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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear inclusions, identical to those characteristic of Paget's disease of bone, were observed in giant cells in four of eight cases of primary oxalosis. The giant cells containing nuclear inclusions were directly involved in phagocytosis of large oxalate crystals in the context of typical foreign body granulomas in the bone marrow. Cytochemically, all of them exhibited strong tartrate-resistant acid phosphatase activity, and a proportion of them also tartrate-resistant acid ATPase. The inclusions consisted of typical arrays of filamentous material as described in Paget's disease, admixed with variable proportions of electron-dense material closely reminiscent of nucleolar pars fibrillaris and fibrillary centres. These data indicate: (a) the occurrence of Paget-like inclusions in a bone disease unrelated to Paget's disease, not causally related to viral infection, and resulting from an inborn metabolic derangement; and (b) the occurrence of Paget-like inclusions in foreign body giant cells as opposed to osteoclasts. We suggest that the occurrence of paramyxovirus-like nuclear inclusions in either osteoclasts or giant cells may represent an epiphenomenon of cell fusion and giant cell formation whenever appropriate stimuli act on latently infected precursor cells. Furthermore, our data suggest that nucleoli may represent the specific site of virus-like inclusion formation.
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PMID:Paramyxovirus-like nuclear inclusions identical to those of Paget's disease of bone detected in giant cells of primary oxalosis. 145 92

Alkaline phosphatase (AlP) and tartrate-resistant acid phosphatase (TRAP) activities have been studied comparatively in needle biopsies of the iliac crest of four cases of secondary hyperparathyroidism (renal osteodystrophy). AlP activity was associated with the plasma membrane of osteoblasts and their processes, of reticular cells of bone marrow and of young osteocytes of osteoid borders and woven bone. Moreover, it was detected in the fibroblast-like cells of the endosteal "fibrosis". These cells were orderly in arrangement and were parallel to the endosteal surfaces near zones of bone formation. They were disorderly near zones of bone resorption. A strong TRAP-positive reaction was present in osteoclasts and mononuclear cells of endosteal "fibrosis" and in osteocytes located near active osteoclasts and in woven bone. These results suggest that the so-called fibrosis of hyperparathyroidism, rather than representing reparative, inert tissue, consists of osteoblast-like cells, probably precursors of osteoblasts derived by parathormone-stimulated proliferation of AlP-positive stromal cells of bone marrow, and of TRAP-positive, mononuclear cells, probably preosteoclasts. Moreover, they show that TRAP activity can be present in osteocytes, probably under stimulation by the same factors which stimulate osteoclast activity. The histochemical demonstration of AlP and TRAP facilitates the morphological diagnosis of metabolic bone disease and may improve knowledge of bone physiopathology.
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PMID:Endosteal surfaces in hyperparathyroidism: an enzyme cytochemical study on low-temperature-processed, glycol-methacrylate-embedded bone biopsies. 175 Jan 88

Osteoclast-mediated bone resorption is increased in response to 1,25 dihydroxyvitamin D (1,25[OH]2D or calcitriol). Osteopetrosis is a metabolic bone disease characterized by defective, osteoclast-mediated bone resorption, which co-exists with elevated serum 1,25-(OH)2D levels in some osteopetrotic children and animals. We examined the effects of high doses of calcitriol on osteoclast number and cytochemistry in both normal and osteopetrotic (os) rabbits. Calcitriol was continuously infused at doses of 0.5, 2.5, or 25 micrograms/kg/day via subcutaneously implanted osmotic minipumps for a period of 7 days. Following treatment, the proximal tibial metaphyses were processed for histomorphometric and cytochemical analyses. Sections were stained for tartrate-resistant acid phosphatase (TrAP) or acid ATPase (TraATPase). Osteoclasts were significantly reduced in untreated os rabbits compared with age-matched normal littermates between birth and 3 weeks of age (41-46% of normal). Whereas most normal osteoclasts (85%) stained heavily for TrAP or TraATPase, less than half of os osteoclasts were heavily stained for these acid hydrolases. Infusions of 1,25(OH)2D resulted in elevations of osteoclast numbers in both normal and os rabbits, but the number of osteoclasts remained significantly lower in mutants than in normal littermates at any given dose. Calcitriol infusions also resulted in a significant increase in the percentage of os osteoclasts staining heavily for TrAP and TraATPase. These results suggest that in response to 1,25(OH)2D normal osteoclasts increase their production of acid hydrolases before increasing cell numbers and that, in spite of high levels of endogenous calcitriol, os rabbits can respond to exogenous 1,25(OH)2D as evidenced by increased osteoclast number and cytochemical staining, even though these osteoclasts fail to resorb the excess skeletal matrix.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of 1,25 dihydroxyvitamin D on osteoclast number and cytochemistry in normal and osteopetrotic (os) rabbits. 214 52

