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INTRODUCTION

  1. Top of page
  2. INTRODUCTION
  3. THE PUBLIC HEALTH PERSPECTIVE
  4. THE CLINICAL PERSPECTIVE
  5. CONCLUSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

NEARLY A decade ago, our group published a Perspective in this journal entitled, “How Many Women Have Osteoporosis?”(1) The article pointed out that the size of the osteoporosis problem could be addressed either with respect to the number of people with low bone mineral density (BMD), a useful in vivo surrogate for “abnormalities in the amount and architectural arrangement of bone tissue leading to impaired skeletal strength,”(2) or in terms of the number of people experiencing characteristic osteoporosis-related fractures, especially those of the hip, spine, or distal forearm. In either instance, a precise delineation of the affected population was limited by the data available at that time, which were restricted almost entirely to white women. However, since that report, an enormous amount of new information has been published about this important problem. In particular, there are now refined estimates of the lifetime risk of osteoporotic fractures that take account of the rising incidence rates observed in some populations as well as improvements in life expectancy. Even more important has been development by the World Health Organization (WHO) of an operational definition of osteoporosis based on bone density(3) that has fostered better estimates of the prevalence of osteoporosis, including a wealth of new data on the prevalence of osteoporosis in men and nonwhite women. On the other hand, the advent of novel densitometric techniques has revealed significant discrepancies in the prevalence estimates depending on which technology is used, and this, in turn, has raised questions about how osteoporosis should be defined.(4) The resulting controversy has exposed a conflict between the need to document the magnitude of the public health problem represented by osteoporosis as opposed to the clinician's need to assess fracture risk in individual patients. Vitriolic attacks on the WHO criteria are a reflection of this growing conflict in perspectives.(5)

THE PUBLIC HEALTH PERSPECTIVE

  1. Top of page
  2. INTRODUCTION
  3. THE PUBLIC HEALTH PERSPECTIVE
  4. THE CLINICAL PERSPECTIVE
  5. CONCLUSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

The public health impact of osteoporosis relates almost entirely to the associated fractures that are the clinical manifestation of the problem. Osteoporotic fractures initially were identified on epidemiological grounds as those in which the incidence increased dramatically with age, affected women more than men, and disproportionately involved diaphyseal skeletal sites.(6) On that basis, fractures of the proximal femur, vertebrae, and distal radius were linked strongly to osteoporosis,(1) broadening a traditional clinical focus on osteoporosis-related vertebral fractures.(7) However, as population-based densitometric studies subsequently made clear, almost all fractures among elderly women are associated with low bone density(8) and bone density also is related to fracture risk in men.(9,10) Although any fracture can have a devastating impact on the affected individual, hip fractures are by far the most important from the public health perspective. They are the predominant cause of deaths from osteoporosis-related fractures,(11,12) and they are the main source of osteoporosis-related morbidity.(13) An estimated 10% of women who sustain a hip fracture become functionally dependent in the activities of daily living compared with only 4% of those with a vertebral fracture and 1% of women with a distal forearm fracture.(14) Moreover, hip fractures account for the lion's share of medical costs.(15) For example, direct expenditures for osteoporotic fracture care in the United States in 1995 were estimated at $13.8 billion, and hip fractures alone were responsible for 63% of the total. (16)

As a result of this disproportionate impact, it is appropriate for health authorities to focus on hip fracture as the primary measure of osteoporosis. Indeed, one of the objectives of Healthy People 2000 was to reduce annual hip fracture incidence in elderly women and men from 714 per 100,000 in 1988 to 607 per 100,000 by 2000.(17) Unfortunately, the rate had risen to 934 per 100,000 in 1996,(18) when 390,000 hip fractures were observed in the United States,(19) and the great concern is that growing numbers of elderly people will drive the number of hip fractures, and their associated costs, even higher in the future.(20) On a global basis, the 323 million individuals 65 years of age and over in 1990 will grow to an estimated 1555 million by 2050, and this demographic trend alone could cause the number of hip fractures worldwide to increase from an estimated 1.7 million in 1990 to a projected 6.3 million in 2050.(21) Although hip fracture incidence has stabilized in some countries,(22,23) increases are still occurring in many areas of the world,(24) and any rise in the incidence rates will increase future fractures still further. Assuming a 1% annual increase in age-adjusted incidence, the projected number of hip fractures worldwide in 2050 could be 8.2 million; if incidence rates stabilized in Europe and North America but increased by 3% annually in the rest of the world, the total could exceed 21 million.(24) Even this alarming figure could be conservative because life expectancy also is rising worldwide. Our estimated lifetime risk of hip fracture (17.5% in white women and 6.0% in white men) was based on a life expectancy in women and men of 78.9 years and 72.3 years, respectively.(1) In a similar analysis, the lifetime risk of hip fracture in Swedish women and men was 13.9% and 4.6%, respectively, but this rose to 22.7% and 11.1%, respectively, when projected improvements in mortality were accounted for.(25) If, in addition, age-adjusted hip fracture incidence rates were to rise by just 1% annually in Sweden, the lifetime risk could increase to an incredible 34.9% in women and 17.0% in men.

