J Bone Metab.  2017 Feb;24(1):37-49. 10.11005/jbm.2017.24.1.37.

The Efficacy of Bisphosphonates for Prevention of Osteoporotic Fracture: An Update Meta-analysis

• Byun JH
• Jang S
• Lee S
• Park S
• Yoon HK
• Yoon BH
• Ha YC

• KMID: 2371831
• DOI: http://doi.org/10.11005/jbm.2017.24.1.37

Abstract

BACKGROUND
The efficacy of bisphosphonates for osteoporotic fracture has been consistently reported in recent randomized controlled trials (RCTs) enrolling hundreds of patients. The objective of this study was to update knowledge on the efficacy of available bisphosphonates in the prevention of vertebral and non-vertebral fractures.
METHODS
An approach "using systematic reviews" on PubMed and Cochrane Library was taken. Twenty-four RCTs investigating the effects of bisphosphonates for the prevention of osteoporotic fracture were included in final analysis. A pairwise meta-analysis was conducted with a random effects model. Subgroup analysis was performed according to the type of bisphosphonate.
RESULTS
The use of bisphosphonate decrease the risk of overall osteoporotic fracture (odds ratio [OR] 0.62; P<0.001), vertebral fracture (OR 0.55; P<0.001) and non-vertebral fracture (OR 0.73; P<0.001). Subgroup analysis indicated that zoledronic acid showed the lowest risk reduction (OR 0.61; P<0.001) for overall osteoporotic fractures but no significance was observed for etidronate (OR 0.34; P=0.127).
CONCLUSIONS
This update meta-analysis re-confirmed that bisphosphonate use can effectively reduce the risk of osteoporotic fracture. However, there is a lack of evidence regarding etidronate for the prevention of osteoporotic fracture.

Keyword

Diphosphonates; Fractures bone; Meta-analysis as topic; Osteoporosis

MeSH Terms

Diphosphonates*
Etidronic Acid
Humans
Meta-Analysis as Topic
Osteoporosis
Osteoporotic Fractures*
Risk Reduction Behavior
Diphosphonates
Etidronic Acid

Figure

• 

  Fig. 1 Flow diagram detailing the selection process of relevant clinical studies.

• 

  Fig. 2 (A) The forest plot of overall osteoporotic fracture reductions relative to placebo by bisphosphonate treatment. The forest plot of odds ratio for (B) vertebral fracture. (C) non-vertebral fracture. OR, odds ratio; CI, confidence interval.

• 

  Fig. 3 The funnel plot shows publication bias for osteoporotic fracture related to the use of bisphosphonate. There was symmetry, suggesting that there was no significant publication bias in the twenty-four studies.

• 

  Fig. 4 The summary of bias risk of randomized controlled trials.

Reference

1. Svensson HK, Olofsson EH, Karlsson J, et al. A painful, never ending story: older women's experiences of living with an osteoporotic vertebral compression fracture. Osteoporos Int. 2016; 27:1729–1736.

2. Park C, Jang S, Lee A, et al. Incidence and mortality after proximal humerus fractures over 50 years of age in South Korea: national claim data from 2008 to 2012. J Bone Metab. 2015; 22:17–21.

3. Im GI, Lee SH. Effect of teriparatide on healing of atypical femoral fractures: a systemic review. J Bone Metab. 2015; 22:183–189.

4. Choi NK, Solomon DH, Tsacogianis TN, et al. Comparative safety and effectiveness of denosumab versus zoledronic acid in patients with osteoporosis: a cohort study. J Bone Miner Res. 2016.

5. Bilezikian JP. Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Am J Med. 2009; 122:S14–S21.

6. van de Glind EM, Willems HC, Eslami S, et al. Estimating the time to benefit for preventive drugs with the statistical process control method: an example with alendronate. Drugs Aging. 2016; 33:347–353.

7. Chao M, Hua Q, Yingfeng Z, et al. Study on the role of zoledronic acid in treatment of postmenopausal osteoporosis women. Pak J Med Sci. 2013; 29:1381–1384.

8. Bai H, Jing D, Guo A, et al. Randomized controlled trial of zoledronic acid for treatment of osteoporosis in women. J Int Med Res. 2013; 41:697–704.

9. Ou YJ, Chiu HF, Wong YH, et al. Bisphosphonate use and the risk of endometrial cancer: a meta-analysis of observational studies. Pharmacoepidemiol Drug Saf. 2016; 25:1107–1115.

