineralised but there issimply less bone. In most forms of osteoporosis theloss of bone is not evenly distributed throughout theskeleton. For reasons that are not clear, some struts oftrabecular bone are resorbed completely, resulting in aloss of connectivity between adjacent bone plates (Fig.5.7). This contributes to markedly decreased bonestrength and fracture risk. Because the remodellingsurface-to-volume ratio of trabecular bone is high,bone loss tends to affect this type of bone, such as thatin the spine and hip, to a greater extent.

An imbalance between resorption and formationoccurs with ageing but also in several other circum-stances. These include:

• when bone is subject to reduced mechanicalloading as a result of bed rest or immobilisation

• the presence of reduced sex hormoneconcentrations such as after the menopause infemales

• the presence of excess corticosteroids usuallygiven as treatment for a variety of conditions suchas arthritis or asthma.

Loss of bone mineral has no clinical effect itself,unless a fracture occurs. Common sites of fracture dueto osteoporosis include the spine (Fig. 5.8), wrist, hipor pelvis after minor trauma, but almost any bone canbe affected. Vertebral fractures can manifest as loss ofanterior height (wedge fractures), loss of midvertebralheight (called codfish vertebrae) or loss of anterior,middle and posterior height (called compression orcrush fractures). Vertebral fractures may present with

SYSTEMS OF THE BODY

5BO

NE

STRU

CTU

RE A

ND

FU

NC

TIO

N IN

NO

RMA

L A

ND

DIS

EASE

STA

TES

74

Osteoporosis box 2

Case note: measurement of bone mineraldensity

In most subjects with hip fractures, bone mineraldensity is not routinely measured since low bonemineral density is evident in virtually all elderly sub-jects. However, Mrs Jones has sustained her hip frac-ture at a relatively early age, so measurement isappropriate in her case. Her bone mineral densityreveals a femoral neck T score of -4.0 and her Z scoreis -2.3 (Fig. 5.6). Her T score confirms that she hasosteoporosis (being below -2.5). However, since herZ score is also considerably below what is expectedfor her age, secondary causes for osteoporosis orother metabolic bone disease should be sought.

Fig. 5.6Mrs Jones’ right hip scan measured by dual energy X-ray absorptiometry showing her values plotted againstthe age-related normal range.

Metabolic bone disease

Metabolic bone disease is a loose term that encom-passes generalised diseases of bone in which abnormalbone remodelling results in a reduced volume of mineralised bone and/or abnormal bone architec-ture. These processes in turn give rise to bone pain and usually an increased risk of fracture. The com-monest metabolic bone diseases are osteoporosis,osteomalacia, Paget’s disease, hyperparathyroidism,and bone disease associated with renal failure (renalosteodystrophy).

Osteoporosis

Osteoporosis is characterised by an imbalance inremodelling – a relative increase in resorption that is

an acute self-limiting episode of back pain or subclin-ically as height loss and increasing thoracic kyphosis(forward bending of the spine).

Osteomalacia

Osteomalacia occurs when there is insufficient calciumand phosphate to mineralise newly formed osteoid.Since bone mineral – hydroxyapatite – gives bone itscompressive strength, osteomalacic bones are softerand more liable to bend, become deformed, or fracture.Rickets is essentially the same problem – impairedmineral deposition in bone – when it occurs in childrenor adolescents. Rickets is only seen before the growthplate disappears. Osteomalacia and rickets usuallyoccur as a result of vitamin D deficiency, such as ininstitutionalised patients, those with reduced sun

exposure and in patients with gut malabsorption orpoor nutrition. Rarely, an inability of the kidney toretain phosphate results in phosphate wasting andchronic hypophosphataemia and osteomalacia/rickets(Fig. 5.9).

