UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Osteoporotic fracture risk assessment

Author
E Michael Lewiecki, MD
Section Editors
Clifford J Rosen, MD
Kenneth E Schmader, MD
Deputy Editor
Jean E Mulder, MD

INTRODUCTION

Osteoporosis is a common disease that is characterized by low bone mass with microarchitectural disruption and skeletal fragility, resulting in an increased risk of fracture, particularly at the spine, hip, wrist, humerus, and pelvis [1]. Osteoporotic fractures (fragility fractures, low-trauma fractures) are those occurring from a fall from a standing height or less, without major trauma such as a motor vehicle accident. There were an estimated nine million osteoporotic fractures worldwide in 2000, of which 1.6 million were hip, 1.7 million forearm, and 1.4 million clinical vertebral fractures [2]. Fractures of the hip and spine are associated with an increased mortality rate of 10 to 20 percent [1,3]. Fractures may result in limitation of ambulation, depression, loss of independence, and chronic pain [4,5].

Properties that contribute to bone strength include bone mineral density (BMD), bone geometry (size and shape of bone), degree of mineralization, microarchitecture, and bone turnover [6]. BMD measurements are available to many patients, and fracture risk has been demonstrated to increase with decreasing BMD [6]. Assessment of bone microarchitecture requires methodologies such as high resolution peripheral quantitative computed tomography (QCT), high resolution or micro magnetic resonance imaging (MRI), or double tetracycline-labeled transiliac bone biopsy with histomorphometry, which are not routinely used in clinical practice.

Non-BMD factors that contribute to fracture risk include advancing age, previous fracture, falls, glucocorticoid therapy, family history of hip fracture and current smoking (table 1) [7-10]. Incorporating risk factors that are independent of BMD increases the sensitivity of fracture risk assessment and thereby improves treatment intervention strategies [11]. Univariate and multivariate analyses suggest that age, prior fracture history, and BMD are the strongest predictors of fracture risk [12].

Risk assessment for osteoporotic fracture will be reviewed here. Detailed information regarding screening, prevention, diagnosis, and treatment is found elsewhere. (See "Screening for osteoporosis" and "Prevention of osteoporosis" and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women" and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men" and "Overview of the management of osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men".)

ASSESSMENT OF FRACTURE RISK

Low bone mineral density (BMD) is associated with increased risk of fracture. However, methodologies for combining BMD with clinical risk factors to quantify fracture probability offer attractive alternatives to relying on BMD testing alone [13]. Thus, assessment of fracture risk should include evaluation of both:

                                

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Thu Dec 17 00:00:00 GMT+00:00 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Riggs BL, Melton LJ 3rd. The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone 1995; 17:505S.
  2. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006; 17:1726.
  3. Ioannidis G, Papaioannou A, Hopman WM, et al. Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study. CMAJ 2009; 181:265.
  4. Poole KE, Compston JE. Osteoporosis and its management. BMJ 2006; 333:1251.
  5. Adachi JD, Adami S, Gehlbach S, et al. Impact of prevalent fractures on quality of life: baseline results from the global longitudinal study of osteoporosis in women. Mayo Clin Proc 2010; 85:806.
  6. Ahlborg HG, Johnell O, Turner CH, et al. Bone loss and bone size after menopause. N Engl J Med 2003; 349:327.
  7. Wainwright SA, Marshall LM, Ensrud KE, et al. Hip fracture in women without osteoporosis. J Clin Endocrinol Metab 2005; 90:2787.
  8. Siris ES, Chen YT, Abbott TA, et al. Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med 2004; 164:1108.
  9. Schuit SC, van der Klift M, Weel AE, et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 2004; 34:195.
  10. Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet 2002; 359:1929.
  11. Kanis JA, Johnell O, Oden A, et al. Ten-year risk of osteoporotic fracture and the effect of risk factors on screening strategies. Bone 2002; 30:251.
  12. Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int 2005; 16:581.
  13. Kanis JA, Oden A, Johnell O, et al. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 2007; 18:1033.
  14. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 1994; 843:1.
  15. Stone KL, Seeley DG, Lui LY, et al. BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures. J Bone Miner Res 2003; 18:1947.
  16. Johnell O, Kanis JA, Oden A, et al. Predictive value of BMD for hip and other fractures. J Bone Miner Res 2005; 20:1185.
  17. Leslie WD, Tsang JF, Caetano PA, et al. Effectiveness of bone density measurement for predicting osteoporotic fractures in clinical practice. J Clin Endocrinol Metab 2007; 92:77.