If hip fractures are most important from a public health perspective and if BMD assessed at the proximal femur is the best predictor of hip fracture risk,(26) then it also is appropriate for health authorities to focus on osteoporosis of the hip to the exclusion of other sites. Based on an older definition of osteopenia as a BMD value of more than 2 SD below the young normal mean, we estimated that 29% of postmenopausal white women might be affected at the proximal femur.(1) However, the WHO definition of osteoporosis requires a BMD value more than 2.5 SD below the young normal mean for white women.(3) Using this definition, about 17% of postmenopausal white women in the United States have osteoporosis at the total hip site based on data from the Third National Health and Nutrition Examination Survey (NHANES III), a large probability sample of the United States population.(27) The proportion varies somewhat when bone density is assessed at the different subregions, ranging from 13% with osteoporosis at the trochanteric region to 20% at the femoral neck. This translates to about 6 million white women in this country with osteoporosis at the femoral neck and another 15 million with low bone mass, that is, BMD more than 1.0 SD but less than 2.5 SD below the young normal mean.(27) An even greater number of women are affected when additional skeletal sites are considered. Based on data from Rochester, MN, the prevalence of osteoporosis at the proximal femur, lumbar spine, or total wrist sites among postmenopausal white women was 35%.(9)

Because of insufficient data about the relationship between BMD and fracture risk in men or nonwhite women, the WHO did not offer a definition of osteoporosis for these other groups,(3) even though together they account for a substantial proportion of the cost of osteoporotic fractures.(16) However, women of all races lose bone from the proximal femur in a similar fashion.(28,29) If normative data for white women are used to define osteoporosis for nonwhite women, then the prevalence of the condition appears to be lower in some of the other groups. For example, only 12% of Hispanic women and just 8% of postmenopausal black women have osteoporosis as assessed at the total hip site by NHANES.(27) The prevalence of osteoporosis is not well established among women of Asian heritage, but their BMD levels appear to be lower than those in white women.(30,31) However, it has become clear that greater bone density in black women compared with white women and white women compared with Asian women is partly artifactual. This is because areal BMD (g/cm2) corrects for the area scanned but does not completely account for the fact that wider bones also are thicker.(32) Thus, areal BMD values are confounded by skeletal size and, when body size is adjusted for, race-specific differences in bone density are reduced or eliminated.(31, 33–36) This might be expected from the fact that the prevalence of vertebral fractures seems similar in women of different races.(37,38) The risk of hip fractures is greater among white women, but lower BMD levels among Asian women would have predicted higher hip fracture incidence rates in that group, not the lower rates actually observed.(39,40) This suggests that lower hip fracture rates in Asian women are caused by some other factor besides bone density, such as biomechanical differences(30) or a reduced risk of falling.(41)

