Effectiveness of Bisphosphonates in Preventing Periprosthetic Bone Loss after Joint Replacement: A Systematic Review and Meta-Analysis

Dr Sachin N C; Dr. Tejal.VV; Dr. Vedavathi H

doi:10.51168/h8tzk046

Autori

Dr Sachin N C Senior Registrar, Apollo Hospital, Bannerghatta Road, Bangalore -560076, Karnataka, India
Dr. Tejal.VV Resident, Indira Maternity and Skin Laser Center, Station Road, Tumkur- 572102, Karnataka, India
Dr. Vedavathi H Professor and Head, Department of Pharmacology, Shimoga Institute of Medical Sciences, Shimoga 577201, Karnataka, India

DOI:

https://doi.org/10.51168/h8tzk046

Cuvinte cheie:

bisphosphonates, arthroplasty, bone mineral density, periprosthetic bone loss, total hip arthroplasty, total knee arthroplasty

Rezumat

Background: Periprosthetic bone loss after joint replacement may compromise bone stock and contribute to implant migration, aseptic loosening, fracture, and technically difficult revision. Bisphosphonates suppress osteoclast-mediated resorption, but trial findings differ by joint, anatomical region, drug, and follow-up.

Objective: To evaluate the effectiveness and safety of bisphosphonates for preventing periprosthetic bone loss after hip and knee joint replacement.

Methods: An updated systematic evidence synthesis was undertaken using PubMed/MEDLINE, publisher full-text databases, and backward and forward citation tracking through 30 November 2025. Randomised comparative trials of a bisphosphonate versus placebo, no treatment, or calcium/vitamin D alone were eligible. The primary de novo meta-analysis combined 12-month total periprosthetic bone mineral density (BMD) change after total hip arthroplasty (THA) when outcomes were reported in g/cm². A restricted maximum-likelihood random-effects model with Hartung–Knapp confidence intervals was used. Anatomically incompatible hip and knee outcomes were retained as prespecified strata.

Results: Twenty-five randomised trial reports involving 1,115 participants were represented across the verified hip, osteoporotic-hip/zoledronic-acid, and knee evidence sets. Ten THA trials (420 analysed participants) contributed to the de novo 12-month analysis. Bisphosphonates preserved total periprosthetic BMD by 0.063 g/cm² (95% CI 0.040–0.085; p<0.001; I²=51.3%; τ²=0.000238); the 95% prediction interval was 0.021–0.104 g/cm². Published random-effects strata also showed benefit at 2–4 years (MD 0.04 g/cm²) and beyond 5 years (MD 0.08 g/cm²) after THA. After total knee arthroplasty (TKA), proximal tibial BMD was higher at 3 and 6 months but not clearly at 12 months, while distal femoral estimates favoured alendronate but were highly heterogeneous. In osteoporotic hip-arthroplasty populations, zoledronic acid preserved BMD most consistently in Gruen zones 1, 6, and 7; influenza-like symptoms were more frequent (RR 7.03, 95% CI 2.63–18.78), without a demonstrated increase in serious adverse events.

Referințe

1. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https://doi.org/10.1136/bmj.n71

2. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane Handbook for Systematic Reviews of Interventions. Version 6.5. Cochrane; 2024.

3. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. https://doi.org/10.1136/bmj.l4898

4. Schünemann HJ, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. GRADE Working Group; 2013.

5. Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc. 2008;83(9):1032-1045. https://doi.org/10.4065/83.9.1032

6. Sundfeldt M, Carlsson LV, Johansson CB, Thomsen P, Gretzer C. Aseptic loosening, not only a question of wear: a review of different theories. Acta Orthop. 2006;77(2):177-197. https://doi.org/10.1080/17453670610045902

7. Shi J, Liang G, Huang R, Liao L, Qin D. Effects of bisphosphonates in preventing periprosthetic bone loss following total hip arthroplasty: a systematic review and meta-analysis. J Orthop Surg Res. 2018;13:225. https://doi.org/10.1186/s13018-018-0918-7

8. Shi M, Chen L, Wu H, Wang Y, Wang W, Yan S, et al. Effect of bisphosphonates on periprosthetic bone loss after total knee arthroplasty: a meta-analysis of randomized controlled trials. BMC Musculoskelet Disord. 2018;19:177. https://doi.org/10.1186/s12891-018-2101-z

9. Lin T, Yan SG, Cai XZ, Ying ZM. Bisphosphonates for periprosthetic bone loss after joint arthroplasty: a meta-analysis of 14 randomized controlled trials. Osteoporos Int. 2012;23(6):1823-1834. https://doi.org/10.1007/s00198-011-1797-5

