Sirolimus protective effects on bone: the need to be demonstrated

Sir, We read with great interest the article by Ralf Westenfeld et al. [1] regarding the reduced serum levels of bone resorption markers (TRAP-5b and sRANKL) in patients treated with sirolimus (SRL) after renal transplantation compared to a calcineurin inhibitor (CI)-based regimen, and in vitro, SRL reduced osteoclast differentiation and osteoclast precursor proliferation. So the authors concluded that SRL may have the potential to balance osteoclast promoting effects of glucocorticoids and CI. Multiple risk factors have been suggested to play a role in the pathogenesis of post-transplant bone disease, such as immunosuppressive drugs, persistent secondary hyperparathyroidism, impaired renal function and several other factors [2]. In this study, the authors emphasize the role of non-glucocorticoid immunosuppressants, SRL versus CI (including cyclosporine and tacrolimus). However, present studies investigating the effects of tacrolimus or cyclosporine on bone metabolism yielded conflicting data: cyclosporine may counterbalance the depressive effect of prednisone [3], while bone resorption effects were seen in both tacrolimus and cyclosporine [4]. So we consider that it is not appropriate to group the patients who took tacrolimus or cyclosporine together. And in vitro, the authors did not study the cyclosporine effect on osteoclast and osteoclast precursors. As there were only 15 patients in the CI group, a large sample analysis is needed to