There are few normative data with which to assess the prevalence of osteoporosis in men. Based on the same absolute bone density cut-off level for men as for women (femoral neck BMD below 0.56 g/cm2), the prevalence of osteoporosis among white, Hispanic, and black men age 50 years and over was 4, 2, and 3%, respectively, in the NHANES study.(27) The lower prevalence in men is consistent with their lower risk of hip fracture(6) and reflects that fact that hip bone density is 12-13% greater in men.(29) However, because of their larger skeletons, bone density is overestimated in men relative to women.(32) When osteoporosis prevalence was calculated on the basis of BMD levels more than 2.5 SD below the mean for young men (femoral neck BMD below 0.59/cm2), the higher mean value caused the figures for white, Hispanic, and black men to increase to 7, 3, and 5%, respectively.(27) However, in Rochester, use of the same absolute cut-off values for defining osteoporosis in men as in women produced an estimated prevalence of osteoporosis of the hip, spine, or distal forearm of only 3%,(9) which appears much too low if the lifetime risk of osteoporotic fractures in men of about 13% is taken as a rough benchmark.(1) Sex-specific normal values produced an estimated prevalence of osteoporosis in men from Rochester of 19%. Again, however, adjusting for bone size by calculating bone mineral apparent density (BMAD; g/cm3) greatly reduces the sex-specific differences.(42,43) Comparable lumbar spine BMAD levels are consistent with recent evidence suggesting that the prevalence of vertebral fracture is similar in men and women,(44) but hip fracture incidence rates are still twice as high in women as in men(6) despite comparable femoral neck BMAD levels in the two sexes.(43)

THE CLINICAL PERSPECTIVE

  1. Top of page
  2. INTRODUCTION
  3. THE PUBLIC HEALTH PERSPECTIVE
  4. THE CLINICAL PERSPECTIVE
  5. CONCLUSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Although public health authorities may be justified in emphasizing hip fractures, clinicians have an equal obligation to deal with the adverse effects on their patients of all fractures. These other osteoporotic fractures, exclusive of the hip, account for over 2 million physician outpatient visits each year in the United States, along with 600,000 emergency room encounters.(16) In aggregate, these other fractures are more common than hip fractures. The lifetime risk of a clinically evident vertebral fracture in white women and men from age 50 years onward is about 15.6% and 5.0%, respectively, whereas that of distal forearm fracture is 16.0% and 2.5%, respectively(1); the lifetime risk of all other fractures in white women has been estimated at 31%.(45) There is some evidence that the incidence of these other fractures also has been increasing over time.(46) Few forearm fracture patients are disabled as a result of the fracture(14) but severe vertebral fractures, which affect up to 10% of postmenopausal white women, (47–50) may cause disfigurement, persistent pain, and a greatly reduced quality of life.(51) Indeed, the adverse influence of vertebral fractures on most activities of daily living is almost as great as that seen for hip fractures, and even wrist fractures interfere significantly with activities such as meal preparation.(52) Finally, there is growing evidence that vertebral fractures, though not distal forearm fractures,(11) are associated with an increased risk of death.(53)

If the focus is on fractures in general, rather than on hip fractures alone, then the various densitometric measurements seem to perform comparably in predicting fracture risk.(26) However, as newer techniques were used more widely, it became obvious that the estimated prevalence of osteoporosis, using the WHO definition, can vary substantially from one skeletal site or technology to another.(54,55) Although the decision to treat a patient involves more considerations than just BMD,(56) and the WHO definition was not meant to be used as an unequivocal treatment threshold,(57) this has become widespread practice.(58) Consequently, discrepancies in osteoporosis prevalence appear to imply important differences in the proportion of patients for whom treatment might be indicated. (59–62) For example, in one population of patients, 17% would have been classified as osteoporotic if BMD was measured at the femoral neck compared with only 6% if an intertrochanteric measurement had been obtained and 34% had BMD been assessed at Ward's triangle.(60) This discrepancy relates partly to the difference in SDs, which can be quite wide for less precise techniques. Thus, only 3% of 60-year-old white women have heel ultrasound measurements more than 2.5 SD below the young normal mean for that technology compared with 38% with lateral spine dual-energy X-ray absorptiometry (DXA) measurements below this level.(63) However, there also are different patterns of age-related bone loss at the various skeletal sites, and this has an influence both on the choice of a “normal” population for setting standards and on the apparent prevalence of osteoporosis later in life.(43) Finally, discrepancies in the normative data used by different densitometer manufacturers create additional problems. (64–66)

