Periodontology 2000, Vol. 23, 2000, 94–102 Copyright C Munksgaard 2000Printed in Denmark ¡ All rights reserved

PERIODONTOLOGY 2000ISSN 0906-6713

Post-menopausal bone loss andits relationship to oral bone lossMARJORIE K. JEFFCOAT, CORA ELIZABETH LEWIS, MICHAEL S. REDDY,

CHING-YUN WANG & MARYANN REDFORD

Osteoporosis and osteopenia are characterized byreductions in bone mass and may lead to skeletalfragility and fracture. In fact, the exact definition ofosteoporosis differs around the world. In much ofEurope, osteoporosis implies a reduced bone massthat results in a predisposition to fracture. Such de-creases in bone mass are measured clinically usingnew techniques described in this paper. Until the ad-vent and widespread use of such methods, such asdual energy X-ray absorption, the definition of os-teoporosis was usually made using the clinical signsof a fracture. In 1994 the World Health Organizationdefined osteoporosis as a bone mineral density levelmore than 2.5 standard deviations below the meanof young, normal women (52).

The effect of osteoporosis on bone is clearlyshown in Fig. 1 and 2. Fig. 1 is a scanning electronmicrograph of normal trabecular bone. This bonewas obtained by iliac crest biopsy. Note the wide tra-becular struts, bone mass, and the absence of micro-fractures. In striking contrast, Fig. 2 is a scanning

Fig. 1. Scanning electron micrograph of normal bone. Thewide trabecular struts are evident.

94

electron micrograph of an iliac crest biopsy from os-teoporotic trabecular bone. There is a relative lack ofbone mass, and narrow trabecular struts. A perfor-ated strut is also evident. Such perforations may be-come microfractures.

The morbidity that may be associated with osteo-porosis should not be underestimated. While loss ofbone mass, per se, does not cause symptoms, once afracture does occur, pain, loss of function, and insome cases deformity, may result. For these reasonsosteoporosis before fracture is termed a ‘‘silent dis-ease’’. Clearly, fractures of the hip, spine and radiushave significant effects of the patients’ quality of life,but serious fracture can also lead to death. The over-all reduction in survival for the most serious frac-tures is illustrated in Fig. 3 and has been estimatedto be 10–20% (3, 33, 41).

Risk factors for osteoporosis have been extensivelystudied and are summarized in Table 1 (1, 8, 20, 47).Some of these risk factors are modifiable, and othersare not. Women are at a greater risk for osteoporosis

Fig. 2. Scanning electron micrograph of osteoporoticbone. Note the relative paucity of trabeculation and theperforation apparent in the center of the micrograph.

Post-menopausal bone loss and its relationship to oral bone loss

Table 1. Risk factors for osteoporosis

Risk factor Modifiable?

Sex No

Age No

Early menopause No

Low bone mass To some extent

Thin, small-framed body No

Race No

Lack of calcium intake Yes

Lack of exercise Yes

Smoking Yes

Alcohol Yes

Heredity No

Diseases such as hyperparathyroidism To some extent

Certain medications (such as steroids) To some extent

Propensity to fall To some extent

after menopause. Estrogen levels present prior tomenopause are protective against loss of bone min-eral, as is hormone replacement therapy after meno-pause (11, 12, 24, 31, 36). Early menopause, eithernaturally occurring or drug or surgically induced,without hormone replacement therapy predisposesto osteoporosis (47). The decision of whether or notto use hormone replacement therapy is dependenton the risk-benefit ratio for the individual woman.

Age is a major non-modifiable risk factor for os-teoporosis (23). In most women, bone mass reachesits peak in the third decade of life (twenties or thir-ties) and declines thereafter. This decline in bonemass is accelerated with the onset of menopause (1,20, 47). While estimates of the rate of post-meno-pausal bone loss may differ by population and meas-urement technology, a rate on the order of 0.5–1.0%per year has been reported.

Other non-modifiable factors include a thin-framed body (1, 8), and the fact that Caucasian andAsian women are at higher risk than African-Ameri-can women (23), as are women with a history of os-teoporosis in the family. Modifiable contributors tolow bone mass include lack of sufficient calcium in-take (18), lack of exercise, smoking and alcohol (17).Certain medications, such as steroids, will alter thebalance between bone formation and resorption re-sulting in a net loss of bone mass. Finally, a propen-sity to fall, for any reason, will make fractures in thepatient with low bone mass more likely (1, 8).

