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Postmenopausal osteoporosis

Nature Reviews Disease Primers volume 2, Article number: 16069 (2016) Cite this article

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Abstract

Osteoporosis is a metabolic bone disorder that is characterized by low bone mass and micro-architectural deterioration of bone tissue. Fractures of the proximal femur, the vertebrae and the distal radius are the most frequent osteoporotic fractures, although most fractures in the elderly are probably at least partly related to bone fragility. The incidence of fractures varies greatly by country, but on average up to 50% of women >50 years of age are at risk of fractures. Fractures severely affect the quality of life of an individual and are becoming a major public health problem owing to the ageing population. Postmenopausal osteoporosis, resulting from oestrogen deficiency, is the most common type of osteoporosis. Oestrogen deficiency results in an increase in bone turnover owing to effects on all types of bone cells. The imbalance in bone formation and resorption has effects on trabecular bone (loss of connectivity) and cortical bone (cortical thinning and porosity). Osteoporosis is diagnosed using bone density measurements of the lumbar spine and proximal femur. Preventive strategies to improve bone health include diet, exercise and abstaining from smoking. Fractures may be prevented by reducing falls in high-risk populations. Several drugs are licensed to reduce fracture risk by slowing down bone resorption (such as bisphosphonates and denosumab) or by stimulating bone formation (such as teriparatide). Improved understanding of the cellular basis for osteoporosis has resulted in new drugs targeted to key pathways, which are under development.

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Figure 1: Osteoporotic bone.
Figure 2: Fracture incidence with increasing age.
Figure 3: Bone remodelling.
Figure 4: Sex-specific differences in bone modelling (and remodelling).
Figure 5: Role of oestrogens in bone remodelling.
Figure 6: Fracture prevention by osteoporotic agents.
Figure 7: Evolution of fracture incidence and bisphosphonate use.

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References

  1. [No authors listed.] Consensus development conference on osteoporosis. Hong Kong, April 1–2, 1993. Am. J. Med. 95, 1S–78S (1993).

  2. Kanis, J. A. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. Osteoporos Int. 4, 368–381 (1994). This paper summarizes the key report from the WHO that defined osteoporosis on the basis of a bone density T-score.

    Article  CAS  PubMed  Google Scholar 

  3. Kanis, J. A. FRAX: WHO Fracture Risk Assessment Tool. QHOhttps://www.shef.ac.uk/FRAX/tool.jsp (2016).

  4. Siris, E. S. et al. The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int. 25, 1439–1443 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Eastell, R. Treatment of postmenopausal osteoporosis. N. Engl. J. Med. 338, 736–746 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Office of the Surgeon General (US). Bone Health and Osteoporosis: A Report of the Surgeon General (Office of the Surgeon General, 2004).

  7. Hernlund, E. et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch. Osteoporos 8, 136–136 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Burge, R. et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J. Bone Miner. Res. 22, 465–475 (2007).

    Article  PubMed  Google Scholar 

  9. van Staa, T. P., Dennison, E. M., Leufkens, H. G. & Cooper, C. Epidemiology of fractures in England and Wales. Bone 29, 517–522 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Cheng, S. Y. et al. Geographic trends in incidence of hip fractures: a comprehensive literature review. Osteoporos Int. 22, 2575–2586 (2011).

    Article  CAS  PubMed  Google Scholar 

  11. Cauley, J. A., Chalhoub, D., Kassem, A. M. & Fuleihan, G. E.-H. Geographic and ethnic disparities in osteoporotic fractures. Nat. Rev. Endocrinol. 10, 338–351 (2014).

    Article  PubMed  Google Scholar 

  12. Johnell, O., Gullberg, B., Allander, E. & Kanis, J. A. The apparent incidence of hip fracture in Europe: a study of national register sources. Osteoporos Int. 2, 298–302 (1992).

    Article  CAS  PubMed  Google Scholar 

  13. Cooper, C. et al. Secular trends in the incidence of hip and other osteoporotic fractures. Osteoporos Int. 22, 1277–1288 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Morin, S. N., Lix, L. M., Majumdar, S. R. & Leslie, W. D. Temporal trends in the incidence of osteoporotic fractures. Curr. Osteoporos Rep. 11, 263–269 (2013).

    Article  CAS  PubMed  Google Scholar 

  15. Leslie, W. D. et al. Trends in hip fracture rates in Canada. JAMA 302, 883–889 (2009).

    Article  CAS  PubMed  Google Scholar 

  16. Xia, W. B. et al. Rapidly increasing rates of hip fracture in Beijing, China. J. Bone Miner. Res. 27, 125–129 (2012).

    Article  PubMed  Google Scholar 

  17. Kinsella, K. & Wan, H. U.S. Census Bureau, International Population Reports, P95/09-1, An Aging World: 2008 (U.S. Government Printing Office, 2009).

    Google Scholar 

  18. Cooper, C., Campion, G. & Melton, L. J. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 2, 285–289 (1992). This paper highlights for the first time the epidemic in hip fractures.

    Article  CAS  PubMed  Google Scholar 

  19. Pocock, N. A. et al. Genetic determinants of bone mass in adults. A twin study. J. Clin. Invest. 80, 706–710 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hernandez-de Sosa, N. et al. Heritability of bone mineral density in a multivariate family-based study. Calcif. Tissue Int. 94, 590–596 (2014).

    Article  CAS  PubMed  Google Scholar 

  21. Michaëlsson, K., Melhus, H., Ferm, H., Ahlbom, A. & Pedersen, N. L. Genetic liability to fractures in the elderly. Arch. Intern. Med. 165, 1825–1830 (2005).