These problems matter little to public health authorities, whose focus is on the population rather than the individual patient. Public health interventions (e.g., adequate nutrition and exercise) are applied broadly, without assessment of or reference to individual risk, and are directed at social and environmental factors most likely responsible for differences in fracture risk within populations. (67–70) By contrast, the clinical approach to osteoporosis management focuses on the identification and treatment of high-risk individuals.(71) In this respect, any specific bone density level, much less the WHO definition, is inherently limited.(57) Fracture risk varies continuously with BMD,(3) and there are numerous predictors of fracture risk that are independent of bone density. In the most comprehensive report, an exhaustive set of potential risk factors for hip fracture was evaluated in a prospective study of 9516 white and Asian-American women.(72) The independent predictors of fracture risk in a multivariate analysis adjusting for age and calcaneus BMD included maternal history of hip fracture, weight gain since the age of 25 years (protective), greater height, poorer self-rated health status, history of hyperthyroidism, use of long-acting benzodiazepines, current caffeine intake, more hours of standing each day, inability to rise from a chair, impaired depth perception or contrast sensitivity, and resting heart rate more than 80 beats per minute. Although other investigators have identified different sets of risk factors,(73) the point to be made is that hip fracture incidence was 17 times greater among 15% of the women who had five or more risk factors, exclusive of bone density, compared with 47% of the women who had two risk factors or less.(72) However, women with five or more risk factors had an even higher risk of hip fracture if their bone density Z score was in the lowest tertile.

How is this information to be used by the practicing clinician? Bone densitometry is essential for guiding therapies directed specifically at skeletal metabolism, but the prediction of fracture risk in the individual patient might still be sharpened by incorporating clinical risk factors and/or by adding a biochemical measurement of bone turnover to complement the bone density data. Moreover, if absolute fracture risk could be estimated accurately, and a clinically significant level of risk could be agreed on,(57) there would be no need for reference to age-, race-, or gender-specific normal databases or any concern about T scores (other than the not inconsiderable fact that reimbursement polices often are based on T scores). Admittedly, the practical difficulties involved are formidable. In particular, it may be difficult to achieve consensus on the level of absolute fracture risk that should be of clinical concern and to adjust payment policies accordingly. Nonetheless, methods for accomplishing this task are now being explored. In one example, a model was constructed to predict absolute fracture risk over the succeeding 5 years for postmenopausal white women depending on their age, hip BMD level, and the presence or absence of several risk factors, including previous fracture history in the patient (after the age of 40 years), low body weight (≤127 lb), cigarette smoker (current), and family history of fractures (mother or father with hip, spine, or forearm fracture ≥ age 50 years); treatment appeared to be more cost-effective at any given BMD level when additional risk factors were present, that is, when the absolute fracture risk was greater.(45) Unique, cost-effective treatment thresholds such as these, if they can be simplified sufficiently for everyday application, can account for the fact that specific therapies have different long-term risks, benefits, and costs, and their use could help ensure that treatment with potent pharmacologic agents is rewarded with commensurate social benefits in terms of reducing the adverse outcomes of osteoporotic fractures.

CONCLUSION

  1. Top of page
  2. INTRODUCTION
  3. THE PUBLIC HEALTH PERSPECTIVE
  4. THE CLINICAL PERSPECTIVE
  5. CONCLUSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

It is clear from the previous discussion that there is no simple answer to the question, Who has osteoporosis? From the clinical perspective, this probably is not even the right question. The clinician is faced with the decision of whether or not to treat and, if so, with what agent. In addition to balancing the risks and benefits of a specific intervention, in conjunction with the patient's preferences, the clinician needs to know the patient's fracture risk. It does not matter so much in this instance whether or not the patient has osteoporosis by WHO criteria. Indeed, the clinician needs sufficient latitude to initiate treatment to prevent the development of osteoporosis in patients who do not already have it or, in some elderly individuals with osteoporosis, to withhold aggressive treatment that might be counterproductive. Instead, what is required is an estimation of the likelihood of fracture over the coming 5-10 years, that is, absolute fracture risk,(57) and efforts are underway to develop this information. However, individual fracture risk and drug-specific treatment thresholds do not provide a basis for the diagnosis of existing osteoporosis, which is sometimes needed for reimbursement of bone densitometry, and neither speaks to the social burden of osteoporosis. Indeed, the prevalence of osteoporosis would appear to vary widely depending on the type of therapy that was envisioned if the definition was linked to the proportion of the population in whom a specific treatment was indicated. Although the WHO definition of osteoporosis is arbitrary, it is well established. From the public health perspective, then, the answer to the question of who has osteoporosis probably can best be addressed by continuing to assess bone density levels in the proximal femur.(57)

ACKNOWLEDGMENTS

  1. Top of page
  2. INTRODUCTION
  3. THE PUBLIC HEALTH PERSPECTIVE
  4. THE CLINICAL PERSPECTIVE
  5. CONCLUSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

The author thanks Mrs. Mary Roberts for help in preparing the manuscript. This study was supported by grants AR27065 and AG04875 from the National Institutes of Health, U.S. Public Health Service.

