SEARCH · PubMed Health

Results for “OSTEOPETROSIS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed2002

Localization of the mutation responsible for osteopetrosis in the op rat to a 1.5-cM genetic interval on rat chromosome 10: identification of positional candidate genes by radiation hybrid mapping.

Osteopetrosis is caused by a heterogenous group of bone diseases that result in an increase in skeletal mass because of inadequate osteoclastic bone resorption. In the op osteopetrotic rat, the disease has been linked to a single genetic locus located at the proximal end of rat chromosome 10. In this study, we identified a 1.5-cM genetic interval that contains the mutation. We then generated an improved radiation hybrid (RH) map of this region to identify potential functional and positional candidates for the op gene. Using the rat genome radiation hybrid panel, we mapped 57 markers including 24 genes (14 that have not yet been mapped in the rat) and 10 expressed sequence tag markers. Included in the mapped genes are several candidate genes that might significantly influence the biochemical pathways involved in osteopetrosis. These include genes involved in osteoclast differentiation, apoptosis, and the functional capabilities of mature osteoclasts to resorb bone. Further analysis of the genes and expressed transcripts mapped to this region may yield important insights into the multifactorial control of osteoclast function and the mechanisms of failed bone homeostasis in diseases such as osteopetrosis, osteoporosis, and rheumatoid arthritis in which failed bone homeostasis is an instigating or exacerbating circumstance of the disease process.

Animals↗

PubMed2002

Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13.

The osteopetroses are a heterogeneous group of genetic conditions characterized by increased bone density due to impaired bone resorption by osteoclasts. Within the autosomal dominant form of osteopetrosis, the radiological type I (ADOI) is characterized by a generalized osteosclerosis, most pronounced at the cranial vault. The patients are often asymptomatic but some suffer from pain and hearing loss. ADOI is the only type of osteopetrosis not associated with an increased fracture rate. Linkage analysis in two families with ADOI from Danish origin enabled us to assign the disease-causing gene to chromosome 11q12-13. A summated maximum lod score of +6.54 was obtained with marker D11S1889 and key recombinants allowed delineation of a candidate region of 6.6 cM between markers D11S1765 and D11S4113. Previously, genes causing other conditions with abnormal bone density have been identified from this chromosomal region. The TCIRG1 gene was shown to underly autosomal recessive osteopetrosis (ARO), and, recently, mutations in the LRP5 gene were found both in the osteoporosis-pseudoglioma syndrome and the high bone mass trait. Because both genes map within the candidate region for ADOI, it can not be excluded that ADOI is caused by mutations in either the TCIRG1 or the LRP5 gene.

Adult↗

PubMed1997

Spondylolysis in children who have osteopetrosis.

Five of seven children who were managed for osteopetrosis had either cervical spondylolysis or lumbar spondylolysis, or both. Three of the children had lumbar spondylolysis only, one had cervical spondylolysis only, and one had spondylolysis in both areas. The five patients were followed for an average of forty-one months (range, sixteen to seventy-two months) after the diagnosis of spondylolysis was made. Three of the patients were managed non-operatively with a lumbosacral corset or a thoracolumbosacral orthosis. One of these three patients, who also had cervical spondylolysis and neck pain, had a posterior cervical arthrodesis, but a stable pseudarthrosis developed. All five patients were asymptomatic at the latest follow-up evaluation, although two had had prolonged low-back pain. We believe that cervical or lumbar spondylolysis is present in children who have osteopetrosis more often than has been previously recognized. The spondylolysis in such children often is associated with low-back pain. The symptoms may be part of the initial presentation that leads to the diagnosis of autosomal dominant osteopetrosis. In one patient, the spondylolysis was associated with a grade-I spondylolisthesis at the time of presentation. This was the only patient who had a slip, and the slip did not progress.

Braces↗

PubMed1989

The role of carbonic anhydrase in autosomal dominant osteopetrosis.

Twenty-eight patients with two different radiological types of the autosomal dominant form of osteopetrosis, from six different kindreds, were investigated and compared with age- and sex-matched controls, in order to evaluate the role of carbonic anhydrase in this disorder. There were 15 patients with Type I and 13 with type II osteopetrosis. The concentrations of haemoglobin and bicarbonate were normal in both types and without differences between the types. The concentration of carbonic anhydrase isoenzyme II (CA II) in the erythrocytes did not differ from controls in any of the two types. It is concluded that CA II does not seem to play any pathogenetic role in these two different forms of autosomal dominant osteopetrosis.

