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At least 667 records · Page 37Linked to original sources
PubMed1986

An experimental study of the healing process of equine chondral and osteochondral defects.

Four full thickness cartilage defects, two linear and two elliptical, and four subchondral cavity defects were created at the point of weightbearing of the medial femoral condyle in four experimental ponies. This study showed that subchondral bone cysts can develop following full thickness (cartilage only) linear cartilage defects at a weightbearing location. Subchondral bone cysts did not develop following the removal of an elliptical piece of cartilage, exposing the subchondral bone. Primary subchondral defects created in communication with the joint cavity did not heal by replacement with bone over a six-month period. Fibrous and cartilaginous repair occurred which appeared to be unrelated to the size or depth of the subchondral defect. Irrespective of the size of the defects, the surrounding bone showed marked woven bone formation with remodelling of existing and newly formed bone. The resulting osteosclerosis indicated a positive balance and a natural limitation of cavity expansion. The positive balance affected only the surrounding bone and did not lead to re-establishment of the bone within the cavity during the period studied.

Animals↗
PubMed2002

Premature aging in mice deficient in DNA repair and transcription.

One of the factors postulated to drive the aging process is the accumulation of DNA damage. Here, we provide strong support for this hypothesis by describing studies of mice with a mutation in XPD, a gene encoding a DNA helicase that functions in both repair and transcription and that is mutated in the human disorder trichothiodystrophy (TTD). TTD mice were found to exhibit many symptoms of premature aging, including osteoporosis and kyphosis, osteosclerosis, early greying, cachexia, infertility, and reduced life-span. TTD mice carrying an additional mutation in XPA, which enhances the DNA repair defect, showed a greatly accelerated aging phenotype, which correlated with an increased cellular sensitivity to oxidative DNA damage. We hypothesize that aging in TTD mice is caused by unrepaired DNA damage that compromises transcription, leading to functional inactivation of critical genes and enhanced apoptosis.

Aging↗
PubMed2006

Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3.

Genetic mutations that disrupt osteoblast function can result in skeletal dysmorphogenesis or, more rarely, in increased postnatal bone formation. Here we show that Schnurri-3 (Shn3), a mammalian homolog of the Drosophila zinc finger adapter protein Shn, is an essential regulator of adult bone formation. Mice lacking Shn3 display adult-onset osteosclerosis with increased bone mass due to augmented osteoblast activity. Shn3 was found to control protein levels of Runx2, the principal transcriptional regulator of osteoblast differentiation, by promoting its degradation through recruitment of the E3 ubiquitin ligase WWP1 to Runx2. By this means, Runx2-mediated extracellular matrix mineralization was antagonized, revealing an essential role for Shn3 as a central regulator of postnatal bone mass.

Animals↗
PubMed1996

Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.

Pycnodysostosis, an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature, maps to chromosome 1q21. Cathepsin K, a cysteine protease gene that is highly expressed in osteoclasts, localized to the pycnodysostosis region. Nonsense, missense, and stop codon mutations in the gene encoding cathepsin K were identified in patients. Transient expression of complementary DNA containing the stop codon mutation resulted in messenger RNA but no immunologically detectable protein. Thus, pycnodysostosis results from gene defects in a lysosomal protease with highest expression in osteoclasts. These findings suggest that cathepsin K is a major protease in bone resorption, providing a possible rationale for the treatment of disorders such as osteoporosis and certain forms of arthritis.

Amino Acid Sequence↗
PubMed1978

Normocalcaemic pseudohypoparathyroidism with unusual phenotype.

We describe a boy who presented at 4 years of age with radiological hyperparathyroidism, osteosclerosis, and necrosis of the femoral heads. Plasma biochemistry was normal but the parathyroid hormone (PTH) level was very high. He was deaf and had an unusual facies but did not have the phenotype of Albright's hereditary osteodystrophy. Plasma and urine cyclic AMP reponses to bovine PTH were markedly subnormal. Vitamin D produced sustained hypercalcaemia and a fall in plasma phosphorus. After four hyperplastic parathyroid glands were removed he became hypocalcaemic and plasma phosphorus rose. After operation he remained unresponsive to exogenous PTH; We suggest that he had a form of pseudohypoparathyroidism without the phenotype of Albright's hereditary osteodystrophy and with some residual skeletal and renal responsiveness to PTH.

Bone and Bones↗
PubMed1992

Condensing osteitis of the clavicle: magnetic resonance imaging as an adjunct method for differential diagnosis.

