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The purpose of this study was to estimate the benefits and drawbacks of bisphosphonates in the treatment of osteoporosis and osteopenia in middle-aged and elderly individuals.
We searched Ovid MEDLINE, Embase, the Web of Science, and Cochrane library databases for randomized clinical trials (RCTs) evaluating the effects of bisphosphonates and performed a network meta-analysis to summarize the direct and indirect evidence on the efficacy and safety of bisphosphonate therapy in middle-aged and elderly individuals with osteoporosis or osteopenia.
A total of 14 RCTs (7, 769 patients with osteoporosis or osteopenia; median age, 67 years; median follow-up, 27 months) were included in this network meta-analysis. Of these, 8, 10, 9, and 6 RCTs provided outcomes on bone mineral density changes, clinical fracture rates, vertebral fracture rates, and nonvertebral fracture rates, respectively. Regarding the primary efficacy outcome, there was a 97% probability for alendronate to be the most effective treatment approach for increasing bone mineral density and an 84% probability for zoledronate to be the most effective treatment approach for clinical fractures. Regarding vertebral fractures and safety outcomes, zoledronate showed an odds ratio (OR) of 0.45 (95% confidence intervals [CI], 0.30–0.69) relative to placebo. For nonvertebral fractures, the OR of zoledronate relative to placebo was 0.51 (95% CI 0.29–0.90).
This study revealed that alendronate was effective in increasing bone mineral density in middle-aged individuals and that zoledronate was a safe treatment option for osteoporosis and osteopenia, conferring a low incidence of fracture. However, further clinical studies are needed to confirm these results.
Rachner, T. D.; Khosla, S.; Hofbauer, L. C. Osteoporosis: Now and the future. Lancet 2011, 377, 1276–1287.
Cummings, S. R.; Melton, L. J. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002, 359, 1761–1767.
Reginster, J. Y.; Burlet, N. Osteoporosis: A still increasing prevalence. Bone 2006, 38, 4–9.
Eastell, R. Treatment of postmenopausal osteoporosis. N. Engl. J. Med. 1998, 338, 736–746.
Bhandari, M.; Swiontkowski, M. Management of acute hip fracture. N. Engl. J. Med. 2017, 377, 2053–2062.
Russell, R. G. G. Bisphosphonates: The first 40 years. Bone 2011, 49, 2–19.
Russell, R. G. G.; Croucher, P. I.; Rogers, M. J. Bisphosphonates: Pharmacology, mechanisms of action and clinical uses. Osteoporos. Int. 1999, 9, S66–S80.
Rogers, M. J.; Frith, J. C.; Luckman, S. P.; Coxon, F. P.; Benford, H. L.; Mönkkönen, J.; Auriola, S.; Chilton, K. M.; Russell, R. G. G. Molecular mechanisms of action of bisphosphonates. Bone 1999, 24, 73S–79S.
De Rosa, G.; Misso, G.; Salzano, G.; Caraglia, M. Bisphosphonates and cancer: What opportunities from nanotechnology? J. Drug Deliv. 2013, 2013, 637976.
Hodgins, N. O.; Wang, J. T. W.; Al-Jamal, K. T. Nano-technology based carriers for nitrogen-containing bisphosphonates delivery as sensitisers of γδ T cells for anticancer immunotherapy. Adv. Drug Deliv. Rev. 2017, 114, 143–160.
Geng, Z.; Wang, X. G.; Yu, Y. M.; Ji, L. L.; Wang, J.; Liu, C. S. Attenuating osteoarthritis by a high efficient anti-bone resorption injectable pH-responsive bisphosphonate-conjugated nano-apatite system. Chem. Eng. J. 2021, 420, 127674.
Drake, M. T.; Clarke, B. L.; Khosla, S. Bisphosphonates: Mechanism of action and role in clinical practice. Mayo Clin. Proceed. 2008, 83, 1032–1045.
Rosen, C. J. Postmenopausal osteoporosis. N. Engl. J. Med. 2005, 353, 595–603.
Serrano, A. J.; Begoña, L.; Anitua, E.; Cobos, R.; Orive, G. Systematic review and meta-analysis of the efficacy and safety of alendronate and zoledronate for the treatment of postmenopausal osteoporosis. Gynecol. Endocrinol. 2013, 29, 1005–1014.