Osteoclasts were isolated from membranous bone from four children without metabolic bone disease who were undergoing craniotomy for either tumor or trauma. Both freshly isolated osteoclasts and those cultured for 4-7 days exhibited the following characteristics: production of tartrate-resistant acid phosphatase (9.5-14.8 units), contraction in response to application of 100 mg/ml of human calcitonin, and formation of resorption lacunae on devitalized bone wafers. Nuclear estrogen and progesterone receptors were demonstrated by immunohistochemical techniques and quantitated in two of the patients by radioimmunoassay (estrogen receptor RIA, 23.6 and 23.8 cpm/micrograms protein; progesterone receptor RIA, 36.7 and 74.2 cpm/micrograms protein). The demonstration of sex steroid hormone receptors in the nucleus of osteoclasts derived from children with normal membranous bone has established a potential mechanism whereby direct modulation of bone resorption by the sex steroid estrogen and progesterone may occur.
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PMID:Osteoclasts isolated from membranous bone in children exhibit nuclear estrogen and progesterone receptors. 223 65

Osteopetrosis is a metabolic bone disease characterized by reduced bone resorption. From experimental studies of various osteopetrotic mutations has emerged the hypothesis that each is unique with respect to mechanisms whereby osteoclast development and/or function are reduced. The osteopetrotic (op) mutation in the rat was discovered in Fatty/ORL stock over a decade ago. The paucity of data about osteoclast biology in this mutation prompted this study of cytological, cytochemical, and ultrastructural features of osteoclasts. In op rats, osteoclasts are significantly reduced in number, but are larger and more vacuolated than in normal littermates. Mutant osteoclasts can form ruffled borders and clear zones, but their ability to fragment and excavate bone surfaces is greatly impaired. Cytoplasmic vacuoles in op osteoclasts are randomly distributed and greatly enlarged, and they stain weakly for two cytochemical characteristics of osteoclasts, tartrate-resistant acid phosphatase and acid ATPase. These findings suggest that an abnormality in the lysosomal/vacuolar system, an important component of the resorptive mechanism, may be involved in the interception of osteoclast function in this mutation.
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PMID:Osteoclast biology in the osteopetrotic (op) rat. 258 17

Studies of osteoclasts and their precursors in normal and pathological states have been severely hampered by the lack of an in vitro system for forming osteoclasts. We developed a human marrow culture system in which multinucleated cells with several characteristics of osteoclasts form. Multinucleated cells began to form during the first week of culture, with maximum numbers formed after 3 weeks. PTH (25-50 ng/ml) and 1,25-dihydroxyvitamin D3 (10(-10)-10(-8) M) increased formation of these cells, and these effects were inhibited by calcitonin. These multinucleated cells contained nonspecific esterase and tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts, and had several ultrastructural features of osteoclasts. We used this marrow cell culture technique to study a patient with hyperparathyroidism and markedly increased osteoclasts on bone marrow biopsy. The marrow from this patient formed increased numbers of multinucleated cells in vitro. After parathyroidectomy both multinucleated cell formation in vitro and osteoclast numbers on bone biopsy decreased significantly. This long term marrow culture system represents the first demonstration of human osteoclast-like cell formation in vitro. This system should permit studies to evaluate factors controlling formation of cells with certain osteoclast characteristics in vitro and their precursors as well as to evaluate abnormalities in osteoclast formation in patients with metabolic bone disease.
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PMID:Formation of multinucleated cells that respond to osteotropic hormones in long term human bone marrow cultures. 356 33

Cytochemical studies were performed on peripheral blood from 30 patients with type 1 Gaucher disease. In 29 of the patients, peripheral blood monocytes stained positively for tartrate-resistant acid phosphatase, whereas monocytes from 18 normal individuals and 14 patients with monocytosis did not. In the Gaucher patients, the percentage of monocyte positivity for tartrate-resistant acid phosphatase ranged from 2 to 97. There was no correlation between the percent monocyte staining and the degree of disease severity, as measured by hepatosplenomegaly, pancytopenia, or extent of bone disease, for the group as a whole. In Gaucher patients who had not undergone splenectomy, however, there was a significant correlation between percent monocyte staining and the degree of hepatosplenomegaly, anemia, and thrombocytopenia. The presence of tartrate-resistant acid phosphatase may be secondary to the lysosomal accumulation of glucosyl ceramide within these monocytes, although this remains to be confirmed. If so, these circulating cells may represent precursors of the Gaucher cells in tissues. Tartrate-resistant acid phosphatase staining of peripheral blood monocytes may be useful as a diagnostic marker for Gaucher type 1 disease and for further studies on the pathogenesis of the disease.
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PMID:Tartrate-resistant acid phosphatase staining of monocytes in Gaucher disease. 401 24

