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PubMed2003

Brick tea fluoride as a main source of adult fluorosis.

An epidemiological survey was conducted in Naqu County, Tibet in September 2001 to investigate the manifestations of fluorosis in adults caused by the habitual consumption of brick tea. Profiles were obtained for the total daily fluoride intake, environmental fluoride levels and average urinary fluoride concentration, and a physical examination and a skeletal radiographic study were conducted. One hundred and eleven 30-78-year-old adults were enrolled. It was found that the fluoride level of water sources in Naqu County was 0.10+/-0.03 mg/l; no evidence of fluoride air pollution was found, but the brick tea water processed foods--zamba and buttered tea--had fluoride contents of 4.52+/-0.74 mg/kg and 3.21+/-0.65 mg/l, respectively. The adult daily fluoride intake reached 12 mg, of which 99% originated from the brick tea-containing foods. The positive rate of clinical symptoms by physical examination was 89%; furthermore, 42 of the 111 subjects were diagnosed by X-ray. The positive examination rate was 83%. Although the osteosclerosis-type skeletal fluorosis (overall increased bone matrix density) affected 74%, arthropathy and arthritis affected a significant number of the patients, resulting in functional disability. The results suggest that this brick tea-type fluorosis had even more severe adverse effects on human health compared with both the water-type and coal combustion-type fluorosis that occurred in other areas of China.

Adult↗
PubMed1997

Diagnostic criteria of the myeloproliferative disorders (MPD): essential thrombocythaemia, polycythaemia vera and chronic megakaryocytic granulocytic metaplasia.

Philadelphia chromosome-positive essential thrombocythaemia (Ph(+)-ET) and chronic granulocytic leukaemia (Ph(+)-CGL) constitute a separate malignant disease entity, whereas essential thrombocythaemia (ET), polycythaemia vera (PV) and chronic megakaryocytic granulocytic metaplasia (CMGM) belong to the Philadelphia chromosome-negative (Ph-) myeloproliferative disorders. The megakaryocytes in Ph(+)-ET and Ph(+)-CGL are abnormal and small with round nuclei, showing little lobulation. Both the number and size of megakaryocytes in Ph-ET, -PV and -CMGM are typically increased. Enlarged megakaryocytes with mature cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or slightly increased cellular bone marrow represent the hallmark of ET. In reactive thrombocytosis the size and morphology of increased megakaryocytes are normal. The characteristic increase and clustering of enlarged mature and pleomorphic megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses is the diagnostic hallmark of untreated PV. In secondary polycythaemia, in which increased cellularity of the erythroid cell line may be present, the number, size and morphology of megakaryocytes remain small and normal. CMGM, including early stages without myelofibrosis and advanced myelofibrotic stages of agnogenic myeloid metaplasia, appears to be a distinct neoplastic proliferation of neutrophilic granulopoiesis and megakaryopoiesis. The histopathology of the bone marrow in CMGM is dominated by atypical, enlarged and immature megakaryocytes with cloud-like nuclei which are not seen in ET and PV. Myelofibrosis in ET, PV and CMGM is graded in no reticulin fibrosis (MFO), early reticulin fibrosis (MF1), advanced reticulin sclerosis with minor collagen fibrosis (MF2) and advanced collagen fibrosis with or without osteosclerosis (MF3). Myelofibrosis is not a feature of ET, may occur in PV, and constitutes a prominent feature of CMGM during the natural history of the disease.

Bone Marrow↗
PubMed1999

Diagnosis, pathogenesis and treatment of the myeloproliferative disorders essential thrombocythemia, polycythemia vera and essential megakaryocytic granulocytic metaplasia and myelofibrosis.

