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

The authors report 12 cases (8 men and 4 women) of sarcomatous degeneration in Paget's bone disease, with an average age of 72.3 years. Sarcomatous degeneration occurred often in polyostotic Paget's disease, and osteitis deformans was seen in 4 cases. Femur and pelvis were the most affected bones. Pain was a constant feature, whereas tumefaction and fracture were less common. Osteolytic lesions were more frequent than condensed or mixed lesions and radiological signs of malignancy were usually found. Seven cases were histologically classified as osteogenic sarcoma and 3 cases as fibrosarcoma. Electron microscopy was performed on 2 osteogenic sarcomas and in 1 case revealed microcylindrical inclusions in Pagetic osteoclasts and in multinucleated giant tumor cells, but none in mononucleated tumor cells. The average survival time for the patients in this study was only 4.5 months.
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PMID:Sarcomatous degeneration in Paget's bone disease. 347 35

The skeleton provides more than only a framework for the body. Bone is a calcified conjunctive tissue sensitive to various mechanical stimuli, mainly to those resulting from gravity and muscular contractions. Numerous animal and human studies demonstrate the importance of weight-bearing physical activity as well as mechanical loading for maintaining skeletal integrity. Lack of weight-bearing activity is dangerous for the skeleton: a decrease in bone mineral density (BMD) has been demonstrated in animals and humans under conditions of weightlessness or immobilization. Other studies have also reported a lower vertebral BMD among young amenorrheic athletes than among athletes with regular cycles and/or non athletes. The main factor responsible for this lower BMD in the amenorrheic athletes is the persistent low level of endogenous estrogen observed among these women. However this does not represent a premature and irreversible loss of bone mass since the resumption of menses following a decrease in training is the primary factor for a significant increase in vertebral BMD in these formerly amenorrheic athletes. A weight-bearing exercise is likely to be more beneficial at weight-bearing than at non weight-bearing sites, and hypogonadism resulting from very intensive training and exercise is more detrimental to trabecular than cortical bone. Bone deficit at non weight-bearing sites may be attenuated by maintenance of body weight. Nevertheless the etiology of "stress fractures" among athletes remains poorly understood, and the exact relationship between soft tissue mass and BMD is not clear. Osteoporosis, the most common bone disorder in France, is a pathological condition associated with increased loss of bone mass, resulting in a greater risk of fracture. Although symptoms of osteoporosis do not generally occur until after menopause, recent evidence suggests that bone loss starts much earlier in life. Therefore osteoporosis might be prevented by increasing peak bone mass and/or by slowering bone loss after menopause. Exercise such as resistance training or weight-bearing activities like running or walking have an osteogenic effect on increasing BMD in young people, and the decrease in BMD is slower in exercised than in non-exercised post-menopausal women. Nevertheless the influence of the length and of the intensity of such physical activities remain to be determined.
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PMID:[Physical exercise and the skeleton]. 869 2

Osteoporosis is a bone disease associated with reduced bone mineral density resulting in debilitating bone fractures. According to the National Institutes of Health Women's Health Initiative, effective interventions for bone loss need to be developed. The osteogenic stimulus provided by weight-bearing exercise indicates it is an important lifestyle factor that can be used for prevention of bone loss. Prospective research studies have documented that both aerobic exercise and weight training can be effective in the maintenance and building of bone mineral density in postmenopausal women. Additional benefits of weight training include increased muscular strength, coordination, and balance which could decrease risk for falling and subsequent fractures.
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PMID:Exercise interventions for osteoporosis prevention in postmenopausal women. 1002 84

Fibrous dysplasia (FD) is a progressive bone disease in which abnormal fibroblast proliferation results in the replacement of normal cancellous bone with an immature fibrous tissue that is poorly mineralized. The disease manifests itself in the monostotic form in which only one bone is involved and the polyostotic form in which multiple bones at different sites are affected. The McCune-Albright syndrome is a variation of the polyostotic form in which patients demonstrate a greater extent of bone involvement and a variety of endocrinopathies. Somatic activating mutations in the GNAS gene have been demonstrated in the fibrotic lesions of patients affected with either monostotic or polyostotic FD. The increased cAMP levels caused by the G-protein mutations lead to increased interleukin-6 (IL-6) levels in the affected tissues, resulting in abnormal osteoblast differentiation and increased osteoclastic activity. Utilizing cell culture techniques that have been developed for mammalian bone marrow stromal cells, we have successfully cultured osteogenic stem cells from the affected stroma of 11 FD patients. Cells cultured from patients with polyostotic FD showed a high frequency of the Gsalpha mutation, whereas cells from monostotic FD patients showed a low frequency of the mutation. Both the normal and FD cells displayed the osteogenic phenotype when exposed to medium containing glucocorticoids. Glucocorticoids also caused a dramatic inhibition of IL-6 mRNA and protein levels in osteogenic cells cultured from the FD patients. These findings suggest that chemical alteration of cellular function may lead to new treatment options for patients with FD.
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PMID:Glucocorticoids decrease interleukin-6 levels and induce mineralization of cultured osteogenic cells from children with fibrous dysplasia. 1040 10

