Lifelong challenge of calcium homeostasis in male mice lacking TRPV5 leads to changes in bone and calcium metabolism

Trpv5 plays an important role in calcium (Ca(2+)) homeostasis, among others by mediating renal calcium reabsorption. Accordingly, Trpv5 deficiency strongly stresses Ca(2+) homeostasis in order to maintain stable serum Ca(2+). We addressed the impact of lifelong challenge of calcium homeostasis on the bone phenotype of these mice. Aging significantly increased serum 1,25(OH)(2)D(3) and PTH levels in both genotypes but they were more elevated in Trpv5(−/−) mice, whereas serum Ca(2+) was not affected by age or genotype. Age-related changes in trabecular and cortical bone mass were accelerated in Trpv5(−/−) mice, including reduced trabecular and cortical bone thickness as well as reduced bone mineralization. No effect of Trpv5 deficiency on bone strength was observed. In 78-week-old mice no differences were observed between the genotypes regarding urinary deoxypyridinoline, osteoclast number, differentiation and activity as well as osteoclast precursor numbers, as assessed by flow cytometry. In conclusion, life-long challenge of Ca(2+) homeostasis present in Trpv5(−/−) mice causes accelerated bone aging and a low cortical and trabecular bone mass phenotype. The phenotype of the Trpv5(−/−) mice suggests that maintenance of adequate circulatory Ca(2+) levels in patients with disturbances in Ca(2+) homeostasis should be a priority in order to prevent bone loss at older age.