    Article  PubMed  Google Scholar 

  22. Ioannidis, J. P. A. et al. Differential genetic effects of ESR1 gene polymorphisms on osteoporosis outcomes. JAMA 292, 2105–2114 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Uitterlinden, A. G. et al. The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. Ann. Intern. Med. 145, 255–264 (2006).

    Article  CAS  PubMed  Google Scholar 

  24. Langdahl, B. L. et al. Large-scale analysis of association between polymorphisms in the transforming growth factor β1 gene (TGFB1) and osteoporosis: the GENOMOS study. Bone 42, 969–981 (2008).

    Article  CAS  PubMed  Google Scholar 

  25. van Meurs, J. B. J. et al. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis. JAMA 299, 1277–1290 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ralston, S. H. et al. Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. PLoS Med. 3, e90 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Xie, W., Ji, L., Zhao, T. & Gao, P. Identification of transcriptional factors and key genes in primary osteoporosis by DNA microarray. Med. Sci. Monit. 21, 1333–1344 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Keupp, K. et al. Mutations in WNT1 cause different forms of bone fragility. Am. J. Hum. Genet. 92, 565–574 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zheng, H.-F. et al. WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. PLoS Genet. 8, e1002745 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Richards, J. B. et al. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 371, 1505–1512 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Estrada, K. et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat. Genet. 44, 491–501 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Garnero, P., Sornay-Rendu, E., Chapuy, M. C. & Delmas, P. D. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J. Bone Miner. Res. 11, 337–349 (1996).

    Article  CAS  PubMed  Google Scholar 

  33. Sims, N. A. & Civitelli, R. Cell–cell signaling: broadening our view of the basic multicellular unit. Calcif. Tissue Int. 94, 2–3 (2014).

    Article  CAS  PubMed  Google Scholar 

  34. Khosla, S. New insights into androgen and estrogen receptor regulation of the male skeleton. J. Bone Miner. Res. 30, 1134–1137 (2015). This review describes the importance of oestrogen action on the male skeleton and its role on bone homeostasis.

    Article  CAS  PubMed  Google Scholar 

  35. Manolagas, S. C. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr. Rev. 31, 266–300 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Seeman, E. & Delmas, P. D. Bone quality — the material and structural basis of bone strength and fragility. N. Engl. J. Med. 354, 2250–2261 (2006).

    Article  CAS  PubMed  Google Scholar 

  37. Manolagas, S. C., O'Brien, C. A. & Almeida, M. The role of estrogen and androgen receptors in bone health and disease. Nat. Rev. Endocrinol. 9, 699–712 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Clowes, J. A., Riggs, B. L. & Khosla, S. The role of the immune system in the pathophysiology of osteoporosis. Immunol. Rev. 208, 207–227 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Bonjour, J.-P. & Chevalley, T. Pubertal timing, bone acquisition, and risk of fracture throughout life. Endocr. Rev. 35, 820–847 (2014).

    Article  CAS  PubMed  Google Scholar 

  40. Szulc, P., Seeman, E., Duboeuf, F., Sornay-Rendu, E. & Delmas, P. D. Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. J. Bone Miner. Res. 21, 1856–1863 (2006).

    Article  PubMed  Google Scholar 

  41. Nishiyama, K. K., Macdonald, H. M., Buie, H. R., Hanley, D. A. & Boyd, S. K. Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: an in vivo HR-pQCT study. J. Bone Miner. Res. 25, 882–890 (2010).

    PubMed  Google Scholar 

  42. Patsch, J. M. et al. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J. Bone Miner. Res. 28, 313–324 (2013).

    Article  PubMed  Google Scholar 

  43. Gennari, L., Khosla, S. & Bilezikian, J. P. Estrogen and fracture risk in men. J. Bone Miner. Res. 23, 1548–1551 (2008).

    Article  PubMed  Google Scholar 

  44. Santen, R. J., Brodie, H., Simpson, E. R., Siiteri, P. K. & Brodie, A. History of aromatase: saga of an important biological mediator and therapeutic target. Endocr. Rev. 30, 343–375 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Khosla, S. Update on estrogens and the skeleton. J. Clin. Endocrinol. Metab. 95, 3569–3577 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kovacs, C. S. Osteoporosis presenting in pregnancy, puerperium, and lactation. Curr. Opin. Endocrinol. Diabetes Obes. 21, 468–475 (2014).

    Article  PubMed  Google Scholar 

  47. Smith, E. P. et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N. Engl. J. Med. 331, 1056–1061 (1994).

    Article  CAS  PubMed  Google Scholar 

  48. Falahati-Nini, A. et al. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J. Clin. Invest. 106, 1553–1560 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Weitzmann, M. N. & Pacifici, R. Estrogen deficiency and bone loss: an inflammatory tale. J. Clin. Invest. 116, 1186–1194 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kousteni, S. et al. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104, 719–730 (2001).

    CAS  PubMed  Google Scholar 

  51. Syed, F. A. et al. Skeletal effects of estrogen are mediated by opposing actions of classical and nonclassical estrogen receptor pathways. J. Bone Miner. Res. 20, 1992–2001 (2005).

    Article  CAS  PubMed  Google Scholar 

  52. Dallas, S. L., Prideaux, M. & Bonewald, L. F. The osteocyte: an endocrine cell … and more. Endocr. Rev. 34, 658–690 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Rachner, T. D., Khosla, S. & Hofbauer, L. C. Osteoporosis: now and the future. Lancet 377, 1276–1287 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Chow, J., Tobias, J. H., Colston, K. W. & Chambers, T. J. Estrogen maintains trabecular bone volume in rats not only by suppression of bone resorption but also by stimulation of bone formation. J. Clin. Invest. 89, 74–78 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Oursler, M. J. Estrogen regulation of gene expression in osteoblasts and osteoclasts. Crit. Rev. Eukaryot. Gene Expr. 8, 125–140 (1998).