Adolescent↗

PubMed1994

Osteopetrosis. A case report.

Osteopetrosis congenita is invariably a fatal disease that is diagnosed within the first decade of the child's life. Although some steps have been taken to overcome this disease by bone marrow transplantation, further research is needed to determine the long-term effectiveness of this treatment. Osteopetrosis tarda is often detected as an incidental finding. Many cases are asymptomatic, yet many patients do suffer from general bone pain, infections, and repeated incidents of pathologic fractures. Such cases may present within the bones of the foot. Treatment is directed at addressing the pathology that may have resulted from the disease state. Osteopetrosis tarda, although rare, can affect the foot. Steps toward treatment of the primary disease entity are still being taken; however, recognition and treatment of the pathology is the primary goal in the adequate treatment of these patients.

Adult↗

PubMed1999

[Osteopetrosis: diagnostic and therapeutic management. Apropos of 5 cases].

PURPOSE OF THE STUDY: The purpose of this study was to analyse 5 cases of osteopetrosis: 2 dominant and 3 recessive forms. MATERIAL AND METHODS: Among five cases of children suffering from osteopetrosis. There were three malignant and two benign forms. Three children affected by malignant form, received a bone marrow transplantation. RESULTS: Only one child who received a bone marrow transplantation was still alive and cured (one died due to transplantation complications, the other child died accidentally). The two children presenting a benign form were periodically followed for iterative fractures and did not present serious complications. DISCUSSION: Our analysis compared to literature review allows us to insist on bone marrow transplantation. This is the only possibility for these children who were condemned in the past. The frequency of iterative fractures on children presenting a dominant form necessitates medical and orthopedic follow-up. Narrowness of the medullary canal, bone fragility contra indicates intramedullary nailing when fixation is indicated. CONCLUSION: Osteopetrosis is an autosomal metabolic bone disease caused by an anomaly of osteoclasts action. Two main forms exist: the dominant form which is benign, and the recessive form which is malignant. Actually recessive forms can be treated and cured by bone marrow transplantation and the children who were in the past condemned are saved. Children with dominant form must be followed up by an orthopaedic surgeon because of bone weakness. The increase in number of cases detected in immigrant populations with a high rate of consanguineous marriages led us to present this study.

Bone Marrow Transplantation↗

PubMed2001

Prenatal diagnosis of malignant osteopetrosis in Bedouin families by linkage analysis.

Autosomal recessive malignant osteopetrosis (MOP) is a lethal disease, unless bone marrow is successfully transplanted. Yet a donor may not always be available, and even when there is one transplantation results are far from optimal. The difficulty in obtaining conclusive results by sonographic and X-ray evaluation of the fetus makes prenatal molecular diagnosis highly desirable. Subsequent to the chromosomal localization of the MOP gene in Arab-Bedouin families from the Negev region in Israel, linkage analysis was used for the prenatal diagnosis of this disease in Bedouin families at risk. Twelve cases were diagnosed, three fetuses were found to be affected, and one of the pregnancies was terminated. The other two pregnancies continued to term and the diagnosis of osteopetrosis was confirmed by X-ray immediately after birth. This is the first report on prenatal diagnosis of autosomal recessive osteopetrosis by linkage analysis.

Adult↗

PubMed1992

Infantile osteopetrosis: report of two cases.

Two cases of infantile osteopetrosis are reported. Both were males aged four and eight months at presentation. They presented with osteosclerotic change of the bone, leukoerythroblastic anemia, optic atrophy, hepatosplenomegaly and frequent infection. The histology of the bone showed thickened bone trabeculae with little osteoclastic activity, although in one patient the number of osteoclasts increased, while in the other they did not. One received a bone marrow transplant (BMT) but died from disseminated cytomegaloviral infection, pulmonary hemorrhage and sepsis. The post-transplant marrow histology showed evidence of engraftment and osteoclastic activity. The other only received a course of prednisolone, which was of little help. His condition has followed a natural course with progressive visual impairment and marrow failure. Our cases suggest that infantile osteopetrosis should be taken into consideration in dealing with infants who present with early marrow failure and that patients of infantile osteopetrosis should receive BMT. BMTs appear to be the only cure. They should be given as early as possible to avoid major consequences and severe infection.

Bone Marrow Transplantation↗

PubMed2003

Bilateral asynchronous humeral shaft fractures in a patient with autosomal dominant osteopetrosis type II (Albers-Schonberg disease).

