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Results for “OSTEOPETROSIS”

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PubMed1988

Osteoclasts in human osteopetrosis contain viral-nucleocapsid-like nuclear inclusions.

We report the discovery of nuclear inclusions in the osteoclasts of three unrelated patients with benign osteopetrosis that resemble the osteoclast inclusions characteristic of Paget's disease of bone. These inclusions are morphologically and dimensionally identical to the nucleocapsids of a virus of the Paramyxoviridae family. Supporting a possible viral association with benign osteopetrosis in the observation of the presence of antigens of respiratory syncytial virus, measles virus, and/or mumps virus in the cells of all five patients whose paraffin-embedded bone specimens were tested. These included two patients whose osteoclasts contained nuclear inclusions. No patients with the malignant form of the disease have been studied. There is as yet no proof that a virus is causally related to human osteopetrosis even though a virus can produce an avian form of the disease.

Adult↗

PubMed1992

Case report 718. Osteopetrosis with carbonic anhydrase II deficiency.

This case report describes the clinical and radiographic findings in an adult woman with osteopetrosis with carbonic anhydrase II deficiency. This uncommon entity is the only one of the five variants of osteopetrosis with a well-defined inborn error of metabolism. The radiographic combination of osteopetrosis and cerebral calcification should suggest the diagnosis, which can be confirmed with a blood sample demonstrating carbonic anhydrase II deficiency.

Adult↗

PubMed1993

Malignant osteopetrosis: c-src kinase is not reduced in fibroblasts.

Targeted disruption of the c-src gene leads to a severe form of osteopetrosis in mice [2]. As the c-src gene is expressed in all tissues and cells tested, we have analyzed fibroblasts from three individuals with malignant, congenital osteopetrosis for the expression of c-src at the protein level. No differences could be detected in c-src protein and c-src kinase activity levels between fibroblasts from healthy controls and affected individuals. Thus, impairment of c-src function as an etiological factor in human osteopetrosis appears unlikely in the individuals investigated.

CSK Tyrosine-Protein Kinase↗

PubMed1995

Benign osteopetrosis, in a patient with sickle-cell beta+ (beta+) thalassaemia.

We describe a case of a patient suffering from benign osteopetrosis and sickle-cell beta+ thalassaemia. This case allows us to study the combined action of various pathogenetic mechanism involved in both diseases. The coexistence of osteopetrosis with sickle-cell beta+ thalassaemia seems to intensify the anaemia and sickling, but does not appear to modify the course of the osteopetrosis.

Adult↗

PubMed1997

[Osteomyelitis of the facial skull in Albers-Schönberg osteopetrosis].

Albers-Schönberg osteopetrosis, a rare heritable bone disease with autosomal dominant or recessive transmission, is generally characterised by diffuse sclerosis of the whole skeleton accompanied by pathological bone fragility and delayed physical development, profound intractable myelophthisic anaemia, neurological deficits, and osteomyelitis, especially of the jaws and the skull. The precise aetiology of the osteopetrosis is not clear. Therefore therapy is restricted to alleviation of symptoms. In this study the case of a patient suffering from the benign form of osteopetrosis is presented. Osteomyelitis of the skull was treated successfully 2 years after the removal of lower and upper jaw teeth by a combined multistage surgical and antibiotic approach.

Abscess↗

PubMed1997

Autosomal dominant osteopetrosis: report of a Norwegian family with radiographic or anamnestic findings differing from the generally accepted classification.

OBJECTIVE: Autosomal dominant osteopetrosis is currently divided into two, possibly three subgroups. The present study of a Norwegian family, however, suggests that such a grouping is not generally valid. PATIENTS AND METHODS: A Norwegian family has been studied over four generations. Information about the two older generations was obtained mainly from hospital files and by interviewing members of the family. Radiographs were obtained from the two younger generations. RESULTS AND CONCLUSION: Of a total 14 family members, nine patients consisting of six women and three men were studied. Within the same family, patients could be classified as belonging to different subgroups of osteopetrosis defined elsewhere, and at least three of them could be classified as belonging to more than one group. The present study suggests that the generally accepted classification of autosomal dominant osteopetrosis should be questioned.

Female↗

PubMed1981

Marrow transplantation for juvenile osteopetrosis.

