Bone structure and remodelling in stroke patients: early effects of zoledronate.

Abstract

We have reported that after an acute stroke, intravenous zoledronate prevented bone loss in the hemiplegic hip. Participants from the trial also volunteered for trans-iliac bone biopsy, to assess the early effects of stroke and zoledronate on iliac bone remodelling. Patients with acute stroke were randomly assigned to a single intravenous dose of zoledronate 4 mg or placebo within 5 weeks of stroke. Biopsies from 14 patients (3 female, 11 male, mean age 71+/-11) were suitable for analysis. These were taken at mean 10 weeks (+/-2) post-stroke, and included 5 patients who had received zoledronate. Histomorphometry was performed on undecalcified sections using light and fluorescence microscopy. Static and dynamic indices of remodelling were compared to a local reference range from healthy controls. Osteoclasts and their precursors were identified on frozen sections using tartrate resistant acid phosphatase (TRAP) staining. Dual-energy x-ray absorptiometry (DXA) of the proximal femora was performed at baseline and 6 months later. The eroded surface in cancellous bone (ES/BS) was significantly higher in stroke patients than controls (5.7% vs. ref 1.6%, p<0.0001). Although ES/BS did not differ between zoledronate and placebo-treated groups, there were significantly fewer osteoclasts and their precursors in zoledronate-treated individuals (p=0.023). Bone formation indices (osteoid surface, OS/BS and mineralising surface, MS/BS) were significantly lower in stroke patients than controls and although OS/BS was higher in the zoledronate group than the placebo group (p=0.033), MS/BS was not different (p=0.924). There were no differences between hemiplegic and unaffected sides for any histomorphometric parameter despite asymmetric reductions in hip bone mineral density (p=0.013). Stroke patients had higher resorption indices and lower bone forming surfaces than controls, consistent with uncoupling of bone remodelling. These findings are preliminary and a larger study is required to evaluate the contributions of gender, age and hemiplegic status to the remodelling imbalance. Zoledronate therapy was associated with a reduction in osteoclastic cell numbers consistent with its known mode of action in bone.