REFERENCES

  1. Top of page
  2. INTRODUCTION
  3. THE PUBLIC HEALTH PERSPECTIVE
  4. THE CLINICAL PERSPECTIVE
  5. CONCLUSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES
  • 1
    Melton LJ III, Chrischilles EA, Cooper C, Lane AW, Riggs BL 1992 Perspective: How many women have osteoporosis? J Bone Miner Res 7:10051010.
  • 2
    Anonymous 1997 Consensus Development Statement: Who are candidates for prevention and treatment for osteoporosis? Osteoporos Int 7:16.
  • 3
    Kanis JA, Melton LJ III, Christiansen C, Johnston CC, Khaltaev N 1994 Perspective: The diagnosis of osteoporosis. J Bone Miner Res 9:11371141.
  • 4
    Delmas PD 2000 Do we need to change the WHO definition of osteoporosis? Osteoporos Int 11:189191.
  • 5
    Wasnich RD 1997 Consensus and the T-score fallacy. Clin Rheumatol 16:337339.
  • 6
    Melton LJ III 1995 Epidemiology of fractures. In: RiggsBL, MeltonLJIII (eds.) Osteoporosis: Etiology, Diagnosis, and Management, 2nd Ed. Lippincott-Raven Publishers, Philadelphia, PA, U.S.A., pp. 225247.
  • 7
    Albright F, Smith PN, Richardson AM 1941 Postmenopausal osteoporosis: Its clinical features. JAMA 116:24652474.
  • 8
    Seeley DG, Browner WS, Nevitt MC, Genant HK, Scott JC, Cummings SR 1991 Which fractures are associated with low appendicular bone mass in elderly women? The Study of Osteoporotic Fractures Research Group. Ann Intern Med 115:837842.
  • 9
    Melton LJ III, Atkinson EJ, O'Connor MK, O'Fallon WM, Riggs BL 1998 Bone density and fracture risk in men. J Bone Miner Res 13:19151923.
  • 10
    Ross PD, Lombardi A, Freedholm D 1999 The assessment of bone mass in men. In: OrwollES (ed.) Osteoporosis in Men. Academic Press, San Diego, CA, U.S.A., pp. 505525.
  • 11
    Cooper C, Atkinson EJ, Jacobsen SJ, O'Fallon WM, Melton LJ III 1993 Population-based study of survival after osteoporotic fractures. Am J Epidemiol 137:10011005.
  • 12
    Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA 1999 Mortality after all major types of osteoporotic fracture in men and women: An observational study. Lancet 353:878882.
  • 13
    Greendale GA, Barrett-Connor E 1996 Outcomes of osteoporotic fractures. In: MarcusR, FreedmanD, KelseyJ (eds.) Osteoporosis. Academic Press, San Diego, CA, U.S.A., pp. 635644.
  • 14
    Chrischilles EA, Butler CD, Davis CS, Wallace RB 1991 A model of lifetime osteoporosis impact. Arch Intern Med 151:20262032.
  • 15
    Tosteson ANA 1999 Economic impact of fractures. In: OrwollES (ed.) Osteoporosis in Men. Academic Press, San Diego, CA, U.S.A., pp. 1527.
  • 16
    Ray NF, Chan JK, Thamer M, Melton LJ III 1997 Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: Report from the National Osteoporosis Foundation. J Bone Miner Res 12:2435.
  • 17
    U.S Department of Health and Human Services 1991 Healthy People 2000: National Health Promotion and Disease Prevention Objectives. Public Health Service (91-50212), U.S. Government Printing Office, Washington, D.C., U.S.A.
  • 18
    National Center for Health Statistics 1999 Healthy People 2000 Review, 1998-99. Public Health Service, Hyattsville, MD, U.S.A., p. 103.
  • 19
    Graves EJ, Kozak LJ 1998 Detailed diagnoses and procedures. National Hospital Discharge Survey 1996. National Center for Health Statistics. Vital Heath Stat 13:110.
  • 20
    Schneider EL, Guralnik JM 1990 The aging of America: Impact on health care costs. JAMA 263:23352340.
  • 21
    Cooper C, Campion G, Melton LJ III 1992 Hip fractures in the elderly: A world-wide projection. Osteoporos Int 2:285289.
