Zinc deficiency decreases bone mineral density of rat by calmodulin-induced change in calcium metabolism

Background Zinc deficiency decreases bone mineral density (BMD), but it is not known whether decreased BMD is a result of altered calcium absorption, excretion, and/or tissue distribution. To identified the associations between zinc deficiency, calcium metabolism and decreased BMD. Methods we performed two zinc deficiency experiments. In the first experiment, male rats (5-week-old) were fed a low zinc diet for four weeks. We measured serum zinc, alkaline phosphatase, Ca2+, osteocalcin, calcitonin, parathyroid hormone (PTH), calcium concentrations in feces and urine, BMD, and femur bone length and weight. In the second experiment, male rats (3-week-old) were fed a low zinc diet for five weeks. In addition to the aforesaid indicators, we measured the concentrations of zinc, total calcium, and calmodulin in multiple tissues. Results In both experiments, serum zinc, alkaline phosphatase, fecal and urine calcium, BMD, and bone weight of the low zinc diet group (LZG) were reduced compared with the normal zinc diet group (NZG)and pair-fed group (PZG); PTH increased significantly. Serum Ca2+, osteocalcin, and calcitonin concentrations were unchanged and not associated with decreased BMD. In the second experiment, zinc concentrations were reduced in serum, skeletal muscle, feces, and urine of LZG animals compared with NZG and PZG. Calmodulin in serum and skeletal muscle of the LZG group was decreased. Zinc deficiency increased total calcium concentrations in serum and skeletal muscle by promoting a decrease in calmodulin. To maintain blood Ca2+ balance, elevated PTH increased calcium reabsorption, reduced calcium excretion, stimulated bone resorption, mobilized bone calcium, and decreased BMD. (4) Conclusions: Decreased calmodulin and increased PTH induced by zinc deficiency altered calcium tissue distribution and decreased BMD of rat. ### Competing Interest Statement The authors have declared no competing interest.