Periodontitis is an inflammatory disease char-acterized by loss of connective tissue and alveolarbone (2). Like osteoporosis, it is a silent disease, not

95

causing symptoms until late in the disease processwhen mobile teeth, abscesses and tooth loss may oc-cur. While the causative agent in periodontitis is apathogenic bacterial plaque in a susceptible patient,periodontitis and osteoporosis have several risk fac-tors in common.

Fig. 4 shows the prevalence of the proportion ofwomen with osteoporosis by age (34). Similarly, theU.S. survey of oral health in adults has shown anincreased prevalence of periodontitis with increasingage (37). In addition to the increased prevalence withincreasing age, risk factors in common for both dis-eases include smoking, and influence of disease ormedications that may interfere with healing (8, 20,46). Whether the rate of progression of periodontitisin women sharply increases immediately aftermenopause is presently unknown.

Fig. 3. Relative survival following hip fractures. Note rela-tive survival decreases with increasing years from the ini-tial diagnosis.

Fig. 4. Percent of women with hip bone mineral densityindicative of osteoporosis. The prevalence increases withage. Data from a population in Rochester, Minnesota.Source: Melton (34).

Jeffcoat et al.

The measurement of bone massand density

The measurement of loss of bone associated withosteopenia and osteoporosis has had many similarproblems to those experienced by clinical re-searchers in periodontics. Both diseases progressslowly, and the usual measures, such as radiographs,are fraught with error. Thus, only large changescould be detected with assurance. It is not surprisingwith such measures the original definition of osteo-porosis was made clinically on the basis of fracture.

Today, early diagnosis of both osteoporosis andperiodontal disease is desirable so that the cliniciancan intervene before significant morbidity such asfracture, tooth mobility or tooth loss has occurred.These methods are summarized in Table 2 (1, 50).

Absorptiometry (1, 50) utilizes a gamma source tomeasure bone mass in grams (approximate ashweight) per cm along the axis of the bone. Singlephoton absorptiometry requires a means to assurethat the soft tissue equivalent material overlying thebone is of constant thickness. The original techniqueinvolved submerging the forearm or leg in a waterbath limiting its use to peripheral sites, such as thedistal radius.

The major technology used today to measurebone mineral density is dual energy X-ray absorption(1, 50). Dual energy X-ray absorption uses an X-raysource for measurements of bone mass. This tech-nology was introduced by Hologic Inc., a majormanufacturer of this equipment in 1987. Dual en-ergy X-ray absorption measures bone density as‘‘areal density’’ in units of grams/cm2 (51). Dual en-ergy X-ray absorption may be used to measure bonemineral density in central sites such as the spine orhip or peripheral sites, such as the radius. Fig. 5

Table 2. Clinical measurement methods to assess bone mineral density

Method Sites Units

Single photon absorptiometry Peripheral due to need for water bath Bone mineral contentg/cmg/cm2

Dual energy X-ray absorption Central or peripheral Bone mineral densityAreal densityg/cm2

Bone mineral contentin grams refersto scanned area

Bone mineral apparent densityg per approximation of volume

Quantitative computed tomography Central or peripheral Apparent bone densitymg/cm3

96

shows a representative bone mineral scan of the hip.At first glance the quality of the image appears tobe poor. In fact, these images are not intended fordiagnosis, but simply to indicate the location of theregions of interest selected by the operator for theassessment of bone mineral density. A typical reportmay also list demographic and identifying infor-mation, as well as the computed information con-cerning each area of interest. Such information in-cludes area of the region of interest (in cm2), bonemineral content (in grams), and bone mineral den-sity (in grams per cm2).

In order to facilitate interpretation of the examina-tion, results are often shown as illustrated in Fig. 5(upper panel). The normal range for women (usuallyaged 20–80 years) is shown, and is the actual meas-ured bone mineral density (marked by a cross). Twostandard deviations below the fracture threshold themean maximal bone mass is usually shown as thefracture threshold, although this may be an over-simplification of the relationship between bone min-eral density and fracture. The Z score is often usedto further interpret the results. Z represents differ-ence of the measured bone mineral density from theappropriate normal population in units of standarddeviations. The Z score is related to a race, age, andsex matched population. Thus a patient who has themean bone mineral density will have a Z score ofzero, and an osteoporotic patient will have a Z scoreat or below ª2.5. The T score also represents thedifference (expressed in terms of standard deviation)from the peak bone mass for the population.

