Abstract
Summary
The present meta-analysis aimed to evaluate the middle-term efficacy of bisphosphonates on maintaining periprosthetic bone mass after joint arthroplasty and the potential influential factors. It was found that the protective effect of bisphosphonates, probably modified by its generation and the prosthesis location, could persist in a middle-term follow-up after surgery and after drug discontinuation.
Introduction
A previous meta-analysis of 6 RCTs with follow-up of 12 months suggested that bisphosphonates (BPs) could prevent bone loss after arthroplasty up to 6 months. Our meta-analysis based on 14 RCTs involving 671 patients with follow-up up to 72 months aimed to evaluate the middle-term efficacy of BPs, understand the sources of heterogeneity, and comprehensively identify the potential influential factors.
Methods
Electronic databases searching and hand searching of conference proceedings were conducted. We evaluated the methodological quality and abstracted relevant data. With fixed effect model we calculated the weighted mean differences to evaluate bone mineral density at different time points. We also conducted a systematic review for BP-related adverse effects.
Results
The significantly less periprosthetic bone loss occurred in the BP-treated group than in the control group at 3, 6, and 12 months, and between 24 and 72 months after the index surgery. The protective effect persisted during 18 to 70 months after discontinuation of BPs. The heterogeneity was minimized with the separation of hip and knee trials during the analysis. The efficacy was more potent for the second and the third generation of BPs than the first generation. None of the trials noted serious or fatal adverse effects related to BPs.
Conclusions
The overall moderate evidence from the RCTs confirmed the significantly short-term and middle-term efficacy of BPs on periprosthetic bone loss after joint arthroplasty. To obtain a better efficacy, the second and the third generation of BPs may be the choice.
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References
Prieto-Alhambra D, Javaid MK, Judge A, Maskell J, Kiran A, de Vries F, Cooper C, Arden NK (2011) Fracture risk before and after total hip replacement in patients with osteoarthritis: potential benefits of bisphosphonate use. Arthritis Rheum 63:992–1001
Cook RE, Jenkins PJ, Walmsley PJ, Patton JT, Robinson CM (2008) Risk factors for periprosthetic fractures of the hip: a survivorship analysis. Clin Orthop Relat Res 466(7):1652–1656
Purdue PE, Koulouvaris P, Nestor BJ, Sculco TP (2006) The central role of wear debris in periprosthetic osteolysis. HSS J 2:102–113
Furnes O, Lie SA, Espehaug B, Vollset SE, Engesaeter LB, Havelin LI (2001) Hip disease and the prognosis of total hip replacements. A review of 53,698 primary total hip replacements reported to the Norwegian Arthroplasty Register 1987–99. J Bone Joint Surg Br 83:579–586
Sundfeldt M, Carlsson LV, Johansson CB, Thomsen P, Gretzer C (2006) Aseptic loosening, not only a question of wear: a review of different theories. Acta Orthop 77:177–197
Brown DL, Robbins R (1999) Developments in the therapeutic applications of bisphosphonates. J Clin Pharmacol 39:651–660
Bhandari M, Bajammal S, Guyatt GH, Griffith L, Busse JW, Schunemann H, Einhorn TA (2005) Effect of bisphosphonates on periprosthetic bone mineral density after total joint arthroplasty. A meta-analysis. J Bone Joint Surg Am 87:293–301
Laupacis A, Straus S (2007) Systematic reviews: time to address clinical and policy relevance as well as methodological rigor. Ann Intern Med 147:273–274
Fokter SK, Komadina R, Repse-Fokter A (2006) Effect of etidronate in preventing periprosthetic bone loss following cemented hip arthroplasty: a randomized, double blind, controlled trial. Wien Klin Wochenschr 118(Suppl 2):23–28
