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Results for “OSTEOPETROSIS”

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At least 199 records · Page 11Linked to original sources

PubMed1989

Biomechanical competence of iliac crest trabecular bone in autosomal dominant osteopetrosis type I.

Cylindrical horizontal iliac crest trabecular bone biopsies were obtained from 9 patients with autosomal dominant osteopetrosis type I and 18 normal controls of comparable age/sex match. Maximum compressive stress, maximum stiffness, energy absorption capacity and maximum strain were calculated from load-deformation curves after a compression test. Ash density of the bone samples was measured after incineration. The maximum compressive stress was significantly increased in the patient group (12.6 +/- 2.6 (SE) MPa vs. 3.3 +/- 0.4 MPa, p less than 0.01), as was the ash density (0.61 +/- 0.05 g/cm3 versus 0.27 +/- 0.02 g/cm3, p less than 0.01). After correction for ash density (normalized maximum stress) the strength of the trabecular bone samples was still significantly increased in the patients (19.7 +/- 6.4 MPa x cm3/g versus 12.0 +/- 1.2 MPa x cm3/g, p less than 0.01). The maximum stiffness and energy absorption capacity were higher in the patients (p less than 0.01), with a corresponding lower maximum strain value (p less than 0.05). The maximum compressive stress correlated closely to the maximum stiffness and energy absorption capacity in both patients and controls, whereas no correlation to maximum strain was found. The maximum compressive stress thus seems to be representative for the two other biomechanical parameters. No significant correlations between age and maximum compressive stress (R = 0.38), ash density (R = 0.08), or normalized maximum stress (R = 0.45) were observed in type I osteopetrosis, whereas significant age-dependent decreases in maximum compressive stress (R = -0.65, p less than 0.02) and in ash density (R = -0.57, p less than 0.02) were observed in normal individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Structural and histomorphometric studies of iliac crest trabecular and cortical bone in autosomal dominant osteopetrosis: a study of two radiological types.

Cylindrical iliac crest biopsies were obtained from 16 patients with autosomal dominant osteopetrosis after intravital double labeling with tetracycline, and compared with normal age- and sex-matched controls. Ten patients had the radiological type I (5 women, 5 men, aged 17-62 years, mean 42) characterized by diffuse, symmetrical osteosclerosis and enlarged thickness of the cranial vault. Six patients had type II (2 women, 4 men, aged 22-44 years, mean 36), where "Rugger Jersey Spine" and endobone are characteristic findings. Structural studies of cortical and trabecular bone were performed, and trabecular bone resorption and formation rates were studied using dynamic histomorphometry. The total biopsy length (C. Wi) were increased in type I (p less than 0.05), and unchanged in type II. Both types showed increased cortical width (Ct. Wi) (p less than 0.01 and p less than 0.05, respectively), and decreased fractional width of cancellous bone (Cn.Wi/C.Wi) (p less than 0.01 and p less than 0.05). The fractional trabecular bone volume (BV/TV) and trabecular thickness (Tb. Th) were both significantly increased in type I (p less than 0.05), while resorptive and formative indices of trabecular bone remodeling were normal. No difference was found in trabecular bone balance, which was slightly positive in both patients and controls. In type II osteopetrosis the eroded surfaces (OS/BS) were significantly increased (p less than 0.01), as was the total resorptive period RP) (p less than 0.05). The resorption depth (R.D.) was normal, while the resorption rate (MRR) was insignificantly decreased. Many big multinucleated osteoclasts were seen in this type suggesting defective resorptive function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Thermal stability of cortical bone collagen in relation to age in normal individuals and in individuals with osteopetrosis.