Previous investigations carried out in our laboratory on secondary osteons have shown that osteocyte lacunae decrease in size from the cement line towards the Haversian canal, and lamellar bone is made up of alternating nonosteocytic dense lamellae and osteocytic loose lamellae, all having an interwoven texture of collagen fibers. Such alternation of acellular and cellular lamellae was hypothesized to depend on osteocyte recruitment from osteogenic laminae in successive layers, assuming that the loose lamellae form because of alignment and fusion of the periosteocytic loosely arranged collagen fibers. In order to discover whether a correlation really exists between osteocyte lacunar size and lamellar thickness, as would be expected if the above-mentioned hypothesis were true, both these parameters were measured in completed secondary osteons in relation to their distance from the Haversian canal. The size of osteocyte lacunae was measured under light microscopy on undecalcified dry-mounted ground section of tibial compact bone from three adult males and three adult females not affected by metabolic bone disease. The measurement of the thickness of bony lamellae was carried out on the same samples under scanning electron microscopy. Statistical analyses of the results showed that the decrease in size of osteocytic lacunae from the outer to the inner osteonal wall is paralleled by a decrease in thickness of osteocytic loose lamellae. The fact that acellular dense lamellae do not follow such a decremental pattern, but remain of the same thickness throughout the osteonic wall, corroborates Marotti's view that the formation of lamellar bone depends on the orderly distribution of the osteocytes in alternating planes. The topographical distribution of osteocyte lacunar size and lamellar thickness is briefly discussed in relation to secondary osteon mechanical function.
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PMID:Osteocyte lacunar size-lamellar thickness relationships in human secondary osteons. 1118 81

The identification of anabolic agents for the treatment of metabolic bone disease is a highly prized, and elusive, goal. In searching for the osteogenic (bone-producing) constituents within mechanical stimuli, it was determined that high frequency (10-100 Hz) and low magnitude (<10 microstrain) stimuli were capable of augmenting bone mass and morphology, thereby benefiting both bone quantity and quality. Using animal models, it is shown that these mechanical signals can double bone-formation rates, inhibit disuse osteoporosis and increase the strength of trabecular bone by 25%. Considering that the magnitude of these mechanical signals are several orders of magnitude below those which cause damage to the bone tissue, it is proposed that this modality could be useful in the treatment of metabolic bone diseases.
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PMID:Inhibition of osteopenia by low magnitude, high-frequency mechanical stimuli. 1149 58

Human bone marrow-derived mesenchymal stem cells (MSCs) represent an ideal source for cell therapy for inherited and degenerative diseases, bone and cartilage repair, and as target for gene therapy. The role of the combination of human parathyroid hormone (PTH) and vitamin D(3) in bone formation and mineralization has been established in several osteoblast cell culture studies. The aim of the present study was to evaluate the role of this hormonal combination alone and in the presence of bone morphogenetic protein-4 (BMP-4) or-6 (BMP-6) in inducing osteogenic differentiation of human MSC. Human MSC derived from adult normal bone marrow that are positive for CD29, CD44, CD105, and CD166 and negative for CD14, CD34, and CD45, were treated with the PTH and 1,25-dihydroxyvitamin D(3) in the presence and absence of recombinant human BMP-4 or BMP6. PTH and vitamin D(3) induced high levels of expression of two key markers of bone formation: osteocalcin and alkaline phosphatase by MSCs. BMP-6 but not BMP-4 increased osteocalcin expression induced by PTH and vitamin D(3). Both BMPs enhanced calcium formation in MSC cultures and this response was potentiated by PTH and vitamin D(3). The present results revealed a novel potent effect of PTH and vitamin D(3) plus BMPs in inducing bone development by human MSCs. These results may facilitate therapeutic utility of MSCs for bone disease and help clarify mechanisms involved in stem cell-mediated bone development.
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PMID:The role of BMP-6, IL-6, and BMP-4 in mesenchymal stem cell-dependent bone development: effects on osteoblastic differentiation induced by parathyroid hormone and vitamin D(3). 1518 23

