OSTEOPETRORICKETS - THE PARADOX OF PLENTY - PATHOPHYSIOLOGY AND TREATMENT

Rickets is a common and paradoxical feature of infantile malignant ost eopetrosis and results from the inability of osteoclasts to maintain a normal calcium-phosphorus balance in the extracellular fluid. Despite a markedly positive total body calcium balance, rickets arises when t he serum calcium, phosphorus product is insufficient to mineralize new ly formed chondroid and osteoid. In five children with malignant infan tile osteopetrosis, there were clinical, radiographic, biochemical, an d histologic findings of rickets. Characteristic biochemical abnormali ties included hypocalcemia, hypophosphatemia, and elevated levels of s erum acid phosphatase, alkaline phosphatase, c-terminal parathyroid ho rmone, and 1,25-dihydroxyvitamin D. The urinary calcium/creatinine rat io was markedly depressed. The serum calcium X phosphorus product was below 30 in all children at the time the rickets was diagnosed, and ab ove 40 by the time the rickets had resolved. Baseline bone density mea surements were markedly elevated in all children (>5 standard deviatio n above normal) and showed even significant increases (>7 SD) when the rickets was treated with vitamin D and calcium. The children showed m arked clinical improvement, decreased lethargy, increase in mobility a nd activity, and stimulation of appetite, without any additional adver se hematologic or neurologic effects. The rickets was reversible in al l children: in one by HLA-identical sibling bone marrow transplantatio n and in four by physiologic doses of vitamin D and calcium. The parat hyroid and renal responses to hypocalcemia were appropriate, but gluco corticoids, used in treating the hematologic complications of the dise ase, may have blunted the intestinal response to maximal vitamin D sti mulation. This latter blockade can be overcome by increasing dietary c alcium. By liberalizing rather than by restricting calcium and phospho rus intake, hypocalcemia can be minimized, phosphorus metabolism can b e improved, and rickets can be cured.