Transplant Trial Watch

Effect of twice-yearly denosumab on prevention of bone mineral density loss in de novo kidney transplant recipients: a randomized controlled trial.

Bonani M, Frey D, et al.

American Journal of Transplantation 2015;16(6):1882-91

To study the efficacy and safety of Receptor Activator of Nuclear Factor κB Ligand (RANKL) inhibition with denosumab in preventing the loss of bone mineral density in de novo kidney transplant recipients.

Participants were randomized to receive subcutaneous injections of 60 mg denosumab at baseline and after 6 months, or no treatment.

90 kidney transplant recipients transplated <28 days prior to the study, receiving standard triple immunosuppression including a calcineurin antagonist, mycophenolate and corticosteroids.

The primary outcome measured was the percentage change in baseline areal bone mineral density (aBMD) at the total lumbar spine. Secondary outcomes included changes in aBMD at total hip and femoral neck, and changes in biomarkers of bone turnover.

12 months

CET Conclusions
This is a carefully done study of a new monoclonal antibody, Denosumab, which interacts with the receptor activator of nuclear factor kB ligand (RANKL). This humanised monoclonal antibody was developed for treatment of osteoporosis and prevention of fractures by inhibiting the development and activity of osteoclasts, thus leading to a decrease in bone absorption and an increase in bone density. It has been shown to be superior to bisphosphonates in improving bone mineral density and preventing fractures in post-menopausal women with osteoporosis. In this study 90 patients were randomised to receive Denosumab or no treatment. All patients received calcium and vitamin D supplements. The Denosumab was given by injections at base line and again at six months and the follow-up was over 12 months. At 12 months total lumbar spine bone mineral density (BMD) was increased by 4.6% and this was a highly significant improvement. Denosumab also increased BMD in the total hip and in a subgroup there was an improvement of volumetric BMD in the distal tibia and radius. Biomarkers of bone turnover were markedly decreased in the Denosumab group. The major adverse events were episodes of cystitis and asymptomatic hypocalcaemia, seen more often in the treatment group but there were no differences in graft function or the rate of rejection episodes. The authors conclude that Denosumab increases BMD in the first year after kidney transplantation but was associated with more frequent episodes of urinary tract infection. This, as I already mentioned, is a very carefully planned study which has produced very interesting results and these findings should be followed up for confirmation.

Jadad score

Data analysis
Strict intention-to-treat analysis

Allocation concealment

Trial registration - NCT01377467

Funding source
Non-industry funded