According to strict clinical, hematological and morphological criteria, the Philadelphia (Ph) chromosome negative chronic myeloproliferative disorders essential thrombocythemia (ET), polycythemia vera (PV), and agnogenic myeloid (megakaryocytic/granulocytic) metaplasia (AMM) or idiopathic myelofibrosis (IMF) are three distinct disease entities with regard to clinical manifestations, natural history and outcome in terms of life expectancy. As clonality studies have clearly demonstrated that fibroblast proliferation in AMM, as well as in many other conditions such as advanced stages of Ph(+)-essential thrombocythemia, Ph(+)-granulocytic leukemia, and Ph(-)-polycythemia vera, is polyclonal indicating that myelofibrosis is secondary to the megakaryocytic granulocytic metaplasia in these various conditions, AMM is illogically labeled as IMF. As abnormal megakaryocytic granulocytic metaplasia is the essential feature preceding the early prefibrotic stage of AMM, the term essential megakaryocytic granulocytic metaplasia (EMGM) can readily be used to characterize this condition more appropriately at the biological level. Clinical, hematological and morphological characteristics, in particular megakaryocytopoiesis and bone marrow cellularity, reveal diagnostic features, which enable a clear-cut distinction between ET, PV and EMGM or classical IMF. The characteristic increase and clustering of enlarged megakaryocytes with mature cytoplasm and multilobulated nuclei and their tendency to cluster in a normal or only slightly increased cellular bone marrow represent the hallmark of ET. The characteristic increase and clustering of enlarged mature and pleiomorphic megakaryocytes with multilobulated nuclei and proliferation of erythropoiesis in a moderate to marked hypercellular bone marrow with hyperplasia of dilated sinuses are the specific diagnostic features of untreated PV. EMGM, including the early prefibrotic stages as well as the various myelofibrotic stages of classical IMF appear to be a distinct neoplastic dual proliferation of abnormal megakaryopoiesis and granulopoiesis. The histopathology of the bone marrow in prefibrotic EMGM and in classical IMF is dominated by atypical, enlarged and immature megakaryocytes with cloud-like immature nuclei, which are not seen in ET and PV at diagnosis and during follow-up. Myelofibrosis in ET, PV and EMGM is graded into: no reticulin fibrosis (MF0), early reticulin fibrosis (MF1), advanced reticulin sclerosis with minor or moderate collagen fibrosis (MF2) and advanced collagen fibrosis with osteosclerosis (MF3). Myelofibrosis is not a feature of ET at diagnosis and during long-term follow-up. Myelofibrosis may be present in a minority of PV-patients at diagnosis and usually becomes apparent during long-term follow-up in the majority of PV-patients. Myelofibrosis secondary to the abnormal megakaryocytic and granulocytic myeloproliferation constitutes a prominent feature in the majority of EMGM/IMF at time of diagnosis and usually progresses more or less rapidly during the natural history of the disease. Life expectancy is normal in ET, normal during the 1st ten years and compromised during the 2nd ten years follow-up in PV, but significantly shortened in the prefibrotic stage of EMGM as well as in the various myelosclerotic stages of classical IMF. First line treatment options in prospective randomized clinical trials of newly diagnosed MPD-patients are control of platelet function with low-dose aspirin versus reduction of platelet count with anagrelide, interferon or hydroxyurea in ET; control of platelet and erythrocyte counts by interferon alone versus bloodletting plus hydroxyurea on indication in PV; interferon versus no treatment in the early stages of EMGM; a wait and see strategy in the fibrotic stages of EMGM or classical IMF with favorable prognostic factors, and bone marrow transplantation in classical IMF with poor prognostic factors at presentation or during short-term follow-up.

Aspirin↗
PubMed1996

"Aging bull'.

An old bull, it is said by those who know, can have his troubles. Included among these are vertebral osteosclerosis and ankylosing spondylosis; this stiffening up limits, rather than accentuates, the value and reproductive potential of a stud bull past his prime. Associated with these abnormalities, however-and not seen in age-matched cows of comparable breeds-are fascinating endocrine neoplasms suggestive of a pattern that could be productive as a model of human hereditary endocrine abnormalities. Adjacent to the thyroid gland in other vertebrates are ultimobranchial bodies that are incorporated into the lateral thyroid lobes in primates as the parafollicular "C cells' of the thyroid. These are the cells in man that give rise to medullary thyroid cancer and are associated with calcitonin secretion, useful as a tumor marker. In aging bulls of whatever breed, nearly half exhibit abnormality of these ultimobranchial bodies: 20% show hyperplasia, and 30% have frank neoplasia. These ultimobranchial tumors appear in bulls passing 6 1/2 years in age, and are absent in young bulls and all cows of any age. Calcitonin can be demonstrated in the ultimobranchial tumors from bulls, and secretion is stimulated by calcium infusion, though serum calcium remains normal. The ultimobranchial tumors themselves can range from hyperplasia through adenoma to metastasizing carcinoma-in fact, representing one of the commoner cattle cancers. Parathyroid glands taken from bulls with these ultimobranchial tumors initially show evidence of inhibited secretory activity and morphologic atrophy, but later go on to develop hyperplasia and, eventually, autonomy. Cattle forage on calcium-rich diets. Bulls appear to respond to this calcium excess from the positive balance, but breeding cows have the unique calcium deficits of the high net loss of calcium through lactation and the large requirements of calcifying a fetal skeleton. Chronic stimulation of the APUD-derived ultimobranchial bodies by high calcium intake, not counterbalanced by calcium losses in the bulls, may account for the development over time of the ultimobranchial neoplasms. Further, a number of the bulls who have the ultimobranchial tumors are found to have multiple endocrine tumors in other glands-bilateral pheochromocytomas and pituitary acidophil adenomas.

