Evaluation of Osteoporotisis Drugs by Histological, Biochemical Approach in Experimental Osteoporosis Model

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Several recent studies have demonstrated that vitamin D affects not only bone but also muscle to prevent falls and osteoporotic fractures. However, these effects on muscle and the mechanisms of fall-prevention are still unclear. In this study, we investigated the effects of alfacalcidol (1α(OH)D3) on muscle strength, muscle fatigue, and bone mineral density (BMD) in normal and ovariectomized rats.Following ovariectomy (OVX) or sham operation in 7-month-old female Wistar rats, alfacalcidol (0.1 μg/kg/day) or its vehicle was administered orally for 4 weeks. On the day after the final administration, the distal end of the Achilles' tendon was cut and attached to a force transducer under general anesthesia, and the sciatic nerve was exposed and electrically stimulated for 20 cycles. The maximum contraction tension of the calf muscles for each stimulation cycle was measured to evaluate muscle strength. Muscle fatigue at each stimulation cycle was evaluated as the percentage strength at each cycle to the initial contraction strength. Muscle strength and fatigue were then normalized using the body weight. After the measurement of muscle strength and fatigue, the right femur was harvested to measure the BMD at the distal third of the femur by dual energy x-ray absorptiometry.Alfacalcidol administration significantly increased the maximum muscle strength in the sham-operated and the OVX groups compared to their respective control groups. However, alfacalcidol administration did not significantly affect muscle fatigue in these groups. The BMD in the alfacalcidol-treated OVX group was significantly higher than that in the vehicle-treated OVX group.We conclude that alfacalcidol increases muscle strength, but does not affect muscle fatigue in the rat model. The effectiveness of vitamin D in preventing fractures may be partly due to its effect on muscle strength in addition to its known effect on bone metabolism.