Comparative Efficacy of Alendronate upon Vertebral Bone Mineral Density and Fracture Rates in East Asians Versus Non-East Asians with Postmenopausal Osteoporosis: A Systematic Review and Meta-Analysis

Abstract

Bisphosphonates, such as alendronate, have become the most widely used and effective anti-resorptive therapy for postmenopausal osteoporosis. Previous genetic studies suggest that ethnicity may drive differing responses to bisphosphonate therapy in East Asians and non-East Asians. Therefore, the aim of this study was to comparatively evaluate the efficacy of alendronate upon lumbar spinal BMD and vertebral fracture rates in East Asians and non-East Asians with postmenopausal osteoporosis. MEDLINE, EMBASE, and Cochrane CENTRAL were searched for relevant randomized controlled trials (RCTs) comparing the efficacy of alendronate versus placebo (or calcium/mineral and/or Vitamin D or hormone replacement therapy) in primary postmenopausal osteoporotic women. We calculated the weighted mean differences (WMDs) for lumbar spinal BMD and the risk ratios (RRs) for vertebral fracture risk along with their respective 95% confidence intervals (CIs). From an initial set of 445 non-duplicate records, 13 full-text articles were finally included in this meta-analysis consisting of four East Asian RCTs and nine non-East Asian RCTs. Alendronate therapy displayed significant effects in improving lumbar spinal BMD in both East Asians [WMD (95% CI)=5.30 (0.32–10.29), p=0.037] and non-East Asians [WMD (95% CI)=5.73 (3.61–7.85), p=0.000]. Alendronate therapy did not display significant effects upon vertebral fracture risk in East Asians [RR (95% CI)=0.41 (0.06–2.73), p=0.358] but did display a significant effect upon lowering vertebral fracture risk in non-East Asians [RR (95% CI)=0.55 (0.42–0.72), p=0.000]. These findings suggest that ethnicity may affect the efficacy of bisphosphonate therapy in postmenopausal osteoporotic women.

Key words

bisphosphonate - alendronate - postmenopausal - osteoporosis - BMD - vertebral fracture - Asian