Aging↗
PubMed1986

Contiguous development of idiopathic osteonecrosis and osteoarthrosis in ischemia of a femoral head (radiological and morphological study).

In a 67 year-old man, an aseptic necrosis of the right hip joint developed side by side with an early oteoarthrosis characterized by an extensive narrowing of the upper interlinear space. The histological study revealed a diffuse ischemia which had evolved differently in the various regions of the femoral head. A well-limited necrosis appeared in a part of the weight-bearing zone, and osteoarthrosis developed in another one. In contrast with classical osteoarthrosis secondary to malformation, the osteoarthrotic lesions of the weight-bearing zone were caused by the ischemic angio-fibrosis of the bone marrow. At the beginning there was a resorption by the subjacent fibro-vascular tissue of the end-plate and of the deep layer of the cartilage. The osteosclerosis of this zone, in particular the eburnated plate, was formed mostly of fibre bone which rapidly became necrotic. Outside the weight-bearing zone, the subchondral angio-fibrosis and the non-inflammatory vascular pannus modified the articular surface.

Aged↗
PubMed1984

Preiser's disease: a case report.

Preiser's disease, or avascular necrosis of the scaphoid, is an exceedingly rare although debilitating pathologic process. A case of progressive avascular necrosis of the carpal scaphoid is presented together with a review of the possible etiology of this rare syndrome. Histologic evaluations of resected specimens have demonstrated a localized sequestrum of necrotic bone, leading to the belief that disruption of blood supply is a major predisposing factor. The diagnosis of Preiser's disease or avascular necrosis of the carpal scaphoid should be exclusively reserved to those cases that demonstrate a progressive clinical and radiographic sequence of osteosclerosis and subsequent fragmentation of the scaphoid.

Adult↗
PubMed1989

Occupational skeletal fluorosis.

A 20-30 years' occupational and/or environmental exposure to fluorine may cause osteosclerosis, especially of the spine and pelvic bones, and calcification of spinal ligaments. The radiological picture may mimic many other diseases, especially ankylosing spondylitis, diffuse idiopathic hyperostosis, and rare bone diseases, such as Albers-Schönberg disease. As clinical findings are often not characteristic, early diagnosis is based on the history of occupational exposure, examination of urinary fluoride excretion (over 8 mg F-/litre in 24 hours) and radiological signs. It is also useful to monitor the concentration of atmospheric fluoride.

Bone Diseases↗
PubMed2003

Erdheim-Chester disease: a rare cause of paraplegia.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis. It is characterized by osteosclerosis of the metaphyseal regions of long bones and several extraskeletal manifestations. Clinically, it ranges from an asymptomatic focal process to systemic disease with life-threatening visceral involvement. Until now, only two cases of Erdheim-Chester disease with paraparesis have been reported. Herein we report the first case of Erdheim-Chester disease with the clinical manifestation of paraplegia. Our patient also had diabetes insipidus, pleural and pericardial effusion, retro-orbital and cavernous sinus masses, fibrotic changes in the retroperitoneal, perirenal, and periaortic areas, and epidural space-occupying lesions. We want to emphasize that ECD may be a very rare cause of paraplegia.

Journal Article↗
PubMed2003

Benign odontogenic tumors of the mandible and maxilla.

