vitamin-d-2 and Bone-Diseases--Developmental

Osteopetrosis is an inherited skeletal condition characterized by increased bone radiodensity. There are three clinical groups: infantile-malignant autosomal recessive, fatal within the first few years of life (in the absence of effective therapy); intermediate autosomal recessive, appears during the first decade of life but does not follow a malignant course; and autosomal dominant, with full-life expectancy but many orthopaedic problems. The infantile variant shows a myelophthisic anemia, granulocytopenia, and thrombocytopenia, and patients eventually die from infection or bleeding or both. Neurologic sequelae include cranial nerve compression (optic nerve, blindness; auditory nerve, deafness; facial nerve, paresis), hydrocephalus, convulsions, and mental retardation. Radiographs show uniform bone density without corticomedulary demarcation, broadened metaphyses, "bone within a bone" or endobone phenomena (tarsals, carpals, phalanges, vertebra, ilium), and thickened growth plates if there is superimposed rickets. Transverse pathologic fractures occur, often followed by massive periosteal bone formation. Computed tomographic scans, magnetic resonance imaging, and bone scans provide specific information. Iliac crest bone biopsy is valuable to quantitate osteoclast and marrow changes by light and electron microscopy. Medical treatments involve high-dose calcitriol to stimulate osteoclast differentiation and bone marrow transplantation to provide monocytic osteoclast precursors. Orthopaedic problems in the intermediate and autosomal dominant forms include increased fractures, coxa vara, long-bone bowing, hip and knee degenerative arthritis, and mandibular and long-bone osteomyelitis. Cranial nerve compression also occurs. Osteotomy, plating, intramedullary rodding, and joint arthroplasty can be done, but are difficult because of bone hardness.

Topics: Anemia, Myelophthisic; Bone Diseases, Developmental; Bone Marrow Transplantation; Calcitriol; Child, Preschool; Diagnostic Imaging; Ergocalciferols; Fractures, Spontaneous; Humans; Ilium; Infant; Nervous System Diseases; Osteopetrosis; Parathyroid Hormone

This study demonstrates the effect of essential fatty acid deficiency on the postnatal skeletal development in the rat. Four groups (n = 10) of newborn Wistar rats were fed diets containing high and low proportions of essential fatty acids in the lipid fraction until day 16 after birth. Suckled littermates were used as controls. X-ray and histological studies showed the occurrence of multiple pathological fractures of the long bones in 1-month-old rats fed a diet deprived of essential fatty acids. No effect of high (51,000 IU/100 g diet) and low (5,100 IU/100 g diet) concentrations of vitamin D2 was observed in our experiment. Thus, these data suggest the importance of essential fatty acids for bone pathology in the rat.

Topics: Animals; Bone Diseases, Developmental; Dietary Fats; Ergocalciferols; Fatty Acids; Femoral Fractures; Rats; Rats, Wistar; Tibial Fractures

Ergocalciferol (320,000 or 480,000 IU/kg) plus cholesterol (60 mg/kg) in olive oil solution was administered daily on 1, 2, or 4 consecutive days to pregnant rats from 9,10, 14, or 18 of gestation. The control animals received only olive oil. Disseminated lesions of metastic calcinosis were found in various tissues, in the coronary arteries and myocardium, in the media of the abnormal aorta, in the lung and pleura, in the gastoinstestinal tract, and in the kidney. This is in contrast to the atherosclerosis described in nonpregnant rats fed a similiar diet. A significant decline in maternal weight as well as a high rate of morbidity and mortality was observed. In mothers killed on day 22 of pregnancy, fetal and placental growths appeared significantly retarded suggesting a direct effect of the steroid or its more active metabolite, 1,25-dihydroxycholecalciferol, on the fetus or the trophoblastic tissue. Fetal bone lesionsassociated with a generalized retardation of ossification, placental edema, or calcification accompanied by a loss of the normal structure of the placenta and degenerative manifestation at this level were observed. Moreover, we noted a striking alteration of the fetal face in 33-39% of experimental fetuses, called by us carnival fetuses.

Topics: Abnormalities, Drug-Induced; Animals; Aorta, Abdominal; Bone Diseases, Developmental; Calcinosis; Cholesterol; Digestive System; Dose-Response Relationship, Drug; Ergocalciferols; Face; Female; Fetal Death; Fetal Diseases; Gestational Age; Intubation, Gastrointestinal; Placenta Diseases; Pregnancy; Pregnancy Complications; Rats