Condensing osteitis of the clavicle is a benign disorder leading to osteosclerosis of the medial end of the clavicle. The differential diagnosis between condensing osteitis of the clavicle and ischaemic necrosis of the medial clavicular epiphysis (Friedrich's disease), osteoid osteoma, and low grade osteomyelitis can be difficult. In the case history reported here, magnetic resonance imaging was a useful non-invasive procedure for the diagnosis of condensing osteitis of the clavicle.

Adult↗
PubMed1986

Working classification of chronic myeloproliferative disorders based on histological, haematological, and clinical findings.

Bone marrow biopsies of 850 patients with chronic myeloproliferative disorders were taken at initial diagnosis; and 169 sequential biopsies over periods of one to 188 months. Three micron sections of all biopsies were evaluated semiquantitatively with reference to the proliferating cell lines, anomalies of megakaryocytes, and fibrosis or osteosclerosis. Correlations between initial histological findings, clinical, haematological, and survival data were analysed statistically. The predominant cell lines distinguished the classical entities of polycythaemia vera, primary thrombocythaemia, and chronic myeloid leukaemia and correlated with their different prognoses, while megakaryocytes characterised subgroups that were prone to fibrotic or blastic transformation. Based on the initial histological, clinical, and haematological data analysed a working classification of chronic myeloproliferative disorders was proposed that permits recognition of both typical and atypical cases of chronic myeloproliferative disorders.

Adolescent↗
PubMed1995

Osteolytic bone lesions in a patient with idiopathic myelofibrosis and bronchial carcinoma.

A 59 year old man with longstanding myelofibrosis and previous splenectomy was incidently found to have a large lytic lesion in his left femur which required operative fixation. He had undergone right upper lobectomy for squamous carcinoma of the bronchus five years earlier. Histological analysis of bone reamings showed no evidence of metastatic carcinoma. Osteosclerosis is frequently noted in patients with myelofibrosis but osteolytic lesions are uncommon and may be confused with metastatic malignancy.

Carcinoma, Bronchogenic↗
PubMed1980

Plasma cell dyscrasia with polyneuritis and dermato-endocrine alterations. Report of a new case outside Japan.

A new syndrome has been described comprising polyneuropathy, oedema, hyperpigmentation and thickening of the skin, gynaecomastia in males and amenorrhoea in females, monoclonal gammopathy, papilloedema and diabetes. There is frequent osteosclerosis with or without plasmacytoma, hepatosplenomegaly and polycythaemia. There is a good response to corticosteroids, immunosuppressive drugs and occasionally to excision or irradiation of the plasmacytoma. This syndrome was first described in Japan, and is still seen predominantly there, and only occasionally in other areas. An example in a 51-year-old Spanish female is described: she had a spectacular response to prednisone and melphalan. The aetiopathogenic possibilities are discussed.

Amenorrhea↗
PubMed1977

Radiological/pathological correlations in uremic bone disease.

Skeletal radiographs and non-decalcified bone specimens from 17 chronically uremic patients with radiographic evidence of bone disease were studied quantitatively. The results of each morphological technique were compared in an attempt to define the roentgenographic manifestations of renal osteodystrophy histologically. The radiographs correlated best with the trabecular bone manifestations of osteitis fibrosa but showed poor correlation with histological evidence of osteomalacia. Radiographic signs of osteosclerosis could not be correlated with any radiographic or histiolgical feature of bone resorption.

Adult↗
PubMed1991

Osteoid osteoma.

Osteoid osteoma is a benign skeletal neoplasm composed of osteoid and woven bone that rarely exceeds 1.5 cm in greatest dimension. The lesion is most commonly located in the cortex of long bones where it is associated with dense, fusiform, reactive sclerosis. Less often, it may be cancellous, where reactive osteosclerosis is usually less intense and may be distant from the lesion. Cancellous lesions are frequently intraarticular (most often in the hip) and may be associated with synovitis and joint effusion. Rarely, osteoid osteomas occur in a subperiosteal location. Patients are usually young, and there is a strong male predominance. Pain is the most common symptom. Radiographs of patients with cortical osteoid osteoma are often diagnostic. Intraarticular lesions, however, may be subtle, and scintigraphy may be required to locate the lesion for subsequent computed tomography (CT). CT is useful to identify and precisely locate the lesion and to provide guidance for percutaneous localization or treatment.

Adolescent↗
PubMed1985

Metabolic bone disease in pseudohypoparathyroidism: radiologic features.

