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01-01-2016 | Osteoporosis | Book Chapter | Article

1. Osteoporosis: Pathophysiology and Epidemiology

Authors: Rebecca J. Moon, BSc, BM, MRCPCH, Cyrus Cooper, OBE, FMedSci, Nicholas C. Harvey, MA, MB, BChir, PhD, FRCP

Publisher: Springer International Publishing

Abstract

Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue resulting in increased bone fragility. Worldwide, there are nearly 9 million osteoporotic fractures each year, generating a massive burden both to individuals, in terms of associated morbidity and reduced survival, and to health services and wider economies. Furthermore, this burden is likely to increase globally as a result of urbanization of developing countries and an aging demographic across the majority of populations. In this chapter, we will review the pathophysiology and epidemiology of osteoporosis and fragility fracture, exploring mechanisms from cell biology to biomechanics and elucidating recent global secular trends in age- and sex-specific fracture rates.

Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993;94(6):646–50.

Cranney A, Jamal SA, Tsang JF, et al. Low bone mineral density and fracture burden in postmenopausal women. CMAJ. 2007;177(6):575–80. doi:10.1503/cmaj.070234 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

Thurner PJ, Erickson B, Jungmann R, Schriock Z, Weaver JC, Fantner GE, Schitter G, Morse DE, Hansma PK. High-speed photography of compressed human trabecular bone correlates whitening to microscopic damage. Eng Fract Mech. 2007;74:1928–41. *Elegant biomechanical demonstration of microdamage to bone and associated nano-structural changes consequent on fracture.CrossRef

Hansen S, Shanbhogue V, Folkestad L, et al. Bone microarchitecture and estimated strength in 499 adult Danish women and men: a cross-sectional, population-based high-resolution peripheral quantitative computed tomographic study on peak bone structure. Calcif Tissue Int. 2013. doi:10.1007/s00223-013-9808-5 [published Online First: Epub Date].PubMedCentral

**Hernandez CJ, Beaupre GS, Carter DR. A theoretical analysis of the relative influences of peak BMD, age-related bone loss and menopause on the development of osteoporosis. Osteoporos Int. 2003;14(10):843–47. **Theoretical analysis demonstrating the importance of peak bone mass, compared with subsequent bone loss, in the determination of osteoporosis.PubMedCrossRef

Ammann P, Rizzoli R. Bone strength and its determinants. Osteoporosis Int. 2003;14 Suppl 3:S13–8. doi:10.1007/s00198-002-1345-4 [published Online First: Epub Date].

*Seeman E. Bone quality: the material and structural basis of bone strength. J Bone Miner Metab. 2008;26(1):1–8. doi:10.1007/s00774-007-0793-5. [publishedOnline First: Epub Date]. *Excellent introduction to bone biomechanics and structural considerations.PubMedCrossRef

Silva MJ, Gibson LJ. Modeling the mechanical behavior of vertebral trabecular bone: effects of age-related changes in microstructure. Bone. 1997;21(2):191–9.PubMedCrossRef

Macdonald HM, Nishiyama KK, Kang J, et al. Age-related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: a population-based HR-pQCT study. J Bone Miner Res. 2011;26(1):50–62. doi:10.1002/jbmr.171 [published Online First: Epub Date].PubMedCrossRef

10.

Zebaze RM, Ghasem-Zadeh A, Bohte A, et al. Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet. 2010;375(9727):1729–36. doi:10.1016/s0140-6736(10)60320-0 [published Online First: Epub Date].PubMedCrossRef

11.

Saito M, Marumo K. Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporosis Int. 2010;21(2):195–214. doi:10.1007/s00198-009-1066-z [published Online First: Epub Date].CrossRef

12.

Davison KS, Siminoski K, Adachi JD, et al. Bone strength: the whole is greater than the sum of its parts. Semin Arthritis Rheum. 2006;36(1):22–31. doi:10.1016/j.semarthrit.2006.04.002 [published Online First: Epub Date].PubMedCrossRef

13.

Xiong J, Onal M, Jilka RL, et al. Matrix-embedded cells control osteoclast formation. Nat Med. 2011;17(10):1235–41. doi:10.1038/nm.2448 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

14.

Nakashima T, Hayashi M, Fukunaga T, et al. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011;17(10):1231–4. doi:10.1038/nm.2452 [published Online First: Epub Date].PubMedCrossRef

15.

Atkins GJ, Findlay DM. Osteocyte regulation of bone mineral: a little give and take. Osteoporosis Int. 2012;23(8):2067–79. doi:10.1007/s00198-012-1915-z [published Online First: Epub Date].CrossRef

16.

Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. 2013;19(2):179–92. doi:10.1038/nm.3074 [published Online First: Epub Date].PubMedCrossRef

17.

Estrada K, Styrkarsdottir U, Evangelou E, et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012;44(5):491–501. doi:10.1038/ng.2249 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

18.

Hughes JM, Petit MA. Biological underpinnings of Frost’s mechanostat thresholds: the important role of osteocytes. J Musculoskelet Neuronal Interact. 2010;10(2):128–35.PubMed

19.

Sibonga JD, Evans HJ, Sung HG, et al. Recovery of spaceflight-induced bone loss: bone mineral density after long-duration missions as fitted with an exponential function. Bone. 2007;41(6):973–8. doi:10.1016/j.bone.2007.08.022 [published Online First: Epub Date].PubMedCrossRef

20.

Kannus P, Haapasalo H, Sankelo M, et al. Effect of starting age of physical activity on bone mass in the dominant arm of tennis and squash players. Ann Intern Med. 1995;123(1):27–31.PubMedCrossRef

21.

Howe TE, Shea B, Dawson LJ, et al. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev. 2011;(7):Cd000333. doi:10.1002/14651858.CD000333.pub2. [published Online First: Epub Date].

22.

Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100(2):197–207.PubMedCrossRef

23.

Silva BC, Costa AG, Cusano NE, et al. Catabolic and anabolic actions of parathyroid hormone on the skeleton. J Endocrinol Invest. 2011;34(10):801–10. doi:10.3275/7925 [published Online First: Epub Date].PubMedPubMedCentral

24.

Thomas T, Gori F, Khosla S, et al. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology. 1999;140(4):1630–38.PubMed

25.

Shinoda Y, Yamaguchi M, Ogata N, et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem. 2006;99(1):196–208. doi:10.1002/jcb.20890 [published Online First: Epub Date].PubMedCrossRef

26.

**Hernlund E, Svedbom A, Ivergard M, 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. 2013;8(1–2):136. doi:10.1007/s11657-013-0136-1. [published Online First: Epub Date]. **Valuable compendium of osteoporosis epidemiology and burden across Europe.PubMedPubMedCentralCrossRef

27.

Bliuc D, Nguyen ND, Milch VE, et al. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. 2009;301(5):513–21.PubMedCrossRef

28.

Haentjens P, Magaziner J, Colon-Emeric CS, et al. Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med. 2010;152(6):380–90. doi:10.7326/0003-4819-152-6-201003160-00008 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

29.

Abrahamsen B, van Staa T, Ariely R, et al. Excess mortality following hip fracture: a systematic epidemiological review. Osteoporosis Int. 2009;20(10):1633–50. doi:10.1007/s00198-009-0920-3 [published Online First: Epub Date].CrossRef

30.

Roche JJ, Wenn RT, Sahota O, et al. Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study. BMJ. 2005;331(7529):1374. doi:10.1136/bmj.38643.663843.55 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

31.

Patel KV, Brennan KL, Brennan ML, et al. Association of a modified frailty index with mortality after femoral neck fracture in patients aged 60 years and older. Clin Orthop Relat Res. 2013. doi:10.1007/s11999-013-3334-7 [published Online First: Epub Date].

32.

Ahmed LA, Center JR, Bjornerem A, et al. Progressively increasing fracture risk with advancing age after initial incident fragility fracture: the Tromso study. J Bone Miner Res. 2013;28(10):2214–21. doi:10.1002/jbmr.1952 [published Online First: Epub Date].PubMedCrossRef

33.

Berry SD, Samelson EJ, Hannan MT, et al. Second hip fracture in older men and women: the Framingham study. Arch Intern Med. 2007;167(18):1971–6. doi:10.1001/archinte.167.18.1971 [published Online First: Epub Date].PubMedCrossRef

34.

Cooper C, Atkinson EJ, Jacobsen SJ, et al. Population-based study of survival after osteoporotic fractures. Am J Epidemiol. 1993;137(9):1001–5.PubMed

35.

Kim SM, Moon YW, Lim SJ, et al. Prediction of survival, second fracture, and functional recovery following the first hip fracture surgery in elderly patients. Bone. 2012;50(6):1343–50. doi:10.1016/j.bone.2012.02.633 [published Online First: Epub Date].PubMedCrossRef

36.

Leibson CL, Tosteson AN, Gabriel SE, et al. Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc. 2002;50(10):1644–50.PubMedCrossRef

37.