Trevisan C, Ortolani S, Romano P, Isaia G, Agnese L, Dallari D, Grappiolo G, Cherubini R, Massari L, Bianchi G (2010) Decreased periprosthetic bone loss in patients treated with clodronate: a 1-year randomized controlled study. Calcif Tissue Int 86:436–446
Arabmotlagh M, Pilz M, Warzecha J, Rauschmann M (2009) Changes of femoral periprosthetic bone mineral density 6 years after treatment with alendronate following total hip arthroplasty. J Orthop Res 27:183–188
Shetty N, Hamer AJ, Stockley I, Eastell R, Willkinson JM (2006) Clinical and radiological outcome of total hip replacement 5 years after pamidronate therapy. A trial extension. J Bone Joint Surg Br 88:1309–1315
Tapaninen TS, Venesmaa PK, Jurvelin JS, Miettinen HJ, Kroger HP (2010) Alendronate reduces periprosthetic bone loss after uncemented primary total hip arthroplasty—a 5-year follow-up of 16 patients. Scand J Surg 99:32–37
Wang CJ, Wang JW, Ko JY, Weng LH, Huang CC (2006) Three-year changes in bone mineral density around the knee after a six-month course of oral alendronate following total knee arthroplasty. A prospective, randomized study. J Bone Joint Surg Am 88:267–272
Yamaguchi K, Masuhara K, Yamasaki S, Fuji T, Seino Y (2004) Effects of discontinuation as well as intervention of cyclic therapy with etidronate on bone remodeling after cementless total hip arthroplasty. Bone 35:217–223
Furlan AD, Pennick V, Bombardier C, van Tulder M (2009) 2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group. Spine 34:1929–1941 (Phila Pa 1976)
Atkins D, Best D, Briss PA et al (2004) Grading quality of evidence and strength of recommendations. BMJ 328:1490
Higgins JPT, Green S, Cochrane Collaboration (2008) Cochrane handbook for systematic reviews of interventions. Wiley-Blackwell, Chichester, England Hoboken NJ
Arabmotlagh M, Rittmeister M, Hennigs T (2006) Alendronate prevents femoral periprosthetic bone loss following total hip arthroplasty: prospective randomized double-blind study. J Orthop Res 24:1336–1341
Hennigs T, Arabmotlagh M, Schwarz A, Zichner L (2002) Dose-dependent prevention of early periprosthetic bone loss by alendronate. Z Orthop Ihre Grenzgeb 140:42–47
Venesmaa PK, Kroger HP, Miettinen HJ, Jurvelin JS, Suomalainen OT, Alhav EM (2001) Alendronate reduces periprosthetic bone loss after uncemented primary total hip arthroplasty: a prospective randomized study. J Bone Miner Res 16:2126–2131
Wang CJ, Wang JW, Weng LH, Hsu CC, Huang CC, Chen HS (2003) The effect of alendronate on bone mineral density in the distal part of the femur and proximal part of the tibia after total knee arthroplasty. J Bone Joint Surg Am 85-A:2121–2126
Wilkinson JM, Eagleton AC, Stockley I, Peel NF, Hamer AJ, Eastell R (2005) Effect of pamidronate on bone turnover and implant migration after total hip arthroplasty: a randomized trial. J Orthop Res 23:1–8
Wilkinson JM, Stockley I, Peel NF, Hamer AJ, Elson RA, Barrington NA, Eastell R (2001) Effect of pamidronate in preventing local bone loss after total hip arthroplasty: a randomized, double-blind, controlled trial. J Bone Miner Res 16:556–564
Fokter SK, Komadina R, Repse-Fokter A, Yerby SA, Kocijancic A, Marc J (2005) Etidronate does not suppress periprosthetic bone loss following cemented hip arthroplasty. Int Orthop 29:362–367
Yamaguchi K, Masuhara K, Yamasaki S, Nakai T, Fuji T (2003) Cyclic therapy with etidronate has a therapeutic effect against local osteoporosis after cementless total hip arthroplasty. Bone 33:144–149
Yamaguchi K, Masuhara K, Yamasaki S, Fuji T (2005) Efficacy of different dosing schedules of etidronate for stress shielding after cementless total hip arthroplasty. J Orthop Sci 10:32–36
Abu-Rajab RB, Watson W, Gallacher P, Walker B, Meek RMD (2009) The effect of 6 months oral alendronate treatment on periprosthetic bone loss after total knee arthroplasty. Eur J Orthop Surg Traumatol 19:231–235