Paget’s disease

Paget’s disease is a condition in which localised areas of bone show markedly increased bone turnover.There is gross disorganisation of newly reformed bone, triggered by overactive osteoclasts. These local areas of increased remodelling may cause defor-mity such as bowing of a limb or enlargement (Fig. 5.10), bone pain, increased fracture risk and,rarely, neoplastic transformation to osteosarcoma. TheX-ray appearance often shows a complex pattern ofradiolucency (owing to early osteolysis) and boneexpansion and sclerosis (generally later). Paget’sdisease is now treated most effectively by drugs calledbisphosphonates, which are discussed later in thischapter (p. 84).

THE MUSCULOSKELETAL SYSTEM

75

5

BON

E STRUC

TURE A

ND

FUN

CTIO

N IN

NO

RMA

L AN

D D

ISEASE STA

TES

A

B

Fig. 5.7Scanning electron micrographs of (A) normal and (B)osteoporotic bone (reproduced with permission: LisMosekilde, Institute of Anatomy, University of Aarhus,Denmark).

Fig. 5.8X-ray of patient with multiple vertebral fractures.

Hyperparathyroidism and renal osteodystrophy

Overproduction of parathyroid hormone, usually by a benign tumour (adenoma) of one of the fourparathyroid glands, leads to increased bone resorptionand elevation of the serum calcium level. Hyper-parathyroidism can occur as a discrete condition(primary hyperparathyroidism) or may be secondaryto renal failure (owing to decreased production of 1,25-dihydroxyvitamin D by the kidney). In patients withrenal failure, the mixed picture of secondary hyper-parathyroidism and osteomalacia is commonly calledrenal osteodystrophy.

Osteoporosis: pathophysiology andrisk factors

Fracture risk is directly related to bone mineral density.Bone mineral density at any age is the result of the peak bone mass achieved and subsequent boneloss (postmenopausal and age-related). This section

SYSTEMS OF THE BODY

5BO

NE

STRU

CTU

RE A

ND

FU

NC

TIO

N IN

NO

RMA

L A

ND

DIS

EASE

STA

TES

76

Mineral Mineral

Matrix Matrix

Normal Osteoporosis

Mineral Mineral

Matrix Matrix

Osteomalacia Osteoporosis/malacia

Fig. 5.9Illustration of the difference between osteoporosis andosteomalacia. In osteoporosis the amount of bone isdecreased but the ratio of matrix to bone mineral isnormal. In osteomalacia, the amount of bone is normalbut the ratio of matrix to bone mineral is decreased.

the skeleton. Serum phosphate generally has an inverseeffect on serum calcium concentration. Serum creati-nine will be elevated in renal impairment. Alkalinephosphatase is an enzyme found in human serum,mainly produced by the liver or osteoblasts. Bone-specific isoenzymes can be measured but automatedbiochemical screens mostly measure total serum alka-line phosphatase (i.e. enzyme from both sources) andit is usually modestly elevated in osteomalacia butmuch higher in Paget’s disease. Serum PTH should bemeasured when the serum calcium is elevated, toconfirm hyperparathyroidism.

Osteoporosis box 3

Case note: screening for metabolic bone disease

We recall that Mrs Jones had poor nutrition, so vitaminD deficiency should be checked for by measuring serum25-hydroxyvitamin D. A simple screen for metabolicbone disease can be performed (Table 5.2). The usualtests to exclude a metabolic bone disease include mea-suring serum calcium, phosphate, creatinine, alkalinephosphatase and PTH. Serum calcium will be elevatedin hyperparathyroidism and often low in osteomalaciaor renal failure. If the serum calcium is elevated in renalfailure, this may be due to so-called tertiary hyper-parathyroidism. Phosphorous is the most abundantintracellular anion in the body and 85% is located in

Table 5.2Differential diagnosis of common metabolic bone disorders

Disorder Blood

Ca P Alkaline PTH 25-OH-vitamin Dphosphatase

Primary hyperparathyroidism ≠ Ø ≠, normal ≠ NormalOsteomalacia Ø Ø ≠ ≠ ØPaget’s disease Normal Normal ≠ ≠ Normal NormalOsteoporosis Normal Normal Normal Normal Normal

THE MUSCULOSKELETAL SYSTEM

77

5

BON

E STRUC

TURE A

ND

FUN

CTIO

N IN

NO

RMA

L AN

D D

ISEASE STA

TES

Fig. 5.10(A) Bone scan showing increased uptake due to Paget’s disease involving the righthemipelvis, right tibia, left scapula, skull and eleventh thoracic vertebra. (B) X-rayof the same patient showing Paget’s disease characterised by expansion of theright hemipelvis with cortical thickening and coarse trabecular pattern.