  18. Black DM, Cummings SR, Genant HK, et al. Axial and appendicular bone density predict fractures in older women. J Bone Miner Res 1992; 7:633.
  19. Kanis JA, Glüer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int 2000; 11:192.
  20. Cummings SR, Black DM, Nevitt MC, et al. Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet 1993; 341:72.
  21. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312:1254.
  22. Cranney A, Jamal SA, Tsang JF, et al. Low bone mineral density and fracture burden in postmenopausal women. CMAJ 2007; 177:575.
  23. Kung AW, Lee KK, Ho AY, et al. Ten-year risk of osteoporotic fractures in postmenopausal Chinese women according to clinical risk factors and BMD T-scores: a prospective study. J Bone Miner Res 2007; 22:1080.
  24. Kanis JA, Johnell O, Oden A, et al. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 2008; 19:385.
  25. WHO Fracture Risk Assessment Tool (FRAX). http://www.shef.ac.uk/FRAX (Accessed on June 05, 2012).
  26. Leslie WD, Morin S, Lix LM, et al. Fracture risk assessment without bone density measurement in routine clinical practice. Osteoporos Int 2012; 23:75.
  27. Kanis JA, Johnell O, Oden A, et al. Risk of hip fracture according to the World Health Organization criteria for osteopenia and osteoporosis. Bone 2000; 27:585.
  28. Kanis JA, Oden A, Johnell O, et al. The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 2001; 12:417.
  29. Engelke K, Lang T, Khosla S, et al. Clinical Use of Quantitative Computed Tomography (QCT) of the Hip in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions-Part I. J Clin Densitom 2015; 18:338.
  30. Leslie WD, Lix LM, Johansson H, et al. Does osteoporosis therapy invalidate FRAX for fracture prediction? J Bone Miner Res 2012; 27:1243.
  31. Leslie WD, Majumdar SR, Lix LM, et al. Can change in FRAX score be used to "treat to target"? A population‐based cohort study. J Bone Miner Res 2014; 29:1074.
  32. Ensrud KE, Lui LY, Taylor BC, et al. A comparison of prediction models for fractures in older women: is more better? Arch Intern Med 2009; 169:2087.
  33. Hippisley-Cox J, Coupland C. Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores. BMJ 2009; 339:b4229.
  34. Marques A, Ferreira RJ, Santos E, et al. The accuracy of osteoporotic fracture risk prediction tools: a systematic review and meta-analysis. Ann Rheum Dis 2015; 74:1958.
  35. Tosteson AN, Melton LJ 3rd, Dawson-Hughes B, et al. Cost-effective osteoporosis treatment thresholds: the United States perspective. Osteoporos Int 2008; 19:437.
  36. Kanis JA, Burlet N, Cooper C, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2008; 19:399.
  37. Kanis JA, Borgstrom F, Zethraeus N, et al. Intervention thresholds for osteoporosis in the UK. Bone 2005; 36:22.
  38. Kanis JA, Borgström F, Johnell O, et al. Cost-effectiveness of raloxifene in the UK: an economic evaluation based on the MORE study. Osteoporos Int 2005; 16:15.
  39. Borgström F, Johnell O, Kanis JA, et al. Cost effectiveness of raloxifene in the treatment of osteoporosis in Sweden: an economic evaluation based on the MORE study. Pharmacoeconomics 2004; 22:1153.
  40. Kanis JA, Borgstrom F, Johnell O, Jonsson B. Cost-effectiveness of risedronate for the treatment of osteoporosis and prevention of fractures in postmenopausal women. Osteoporos Int 2004; 15:862.
  41. Borgström F, Johnell O, Kanis JA, et al. At what hip fracture risk is it cost-effective to treat? International intervention thresholds for the treatment of osteoporosis. Osteoporos Int 2006; 17:1459.
  42. Dawson-Hughes B, Tosteson AN, Melton LJ 3rd, et al. Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA. Osteoporos Int 2008; 19:449.
  43. Leib ES, Saag KG, Adachi JD, et al. Official Positions for FRAX(®) clinical regarding glucocorticoids: the impact of the use of glucocorticoids on the estimate by FRAX(®) of the 10 year risk of fracture from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(®). J Clin Densitom 2011; 14:212.