Karpf, D. B.; Shapiro, D. R.; Seeman, E.; Ensrud, K. E.; Johnston, C. C. Jr.; Adami, S.; Harris, S. T.; Santora Ⅱ, A. C.; Hirsch, L. J.; Oppenheimer, L. et al. Prevention of nonvertebral fractures by alendronate: A meta-analysis. JAMA, 1997, 277, 1159–1164.
Byun, J. H.; Jang, S.; Lee, S.; Park, S.; Yoon, H. K.; Yoon, B. H.; Ha, Y. C. The efficacy of bisphosphonates for prevention of osteoporotic fracture: An update meta-analysis. J. Bone Metab. 2017, 24, 37–49.
Sanderson, J.; James, M. M. S.; Stevens, J.; Goka, E.; Wong, R.; Campbell, F.; Selby, P.; Gittoes, N.; Davis, S. Clinical effectiveness of bisphosphonates for the prevention of fragility fractures: A systematic review and network meta-analysis. Bone 2016, 89, 52–58.
Kanis, J. A. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report. Osteoporos. Int. 1994, 4, 368–381.
Salanti, G.; Ades, A. E.; Ioannidis, J. P. A. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: An overview and tutorial. J. Clin. Epidemiol. 2011, 64, 163–171.
Adami, S.; Baroni, M. C.; Broggini, M.; Carratelli, L.; Caruso, I.; Gnessi, L.; Laurenzi, M.; Lombardi, A.; Norbiato, G.; Ortolani, S. et al. Treatment of postmenopausal osteoporosis with continuous daily oral alendronate in comparison with either placebo or intranasal salmon calcitonin. Osteoporos. Int. 1993, 3, 21–27.
Bone, H. G.; Downs, R. W. Jr.; Tucci, J. R.; Harris, S. T.; Weinstein, R. S.; Licata, A. A.; McClung, M. R.; Kimmel, D. B.; Gertz, B. J.; Hale, E. et al. Dose–response relationships for alendronate treatment in osteoporotic elderly women. J. Clin. Endocrinol. Metab. 1997, 82, 265–274.
Hosking, D.; Chilvers, C. E. D.; Christiansen, C.; Ravn, P.; Wasnich, R.; Ross, P.; McClung, M.; Balske, A.; Thompson, D.; Daley, M. et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. N. Engl. J. Med. 1998, 338, 485–492.
Lau, E. M. C.; Woo, J.; Chan, Y. H.; Griffith, J. Alendronate prevents bone loss in Chinese women with osteoporosis. Bone 2000, 27, 677–680.
Greenspan, S. L.; Resnick, N. M.; Parker, R. A. Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: A randomized controlled trial. JAMA, 2003, 289, 2525–2533.
Hosking, D.; Adami, S.; Felsenberg, D.; Andia, J. C.; Välimäki, M.; Benhamou, L.; Reginster, J. Y.; Yacik, C.; Rybak-Feglin, A.; Petruschke, R. A. et al. Comparison of change in bone resorption and bone mineral density with once-weekly alendronate and daily risedronate: A randomised, placebo-controlled study. Curr. Med. Res. Opin. 2003, 19, 383–394.
Hooper, M. J.; Ebeling, P. R.; Roberts, A. P.; Graham, J. J.; Nicholson, G. C.; D'Emden, M.; Ernst, T. F.; Wenderoth, D. Risedronate prevents bone loss in early postmenopausal women: A prospective randomized, placebo-controlled trial. Climacteric 2005, 8, 251–262.
Choi, H. J.; Im, J. A.; Kim, S. H. Changes in bone markers after once-weekly low-dose alendronate in postmenopausal women with moderate bone loss. Maturitas 2008, 60, 170–176.
McClung, M. R.; Bolognese, M. A.; Sedarati, F.; Recker, R. R.; Miller, P. D. Efficacy and safety of monthly oral ibandronate in the prevention of postmenopausal bone loss. Bone 2009, 44, 418–422.
Nakamura, T.; Nakano, T.; Ito, M.; Hagino, H.; Hashimoto, J.; Tobinai, M.; Mizunuma, H.; For the MOVER Study Group. Clinical efficacy on fracture risk and safety of 0.5 mg or 1 mg/month intravenous ibandronate versus 2.5 mg/day oral risedronate in patients with primary osteoporosis. Calcif. Tissue Int. 2013, 93, 137–146.