    Article  CAS  PubMed  Google Scholar 

  56. Khastgir, G. et al. Anabolic effect of estrogen replacement on bone in postmenopausal women with osteoporosis: histomorphometric evidence in a longitudinal study. J. Clin. Endocrinol. Metab. 86, 289–295 (2001).

    CAS  PubMed  Google Scholar 

  57. Hofbauer, L. C. & Schoppet, M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292, 490–495 (2004).

    Article  CAS  PubMed  Google Scholar 

  58. Eghbali-Fatourechi, G. et al. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J. Clin. Invest. 111, 1221–1230 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Nakashima, T. et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat. Med. 17, 1231–1234 (2011).

    Article  CAS  PubMed  Google Scholar 

  60. Mödder, U. I. et al. Regulation of circulating sclerostin levels by sex steroids in women and in men. J. Bone Miner. Res. 26, 27–34 (2011).

    Article  CAS  PubMed  Google Scholar 

  61. Fujita, K. et al. Effects of estrogen on bone mRNA levels of sclerostin and other genes relevant to bone metabolism in postmenopausal women. J. Clin. Endocrinol. Metab. 99, E81–E88 (2014).

    Article  PubMed  Google Scholar 

  62. Lee, K., Jessop, H., Suswillo, R., Zaman, G. & Lanyon, L. Endocrinology: bone adaptation requires oestrogen receptor-α. Nature 424, 389–389 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Almeida, M. et al. Estrogens attenuate oxidative stress and the differentiation and apoptosis of osteoblasts by DNA-binding-independent actions of the ERα. J. Bone Miner. Res. 25, 769–781 (2010).

    CAS  PubMed  Google Scholar 

  64. Goettsch, C. et al. NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis. J. Clin. Invest. 123, 4731–4738 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kanis, J. A., Johnell, O., Oden, A., Johansson, H. & McCloskey, E. FRAX™ and the assessment of fracture probability in men and women from the UK. Osteoporos Int. 19, 385–397 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Nguyen, N. D., Frost, S. A., Center, J. R., Eisman, J. A. & Nguyen, T. V. Development of prognostic nomograms for individualizing 5-year and 10-year fracture risks. Osteoporos Int. 19, 1431–1444 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. 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 339, b4229 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  68. [No authors listed.] Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ. Techn. Rep. Ser. 843, 1–129 (1994).

  69. Marshall, D., Johnell, O. & Wedel, H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 312, 1254–1259 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kanis, J. A. Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359, 1929–1936 (2002).

    Article  PubMed  Google Scholar 

  71. Vasikaran, S. et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. 22, 391–420 (2011).

    Article  CAS  PubMed  Google Scholar 

  72. Diez-Perez, A. et al. Treatment failure in osteoporosis. Osteoporos Int. 23, 2769–2774 (2012).

    Article  CAS  PubMed  Google Scholar 

  73. Hernandez, C. J., Beaupré, G. S. & Carter, D. R. A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis. Osteoporos Int. 14, 843–847 (2003).

    Article  CAS  PubMed  Google Scholar 

  74. Cadogan, J., Eastell, R., Jones, N. & Barker, M. E. Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial. BMJ 315, 1255–1260 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Chevalley, T., Rizzoli, R., Hans, D., Ferrari, S. & Bonjour, J.-P. Interaction between calcium intake and menarcheal age on bone mass gain: an eight-year follow-up study from prepuberty to postmenarche. J. Clin. Endocrinol. Metab. 90, 44–51 (2005).

    Article  CAS  PubMed  Google Scholar 

  76. Winzenberg, T., Shaw, K., Fryer, J. & Jones, G. Effects of calcium supplementation on bone density in healthy children: meta-analysis of randomised controlled trials. BMJ 333, 775–775 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Bischoff-Ferrari, H. A. et al. Dietary calcium and serum 25-hydroxyvitamin D status in relation to BMD among U. S. adults. J. Bone Miner. Res. 24, 935–942 (2009).

    Article  CAS  PubMed  Google Scholar 

  78. Shea, B. et al. Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis. Endocr. Rev. 23, 552–559 (2002).

    Article  CAS  PubMed  Google Scholar 

  79. Elders, P. J. et al. Long-term effect of calcium supplementation on bone loss in perimenopausal women. J. Bone Miner. Res. 9, 963–970 (1994).

    Article  CAS  PubMed  Google Scholar 

  80. Bischoff-Ferrari, H. A. et al. Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials. Am. J. Clin. Nutr. 86, 1780–1790 (2007).

    Article  CAS  PubMed  Google Scholar 

  81. Bolland, M. J. et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 341, c3691 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wang, L., Manson, J. E., Song, Y. & Sesso, H. D. Systematic review: vitamin D and calcium supplementation in prevention of cardiovascular events. Ann. Intern. Med. 152, 315–323 (2010).

    Article  PubMed  Google Scholar 

  83. Lewis, J. R. et al. The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: a collaborative meta-analysis of randomized controlled trials. J. Bone Miner. Res. 30, 165–175 (2015).

    Article  CAS  PubMed  Google Scholar 

  84. Wallace, R. B. et al. Urinary tract stone occurrence in the Women's Health Initiative (WHI) randomized clinical trial of calcium and vitamin D supplements. Am. J. Clin. Nutr. 94, 270–277 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Serio, A. & Fraioli, A. Epidemiology of nephrolithiasis. Nephron 81 (Suppl. 1), 26–30 (1999).