10. Wang J, Yao M, Xu JH, et al. Bisphosphonates for prevention of osteopenia in kidney-transplant recipients: a systematic review of randomized controlled trials. Osteoporos Int. 2016; 27:1683–1690.

11. Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 349:g7647.

12. Shea BJ, Grimshaw JM, Wells GA, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007; 7:10.

13. Wells G, Cranney A, Peterson J, et al. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev. 2008; Cd004523.

14. Wells GA, Cranney A, Peterson J, et al. Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev. 2008; Cd003376.

15. Wells GA, Cranney A, Peterson J, et al. Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev. 2008; Cd001155.

16. Zhou J, Wang T, Zhao X, et al. Comparative efficacy of bisphosphonates to prevent fracture in men with osteoporosis: a systematic review with network meta-analyses. Rheumatol Ther. 2016; 3:117–128.

17. Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.0.0. London, UK: The Cochrane Collaboration;2008.

18. Borenstein M, Hedges LV, Higgins JPT, et al. Introduction to meta-analysis. West Sussex, UK: John Wiley & Sons;2009.

19. Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet. 1996; 348:1535–1541.

20. Boonen S, Orwoll ES, Wenderoth D, et al. Once-weekly risedronate in men with osteoporosis: results of a 2-year, placebo-controlled, double-blind, multicenter study. J Bone Miner Res. 2009; 24:719–725.

21. Boonen S, Reginster JY, Kaufman JM, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012; 367:1714–1723.

22. Chesnut CH, 3rd , Skag A, Christiansen C, et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004; 19:1241–1249.

23. Clemmesen B, Ravn P, Zegels B, et al. A 2-year phase II study with 1-year of follow-up of risedronate (NE-58095) in postmenopausal osteoporosis. Osteoporos Int. 1997; 7:488–495.

24. Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA. 1998; 280:2077–2082.

25. Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA. 1999; 282:1344–1352.

26. Herd RJ, Balena R, Blake GM, et al. The prevention of early postmenopausal bone loss by cyclical etidronate therapy: a 2-year, double-blind, placebo-controlled study. Am J Med. 1997; 103:92–99.

27. Hosking D, Chilvers CE, Christiansen C, et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group. N Engl J Med. 1998; 338:485–492.

28. Liberman UA, Weiss SR, Bröll J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med. 1995; 333:1437–1443.

29. Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007; 357:1799–1809.

30. Matsumoto T, Hagino H, Shiraki M, et al. Effect of daily oral minodronate on vertebral fractures in Japanese postmenopausal women with established osteoporosis: a randomized placebo-controlled double-blind study. Osteoporos Int. 2009; 20:1429–1437.

31. McCloskey E, Selby P, Davies M, et al. Clodronate reduces vertebral fracture risk in women with postmenopausal or secondary osteoporosis: results of a double-blind, placebo-controlled 3-year study. J Bone Miner Res. 2004; 19:728–736.

32. McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001; 344:333–340.

33. Meunier PJ, Confavreux E, Tupinon I, et al. Prevention of early postmenopausal bone loss with cyclical etidronate therapy (a double-blind, placebo-controlled study and 1-year follow-up). J Clin Endocrinol Metab. 1997; 82:2784–2791.

34. Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med. 2000; 343:604–610.

35. Pouilles JM, Tremollieres F, Roux C, et al. Effects of cyclical etidronate therapy on bone loss in early postmenopausal women who are not undergoing hormonal replacement therapy. Osteoporos Int. 1997; 7:213–218.

36. Reginster J, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int. 2000; 11:83–91.

37. Reid IR, Wattie DJ, Evans MC, et al. Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis. J Clin Endocrinol Metab. 1994; 79:1595–1599.

38. Storm T, Thamsborg G, Steiniche T, et al. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med. 1990; 322:1265–1271.

39. McCloskey EV, Beneton M, Charlesworth D, et al. Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled randomized study. J Bone Miner Res. 2007; 22:135–141.

40. Johnell O, Kanis JA. An estimate of the worldwide prevalence, mortality and disability associated with hip fracture. Osteoporos Int. 2004; 15:897–902.

41. Jansen JP, Bergman GJ, Huels J, et al. The efficacy of bisphosphonates in the prevention of vertebral, hip, and nonvertebral-nonhip fractures in osteoporosis: a network meta-analysis. Semin Arthritis Rheum. 2011; 40:275–284.

42. Lee YJ, Park CH, Lee YK, et al. Which bisphosphonate? It's the compliance!: Decision analysis. J Bone Metab. 2016; 23:79–83.