  44. The International Society for Clinical Densitometry, International Osteoporosis Foundation 2010 Official Positions on FRAX. http://www.iscd.org/wp-content/uploads/2012/10/Official-Positions-ISCD-IOF-FRAX.pdf.
  45. Sornay-Rendu E, Munoz F, Delmas PD, Chapurlat RD. The FRAX tool in French women: How well does it describe the real incidence of fracture in the OFELY cohort? J Bone Miner Res 2010; 25:2101.
  46. Giangregorio LM, Leslie WD, Lix LM, et al. FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res 2012; 27:301.
  47. Leslie WD, Lix LM, Johansson H, et al. Spine-hip discordance and fracture risk assessment: a physician-friendly FRAX enhancement. Osteoporos Int 2011; 22:839.
  48. Kanis JA, Johansson H, Oden A, McCloskey EV. Guidance for the adjustment of FRAX according to the dose of glucocorticoids. Osteoporos Int 2011; 22:809.
  49. Bauer DC, Glüer CC, Genant HK, Stone K. Quantitative ultrasound and vertebral fracture in postmenopausal women. Fracture Intervention Trial Research Group. J Bone Miner Res 1995; 10:353.
  50. Schott AM, Weill-Engerer S, Hans D, et al. Ultrasound discriminates patients with hip fracture equally well as dual energy X-ray absorptiometry and independently of bone mineral density. J Bone Miner Res 1995; 10:243.
  51. Khaw KT, Reeve J, Luben R, et al. Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus: EPIC-Norfolk prospective population study. Lancet 2004; 363:197.
  52. Bauer DC, Glüer CC, Cauley JA, et al. Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women. A prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med 1997; 157:629.
  53. Hans D, Dargent-Molina P, Schott AM, et al. Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet 1996; 348:511.
  54. Glüer CC, Eastell R, Reid DM, et al. Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population-based sample: the OPUS Study. J Bone Miner Res 2004; 19:782.
  55. Stewart A, Torgerson DJ, Reid DM. Prediction of fractures in perimenopausal women: a comparison of dual energy x ray absorptiometry and broadband ultrasound attenuation. Ann Rheum Dis 1996; 55:140.
  56. Thompson P, Taylor J, Fisher A, Oliver R. Quantitative heel ultrasound in 3180 women between 45 and 75 years of age: compliance, normal ranges and relationship to fracture history. Osteoporos Int 1998; 8:211.
  57. Marín F, González-Macías J, Díez-Pérez A, et al. Relationship between bone quantitative ultrasound and fractures: a meta-analysis. J Bone Miner Res 2006; 21:1126.
  58. Seeley DG, Browner WS, Nevitt MC, et al. Which fractures are associated with low appendicular bone mass in elderly women? The Study of Osteoporotic Fractures Research Group. Ann Intern Med 1991; 115:837.
  59. Ross PD, Davis JW, Epstein RS, Wasnich RD. Pre-existing fractures and bone mass predict vertebral fracture incidence in women. Ann Intern Med 1991; 114:919.
  60. Cummings SR, Black DM, Nevitt MC, et al. Appendicular bone density and age predict hip fracture in women. The Study of Osteoporotic Fractures Research Group. JAMA 1990; 263:665.
  61. Picard D, Brown JP, Rosenthall L, et al. Ability of peripheral DXA measurement to diagnose osteoporosis as assessed by central DXA measurement. J Clin Densitom 2004; 7:111.
  62. Cauley JA, Hochberg MC, Lui LY, et al. Long-term risk of incident vertebral fractures. JAMA 2007; 298:2761.
  63. De Laet CE, Van Hout BA, Burger H, et al. Hip fracture prediction in elderly men and women: validation in the Rotterdam study. J Bone Miner Res 1998; 13:1587.
  64. Khosla S. High-trauma fractures and bone mineral density. JAMA 2007; 298:2418.
  65. Sanders KM, Pasco JA, Ugoni AM, et al. The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study. J Bone Miner Res 1998; 13:1337.
  66. Mackey DC, Lui LY, Cawthon PM, et al. High-trauma fractures and low bone mineral density in older women and men. JAMA 2007; 298:2381.
  67. Huang C, Ross PD, Wasnich RD. Short-term and long-term fracture prediction by bone mass measurements: a prospective study. J Bone Miner Res 1998; 13:107.
  68. Melton LJ 3rd, Crowson CS, O'Fallon WM, et al. Relative contributions of bone density, bone turnover, and clinical risk factors to long-term fracture prediction. J Bone Miner Res 2003; 18:312.