    Article  PubMed  Google Scholar 

  86. Bischoff-Ferrari, H. A. et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch. Intern. Med. 169, 551–561 (2009).

    Article  CAS  PubMed  Google Scholar 

  87. Avenell, A., Mak, J. C. S. & O'Connell, D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst. Rev. 4, CD000227 (2014). This paper stresses that, although vitamin D alone may not prevent fracture, when given along with calcium, it may prevent fracture.

    Google Scholar 

  88. Ceglia, L. Vitamin D and its role in skeletal muscle. Curr. Opin. Clin. Nutr. Metab. Care 12, 628–633 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Cao, J. J. & Nielsen, F. H. Acid diet (high-meat protein) effects on calcium metabolism and bone health. Curr. Opin. Clin. Nutr. Metab. Care 13, 698–702 (2010).

    Article  CAS  PubMed  Google Scholar 

  90. Byberg, L., Bellavia, A., Orsini, N., Wolk, A. & Michaëlsson, K. Fruit and vegetable intake and risk of hip fracture: a cohort study of Swedish men and women. J. Bone Miner. Res. 30, 976–984 (2015).

    Article  PubMed  Google Scholar 

  91. Fenton, T. R., Eliasziw, M., Lyon, A. W., Tough, S. C. & Hanley, D. A. Meta-analysis of the quantity of calcium excretion associated with the net acid excretion of the modern diet under the acid-ash diet hypothesis. Am. J. Clin. Nutr. 88, 1159–1166 (2008).

    Article  CAS  PubMed  Google Scholar 

  92. Dawson-Hughes, B. & Harris, S. S. Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. Am. J. Clin. Nutr. 75, 773–779 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Sahni, S. et al. Protective effect of high protein and calcium intake on the risk of hip fracture in the Framingham offspring cohort. J. Bone Miner. Res. 25, 2770–2776 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ensrud, K. E., Cauley, J., Lipschutz, R. & Cummings, S. R. Weight change and fractures in older women. Study of Osteoporotic Fractures Research Group. Arch. Intern. Med. 157, 857–863 (1997).

    Article  CAS  PubMed  Google Scholar 

  95. Cummings, S. R. et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N. Engl. J. Med. 332, 767–773 (1995).

    Article  CAS  PubMed  Google Scholar 

  96. Crandall, C. J. et al. Postmenopausal weight change and incidence of fracture: post hoc findings from Women's Health Initiative Observational Study and Clinical Trials. BMJ 350, h25 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Clynes, M. A. et al. Definitions of sarcopenia: associations with previous falls and fracture in a population sample. Calcif. Tissue Int. 97, 445–452 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Lang, T. et al. Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J. Bone Miner. Res. 19, 1006–1012 (2004).

    Article  PubMed  Google Scholar 

  99. Heinonen, A. et al. Bone mineral density in female athletes representing sports with different loading characteristics of the skeleton. Bone 17, 197–203 (1995).

    Article  CAS  PubMed  Google Scholar 

  100. Leichter, I. et al. Gain in mass density of bone following strenuous physical activity. J. Orthop. Res. 7, 86–90 (1989).

    Article  CAS  PubMed  Google Scholar 

  101. McKay, H. A. et al. “Bounce at the Bell”: a novel program of short bouts of exercise improves proximal femur bone mass in early pubertal children. Br. J. Sports Med. 39, 521–526 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Colberg, S. R. et al. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement executive summary. Diabetes Care 33, 2692–2696 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Rubin, C. T., Bain, S. D. & McLeod, K. J. Suppression of the osteogenic response in the aging skeleton. Calcif. Tissue Int. 50, 306–313 (1992).

    Article  CAS  PubMed  Google Scholar 

  104. Iwamoto, J., Takeda, T. & Ichimura, S. Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis. J. Orthop. Res. 6, 128–132 (2001).

    CAS  Google Scholar 

  105. Bolton, K. L. et al. Effects of exercise on bone density and falls risk factors in post-menopausal women with osteopenia: a randomised controlled trial. J. Sci. Med. Sport 15, 102–109 (2012).

    Google Scholar 

  106. Kemmler, W. et al. Exercise and fractures in postmenopausal women: 12-year results of the Erlangen Fitness and Osteoporosis Prevention Study (EFOPS). Osteoporos Int. 23, 1267–1276 (2012).

    Article  CAS  PubMed  Google Scholar 

  107. von Stengel, S., Kemmler, W., Engelke, K. & Kalender, W. A. Effects of whole body vibration on bone mineral density and falls: results of the randomized controlled ELVIS study with postmenopausal women. Osteoporos Int. 22, 317–325 (2011).

    Article  CAS  PubMed  Google Scholar 

  108. Leung, K. S. et al. Effects of 18-month low-magnitude high-frequency vibration on fall rate and fracture risks in 710 community elderly — a cluster-randomized controlled trial. Osteoporos Int. 25, 1785–1795 (2014).

    Article  CAS  PubMed  Google Scholar 

  109. Kanis, J. A. et al. Smoking and fracture risk: a meta-analysis. Osteoporos Int. 16, 155–162 (2005).

    Article  CAS  PubMed  Google Scholar 

  110. Krall, E. A. & Dawson-Hughes, B. Smoking increases bone loss and decreases intestinal calcium absorption. J. Bone Miner. Res. 14, 215–220 (1999).

