cholecalciferol and Osteopetrosis

Topics: Bone Marrow Transplantation; Calcium; Cholecalciferol; Female; Humans; Infant; Osteopetrosis; Prognosis; Rickets

Rickets is a common and paradoxical feature of infantile malignant osteopetrosis 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 the serum calcium x phosphorus product is insufficient to mineralize newly formed chondroid and osteoid. In five children with malignant infantile osteopetrosis, there were clinical, radiographic, biochemical, and histologic findings of rickets. Characteristic biochemical abnormalities included hypocalcemia, hypophosphatemia, and elevated levels of serum acid phosphatase, alkaline phosphatase, c-terminal parathyroid hormone, and 1,25-dihydroxyvitamin D. The urinary calcium/creatinine ratio was markedly depressed. The serum calcium x phosphorus product was below 30 in all children at the time the rickets was diagnosed, and above 40 by the time the rickets had resolved. Baseline bone density measurements were markedly elevated in all children (> 5 standard deviation above normal) and showed even significant increases (> 7 SD) when the rickets was treated with vitamin D and calcium. The children showed marked clinical improvement, decreased lethargy, increase in mobility and activity, and stimulation of appetite, without any additional adverse hematologic or neurologic effects. The rickets was reversible in all children: in one by HLA-identical sibling bone marrow transplantation and in four by physiologic doses of vitamin D and calcium. The parathyroid and renal responses to hypocalcemia were appropriate, but glucocorticoids, used in treating the hematologic complications of the disease, may have blunted the intestinal response to maximal vitamin D stimulation. This latter blockade can be overcome by increasing dietary calcium. By liberalizing rather than by restricting calcium and phosphorus intake, hypocalcemia can be minimized, phosphorus metabolism can be improved, and rickets can be cured.

Topics: Bone Marrow Transplantation; Calcium; Cholecalciferol; Female; Humans; Infant; Infant, Newborn; Male; Osteopetrosis; Rickets

Utilizing the microphthalamic mouse, (mi/mi) as a model of osteopetrosis, vitamin D3 (cholecalciferol) was administered prenatally and postnatally to study its effects on tooth development and subsequent eruption. It has previously been reported that vitamin D3 crosses the placental barrier and is absorbed into mammary gland milk. Fifteen heterozygotes (+/mi) were used as breeders. There were three study groups: A) 5.0 ng/gm cholecalciferol sulfate; B) 2.5 ng/gm cholecalciferol sulfate; and C) no therapy. Intraperitoneal injections were administered three times per week, beginning when pregnancy was evident, and continuing for 4 additional weeks during lactation. Approximately half of the 59 offspring were sacrificed at age 1 day and the other half at 4 weeks. The former group was studied for crown development, and the latter group was studied for root development and eruption. When the osteopetrotic offspring of group A were compared with osteopetrotic offspring of group C, crown development and tooth eruption were substantially more advanced. Parameters examined were maturity of the ameloblasts and odontoblasts, dentin and enamel formation, root sheath development, status of eruption, and degree of apex closure. It was concluded that cholecalciferol sulfate significantly improves tooth development and subsequent eruption in the osteopetrotic mouse. A genetic disease has had its phenotype modified by vitamin therapy during gestation.

Topics: Animals; Cholecalciferol; Female; Genetic Carrier Screening; Maternal-Fetal Exchange; Mice; Mice, Mutant Strains; Osteopetrosis; Pregnancy; Reference Values; Tongue; Tooth Germ

Young rabbits on high (0.57%) or low (0.24%) calcium were given an aqueous extract of Solanum malacoxylon (S.m.) leaves (20 g dried leaves/200 ml distilled water) intragastrically at 0, 12 and 36 hours. On bothe diets S.m. induced progressive hypophosphatasemia but serum calcium and phosphorus underwent only minor changes. In rabbits necropsied at 0, 12, 36, 60, 84 and 108 hours, S.m. was shown to have a negative effect on the resorbing osteocytes. With retarded osteocytic osteolysis, osteopetrosis resulted. Further regressive changes in the osteocytes resulted in osteonecrosis which was observed within 12 hours after administration of S.m. extract. The osteonecrosis, combined with retarded apposition, later resulted in osteopenia. It was concluded that the recommended dietary calcium for growing rabbits--about 0.6%--is too high. Whereas the histologic appearance of bone in rabbits fed low calcium was normal, bones from rabbits on high calcium showed retarded resorption and the rabbits had a relative hypophosphatasemia.

Topics: Alkaline Phosphatase; Animals; Bone Resorption; Calcium; Cholecalciferol; Female; Male; Osteonecrosis; Osteopetrosis; Phosphorus; Plant Extracts; Plant Poisoning; Rabbits