Osteoporosis International

, Volume 29, Issue 7, pp 1525–1537 | Cite as

Bisphosphonates for the preservation of periprosthetic bone mineral density after total joint arthroplasty: a meta-analysis of 25 randomized controlled trials

  • M. Shi
  • L. Chen
  • Z. Xin
  • Y. Wang
  • W. Wang
  • S. Yan
Original Article



The present meta-analysis aimed to evaluate the long-term efficacy of bisphosphonates (BPs) on preservation of periprosthetic bone mineral density (BMD) after joint arthroplasty. It confirmed the protective effect of BPs in a long-term follow-up, and found the influence factors on this effect.


Periprosthetic bone loss is believed to cause aseptic loosening and failed prosthetic fixation in joint arthroplasty. This meta-analysis which included high-quality randomized controlled trials aimed to analyze the effect of bisphosphonates on maintaining periprosthetic bone mineral density after total joint arthroplasty.


Twenty-five RCTs were included and the total number of participants was 1163 by computerized searches of bibliographic databases. The weighted mean differences with 95% confidence interval were calculated to evaluate the efficacy of BPs on total periprosthetic BMD and the BMD of different Gruen zones. Subgroup analyses identified the potentially influencing factors such as surgical site, cement fixation, and generation of BPs. A descriptive review was conducted for BP-related adverse effects.


The BPs group presented significantly higher total periprosthetic BMD in the BPs group than that in the control group at 3, 6, 12 months, 2–4 years, and 5–10 years after arthroplasty (P < 0.05). The BPs group presented significantly higher periprosthetic BMD in femoral Gruen Zone 1 and 7 than that in the control group at 3, 6, 12 months, 2–4 years, and 5–10 years (P < 0.05). The heterogeneity was minimized by dividing THA and TKA into two subgroups. Subgroup analyses revealed that the effect of BPs on preservation of BMD was significantly greater in arthroplasty with cemented component than in that with uncemented component at 12 months and 5–10 years (P < 0.05), and the administration of the second and third generation BPs was significantly more effective than the first-generation BPs at 6 and 12 months (P < 0.05). None of the included studies described severe or fatal adverse effects related to BPs.


BPs have significantly long-term efficacy on the preservation of periprosthetic BMD after joint arthroplasty. To obtain a better efficacy, the cemented components and the second and third generation BPs are recommended.


Arthroplasty Bisphosphonates Bone mineral density Meta-analysis 



This research was supported by Zhejiang Province Natural Science Foundation of China under Grant No. LQ16H060002 and Medical and Health Science and Technology Project of Zhejiang Province under Grant No. 2016KYB120.

Compliance with ethical standards

Conflicts of interest


Supplementary material

198_2018_4488_Fig3_ESM.gif (111 kb)

The seven regions of interest based on Gruen zones. (GIF 111 kb)

198_2018_4488_MOESM1_ESM.tif (156 kb)
High Resolution (TIFF 156 kb)
198_2018_4488_MOESM2_ESM.docx (16 kb)
ESM 2 Characteristics of 19 excluded trials. (DOCX 16 kb)
198_2018_4488_Fig4_ESM.gif (1 kb)

The funnel plots asymmetry for the outcome showed the evidence of publication bias at 3 months (a), 6 months (b), 12 months (c), 2 to 4 years (d) and 5–10 years (e) after the arthroplasty. (GIF 971 bytes)

198_2018_4488_MOESM3_ESM.tif (1 mb)
High Resolution (TIFF 1045 kb)
198_2018_4488_MOESM4_ESM.doc (189 kb)
ESM 4 GRADE evidence profile of RCTs for effect of BPs on periprosthetic bone loss after joint arthroplasty. (DOC 189 kb)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  1. 1.Department of Orthopaedic Surgery, Second Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouPeople’s Republic of China
  2. 2.Department of Endocrinology and Metabolism, Sir Run Run Shaw Hospital Affiliated with School of MedicineZhejiang UniversityHangzhouPeople’s Republic of China

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