    Article  CAS  PubMed  Google Scholar 

  111. Jensen, J., Christiansen, C. & Rødbro, P. Cigarette smoking, serum estrogens, and bone loss during hormone-replacement therapy early after menopause. N. Engl. J. Med. 313, 973–975 (1985).

    Article  CAS  PubMed  Google Scholar 

  112. Oncken, C. et al. Impact of smoking cessation on bone mineral density in postmenopausal women. J. Womens Health (Larchmt) 15, 1141–1150 (2006).

    Article  Google Scholar 

  113. Schwartz, A. V., Nevitt, M. C., Brown, B. W. & Kelsey, J. L. Increased falling as a risk factor for fracture among older women: the study of osteoporotic fractures. Am. J. Epidemiol. 161, 180–185 (2005).

    Article  PubMed  Google Scholar 

  114. Oliver, D. et al. Strategies to prevent falls and fractures in hospitals and care homes and effect of cognitive impairment: systematic review and meta-analyses. BMJ 334, 82–82 (2007).

    Article  PubMed  Google Scholar 

  115. Harwood, R. H. et al. Falls and health status in elderly women following first eye cataract surgery: a randomised controlled trial. Br. J. Ophthalmol. 89, 53–59 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Bischoff-Ferrari, H. A. et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 339, b3692 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Panel on Prevention of Falls in Older Persons, American Geriatrics Society and British Geriatrics Society. Summary of the Updated American Geriatrics Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J. Am. Geriatr. Soc. 59, 148–157 (2011).

    Article  Google Scholar 

  118. Institute of Medicine. Dietary Reference Ranges for Calcium and Vitamin D (National Academies Press, 2011).

  119. Michael, Y. L. et al. Primary care-relevant interventions to prevent falling in older adults: a systematic evidence review for the U. S. Preventive Services Task Force. Ann. Intern. Med. 153, 815–825 (2010).

    Article  PubMed  Google Scholar 

  120. Dawson-Hughes, B. et al. IOF position statement: vitamin D recommendations for older adults. Osteoporos Int. 21, 1151–1154 (2010).

    Article  CAS  PubMed  Google Scholar 

  121. Garvan Institute. Fracture Risk Calculator. Garvan Institutehttp://www.garvan.org.au/promotions/bone-fracture-risk/calculator/ (2016).

  122. Billington, E. O., Gamble, G. D. & Reid, I. R. Reasons for discrepancies in hip fracture risk estimates using FRAX and Garvan calculators. Maturitas 85, 11–18 (2016).

    Article  PubMed  Google Scholar 

  123. Dawson-Hughes, B. et al. Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA. Osteoporos Int. 19, 449–458 (2008).

    Article  CAS  PubMed  Google Scholar 

  124. Reid, I. R. Efficacy, effectiveness and side effects of medications used to prevent fractures. J. Intern. Med. 277, 690–706 (2015).

    Article  CAS  PubMed  Google Scholar 

  125. Ebetino, F. H. et al. The relationship between the chemistry and biological activity of the bisphosphonates. Bone 49, 20–33 (2011).

    Article  CAS  PubMed  Google Scholar 

  126. Murad, M. H. et al. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J. Clin. Endocrinol. Metab. 97, 1871–1880 (2012).

    Article  CAS  PubMed  Google Scholar 

  127. Black, D. M. et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N. Engl. J. Med. 356, 1809–1822 (2007).

    Article  CAS  PubMed  Google Scholar 

  128. Khosla, S. et al. Benefits and risks of bisphosphonate therapy for osteoporosis. J. Clin. Endocrinol. Metab. 97, 2272–2282 (2012).

    Article  CAS  PubMed  Google Scholar 

  129. Cartsos, V. M., Zhu, S. & Zavras, A. I. Bisphosphonate use and the risk of adverse jaw outcomes. J. Am. Dent. Assoc. 139, 23–30 (2008).

    Article  PubMed  Google Scholar 

  130. Pazianas, M., Blumentals, W. A. & Miller, P. D. Lack of association between oral bisphosphonates and osteonecrosis using jaw surgery as a surrogate marker. Osteoporos Int. 19, 773–779 (2008).

    Article  CAS  PubMed  Google Scholar 

  131. Lin, T. C., Yang, C. Y., Kao Yang, Y. H. & Lin, S. J. Incidence and risk of osteonecrosis of the jaw among the Taiwan osteoporosis population. Osteoporos Int. 25, 1503–1511 (2014).

    Article  PubMed  Google Scholar 

  132. Schilcher, J., Michaelsson, K. & Aspenberg, P. Bisphosphonate use and atypical fractures of the femoral shaft. N. Engl. J. Med. 364, 1728–1737 (2011).

    Article  CAS  PubMed  Google Scholar 

  133. Shane, E. et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J. Bone Miner. Res. 29, 1–23 (2014).

    Article  PubMed  Google Scholar 

  134. Schilcher, J., Koeppen, V., Aspenberg, P. & Michaëlsson, K. Risk of atypical femoral fracture during and after bisphosphonate use. N. Engl. J. Med. 371, 974–976 (2014).

    Article  PubMed  Google Scholar 

  135. Dell, R. M. et al. Incidence of atypical nontraumatic diaphyseal fractures of the femur. J. Bone Miner. Res. 27, 2544–2550 (2012).

    Article  PubMed  Google Scholar 

  136. Cummings, S. R. et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med. 361, 756–765 (2009).

    Article  CAS  PubMed  Google Scholar 

  137. Papapoulos, S. et al. The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporos Int. 26, 2773–2783 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Miller, P. D. et al. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 43, 222–229 (2008).

