Additive effects of combined treatment with etidronate and alfacalcidol onbone mass and mechanical properties in ovariectomized rats

The present study was undertaken to evaluate the effects of combined treatm ent with intermittent cyclical etidronate and daily alfacalcidol on the mas s and the mechanical properties of bone in ovariectomized rats, and to comp are the effects with those of single treatments, Seventy 14-week-old female rats underwent ovariectomy (ovx) or sham operation, and were assigned to s even groups (n = 10 each): sham-operated; ovx; ovx treated with etidronate; ovx treated with 0.1 mug/kg alfacalcidol; ovx treated with 0.2 mug/kg alfa calcidol; ovx treated with etidronate and 0.1 mug/kg alfacalcidol; and ovx treated with etidronate and 0.2 mug/kg alfacalcidol, One week after the ope ration, etidronate (4 mg/kg per day) was intermittently injected into rats for 2 weeks followed by a 10 week period of no treatment, and alfacalcidol was administered orally every day, After 24 weeks of treatment, all single and combined treatments increased the bone mineral densities (BMDs) of the proximal tibiae, midfemurs, and the fourth and fifth vertebral bodies, whic h had been decreased by ovx, Combined treatment groups showed higher BMDs t han single treatment groups, and the effects were almost equal to the addit ion of those of respective single treatment groups. The combined treatment also showed additive effects on the mechanical properties of both midfemurs and L4 vertebral bodies. The increases in mechanical properties were propo rtional to those in BMDs, Analyses of microcomputed tomography images and h istology confirmed the strong effects of combined treatments on both trabec ular and cortical bone mass without impairment of mineralization or connect ivity. We conclude that the combined treatment with etidronate and alfacalc idol additively increases the mass of bone with normal quality, resulting i n bone strengthening in ovx rats, (C) 2000 by Elsevier Science Inc. All rig hts reserved.