Bone loss after liver transplantation is not prevented by cyclical etidronate, calcium and alphacalcidol

Abstract

After orthotopic liver transplantation (OLT) bone mass rapidly declines and vertebral fracture rate increases. We studied bone loss and parameters of bone turnover in 53 consecutive patients. In an attempt to reduce bone loss the patients were prophylactically treated with cyclical etidronate in addition to daily 1 alpha-hydroxyvitamin D3 and calcium. During the first 3 months after transplantation median lumbar spinal bone mineral density (BMD) decreased 4.5%; subsequently no significant changes occurred. Median hip BMD continued to fall during the first post-transplantation year and deteriorated 7% over the whole study period. New vertebral fractures were seen in 25% of the patients, which is not lower than previously reported rates in patients not receiving cyclical etidronate. Parathyroid hormone levels increased after OLT (p = 0.01), but remained within normal ranges. Urinary hydroxyproline levels were increased and normalized in the second half-year after OLT. Elevated fasting calciuria increased further after OLT. 1,25-Dihydroxy-vitamin D3 levels were lowered pre-OLT (25 vs 66 pmol/ 1, p< 0.001) and normalized at 3 months after OLT. Serum osteocalcin concentrations remained unchanged and were reduced compared with levels in healthy controls. In summary, increased bone resorption occurs after OLT with persistent decreased bone formation, leading to vertebral fracture in 25% of patients. Etidronate, 1 alpha-calcidol and calcium treatment did not prevent bone loss.

Effects of a single infusion of pamidronate prior to liver transplantation: a bone histomorphometric study

“…Several intervention studies have been reported in patients undergoing liver transplantation but these have mostly been small and non-randomised. Combined treatment with calcium, alphacalcidol and cyclic etidronate did not prevent bone loss after liver transplantation in a nonrandomised study reported by Riemens et al [29]; moreover, 24% of treated patients suffered new vertebral fractures during the 1st year after transplantation. However, in another study both calcitonin and cyclic etidronate were reported to result in significant increases in vertebral bone-mineral density after 1 year's treatment in patients undergoing liver transplantation [30].…”

Evidence of continuing bone recovery at a mean of 7 years after liver transplantation

“…A trial of calcitonin in the first 6 months after OLT was not useful in preventing post-OLT bone loss, 37 although a combination of calcitonin and biphosphonates for 12 months after OLT showed some improvement in BMD. 38 However, Riemens et al 39 reported no benefit from prophylactic treatment with etidronate, calcium, and vitamin D.…”

Osteoporosis after liver transplantation

“…7,8,15,17,[20][21][22][23][24][25] Bone loss affects the spine and the proximal femur, some studies suggesting greater bone loss at the latter site. 17,18,26 The majority of studies indicate that there is at least some recovery of bone mineral density after the first year or so of transplantation, although this finding has not been universal.…”

“…In a subsequent study, cyclic etidronate was not found to be effective in the prevention of post-transplantation bone loss in the spine or hip when combined with alfacalcidol and calcium, although again no control group was studied. 21 In a non-randomised study, Neuhaus et al 72 investigated the effects of calcitriol, with or without calcium Ϯ sodium fluoride, started 6 months after liver transplantation. Increases in bone mineral density and the spine were demonstrated in all treatment groups, the greatest improvement being seen in patients treated with daily doses of calcitriol 0.5 g, calcium 1g and sodium fluoride 25mg.…”