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Efficacy and Safety of Bisphosphonates for Low Bone Mineral Density After Kidney Transplantation: A Meta-Analysis.

ABSTRACT: In patients with low bone mineral density (BMD) after kidney transplantation, the role of bisphosphonates remains unclear. We performed a systematic review and meta-analysis to investigate the efficacy and safety of bisphosphonates.We retrieved trials from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception through May 2015. Only randomized controlled trials that compared bisphosphonate-treated and control groups of patients with low bone mineral density after kidney transplantation were included. The primary outcomes were the percent change in BMD, the absolute change in BMD, and the BMD at the end of study at the lumbar spine. The results were expressed as the mean difference (MD) or relative risk (RR) with the 95% confidence interval (CI). We used a random-effects model to pool the outcomes.We included 17 randomized controlled trials with 1067 patients. Only 1 included trial was found to be at low risk of bias. The rest of the included studies were found to have high to uncertain risk of bias. Compared with the control group, those who received bisphosphonates had a significant increase in percent change in BMD (mean difference [MD] = 5.51, 95% confidence interval [CI] 3.22-7.79, P < 0.00001) and absolute change in BMD (MD = 0.05, 95% CI 0.04-0.05, P < 0.00001), but a nonsignificant increase in BMD at the end of the study (MD = 0.02, 95% CI -0.01 to 0.05, P = 0.25) at the lumbar spine. Bisphosphonates resulted in a significant improvement in percent change in BMD (MD = 4.95, 95% CI 2.57-7.33, P < 0.0001), but a nonsignificant improvement in absolute change in BMD (MD = 0.03, 95% CI -0.00 to 0.06, P = 0.07) and BMD at the end of the study (MD = -0.01, 95% CI -0.04 to 0.02, P = 0.40) at the femoral neck. No significant differences were found in vertebral fractures, nonvertebral fractures, adverse events, and gastrointestinal adverse events.Bisphosphonates appear to have a beneficial effect on BMD at the lumbar spine and do not significantly decrease fracture events in recipients. However, the results should be interpreted cautiously due to the lack of robustness and the heterogeneity among studies.

SUBMITTER: Kan SL

PROVIDER: S-EPMC4748922 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Mineral and bone disorder is one of the severe complications in kidney transplant recipients (KTRs). Previous studies showed that bisphosphonates had favorable effects on bone mineral density (BMD). We sought to compare different bisphosphonate regimens and rank their strategies.We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to April 01, 2017, for randomized controlled trials (RCTs) comparing bisphosphonate treatments in adult KTRs. The primary outcome was BMD change. We executed the tool recommended by the Cochrane Collaboration to evaluate the risk of bias. We performed pairwise meta-analyses using random effects models and network meta-analysis (NMA) using Bayesian models and assessed the quality of evidence.A total of 21 RCTs (1332 participants) comparing 6 bisphosphonate regimens were included. All bisphosphonates showed a significantly increased percentage change in BMD at the lumbar spine compared to calcium except clodronate. Pamidronate with calcium and Vitamin D analogs showed improved BMD in comparison to clodronate with calcium (mean difference [MD], 9.84; 95% credibility interval [CrI], 1.06-19.70). The combination of calcium and Vitamin D analogs had a significantly lower influence than adding either pamidronate or alendronate (MD, 6.34; 95% CrI, 2.59-11.01 and MD, 6.16; 95% CrI, 0.54-13.24, respectively). In terms of percentage BMD change at the femoral neck, both pamidronate and ibandronate combined with calcium demonstrated a remarkable gain compared with calcium (MD, 7.02; 95% CrI, 0.30-13.29 and MD, 7.30; 95% CrI, 0.32-14.22, respectively). The combination of ibandronate with calcium displayed a significant increase in absolute BMD compared to any other treatments and was ranked best.Our NMA suggested that new-generation bisphosphonates such as ibandronate were more favorable in KTRs to improve BMD. However, the conclusion should be treated with caution due to indirect comparisons.

Project description:ABSTRACT Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone mass and may have already sustained fractures. Short or intermittent courses of bisphosphonate therapy, initiated around the time of menopause, might prevent excessive bone loss and lower long‐term fracture risk. We undertook a systematic review and meta‐analysis of randomized controlled trials (RCTs) to determine the effects of nitrogen‐containing bisphosphonates on fracture incidence, bone mineral density (BMD), and bone turnover markers in early menopausal women (ie, perimenopausal or <5 years postmenopausal) over ≥12 months. Medline, Embase, CENTRAL, and CINAHL were searched in July 2022. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Random effect meta‐analysis was undertaken using RevMan v5.3. In total, 12 trials were included (n = 1722 women); five evaluated alendronate, three risedronate, three ibandronate, and one zoledronate. Four were at low risk of bias; eight raised some concerns. Fractures were infrequent in the three studies that reported them. Compared with placebo, bisphosphonates improved BMD over 12 months (mean percentage difference, 95% confidence interval [CI]) at the spine (4.32%, 95% CI, 3.10%–5.54%, p < 0.0001, n = 8 studies), the femoral neck (2.56%, 95% CI, 1.85%–3.27%, p = 0.001, n = 6 studies), and the total hip (1.22%, 95% CI 0.16%–2.28%, p = 0.002, n = 4 studies). Over treatment durations of 24 to 72 months, bisphosphonates improved BMD at the spine (5.81%, 95% CI 4.71%–6.91%, p < 0.0001, n = 8 studies), femoral neck (3.89%, 95% CI 2.73%–5.05%, p = 0.0001, n = 5 studies) and total hip (4.09%, 95% CI 2.81%–5.37%, p < 0.0001, n = 4 studies). Bisphosphonates reduced urinary N‐telopeptide (−52.2%, 95% CI −60.3% to −44.2%, p < 0.00001, n = 3 studies) and bone‐specific alkaline phosphatase (−34.2%, 95% CI −42.6% to −25.8%, p < 0.00001, n = 4 studies) more than placebo at 12 months. This systematic review and meta‐analysis shows that bisphosphonates improve BMD and lower bone turnover markers in early menopause, warranting further investigation of these agents for osteoporosis prevention. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This systematic review and meta‐analysis of randomized controlled trials demonstrates that nitrogen‐containing bisphosphonates improve bone density and lower bone turnover markers in early menopausal women (i.e. perimenopausal or <5 year postmenopausal), warranting further investigation of these agents for osteoporosis prevention.

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Efficacy and Safety of Bisphosphonates for Low Bone Mineral Density After Kidney Transplantation: A Meta-Analysis.

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