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(9):806–13. doi:10.4065/mcp.2010.0082 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

38.

Cooper C, Dennison EM, Leufkens HG, et al. Epidemiology of childhood fractures in Britain: a study using the general practice research database. J Bone Miner Res. 2004;19(12):1976–81. doi:10.1359/JBMR.040902 [published Online First: Epub Date].PubMedCrossRef

39.

Garraway WM, Stauffer RN, Kurland LT, et al. Limb fractures in a defined population. I. Frequency and distribution. Mayo Clin Proc. 1979;54(11):701–7.PubMed

40.

Sambrook P, Cooper C. Osteoporosis. Lancet. 2006;367(9527):2010–8. doi:10.1016/s0140-6736(06)68891-0 [published Online First: Epub Date].PubMedCrossRef

41.

Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312(7041):1254–59.PubMedPubMedCentralCrossRef

42.

Edwards MH, Jameson K, Denison H, et al. Clinical risk factors, bone density and fall history in the prediction of incident fracture among men and women. Bone. 2013;52(2):541–7. doi:10.1016/j.bone.2012.11.006 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

43.

Gillespie LD, Robertson MC, Gillespie WJ, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2012;9:Cd007146. doi:10.1002/14651858.CD007146.pub3 [published Online First: Epub Date].PubMed

44.

Stenhagen M, Ekstrom H, Nordell E, et al. Falls in the general elderly population: a 3- and 6- year prospective study of risk factors using data from the longitudinal population study ‘Good ageing in Skane’. BMC Geriatr. 2013;13:81. doi:10.1186/1471-2318-13-81 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

45.

**van Staa TP, Dennison EM, Leufkens HG, et al. Epidemiology of fractures in England and Wales. Bone. 2001;29(6):517–22. **Comprehensive description of UK fracture epidemiology.PubMedCrossRef

46.

Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Mineral Res. 2007;22(3):465–75. doi:10.1359/jbmr.061113 [published Online First: Epub Date].CrossRef

47.

Sterling RS. Gender and race/ethnicity differences in hip fracture incidence, morbidity, mortality, and function. Clin Orthop Relat Res. 2011;469(7):1913–8. doi:10.1007/s11999-010-1736-3 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

48.

Cawthon PM. Gender differences in osteoporosis and fractures. Clin Orthop Relat Res. 2011;469(7):1900–5. doi:10.1007/s11999-011-1780-7 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

49.

Wright NC, Saag KG, Curtis JR, et al. Recent trends in hip fracture rates by race/ethnicity among older US adults. J Bone Miner Res. 2012;27(11):2325–32. doi:10.1002/jbmr.1684 [published Online First: Epub Date].PubMedCrossRef

50.

Looker AC, Melton 3rd LJ, Harris TB, et al. Prevalence and trends in low femur bone density among older US adults: NHANES 2005–2006 compared with NHANES III. J Bone Miner Res. 2010;25(1):64–71. doi:10.1359/jbmr.090706 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

51.

Cauley JA, Lui LY, Ensrud KE, et al. Bone mineral density and the risk of incident nonspinal fractures in black and white women. JAMA. 2005;293(17):2102–8. doi:10.1001/jama.293.17.2102 [published Online First: Epub Date].PubMedCrossRef

52.

Wetzsteon RJ, Hughes JM, Kaufman BC, et al. Ethnic differences in bone geometry and strength are apparent in childhood. Bone. 2009;44(5):970–5. doi:10.1016/j.bone.2009.01.006 [published Online First: Epub Date].PubMedCrossRef

53.

Gilsanz V, Skaggs DL, Kovanlikaya A, et al. Differential effect of race on the axial and appendicular skeletons of children. J Clin Endocrinol Metab. 1998;83(5):1420–7. doi:10.1210/jcem.83.5.4765 [published Online First: Epub Date].PubMed

54.

Putman MS, Yu EW, Lee H, et al. Differences in skeletal microarchitecture and strength in African-American and white women. J Bone Miner Res. 2013;28(10):2177–85. doi:10.1002/jbmr.1953 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

55.

Benetou V, Orfanos P, Benetos IS, et al. Anthropometry, physical activity and hip fractures in the elderly. Injury. 2011;42(2):188–93. doi:10.1016/j.injury.2010.08.022 [published Online First: Epub Date].PubMedCrossRef

56.

