Ovariectomy abolishes the normalization of femoral mineral content in 40-week-old female X-linked hypophosphatemic mice.

All young adult X-linked hypophosphatemic (Hyp) mice exhibit low bone mineral content. However, between the ages of 13 and 40 weeks, the female Hyp mice have an increase in bone mineral content per centimeter length to the level of the normal mice. Older Hyp male mice do not normalize in mineral content/length ratio. To explore the mechanisms for this, gonadectomy was performed in 3- to 4-week-old normal and Hyp mice to determine whether the increase in mineral content was related to gonadal secretions. Sham-operated and gonadectomized mice of both sexes and genotypes were sacrificed at 7, 13, and 40 weeks of age. Gonadectomy had little effect on the development of low mineral content in young adult Hyp mice. However, gonadectomy blocked the increase in femoral mineral content and mineral content/length ratio in Hyp female mice at 40 weeks of age. Gonadectomy blocked the increase in femoral mineral content in Hyp females while femoral length was increased somewhat. Femoral midshaft diameter was significantly smaller in Hyp female mice, which suggested a decrease in periosteal bone growth due to gonadectomy between 13 and 40 weeks of age. In general, plasma phosphate and calcium values could not be used to explain bone mineral increases since no consistent changes were found. In conclusion, the increase in bone mineral content which occurs in older Hyp female mice is dependent upon the presence of the ovary.