  69. Hillier TA, Stone KL, Bauer DC, et al. Evaluating the value of repeat bone mineral density measurement and prediction of fractures in older women: the study of osteoporotic fractures. Arch Intern Med 2007; 167:155.
  70. Kanis JA, Johnell O, Oden A, et al. Prediction of fracture from low bone mineral density measurements overestimates risk. Bone 2000; 26:387.
  71. Duppe H, Gardsell P, Nilsson B, Johnell O. A single bone density measurement can predict fractures over 25 years. Calcif Tissue Int 1997; 60:171.
  72. Binkley N, Bilezikian JP, Kendler DL, et al. Official positions of the International Society for Clinical Densitometry and Executive Summary of the 2005 Position Development Conference. J Clin Densitom 2006; 9:4.
  73. Dobnig H, Piswanger-Sölkner JC, Obermayer-Pietsch B, et al. Hip and nonvertebral fracture prediction in nursing home patients: role of bone ultrasound and bone marker measurements. J Clin Endocrinol Metab 2007; 92:1678.
  74. Hodson J, Marsh J. Quantitative ultrasound and risk factor enquiry as predictors of postmenopausal osteoporosis: comparative study in primary care. BMJ 2003; 326:1250.
  75. Stewart A, Reid DM. Quantitative ultrasound or clinical risk factors--which best identifies women at risk of osteoporosis? Br J Radiol 2000; 73:165.
  76. Yamada M, Ito M, Hayashi K, et al. Dual energy X-ray absorptiometry of the calcaneus: comparison with other techniques to assess bone density and value in predicting risk of spine fracture. AJR Am J Roentgenol 1994; 163:1435.
  77. Pacifici R, Rupich R, Griffin M, et al. Dual energy radiography versus quantitative computer tomography for the diagnosis of osteoporosis. J Clin Endocrinol Metab 1990; 70:705.
  78. Genant HK, Engelke K, Fuerst T, et al. Noninvasive assessment of bone mineral and structure: state of the art. J Bone Miner Res 1996; 11:707.
  79. Mackey DC, Eby JG, Harris F, et al. Prediction of clinical non-spine fractures in older black and white men and women with volumetric BMD of the spine and areal BMD of the hip: the Health, Aging, and Body Composition Study*. J Bone Miner Res 2007; 22:1862.
  80. Link TM, Lang TF. Axial QCT: clinical applications and new developments. J Clin Densitom 2014; 17:438.
  81. Silva BC, Broy SB, Boutroy S, et al. Fracture Risk Prediction by Non-BMD DXA Measures: the 2015 ISCD Official Positions Part 2: Trabecular Bone Score. J Clin Densitom 2015; 18:309.
  82. Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res 2007; 22:425.
  83. Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab 2005; 90:6508.
  84. Majumdar S, Link TM, Augat P, et al. Trabecular bone architecture in the distal radius using magnetic resonance imaging in subjects with fractures of the proximal femur. Magnetic Resonance Science Center and Osteoporosis and Arthritis Research Group. Osteoporos Int 1999; 10:231.
  85. Link TM. Osteoporosis imaging: state of the art and advanced imaging. Radiology 2012; 263:3.
  86. Yang L, Peel N, Clowes JA, et al. Use of DXA-based structural engineering models of the proximal femur to discriminate hip fracture. J Bone Miner Res 2009; 24:33.
  87. Broy SB, Cauley JA, Lewiecki ME, et al. Fracture Risk Prediction by Non-BMD DXA Measures: the 2015 ISCD Official Positions Part 1: Hip Geometry. J Clin Densitom 2015; 18:287.
  88. Orwoll ES, Marshall LM, Nielson CM, et al. Finite element analysis of the proximal femur and hip fracture risk in older men. J Bone Miner Res 2009; 24:475.
  89. Zysset P, Qin L, Lang T, et al. Clinical Use of Quantitative Computed Tomography-Based Finite Element Analysis of the Hip and Spine in the Management of Osteoporosis in Adults: the 2015 ISCD Official Positions-Part II. J Clin Densitom 2015; 18:359.
  90. Siris ES, Miller PD, Barrett-Connor E, et al. Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment. JAMA 2001; 286:2815.
  91. Blake GM, Fogelman I. Peripheral or central densitometry: does it matter which technique we use? J Clin Densitom 2001; 4:83.
  92. Eastell R, Wahner HW, O'Fallon WM, et al. Unequal decrease in bone density of lumbar spine and ultradistal radius in Colles' and vertebral fracture syndromes. J Clin Invest 1989; 83:168.