Two children with the juvenile form of osteopetrosis were treated with marrow transplants from their HLA identical siblings. Following transplantation each child exhibited extensive bone reabsorption with a marked augmentation of osteoclastic function attributable to donor osteoclasts, including remodeling of bone with expansion of intramedullary hematopoiesis and correction of associated abnormalities of thymic factor and natural killer cells. Osteopetrosis ultimately recurred in one patient in whom engraftment of donor hematopoietic elements was not achieved. Our studies indicate that marrow transplantation will correct osteopetrosis but that permanent reconstitution necessitates sustained engraftment of marrow precursors of cells with osteoclastic activity.

Bone Marrow Transplantation↗

PubMed1991

Decreased thyroid hormone-stimulated oxygen consumption and glucose uptake in mononuclear blood cells from patients with autosomal dominant osteopetrosis type I.

Nine patients, from four different families, with autosomal dominant osteopetrosis were investigated. They all had roentgenological type I disease, characterized by universal, symmetrical osteosclerosis and enlarged thickness of the cranial vault. All patients appeared clinically euthyroid. Thyroxine (T4) and tri-iodothyronine (T3) induced oxygen consumption and glucose uptake were studied in vitro in mononuclear blood cells from patients and control persons. Unstimulated oxygen consumption from patients and controls did not differ, and no difference in unstimulated glucose uptake was observed. The increase in T4 and T3 stimulated oxygen consumption was significantly lower in cells from patients with osteopetrosis (T4: 0.007 +/- 0.004 mumol/mg DNA per h, T3: 0.011 +/- 0.004 mumol/mg DNA per h) compared with controls (T4: 0.017 +/- 0.003 mumol/mg DNA per h, T3: 0.023 +/- -0.013 mumol/mg DNA per h; p less than 0.05, p less than 0.05). Cellular glucose uptake after T4 and T3 stimulation was significantly lower in patients (T4: 0.032 +/- 0.017 mmol/l per mg DNA per h, T3: 0.02 +/- 0.017 mmol/l per mg DNA per h) compared with controls (T4: 0.09 +/- 0.017 mmol/l per mg DNA per h, T3: 0.08 +/- 0.01 mmol/l per mg DNA per h; p less than 0.05, p less than 0.01). The reduced oxygen consumption and glucose uptake indicate thyroid hormone resistance which may be of pathogenetic importance for the development of autosomal dominant osteopetrosis type I.

Adult↗

PubMed1988

Osteomyelitis of the mandible associated with osteopetrosis: report of a case.

A 45-year-old Nigerian housewife with chronic osteomyelitis associated with osteopetrosis is described and discussed. Haematological and radiographical investigations on routine admission led to the secondary diagnosis of osteopetrosis. To our knowledge, this is the first case of osteomyelitis of jaws associated with osteopetrosis reported in an African.

Female↗

PubMed1991

Morphologic features of bone in human osteopetrosis.

Trabecular bone biopsies obtained from six patients with malignant osteopetrosis, one patient with benign osteopetrosis, and two controls were examined by light and electron microscopy. Osteopetrotic osteoclasts showed little to no signs of active involvement in bone resorption. Ruffled borders and clear zones were absent in most cells. In all patients there were large numbers of osteoclasts. Numbers of osteoblasts, bone lining cells, and bone marrow stromal cells were extremely low in all patients with malignant osteopetrosis. In six of the patients a mineralized layer of amorphous organic material lacking collagen fibrils was seen covering large areas of the bone or cartilage matrix. We suggest that this layer represents a pathological calcification on which subsequently organic material has accumulated. The abnormalities in osteopetrotic bone are discussed in the light of the pathogenesis of this disease.

Bone and Bones↗

PubMedDate not supplied

Histomorphometric and immunocytochemical studies of src-related osteopetrosis.