    Article  CAS  PubMed  Google Scholar 

  139. Aubry-Rozier, B., Gonzalez-Rodriguez, E., Stoll, D. & Lamy, O. Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports. Osteoporos Int. 27, 1923–1925 (2016).

    Article  CAS  PubMed  Google Scholar 

  140. Leder, B. Z. et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA Switch study): extension of a randomised controlled trial. Lancet 386, 1147–1155 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. McClung, M. R. et al. Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch. Intern. Med. 165, 1762–1768 (2005).

    Article  CAS  PubMed  Google Scholar 

  142. Neer, R. M. et al. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. 344, 1434–1441 (2001).

    Article  CAS  PubMed  Google Scholar 

  143. Nakamura, T. et al. Randomized teriparatide human parathyroid hormone (PTH) 1–34 once-weekly efficacy research (TOWER) trial for examining the reduction in new vertebral fractures in subjects with primary osteoporosis and high fracture risk. J. Clin. Endocrinol. Metab. 97, 3097–3106 (2012).

    Article  CAS  PubMed  Google Scholar 

  144. Bang, U. C., Hyldstrup, L. & Jensen, J. E. B. The impact of recombinant parathyroid hormone on malignancies and mortality: 7 years of experience based on nationwide Danish registers. Osteoporos Int. 25, 639–644 (2014).

    Article  CAS  PubMed  Google Scholar 

  145. Cosman, F. et al. Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis. J. Bone Miner. Res. 26, 503–511 (2011).

    Article  CAS  PubMed  Google Scholar 

  146. Cosman, F. et al. Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the antiresorptive agent. J. Clin. Endocrinol. Metab. 94, 3772–3780 (2009).

    Article  CAS  PubMed  Google Scholar 

  147. Recker, R. R. et al. Comparative effects of teriparatide and strontium ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis. J. Bone Miner. Res. 24, 1358–1368 (2009).

    Article  CAS  PubMed  Google Scholar 

  148. Chavassieux, P. et al. Bone histomorphometry of transiliac paired bone biopsies after 6 or 12 months of treatment with oral strontium ranelate in 387 osteoporotic women: randomized comparison to alendronate. J. Bone Miner. Res. 29, 618–628 (2014).

    Article  CAS  PubMed  Google Scholar 

  149. Meunier, P. J. et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N. Engl. J. Med. 350, 459–468 (2004).

    Article  CAS  PubMed  Google Scholar 

  150. Reginster, J. Y. et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. J. Clin. Endocrinol. Metab. 90, 2816–2822 (2005).

    Article  CAS  PubMed  Google Scholar 

  151. Tan, K. W., Wang, Y. S. & Tay, Y. K. Stevens–Johnson syndrome due to strontium ranelate. Ann. Acad. Med. Singapore 40, 510–511 (2011).

    PubMed  Google Scholar 

  152. Medicines and Healthcare Products Regulatory Agency (MHRA). Strontium ranelate (Protelos): risk of serious cardiac disorders — restricted indications, new contraindications, and warnings. Drug Safety Updatehttp://pad.res360.net/Content/Documents/Strontium%20Safety%20Alert%20April%202013.pdf (2013).

  153. European Medicines Agency. Protelos/Osseor to remain available but with further restrictions. EMAhttp://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Protelos_and_Osseor/European_Commission_final_decision/WC500173034.pdf (2014).

  154. Lindsay, R., Hart, D. M., Forrest, C. & Baird, C. Prevention of spinal osteoporosis in oophorectomised women. Lancet 2, 1151–1153 (1980).

    Article  CAS  PubMed  Google Scholar 

  155. Rossouw, J. E. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women — principal results from the Women's Health Initiative randomized controlled trial. JAMA 288, 321–333 (2002).

    Article  CAS  PubMed  Google Scholar 

  156. Anderson, G. L. et al. Effects of conjugated, equine estrogen in postmenopausal women with hysterectomy — the Women's Health Initiative randomized controlled trial. JAMA 291, 1701–1712 (2004).

    Article  CAS  PubMed  Google Scholar 

  157. Rossouw, J. E. et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 297, 1465–1477 (2007).

    Article  CAS  PubMed  Google Scholar 

  158. Reid, I. R. et al. A comparison of the effects of raloxifene and conjugated equine estrogen on bone and lipids in healthy postmenopausal women. Arch. Intern. Med. 164, 871–879 (2004).

    Article  CAS  PubMed  Google Scholar 

  159. Ettinger, B. et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene — results from a 3-year randomized clinical trial. JAMA 282, 637–645 (1999).

    Article  CAS  PubMed  Google Scholar 

  160. Barrett-Connor, E. et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N. Engl. J. Med. 355, 125–137 (2006).

    Article  CAS  PubMed  Google Scholar 

  161. Sharifi, M. & Lewiecki, E. M. Conjugated estrogens combined with bazedoxifene: the first approved tissue selective estrogen complex therapy. Expert Rev. Clin. Pharmacol. 7, 281–291 (2014).

    Article  CAS  PubMed  Google Scholar 

  162. Mirkin, S., Ryan, K. A., Chandran, A. B. & Komm, B. S. Bazedoxifene/conjugated estrogens for managing the burden of estrogen deficiency symptoms. Maturitas 77, 24–31 (2014).

    Article  CAS  PubMed  Google Scholar 

  163. Lindsay, R., Gallagher, J. C., Kagan, R., Pickar, J. H. & Constantine, G. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil. Steril. 92, 1045–1052 (2009).

    Article  CAS  PubMed  Google Scholar 

  164. Silverman, S. L. et al. Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J. Bone Miner. Res. 23, 1923–1934 (2008).

