Bisphosphonate drugs increase bone mineral density (BMD) in kidney transplant recipients, a new systematic review and meta-analysis confirms. Early bisphosphonate therapy within the first 6 months of transplant is the most beneficial. Whether the drugs prevent fractures remains unclear.

Study findings strengthen the case for bisphosphonate therapy in kidney transplantation recipients, said investigator Craig Gordon, MD, MS, of Boston University School of Medicine. Selection of this treatment needs to be individualized, however, because concerns remain about these agents causing higher rates of adynamic bone disease. “So, the benefit in BMD may be offset by this increase in adynamic bone disease, which is perhaps why at this point the evidence is not strong enough to recommend bisphosphonates universally to all kidney transplant recipients with reduced BMD,” Dr Gordon told Renal & Urology News.

Mineral and bone disorders develop in kidney transplant patients due to a combination of factors, he explained, such as abnormal bone turnover from chronic kidney disease that is exacerbated by corticosteroid use or tertiary hyperparathyroidism after transplantation, among other causes. BMD of the lumbar spine drops in the first 6 months of transplant and declines still further for up to 18 months.  Fracture rates are high among kidney recipients, ranging up to 44%, likely due to the bone loss. 

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To update estimates of BMD and fracture rates, Dr Gordon and colleagues performed a systematic review of 12 randomized controlled trials and prospective studies with a reference group published before October 2015. All 12 studies of 625 patients reported on lumbar spine BMD, whereas 7 studies with 287 patients also reported on femoral neck BMD. At baseline, mean creatinine was 1.49 mg/dL, calcium was 9.66 mg/dL, and phosphorus was 4.83 mg/dL. Pre-treatment BMD in the femoral neck and lumbar spine was 0.845 and 1.057 g/cm2, respectively.

Results published in Clinical Transplantation showed that bisphosphonate therapy improved femoral neck and lumbar spine BMD in transplant recipients compared with control patients by 0.055 g/cm2 and 0.053 g/cm2, respectively, without worsening serum creatinine in the allograft or serum calcium levels. By percentage, BMD improved by 6.0% and 7.4%, respectively. BMD did not differ by route of bisphosphonate administration (oral or intravenous). 

Notably, the investigators found no difference in fracture incidence between groups. “Although we did not find a difference in fracture rates, this is a question that still requires answering,” Dr Gordon said. “The studies in our meta-analysis had relatively small sample sizes, relatively short follow-up times, and did not assess for occult fractures, each of which might have increased the statistical power to detect a difference in fracture risk, if one exists.”

The findings corroborate 2 previous meta-analyses that showed an association between bisphosphonate therapy and increased BMD (Nephrol Dial Transplant 2006;21:2275-2281 and Cochrane Database Syst Rev 2007;3:CD005015).

The 2009 Kidney Disease Improving Global Outcomes (KIDGO) guidelines on Caring for the Kidney Transplant Recipient suggest clinicians consider bisphosphonate therapy in kidney transplant recipients based on limited evidence.

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1.    1. Toth-Manikowski SM, Francis JM, Gautam A, and Gordon CE. Outcomes of Bisphosphonate Therapy in Kidney Transplant Recipients: A Systematic Review and Meta-analysis. Clin Transplant. 2016 Sep;30(9):1090-6. doi: 10.1111/ctr.12792.