We reviewed the radiographs of six patients with pseudohypoparathyroidism (PHP) manifested by variable renal and skeletal resistance to parathyroid hormone (PTH). Features compatible with hyperparathyroid bone disease, osteomalacia, and rickets were observed. Skeletal changes of hyperparathyroidism included (a) subperiosteal bone resorption, (b) radiolucent lesions, caused by either brown tumors or bone cysts, (c) slipped capital femoral epiphyses, (d) focal areas of osteosclerosis, (e) periosteal neostosis, and (f) osteopenia with reduced cortical and trabecular bone volume. Histologic bone features were compatible with osteitis fibrosa in all patients, which suggests that the skeleton responded to the bone-remodeling effects of PTH despite hormonal resistance at other target sites. Skeletal changes of rickets included metaphyseal irregularities, cupping, and widening of the growth plates. Osteomalacia was indicated by Looser zones in one patient and confirmed by histologic evidence in three patients.

Adolescent↗
PubMed1987

Heterogeneity of autosomal dominant osteopetrosis.

A review of the radiographs of 26 patients with autosomal dominant osteopetrosis disclosed two distinct and strictly family-related radiographic types. Both types had universal osteosclerosis. In type 1 the most striking finding was pronounced sclerosis of the cranial vault while the spine was almost unaffected. In type 2 the sclerosis of the skull was most pronounced at the base, the vertebrae always had end-plate thickening, and in the pelvis the iliac wings contained convex arcs of sclerotic bone. Age and sex distribution did not differ between the types. Autosomal dominant osteopetrosis may be a heterogeneous group of inherited bone disorders.

Adolescent↗
PubMed1987

Aluminum toxicity in patients undergoing dialysis: radiographic findings and prediction of bone biopsy results.

Aluminum toxicity in patients undergoing dialysis currently requires bone biopsy for definitive diagnosis. The authors retrospectively reviewed clinical, histologic, and radiographic findings in 63 patients undergoing dialysis. In 30 patients, biopsy specimens were negative for aluminum toxicity, and in 33 patients, specimens were positive. In 21 of the 30 patients who had a negative biopsy specimen, absence of aluminum toxicity could be predicted by a high immunoreactive parathyroid hormone level (greater than 2,000 microliter Eq/ml [2,210 pM]) and fewer than three fractures, by the presence of osteosclerosis on radiographs, or if serum aluminum levels were less than 30 ng/ml. None of the patients who had a positive biopsy specimen met these criteria. In 18 of 33 patients who had a positive biopsy specimen, aluminum toxicity could be predicted by a low immunoreactive parathyroid hormone level (less than 500 microliter Eq/ml [553 pM]) and more than three fractures, or if serum aluminum levels were greater than 300 ng/ml. None of the patients who had a negative biopsy specimen met these criteria. Thus, based on the criteria identified, the aluminum status of 62% of these patients would have been correctly diagnosed.

Adult↗
PubMed2004

Vascular endothelial growth factor contributes to the prostate cancer-induced osteoblast differentiation mediated by bone morphogenetic protein.

Human prostate cancer has a high predisposition to metastasize to bone, resulting in the formation of osteoblastic metastases. The mechanism through which prostate cancer cells promote osteoblastic lesions is undefined. Vascular endothelial growth factor (VEGF) has been implicated as a mediator of osteoblast activity. In the present study, we examined if prostate cancer cells promote osteoblastic activity through VEGF. We found that LNCaP and C4-2B prostate cancer cell lines and primary tumor and metastatic prostate cancer tissues from patients expressed VEGF. Bone morphogenetic proteins (BMPs), which are normally present in the bone environment, induced VEGF protein and mRNA expression in C4-2B cells. Furthermore, BMP-7 activated the VEGF promoter. Noggin, a BMP inhibitor, diminished VEGF protein expression and promoter activity in C4-2B cells. Conditioned media (CM) from C4-2B cells induced pro-osteoblastic activity (increased alkaline phosphatase, osteocalcin, and mineralization) in osteoblast cells. Both noggin alone and anti-VEGF antibody alone diminished C4-2B CM-induced pro-osteoblastic activity. Transfection of C4-2B cells with VEGF partially rescued the C4-2B CM-induced pro-osteoblastic activity from noggin inhibition. These observations indicate that BMPs promote osteosclerosis through VEGF in prostate cancer metastases. These results suggest a novel function for VEGF in skeletal metastases. Specifically, VEGF promotes osteoblastic lesion formation at prostate cancer bone metastatic sites.