    Article  CAS  PubMed  Google Scholar 

  165. Cummings, S. R. et al. Lasofoxifene in postmenopausal women with osteoporosis. N. Engl. J. Med. 362, 686–696 (2010).

    Article  CAS  PubMed  Google Scholar 

  166. Lips, P. & van Schoor, N. M. Quality of life in patients with osteoporosis. Osteoporos Int. 16, 447–455 (2005).

    Article  PubMed  Google Scholar 

  167. Gold, D. T. The clinical impact of vertebral fractures: quality of life in women with osteoporosis. Bone 18, 185S–189S (1996).

    Article  CAS  PubMed  Google Scholar 

  168. Cauley, J. A., Thompson, D. E., Ensrud, K. C., Scott, J. C. & Black, D. Risk of mortality following clinical fractures. Osteoporos Int. 11, 556–561 (2000). This study, using data from the Fracture Intervention Trial, was one of the first to examine mortality resulting from major osteoporotic fractures and the first to identify excess mortality associated with clinical vertebral fractures.

    Article  CAS  PubMed  Google Scholar 

  169. Randell, A. G. et al. Deterioration in quality of life following hip fracture: a prospective study. Osteoporos Int. 11, 460–466 (2000).

    Article  CAS  PubMed  Google Scholar 

  170. Papaioannou, A. et al. Determinants of health-related quality of life in women with vertebral fractures. Osteoporos Int. 17, 355–363 (2006).

    Article  PubMed  Google Scholar 

  171. Bhattacharya, R., Shen, C. & Sambamoorthi, U. Excess risk of chronic physical conditions associated with depression and anxiety. BMC Psychiatry 14, 10 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  172. Silverman, S. L. Quality-of-life issues in osteoporosis. Curr. Rheumatol. Rep. 7, 39–45 (2005).

    Article  PubMed  Google Scholar 

  173. Pike, C. et al. Direct and indirect costs of non-vertebral fracture patients with osteoporosis in the US. PharmacoEconomics 28, 395–409 (2010).

    Article  PubMed  Google Scholar 

  174. Eekman, D. A. et al. Indirect costs account for half of the total costs of an osteoporotic fracture: a prospective evaluation. Osteoporos Int. 25, 195–204 (2014).

    Article  CAS  PubMed  Google Scholar 

  175. Gold, D. T. & Silverman, S. L. The Downward Spiral of Vertebral Osteoporosis: Consequences (Cedars-Sinai Medical Center, 2003).

    Google Scholar 

  176. Ballane, G., Cauley, J. A., Luckey, M. M. & Fuleihan Gel, H. Secular trends in hip fractures worldwide: opposing trends East versus West. J. Bone Miner. Res. 29, 1745–1755 (2014).

    Article  PubMed  Google Scholar 

  177. Brauer, C. A., Coca-Perraillon, M., Cutler, D. M. & Rosen, A. B. Incidence and mortality of hip fractures in the United States. JAMA 302, 1573–1579 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Hiligsmann, M. et al. Trends in hip fracture incidence and in the prescription of antiosteoporosis medications during the same time period in Belgium (2000–2007). Arthritis Care Res. (Hoboken) 64, 744–750 (2012).

    Article  Google Scholar 

  179. Wright, N. C. et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J. Bone Miner. Res. 29, 2520–2526 (2014).

    Article  PubMed  Google Scholar 

  180. Looker, A. C., Melton, L. J. 3rd, Borrud, L. G. & Shepherd, J. A. Changes in femur neck bone density in US adults between 1988–1994 and 2005–2008: demographic patterns and possible determinants. Osteoporos Int. 23, 771–780 (2012).

    Article  CAS  PubMed  Google Scholar 

  181. Jha, S., Wang, Z., Laucis, N. & Bhattacharyya, T. Trends in media reports, oral bisphosphonate prescriptions, and hip fractures 1996–2012: an ecological analysis. J. Bone Miner. Res. 30, 2179–2187 (2015). This paper shows the recent trend for fewer prescriptions of oral bisphosphonates and relates this to media announcements.

    Article  CAS  PubMed  Google Scholar 

  182. Eisman, J. A. et al. Making the first fracture the last fracture: ASBMR Task Force report on secondary fracture prevention. J. Bone Miner. Res. 27, 2039–2046 (2012).

    Article  PubMed  Google Scholar 

  183. McClung, M. R. et al. Romosozumab in postmenopausal women with low bone mineral density. N. Engl. J. Med. 370, 412–420 (2014).

    Article  CAS  PubMed  Google Scholar 

  184. Fierce Biotech. Amgen and UCB announce positive top-line results from the phase 3 study of Romosozumab in postmenopausal women with osteoporosis. Fierce Biotechhttp://www.fiercebiotech.com/press-releases/amgen-and-ucb-announce-positive-top-line-results-phase-3-study-romosozumab (2016).

  185. Leder, B. Z. et al. Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. J. Clin. Endocrinol. Metab. 100, 697–706 (2015).

    Article  CAS  PubMed  Google Scholar 

  186. Tucker, M. E. Novel agent abaloparatide reduces fractures, including wrist. Medscapehttp://www.medscape.com/viewarticle/841015 (2015).

  187. Rizzoli, R. et al. Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study. Osteoporos Int. 27, 2099–2107 (2016).

    Article  CAS  PubMed  Google Scholar 

  188. [No authors listed.] Merck announces data from pivotal phase 3 fracture outcomes study for odanacatib, an investigational oral, once-weekly treatment for osteoporosis. Business Wirehttp://www.businesswire.com/news/home/20140915006286/en/Merck-Announces-Data-Pivotal-Phase-3-Fracture (2014).

