Osteosclerosis associated with urinary tract malignancy may not be dependent upon bone metastases.
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Full-mouth radiographs of 1321 patients were examined for the presence of radiopacitics that could not be attributed to any known sources of bone formation.A total of 75 patients exhibited these foci of idiopathic osteosclerosis.The incidence of disease is 5.7%,including SIO 46.3%,PIO 37.5%,IIO 16.2%.The majority of the opacities were found in the mandible,especially from the mandibular first premolar to first molar region(65%).The lesion was most prevalent in the first three decades of life.
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The osteosclerosis of idiopathic myeloid metaplasia was investigated by a histodynamic study of undecalcified bone from nine patients. In all cases osteosclerosis resulted from woven bone formation. In moderate osteosclerosis only intrabecular woven bone was observed, with osteoclastic hyperresorption, hyperosteoidosis with many osteoblasts, and an increased calcification rate. This may represent an early stage of the disease, osteosclerosis resulting from increased bone remodelling, with woven bone formation by osteoblasts. However, in extensive osteosclerosis both intratrabecular and medullary woven bone was observed, with moderate osteoclastic hyperresorption, hyperosteoidosis without osteoblasts and a very low calcification rate. The latter pattern could correspond to an advanced stage, and could result from stromal bone formation without osteoblasts. The classical histodynamic profile of osteomalacia was sometimes observed. The link between bone pain and possible osteomalacia remains vague.
UNLABELLED: Fra1 transgenic (Tg) mice develop osteosclerosis and exhibit altered expression of bone matrix proteins. We found that expression of Thbs1 and Thbs2 was reduced in Fra1 Tg osteoblasts. Fra1 Tg and non-osteosclerotic Thbs1-/-Thbs2-/- mice share an edge-to-edge bite. Therefore, reduced expression of thrombospondins may contribute to craniofacial dysmorphism independently of osteosclerosis. INTRODUCTION: Tg mice overexpressing Fra1, a component of the transcription factor activator protein-1 (AP-1), show progressive osteosclerosis caused by cell autonomous abnormalities in osteoblasts. The expression of several bone matrix proteins, including matrix gla protein, is dysregulated in Fra1 Tg osteoblasts. MATERIALS AND METHODS: In osteoblastogenic cultures, altered bone matrix production by Fra1 overexpression was monitored using Alizarin red staining, quantitative RT-PCR, and Western blotting. Responsiveness to ovariectomy was examined by bone histomorphometry. Craniofacial parameters were measured on radiographs and using CT. RESULTS: Thrombospondin-1 (Thbs1) and thrombospondin-2 (Thbs2) were reduced in Fra1 Tg osteoblasts differentiated in vitro and in bones from Fra1 Tg mice. Despite alterations in bone matrix proteins, ovariectomy induces high turnover bone loss in Fra1 Tg mice as in wildtype mice. Fra1 Tg mice, as well as Thbs1-/- Thbs2-/- mice, which do not show osteosclerosis, exhibit an edge-to-edge bite phenotype associated with craniofacial dysmorphism. CONCLUSIONS: These data suggest that reduced expression of thrombospondins in Fra1 Tg mice underlies craniofacial dysmorphism, independent of osteosclerosis.
Bone architecture and mineralization are generally considered to be important components of bone quality, and determine bone strength in conjunction with bone mineral density. Although the features of bone quality have recently been studied under conditions in which bone density decreases, such as osteoporosis, little is known in osteosclerotic diseases. In this study, we compared the trabecular bone microarchitecture and degree of mineralization between osteoblastic bone metastasis and degenerative osteosclerosis using synchrotron radiation microcomputed tomography (SR-microCT). Small cubes of lumbar vertebrae were excised postmortem from the sites of osteoblastic metastasis, degenerative osteosclerosis, and comparative sites of normal subjects without skeletal lesions. The samples were imaged at high spatial resolution (voxel size = 6 microm) using the SR-microCT system developed at the synchrotron facility (SPring-8), Hyogo, Japan. The three-dimensional (3D) image data were then analyzed for the morphological parameters and the degree of mineralization of bone (DMB). Trabecular bone in metastatic lesions showed a highly connected and isotropic network pattern compared with the normal samples. Although the trabecular surface was markedly irregular in osteoblastic metastases, no significant difference was found in the mean trabecular thickness (Tb.Th) between osteoblastic metastases and normal tissue. The DMB of trabeculae in metastatic lesions had a broader range and lower mean than that of the normal tissue. In contrast, trabecular bone in degenerative osteosclerotic lesions showed a similar degree of anisotropy (DA) and connectivity to the normal tissue, whereas the trabecular thickness was greater in the degenerative osteosclerotic lesions. No significant difference in DBM between degenerative osteosclerosis and normal tissue was detected. These results characterize the difference in bone quality between osteoblastic bone metastasis and degenerative osteosclerosis. Further study on the relationship between bone quality and bone strength in these osteosclerotic lesions would improve our understanding of the pathogenesis of bone fragility.
The method of gamma-ray computed tomography (gamma-ray CT) bone densitometry described in the preceding article provides selective determination of trabecular bone density (TBD), the relative amount of compact bone (bone density, BD), and the total absorption (TA) within a bone cross section. Seven of nine children with chronic renal failure (CRF), and selected only on the basis of their serum creatinine value (greater than 5 mg/100 ml), had increased TBD values above the normal range, whereas the other bone mineral parameters were normal. Radiographic signs of secondary hyperparathyroidism (subperiosteal erosions, cysts) were reported in the five patients with the highest TBD values, whereas the subjective diagnosis of osteosclerosis reported in three of these five and in one other patient correlated less well with the TBD increases. However, this is the first report of an objective, non-invasive documentation of the radiological finding of osteosclerosis in CRF. It also explains why methods for bone mineral measurements used previously, such as a photon absorptiometry which provides only a parameter equivalent to TA, failed to reveal increases in bone mineral content in renal osteodystrophy even when signs of osteosclerosis were present. Thus, gamma-ray CT helps to document objectively the degree of osteosclerosis and its location.