Nishioka T, Yagi S, Mitsuhashi T, Miyamoto M, Tamura T, Kobayashi T, Enishi T (2007) Alendronate inhibits periprosthetic bone loss around uncemented femoral components. J Bone Miner Metab 25:179–183
Soininvaara TA, Jurvelin JS, Miettinen HJ, Suomalainen OT, Alhava EM, Kroger PJ (2002) Effect of alendronate on periprosthetic bone loss after total knee arthroplasty: a one-year, randomized, controlled trial of 19 patients. Calcif Tissue Int 71:472–477
Nehme A, Maalouf G, Tricoire JL, Giordano G, Chiron P, Puget J (2003) Effect of alendronate on periprosthetic bone loss after cemented primary total hip arthroplasty: a prospective randomized study. Rev Chir Orthop Reparatrice Appar Mot 89:593–598
Huang JF, Liu JB (2007) Alendronate prevents early femoral periprosthetic bone loss following total hip arthroplasty. Journal of Jiangsu University 17:542–544 (Medicine Edition)
Wang YM, Li X, Wang JQ, Guo SY (2005) Study on the periprosthetic bone loss after cemented primary total hip replacement. Tianjin Medical Journal 33:492–494
Yamasaki S, Masuhara K, Yamaguchi K, Nakai T, Fuji T, Seino Y (2007) Risedronate reduces postoperative bone resorption after cementless total hip arthroplasty. Osteoporos Int 18:1009–1015
Takeyama S, Shinoda H (2003) Pharmacological actions and pharmacokinetics of bisphosphonates. Clin Calcium 13:115–121
Jansen JP, Bergman GJ, Huels J, Olson M (2011) The efficacy of bisphosphonates in the prevention of vertebral, hip, and nonvertebral-nonhip fractures in osteoporosis: a network meta-analysis. Semin Arthritis Rheum 40:275–284
Uusi-Rasi K, Sievanen H, Heinonen A, Kannus P, Vuori I (2004) Effect of discontinuation of alendronate treatment and exercise on bone mass and physical fitness: 15-month follow-up of a randomized, controlled trial. Bone 35:799–805
Antic VN, Fleisch H, Muhlbauer RC (1996) Effect of bisphosphonates on the increase in bone resorption induced by a low calcium diet. Calcif Tissue Int 58:443–448
Shapses SA, Kendler D, Robson R, Hansen KE, Sherrel R, Field MP, Woolf E, Berd Y, Mantz AM, Santora A (2011) Effect of alendronate and vitamin D(3) on fractional calcium absorption in a double-blind, randomized, placebo-controlled trial in postmenopausal osteoporotic women. J Bone Miner Res 26:1836–1844
Tanko LB, Mouritzen U, Lehmann HJ et al (2003) Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens. Bone 32:687–693
Bonnick S, Broy S, Kaiser F, Teutsch C, Rosenberg E, DeLucca P, Melton M (2007) Treatment with alendronate plus calcium, alendronate alone, or calcium alone for postmenopausal low bone mineral density. Curr Med Res Opin 23:1341–1349
Acknowledgments
The authors wish to thank Dr. Fokter SK and Dr. Nehme A for providing additional data and information of their trials. The funding for this study was provided by Zhejiang Provincial Natural Science Foundation of China (Y2110239), Medical Research Foundation of Zhejiang Province (2010KYA105), and the National Natural Science Foundation of China (30872643, 81101345).
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Tiao Lin and Shi-Gui Yan contributed equally to this work and should be considered as co-first authors
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Supple. 1
Funnel plots of effects of BP on periprosthetic BMD at 3 (A), 6 (B), 12 (C), 24 to 72 months (D) after the index arthroplasty, at the end of BP treatment (E), and 18 to 70 months (F) after the end of BP treatment. (JPEG 6 kb)
Supple. 2
Trim and fill plots. (JPEG 11 kb)
Supple. 3
Characteristics of 14 included trials. (GIF 515 kb)
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Lin, T., Yan, SG., Cai, XZ. et al. Bisphosphonates for periprosthetic bone loss after joint arthroplasty: a meta-analysis of 14 randomized controlled trials. Osteoporos Int 23, 1823–1834 (2012). https://doi.org/10.1007/s00198-011-1797-5
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DOI: https://doi.org/10.1007/s00198-011-1797-5