The thermal stability of cortical bone collagen was determined in iliac crest biopsies obtained from 41 normal individuals (21 women aged 20-96 years and 20 men aged 21-84 years) and 8 individuals with autosomal dominant osteopetrosis type I (4 women and 4 men aged 17-63 years). The cortical bone was decalcified and the bone matrix was cut into 80-microns-thick freeze sections parallel to the bone surface. Circular specimens punched out from the sections were used for determination of area shrinkage during gradual heating and shrinkage temperature, Ts (representing the temperature for 50% of the area shrinkage). In normal men, Ts was not found to decrease until the age of 60-65 years, but was markedly decreased in the elderly individuals. In normal women, Ts varied considerably throughout the age range tested, without relationship to age. In contrast to age-matched controls, Ts decreased with age in men with osteopetrosis, whereas Ts in affected women was neither related to age nor different from the highly variable values found in age-matched normal women. Previous findings in rats indicate that Ts decreases with the chronological age of the bone collagen. The present results agree with these findings, which imply that a reduction in turnover rate of bone results in an increasing age and a reduced Ts of the constituent collagen. Following this assumption, the turnover rate of bone seems to be more variable in women than in men and reduced in osteopetrotic men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Autosomal dominant osteopetrosis and maxillomandibular osteomyelitis.

Osteopetroses represent a heterogeneous group of rare, hereditary bony dysplasias. They range from a devastating neurometabolic disease (including severe malignant infantile osteopetrosis) to 2 more benign conditions principally affecting adults: autosomal dominant osteopetrosis (ADO) type I and type II. The present study describes the maxillofacial manifestations associated with the 2 subgroups of ADO. In this paper, we present the oldest patient described in the literature with ADO type I (76 years old). We also document the first ADO type II patient described in the literature with synchronic osteomyelitis of the mandible and the maxilla.

Aged↗

PubMed2005

Total hip arthroplasty in osteopetrosis using computer-assisted fluoroscopic navigation.

Hybrid total hip arthroplasty with computer-assisted fluoroscopic navigation was performed on a patient with osteoarthritis due to an autosomal dominant form of osteopetrosis. The surgical procedures were difficult because the bone was extremely hard and brittle with obliteration of the medullary cavity. Especially, preparation of a femoral canal for the stem was technically challenging and required changes from a conventional surgical procedure. Therefore, we used a computer-assisted fluoroscopic navigation system to create the femoral cavity for the stem, and an accurate placement of the prosthesis was achieved. Navigation guidance can be a useful tool when performing arthroplasty in patients with hip osteoarthritis associated with osteopetrosis.

Arthroplasty, Replacement, Hip↗

PubMed2006

Neonatal hematopoietic stem cell transplantation cures oc/oc mice from osteopetrosis.

OBJECTIVE: Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disorder affecting osteoclast function. Fifty percent of the patients have a mutation in the TCIRG1 gene coding for one subunit of an osteoclast proton pump. The only curative treatment is hematopoietic stem cell transplantation (SCT). The oc/oc mouse has a mutation in the gene homologous to TCIRG1 and its expected lifespan is only 3 to 4 weeks. Previous attempts to cure these mice with SCT have been unsuccessful. We wanted to determine if early hematopoietic SCT using enriched and MHC-matched stem cells can cure oc/oc mice from osteopetrosis. METHODS: One- and 8-day-old oc/oc and control mice were radiated with 200, 400, or 600 cGy and transplanted intraperitoneally with 1 or 5 x 10(6) normal lineage-depleted bone marrow cells. Blood, x-ray, and pathology analyses were performed on transplanted mice. RESULTS: All 1-day-old mice irradiated with 400 cGy and transplanted with 5 x 10(6) cells survived long term. An engraftment level of 20% is sufficient to correct most features of the disease. X-ray and histopathology examination of transplanted animals showed normalization of bone structure. However, although a correction of bone structure occurred, the transplanted oc/oc mice were smaller in size than their littermates. In contrast to untreated animals, oc/oc mice developed teeth after transplantation, but with abnormal structure and shape making them unusable. CONCLUSION: We have shown that this murine form of IMO is curable with neonatal SCT using enriched stem cells.

Animals↗

PubMed2006

Osteopetrosis complicated by osteomyelitis of the mandible: a case report including characterization of the osteopetrotic bone.