Osteopetrosis is a rare metabolic disease which presents with fragile osteosclerotic bone. A thirteen-year-old girl with an underlying autosomal dominant osteopetrosis (ADO) type II who sustained a left oblique humeral shaft fracture after trivial trauma is presented. Radiographic results showed many characteristic features of osteopetrosis, including incomplete remodeling of a previous fracture of the contralateral humeral shaft. The authors obtained good healing and alignment of the left humeral shaft fracture by sugar tong slab.

Adolescent↗

PubMedDate not supplied

Osteopetrosis of the jaws.

Osteopetrosis is a rare hereditary condition characterized by increased bone density. The jaws, bones, and teeth invariably are affected and the osteopetrosis is directly proportional with the severity of the disease. This article describes a clinical case of osteopetrosis and reviews the clinicopathologic, radiographic, and treatment features.

Adult↗

PubMed2004

Autosomal malignant osteopetrosis. From diagnosis to therapy.

Osteopetrosis is a heterogeneous family of rare human genetic disorders due to markedly decreased bone resorption. It is one among disorders causing osteosclerosis of the trabecular bone and/or hyperostosis of the cortical bone. Four types of human osteopetrosis have been clearly defined, but patients with atypical symptoms are frequent, suggesting that there are additional forms. The most severe expression of this condition in its malignant form is inherited as an autosomal recessive disorder and it is usually fatal before school age. It presents with failure to thrive, severe hepatosplenomegaly, pancytopenia and nerve compression leading to blindness and deafness during infancy. The case of a 2-month-old female child with severe hepatosplenomegaly, failure to thrive, nystagmus, pancytopenia, gengival hyperplasia, optic atrophy, absent evoked visual potential and increased bone density within the total skeleton, is reported. Diagnosis of autosomal recessive malignant osteopetrosis was established by transiliac bone biopsy. She underwent bone marrow transplantation, but died soon afterwards. This rare and mortal disorder of bone formation requires early diagnosis and immediate pharmacological treatment, consisting in administration of vitamin D, in order to enhance bone resorption and of prednisone to improve hematological indexes and, if possible, bone marrow transplantation in order to ameliorate quality of life and survival.

Anti-Infective Agents↗

PubMed2006

Interferon gamma-1b: new indication. Severe malignant osteopetrosis: too many unknowns.

(1) Severe malignant osteopetrosis is a very rare disease. The principal manifestations are anaemia, infections, sensory disorders and fractures, due to generalised bone condensation. The disease is generally fatal in childhood. The only treatment capable of modifying the natural outcome is bone marrow transplantation. The benefits of high-dose steroids and calcitriol are usually modest and transient. (2) Severe malignant osteopetrosis is a new licensed indication for interferon gamma-1b, a drug known to reduce the incidence of severe infections in children with chronic septic granulomatosis. (3) An unblinded trial involving 15 children with a mean age of about one year compared calcitriol plus interferon gamma-1b with calcitriol alone. The time to treatment failure was longer with the combination, based on a combined endpoint chosen to make the statistical analysis more sensitive. (4) A clinical trial involving 15 patients, who were compared with a historical series of 94 untreated patients, provided ambiguous results. (5) In these trials the main adverse effect of interferon gamma-1b was a flu-like syndrome. (6) Given the gravity of severe malignant osteopetrosis, the limited available treatment options, and the rarity of serious adverse events with interferon gamma-1b, evaluation of this therapy should continue.

Calcitriol↗

PubMedDate not supplied

[Osteopetrosis: description of 2 cases, non-familial, of the fatal infantile form and of a case of the mild adult form. Impossibility of performing early prenatal diagnosis].

Two non familial cases of the juvenile lethal form of osteopetrosis and one case of the mild adult type are reported. In one case at risk of lethal osteopetrosis an early prenatal diagnosis was attempted, after informing the parents about the extreme difficulty to obtain conclusive results by such investigation. Although several ultrasonographic and one radiological examinations showed an apparently normal foetus, the newborn was affected by the lethal form of osteopetrosis.

Child↗

PubMed1989

Osteoarthritis associated with osteopetrosis treated by total knee arthroplasty. Report of a case.

Osteopetrosis is due to a defect in osteoclastic cell function and results in osteosclerosis and progressive obliteration of the marrow spaces. Early onset osteoarthritis is associated with osteopetrosis. The authors describe a case of early onset osteoarthritis associated with osteopetrosis treated by total knee arthroplasty. The marblelike quality of osteopetrotic bone makes surgical treatment of these patients technically challenging and requires modification of standard surgical technique.