Quantitative computed tomography (1, 50) is arelatively new method that permits direct measure-ment of either trabecular or total bone density byfurther analysis of the information obtained fromspecial computed tomography protocols. Quantitat-

Post-menopausal bone loss and its relationship to oral bone loss

Fig. 5. Print-out from a dual energy X-ray absorption ex-amination. The lower panel shows the region of interestin the hip selected for study. The upper panel shows theage-matched and population-matched normal values byage. The cross hair represents the individual patient’sbone mineral density and the age of the patient.

ive computed tomography provides measures ofbone ‘‘apparent’’ density in units of grams/cm3.

Radiographs also can provide the basis of meas-urements such as the thickness of cortical bone,radiographic densitometry or the use of indices de-veloped for research protocols. The errors inherentto non-standardized radiographs have limited theusefulness of these older methods for the sensitivemeasurement of osteoporosis (1, 50).

The mathematics of fractals has also been appliedto the detection of osteoporosis. The fractal dimen-sion describes the similarity of an object such as tra-becular bone’s surface roughness, over a range ofmagnification. The underlying concept is that osteo-porotic bone has a different surface roughness thannormal bone (as can be seen in Fig. 1 and 2). Fractaldimensions have been used in research, and differ-ences in fractal dimension have been reported for

97

subjects exhibiting high and low bone mineral den-sity (4, 5, 50).

A review of biochemical markers of bone forma-tion and resorption (9, 10) is beyond the scope ofthis chapter. Markers of formation in serum includeosteocalcin (bone-gla-protein), alkaline phosphataseand procollagen I carboxy-terminal extension pep-tide. Markers of bone resorption are found in plasmaand urine. Plasma markers include tartrate-resistantacid phosphatase, pyridinoline and possibly pyridin-oline containing peptides. Urinary markers of re-sorption include urinary pyridinoline and deoxypyri-dinoline (collagen cross-link) containing peptides,fasting urinary calcium and hydroxyproline and uri-nary hydroxylysine glycosides. Interpretation ofthese markers as diagnostic tests for active osteopor-osis is an emerging field and remains controversial.Ongoing studies are addressing their usefulness indetecting progressive periodontitis (Reddy, M.S.,personal communication).

For assessment of intraoral sites, research toolshave been and are being utilized. Both absorptiome-try and dual energy X-ray absorption have beenadapted for intraoral use (14, 16). Most studies have,however, used radiographs to assess anatomy andbone density. Methods using both panoramic andintraoral, periapical or bitewing films have been de-scribed (14, 15, 25, 42–45). Measures of corticalthickness, other image features, and indices de-signed for specific studies have been reported.

Relationship between systemic andmandibular bone density

It has long been postulated that mandibular bonedensity may be indicative of systemic bone mineraldensity. In a classic series of studies, Kribbs et al.addressed this relationship in both normal and oste-oporotic women. In an early study (30), total bodycalcium as assessed by neutron activation analysiswas found to be associated with mandibular densityas measured by quantitative analysis of intraoralradiographs. A later study (29) in normal, non-osteo-porotic women revealed that bone mass was notaffected by age but was significantly associated withskeletal bone mass at the spine and wrist. A com-parison of 85 osteoporotic women with 27 normalwomen showed less mandibular bone mass anddensity and a thinner cortex at the gonion in osteo-porotic compared with non-osteoporotic women(27, 28). Similarly, von Wowern et al. reported that12 osteoporotic subjects with a history of fractures

Jeffcoat et al.

had less mandibular bone mineral content as meas-ured by dual photon absorptiometry than 14 normalwomen (48). It is noteworthy that both Kribbs et al.and von Wowern et al. described cross-sectionalstudies. More recent studies in postmenopausalwomen have indicated that a relationship may existbetween osteoporosis and recession (35).

