SKELETAL RESPONSE TO DIETARY ZINC IN ADULT FEMALE MICE

The current studies were intended to assess dose- and time-dependent e ffects of dietary zinc (Zn) on alkaline phosphatase (ALP) activity and tartrate-resistant acid phosphatase (TRAP) activity in adult female m ice. In the first study, mice were given 0, 1x, 2x, 3x, or 4x normal d ietary Zn for 2 weeks, 4 weeks, or 6 weeks. In the second study, mice were given 0, Ix, 2x, 3x, 4x, and 5x normal dietary Zn for 4 weeks. Se ra were collected for measurements of ALP and (in the second study) os teocalcin. Tibiae and calvaria were extracted for measurements of ALP, protein, and TRAP. The first study showed positive correlations betwe en dietary Zn and serum ALP (4 and 6 weeks, P < 0.001), Zn and tibial ALP (2, 4, and 6 weeks, P < 0.03), and Zn and tibial protein (2, 4, an d 6 weeks, P < 0.001), as well as a negative correlation between dieta ry Zn and tibial TRAP (2, 4, and 6 weeks, P < 0.001). Covariant analys es showed that serum ALP, tibial ALP, tibial protein, and tibial TRAP were affected by the dose of Zn (P < 0.005) and by the treatment time (P < 0.03). Supplemental studies showed that (1) the dose-dependent ef fect of dietary Zn on serum ALP (at 6 weeks) was proportional to the e ffects on tibial ALP and calvarial ALP, but not to the effects of Zn o n renal, hepatic, or intestinal ALP; (2) 6 weeks of dietary Zn caused dose-dependent increases in ALP specific activity in the tibia, calvar ia, and liver, but not kidneys or intestines; and (3) Zn increased ALP activity and cell layer protein and decreased TRAP activity in monola yer cultures of the murine osteoblastic cell line, MC3T3-E1. The secon d dietary study confirmed the results of the first: 4 weeks of treatme nt with Zn caused significant increases in serum ALP, calvarial ALP, a nd tibial ALP activities, and a significant decrease in tibial TRAP (P < 0.05-0.005 for each). This study also revealed an effect of Zn to i ncrease serum osteocalcin (P < 0.03 at 2x normal Zn). Together, these data indicate that incremental increases in dietary Zn are associated with increases in ALP activity in serum and in bone. The effect of Zn to decrease TRAP activity in osteoblast-line cells precludes the inter pretation of a Zn-dependent decrease in tibial TRAP activity as eviden ce of decreased bone resorption.