Discontinuing antiresorptive therapy one year after cardiac transplantation: effect on bone density and bone turnover

We have previously reported that subjects randomized to alendronate or calcitriol immediately after cardiac transplantation sustained minimal bone loss during the first year, significantly less than a concurrently transplanted reference group that received calcium and parent vitamin D. In this extension, we evaluated the effect of discontinuing alendronate or calcitriol on bone loss and biochemical markers of bone turnover during the second year. We hypothesized that subjects who discontinued alendronate, which has a long half-life in bone, would not sustain significant bone loss. As the half-life of calcitriol is short, we hypothesized that there would be significant bone loss after discontinuing calcitriol.

We measured bone density (BMD), calciotropic hormones and bone turnover markers at 12, 18, and 24 months after transplantation in adherent subjects who completed the randomized trial on alendronate or calcitriol, and in reference subjects who had received no preventive therapy.

In all, 75 subjects (34 alendronate, 25 calcitriol, 16 reference) participated. During the second year, the bone resorption marker, serum N-telopeptide, rose by 27% in the calcitriol group (P< or =0.001). Bone alkaline phosphatase, a bone formation marker, increased by 54% in the calcitriol group (P< or =0.001) and by 32% in the alendronate group (P< or =0.001). BMD did not change significantly at any site in either randomized group.

After discontinuing alendronate or calcitriol, BMD remained stable during the second year after cardiac transplantation, despite a significant increase in a biochemical marker of bone resorption in the calcitriol group. This suggests that antiresorptive therapy may be discontinued at the end of the first posttransplantation year in cardiac transplant recipients without resumption of rapid bone loss. However, as increased bone turnover may predict future bone loss and fractures, such patients warrant observation to ensure that BMD remains stable long-term.