70 post-menopausal women with clinical evi-dence of periodontitis have been studied by Wactaw-ski-Wende et al. (49) in order to test the hypothesisthat systemic bone mineral density is related to peri-odontitis. Positive and significant correlations wereseen between alveolar bone loss and bone mineraldensity at the spine, trochanter, Ward’s triangle andtotal femur (49).

Preliminary data from theWomen’s Health Initiative OralAncillary Study

The Women’s Health Initiative is an unprecedentedstudy in the United States of women’s health aftermenopause. Specific risk factors for diseases includ-ing heart disease and osteoporosis are being ad-dressed nationwide. Building on a unique oppor-tunity for collaboration with the Women’s HealthInitiative at the University of Alabama at Birming-ham, this oral ancillary study was established to de-termine if an association between systemic osteo-porosis and oral bone loss exists. In this report, pre-liminary cross-sectional data on the first 158subjects enrolled in the oral ancillary study at theUniversity of Alabama at Birmingham are presented.One goal was to determine whether or not imageanalysis of intraoral radiographs could be used todetermine if basal bone mineral density of the man-dible is correlated with hip bone mineral density de-termined by dual energy X-ray absorption. All sub-jects enrolled in the study were post-menopausal fe-males, with a hip bone mineral density confirmed bydual energy X-ray absorption to be within or belowone standard deviation of young normal subjects.Subjects with a hip bone mineral density confirmedby dual energy X-ray absorption one standard devi-ation or more above that of young normal subjectswere excluded.

Comprehensive medical histories and examina-tions were linked with results of oral examinationsand quantitative digital intraoral radiography. Theintraoral radiographic techniques used in this studyhave been validated and are over 90% sensitive and

98

specific in detecting small changes in bone mass anddensity (15, 21, 22). In brief, radiographs are digitizedand corrected for contrast and angulation errors,and areal bone density is calculated relative to a ref-erence wedge in the film holder. The referencewedge is used so that each patient’s radiographic im-age can be displayed with the same brightness andcontrast and that the bone mineral density relativeto the wedge may be determined. A region of interestin the area of the first mandibular basal bone wasselected for measurements of basal bone mineraldensity. Areal densities for the basal bone densitywere calculated in the similar units as dual energyX-ray absorption measurements of systemic bonemineral density (gm/cm2).

This population had a mean age of 62.2∫7.6 years;66% of subjects reported taking hormone replace-ment therapy, and 57.1% of subjects classified them-selves as Caucasian, 42.5% were African-American,and 0.4% were American Indian.

General linear models of basal bone mineral den-sity (of the mandible), hip bone mineral density,mid-root density, age, race, hormone replacementtherapy and calcium supplements were created. Theresult of the generalized linear model for these first158 subjects are shown in Table 3. Fig. 6 plots the hipbone mineral density as measured by dual energy X-ray absorption versus the basal bone mineral densitymeasured from the intraoral radiographs. Significantcorrelations were found between mandibular basalbone mineral density and hip bone mineral density(rΩ0.74, P∞0.001). It is important to note that thesedata represent a subset of the subjects to be evalu-ated in this study. Further multivariate analyses willbe performed after the baseline data set is locked.

These preliminary results may lead the clinicianto pose an additional question. That is, can high-quality intraoral radiographs be used as the basis ofa screening test for osteopenia? Since radiographsare often taken as part of the periodontal examina-tion, such analyses would pose no additional risk tothe patient. These analyses would not be used as adiagnostic, but rather to refer patients for appropri-ate evaluation and treatment as necessary.

Common strategies fortreatment of osteoporosis andperiodontal disease

Avoidance of the morbidity of osteoporosis beginswith prevention. Adequate calcium intake during

Post-menopausal bone loss and its relationship to oral bone loss

Table 3. General linear model relating mandibular basal bone mineral density to covariate variablesa

Coefficient Standard Test ConfidenceVariable estimation error statistic P interval

Hip bone mineral density 5.068 0.985 5.145 ∞0.0001 1.122–7.014

Bone mineral density at the mid-root of 0.401 0.051 7.922 ∞0.0001 0.301–0.501first molar of the mandible