B

A

will discuss factors contributing to bone loss that areconsidered important in the aetiology of osteoporosis.

Sex hormone deficiency

Since Albright first observed that the majority ofwomen with osteoporosis were postmenopausal, sexhormone deficiency, resulting from natural or surgicalmenopause, has been recognised to cause bone loss.Replacement of oestrogen following the menopauseprevents bone loss and fractures. In men, testosteronedeficiency is similarly associated with bone loss andcan be reversed with testosterone replacement.

Menopausal status is probably the most importantrisk factor for osteoporosis of all. Women with an earlymenopause (considered to be present in women who

become menopausal before 45 years of age) or havingbilateral oophorectomy have lower bone mineraldensity at all sites and increased risk of subsequentfracture. The earlier the menopause, the greater therisk appears to be.

Race and genetic influences

Racial factors influence bone mineral density. Forexample, blacks, whether in Africa or in the USA,appear to have greater bone density than whites of thesame age and sustain fewer related fractures. Peopleof Asian origin often have lower bone densities andoften higher fracture rates than whites.

Similarly, it is established from twin and familystudies that bone mineral density at both the appen-

Epidemiology of fractured hip

Hip fractures, or fractures of the neck of the femur, arethe most serious fractures in older people, at both anindividual and population level. Their economic costis enormous because of the need for hospitalisation,surgery and rehabilitation. Complications are fre-quent, especially in those with co-morbid conditions(which are common in subjects aged >80 years). 20%of those who fracture their hip die within a year andmost survivors never regain their pre-fracture level ofphysical function. Hip fractures lead to permanentadmission to a nursing home in approximately 20% ofpatients.

The incidence of hip fracture rises dramatically withincreasing age in most countries. Hip fractures aremore common in women than in men: epidemiologi-cal studies suggest a white woman has a 16% lifetimerisk of suffering a hip fracture and a white man has a5% lifetime risk.

Risk factors for falls

The high rate of hip fracture in older people is due notonly to their lower bone strength and but also to their

dicular and axial skeleton is strongly genetically in-fluenced. A family history of a relative sustaining afracture after age 50 should be viewed as suggestive.

Physical activity and muscle strength

Bone is responsive to physical strain. Changes in theforces applied to bone produce effects in bone. Forexample, weightlessness and immobilisation inducemarked degrees of bone loss. On the other hand, athletes tend to have greater bone mineral density,although this effect is often site specific. For example,tennis players have increased bone density in theirdominant but not non-dominant arm and weightlifters have greater femoral bone density than otherathletes. This is consistent with a local effect of exer-cise on bone.

Nutrition

Although the majority of body calcium is stored in theskeleton, there has been controversy about the role of dietary calcium intake in the aetiology and preven-tion of osteoporosis. However, published data supporta role for dietary calcium intake in the attainment of peak adult bone density. Moreover, a daily dietary calcium intake of around 800mg/day inpremenopausal women and 1200 mg/day in post-menopausal women is necessary to avoid negativecalcium balance.

Other dietary factors have been postulated to play arole in skeletal homeostasis. Sodium intake may haveimportant effects on bone and calcium metabolism.Sodium loading results in increased renal calciumexcretion, which has led to the suggestion that lower-ing dietary sodium intake diminishes age-related boneloss. Excessive protein and caffeine intakes are associ-ated with bone loss.

