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Osteoporosis International

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Open Access 01-04-2018 | Original Article

Bisphosphonate use after clinical fracture and risk of new fracture

Authors: J. Bergman, A. Nordström, P. Nordström

Published in: Osteoporosis International | Issue 4/2018

Abstract

Summary

Among older adults with a previous fracture, treatment for osteoporosis was initially associated with a higher risk of new fracture. However, the relative risk of new fracture decreased over time, a trend that is consistent with a beneficial effect, as treatment for osteoporosis is prescribed to reduce high fracture risks.

Introduction

The purpose of this study was to examine whether bisphosphonate use is associated with a lower risk of new fracture after a clinical fracture in older adults.

Methods

Data were available for 3,329,400 adults in Sweden who were aged ≥ 50 years between 2006 and 2011. During this period, 260,353 sustained a clinical fracture and were naïve to bisphosphonates at the time. Those who subsequently received a bisphosphonate were matched to up to three others on sex, year of birth, and type and year of initial fracture. The final cohort comprised 83,104 adults (26.3% bisphosphonate users).

Results

During the period from initial fracture to initiation of bisphosphonate treatment, the incidence rate of any new clinical fracture was higher in those who later became bisphosphonate users than in those who remained nonusers (175.1 vs. 75.9 per 1000 person-years; hazard ratio 2.30, 95% confidence interval 2.19 to 2.41). Similarly, during the first 6 months of treatment, the incidence rate was higher in bisphosphonate users than in nonusers (128.8 vs. 90.2 per 1000 person-years; hazard ratio 1.41, 95% confidence interval 1.32 to 1.51). However, this difference decreased over time: by months 12 to 18, the incidence rate was similar in users and nonusers (59.3 vs. 55.3 per 1000 person-years; hazard ratio 1.03, 95% confidence interval 0.91 to 1.16).

Conclusions

There was a decrease in the relative risk of new fracture during bisphosphonate treatment, a trend that is consistent with a beneficial treatment effect, as bisphosphonates are prescribed to reduce high fracture risks.

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Klotzbuecher CM, Ross PD, Landsman PB et al (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–739. https://doi.org/10.1359/jbmr.2000.15.4.721 CrossRefPubMed

Kanis JA, Johnell O, De Laet C et al (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone 35:375–382. https://doi.org/10.1016/j.bone.2004.03.024 CrossRefPubMed

Bliuc D, Alarkawi D, Nguyen TV et al (2015) Risk of subsequent fractures and mortality in elderly women and men with fragility fractures with and without osteoporotic bone density: the Dubbo osteoporosis epidemiology study. J Bone Miner Res 30:637–646. https://doi.org/10.1002/jbmr.2393 CrossRefPubMed

Center JR, Bliuc D, Nguyen TV, Eisman JA (2007) Risk of subsequent fracture after low-trauma fracture in men and women. JAMA 297:387–394. https://doi.org/10.1001/jama.297.4.387 CrossRefPubMed

Ahmed LA, Center JR, Bjørnerem Å et al (2013) Progressively increasing fracture risk with advancing age after initial incident fragility fracture: the Tromsø study. J Bone Miner Res 28:2214–2221. https://doi.org/10.1002/jbmr.1952 CrossRefPubMed

Cosman F, de Beur SJ, LeBoff MS et al (2014) Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 25:2359–2381. https://doi.org/10.1007/s00198-014-2794-2 CrossRefPubMedPubMedCentral

Papaioannou A, Morin S, Cheung AM et al (2010) 2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 182:1864–1873. https://doi.org/10.1503/cmaj.100771 CrossRefPubMedPubMedCentral

Głuszko P, Lorenc RS, Karczmarewicz E et al (2014) Polish guidelines for the diagnosis and management of osteoporosis: a review of 2013 update. Pol Arch Med Wewn 124:255–263PubMed

Hwang JS, Chan DC, Chen JF et al (2014) Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: summary. J Bone Miner Metab 32:10–16. https://doi.org/10.1007/s00774-013-0495-0 CrossRefPubMed

10.

