Metabolic bone disease & related research最新文献

Quantitative bone histology was carried out in five osteosclerotic adults. The bone was extremely hard in all patients, and open biopsy was usually required. One patient, aged 18 years, presented with hypoplastic anemia, and the most probable explanation for the osteosclerosis is a marrow stem cell defect leading to defective osteoclasts. Another had the dominant form of osteopetrosis. Her bone contained cartilage remnants, and there were many large, morphologically abnormal osteoclasts, which lacked normal cytoplasmic acid phosphatase activity. The third patient had chronic renal failure and osteomalacia; here the increased bone mass might have resulted from an inability of normal osteoclasts to resorb bone, due to the surface coating of osteoid, though an earlier increase of bone formation cannot be excluded. The fourth patient, who suffered from systemic mastocytosis, had high turnover bone, with greatly, increased bone formation. The fifth patient, with fluorosis of bone, also had increased bone formation and resorption, the process being much more pronounced in the head of her pathologically fractured femur than it was in the iliac crest. In this patient some osteoclasts had reduced acid phosphatase activity and long cytoplasmic extensions, both changes similar to those observed in diphosphonate-treated animals. Very diverse processes can result in the increased cancellous bone mass producing the radiographic appearance of diffuse osteosclerosis.

A 54-year-old male with a 10-year history of seropositive rheumatoid arthritis subsequently developed generalized osteoporosis, multiple cervical spine subluxation, vertebral collapses, and massive osteolysis of the humeral and femoral heads and carpal bones. These lesions were accompanied by neurologic manifestations in both the upper and lower extremities. Bone matrix collagen and noncollagenous proteins in this rare syndrome were analyzed. The pathogenesis of this rare phenomenon is discussed.

Light and electron microscopic examination of bone in reflex sympathetic dystrophy syndrome confirms that vascular disorders play an important role in the genesis of bone lesions. These vascular disorders lead to degeneration of osteocytes and demineralization of bone, with the disappearance of hydroxyapatite crystals. The neo-osteogenesis that follows resembles the different stages of fracture repair, with precocious elaboration of irregular, replacement woven bone, followed by osteoclastic resorption and the laying down of lamellar bone trabeculae. The bone lesions clearly appear to be a consequence of autonomic nervous system circulatory disorders.

A newly synthesized diphosphonate, difluoromethylene diphosphonate (F₂MDP), was studied for its effects on bone resorption, as measured by the release of previously incorporated ⁴⁵Ca. F₂MDP (10 μM to 1000 μM) effectively inhibited both unstimulated and parathyroid hormonestimulated resorption, and the amount of ⁴⁵Ca release decreased with time. Dichloromethylene diphosphonate (Cl₂MDP) and ethane- 1-hydroxyl-1,1-diphosphonate (EHDP) inhibited resorption to similar extents with two exceptions: At concentrations of 10 μM and 100 μM F₂MDP was more effective than EHDP and less effective than Cl₂MDP. No greater inhibition was observed when bones had been stimulated with PTH prior to the addition of F₂MDP In addition, bones treated with F₂MDP only during the first half of the incubation period exhibited reductions in tha amount of ⁴⁵Ca released during the second half similar to that observed when F2MDP was continuously in the medium, indicating a prolonged effect. Morphologic alterations of osteoclasts suggestive of cell degeneration were observed in F₂MDP-treated bones, which were similar to those observed in bones treated with Cl₂MDP and EHDP. Due to the presence of fluorine, F₂MDP may be useful as an experimental tool to investigate the mode of action of all diphosphonates, in addition to its possible use as a therapeutic agent for diseases of increased bone resorption.