Age ª0.022 0.017 ª1.286 0.201 ª0.055–0.012

Race 0.099 0.302 0.327 0.744 ª0.497–0.695

History of hormone replacement therapy ª0.005 0.307 ª0.015 0.988 ª0.611–0.602

Use of calcium supplements ª0.120 0.264 ª0.454 0.651 ª0.642–0.402

Smoking ª0.533 0.418 ª1.276 0.204 ª1.358–0.292a Basal bone measurements taken at the mandibular first molar.Race, history of hormone replacement therapy, calcium supplement use and smoking status are indicator variables.

adolescence and early adulthood is critical to form-ing the peak bone mass. The 1994 US National Insti-tutes of Health Consensus Development Conferencerecommended 1000 mg of calcium per day for pre-menopausal women and 1500 mg per day for post-menopausal women. In order to maximize the likeli-hood that bone mass is maintained over a lifetime,load-bearing exercise is necessary. Like periodontaldisease, smoking is a major risk factor for osteopor-osis and avoidance of smoking or smoking cessationcontributes to osseous health.

Bone loss in women occurs most rapidly in theyears immediately following menopause whennatural levels of estrogen are greatly reduced. Hor-mone replacement therapy is designed to replaceestrogen after menopause since this immediatepost-menopausal period is a time of rapid loss ofbone mineral density (6, 11, 12, 31, 36). For

Fig. 6. Hip versus basal bone mineral density (BMD). Thescatterplot demonstrates that hip bone mineral densityand basal bone mineral density are correlated (rΩ0.74,P∞0.01).

99

women with a uterus, a combination of estrogenand progesterone are used; while in women with-out a uterus estrogen replacement therapy alone isutilized. Many studies have reported that hormonereplacement therapy and estrogen replacementtherapy is efficacious in sparing bone mineral andreducing fractures (11, 12, 31).

Therapy for osteoporosis is a rapidly changingfield. The use of sodium fluoride, as well as vit-amin D metabolites to correct malabsorption ofcalcium (1, 8), has been shown to be of somevalue in established osteoporosis. Recent advanceshave, however, added to the armamentarium forthe treatment of osteoporosis. Calcitonin, whichmay be administered by injection or nasal spray,inhibits osteoclastic activity and over time de-creases bone turnover (7).

The latest generation of bisphosphonate drugs,such as alendronate, chemisorb onto bone decreas-ing osteoclast number and activity, thereby decreas-ing bone resorption. Alendronate has been shown toinhibit loss of bone density and decrease the risk offracture without disturbance of bone healing ob-served in earlier drugs (40).

Few studies have directly assessed the relationshipbetween periodontal disease and its sequelae inwomen receiving hormone replacement therapy.Most of these studies have involved hormone re-placement therapy, either estrogen or estrogen plusprogesterone, and assessed tooth loss, alveolar boneloss, or other measures of periodontal health. In alongitudinal, unblinded study of 69 women receivinghormone replacement therapy, Jacobs et al. com-pared lumbar spine bone mineral density, measuredby dual photon absorptiometry, with mandibularbone mass assessed by quantitative measures ofstandardized intraoral radiographs (19). The averagelength of study was 5.1 years. A significant but mod-

Jeffcoat et al.

erate correlation was observed at the second exami-nation. In contrast, in a cross-sectional study of 228women, Nordeyd reported no difference in clinicalattachment level or alveolar bone loss (38). Estrogenreplacement therapy was associated with less gingi-val bleeding after correcting for age.

Two major cohorts of women have been studiedin an attempt to determine if hormone replacementtherapy has reduced the number of lost teeth inpost-menopausal women. Both studies were longi-tudinal. These include the three year study of 42,171postmenopausal women in the Nurses Health Co-hort (13), and the 10-year study of 3,921 women liv-ing in a retirement community in the Leisure WorldCohort (39). The Leisure World Cohort taking estro-gen experienced a 36% reduction in tooth loss, andthe Nurses Health Cohort showed an inverse re-lationship between hormone replacement therapyand loss of teeth after correcting for smoking andage. One potential source of bias in these importantstudies (and, in fact, addressed in the reports) is thefact that the same patients who seek to prevent os-teoporosis may seek preventive dental care as well.Both of these populations are large, but composedof relatively well educated, higher socioeconomicgroups. Ongoing longitudinal studies are collectingthe data to address such potential sources of biasand performing examinations so that assessments oftooth loss, loss of bone height and bone density canbe made.

