Dietary zinc reduces osteoclast resorption activities and increases markers of osteoblast differentiation, matrix maturation, and mineralization in the long bones of growing rats

The nutritional influence of zinc on markers of bone extracellular matrix resorption and mineralization was investigated in growing rats. Thirty male weanling rats were randomly assigned to consume AIN-93G based diets containing 2.5, 5, 7.5, 15 or 30 μg Zn/g diet for 24 days. Femur zinc increased substantially as zinc increased from 5 to 15 μg/g diet and modestly between 15 and 30 μg/g (P<.05). By morphological assessment, trabecular bone increased steadily as dietary zinc increased to 30 μg/g. Increasing dietary zinc tended to decrease Zip2 expression nonsignificantly and elevated the relative expression of metallothionen-I at 15 but not 30 μg Zn/g diet. Femur osteoclastic resorption potential, indicated by matrix metalloproteinases (MMP-2 and MMP-9) and carbonic anhydrase-2 activities decreased with increasing dietary zinc. In contrast to indicators of extracellular matrix resorption, femur tartrate-resistant acid and alkaline phosphatase activities increased fourfold as dietary zinc increased from 2.5 to 30 μg Zn/g. Likewise, 15 or 30 μg Zn/g diet resulted in maximum relative expression of osteocalcin, without influencing expression of core-binding factor α-1, collagen Type 1 alpha-1, or nuclear factor of activated T cells c1. In conclusion, increased trabecular bone with additional zinc suggests that previous requirement estimates of 15 μg Zn/g diet may not meet nutritional needs for optimal bone development. Overall, the up-regulation of extracellular matrix modeling indexes and concomitant decrease in resorption activities as dietary zinc increased from 2.5 to 30 μg/g provide evidence of one or more physiological roles for zinc in modulating the balance between bone formation and resorption.