Benign odontogenic tumors are characterized by imaging findings of expansile growth and well-defined margins with smooth borders, and their appearance is very similar to that of odontogenic and nonodontogenic cysts. From the viewpoint of diagnostic imaging of odontogenic tumors, teeth are designed differently according to their origin from the apex or crown. Therefore, for differential diagnosis, it is necessary to select diagnostic methods that make it possible to evaluate these findings in detail. Intraoral and panoramic radiography are highly effective in examining the relationship between teeth and lesions, especially the vertical relationship. When a lesion is suspected in the mandible or maxilla on CT, MR imaging, or nuclear medicine, these procedures must be performed as supplementary imaging techniques. CT demonstrates well the degree of bone resorption, osteosclerosis, cortical bone swelling, destruction, and calcification. MR imaging is effective in differentiating between tumors and cysts, evaluating the infiltration of malignant tumors in the jawbone and surrounding soft tissue, and detecting bone marrow changes of the jaw. Differentiation between tumors and cysts must be achieved by contrast-enhanced studies. Combining plain radiography with advanced imaging techniques, including CT and MR imaging, can improve the accuracy of diagnosing odontogenic tumors.

Diagnosis, Differential↗
PubMed1995

Efficacy of FDA guidelines for prescribing radiographs to detect dental and intraosseous conditions.

OBJECTIVES: This study compared the FDA guidelines for ordering dental radiographs to a conventional full-mouth examination for the detection of intraosseous disease and conditions affecting teeth other than caries. STUDY DESIGN: We examined 490 patients and selected posterior bite-wing and periapical views as indicated by the patient's signs or symptoms. We compared the radiographic findings with the use of this selected set of radiographs to those from a full-mouth set of radiographs to determine the rates of missed disease when the FDA guidelines were used. RESULTS: The most commonly missed intraosseous findings were osteosclerosis, unerupted teeth, periapical radiolucencies, and primary root tips. Periapical radiolucencies that were most probably periapical cemental dysplasia were missed in six patients. The most commonly missed dental findings were resorbed roots and pulp stones. Three instances of dens in dente were missed. CONCLUSIONS: When we used the FDA guidelines, the number of missed intraosseous and dental conditions was small and most likely inconsequential given the range of variability in dental diagnosis and treatment.

Adolescent↗
PubMed2002

Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis.

Elevated serum levels of insulin-like growth factor binding protein-2 (IGFBP-2) and a precursor form of IGF-II are associated with marked increases in bone formation and skeletal mass in patients with hepatitis C-associated osteosclerosis. In vitro studies indicate that IGF-II in complex with IGFBP-2 has high affinity for bone matrix and is able to stimulate osteoblast proliferation. The purpose of this study was to determine the ability of the IGF-II/IGFBP-2 complex to increase bone mass in vivo. Osteopenia of the femur was induced by unilateral sciatic neurectomy in rats. At the time of surgery, 14-day osmotic minipumps containing vehicle or 2 microg IGF-II+9 microg IGFBP-2/100g body weight/day were implanted subcutaneously in the neck. Bone mineral density (BMD) measurements were taken the day of surgery and 14 days later using a PIXImus small animal densitometer. Neurectomy of the right hindlimb resulted in a 9% decrease in right femur BMD (P<0.05 vs. baseline). This loss in BMD was completely prevented by treatment with IGF-II/IGFBP-2. On the control limb, there was no loss of BMD over the 14 days and IGF-II/IGFBP-2 treatment resulted in a 9% increase in left femur BMD (P<0.05). Bone histomorphometry indicated increases in endocortical and cancellous bone formation rates and in trabecular thickness. These results demonstrate that short-term administration of the IGF-II/IGFBP-2 complex can prevent loss of BMD associated with disuse osteoporosis and stimulate bone formation in adult rats. Furthermore, they provide proof of concept for a novel anabolic approach to increasing bone mass in humans with osteoporosis.

Animals↗
PubMed2000

Type II autosomal dominant osteopetrosis (Albers-Schönberg disease): clinical and radiological manifestations in 42 patients.