  • 22
    Melton LJ III, Therneau TM, Larson DR 1998 Long-term trends in hip fracture prevalence: The influence of hip fracture incidence and survival. Osteoporos Int 8:6874.
  • 23
    Rogmark C, Sernbo I, Johnell O, Nilsson J-Å 1999 Incidence of hip fractures in Malmö, Sweden, 1992-1995. Acta Orthop Scand 70:1922.
  • 24
    Gullberg B, Johnell O, Kanis JA 1997 World-wide projections for hip fracture. Osteoporos Int 7:407413.
  • 25
    Oden A, Dawson A, Dere W, Johnell O, Jonsson B, Kanis JA 1998 Lifetime risk of hip fractures is underestimated. Osteoporos Int 8:599603.
  • 26
    Marshall D, Johnell O, Wedel H 1996 Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312:12541259.
  • 27
    Looker AC, Orwoll ES, Johnston CC Jr, Lindsay RL, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP 1997 Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res 12:17611768.
  • 28
    Sugimoto T, Tsutsumi M, Fujii Y, Kawakatsu M, Negishi H, Lee MC, Tsai K-S, Fukase M, Fujita T 1992 Comparison of bone mineral content among Japanese, Koreans, and Taiwanese assessed by dual-photon absorptiometry. J Bone Miner Res 7:153159.
  • 29
    Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston CC Jr, Lindsay RL 1995 Proximal femur bone mineral levels of US adults. Osteoporos Int 5:389409.
  • 30
    Cummings SR, Cauley JA, Palermo L, Ross PD, Wasnich RD, Black D, Faulkner KG 1994 Racial differences in hip axis lengths might explain racial differences in rates of hip fracture. The Study of Osteoporotic Fractures Research Group. Osteoporos Int 4:226229.
  • 31
    Ross PD, He Y-F, Yates AJ, Coupland C, Ravn P, McClung M, Thomson D, Wasnich RD 1996 Body size accounts for most differences in bone density between Asian and Caucasian women. The EPIC Study Group. Calcif Tissue Int 59:339343.
  • 32
    Seeman E 1998 Growth in bone mass and size—are racial and gender differences in bone mineral density more apparent than real? J Clin Endocrinol Metab 83:14141419.
  • 33
    Marcus R, Greendale G, Blunt BA, Bush TL, Sherman S, Sherwin R, Wahner H, Wells B 1994 Correlates of bone mineral density in the postmenopausal estrogen/progestin interventions trial. J Bone Miner Res 9:14671476.
  • 34
    Tobias JH, Cook DG, Chambers TJ, Dalzell N 1994 A comparison of bone mineral density between Caucasian, Asian and Afro-Caribbean women. Clin Sci 87:587591.
  • 35
    Cundy T, Cornish J, Evans MC, Gamble G, Stapleton J, Reid IR 1995 Sources of interracial variation in bone mineral density. J Bone Miner Res 10:368373.
  • 36
    Bhudhikanok GS, Wang M-C, Eckert K, Matkin C, Marcus R, Bachrach LK 1996 Differences in bone mineral in young Asian and Caucasian Americans may reflect differences in bone size. J Bone Miner Res 11:15451556.
  • 37
    Ross PD, Fujiwara S, Huang C, Davis JW, Epstein RS, Wasnich RD, Kodama K, Melton LJ III 1995 Vertebral fracture prevalence in women in Hiroshima compared to Caucasians or Japanese in the U.S. Int J Epidemiol 24:11711177.
  • 38
    Lau EMC, Chan HHL, Woo J, Lin F, Black D, Nevitt M, Leung PC 1996 Normal ranges for vertebral height ratios and prevalence of vertebral fracture in Hong Kong Chinese: A comparison with American Caucasians. J Bone Miner Res 11:13641368.
  • 39
    Ross PD, Norimatsu H, Davis JW, Yano K, Wasnich RD, Fujiwara S, Hosoda Y, Melton LJ III 1991 A comparison of hip fracture incidence among native Japanese, Japanese Americans, and American Caucasians. Am J Epidemiol 133:801809.