Trimpou P, Landin-Wilhelmsen K, Oden A, et al. Male risk factors for hip fracture-a 30-year follow-up study in 7,495 men. Osteoporos Int. 2010;21(3):409–16. doi:10.1007/s00198-009-0961-7 [published Online First: Epub Date].PubMedCrossRef

57.

Tang X, Liu G, Kang J, et al. Obesity and risk of hip fracture in adults: a meta-analysis of prospective cohort studies. PLoS One. 2013;8(4), e55077. doi:10.1371/journal.pone.0055077 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

58.

Johansson H, Kanis JA, Oden A, et al. A meta-analysis of the association of fracture risk and body mass index in women. J Bone Miner Res. 2013. doi:10.1002/jbmr.2017 [published Online First: Epub Date].

59.

Compston JE, Watts NB, Chapurlat R, et al. Obesity is not protective against fracture in postmenopausal women: GLOW. Am J Med. 2011;124(11):1043–50. doi:10.1016/j.amjmed.2011.06.013 [published Online First: Epub Date].PubMedCrossRef

60.

Pocock NA, Eisman JA, Hopper JL, et al. Genetic determinants of bone mass in adults. A twin study. J Clin Invest. 1987;80(3):706–10. doi:10.1172/jci113125 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

61.

Slemenda CW, Christian JC, Williams CJ, et al. Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res. 1991;6(6):561–7. doi:10.1002/jbmr.5650060606 [published Online First: Epub Date].PubMedCrossRef

62.

Park JH, Song YM, Sung J, et al. Genetic influence on bone mineral density in Korean twins and families: the healthy twin study. Osteoporos Int. 2012;23(4):1343–9. doi:10.1007/s00198-011-1685-z [published Online First: Epub Date].PubMedCrossRef

63.

Arden NK, Baker J, Hogg C, et al. The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins. J Bone Miner Res. 1996;11(4):530–4. doi:10.1002/jbmr.5650110414 [published Online First: Epub Date].PubMedCrossRef

64.

Hunter D, De Lange M, Snieder H, et al. Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. J Bone Miner Res. 2001;16(2):371–8. doi:10.1359/jbmr.2001.16.2.371 [published Online First: Epub Date].PubMedCrossRef

65.

Morris DH, Jones ME, Schoemaker MJ, et al. Familial concordance for age at natural menopause: results from the Breakthrough Generations Study. Menopause. 2011;18(9):956–61. doi:10.1097/gme.0b013e31820ed6d2 [published Online First: Epub Date].PubMedCrossRef

66.

Arden NK, Spector TD. Genetic influences on muscle strength, lean body mass, and bone mineral density: a twin study. J Bone Miner Res. 1997;12(12):2076–81. doi:10.1359/jbmr.1997.12.12.2076 [published Online First: Epub Date].PubMedCrossRef

67.

Rivadeneira F, Styrkarsdottir U, Estrada K, et al. Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet. 2009;41(11):1199–206. doi:10.1038/ng.446 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

68.

Dennison EM, Arden NK, Keen RW, et al. Birthweight, vitamin D receptor genotype and the programming of osteoporosis. Paediatr Perinat Epidemiol. 2001;15(3):211–9.PubMedCrossRef

69.

Ferrari SL, Karasik D, Liu J, et al. Interactions of interleukin-6 promoter polymorphisms with dietary and lifestyle factors and their association with bone mass in men and women from the Framingham Osteoporosis Study. J Bone Miner Res. 2004;19(4):552–9. doi:10.1359/jbmr.040103 [published Online First: Epub Date].PubMedCrossRef

70.

Holroyd C, Harvey N, Dennison E, et al. Epigenetic influences in the developmental origins of osteoporosis. Osteoporos Int. 2012;23(2):401–10. doi:10.1007/s00198-011-1671-5 [published Online First: Epub Date].PubMedCrossRef

71.

Kanis JA, Oden A, McCloskey EV, et al. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int. 2012;23(9):2239–56. doi:10.1007/s00198-012-1964-3 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

72.

Ross PD, Norimatsu H, Davis JW, et al. A comparison of hip fracture incidence among native Japanese, Japanese Americans, and American Caucasians. Am J Epidemiol. 1991;133(8):801–9.PubMed

73.

Albin B, Hjelm K, Elmstahl S. Lower prevalence of hip fractures in foreign-born individuals than in Swedish-born individuals during the period 1987–1999. BMC Musculoskelet Disord. 2010;11:203. doi:10.1186/1471-2474-11-203 [published Online First: Epub Date].PubMedPubMedCentralCrossRef

74.