We have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreases the serum phosphate. Most recently, these observations were rediscovered in low-density lipoprotein receptor null mice fed high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia, and insulin resistance). We had demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial type. We have shown that VC is worsened by CKD and ameliorated by bone morphogenetic protein -7 (BMP-7). The finding that high-fat-fed low-density lipoprotein receptor null animals without CKD have hyperphosphatemia led us to examine the skeletons of these mice. We found significant reductions in bone formation rates, associated with increased VC and superimposing CKD results in the adynamic bone disorder (ABD), while VC was worsened and hyperphosphatemia persisted. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. BMP-7 treatment corrected the ABD and corrected hyperphosphatemia, compatible with BMP-7-driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC. Thus, in the metabolic syndrome with CKD, a reduction in bone-forming potential of osteogenic cells leads to ABD producing hyperphosphatemia and VC, processes ameliorated by the skeletal anabolic agent BMP-7, in part through increased bone formation and skeletal deposition of phosphate, and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury before demonstrable hyperphosphatemia, and they are preventable and treatable. Therefore, early intervention in CKD is warranted and may affect mortality of the disease.
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PMID:Connections between vascular calcification and progression of chronic kidney disease: therapeutic alternatives. 1633 68

In two independent and separate studies, we have shown that renal injury and chronic kidney disease (CKD) directly inhibit skeletal anabolism, and that stimulation of bone formation decreased the serum phosphate. In the first study, the serum Ca PO(4), parathyroid hormone (PTH), and calcitriol were maintained normal after renal ablation in mice, and even mild renal injury equivalent to stage 3 CKD decreased bone formation rates. More recently, these observations were rediscovered in low-density lipoprotein receptor null (LDLR-/-) mice fed high-fat/cholesterol diets, a model of the metabolic syndrome (hypertension, obesity, dyslipidemia and insulin resistance). We demonstrated that these mice have vascular calcification (VC) of both the intimal atherosclerotic type and medial calcification. We have also shown that VC is made worse by CKD and ameliorated by bone morphogenetic protein-7 (BMP-7). The finding that high-fat fed LDLR-/- animals with CKD had hyperphosphatemia which was prevented in BMP-7-treated animals lead us to examine the skeletons of these mice. It was found that significant reductions in bone formation rates were associated with high-fat feeding, and superimposing CKD resulted in the adynamic bone disorder (ABD), while VC was made worse. The effect of CKD to decrease skeletal anabolism (decreased bone formation rates and reduced number of bone modelling units) occurred despite secondary hyperparathyroidism. The BMP-7 treatment corrected the ABD and hyperphosphatemia, owing to BMP-7-driven stimulation of skeletal phosphate deposition reducing plasma phosphate and thereby removing a major stimulus to VC. A pathological link between abnormal bone mineralization and VC through the serum phosphorus was demonstrated by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. Thus, in the metabolic syndrome with CKD, a reduction in bone forming potential of osteogenic cells leads to the ABD producing hyperphosphatemia and VC, processes ameliorated by BMP-7, in part through increased bone formation and skeletal deposition of phosphate and in part through direct actions on vascular smooth muscle cells. We have demonstrated that the processes leading to vascular calcification begin with even mild levels of renal injury affecting the skeleton before demonstrable hyperphosphatemia and that they are preventable and treatable. Therefore, early intervention in the skeletal disorder associated with CKD is warranted and may affect mortality of the disease.
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PMID:Function and effect of bone morphogenetic protein-7 in kidney bone and the bone-vascular links in chronic kidney disease. 1688 97

The study was purposed to explore the role of mesenchymal stem cells (MSCs) in the pathogenesis of bone disease particularly observed in multiple myeloma (MM), the biological features of marrow derived MSCs from patients with MM have been investigated. Marrow aspirates were harvested from 11 newly diagnosed patients with MM and 5 normal adults and MSCs were isolated and culture-expanded by the cell properties of adherence to plastic flasks, The phenotype was analyzed by flow cytometric technique. The proliferation of MSCs was observed by MTT assay and their differentiation capacities into osteoblasts and adipoblasts were assessed with lineage-specific histochemical staining. The concentrations of IL-6 and SCF in the culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). MSC culture supernatants were collected and MTT assay was performed to evaluate their support on the proliferation of an MM cell line SKO007 cells. The results showed that bone marrow-derived MSCs from MM patients were homogeneously positive for CD29, CD73, CD166 and HLA-ABC and negative for hematopoietic cell marker CD45 and endothelial cell marker CD31, the phenotype of which was similar to that of marrow counterparts from normal adults. MTT assay indicated that MSCs from MM patients or normal adults proliferated at similar rates. MSCs from MM patients occupied in vitro osteogenic and adipogenic capacity as those from normal adults. The levels of IL-6 and SCF in culture supernatant were greatly up-regulated in MM patients by ELISA assay. Furthermore, MSC culture supernatants from MM bone marrow displayed enhanced activity to promote the proliferation of SKO007 cells. It is concluded that marrow-derived MSCs from bone marrow of MM patients are normal in their proliferation and differentiation capacities, and myeloma bone disease may not be ascribed to the differentiation of MSCs while the elevated secretion of IL-6 and SCF may provide necessary cues for the survival of malignant myeloma cells.
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PMID:[Biological properties of mesenchymal stem cells derived from bone marrow of patients with multiple myeloma]. 1720 80


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