Maternal High Calcium Diet Fails to Reverse Rickets in the Osteosclerotic Mouse

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Abstract
The coexistence of osteopetrosis and rickets (osteopetrorickets) in humans has been described frequently. The osteosclerotic mouse is a unique, lethal osteopetrotic mutation that also has rickets. Attempts to cure this mutation by bone marrow transplantation have been largely unsuccessful, and its resistance to cure presumably is attributable to hypomineralized skeletal tissue that does not support osteoclast neogenesis, differentiation, and function. Current opinion regarding the clinical treatment of patients with osteopetrorickets involves first, the resolution of the rickets, followed by bone marrow transplantation to resolve the osteopetrosis, although this has not been successfully performed in humans. Attempts were made in the current study to reverse the rachitic lesion in the osteosclerotic mouse by feeding female breeders a high calcium (2.0%) diet throughout pregnancy and lactation. Mutant offspring (2 to 3 weeks of age) from such mothers remained hypocalcemic and hypophosphatemic, showed no decrease in growth plate cartilage thickness, and did not have enhanced cartilage or skeletal mineralization. For this unique mutation, efforts should be continued toward developing the appropriate therapies for reversal of its rachitic and skeletal defects; such therapies may yield insights into the clinical care of human infants with osteopetrorickets.