Type II autosomal dominant osteopetrosis (ADO II, Albers-Schonberg disease) is a genetic condition characterized by generalized osteosclerosis predominating in some skeletal sites such as the spine and pelvis. ADO II is rare, and most available clinical descriptions are based on small numbers of patients. We report the clinical and radiological manifestations in 42 ADO II patients. To our knowledge, this is the largest series reported so far. Our inclusion criterion was presence on radiographs of the spine of vertebral endplate thickening, producing the classic sandwich vertebra appearance. We found various patterns of sandwich vertebra, of which we provide a description to assist physicians in diagnosing ADO II. The classic bone-within-bone appearance was present in most but not all skeletal sites. The radiological penetrance of the disease was high (90%) and increased after 20 years of age. As many as 81% of our patients experienced clinical manifestations. Fractures were common (78% of patients) and healed slowly. Hip osteoarthritis developed in 27% of patients and required arthroplasty in 9 of the 16 affected hips. Nonmandibular osteomyelitis occurred in 4 cases (11%). Twenty-four percent of patients had thoracic or lumbar scoliosis. Orthopedic surgery was performed in 52.8% of patients, of whom half had at least three surgical procedures for internal fracture fixation, arthroplasty, limb deformity correction, or treatment of surgical complications. There was a high rate of surgical complications including nonunion, infection, prosthesis loosening, and intraoperative fractures. Nearly two-thirds of patients (64%) had stomatologic manifestations, including mandibular osteomyelitis in 4 patients (11%). Cranial nerve involvement responsible for hearing loss, bilateral optic atrophy, and/or facial palsy was present in 14 patients but was clearly attributable to ADO II in only 6 cases (16%). This large series sheds new light on several aspects of ADO II, most notably the possibility of severe clinical complications. Although other forms of osteopetrosis are considerably more severe, the name "benign osteopetrosis" previously used for ADO II is probably a misnomer.

Adolescent↗
PubMed1999

New' manifestations of BOR syndrome.

Defined in 1975, branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder consisting of branchial arch anomalies, hearing loss, and urinary tract malformations. It is the prototype of the non-chromosomal syndromes that have branchial arch anomalies as major clinical manifestations: BOR, branchio-otic (BO), branchio-otic-facial (BOF), and Townes-Brock syndromes. Subsequently, several clinical manifestations have expanded its phenotype. Retrospective analysis of 31020 families evaluated between January 2, 1982 and December 31, 1996 at the genetic clinics of the University of South Florida, showed seven probands with BOR/?BOR syndrome. Four of the probands and affected relatives had manifestations that further expanded the phenotype: gustatory lacrimation, hypospadias, imperforate anus, osteosclerosis, microcephaly, hypodontia, congenital vocal cord paresis, and congenital incomplete fixation of the transverse colon. Thus, BOR/ ?BOR syndrome appears to be a clinically and genetically heterogeneous multiorgan/system entity that manifests itself predominantly during organogenesis. Clinicians and researchers alike should be cognizant of the expanded phenotype and heterogeneity, while in the DNA laboratories the latter will be sorted out.

Adult↗
PubMed1986

Importance of quantitative histology of bone changes in monoclonal gammopathy.

Quantitative histology of bone changes, using undecalcified transiliac bone biopsies (UTBB), was performed blindly in 46 individuals with monoclonal gammopathy (MG), including 17 with MG of undetermined significance (MGUS) and 29 with overt multiple myeloma (MM). Three MGUS presented an excess of osteoclastic resorption (OR) in the vicinity of clusters of tumour cells and developed overt B cell malignancies, chronic lymphocytic leukaemia, Waldenström's disease and MM respectively. On the other hand, MGUS with normal OR remained stable (median follow-up = 28 months), with one exception who developed a systemic amyloidosis. In MM, excessive OR was only observed in areas invaded by myeloma cells. OR was frequently normal in active MM lacking myeloma cells in UTBB. Active MM without lesions on radiography had excessive OR. IgA and pure Bence Jones MM appeared more osteoclastic than IgG cases (P less than 0.05). Of major interest was the finding that one third of MM presented histological bone changes similar to osteoporosis, osteosclerosis or osteoblastic metastasis. Two major findings must be emphasized from the current data: UTBB could be of major interest for the early detection of a B cell malignancy; heterogeneity of myeloma bone condition is unexpected. If some changes appear directly related to the tumour (i.e. excessive OR or osteoblastic dysfunction), some others are probably accidentally associated with it (i.e. osteoporosis), both needing treatment other than chemotherapy.

Aged↗
PubMed1978

Skeletal X-ray findings and bone histology in patients on hemodialysis.