  • 40
    Lauderdale DS, Jacobsen SJ, Furner SE, Levy PS, Brody JA, Goldberg J 1997 Hip fracture incidence among elderly Asian-American populations. Am J Epidemiol 146:502509.
  • 41
    Lipsitz LA, Nakajima I, Gagnon M, Hirayama T, Connelly CM, Izumo H, Hirayama T 1994 Muscle strength and fall rates among residents of Japanese and American nursing homes: An International Cross-Culture Study. J Am Geriatr Soc 42:953959.
  • 42
    Faulkner RA, McCulloch RG, Fyke SL, De Couteau WE, McKay HA, Bailey DA, Houston CS, Wilkinson AA 1995 Comparison of areal and estimated volumetric bone mineral density values between older men and women. Osteoporos Int 5:271275.
  • 43
    Melton LJ III, Khosla S, Achenbach SJ, O'Connor MK, O'Fallon WM, Riggs BL 2000 Effects of body size and skeletal site on the estimated prevalence of osteoporosis on women and men. Osteoporos Int (in press)
  • 44
    O'Neill TW, Felsenberg D, Varlow J, Cooper C, Kanis JA, Silman AJ 1996 The prevalence of vertebral deformity in European men and women: The European Vertebral Osteoporosis Study. J Bone Miner Res 11:10101018.
  • 45
    Eddy D, Johnston CC, Cummings SR, Dawson-Hughes B, Lindsay R, Melton LJ III, Slemenda CW 1998 Osteoporosis: Review of the evidence for prevention, diagnosis, and treatment and cost-effectiveness analysis. Osteoporos Int 8(Suppl 4):188.
  • 46
    Obrant KJ, Bengnér U, Johnell O, Nilsson BE, Sernbo I 1989 Increasing age-adjusted risk of fragility fractures: A sign of increasing osteoporosis in successive generations? Calcif Tissue Int 44:157167.
  • 47
    Ettinger B, Black DM, Nevitt MC, Rundle AC, Cauley JA, Cummings SR, Genant HK 1992 Contribution of vertebral deformities to chronic back pain and disability. Study of Osteoporotic Fractures Research Group. J Bone Miner Res 7:449456.
  • 48
    Melton LJ III, Lane AW, Cooper C, Eastell R, O'Fallon WM, Riggs BL 1993 Prevalence and incidence of vertebral deformities. Osteoporos Int 3:113119.
  • 49
    Burger H, van Daele PLA, Grashuis K, Hofman A, Grobbee DE, Schutte HE, Birkenhager JC, Pols HA 1997 Vertebral deformities and functional impairment in men and women. J Bone Miner Res 12:152157.
  • 50
    Matthis C, Weber U, O'Neill TW, Raspe H 1998 Health impact associated with vertebral deformities: Results from the European Vertebral Osteoporosis Study (EVOS). Osteoporos Int 8:364372.
  • 51
    Gold DT, Lyles KW, Shipp KM, Harper KD, Drezner MK 1996 Unexpected consequences of osteoporosis: An evolving basis for treatment decisions. In: MarcusR, FeldmanD, KelseyJ (eds.) Osteoporosis. Academic Press, San Diego, CA, U.S.A., pp. 10891095.
  • 52
    Greendale GA, Barrett-Connor E, Ingles S, Haile R 1995 Late physical and functional effects of osteoporotic fracture in women: The Rancho Bernardo Study. J Am Geriatr Soc 43:955961.
  • 53
    Melton LJ III 2000 Excess mortality following vertebral fracture. J Am Geriatr Soc 48:338339.
  • 54
    Arlot ME, Sornay-Rendu E, Garnero P, Vey-Marty B, Delmas PD 1997 Apparent pre- and postmenopausal bone loss evaluated by DXA at different skeletal sites in women: The OFELY cohort. J Bone Miner Res 12:683690.
  • 55
    Abrahamsen B, Hansen TB, Jensen LB, Hermann AP, Eiken P 1997 Site of osteodensitometry in perimenopausal women: Correlation and limits of agreement between anatomic regions. J Bone Miner Res 12:14711479.
  • 56
    Guyatt GH 1998 Evidence-based management of patients with osteoporosis. J Clin Densitometry 1:395402.
  • 57
