Calcitriol and Calcitonin prevent cyclosporine – induced alveolar bone loss

Background and Objective: Bone loss is reported as a significant side-effect of cyclosporine-A (CsA) therapy because this can result in serious morbidity of the patients. Intermittent combination of Calcitriol and Salmon thyrocalcitonin have been recognized to potentiate both bone resorption and formation, increase bone volume by inhibiting accelerated bone resorption at pharmacological doses. Since we have shown that CsA-associated bone loss can also affect the alveolar bone, the purpose of this study was to evaluate the effects of intermittent combination of calcitriol and calcitonin as therapy on CsA-induced alveolar bone loss in rats. Methods: Groups of rats (n=10) were treated with either CsA (10mg/kg/day, s.c.), Calcitriol (2µg/kg; p.o.) + calcitonin (2µg/kg;i.p.) or drug vehicle during 60 days, and an additional group received CsA concurrently with intermittent administration of Calcitriol (at weeks 1,3,5, and 7) and Calcitonin (at weeks 2,4,6, and 8) during the same experimental period. Bone-specific alkaline phosphatase (BALP), tartrate-resistent acid phosphatase (TRAP-5b), osteocalcin, interleukin (IL)-1 beta, IL-6, tumor necrosis factor (TNF-alpha) concentrations was evaluated in the serum. Analysis of bone volume, bone surface, number of osteblasts and osteoclasts were performed. Results: The results confirmed that CsA therapy was associated with bone resorption, represented by lower bone volume and increased number of osteoclasts; serum BALP, TRAP-5b, IL-1 beta, IL-6 and TNF-alpha were also higher in these animals. The intermittent administration of Calcitriol /Calcitonin together with CsA altered serum markers returned to the control values, in addition to the significant increase of bone volume and the lower number of osteoclasts. Conclusion: This study shows that intermittent Calcitriol/Calcitonin therapy can prevent CsA-induced bone loss.