A Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year after Kidney Transplantation

Abstract

Background: Bone and mineral disorders commonly affect kidney transplant (KTx) recipients and have been associated with a high risk of fracture. Bisphosphonates may prevent or treat bone loss in such patients, but there is concern that these drugs might induce adynamic bone disease (ABD).

Methods: In an open label, randomized trial to assess the safety and efficacy of zoledronate for preventing bone loss in the first year after kidney transplant, we randomized 34 patients before transplant to receive zoledronate or no treatment. We used dual-energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone biopsies to evaluate changes in bone in the 32 evaluable participants between the time of KTx and 12 months post-transplant.

Results: Both groups of patients experienced decreased bone turnover after KTx, but zoledronate itself did not affect this outcome. Unlike previous studies, DXA showed no post-transplant bone loss in either group; we instead observed an increase of bone mineral density in both lumbar spine and total hip sites, with a significant positive effect of zoledronate. However, bone biopsies showed post-transplant impairment of trabecular connectivity (and no benefit from zoledronate); HR-pQCT detected trabecular bone loss at the peripheral skeleton, which zoledronate partially attenuated.

Conclusions: Current immunosuppressive regimens do not contribute to post-transplant central skeleton trabecular bone loss, and zoledronate does not induce ABD. Because fractures in transplant recipients are most commonly peripheral fractures, clinicians should consider bisphosphonate use in patients at high fracture risk who have evidence of significantly low bone mass at these sites at the time of KTx.

Keywords: bone biopsy; kidney disease; kidney transplantation; mineral metabolism; renal osteodystrophy; zoledronic acid.

Graphical abstract

Figure 1.

Participant randomization flow chart. F, women; M, men.

Figure 2.

Distribution of bone turnover, mineralization and volume at baseline and 12 months in the zoledronate and control study groups. One year after kidney transplant, we observed an increase in low turnover bone disease in both groups. The prevalence of high trabecular volume decreased in the control and zoledronate groups. No significant changes were seen in mineralization. KTx, kidney transplantation.

Figure 3.

Bone biopsies of a patient in the zoledronate group (A) at baseline and (B) after 12 months showing a worsening of trabecular connectivity, which was characterized by an increase in trabecular separation and a decrease in trabecular number.