A case of a 53-year-old Japanese man with osteopetrosis complicated by osteomyelitis of the mandible is presented. The patient experienced frequent exacerbations and remissions of osteomyelitis of the mandible, despite undergoing several surgical debridements and sequesterectomies with appropriate antimicrobial therapy, for 3 years. Finally, the patient underwent mandibular segmental resection followed by reconstruction with a titanium reconstruction plate. Fifty-one months after surgery there is no evidence of recurrent osteomyelitis of the mandible, suggesting that a more radical surgical approach is preferable for patients with severe complications resulting from osteopetrosis. Also presented here are the histopathological and biochemical features of the osteopetrotic bone. The osteopetrotic cortical bone was morbidly sclerotic with compact and irregular laminations. Degradation of osteocytes in the osteopetrotic bone was due to hypoxia and lack of nutrition resulting from osteosclerosis. There were no significant differences between osteopetrotic and normal bone according to X-ray diffraction, Fourier transform infrared spectroscopy, collagen content or mineral content. Micro-Vickers hardness measurements showed that osteopetrotic bone was significantly harder than normal bone, and the standard deviation of hardness was greater in osteopetrotic bone. Such a loss of integrity in osteopetrotic bone is considered to be a primary reason for the greater risk of a variety of complications such as pathological fracture and refractory osteomyelitis.

Bone Plates↗

PubMed1990

Chorioretinal degeneration in infantile malignant osteopetrosis.

We studied two patients who had infantile malignant osteopetrosis, severe visual loss, and diminished electroretinogram amplitudes with visible macular chorioretinal degenerative changes. The findings support the hypothesis that a subgroup of patients with infantile malignant osteopetrosis exists in whom the visual loss is caused by a primary retinal degeneration that may be associated with generalized central nervous system neuronal degeneration.

Choroid Diseases↗

PubMed1984

Fatal overwhelming postsplenectomy sepsis following autologous splenic transplantation in severe congenital osteopetrosis.

We report a boy with severe congenital osteopetrosis who underwent splenectomy at age 4, with simultaneous transplantation of portions of the spleen into the anterior rectus compartments. Despite demonstrated survival and partial functioning of the splenic implants, the patient died 9 years later from an overwhelming postsplenectomy infection (OPSI). This report suggests that the presence of the amount of retained splenic tissue transplanted in this case after splenectomy ultimately provides relatively ineffective protection against OPSI in congenital osteopetrosis.

Adolescent↗

PubMed1979

The hematopoietic effects of prednisone therapy in four infants with osteopetrosis.

Sequential hematologic studies were performed in four infants with malignant osteopetrosis who received prednisone. Prednisone therapy resulted in decreased liver and spleen size, decreased numbers of circulating immature blood cells, and increased hemoglobin concentration and platelet counts in all infants. The quantity and quality of hematopoietic tissue in bone marrow biopsies improved during prednisone therapy but showed no significant improvement without therapy. Sequential indium 111 chloride scans in one infant showed increased uptake in long bones and pelvis and decreased uptake in liver and spleen during therapy. We conclude that prednisone therapy of infantile osteopetrosis results in increased bone marrow hematopoiesis and decreased extramedullary hematopoiesis.

Hematopoiesis↗

PubMed1980

Osteopetrosis: further heterogeneity.

A form of osteopetrosis is described in two sibs which differs from the well-established autosomal dominant and recessive forms. The clinical course is mild with no evidence of clinically important encroachment upon the bone marrow or cranial nerve foramina; the skeletal radiographs show a mild generalized increase in bone density and metaphyseal modeling defects affecting primarily the distal femurs. The inheritance pattern is compatible with either an autosomal or X-linked recessive mode. The histologic features are distinct as well, and suggest that the pathogenesis of the condition differs from that of the usual forms of osteopetrosis.

Child↗

PubMed2001

Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man.