Female↗

PubMed1986

Retroviruses, immunosuppression and osteopetrosis.

Since decades, retroviruses are known to induce the formation of dense bones (osteopetrosis) in animals, either by increasing osteoblastic proliferation (ALVs viruses) or by decreasing osteoclastic bone resorption (FeLV virus). The latter is a good model of the inherited disease since neonatally infected cats die from wasting disease, like mutant op/op rats and children suffering from juvenile-malignant osteopetrosis. These similarities have prompted this review of retrovirus-induced osteopetrosis in animals. We suggest the possibility that retroviruses might be involved, at least in part, in the induction of the human disease.

Animals↗

PubMed1986

Neutrophil defect associated with malignant infantile osteopetrosis.

We studied the phagocytes from three infants with malignant osteopetrosis and from their families in an attempt to define further the phagocyte abnormalities associated with this disorder. The rapid membrane potential depolarization in response to the soluble stimuli formylmethionylleucylphenylalanine (FMLP) and phorbol myristate acetate (PMA) served as a measure of neutrophil activation, with 3,3-dipentyloxacarbocyanine (diOC5 [3]) used as the probe. A fluorescence-activated cell sorter (FACS) allowed us to use small volumes of blood in a new quantitative evaluation of neutrophil response. The neutrophils from the infants with malignant osteopetrosis were very minimally activated with either stimulus, as demonstrated by incomplete membrane potential depolarization (10% to 15% of normal controls). This finding indicates that malignant osteopetrosis is accompanied by a significantly reduced neutrophil response to stimulation. The abnormal activation process was also reflected in the respiratory burst response of the patients' neutrophils and monocytes. Fifty percent to 60% of the infants' neutrophils totally failed to reduce nitro blue tetrazolium dye (NBT), 30% to 40% of the cells showed only slight reduction after PMA or FMLP stimulation, and only 5% to 10% demonstrated normal reduction. Peripheral blood monocytes failed to reduce NBT in 35% to 70% of the cells tested. Similar testing of granulocyte-macrophage colonies grown in vitro from circulating progenitor cells also showed an abnormal distribution of response to PMA, with a majority of colonies showing a decrease or absence of NBT reduction. Thus control of expression of the osteopetrotic defect occurs at or before the progenitor cell level.

Flow Cytometry↗

PubMed1979

Osteopetrosis in South Africa. The benign, lethal and intermediate forms.

Osteopetrosis is an unusual bone disorder in which the skeleton is radiographically dense. The condition is conventionally subclassified into a benign autosomal dominant adult form and a malignant autosomal recessive variety. Among 14 affected individuals whom we have studied, 4 adults had an intermediate type of osteopetrosis in which serious complications included osteomyelitis, pathological fractures and dyshaemopoiesis. The fundamental biochemical relationship of this disorder with the classic forms of osteopetrosis is uncertain. The osteopetroses must be distinguished from other sclerosing bone conditions which have a different course and prognosis. Sclerosteosis and craniometaphyseal dysplasia, both of which occur in South Africa, are of practical importance in this context.

Adolescent↗

PubMed1980

Human osteopetrosis: a histological, ultrastructural, and biochemical study.

UNLABELLED: Histological ultrastructural, and biochemical studies of the tissues of a patient with osteopetrosis were done. The bone contained an increased number of osteoclasts which were characterized ultrastructurally by the absence of ruffled borders and clear zones, hallmarks of actively resorbing osteoclasts. In contrast with normal human bone, tissue collagenase was not detected in osteopetrotic bone cultured in vitro, nor was tissue collagenase activity released when the osteopetrotic bone was incubated with parathyroid hormone. No striking abnormalities of parathyroid hormone or calcitonin were found in the blood or parathyroid and thyroid glands. Except for a slight increase in the extent of lysine hydroxylation of bone collagen, no significant biochemical abnormality of collagen was found. The histological, ultrastructural, and biochemical data support the hypothesis that the basic defect in osteopetrosis is cellular and the osteoclasts, in particular, are abnormal. They appear to be unable to resorb bone and cartilage, and they do not appear to respond to parathyroid hormone in a completely normal way. CLINICAL RELEVANCE: Bone marrow transplantation has produced improvement in both experimental animals and humans and should be actively considered in a child with osteopetrosis who is not thriving.

Amino Acids↗