• References

• 1 Edwards M, Moon R, Harvey N, Cooper C. Epidemiology and Genetics of Postmenopausal Osteoporosis. Osteoporosis 2013; 1-14 http://dx.doi.org/10.1002/9781118316290.ch1
• 2 Compston J. The use of combination therapy in the treatment of postmenopausal osteoporosis. Endocrine 2012; 41: 11-18
• 3 Bone HG, Hosking D, Devogelaer J-P, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC. Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Eng J Med 2004; 350: 1189-1199
• 4 Eriksen EF, Díez-Pérez A, Boonen S. Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: A systematic review. Bone 2014; 58: 126-135
• 5 Marini F, Brandi ML. Pharmacogenetics of osteoporosis: What is the evidence?. Curr Osteoporos Rep 2012; 10: 221-227
• 6 Marini F, Falchetti A, Silvestri S, Bagger Y, Luzi E, Tanini A, Christiansen C, Brandi ML. Modulatory effect of farnesyl pyrophosphate synthase (FDPS) rs2297480 polymorphism on the response to long-term amino-bisphosphonate treatment in postmenopausal osteoporosis. Curr Med Res Opin 2008; 24: 2609-2615
• 7 Olmos J, Zarrabeitia M, Hernández J, Sanudo C, Gonzalez-Macias J, Riancho J. Common allelic variants of the farnesyl diphosphate synthase gene influence the response of osteoporotic women to bisphosphonates. Pharmacogenom J 2012; 12: 227-232
• 8 Choi HJ, Choi JY, Cho SW, Kang D, Han KO, Kim SW, Kim SY, Chung Y-S, Shin CS. Genetic polymorphism of geranylgeranyl diphosphate synthase (GGSP1) predicts bone density response to bisphosphonate therapy in Korean women. Yonsei Med J 2010; 51: 231-238
• 9 Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann Intern Med 2009; 151: 264-269
• 10 Moher D, Jones A, Cook DJ, Jadad AR, Moher M, Tugwell P, Klassen TP. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?. Lancet 1998; 352: 609-613
• 11 Min Y-K, Lee D-Y, Choi S-J, Kim JH, Choi D, Yoon B-K. Effects of adding alendronate to ongoing hormone therapy on bone mineral density in postmenopausal Korean women: A randomized, double-blind, placebo-controlled clinical trial. Menopause 2013; 20: 761-766
• 12 Shiraki M, Kushida K, Fukunaga M, Kishimoto H, Kaneda K, Minaguchi H, Inoue T, Tomita A, Nagata Y, Nakashima M. A placebo-controlled, single-blind study to determine the appropriate alendronate dosage in postmenopausal Japanese patients with osteoporosis. Endocr J Tokyo 1998; 45: 191-202
• 13 Tseng L-N, Sheu WH-H, Ho ES-C, Lan HH-C, Hu C-C, Kao C-H. Effects of alendronate combined with hormone replacement therapy on osteoporotic postmenopausal Chinese women. Metabolism 2006; 55: 741-747
• 14 Yan Y, Wang W, Zhu H, Li M, Liu J, Luo B, Xie H, Zhang G, Li F. The efficacy and tolerability of once-weekly alendronate 70 mg on bone mineral density and bone turnover markers in postmenopausal Chinese women with osteoporosis. J Bone Mineral Metab 2009; 27: 471-478
• 15 Bell NH, Bilezikian JP, Bone III HG, Kaur A, Maragoto A, Santora AC. Alendronate increases bone mass and reduces bone markers in postmenopausal African-American women. J Clin Endocrinol Metab 2002; 87: 2792-2797
• 16 Bone HG, Downs Jr RW, Tucci JR, Harris ST, Weinstein RS, Licata AA, McClung MR, Kimmel DB, Gertz BJ, Hale E. Dose-Response Relationships for Alendronate Treatment in Osteoporotic Elderly Women 1. J Clin Endocrinol Metab 1997; 82: 265-274
• 17 Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC. 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
• 18 Devogelaer J-P, Broll H, Correa-Rotter R, Cumming D, De Deuxchaisnes CN, Geusens P, Hosking D, Jaeger P, Kaufman J, Leite M. Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis. Bone 1996; 18: 141-150
• 19 Greenspan SL, Resnick NM, Parker RA. Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: A randomized controlled trial. JAMA 2003; 289: 2525-2533
• 20 Hosking D, Chilvers CE, Christiansen C, Ravn P, Wasnich R, Ross P, McClung M, Balske A, Thompson D, Daley M. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. N Eng J Med 1998; 338: 485-492
• 21 Liberman UA, Weiss SR, Bröll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs Jr RW, Dequeker J, Favus M. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Eng J Med 1995; 333: 1437-1444
• 22 McClung MR, Wasnich RD, Hosking DJ, Christiansen C, Ravn P, Wu M, Mantz AM, Yates J, Ross PD, Santora AC. Prevention of postmenopausal bone loss: Six-year results from the Early Postmenopausal Intervention Cohort Study. J Clin Endocrinol Metab 2004; 89: 4879-4885
• 23 Tucci JR, Tonino RP, Emkey RD, Peverly CA, Kher U, Santora AC. Group UAPIOTS . Effect of three years of oral alendronate treatment in postmenopausal women with osteoporosis. Am J Med 1996; 101: 488-501
• 24 Kanis JA. Diagnosis of osteoporosis and assessment of fracture risk. Lancet 2002; 359: 1929-1936
• 25 World Health Organizaztion. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Report of a WHO study group [meeting held in Rome from 22 to 25 June 1992]; 1994; http://www.who.int/iris/handle/10665/39142
• 26 Coxon FP, Thompson K, Rogers MJ. Recent advances in understanding the mechanism of action of bisphosphonates. Curr Opin Pharmacol 2006; 6: 307-312
• 27 Rogers MJ, Crockett JC, Coxon FP, Mönkkönen J. Biochemical and molecular mechanisms of action of bisphosphonates. Bone 2011; 49: 34-41
• 28 Levy ME, Parker RA, Ferrell RE, Zmuda JM, Greenspan SL. Farnesyl diphosphate synthase: a novel genotype association with bone mineral density in elderly women. Maturitas 2007; 57: 247-252