"Knockout" of the src proto-oncogene in mice resulted in the unexpected development of osteopetrosis which was shown subsequently in 4-6 week old src-mutants to be due to failure of src-mutant osteoclasts to form ruffled borders. Histomorphometric analysis of vertebrae and humeri from 9-10 month old src-mutant mice has revealed that the osteopetrosis persists and that osteoclasts from these older mice also fail to form ruffled borders. Deficiency of src, however, does not impair formation of other complex cytoplasm extensions, such as respiratory cilia or intestinal villi. Immunocytochemistry using antibodies to pp60src has shown that the src tyrosine kinase is not localized along ruffled borders of normal osteoclasts in human bone, but is expressed diffusely throughout their cytoplasm. Furthermore, pp60src is expressed diffusely throughout the cytoplasm of non-resorbing osteoclasts in a human giant cell tumor of bone. These findings indicate that, unlike some other forms of the disorder, remission does not occur in src-deficiency-related osteopetrosis, at least by ten months of age. They also show that high expression of the pp60src protein is not confined to actively resorbing osteoclasts, but can also occur in osteoclasts unattached to bone surfaces, and suggest that there may be a critical substrate for src that is involved in ruffled border formation.

Animals↗

PubMed2006

Osteomyelitis of the mandible associated with autosomal dominant osteopetrosis: a case report.

Osteopetrosis is a rare hereditary bone disorder presenting with variable clinical features and is characterized by an increase in bone density. The main clinical findings of the benign-type of osteopetrosis (autosomal dominant) are fractures and osteomyelitis of the mandible, leading to the detection of the disease. We report a case of autosomal dominant osteopetrosis with secondary mandibular osteomyelitis. Clinical and radiological patterns and treatment evaluation were assessed. The patient was referred for evaluation and treatment of an acute abscess in the left side of the face and osteomyelitis of the mandible. Several imaging studies were performed to assess the lesion and the adjacent bone and soft tissue structures. Treatment consisted of intravenous antibiotic therapy, debridement of the necrotic bone and sequestrum, and extra-oral drainage of the abscess, with submandibular access. Healing was uneventful.

Abscess↗

PubMed2005

Distinct roles of enhancer nuclear factor 1 (NF1) sites in plasmacytoma and osteopetrosis induction by Akv1-99 murine leukemia virus.

Murine leukemia viruses (MLVs) can be lymphomagenic and bone pathogenic. In this work, the possible roles of two distinct proviral enhancer nuclear factor 1 (NF1) binding sites in osteopetrosis and tumor induction by B-lymphomagenic Akv1-99 MLV were investigated. Akv1-99 and mutants either with NF1 site 1, NF1 site 2 or both sites disrupted induced tumors (plasma cell proliferations by histopathology) with remarkably similar incidence and mean latency in inbred NMRI mice. Clonal immunoglobulin gene rearrangement detection, by Southern analysis, confirmed approximately half of the tumors induced by each virus to be plasmacytomas while the remaining lacked detectable clonally rearranged Ig genes and were considered polyclonal; a demonstration that enhancer NF1 sites are dispensable for plasmacytoma induction by Akv1-99. In contrast, X-ray analysis revealed significant differences in osteopetrosis induction by the four viruses strongly indicating that NF1 site 2 is critical for viral bone pathogenicity, whereas NF1 site 1 is neutral or moderately inhibitory. In conclusion, enhancer NF1 sites are major determinants of osteopetrosis induction by Akv1-99 without significant influence on viral oncogenicity.

Animals↗

PubMed2000

Reversal of optic canal stenosis in osteopetrosis after bone marrow transplant.

PURPOSE: To describe a patient with infantile osteopetrosis and optic atrophy secondary to optic canal stenosis who demonstrated optic canal enlargement after bone marrow transplant. METHODS: Case report. A 3-month-old infant with infantile "malignant" osteopetrosis underwent ophthalmic examination, including visual evoked potentials, electroretinogram, and computed tomography (CT). Bone marrow transplant was performed at 8 months of age. RESULTS: Examination revealed visual loss and optic atrophy, left eye greater than right eye, secondary to optic canal stenosis. Flash visual evoked potentials revealed a normal waveform in both eyes with increased latency in the left eye. Electroretinogram was normal in both eyes. CT after bone marrow transplant showed enlargement of the optic canals. Vision remains stable 43 months after bone marrow transplant. CONCLUSIONS: Bone marrow transplant in infantile osteopetrosis may be followed by reversal of optic canal stenosis and preservation of vision.

Bone Marrow Transplantation↗

PubMed2002

Mutation of macrophage colony stimulating factor (Csf1) causes osteopetrosis in the tl rat.