  189. [No authors listed.] Merck provides update on odanacatib development program. Business Wirehttp://www.businesswire.com/news/home/20160902005107/en/Merck-Update-Odanacatib-Development-Program (2016).

  190. Cosman, F. et al. Clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 25, 2359–2381 (2014). This is a recent guide for clinicians who manage osteoporosis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Compston, J. et al. Diagnosis and management of osteoporosis in postmenopausal women and older men in the UK: National Osteoporosis Guideline Group (NOGG) update 2013. Maturitas 75, 392–396 (2013).

    Article  CAS  PubMed  Google Scholar 

  192. Kanis, J. A. et al. Goal-directed treatment of osteoporosis in Europe. Osteoporos Int. 25, 2533–2543 (2014).

    Article  CAS  PubMed  Google Scholar 

  193. International Osteoporosis Foundation. Guideline references. IOFhttps://www.iofbonehealth.org/guideline-references (accessed 12 Sep 2016).

  194. Cummings, S. R. et al. Goal-directed treatment of osteoporosis. J. Bone Miner. Res. 28, 433–438 (2013).

    Article  PubMed  Google Scholar 

  195. Austin, M. et al. Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures. J. Bone Miner. Res. 27, 687–693 (2012).

    Article  CAS  PubMed  Google Scholar 

  196. Jacques, R. M. et al. Relationship of changes in total hip bone mineral density to vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis treated with once-yearly zoledronic acid 5 mg: the HORIZON-Pivotal Fracture Trial (PFT). J. Bone Miner. Res. 27, 1627–1634 (2012).

    Article  CAS  PubMed  Google Scholar 

  197. Felsenberg, D. et al. Incidence of vertebral fracture in Europe: results from the European Prospective Osteoporosis Study (EPOS). J. Bone Miner. Res. 17, 716–724 (2002).

    Article  CAS  PubMed  Google Scholar 

  198. Curtis, E. M. et al. Epidemiology of fractures in the United Kingdom 1988–2012: variation with age, sex, geography, ethnicity and socioeconomic status. Bone 87, 19–26 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  199. McClung, M. et al. Odanacatib anti-fracture efficacy and safety in postmenopausal women with osteoporosis: results from the phase III long-term odanacatib fracture trial. ACRhttp://acrabstracts.org/abstract/odanacatib-anti-fracture-efficacy-and-safety-in-postmenopausal-women-with-osteoporosis-results-from-the-phase-iii-long-term-odanacatib-fracture-trial/ (2014).

  200. Greenspan, S. L. et al. Effect of recombinant human parathyroid hormone (1–84) on vertebral fracture and bone mineral density in postmenopausal women with osteoporosis — a randomized trial. Ann. Intern. Med. 146, 326–339 (2007).

    Article  PubMed  Google Scholar 

  201. Reid, I. R. Short-term and long-term effects of osteoporosis therapies. Nat. Rev. Endocrinol. 11, 418–428 (2015).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

R.E. was supported by a Senior Investigator Award from the National Institute of Health Research. L.C.H. was funded by Deutsche Forschungsgemeinschaft, SFB-655 and Transregio-67.

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Authors and Affiliations

  1. Academic Unit of Bone Metabolism, and Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK

    Richard Eastell

  2. Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre (MAHSC), The University of Manchester, Manchester, UK

    Terence W. O'Neill

  3. Division of Endocrinology, Diabetes, and Bone Diseases and Centre for Healthy Aging, Technische Universität Dresden Medical Center, Dresden, Germany

    Lorenz C. Hofbauer

  4. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

    Bente Langdahl

  5. Department of Medicine, University of Auckland, Auckland, New Zealand

    Ian R. Reid

  6. Departments of Psychiatry & Behavioral Sciences, Sociology, and Psychology & Neuroscience, Duke University Medical Center, Durham, North Carolina, USA

    Deborah T. Gold

  7. San Francisco Coordinating Center, California Pacific Medical Center Research Institute and the University of California, San Francisco, San Francisco, California, USA

    Steven R. Cummings

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  1. Richard Eastell
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Contributions

Introduction (R.E.); Epidemiology (T.W.O.); Mechanisms/pathophysiology (L.C.H.); Diagnosis, screening and prevention (B.L.); Management (I.R.R.); Quality of life (D.T.G.); Outlook (S.R.C.); Overview of Primer (R.E.).

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Correspondence to Richard Eastell.

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Competing interests

R.E. has received consulting fees from Amgen, AstraZeneca, GlaxoSmithKline (GSK), Immunodiagnostic Systems, Ono Pharma, Lilly and Roche Diagnostics, and grant support from Amgen, Immunodiagnostic Systems, Lilly and AstraZeneca. L.C.H. has received honoraria for serving on the advisory board and for giving lectures from Amgen, Eli Lilly, Merck, Novartis and UCB. B.L. has received consulting fees from Amgen, Merck, Eli Lilly and UCB, and grant support from Novo Nordisk, Eli Lilly and Orkla Health. I.R.R. has received research funding and honoraria from Merck, Amgen and Novartis. S.R.C. serves as a consultant to Amgen, Radius, Merck and Eli Lilly about the design of studies and interpretation of results, and has received grant support from Amgen for systematic review of medical risk factors for hip fracture. He has not received funds for lectures or other promotional activities. D.T.G. and T.W.O. have no conflicts of interest or competing interests to report.

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Eastell, R., O'Neill, T., Hofbauer, L. et al. Postmenopausal osteoporosis. Nat Rev Dis Primers 2, 16069 (2016). https://doi.org/10.1038/nrdp.2016.69

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