Compston J, Bowring C, Cooper A et al (2013) 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. https://doi.org/10.1016/j.maturitas.2013.05.013 CrossRefPubMed

11.

Briot K, Cortet B, Thomas T et al (2012) 2012 update of French guidelines for the pharmacological treatment of postmenopausal osteoporosis. Joint Bone Spine 79:304–313. https://doi.org/10.1016/j.jbspin.2012.02.014 CrossRefPubMed

12.

Makras P, Vaiopoulos G, Lyritis GP (2012) 2011 guidelines for the diagnosis and treatment of osteoporosis in Greece. J Musculoskelet Neuronal Interact 12:38–42PubMed

13.

Yeap SS, Hew FL, Lee JK et al (2013) The Malaysian clinical guidance on the management of postmenopausal osteoporosis, 2012: a summary. Int J Rheum Dis 16:30–40. https://doi.org/10.1111/1756-185x.12037

14.

Kanis JA, McCloskey EV, Johansson H et al (2010) Development and use of FRAX® in osteoporosis. Osteoporos Int 21:407–413. https://doi.org/10.1007/s00198-010-1253-y CrossRef

15.

Mackey DC, Lui LY, Cawthon PM et al (2007) High-trauma fractures and low bone mineral density in older women and men. JAMA 298:2381–2388. https://doi.org/10.1001/jama.298.20.2381 CrossRefPubMed

16.

Hernlund E, Svedbom A, Ivergård M et al (2013) 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. https://doi.org/10.1007/s11657-013-0136-1 CrossRefPubMedPubMedCentral

17.

Black DM, Cummings SR, Karpf DB et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541CrossRefPubMed

18.

Harris S, Watts N, Genant H et al (1999) Effects of Risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA 282:1344–1352. https://doi.org/10.1001/jama.282.14.1344 CrossRefPubMed

19.

Reginster JY, Minne HW, Sorensen OH et al (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Osteoporos Int 11:83–91CrossRefPubMed

20.

Lyles KW, Colón-Emeric C, Magaziner JS et al (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799–1809. https://doi.org/10.1056/NEJMoa074941 CrossRefPubMed

21.

Bawa HS, Weick J, Dirschl DR (2015) Anti-osteoporotic therapy after fragility fracture lowers rate of subsequent fracture: analysis of a large population sample. J Bone Joint Surg Am 97:1555–1562. https://doi.org/10.2106/JBJS.N.01275 CrossRefPubMed

22.

Axelsson KF, Wallander M, Johansson H et al (2017) Hip fracture risk and safety with alendronate treatment in the oldest old. J Intern Med 282:546–559. https://doi.org/10.1111/joim.12678 CrossRefPubMed

23.

Ludvigsson JF, Andersson E, Ekbom A et al (2011) External review and validation of the Swedish national inpatient register. BMC Public Health 11:450. https://doi.org/10.1186/1471-2458-11-450 CrossRefPubMedPubMedCentral

24.

Wettermark B, Hammar N, MichaelFored C et al (2007) The new Swedish prescribed drug register—opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf 16:726–735. https://doi.org/10.1002/pds CrossRefPubMed

25.

Swedish National Board of Health and Welfare (2009) Cancer incidence in Sweden 2008. Swedish National Board of Health and Welfare, Stockholm

26.

Cramer JA, Silverman SL, Gold DT (2007) Methodological considerations in using claims databases to evaluate persistence with bisphosphonates for osteoporosis. Curr Med Res Opin 23:2369–2377. https://doi.org/10.1185/030079907X226311 CrossRefPubMed

27.

Looker AC, Wahner HW, Dunn WL et al (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468–489. https://doi.org/10.1007/s001980050093 CrossRefPubMed

28.

Brozek W, Reichardt B, Zwerina J et al (2016) Antiresorptive therapy and risk of mortality and refracture in osteoporosis-related hip fracture: a nationwide study. Osteoporos Int 27:387–396. https://doi.org/10.1007/s00198-015-3415-4 CrossRefPubMed

29.