The effect of calcium supplementation on toothloss has also been assessed, and there is limited evi-dence that calcium supplementation may be bene-ficial. In a 7-year study of 189 postmenopausalwomen not taking hormone replacement therapy,the subjects were assigned to receive either placebo,calcium supplementation, or vitamin D plus calciumsupplementation (26). Twelve percent of the pla-cebo-treated women lost teeth during the studyperiod compared with 3% of the calcium supple-mentation group. No effect was observed with vit-amin D.

In a pilot clinical trial the efficacy of the bisphos-phonate drug alendronate in slowing alveolar boneloss due to periodontitis has been investigated (21).This double-blind placebo-controlled randomizedclinical trial measured loss of bone height and den-sity using digital subtraction radiography over a 9-month period. Alendronate reduced the risk of pro-gressive loss of alveolar bone. The relative risk ofprogressive loss of bone height and density was 0.45for the alendronate-treated patients compared withplacebo-treated patients.

100

Conclusions

While a possible relationship between osteoporosisand oral bone loss has long been postulated, theexisting studies have been preliminary in nature.Most studies have used a small number of subjects,and have been cross-sectional in design. Thesestudies utilized different outcomes and many did nothave the power or diagnostic techniques to ad-equately address the questions at hand. The 1992 USNational Institutes of Health Workshop on Osteopor-osis and Oral Bone Loss recommended population-based prospective studies of the association betweenoral bone loss and systemic bone with particular em-phasis on cohorts of postmenopausal women bothwith and without hormone replacement (32). Longi-tudinal studies will make it possible to determine ifthe progression of periodontal disease is more rapidin patients with osteopenia than in patients withnormal bone density, as it is impossible to determineif such a relationship exists from cross-sectionalstudies alone. Several centers are currently perform-ing studies to better elucidate the inter-relationshipbetween oral and systemic bone loss.

References

1. Osteoporosis research, education and health promotion.Bethesda, MD: U.S. Department of Health and Human Ser-vices, Public Health Service, National Institutes of Healthpublication, 1991.

2. AAP. Glossary of periodontic terms. J Periodontol 1986:suppl: 1–31.

3. Arneson TJ, Melton LJI, Lewallen DG, O’Fallon WM. Epi-demiology of diaphyseal and distal femoral fractures inRochester Minnesota, 1965–1984. Clin Orthop 1988: 234:188–194.

4. Buckland-Wright JC, Lynch JA, Rymer J, Fogelman I. Fractalsignature analysis of macroradiographs measures trabecu-lar organization in lumbar vertebrae of postmenopausalwomen. Calcif Tissue Int 1994: 54: 106–112.

5. Caligiuri P, Giger ML, Favus M. Multifractal radiographicanalysis of osteoporosis. Med Phys 1994: 21: 503–508.

6. Christiansen C, Transbol I. Bone mass in postmenopausalwomen after withdrawal of oestrogen/gestagen replace-ment therapy. Lancet 1981: ii: 459–461.

7. Civitelli R. Calitonin. In: Marcus RE, Feldman D, Kelsey J,ed. Osteoporosis. San Diego: Academic Press, 1996: 1235–1258.

8. Cooper C, Melton LJ III. Magnitude and impact of osteo-porosis and fractures. In: Marcus R, Feldman D, Kelsey J,ed. Osteoporosis. San Diego: Academic Press, 1996: 419–434.

9. Delmas PD. Biochemical markers of bone turnover: meth-odology and clinical use in osteoporosis. Am J Med 1991:91: 59S–63S.

Post-menopausal bone loss and its relationship to oral bone loss

10. Delmas PD, Garnero P. Utility of biochemical markers ofbone turnover in osteoporosis. In: Marcus R, Feldman D,Kelsey J, ed. Osteoporosis. San Diego: Academic Press,1996: 1075–1087.

11. Ettinger B, Genant HK, Cann C. Long-term estrogen re-placement therapy prevents bone loss and fractures. AnnIntern Med 1985: 102: 319–324.

12. Felson DT, Zhang Y, Hannan MT, Kiel DP, Wilson PWF, And-erson JJ. The effect of postmenopausal estrogen therapy onbone density in elderly women. N Engl J Med 1993: 329:1141–1146.