Corticosteroids

Corticosteroids are commonly used to treat inflamma-tory diseases, including arthritis and asthma. Corti-costeroids affect calcium metabolism deleteriously in a variety of ways. The most important effect is to in-hibit osteoblastic bone formation directly. They also decrease calcium absorption in the intestine andincrease urinary calcium excretion, leading to sec-ondary hyperparathyroidism and enhanced osteoclastactivity by inhibiting OPG. These mechanisms causerapid bone loss when corticosteroids are used in highdoses for prolonged periods.

SYSTEMS OF THE BODY

5BO

NE

STRU

CTU

RE A

ND

FU

NC

TIO

N IN

NO

RMA

L A

ND

DIS

EASE

STA

TES

78

Osteoporosis box 4

Case note: Risk factors

We recall that on admission to hospital, Mrs Jones’past medical history revealed several risk factors forosteoporosis. These include an early menopause, apositive family history, smoking, and poor nutrition.

• An early menopause is one that occurs before 45years of age.

• A positive family history could include a motherwho sustained any peripheral fracture after age50 or early height loss due to kyphosis.

• Smoking exposure can be quantified in terms ofpack years. One pack year is smoking 20cigarettes per day for 1 year. Someone whosmokes 10 cigarettes per day for 10 years thushas 5 pack years of exposure.

• Poor nutrition includes avoidance of dairyproducts, and thus a low dietary intake ofcalcium, or a poor diet overall.

Mrs Jones’ medications also include corticosteroidtherapy. Although corticosteroid-induced osteoporo-sis is dose dependent, even inhaled corticosteroidscan cause bone loss if used in excessive doses.

Essential anatomy of the hip

The hip joint, like most of the lower limb joints, is asynovial joint. Synovial joints are characterised by thefollowing features:

• articular cartilage covering the bony surfaces• a joint cavity containing viscous synovial fluid• a surrounding articular capsule that consists of

outer fibrous tissue and an inner lining called asynovial membrane.

The hip joint is also a ball-and-socket joint, formedby the articulation of the rounded head of the femurwith the cup-shaped acetabulum of the pelvis. It com-bines a wide range of motion with great stability. Thisis possible because of the deep insertion of the head of the femur into the acetabulum, the strong articularcapsule and the muscles that pass over the joint and

insert at a distance below the head of the femur. Theseanatomical features provide leverage for the femurand stabilisation for the joint. When a hip fractureoccurs, it is usually at one of three sites (Fig. 5.11):either high in the femoral neck (subcapital), across theneck itself (cervical) or in the trochanteric region(pertrochanteric).

The acetabulum is formed by fusion of three pelvic bones: the ischium, ilium and pubis (Fig. 5.12).There is a circular rim of fibrocartilage, which forms the glenoid labrum around the acetabular cavity, the lower portion of which is incomplete, forming the acetabular notch. Blood vessels pass into the joint through a foramen formed by a transverse ligament over this notch. The acetabulum is deepestand strongest superiorly and posteriorly, where it issubject to the greatest strain when a person is in theerect position.

The hip joint has a strong, dense articular capsule. Itis attached proximally to the edge of the acetabulum,the glenoid labrum and the transverse ligamentpassing over the acetabular notch. All of the anteriorsurface and the medial half of the posterior surface ofthe femoral neck are intracapsular. The articularcapsule is strong and thick over the upper and ante-

THE MUSCULOSKELETAL SYSTEM

79

5

BON

E STRUC

TURE A

ND

FUN

CTIO

N IN

NO

RMA

L AN

D D

ISEASE STA

TES

Osteoporosis box 5

Case note: Preoperative management of hip fracture

After admission to hospital, Mrs Jones is transferredto the Orthopaedic Ward, 24 of whose 30 beds areoccupied by elderly subjects recovering from hip frac-tures. These fractures all occurred following a fall ortrivial trauma. Like many older subjects, Mrs Jones ison a large number of drugs (polypharmacy) and her10 current medications should be critically reviewedto determine if they are all necessary. Her sleepingtablets should be stopped, as these types of medica-tions are commonly associated with falls. Since shealso takes diuretics, postural hypotension should bechecked for as a cause of her falls. To reduce the riskof morbidity or mortality, Mrs Jones must be assessedby her anaesthetist prior to surgery for co-morbidconditions, and her cardiopulmonary and fluid–electrolyte state should be evaluated. Fluid and elec-trolyte imbalance is common in an elderly patienttaking diuretics and anti-inflammatory drugs andwith poor nutrition. Any imbalance must be cor-rected before surgery.

