beta-Alanyl-L-histidinato zinc and bone resorption

1. beta-Alanyl-L-histidinato zinc (AHZ), in which zinc is chelated to beta-alanyl-L-histidine, is a new zinc compound. beta-Alanyl-L-histidine can uniquely chelated zinc ion in various essential trace metals. More recently, it has been demonstrated that this compound has more intensive effect than zinc sulfate on bone metabolism, suggesting a role as pharmacological tool in osteoporosis. This review describes mainly the action of AHZ on bone resorption as summarized in the following. 2. The prolonged oral administration of AHZ (10-100 mg/kg/day) can completely prevent bone loss in the femur of ovariectomized rats, indicating the preventive effect of AHZ on bone resorption in vivo. 3. The decrease in bone calcium content induced by various bone resorbing factors was completely inhibited by the presence of AHZ (10(-6)-10(-4) M) in bone tissue culture system in vitro. 4. Many bone resorbing agents can stimulate the formation (differentiation) of osteoclasts from marrow cells. AHZ (10(-6)-10(-4) M) clearly inhibited osteoclast-like cell formation in mouse marrow culture in vitro. 5. AHZ may act on the process of parathyroid hormone-induced protein kinase C activation which is involved in Ca(2+)-signaling in osteoclastic cells.