Bone Morphogenetic Proteins↗
PubMed2005

Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism.

Prostate cancer frequently metastasizes to bone where it forms osteoblastic lesions through unknown mechanisms. Bone morphogenetic proteins (BMP) are mediators of skeletal formation. Prostate cancer produces a variety of BMPs, including BMP-6. We tested the hypothesis that BMP-6 contributes to prostate cancer-induced osteosclerosis at bone metastatic sites. Prostate cancer cells and clinical tissues produced BMP-6 that increased with aggressiveness of the tumor. Prostate cancer-conditioned medium induced SMAD phosphorylation in the preosteoblast MC3T3 cells, and phosphorylation was diminished by anti-BMP-6 antibody. Prostate cancer-conditioned medium induced mineralization of MC3T3 cells, which was blocked by both the BMP inhibitor noggin and anti-BMP-6. Human fetal bones were implanted in severe combined immunodeficient mice and after 4 weeks, LuCaP 23.1 prostate cancer cells were injected both s.c. and into the bone implants. Anti-BMP-6 or isotype antibody administration was then initiated. Anti-BMP-6 reduced LuCaP 23.1-induced osteoblastic activity, but had no effect on its osteolytic activity. This was associated with increased osteoblast numbers and osteoblast activity based on bone histomorphometric evaluation. As endothelin-1 has been implicated in bone metastases, we measured serum endothelin-1 levels but found they were not different among the treatment groups. In addition to decreased bone production, anti-BMP-6 reduced intraosseous, but not s.c., tumor size. We found that BMP-2, BMP-4, BMP-6, and BMP-7 had no direct effect on prostate cancer cell growth, but BMP-2 and BMP-6 increased the in vitro invasive ability of prostate cancer cell. These data show that prostate cancer promotes osteoblastic activity through BMP-6 and that, in addition to its bone effects, suggest that BMPs promote the ability of the prostate cancer cells to invade the bone microenvironment.

Animals↗
PubMed1995

POEMS syndrome in Chinese.

POEMS (polyneuropathy, organomegaly, endocrine disturbance, M-protein and skin hyperpigmentation) syndrome occurring in Chinese has been inadequately described. Here we report our experience of 12 Chinese patients with the syndrome. This series is similar to those reported from Japan and from the Western world by the predominance of middle-aged males. Diabetic mellitus, a common feature in POEMS syndrome, was not present in our patients. M-protein of the lambda type was demonstrated in 7 patients by immunoelectrophoresis or by immunofixation electrophoresis. Osteosclerosis in Chinese patients is not as common as in patients reported from Japan or from the Western world; a common radiographic finding in our patients was a compression fracture of the thoraco-lumbar spine with or without sclerotic and lytic lesions. The condition has a grave prognosis; 9 patients die within 4 years after onset of the disease despite various kinds of treatment.

Adult↗
PubMed1986

Comparison of histomorphometry and computerized tomography of the spine in quantitating trabecular bone in renal osteodystrophy.

Computerized tomography (CT) has the advantage of allowing the isolation of trabecular bone of the axial skeleton, which is the more sensitive to metabolic changes. By means of single-energy X-ray CT we have devised a method for assessing trabecular bone mass (TBM) at L-4 vertebral body, which has an acceptable reproducibility (CV = 2.76%). Normal values where obtained after studying 29 normal individuals from both sexes and different ages. In order to know if the method is accurate, TBM was assessed in 17 patients (6 with creatinine clearance less than 6 ml/min and 11 on chronic hemodialysis), and in all of them the results were compared with the histomorphometry of the iliac crest bone biopsy. TBM assessed by CT correlated with trabecular bone volume (TBV; mineralized bone + osteoid) (r = 0.82; p less than 0.001) and this correlation was not improved after adding the volume of marrow fibrosis to TBV. TBM assessed by CT also correlated with mineralized bone volume but at a lower level of significance (r = 0.72; p = 0.001), and no correlation was found with relative osteoid volume alone. These findings suggest that final CT value is an integral of mineralized bone and osteoid but with a higher influence of mineralized bone. Osteomalacia and osteitis fibrosa were seen in situations of normal, decreased, or increased TBM assessed by CT, although the 2 patients with severe osteosclerosis suffered osteomalacia. We conclude that the assessment of TBM by CT at the axial skeleton of uremic patients has an acceptable reproducibility and accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