13. Grodstein F, Colditz G, Stampfer G. Post-menopausal hor-mone use and tooth loss: a prospective study. J Am DentAssoc 1996: 127: 370–377.

14. Hausmann E. A contemporary perspective on techniquesfor the clinical assessment of alveolar bone. J Periodontol1990: 61: 149–156.

15. Hausmann E, Christersson L, Dunford R, Wikesjo U, PhyoJ, Genco RJ. Usefulness of subtraction radiography in theevaluation of periodontal therapy. J Periodontol 1985: 56:4–7.

16. Hausmann E, McHenry K, Christersson L, Rosling B, Ort-man LF. Techniques for assessing alveolar bone masschanges in periodontal disease with emphasis on 125I ab-sorptiometry. J Clin Periodontol 1983: 10: 455–464.

17. Hemenway D, Colditz GA, Willett WC, Stampfer MJ, SpeizerFE. Fractures and lifestyle: Effect of cigarette smoking, alco-hol intake, and relative weight on the risk of hip and fore-arm fractures in middle-aged women. Am J Public Health1988: 78: 1154–1158.

18. Holbrook TL, Barrett-Connor E, Wingard DL. Dietary cal-cium and risk of hip fracture: 14-year prospective popula-tion study. Lancet 1988: ii: 1046–1049.

19. Jacobs R, Ghyselen J, Koninckx P, van Steenberghe D. Longterm bone mass evaluation of mandible and lumbar spinein a group of women receiving hormone replacemnt ther-apy. Eur J Oral Sci 1996: 104: 10–16.

20. Jeffcoat MK, Chesnut C. Systemic osteoporosis and oralbone loss. J Am Dent Assoc 1993: 124: 49–56.

21. Jeffcoat MK, Reddy MS. Alveolar bone loss and osteopor-osis: Evidence for a common mode of therapy using thebisphonate alendronate. In: Davidovitch Z, ed. The biologicmechanism of tooth resorption and replacement by im-plants. Boston: Harvard Society for the Advancement of Or-thodontics, 1996: 365–373.

22. Jeffcoat MK, Reddy MS, Magnusson I, Johnson B, MeredithMP, Cavanaugh PF Jr, Gerlach RW. Efficacy of quantitativedigital subtraction radiography using radiographs exposedin a multicenter trial. J Periodontal Res 1996: 31: 157–160.

23. Kellie SE, Body JA. Sex-specific and race-specific hip frac-ture rates. Am J Public Health 1990: 80: 326–330.

24. Kiel DP, Felson DT, Anderson JJ, Wilson PWF, MoskowitzMA. Hip fracture and the use of estrogens in postmenopau-sal women. The Framingham Study. N Engl J Med 1987:317: 1169–1174.

25. Klemetti E, Kolmakow S, Kroger H. Pantomography in theassessment of the osteoporosis risk group. Scand J DentRes 1994: 102: 68–72.

26. Krall EA, Garcia RI, Dawson-Hughes B. Increased risk oftooth loss is related to bone loss at the whole body, hip andspine. Calcif Tissue Int 1996: 59: 433–437.

27. Kribbs PJ. Comparison of mandibular bone in normal andosteoporotic women. J Prosthet Dent 1990: 63: 218–222.

101

28. Kribbs PJ, Chesnut CH. Relationships between mandibularand skeletal bone in an osteoporotic population. J ProsthetDent 1989: 62: 703–707.

29. Kribbs PJ, Chesnut CH, Ott SM, Kilcyne RF. Relationshipsbetween mandibular and skeletal bone in a population ofnormal women. J Prosthet Dent 1990: 63: 86–89.

30. Kribbs PJ, Smith DE, Chesnut CH. Oral findings in osteo-porosis. II. Relationship between residual ridge and al-veolar bone resorption and generalize skeletal osteopenia.J Prosthet Dent 1983: 50: 719–724.

31. Lindsay R. Estrogens, bone mass and osteoporotic fracture.Am J Med 1991: 91: 10S–13S.

32. McGowan J, Redford M. Proceeding of the Workshop onOsteoporosis and oral bone loss. Executive summary andresearch recommendations. J Bone Miner Res 1993: 8:S451–454.