On the basis of earlier findings of increased serum beta 2-microglobulin concentration in women with postmenopausal osteoporosis, we decided to study serum beta 2-microglobulin concentration in other bone diseases. In 28 patients with untreated Paget's bone disease, serum beta 2-microglobulin concentration was normal (1.49 +/- 0.41 mg/liter versus 1.36 +/- 0.21 mg/liter in 42 control subjects, P = ns), a finding that contradicts reports in the literature. We found that serum beta 2-microglobulin concentration was related negatively and significantly (r2 = -0.154, P = 0.0354) with serum total alkaline phosphatase concentration, but not with serum tartrate-resistant acid phosphatase concentration (p = ns). Urinary elimination of beta 2-microglobulin was lower in the patients with Paget's disease than in the controls (34 +/- 28 versus 120 +/- 21 mg/liter, P < 0.001). These findings suggest that beta 2-microglobulin behaves similarly to osteocalcin (BGP) in Paget's bone disease and that its concentration remains within normal levels perhaps because of the rate of reuptake of beta 2-microglobulin in bone neoformation.
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PMID:beta 2-Microglobulin in Paget's bone disease. 806 56

Beta2-microglobulin has been observed to behave as a biological marker of bone remodeling. We measured beta2-microglobulin and tartrate-resistant acid phosphatase (TRAP), a specific biological marker of bone remodeling, in 225 women: healthy premenopausal controls, healthy postmenopausal control, and patients with diseases characterized by enhanced bone turnover (postmenopausal osteoporosis, primary hyperparathyroidism, primary hyperthyroidism, polyostotic Paget's bone disease), and in other Paget's group before and after calcitonin treatment. Beta2-microglobulin levels differed significantly between the healthy premenopausal women (n = 20) compared with all the other groups. However, beta2-microglobulin levels did not differ significantly between healthy postmenopausal women (n = 38) and patient's with Paget's bone disease (n = 40)(P = 0.5095), or between women with postmenopausal osteoporosis (n = 30) and women with hyperthyroidism (n = 20)(P = 0.7890). TRAP concentrations differed significantly in all the groups paired except for women with Paget's bone disease and women with either hyperparathyroidism or hyperthyroidism (P = 0.5179 and 0.6993, respectively); likewise, TRAP levels did not differ significantly between the women with hyperparathyroidism and those with hypothyroidism (P = 0.7804). After calcitonin treatment, there was a 22% increase in beta2-microglobulin, a 17% decrease in TRAP, and a 39% decrease in alkaline phosphatase, all of which were significant at P < 0.0001. Our findings indicate that serum beta2-microglobulin, like osteocalcin, behaves as a biological marker of remodeling in a number of diseases with enhanced bone remodeling but not in Paget's bone disease.
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PMID:Beta-2-microglobulin in diseases with high bone remodeling. 867 64

Although the etiology of Paget bone disease (PBD) is unknown, increasing evidence implicates a "slow virus" infection of the skeleton, perhaps in genetically predisposed individuals. PBD is rare in Asia. We describe a Korean family with PBD. The propositus noticed bowed limbs at approximately 25 years of age. Radiologic studies made when he was 55 years old revealed essentially panostotic PBD. Serum alkaline phosphatase (ALP) activity and osteocalcin (OC) levels were markedly elevated. An iliac crest specimen showed classic histopathologic changes of PBD. Additionally, palpable swellings were first observed at age 45 years at his occiput, pubic ramus, ileum, and facial bones. They contained numerous multinucleated cells and were originally diagnosed as giant cell tumors. However, we found that, like osteoclasts, these cells expressed considerable tartrate-resistant acid phosphatase activity. These "extraskeletal osteoclastomas" resolved rapidly with dexamethasone treatment. Two daughters, 20- and 24-years-of-age, were discovered by study of his 5 children to have elevated serum ALP activity and OC levels and widespread PBD. Both women, however, are without palpable masses and are asymptomatic. The propositus' father, who died at age 55 years, had similar skeletal deformities beginning at age 20 years, but was not examined. Leukocytopenia was found in the 3 living family members with PBD. There was no evidence for linkage of the PBD to HLA loci. The condition appears to be transmitted as an autosomal dominant trait and is manifest in young adult life. Multicentric extraskeletal osteoclastomas with remarkable sensitivity to dexamethasone treatment appear to be another unusual feature of this family's disorder. In this family, the stimulus for PBD is so great that the PBD is apparent at an early age, affects essentially the entire skeleton, and leads to the formation or extension of osteoclast-like cells into nonosseous tissues (extraskeletal osteoclastomas). This 3-generation kindred in Korea, where PBD is rare, shows a strong clustering of PBD compatible with autosomal dominant inheritance. Leukocytopenia appears to distinguish affected family members, but any role for this abnormality in the pathogenesis of PBD is unclear. Our findings support a heritable diathesis for PBD, perhaps mediated by an immune deficiency.
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PMID:Paget bone disease involving young adults in 3 generations of a Korean family. 919 51


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