X-ray films of the hand skeleton (mammography technique), serum chemistry, and quantitative bone histology (micromorphometry of undecalcified sections, iliac crest spongiosa) were compared in 25 patients on maintenance hemodialysis. The X-ray findings correlated better with serum PTH levels than with bone histology. Of all radiological signs of renal osteodystrophy, pronounced subperiosteal resorption (radial aspect, second finger, middle phalanx) and periosteal new bone formation (middle phalanx) correlated best with histological indicators of osteitis fibrosa. These signs were never seen in control patients. Acroosteolysis (endphalanx) and intracortical or endosteal resorption (middle phalanx) were less specific (i.e., seen even in the absence of metabolic bone disease) and correlated less with bone histology. Osteosclerosis in iliac cancellous bone was paralleled by abnormal texture of spongy bone in the proximal metaphysis of the middle phalanx (second finger).

Adult↗
PubMed1995

Linkage of pycnodysostosis to chromosome 1q21 by homozygosity mapping.

Pycnodysostosis is an autosomal recessive sclerosing skeletal dysplasia of unknown aetiology which is inherited with complete penetrance. The clinical features, fully delineated in 1962 by Maroteaux & Lamy and by Andrén et al., include osteosclerosis, acro-osteolysis of the distal phalanges, bone fragility, clavicular dysplasia, reduced stature and skull deformities with delayed suture closure. Although rare, pycnodysostosis has attained prominence because the French artist Henri de Toulouse-Lautrec was retrospectively diagnosed as having been affected with this disorder. For rare autosomal recessive traits, homozygosity mapping provides a powerful approach to disease gene mapping. We have now used this approach to map the locus for pycnodysostosis. Following a genome-wide search in a large Arab family with 16 affected relatives, we established linkage to a narrow region on chromosome 1q21, with a maximal lod score of 11.72. A single marker, D1S498, was homozygous-by-descent in all affecteds and defined the gene locus to a region of 4 cM. Two candidate genes in the region--the interleukin-6 receptor gene (IL6R) and the myeloid cell leukaemia-1 gene (MCL1)--are involved in the differentiation of monocyte/macrophages into osteoclasts, the most likely site of the primary defect in pycnodysostosis.

Abnormalities, Multiple↗
PubMed1990

Neurological complications of endemic skeletal fluorosis, with special emphasis on radiculo-myelopathy.

The results of surveys carried out between 1976 and 1985 in the fluorosis-endemic area of the Ethiopian Rift Valley is summarised, with emphasis on the neurological complications resulting from the crippling osteofluorosis. The neurological manifestations in the forms of myelopathy with and without radiculopathy (respectively 72% and 28%) occurred after exposure to high fluoride (greater than 4 ppm) for longer than 10 years. These deficits were clearly found to be a consequence of fluoride deposition in bones, resulting in generalised sclerosis and osteophytosis, with reduction in the diameter of the intervertebral foramina and of the spinal conal. Advanced osteosclerosis commonly causes severe spastic quadriparesis in flexion, accompanied by distressing spasms and urinary incontinence. The dilemma of these medical problems in relation to the agro-industrial economic developments of the Ethiopian Rift Valley is discussed.

Agriculture↗
PubMed2004

The Fos-related antigen Fra-1 is an activator of bone matrix formation.

Ectopic expression of the transcription factor Fra-1 in transgenic mice leads to osteosclerosis, a bone disorder characterized by increased bone mass. The molecular basis for this phenotype is unknown and Fra-1 functions cannot be studied by a conventional loss-of-function approach, since fra-1-knockout mice die in utero likely due to placental defects. Here we show that the lethality of fra-1-knockout mice can be rescued by specific deletion of Fra-1 only in the mouse embryo and not in the placenta. Mice lacking Fra-1 (fra-1(delta/delta)) are viable and develop osteopenia, a low bone mass disease. Long bones of fra-1(delta/delta) mice appear to have normal osteoclasts but express reduced amounts of bone matrix components produced by osteoblasts and chondrocytes such as osteocalcin, collagen1a2 and matrix Gla protein. The gene for matrix Gla protein seems to be a specific target of Fra-1 since its expression was markedly increased in the long bones of fra-1-transgenic mice. These results uncover a novel function of Fra-1 in regulating bone mass through bone matrix production by osteoblasts and chondrocytes.

Animals↗