Brennan SL, Pasco JA, Urquhart DM, et al. The association between urban or rural locality and hip fracture in community-based adults: a systematic review. J Epidemiol Community Health. 2010;64(8):656–65. doi:10.1136/jech.2008.085738 [published Online First: Epub Date].PubMedCrossRef

75.

Alver K, Meyer HE, Falch JA, et al. Outdoor air pollution, bone density and self-reported forearm fracture: the Oslo Health Study. Osteoporos Int. 2010;21(10):1751–60. doi:10.1007/s00198-009-1130-8 [published Online First: Epub Date].PubMedCrossRef

76.

Douglas S, Bunyan A, Chiu KH, et al. Seasonal variation of hip fracture at three latitudes. Injury. 2000;31(1):11–9.PubMedCrossRef

77.

Gronskag AB, Forsmo S, Romundstad P, et al. Incidence and seasonal variation in hip fracture incidence among elderly women in Norway. The HUNT Study. Bone. 2010;46(5):1294–8. doi:10.1016/j.bone.2009.11.024 [published Online First: Epub Date].PubMedCrossRef

78.

Bischoff-Ferrari HA, Orav JE, Barrett JA, et al. Effect of seasonality and weather on fracture risk in individuals 65 years and older. Osteoporos Int. 2007;18(9):1225–33. doi:10.1007/s00198-007-0364-6 [published Online First: Epub Date].PubMedCrossRef

79.

Pedrazzoni M, Alfano FS, Malvi C, et al. Seasonal variation in the incidence of hip fractures in Emilia-Romagna and Parma. Bone. 1993;14 Suppl 1:S57–63.PubMedCrossRef

80.

Leavy B, Aberg AC, Melhus H, et al. When and where do hip fractures occur? A population-based study. Osteoporos Int. 2013;24(9):2387–96. doi:10.1007/s00198-013-2333-6 [published Online First: Epub Date].PubMedCrossRef

81.

Oyen J, Rohde GE, Hochberg M, et al. Low-energy distal radius fractures in middle-aged and elderly women-seasonal variations, prevalence of osteoporosis, and associates with fractures. Osteoporos Int. 2010;21(7):1247–55. doi:10.1007/s00198-009-1065-0 [published Online First: Epub Date].PubMedCrossRef

82.

Emaus N, Olsen LR, Ahmed LA, et al. Hip fractures in a city in Northern Norway over 15 years: time trends, seasonal variation and mortality : the Harstad Injury Prevention Study. Osteoporos Int. 2011;22(10):2603–10. doi:10.1007/s00198-010-1485-x [published Online First: Epub Date].PubMedPubMedCentralCrossRef

83.

*Cooper C, Campion G, Melton 3rd LJ. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992;2(6):285–9. *Helpful projection of global hip fracture rates accounting for anticipated population changes.PubMedCrossRef

84.

**Cooper C, Cole ZA, Holroyd CR, et al. Secular trends in the incidence of hip and other osteoporotic fractures. Osteoporos Int. 2011;22(5):1277–88. doi:10.1007/s00198-011-1601-6. [published Online First: Epub Date]. **Comprehensive assessment of secular trends in hip fracture since the mid 1900s.PubMedPubMedCentralCrossRef

85.

Amin S, Achenbach SJ, Atkinson EJ, et al. Trends in fracture incidence: a population-based study over 20 years. J Bone Miner Res. 2013. doi:10.1002/jbmr.2072 [published Online First: Epub Date].

86.

Rosengren BE, Ahlborg HG, Mellstrom D, et al. Secular trends in Swedish hip fractures 1987–2002: birth cohort and period effects. Epidemiology. 2012;23(4):623–30. doi:10.1097/EDE.0b013e318256982a [published Online First: Epub Date].PubMedCrossRef

87.

Hiligsmann M, Bruyere O, Roberfroid D, 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. 2012;64(5):744–50. doi:10.1002/acr.21607 [published Online First: Epub Date].CrossRef

88.

Alves SM, Economou T, Oliveira C, et al. Osteoporotic hip fractures: bisphosphonates sales and observed turning point in trend. A population-based retrospective study. Bone. 2013;53(2):430–6. doi:10.1016/j.bone.2012.12.014 [published Online First: Epub Date].PubMedCrossRef

89.

Abrahamsen B, Vestergaard P. Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997–2006. Osteoporos Int. 2010;21(3):373–80. doi:10.1007/s00198-009-0957-3 [published Online First: Epub Date].PubMedCrossRef

Medicine Matters Rheumatology

Abstract