  93. Melton LJ 3rd, Atkinson EJ, O'Fallon WM, et al. Long-term fracture prediction by bone mineral assessed at different skeletal sites. J Bone Miner Res 1993; 8:1227.
  94. Cummings SR, Black D. Bone mass measurements and risk of fracture in Caucasian women: a review of findings from prospective studies. Am J Med 1995; 98:24S.
  95. Miller PD, Barlas S, Brenneman SK, et al. An approach to identifying osteopenic women at increased short-term risk of fracture. Arch Intern Med 2004; 164:1113.
  96. Miller PD, Siris ES, Barrett-Connor E, et al. Prediction of fracture risk in postmenopausal white women with peripheral bone densitometry: evidence from the National Osteoporosis Risk Assessment. J Bone Miner Res 2002; 17:2222.
  97. Robbins J, Aragaki AK, Kooperberg C, et al. Factors associated with 5-year risk of hip fracture in postmenopausal women. JAMA 2007; 298:2389.
  98. Liu H, Paige NM, Goldzweig CL, et al. Screening for osteoporosis in men: a systematic review for an American College of Physicians guideline. Ann Intern Med 2008; 148:685.
  99. Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 1995; 332:767.
  100. Sambrook PN, Flahive J, Hooven FH, et al. Predicting fractures in an international cohort using risk factor algorithms without BMD. J Bone Miner Res 2011; 26:2770.
  101. Kanis JA, Johnell O, Oden A, et al. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporos Int 2001; 12:989.
  102. Center JR, Bliuc D, Nguyen TV, Eisman JA. Risk of subsequent fracture after low-trauma fracture in men and women. JAMA 2007; 297:387.
  103. Klotzbuecher CM, Ross PD, Landsman PB, et al. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 2000; 15:721.
  104. Kanis JA, Johnell O, De Laet C, et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone 2004; 35:375.
  105. Hodsman AB, Leslie WD, Tsang JF, Gamble GD. 10-year probability of recurrent fractures following wrist and other osteoporotic fractures in a large clinical cohort: an analysis from the Manitoba Bone Density Program. Arch Intern Med 2008; 168:2261.
  106. Gehlbach S, Saag KG, Adachi JD, et al. Previous fractures at multiple sites increase the risk for subsequent fractures: the Global Longitudinal Study of Osteoporosis in Women. J Bone Miner Res 2012; 27:645.
  107. Van Staa TP, Leufkens HG, Abenhaim L, et al. Use of oral corticosteroids and risk of fractures. J Bone Miner Res 2000; 15:993.
  108. Ensrud KE, Cauley J, Lipschutz R, Cummings SR. Weight change and fractures in older women. Study of Osteoporotic Fractures Research Group. Arch Intern Med 1997; 157:857.
  109. Ensrud KE, Lipschutz RC, Cauley JA, et al. Body size and hip fracture risk in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Am J Med 1997; 103:274.
  110. Langlois JA, Visser M, Davidovic LS, et al. Hip fracture risk in older white men is associated with change in body weight from age 50 years to old age. Arch Intern Med 1998; 158:990.
  111. Green AD, Colón-Emeric CS, Bastian L, et al. Does this woman have osteoporosis? JAMA 2004; 292:2890.
  112. Langlois JA, Harris T, Looker AC, Madans J. Weight change between age 50 years and old age is associated with risk of hip fracture in white women aged 67 years and older. Arch Intern Med 1996; 156:989.
  113. Meyer HE, Falch JA, O'Neill T, et al. Height and body mass index in Oslo, Norway, compared to other regions of Europe: do they explain differences in the incidence of hip fracture? European Vertebral Osteoporosis Study Group. Bone 1995; 17:347.
  114. Villareal DT, Fontana L, Weiss EP, et al. Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch Intern Med 2006; 166:2502.
  115. Ward KD, Klesges RC. A meta-analysis of the effects of cigarette smoking on bone mineral density. Calcif Tissue Int 2001; 68:259.
  116. Kanis JA, Johnell O, Oden A, et al. Smoking and fracture risk: a meta-analysis. Osteoporos Int 2005; 16:155.
  117. Kanis JA, Johansson H, Johnell O, et al. Alcohol intake as a risk factor for fracture. Osteoporos Int 2005; 16:737.
  118. Berg KM, Kunins HV, Jackson JL, et al. Association between alcohol consumption and both osteoporotic fracture and bone density. Am J Med 2008; 121:406.
