vitamin-d-2 and Osteopetrosis

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

Four Thai infants, aged between 4 and 23 months, had progressive abdominal distension, pallor and delayed or regressed developmental milestones, with age at onset of 1 month, 3 months, 4 months and 1 month, respectively. Clinical findings consisted of growth and developmental retardation, anemia, frontal bossing, marked hepatosplenomegaly, and hearing and visual impairment. Laboratory findings revealed moderate anemia, leukocytosis and thrombocytopenia. The radiographic findings comprised generalized sclerosis of all bones, including the cranial base, and obliteration of the medullary canals and trabecular patterns. The first and second patients, who had swelling of the wrist joints and prominent costochondral junctions, had hypophosphatemia, elevated levels of serum alkaline phosphatase, and metaphyseal flaring on their radiographs, which was consistent with infantile osteopetrosis complicated by rickets. After Stoss therapy, there were biochemical and radiological responses suggesting vitamin D deficiency in the first patient, but not in the second. The third patient, who had hypocalcemia, hypophosphatemia and normal levels of serum alkaline phosphatase, received vitamin D at 3000 units per day, without improvement. Despite frequent blood transfusions, all patients continued to deteriorate and were finally lost to follow-up. Rickets should be identified and treated at the onset, because treatment of rickets leads to improvement in well-being and an adequate clinical response to bone marrow transplantation.

Topics: Blood Transfusion; Ergocalciferols; Female; Humans; Hypophosphatemia; Infant; Male; Osteopetrosis; Rickets; Treatment Outcome; Vitamin D

We have used dual-energy x-ray absorptiometry (DXA) in evaluation and follow-up of a patient with osteopetrosis, before and after cord blood transplantation. Other methods of follow-up in such cases have been described, but the use of DXA has not previously been reported. We have shown that DXA offers a safe means of assessing disease progression, the timing of treatment, and response after therapy for osteopetrosis.

Topics: Absorptiometry, Photon; Adjuvants, Immunologic; Blood Transfusion; Disease Progression; Ergocalciferols; Fetal Blood; Follow-Up Studies; Humans; Infant; Interferon-gamma; Male; Osteopetrosis; Time Factors; Treatment Outcome

A male patient, afflicted with malignant congenital osteopetrosis, was studied over a 5 year period. Hypocalcemia (less than 8 mg/dl) with lack of an appropriate increase in serum immunoreactive parathyroid hormone (iPTH) prevailed at all times. Under a calcium restricted diet, a 6-hour infusion of parathyroid extract normalized serum calcium, and increased the urinary hydroxyproline excretion suggesting that bone resorption had been induced. A second attempt to induce resorption was made by infusing a synthetic amino terminal fragment of bovine PTH over a period of 3 weeks at the dose of 1.5 units/kg/hr. This infusion evoked an increase in serum calcium (8.1 to 10.5 mg/dl), urinary calcium (0.03 to 0.65 mg/g creatinine) and urinary hydroxyproline (160 to 372 mg/g creatinine); and urinary hydroxyproline (160 to 372 mg/g creatinine); increases which were reversed by calcitonin administration. Iliac crest bone biopsies were obtained before and on the last day of the 3-week infusion. Quantitative comparison of the two specimens showed that, during PTH infusion, there was a 23% decrease in bone volume due to the increase in marrow space, a 93% increase in the number of osteoclasts and 136% increment in the osteoclastic resorption surface. Electron microscopic examination of the osteoclasts in the first tissue sample showed no evidence of ruffled borders, while in the second biopsy, numerous cytoplasmic processes indicative of resorptive activity were visible at the matrix-cell interface. It is proposed that, in our patient, the osteopetrotic phenotype is the consequence of an abnormality in the interaction between PTH and osteoclasts that may be related to the synthesis of a physiologically "defective" PTH.

Topics: 25-Hydroxyvitamin D 2; Alkaline Phosphatase; Bone and Bones; Bone Resorption; Calcitonin; Calcitriol; Calcium; Child; Ergocalciferols; Humans; Kidney; Male; Osteopetrosis; Parathyroid Hormone; Phosphates

Topics: Androgens; Blood Chemical Analysis; Bone Diseases; Calcium Isotopes; Calcium Metabolism Disorders; Citrates; Ergocalciferols; Estrogens; Hypocalcemia; Osteomalacia; Osteopetrosis; Osteoporosis; Parathyroid Glands; Pharmacology; Phosphates; Physiology; Radiometry; Strontium Isotopes; Urine