Effects of magnesium and lactose supplementation on bone metabolism in the X-linked hypophosphatemic mouse

Besides rickets and osteomalacia, the X-linked hypophosphatemic male mouse ($\text{Hyp}\text{Y}$) presents with low serum calcium (Ca) and increased urinary hydroxyproline (OH-Pro) excretion, suggesting a parathyroid hormone (PTH)-stimulated bone resorption despite reduced magnesium (Mg) bone content. In this study, we have investigated by histochemical methods the state of bone resorption in 50-day-old untreated $\text{Hyp}\text{Y}$ mice and the effects of 4 wk of Mg therapy or dietary lactose supplementation on bone formation and resorption. Mineral and skeletal changes were evaluated on serum, urinary and bone ash concentrations of Ca, phosphorus (P) and Mg, and by histomorphometric analysis of tetracycline double labeled undecalcified caudal vertebrae. The number of acid phosphatase stained chondroclasts and osteoclasts was lower than normal in untreated $\text{Hyp}\text{Y}$ and was restored after Mg therapy while the osteoclastic surface was increased above normal. Accordingly, serum P and urinary Ca, P, Mg, cAMP and OH-Pro were increased while $\text{TmP}\text{GFR}$ was unchanged. On the other hand, dietary lactose corrected serum Ca which probably suppressed PTH secretion since the renal P conservation was improved and the osteoclast number and the osteoclastic surface were decreased. Both treatments reduced the growthplate and osteoid seam thickness and increased the bone calcification rate. The results indicate that the low skeletal Mg present in $\text{Hyp}\text{Y}$ partially impairs bone responsiveness to PTH since Mg therapy restored the osteoclastic bone resorption which secondarily provided new minerals for bone mineralization. The greater than normal bone resorption found in Mg $\text{treated}\text{-}\text{Hyp}\text{Y}$ and the decreased bone resorption observed in lactose treated animals indicate that the chronic hypocalcemia induces secondary hyperparathyroidism in $\text{Hyp}\text{Y}$ mice.