  119. Ensrud KE, Lui LY, Taylor BC, et al. Renal function and risk of hip and vertebral fractures in older women. Arch Intern Med 2007; 167:133.
  120. Jassal SK, von Muhlen D, Barrett-Connor E. Measures of renal function, BMD, bone loss, and osteoporotic fracture in older adults: the Rancho Bernardo study. J Bone Miner Res 2007; 22:203.
  121. Mezuk B, Eaton WW, Golden SH. Depression and osteoporosis: epidemiology and potential mediating pathways. Osteoporos Int 2008; 19:1.
  122. Gankam Kengne F, Andres C, Sattar L, et al. Mild hyponatremia and risk of fracture in the ambulatory elderly. QJM 2008; 101:583.
  123. Schulz E, Arfai K, Liu X, et al. Aortic calcification and the risk of osteoporosis and fractures. J Clin Endocrinol Metab 2004; 89:4246.
  124. Schett G, Kiechl S, Weger S, et al. High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med 2006; 166:2495.
  125. Cauley JA, Danielson ME, Boudreau RM, et al. Inflammatory markers and incident fracture risk in older men and women: the Health Aging and Body Composition Study. J Bone Miner Res 2007; 22:1088.
  126. Gregg EW, Cauley JA, Seeley DG, et al. Physical activity and osteoporotic fracture risk in older women. Study of Osteoporotic Fractures Research Group. Ann Intern Med 1998; 129:81.
  127. van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 2004; 350:2033.
  128. McLean RR, Jacques PF, Selhub J, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 2004; 350:2042.
  129. Dhonukshe-Rutten RA, Pluijm SM, de Groot LC, et al. Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res 2005; 20:921.
  130. Sato Y, Iwamoto J, Kanoko T, Satoh K. Homocysteine as a predictive factor for hip fracture in elderly women with Parkinson's disease. Am J Med 2005; 118:1250.
  131. Gerdhem P, Ivaska KK, Isaksson A, et al. Associations between homocysteine, bone turnover, BMD, mortality, and fracture risk in elderly women. J Bone Miner Res 2007; 22:127.
  132. Périer MA, Gineyts E, Munoz F, et al. Homocysteine and fracture risk in postmenopausal women: the OFELY study. Osteoporos Int 2007; 18:1329.
  133. McLean RR, Jacques PF, Selhub J, et al. Plasma B vitamins, homocysteine, and their relation with bone loss and hip fracture in elderly men and women. J Clin Endocrinol Metab 2008; 93:2206.
  134. Leboff MS, Narweker R, LaCroix A, et al. Homocysteine levels and risk of hip fracture in postmenopausal women. J Clin Endocrinol Metab 2009; 94:1207.
  135. Lloyd T, Rollings N, Eggli DF, et al. Dietary caffeine intake and bone status of postmenopausal women. Am J Clin Nutr 1997; 65:1826.
  136. Wu CH, Yang YC, Yao WJ, et al. Epidemiological evidence of increased bone mineral density in habitual tea drinkers. Arch Intern Med 2002; 162:1001.
  137. Barrett-Connor E, Chang JC, Edelstein SL. Coffee-associated osteoporosis offset by daily milk consumption. The Rancho Bernardo Study. JAMA 1994; 271:280.
  138. Kim SH, Morton DJ, Barrett-Connor EL. Carbonated beverage consumption and bone mineral density among older women: the Rancho Bernardo Study. Am J Public Health 1997; 87:276.
  139. Tucker KL, Morita K, Qiao N, et al. Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study. Am J Clin Nutr 2006; 84:936.
  140. Christiansen C, Riis BJ, Rødbro P. Prediction of rapid bone loss in postmenopausal women. Lancet 1987; 1:1105.
  141. Hansen MA, Overgaard K, Riis BJ, Christiansen C. Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study. BMJ 1991; 303:961.
  142. Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 2000; 15:1526.
  143. Delmas PD, Eastell R, Garnero P, et al. The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 2000; 11 Suppl 6:S2.
  144. Johnell O, Kanis JA, Black DM, et al. Associations between baseline risk factors and vertebral fracture risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. J Bone Miner Res 2004; 19:764.
  145. Srivastava AK, Vliet EL, Lewiecki EM, et al. Clinical use of serum and urine bone markers in the management of osteoporosis. Curr Med Res Opin 2005; 21:1015.