    Kanis JA, Glüer C-C for the Committee of Scientific Advisors, International Osteoporosis Foundation 2000 An update on the diagnosis and assessment of osteoporosis with densitometry. Osteoporos Int 11:192202.
  • 58
    Miller PD, Bonnick SL 1999 Clinical application of bone densitometry. In: FavusMJ (ed.) Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 4th Ed. Lippincott Williams & Wilkins, Philadelphia, PA, U.S.A., pp. 152159.
  • 59
    Greenspan SL, Maitland-Ramsey L, Myers E 1996 Classification of osteoporosis in the elderly is dependent on site-specific analysis. Calcif Tissue Int 58:409414.
  • 60
    Varney LF, Parker RA, Vincelette A, Greenspan SL 1999 Classification of osteoporosis and osteopenia in postmenopausal women is dependent on site-specific analysis. J Clin Densitometry 2:275283.
  • 61
    Nelson DA, Molloy R, Kleerekoper M 1998 Prevalence of osteoporosis in women referred for bone density testing: Utility of multiple skeletal sites. J Clin Densitometry 1:511.
  • 62
    Kröger H, Lunt M, Reeve J, Dequeker J, Adam JE, Birkenhager JC, Diaz Curiel M, Felsenberg D, Hyldstrup L, Kotzki P, Laval-Jeantet A-M, Lips P, Louis O, Perez Cano R, Reiners C, Ribot C, Ruegsegger P, Schneider P, Braillon P, Pearson J 1999 Bone density reduction in various measurement sites in men and women with osteoporotic fractures of spine and hip: The European Quantitation of Osteoporosis Study. Calcif Tissue Int 64:191199.
  • 63
    Faulkner KG, von Stetten E, Miller P 1999 Discordance in patient classification using T-scores. J Clin Densitometry 2:343350.
  • 64
    Laskey MA, Crisp AJ, Cole TJ, Compston JE 1992 Comparison of the effect of different reference data on Lunar DPX and Hologic QDR-1000 dual-energy x-ray absorptiometers. Br J Radiol 65:11241129.
  • 65
    Faulkner KG, Roberts LA, McClung MR 1996 Discrepancies in normative data between Lunar and Hologic DXA systems. Osteoporos Int 6:432436.
  • 66
    Ahmed AIH, Blake GM, Rymer JM, Fogelman I 1997 Screening for osteopenia and osteoporosis: Do the accepted normal ranges lead to overdiagnosis? Osteoporos Int 7:432438.
  • 67
    Jacobsen SJ, Goldberg J, Miles TP, Brody JA, Stiers W, Rimm A 1990 Regional variation in the incidence of hip fracture: U.S. white women aged 65 years and older. JAMA 264:500502.
  • 68
    Johnell O, Gullberg B, Allander E, Kanis JA 1992 The apparent incidence of hip fracture in Europe: A study of national register sources. MEDOS Study Group. Osteoporos Int 2:298302.
  • 69
    Elffors I, Allander E, Kanis JA, Gullberg B, Johnell O, Dequeker J, Dilsen G, Gennari C, Lopes Vaz AA, Lyritis G, Mazzuoli GF, Miravet L, Passeri M, Perez Cano R, Rapado A, Ribot C 1994 The variable incidence of hip fracture in southern Europe: The MEDOS Study. Osteoporos Int 4:253263.
  • 70
    Karagas MR, Baron JA, Barrett JA, Jacobsen SJ 1996 Patterns of fracture among the United States elderly: Geographic and fluoride effects. Ann Epidemiol 6:209216.
  • 71
    Rose G 1993 The Strategy of Preventive Medicine. Oxford University Press, New York, NY, U.S.A.
  • 72
    Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM 1995 Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 332:767773.
  • 73
    Johnell O, Gullberg B, Kanis JA, Allander E, Elffors L, Dequeker J, Dilsen G, Gennari C, Lopes Vas A, Lyritis G, Mazzuoli G, Miravet L, Passeri M, Cano RP, Rapado A, Ribot C 1995 Risk factors for hip fracture in European Women: The MEDOS Study. J Bone Miner Res 10:18021815.