Iliac crest

Tubercle of crest

Anterior superioriliac spine

Anterior inferioriliac spine

Head of femur

Greater trochanter

Intertrochanteric line

Lesser trochanterSubcapital

Cervical

Pertrochanteric

Pubicsymphysis

Femur

Fig. 5.11Anterior view of bones of the hip joint showing threemain sites of fracture: high in the femoral neck(subcapital), across the neck itself (cervical) or in thetrochanteric region (pertrochanteric).

increased risk of falling. Established risk factors forfalls and hence hip fracture include impaired balance,muscle weakness and psychotropic medication. Al-though physical activity levels are related to bonedensity, the benefits of exercise in the elderly probablyrelate more to reduced risk of falling than increases inbone strength.

by other vessels via the femoral neck, these may bedamaged in cervical fractures. If the blood supply viathe ligamentum teres is insufficient, avascular necrosisof the femoral head may occur.

The iliotibial band is a portion of the fascia lata ofthe thigh that extends inferiorly from the sacrum, theiliac crest and the ischium, over the greater trochanterof the femur and lateral aspect of the thigh to insertinto the lateral condyle of the femur and tibia.

rior portions of the joint but becomes thinner andweaker over the lower and posterior portions of thejoint.

Important structures around the hip joint

Ligaments (Fig. 5.13A)The fibrous tissue of the articular capsule of any jointusually shows localised thickenings, which form theligaments of the joint. There are a number of impor-tant ligaments around the hip joint. The iliofemoral lig-ament is the strongest of these. Crossing the front ofthe capsule, it extends from the ilium to the anteriorportion of the base of the neck. Its lower portiondivides into two bands, forming an inverted Y shape.It is relaxed in flexion and taut in extension of the thigh and prevents excessive extension of the hip. Inthe upright position, the iliofemoral ligament stabilisesthe hip by pulling the femoral head firmly into itssocket.

The pubofemoral and ischiocapsular ligaments areweaker than the iliofemoral ligament but help rein-force the posterior portion of the capsule. The liga-mentum teres is an intracapsular ligament that looselyattaches the femoral head to the lower portion of theacetabulum and adjacent ligaments. It has little effecton the normal motion or stability of the joint but is achannel for blood vessels to the head of the femur.Although the femoral head’s blood supply is mainly

SYSTEMS OF THE BODY

5BO

NE

STRU

CTU

RE A

ND

FU

NC

TIO

N IN

NO

RMA

L A

ND

DIS

EASE

STA

TES

80

Lateral view

Ilium

Pubis

Ischium

Fig. 5.12Lateral view of the right hip of a child showing thethree bones that form the acetabulum before fusionoccurs.

A

B

Anterior superioriliac spine

Inguinal ligament

Inguinalligament

Iliopectinealbursa

Femoral artery

Ischiogluteal bursaTrochanteric

bursa

Iliofemoral ligament

Pubofemoral ligamentGreater

trochanter

Ischial tuberosity

Lesser trochanterFemur

Fig. 5.13Anterior view of the right hip joint showing: (A) themain ligaments; (B) the key bursae.

Surgical management of hip fractures

Surgical management followed by early mobilisationis the treatment of choice for hip fractures. Surgicalmanagement varies according to the type of fractureand can be broadly divided into two types.

Femoral neck fractures

Undisplaced femoral neck fractures are most com-monly fixed with multiple parallel screws or pins. Thetreatment of displaced femoral neck fractures dependson the patient’s age and activity level: young activepatients should undergo open reduction and internalfixation; older, less active patients are usually treatedwith hip replacement (hemiarthroplasty), eithercemented or uncemented. The ultimate goal is toreturn patients to their pre-fracture level of function byrapid rehabilitation.