33. Melton LJ. Epidemiology of fractures. In: Riggs BL, MeltonLJ, ed. Osteoporosis: etiology, diagnosis and management.New York: Raven Press, 1988: 133–154.

34. Melton LJ. How many women have osteoporosis now? JBone Miner Res 1995: 10: 175–177.

35. Mohammad AR, Brunsvold M, Bauer R. The strength of as-sociation between systemic postmenopausal osteoporosisand periodontal disease. Int J Prosthodont 1996: 9: 479–483.

36. Naessen T, Persson I, Adami HO, Bergstrom R, BergkvistL. Hormone replacement therapy and the risk for first hipfracture. A prospective, population-based cohort study.Ann Intern Med 1990: 113: 95–103.

37. NIDR. Oral health of United States adults. The national sur-vey of oral health in the U.S. of employed adults andseniors: 1985–1986. Bethesda, MD: National Institute ofDental Research, 1987.

38. Nordyred OM, Grossi SG, Matchei EE, Zambon JJ, Haus-mann E, Dunford RG, Genco RJ. Periodontal status ofwomen taking postmenopausal estrogen supplementation.J Periodontol 1993: 64: 957–962.

39. Paganini-Hill A. Benefits of estrogen replacement therapyon oral health:the leisure world cohort. Arch Intern Med1995: 155: 2325–2329.

40. Papapoulos SE. Bisphosphonates. Pharmacology and usein the treatment of osteoporosis. In: Marcus RE, FeldmanD, Kelsey J, ed. Osteoporosis. San Diego: Academic Press,1996: 1209–1234.

41. Poor G, Jacobson SJ, Melton LJ. Mortality following hipfracture. Facts Res Gerontol 1994: 7: 91–109.

42. Ruttimann UE, Webber RL, Hazelrig JB. Fractal dimensionfrom radiographs of peridental alveolar bone. A possibleindicator of osteoporosis. Oral Surg Oral Med Oral PatholOral Radiol Endod 1992: 74: 98–110.

43. Southard KA, Southard TE. Comparison of digitized radio-graphic alveolar feature between 20 and 70 year oldwomen. Oral Surg Oral Med Oral Pathol Oral Radiol Endod1992: 74: 111–117.

44. Taguchi A, Tanimoto K, Suei Y, Otani K, Wada T. Oral signsas indicators of possible osteoporosis in older women. OralSurg Oral Med Oral Pathol Oral Radiol Endod 1995: 80: 612–616.

45. Taguchi A, Tanimoto K, Suei Y, Wada T. Tooth loss and man-dibular osteopenia. Oral Surg Oral Med Oral Pathol OralRadiol Endod 1995: 79: 127–132.

46. Villa ML, Nelson L. Race, Ethnicity and osteoporosis. In:Marcus R, Feldman D, Kelsey J, ed. Osteoporosis. San Di-ego: Academic Press, 1996.

Jeffcoat et al.

47. Vinco L, Prallet B, Chappard D, Pallot-Prades B, Pupier R,Alexandre C. Contributions of chronological age, age atmenarche and menopause and of anthropometric par-ameters to axial and peripheral bone densities. Osteopor-osis Int 1992: 2: 153–158.

48. von Wowern N, Klausen B, Kollerup G. Osteoporosis: a riskfactor in periodontal disease. J Periodontol 1994: 65: 1134–1138.

49. Wactawski-Wende J, Grossi SG, Trevisan M, Genco RJ, TezalM, Dunford RG, Ho AW, Hausmann E, Hreshchyshyn MM.The role of osteopenia in oral bone loss and periodontaldisease. J Periodontol 1996: 67: 1076–1084.

102

50. Wahner HW. Use of densitometry in management of osteo-porosis. In: Marcus R, Feldman D, Kelsey J, ed. Osteopor-osis. San Diego: Academic Press, 1996: 1055–1074.

51. Wahner HW, Fogelman I. The evaluation of osteoporosis:dual energy X-ray absorptiometry in clinical practice. Lon-don: Martin Dunitz, 1994.

52. World Health Organization. Assessment of fracture risk andits application to screening for postmenopausal osteopor-osis. Report of a WHO study group. World Health OrganTech Rep Series 1994: 843.