Osteopetrosis results from a heterogeneous group of congenital bone diseases that display inadequate osteoclastic bone resorption. We recently mapped tl (toothless), a mutation that causes osteopetrosis in rats, to a genetic region predicted to include the rat Csf1 gene. In this study, we sequenced the coding sequence of the rat Csf1 gene to determine if a mutation in Csf1 could be responsible for the tl phenotype. Sequencing revealed a 10-base insertion in the coding sequence of mutant animals that produces a frameshift and generates a stop codon early in the mutant Csf1 coding sequence. The 41 amino acid polypeptide predicted to be produced from the Csf1 promoter would have only the first nine amino acids of the wild-type rat protein. These data suggest that osteopetrosis develops in tl/tl rats because they cannot produce functional mCsf, a growth factor required for osteoclast differentiation and activation.

Amino Acid Sequence↗

PubMed1994

Bone marrow transplantation for autosomal recessive osteopetrosis. A report from the Working Party on Inborn Errors of the European Bone Marrow Transplantation Group.

The outcomes of 69 patients who received allogeneic bone marrow grafts for autosomal recessive osteopetrosis in the period between 1976 and 1994 were analyzed retrospectively. Four patients received bone marrow transplants (BMT) without prior myeloablative conditioning; transient osteoclast function was demonstrated in one of them. Sixty-five patients received myeloablative pretreatment. Recipients of a genotypically human leukocyte antigen (HLA)-identical BMT had an actuarial probability for 5-year survival, with osteoclast function, of 79%; recipients of a phenotypically HLA-identical bone marrow graft from a related or unrelated donor, or one HLA-mismatched graft from a related donor, had an actuarial probability for 5-year survival, with osteoclast function, of 38%; patients who received a graft from an HLA-haplotype mismatched related donor had a probability for 5-year survival of only 13%. The main problems in haplotype-nonidentical BMT were graft failure and BMT-related complications such as sepsis, bleeding, and interstitial pneumonia. Osteoclast function developed in all patients with full engraftment. Recovery of osteoclast function was associated with severe hypercalcemia in 24% of the patients with engraftment, especially those older than 2 years of age. At the time of BMT, severe visual impairment was present in 35% of the patients; of the 15 patients who had visual impairment at the time that a successful BMT was performed, two had improvement after BMT (13%). Within the total group, one patient had neurodegeneration. Engraftment of healthy donor cells had no influence on the progression of that abnormality and BMT thus had no beneficial effect on this phenotype of osteopetrosis. In general, however, early BMT remains the only curative treatment for autosomal recessive osteopetrosis.

Actuarial Analysis↗

PubMed1992

Recombinant human interferon gamma therapy for osteopetrosis.

A defect in leukocytic superoxide formation has been demonstrated in patients with congenital osteopetrosis. This leukocyte defect appears to be related to defective bone resorption. Because recombinant human interferon gamma therapy enhances superoxide production in patients with chronic granulomatous disease, we sought to determine whether a similar strategy could reverse the osteopetrotic condition. Interferon gamma, 1.5 micrograms/kg three times a week, was administered by subcutaneous injection for 6 months to eight patients with osteopetrosis. Urinary hydroxyproline and urinary calcium excretion increased markedly during therapy in parallel with a significant decrease in trabecular bone volume. Bone marrow scans demonstrated increased bone marrow production. The hemoglobin concentration, platelet count, and leukocyte production of superoxide increased significantly. No serious infections were encountered during the therapy. These data suggest that interferon gamma administration enhances bone resorption and leukocyte function in patients with osteopetrosis.

Bone Marrow↗

PubMed1981

Osteopetrosis: a scanning electron microscopic study.

Scanning electron microscopic investigation was conducted with bone in a case of osteopetrosis by comparing it with normal cortical bone. The fractured surface of the osteopetrotic bone was devoid of the orderly constructed lamellar haversian system seen in normal bone. It was occupied by a massive smooth cartilaginous matrix containing scattered rough areas of abnormal ossification. Tortuous channels were randomly distributed and corresponded to the abortive marrow spaces. The presence of many irregular fracture lines reflected the fragility of the bone. The findings support the concept of defective remodeling in the pathogenesis of osteopetrosis and provide a further explanation for the abnormal fragility of bone in osteopetrosis.

Adult↗