Trochanteric fractures

A sliding hip screw is the device most commonly used for fracture stabilisation in both undisplaced

THE MUSCULOSKELETAL SYSTEM

81

5

BON

E STRUC

TURE A

ND

FUN

CTIO

N IN

NO

RMA

L AN

D D

ISEASE STA

TES

Synovial membraneA synovial membrane lines the deep surface of thearticular capsule. It is a common site of pathology inseptic arthritis in children (see Ch. 11) and chronicinflammatory diseases in adults such as rheumatoidarthritis and ankylosing spondylitis (see Ch. 1).

Bursae (Fig. 5.13B)In areas of the skeleton where friction occurs, a defi-nite sac lined with a synovial membrane called a bursais often present. There are several bursae around thehip joint that are of clinical importance.

The largest and most important is the trochantericbursa, situated between the gluteus maximus muscleand the posterolateral surface of the greater trochanter.It is usually a multilocular bursa but is not palpable orvisible unless distended. Inflammation of this bursa(called trochanteric bursitis) can occur in various typesof arthritis (e.g. rheumatoid arthritis) or as a separateentity. It often occurs in patients with lumbar spinepathology or gait disturbances.

The iliopectineal bursa lies between the deep surfaceof the iliopsoas muscle and the anterior surface of the joint. It lies over the anterior portion of the articular capsule and since it communicates with thejoint cavity in about 15% of normal individuals,swelling of the bursa may present as a synovial cyst ofthe hip near the inguinal ligament. The ischioglutealbursa is situated near the ischial tuberosity and over-lies the sciatic nerve and the posterior femoral cuta-neous nerve.

Muscles (Fig. 5.14)The hip joint is surrounded by powerful and well-bal-anced muscles that not only move the extremity butalso help maintain the upright position of the trunk.Extension of the femur on the pelvis is performedlargely by the gluteus maximus and hamstringmuscles. Flexion of the hip is carried out mainly by theiliopsoas, iliacus and rectus femoris muscles. Abduc-tion is achieved by the glutei medius and minimus,and adduction by the adductors magnus, longus, andbrevis, the pectineus, and the gracilis muscles.

Femoral triangleThe femoral triangle is a clinically important subfas-cial space whose main contents are the femoral arteryand vein, and branches of the femoral nerve. It islocated in the superomedial third of the thigh andappears as a depression below the inguinal ligamentwhen the leg is actively flexed at the hip joint. Theboundaries of the femoral triangle are shown in Figure5.15. Of clinical importance, the femoral artery is easilyexposed and cannulated in the femoral triangle. More-over, the superficial position of the femoral artery in

Osteoporosis box 6

Case note: Relating clinical features to pathology

We can now understand why Mrs Jones is tender overthe lateral aspect of the right hip. Tenderness overthe right greater trochanter is likely to be a sign oftrochanteric bursitis. Her history includes recurrentlow back pain, which is commonly associated withaltered gait and trochanteric bursitis. We can also appreciate why Mrs Jones’ leg is shortened andexternally rotated. Key muscles around the hip suchas the iliopsoas muscle are de-functioned by the frac-ture and the normal lever arm of the femoral neck isdisrupted.

the triangle makes it vulnerable to lacerations andpuncture. The femoral nerve is the largest branch ofthe lumbar plexus (L2–L4) and passes lateral to thefemoral vessels in the triangle.

Adductor canalThe adductor canal is a narrow fascial tunnel in thethigh, providing an intramuscular passage throughwhich the femoral artery and vein pass into thepopliteal fossa of the knee (Fig. 5.15).