10. Liu Y, Xu JW, Li MY, Wu LM, Zeng Y, Shen B. Zoledronic acid for periprosthetic bone mineral density changes in patients with osteoporosis after hip arthroplasty: an updated meta-analysis of six randomized controlled trials. Front Med (Lausanne). 2021;8:801282. https://doi.org/10.3389/fmed.2021.801282

11. Liu Y, Xu J, Wang X, et al. Zoledronic acid for periprosthetic bone mineral density changes in patients with osteoporosis after hip arthroplasty: an updated meta-analysis of six randomized controlled trials. Front Med (Lausanne). 2021;8:801282. https://doi.org/10.3389/fmed.2021.801282

12. Tang Y, Jin Z, Lu Y, Chen L, Lv S, Xu T, et al. Comparing the efficacy of antiosteoporotic drugs in preventing periprosthetic bone loss following total hip arthroplasty: a systematic review and Bayesian network meta-analysis. Orthop Surg. 2024;16(10):2344-2354. https://doi.org/10.1111/os.14165

13. Tapaninen TS, Venesmaa PK, Jurvelin JS, Miettinen HJA, Kröger HPJ. Alendronate reduces periprosthetic bone loss after uncemented primary total hip arthroplasty-a 5-year follow-up of 16 patients. Scand J Surg. 2010;99(1):32-37. https://doi.org/10.1177/145749691009900108

14. Trevisan C, Ortolani S, Romano P, Isaia G, Agnese L, Dallari D, et al. Decreased periprosthetic bone loss in patients treated with clodronate: a 1-year randomized controlled study. Calcif Tissue Int. 2010;86(6):436-446. https://doi.org/10.1007/s00223-010-9356-1

15. Arabmotlagh M, Pilz M, Warzecha J, Rauschmann M. Changes of femoral periprosthetic bone mineral density 6 years after treatment with alendronate following total hip arthroplasty. J Orthop Res. 2009;27(2):183-188. https://doi.org/10.1002/jor.20748

16. Yamasaki S, Masuhara K, Yamaguchi K, Nakai T, Fuji T, Seino Y. Risedronate reduces postoperative bone resorption after cementless total hip arthroplasty. Osteoporos Int. 2007;18(7):1009-1015. https://doi.org/10.1007/s00198-007-0339-7

17. Fokter SK, Komadina R, Repse-Fokter A. Effect of etidronate in preventing periprosthetic bone loss following cemented hip arthroplasty: a randomized, double-blind, controlled trial. Wien Klin Wochenschr. 2006;118(Suppl 2):23-28. https://doi.org/10.1007/s00508-006-0556-7

18. Arabmotlagh M, Rittmeister M, Hennigs T. Alendronate prevents femoral periprosthetic bone loss following total hip arthroplasty: prospective randomized double-blind study. J Orthop Res. 2006;24(7):1336-1341. https://doi.org/10.1002/jor.20162

19. Yamaguchi K, Masuhara K, Yamasaki S, Fuji T, Seino Y. Effects of discontinuation as well as intervention of cyclic therapy with etidronate on bone remodeling after cementless total hip arthroplasty. Bone. 2004;35(1):217-223. https://doi.org/10.1016/j.bone.2004.03.017

20. Iwamoto N, Inaba Y, Kobayashi N, Ishida T, Yukizawa Y, Saito T. A comparison of the effects of alendronate and alfacalcidol on bone mineral density around the femoral implant and in the lumbar spine after total hip arthroplasty. J Bone Joint Surg Am. 2011;93(13):1203-1209. https://doi.org/10.2106/JBJS.I.01714

21. Kinov P, Tivchev P, Doukova P, Leithner A. Effect of risedronate on bone metabolism after total hip arthroplasty: a prospective randomised study. Acta Orthop Belg. 2006;72(1):44-50.

22. Shetty N, Hamer AJ, Stockley I, Eastell R, Wilkinson JM. Clinical and radiological outcome of total hip replacement five years after pamidronate therapy: a trial extension. J Bone Joint Surg Br. 2006;88(10):1309-1315. https://doi.org/10.1302/0301-620X.88B10.17308

23. Scott DF, Woltz JN, Smith RR. Effect of zoledronic acid on reducing femoral bone mineral density loss following total hip arthroplasty: preliminary results of a prospective randomized trial. J Arthroplasty. 2013;28(4):671-675. https://doi.org/10.1016/j.arth.2012.08.007

24. Yukizawa Y, Inaba Y, Kobayashi N, Choe H, Kubota S, Saito T. Efficacy of alendronate for the prevention of bone loss in the calcar region following total hip arthroplasty. J Arthroplasty. 2017;32(7):2176-2180. https://doi.org/10.1016/j.arth.2017.02.036

25. Muren O, Akbarian E, Salemyr M, Bodén H, Eisler T, Stark A, et al. No effect of risedronate on femoral periprosthetic bone loss following total hip arthroplasty: a 4-year follow-up of 61 patients in a double-blind, randomized placebo-controlled trial. Acta Orthop. 2015;86(5):569-574. https://doi.org/10.3109/17453674.2015.1041846

26. Nehme A, Maalouf G, Tricoire JL, Giordano G, Chiron P, Puget J. Effect of alendronate on periprosthetic bone loss after cemented primary total hip arthroplasty: a prospective randomized study. Rev Chir Orthop Reparatrice Appar Mot. 2003;89(7):593-598.