Chloride channels play important roles in the plasma membrane and in intracellular organelles. Mice deficient for the ubiquitously expressed ClC-7 Cl(-) channel show severe osteopetrosis and retinal degeneration. Although osteoclasts are present in normal numbers, they fail to resorb bone because they cannot acidify the extracellular resorption lacuna. ClC-7 resides in late endosomal and lysosomal compartments. In osteoclasts, it is highly expressed in the ruffled membrane, formed by the fusion of H(+)-ATPase-containing vesicles, that secretes protons into the lacuna. We also identified CLCN7 mutations in a patient with human infantile malignant osteopetrosis. We conclude that ClC-7 provides the chloride conductance required for an efficient proton pumping by the H(+)-ATPase of the osteoclast ruffled membrane.

Adenosine Triphosphatases↗

PubMed1986

Bone-marrow transplantation for immunodeficiencies and osteopetrosis: European survey, 1968-1985.

In this retrospective analysis of allogeneic bone-marrow transplantation (BMT) carried out between 1969 and 1985 at fourteen European centres in 162 patients with sixteen different types of inherited immunodeficiencies and osteopetrosis, the overall survival with functional grafts was 51.7% (85 patients), with a minimum follow-up of 5 months. In patients with severe combined immunodeficiency HLA-matched (n = 41) and T-cell-depleted HLA-mismatched BMT (n = 46) resulted in 68% and 57% disease-free survival, respectively; after HLA-mismatched transplants, older age (greater than 6 months) and adenosine-deaminase deficiency resulted in poorer survival. Eight other lethal immunodeficiencies, including profound T-cell deficiencies, Wiskott-Aldrich syndrome, Kostmann syndrome, LFA-1/CR 3/p150,95 deficiency, and Chediak-Higashi syndrome as well as malignant osteopetrosis, have been successfully treated by BMT. In this group, survival with functional graft was 47% with HLA-matched and 29% with T-cell-depleted HLA-mismatched BMT. Engraftment failure was the major complication in this group. Poorer prognosis was associated with older patients, profound T-cell deficiencies, and the degree of HLA incompatibility.

Adolescent↗

PubMed1990

Infantile osteopetrosis complicating neuronal ceroid lipofuscinosis.

An autopsy case of infantile osteopetrosis complicating neuronal ceroid-lipofuscinosis is reported. Autopsy revealed generalized sclerosis and thickening of cortical and spongy bones, formation of mineralized cartilagenous tissues, and narrowing of the marrow cavities associated with decreased hematopoietic cell components. Around the thickened bone trabecles, osteoclasts lacked a ruffled border and clear zone along the cell membrane facing the bone matrix surface. The brain was markedly atrophic with neuronal cell loss and focal gliosis, and the remaining neuronal cells accumulated brown granular pigments, which were confirmed histochemically and electron-microscopically to be ceroid and lipofuscin. In the cerebral medulla, the development of myelin sheaths was extremely poor. Also, the occurrence of Lex type glycolipids and GM3 and the apparent absence of cerebroside and cerebroside sulfate were proved by biochemical analysis, suggesting that the brain was still in a stage of embryonic development or still in the process of differentiation. Except for one suggestive case, this is the first case of complicating neuronal ceroid-lipofuscinosis in infantile osteopetrosis.

Atrophy↗

PubMed1991

Osteopetrosis presenting with paroxysmal trigeminal neuralgia. A case report.

Osteopetrosis is a rare disease of unknown aetiology. The relentless bone growth may progressively obliterate the various craniofacial skeletal foramina leading to nerve compression and a diversity of neurological disorders. A case is reported of a 37-year-old woman who was seen because of frequent attacks of paroxysmal trigeminal neuralgia (PTN); other orofacial neurologic deficits and generalised craniofacial skeletal thickening. The prompt recognition and management of associated disorders such as PTN is emphasized. Despite the lack of definitive treatment modalities for both osteopetrosis and PTN, the patient's quality of life must be sustained.

Adult↗

PubMed2002

Macrophage colony-stimulating factor and receptor activator NF-kappaB ligand fail to rescue osteoclast-poor human malignant infantile osteopetrosis in vitro.