SYSTEMS OF THE BODY

5BO

NE

STRU

CTU

RE A

ND

FU

NC

TIO

N IN

NO

RMA

L A

ND

DIS

EASE

STA

TES

82

Iliacus

Anteriorsuperior

iliac spine

Fascialata

Tensorfasciae latae

Sartorius

Rectusfemoris

Iliotibialtract

Vastuslateralis

Patella

Patellarligaments

Psoasminor

Add

ucto

rs

Psoasmajor

Pectineus

Pubictubercle

Adductorlongus

Gracilis

Vastusmedialis

Sartorius

A B

Ham

string muscles

Gluteusmaximus

Iliotibial tract

Long head

Gluteusmedius

Short head

Tibial nerve

Plantaris

Commonfibular nerve

Gastrocnemius,lateral head

Semitendinosus

Semimembranosus

Biceps femoris

Gracilis

Adductor magnus

Gastrocnemius,medial head

Fig. 5.14The key muscles of the hip joint: (A) anterior view of the right hip joint; (B) posterior view of the right hip joint.

and displaced intertrochanteric fractures. Fracture stability is dependent on the status of the posterome-dial cortex of the femur. The most important aspect ofits insertion is secure placement in the femoral head. Although the sliding hip screw allows postop-erative fracture impaction, it is essential to obtain animpacted reduction at the time of surgery. If there is alarge posteromedial fragment, an attempt should bemade to internally fix the fragment with a screw orwire.

Medical management of osteoporotichip fracture

Hip fractures are particularly common problems in thevery elderly. After initial surgical management, diag-nostic approaches should be directed at a generalmedical assessment. Elderly patients often have sig-nificant unrecognised multisystem disease that mayimpair the rehabilitation process. Investigations toexclude different types of underlying metabolic bone

disease should include looking for the possibility ofsubclinical vitamin D deficiency as a contributingfactor to falls (due to muscle weakness) and fracture(due to osteomalacia), especially in institutionalisedpatients.

Measurement of bone mineral density is the bestmethod for confirming the diagnosis of osteoporosisand is commonly used for monitoring the response totherapy. Bone density is usually measured at two sites,most commonly the spine and hip, using the techniqueof dual energy X-ray absorptiometry. Bone density canalso be assessed by quantitative CT scanning. Theability of bone density to predict fracture is at least asgood as cholesterol level to predict heart disease andblood pressure to predict stroke. Bone biopsy mayrarely be performed to exclude diseases like osteoma-lacia. Ultrasound measurements, usually of the heel(calcaneus), can also be used to provide an assessmentof bone density and structure. Spinal X-rays may beappropriate to examine for vertebral wedge or com-pression fractures. These fractures may be associatedwith pain but often occur silently and result in heightloss and increased kyphosis.

Treatment of osteoporosis is aimed at preventingfurther fractures. It is important to select treatmentindividually for each patient. Treatment with calcium,vitamin D metabolites, oestrogen, selective oestrogen-receptor modulators, bisphosphonates or calcitoninmay be considered.

Calcium

Calcium is weakly antiresorptive (i.e. a weak inhibitorof bone resorption) and supplementation may reducenegative calcium balance and so reduce bone resorp-tion, particularly in older age. Controlled trials havedemonstrated calcium supplementation can preventbone loss in postmenopausal women and this has beenassociated with a modest reduction in fracture risk inlonger-term studies. There is also evidence that calciumsupplementation augments the effect of oestrogen onbone density.

Vitamin D

Since a substantial proportion of institutionalised (or house-bound) elderly may be vitamin D deficient,vitamin D supplementation is recommended in institutionalised or house-bound elderly subjects.Active vitamin D metabolites may be appropriate in patients with known or presumed calcium malabsorption.

Oestrogen and selective oestrogen-receptormodulators

Oestrogen replacement therapy is the treatment of first choice in most perimenopausal women. Oestrogen reduces osteoclastogenesis by decreasingproduction of cytokines such as IL-1 and RANK (Fig. 5.4). Treatment should be given for at least 5years. Compliance will be enhanced by explaining therisks and benefits, regular monitoring and usingpreparations that minimise side-effects like bleeding,such as continuous regimens of oestrogen and progestagen.

Controversy exists over whether there may be an increased risk of breast cancer with long-term oestrogen use. This has led to the development ofselective oestrogen-receptor modulators, which act to decrease bone resorption, like oestrogen, whilst not stimulating the breast or uterus. Controlledclinical trials have shown modest increases in bone density and significant reductions in vertebralfractures.