27. Soininvaara TA, Jurvelin JS, Miettinen HJA, Suomalainen OT, Alhava EM, Kröger PJ. Effect of alendronate on periprosthetic bone loss after total knee arthroplasty: a one-year, randomized, controlled trial of 19 patients. Calcif Tissue Int. 2002;71(6):472-477. https://doi.org/10.1007/s00223-002-1022-9

28. Han H, Li X, Wang Y, Zeng X, Xu C. Preventing prosthesis from loosening after joint replacement. Chinese Journal of Surgery of Integrated Traditional and Western Medicine. 2003;9(3):179-182.

29. Wang CJ, Wang JW, Ko JY, Weng LH, Huang CC. 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. 2006;88(2):267-272. https://doi.org/10.2106/JBJS.E.00051

30. Abu-Rajab RB, Watson W, Gallacher P, Walker B, Meek RMD. The effect of 6 months oral alendronate treatment on periprosthetic bone loss after total knee arthroplasty. Eur J Orthop Surg Traumatol. 2009;19:231-235. https://doi.org/10.1007/s00590-008-0412-8

31. Jaroma AVJ, Soininvaara TA, Kröger H. Effect of one-year postoperative alendronate treatment on periprosthetic bone after total knee arthroplasty: a seven-year randomised controlled trial of 26 patients. Bone Joint J. 2015;97-B(3):337-345. https://doi.org/10.1302/0301-620X.97B3.33643

32. Aro E, Moritz N, Mattila K, Aro HT. A long-lasting bisphosphonate partially protects periprosthetic bone, but does not enhance initial stability of uncemented femoral stems: a randomized placebo-controlled trial of women undergoing total hip arthroplasty. J Biomech. 2018;75:35-45. https://doi.org/10.1016/j.jbiomech.2018.04.041

33. Friedl G, Radl R, Stihsen C, Rehak P, Aigner R, Windhager R. The effect of a single infusion of zoledronic acid on early implant migration in total hip arthroplasty: a randomized, double-blind, controlled trial. J Bone Joint Surg Am. 2009;91:274-281. https://doi.org/10.2106/JBJS.G.01193

34. Huang TW, Wang CJ, Shih HN, Chang Y, Huang KC, Peng KT, et al. Bone turnover and periprosthetic bone loss after cementless total hip arthroplasty can be restored by zoledronic acid: a prospective, randomized, open-label, controlled trial. BMC Musculoskelet Disord. 2017;18:209. https://doi.org/10.1186/s12891-017-1577-2

35. Lacko M, Schreierová D, Čellár R, Vaško G. Bone remodelling in the proximal femur after uncemented total hip arthroplasty in patients with osteoporosis. Acta Chir Orthop Traumatol Cech. 2015;82(6):430-436. https://doi.org/10.55095/achot2015/071

36. Zhou W, Liu Y, Guo X, Yang H, Xu Y, Geng D. Effects of zoledronic acid on bone mineral density around prostheses and bone metabolism markers after primary total hip arthroplasty in females with postmenopausal osteoporosis. Osteoporos Int. 2019;30:1581-1589. https://doi.org/10.1007/s00198-019-05005-7

37. Zhu K, Zhang J, Zhang C, Zhao Z, Gao J, Li X, et al. Therapeutic efficacy of zoledronic acid combined with calcitriol in elderly patients receiving total hip arthroplasty or hemiarthroplasty for osteoporotic femoral neck fracture. Osteoporos Int. 2021;32:559-564. https://doi.org/10.1007/s00198-020-05637-0

38. Prieto-Alhambra D, Javaid MK, Judge A, Murray D, Carr A, Cooper C, et al. Association between bisphosphonate use and implant survival after primary total arthroplasty of the knee or hip: population-based retrospective cohort study. BMJ. 2011;343:d7222. https://doi.org/10.1136/bmj.d7222

39. Khatod M, Inacio MCS, Dell RM, Bini SA, Paxton EW, Namba RS. Association of bisphosphonate use and risk of revision after THA: outcomes from a US total joint replacement registry. Clin Orthop Relat Res. 2015;473(11):3412-3420. https://doi.org/10.1007/s11999-015-4263-4

40. Adler RA, El-Hajj Fuleihan G, Bauer DC, Camacho PM, Clarke BL, Clines GA, et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016;31(1):16-35. https://doi.org/10.1002/jbmr.2708