Bondo L, Eiken P, Abrahamsen B (2013) Analysis of the association between bisphosphonate treatment survival in Danish hip fracture patients—a nationwide register-based open cohort study. Osteoporos Int 24:245–252. https://doi.org/10.1007/s00198-012-2024-8 CrossRefPubMed

30.

Abrahamsen B, Eiken P, Eastell R (2009) Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. J Bone Miner Res 24:1095–1102. https://doi.org/10.1016/S0276-1092(10)79672-3 CrossRefPubMed

31.

Slone D, Shapiro S, Miettinen OS et al (1979) Drug evaluation after marketing. Ann Intern Med 90:257–261CrossRefPubMed

32.

Ryder KM, Cummings SR, Palermo L et al (2008) Does a history of non-vertebral fracture identify women without osteoporosis for treatment? J Gen Intern Med 23:1177–1181. https://doi.org/10.1007/s11606-008-0622-0 CrossRefPubMedPubMedCentral

33.

Ringe JD, Farahmand P, Faber H, Dorst A (2009) Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year study. Rheumatol Int 29:311–315. https://doi.org/10.1007/s00296-008-0689-2 CrossRefPubMed

34.

Boonen S, McClung MR, Eastell R et al (2004) Safety and efficacy of risedronate in reducing fracture risk in osteoporotic women aged 80 and older: implications for the use of antiresorptive agents in the old and oldest old. J Am Geriatr Soc 52:1832–1839. https://doi.org/10.1111/j.1532-5415.2004.52506.x CrossRefPubMed

35.

Boonen S, Black DM, Colón-Emeric CS et al (2010) Efficacy and safety of a once-yearly intravenous zoledronic acid 5 mg for fracture prevention in elderly postmenopausal women with osteoporosis aged 75 and older. J Am Geriatr Soc 58:292–299. https://doi.org/10.1111/j.1532-5415.2009.02673.x CrossRefPubMedPubMedCentral

36.

Hochberg MC, Thompson DE, Black DM et al (2005) Effect of alendronate on the age-specific incidence of symptomatic osteoporotic fractures. J Bone Miner Res 20:971–976. https://doi.org/10.1359/JBMR.050104 CrossRefPubMed

37.

van Geel TAMC, van Helden S, Geusens PP et al (2009) Clinical subsequent fractures cluster in time after first fractures. Ann Rheum Dis 68:99–102. https://doi.org/10.1016/j.maturitas.2010.09.002 CrossRefPubMed

38.

Harrington JT, Ste-Marie LG, Brandi ML et al (2004) Risedronate rapidly reduces the risk for nonvertebral fractures in women with postmenopausal osteoporosis. Calcif Tissue Int 74:129–135. https://doi.org/10.1007/s00223-003-0042-4 CrossRefPubMed

39.

Miller PD, Jamal SA, Evenepoel P et al (2013) Renal safety in patients treated with bisphosphonates for osteoporosis: a review. J Bone Miner Res 28:2049–2059. https://doi.org/10.1002/jbmr.2058 CrossRefPubMed

40.

Hernán MA (2010) The hazards of hazard ratios. Epidemiology 21:13–15. https://doi.org/10.1097/EDE.0b013e3181c1ea43 CrossRefPubMedPubMedCentral

41.

Swedish National Board of Health and Welfare, Swedish Association of Local Authorities and Regions (2014) Öppna jämförelser 2014: Hälso- och sjukvård - jämförelser mellan landsting. Del 2. Indikatorer om sjukdomar och behandlingar [Open comparisons 2014: Healthcare - comparisons of regions. Part 2. Indications of diseases and treatments]. Swedish National Board of Health and Welfare, Stockholm

Title: Bisphosphonate use after clinical fracture and risk of new fracture
Authors: J. Bergman
A. Nordström
P. Nordström
Publication date: 01-04-2018
Publisher: Springer London
Published in: Osteoporosis International / Issue 4/2018
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-017-4367-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Bisphosphonate use after clinical fracture and risk of new fracture

Abstract

Summary

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

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