Greenspan, S. L.; Perera, S.; Ferchak, M. A.; Nace, D. A.; Resnick, N. M. Efficacy and safety of single-dose zoledronic acid for osteoporosis in frail elderly women: A randomized clinical trial. JAMA Intern. Med. 2015, 175, 913–921.
Nakamura, T.; Fukunaga, M.; Nakano, T.; Kishimoto, H.; Ito, M.; Hagino, H.; Sone, T.; Taguchi, A.; Tanaka, S.; Ohashi, M. et al. Efficacy and safety of once-yearly zoledronic acid in Japanese patients with primary osteoporosis: Two-year results from a randomized placebo-controlled double-blind study (ZOledroNate treatment in Efficacy to osteoporosis; ZONE study). Osteoporos. Int. 2017, 28, 389–398.
Reid, I. R.; Horne, A. M.; Mihov, B.; Stewart, A.; Garratt, E.; Wong, S.; Wiessing, K. R.; Bolland, M. J.; Bastin, S.; Gamble, G. D. Fracture prevention with zoledronate in older women with osteopenia. N. Eng. J. Med. 2018, 379, 2407–2416.
Liu, Z.; Li, C. W.; Mao, Y. F.; Liu, K.; Liang, B. C.; Wu, L. G.; Shi, X. L. Study on zoledronic acid reducing acute bone loss and fracture rates in elderly postoperative patients with intertrochanteric fractures. Orthop. Surg. 2019, 11, 380–385.
Karabatsos, G.; Talbott, E.; Walker, S. G. A Bayesian nonparametric meta-analysis model. Res. Synth. Methods 2015, 6, 28–44.
Handl, J.; Knowles, J.; Kell, D. B. Computational cluster validation in post-genomic data analysis. Bioinformatics 2005, 21, 3201–3212.
Jung, Y.; Park, H.; Du, D. Z.; Drake, B. L. A decision criterion for the optimal number of clusters in hierarchical clustering. J. Glob. Optim. 2003, 25, 91–111.
Imaz, I.; Zegarra, P.; González-Enríquez, J.; Rubio, B.; Alcazar, R.; Amate, J. M. Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: Systematic review and meta-analysis. Osteoporos. Int. 2010, 21, 1943–1951.
Nayak, S.; Greenspan, S. L. A systematic review and meta-analysis of the effect of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk. Osteoporos. Int. 2019, 30, 705–720.
Yeam, C. T.; Chia, S.; Tan, H. C. C.; Kwan, Y. H.; Fong, W.; Seng, J. J. B. A systematic review of factors affecting medication adherence among patients with osteoporosis. Osteoporos. Int. 2018, 29, 2623–2637.
Viswanathan, M.; Reddy, S.; Berkman, N.; Cullen, K.; Middleton, J. C.; Nicholson, W. K.; Kahwati, L. C. Screening to prevent osteoporotic fractures: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2018, 319, 2532–2551.
Lumley, T. Network meta-analysis for indirect treatment comparisons. Stat. Med. 2002, 21, 2313–2324.
Cipriani, A.; Higgins, J. P. T.; Geddes, J. R.; Salanti, G. Conceptual and technical challenges in network meta-analysis. Ann. Intern. Med. 2013, 159, 130–137.
Zhu, W. W.; Xu, R. Y.; Du, J. Y.; Fu, Y.; Li, S.; Zhang, P.; Liu, L. K.; Jiang, H. B. Zoledronic acid promotes TLR-4-mediated M1 macrophage polarization in bisphosphonate-related osteonecrosis of the jaw. FASEB J. 2019, 33, 5208–5219.
Bilezikian, J. P. Osteonecrosis of the jaw-do bisphosphonates pose a risk? N. Engl. J. Med. 2006, 355, 2278–2281.
Alsalleeh, F.; Keippel, J.; Adams, L.; Bavitz, B. Bisphosphonate- associated osteonecrosis of jaw reoccurrence after methotrexate therapy: A case report. J. Endod. 2014, 40, 1505–1507.
Ulmner, M.; Jarnbring, F.; Törring, O. Osteonecrosis of the jaw in Sweden associated with the oral use of bisphosphonate. J. Oral Maxillofac. Surg. 2014, 72, 76–82.
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