Malignant infantile osteopetrosis (MIOP) is a disease characterized by failure in bone resorption, leading to dense fragile bones with a severely reduced bone marrow cavity. Normal or increased numbers of osteoclasts are present in the common variant of this disease; in such cases, the defect is likely to be inherent to the mature osteoclast and can be cured by bone marrow transplantation. However, MIOP also results from failure of osteoclast formation (osteoclast-poor MIOP). We report on two infants diagnosed with osteoclast-poor MIOP and utilize modern cell culture techniques to investigate the pathogenesis of disease. Peripheral blood mononuclear cells (PBMNCs) from these children were cultured in the presence of recombinant macrophage colony-stimulating factor and receptor activator NF-kappaB ligand for up to 3 weeks. Control cultures included PBMNCs from age-matched children, one of whom had an osteoclast-rich form of MIOP. Formation of osteoclasts (cells coexpressing vitronectin receptor and F-actin rings) occurred in all the control cultures. Significant bone resorption occurred in cultures from PBMNCs of the healthy individuals, whereas almost no bone resorption occurred in the osteoclast-rich MIOP cultures. In contrast, PBMNC cultures from the osteoclast-poor MIOP child formed only very occasional small F-actin ring-positive osteoclasts, which coexpressed vitronectin receptor and cathepsin K, and extremely rare foci of resorption. Because neither macrophage colony-stimulating factor nor receptor activator NF-kappaB ligand rescued the defect in osteoclast differentiation in the two cases of osteoclast-poor MIOP in vitro, there would be little benefit in treating these children with either of these recombinant proteins. Finally, these results demonstrate that this experimental culture model replicates the human osteopetrosis phenotype observed in vivo and should prove useful in analyzing the pathogenesis of the various forms of MIOP.

Actins↗

PubMed2002

Novel mutations in the a3 subunit of vacuolar H(+)-adenosine triphosphatase in a Japanese patient with infantile malignant osteopetrosis.

A case of infantile malignant osteopetrosis is described. The patient died from respiratory hemorrhage at 7 months of age despite treatment that included high doses of active vitamin D and administration of interferon-gamma. A postmortem examination revealed the presence of many osteoclasts in the bone, which lacked ruffled borders. This observation was consistent with the histology of bone reported in Atp6i-knockout mice, which lack the gene encoding the a3 subunit of vacuolar-type H(+)-adenosine triphosphatase (ATPase). Sequence analysis of the TCIRG1 gene encoding the a3 subunit revealed two novel mutations: a deletion/insertion mutation in exon 9 and a T-to-C transition at the splice donor site of intron 19. The former mutation caused a frame shift and premature stop codon. The latter was associated with abnormal splicing, which was confirmed by sequencing the products amplified by reverse transcription-polymerase chain reaction (RT-PCR), using total RNA from the liver specimen as template. Although several mutations in the TCIRG1 gene in infantile malignant osteopetrosis have been reported in other populations, this is the first case of a Japanese patient with a mutation identified in this gene. These results support the important role of the subunit in the function of the proton pump.

Codon, Terminator↗

PubMed2003

Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human.

The spontaneous mouse grey-lethal (gl) mutation is responsible for a coat color defect and for the development of the most severe autosomal recessive form of osteopetrosis. Using a positional cloning approach, we have mapped and isolated the gl locus from a approximately 1.5 cM genetic interval. The gl locus was identified in a bacterial artificial chromosome (BAC) contig by functional genetic complementation in transgenic mice. Genomic sequence analysis revealed that the gl mutation is a deletion resulting in complete loss of function. The unique approximately 3 kb wild-type transcript is expressed primarily in osteoclasts and melanocytes as well as in brain, kidney, thymus and spleen. The gl gene is predicted to encode a 338-amino acid type I transmembrane protein that localizes to the intracellular compartment. Mutation in the human GL gene leads to severe recessive osteopetrosis. Our studies show that mouse Gl protein function is absolutely required for osteoclast and melanocyte maturation and function.

Amino Acid Sequence↗