THE MUSCULOSKELETAL SYSTEM

83

5

BON

E STRUC

TURE A

ND

FUN

CTIO

N IN

NO

RMA

L AN

D D

ISEASE STA

TES

Anterior superior iliac spine

Inguinal ligament

Femoralartery

Sartorius

Pubic tubercle

Beginning ofadductor canal

Adductor longus

Adductor tubercle

Apex offemoral triangle

Fig. 5.15Boundaries of the femoral triangle in the right thighand the adductor canal.

Further reading

Moore K L, Dalley A F 1999 Clinically oriented anatomy, 4th edn.Williams & Wilkins, Baltimore

Favus M J (ed) 1999 Primer on the metabolic bone diseases anddisorders of mineral metabolism, 4th edn. Lippincott Williams &Wilkins, Philadelphia

Marcus R, Feldman D, Kelsey J (eds) 1999 Osteoporosis, 2nd edn.Academic Press, San Diego

Bisphosphonates

Bisphosphonates are an effective alternative to oestro-gen therapy. Bisphosphonates are potent inhibitors ofbone resorption, acting through the inhibition of osteo-clast function (Fig. 5.4). Randomised controlled trialshave shown that treatment with these agents can sig-nificantly increase bone density and reduce furtherfracture risk by about 50%. The benefits of oestrogenand bisphosphonates may not persist after treatmentis stopped.

Exercise programmes are most useful in relation topreventing further falls, even though little effect onbone density may be achieved. Biochemical markers ofbone turnover such as bone-specific alkaline phos-phatase (a marker of bone formation) or urinarypyridinoline (a marker of bone resorption) may beused to monitor compliance with therapy.

A period of weeks to months in a specialist rehabil-itation unit may be necessary to improve coordinationand gradually strengthen muscle power. However,functional impairment in activities of daily livingbecause of poor mobility will be present in many ofthese patients. For example, about 50% of hip fracturesurvivors are discharged to nursing homes. Rehabili-tation will enable many patients to regain inde-pendence. Prior to discharge, a home visit by theoccupational therapist may be necessary to ensure thatthe home environment is safe. In addition, a variety ofaids may be recommended by the occupational thera-pist to promote independent living.

SYSTEMS OF THE BODY

5BO

NE

STRU

CTU

RE A

ND

FU

NC

TIO

N IN

NO

RMA

L A

ND

DIS

EASE

STA

TES

84

Osteoporosis box 7

Case note: Postoperative management of hip fracture

A multidisciplinary team comprising her orthopaedicsurgeon, a physician, a physiotherapist, an occupa-tional therapist and a social worker were all involvedin Mrs Jones’ postoperative progress. The main goalswere re-establishing her independence and earlymobilisation to avoid pressure sores and throm-boembolism.

As falls were involved in Mrs Jones’ case, a generalmedical assessment that included her visual function,and neuromuscular and cardiovascular systems wasmade. Calcium and vitamin D supplements wereadded to her treatment and she was transferred to arehabilitation unit on day 8 after her surgery.

Self-assessment case study

A 65-year-old woman complains of acute thoracic back painfor 2 weeks. She recalls opening a window at the time of itsonset but gives no history of trauma. X-rays reveal a crushfracture of the 10th thoracic vertebra. She describes no feveror weight loss but has been taking low-dose inhaledcorticosteroids for asthma. Her menopause was at age 45 butshe has never taken hormone replacement therapy becausethere is a family history of breast cancer.

After studying this chapter you should be able to answerthe following questions:

b What investigations are indicated and why?

c What are the common clinical risk factors for osteoporoticfracture?

d What is the appropriate treatment in this patient?

Answers see page 183

Self-assessment questions

b What are the two different types of bone and theirdifferences?

c What are the major hormones regulating calciummetabolism?

d What is the normal bone remodelling sequence?

Answers see page 184