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Bisphosphonate therapy after liver transplant improves bone mineral density and reduces fracture rates: an updated systematic review and meta-analysis

Transpl Int. 2021 Aug;34(8):1386-1396 doi: 10.1111/tri.13887.
Abstract

To investigate the efficacy of bisphosphonates and compare oral and IV formulations on bone mineral density (BMD) and fracture incidence in post-orthotopic liver transplant (OLT) patients. Electronic databases were searched, and six RCTs and three cohort studies were included out of 711 articles. Main outcomes included post-OLT BMD changes, fracture incidence, and treatment adverse reactions. Pairwise meta-analysis was conducted for binary and continuous outcomes, while pooled fracture incidence utilized single-arm meta-analysis. Post-OLT fracture incidence was reported in nine studies (n = 591). Total fracture incidence was 6.6% (CI: 3.4-12.4%) in bisphosphonate group and 19.1% (CI: 14.3-25.1%) in calcium and vitamin D group. Total fractures were significantly lower in patients on bisphosphonate, compared to calcium and vitamin D (n = 591; OR = 0.037; CI: 0.18-0.77; P = 0.008). Overall fractures were significantly lower in the oral group (n = 263; OR = 0.26; CI: 0.08-0.85; P = 0.02) but not in the IV group (n = 328; OR = 0.45; CI: 0.16-1.26; P = 0.129). Both oral and IV bisphosphonates are effective in reducing fracture incidence post-OLT compared to calcium and vitamin D. Oral formulations may also have an advantage over IV in reducing bone loss and fracture incidence post-OLT.

CET Conclusion
Reviewer: Dr Liset Pengel, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: The systematic review and meta-analysis investigates the efficacy of bisphosphonates regarding the incidence of fractures, bone mineral density (BMD) changes and adverse reactions in liver transplant recipients. Medline and Embase were searched and six randomised controlled trials and three cohort studies met the inclusion criteria (n=645). Most studies were considered to be of good methodological quality. Study selection was done by independent reviewers but it was unclear if data extraction and methodological quality assessment was done in duplicate. The majority of patients started on bisphosphonates irrespective of BMD changes. The total and vertebral fracture incidence was significantly lower in patients taking bisphosphonates compared with patients on vitamin D and calcium. BMD of the lumbar spine and neck of femur were also significantly improved in patients taking bisphosphonates. Subgroup analyses of patients taking oral versus intravenous bisphosphonates showed improvements in BMD and the rate of fractures for patients taking oral bisphosphonates but the same effect was not seen in patients who received intravenous bisphosphonates. None of the studies reported serious adverse events.
Study Details
Aims: This study aimed to determine the efficacy of bisphosphonates in reducing the incidence of fracture, and to compare the effects of oral versus intravenous (IV) administration of bisphosphonate therapy on bone mineral density (BMD) and the incidence of fracture in post-orthotopic liver transplant (OLT) recipients.
Interventions: Electronic databases including Medline and Embase were searched. Two independent reviewers selected studies for inclusion. The methodological quality of the included studies were assessed using the Newcastle-Ottowa Scale and Jadad Scale for cohort studies and randomised controlled trials.
Participants: 9 studies were included in the review.
Outcomes: The main outcomes were changes in post-OLT BMD, the incidence of fracture and adverse reactions.
Follow Up: N/A
Metadata
Funding: No funding was received for this study
Publication type: Meta-Analysis, Systematic Review
Organ: Liver
Language: English
Author email: mdcmdm@nus.edu.sg
MeSH terms: Bone Density; Bone Density Conservation Agents; Diphosphonates; Fractures, Bone; Humans; Liver Transplantation; 0 (Bone Density Conservation Agents); 0 (Diphosphonates)