Osteopetrosis

Excessive formation of dense trabecular bone leading to pathological fractures; OSTEITIS; SPLENOMEGALY with infarct; ANEMIA; and extramedullary hemopoiesis (HEMATOPOIESIS, EXTRAMEDULLARY).

Also Known As:

Networked: 702 relevant articles (25 outcomes, 42 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Sclerosis
2.	Chronic Granulomatous Disease
3.	Bone Resorption
4.	Thalassemia
5.	Rickets (Rachitis)

Experts

1.	Henriksen, Kim: 9 articles (11/2015 - 11/2005)
2.	Vezzoni, Paolo: 9 articles (07/2014 - 01/2003)
3.	Pangrazio, Alessandra: 9 articles (07/2014 - 10/2003)
4.	Villa, Anna: 9 articles (07/2014 - 10/2003)
5.	Sobacchi, Cristina: 8 articles (07/2014 - 10/2003)
6.	Steward, C G: 8 articles (02/2005 - 07/2000)
7.	Whyte, Michael P: 7 articles (08/2015 - 10/2008)
8.	Richter, Johan: 7 articles (12/2013 - 02/2006)
9.	Frattini, Annalisa: 7 articles (06/2009 - 10/2003)
10.	Jentsch, Thomas J: 6 articles (09/2015 - 11/2004)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Osteopetrosis:

1.	Macrophage Colony-Stimulating FactorIBA 12/01/2005 - "The culture data reflect the histopathology and radiological findings and also support previous studies showing that neither M-CSF nor RANKL rescues osteoclast-poor osteopetrosis. " 09/27/1994 - "The study of colony stimulating factor 1 (CSF-1), a homodimeric serum growth factor that regulates mononuclear phagocytes and is involved in maternal-fetal interactions during pregnancy, was dramatically enhanced by the observation that the recessive mutation osteopetrosis, op, is an inactivating mutation in the CSF-1-encoding gene. " 01/01/2013 - "DAP12-deficient mice suffer from a mild osteopetrosis and culture of their bone marrow cells in the presence of M-CSF and RANKL, fails to give rise to multinucleated osteoclasts. " 01/01/2012 - "Homozygous CSF-1KO mice lacked CSF-1 in all tissues and displayed, in part, a similar phenotype to op/op mice that included: failure of tooth eruption, osteopetrosis, reduced macrophage densities in reproductive and other organs and altered hematopoiesis with decreased marrow cellularity, circulating monocytes and B cell lymphopoiesis. " 01/01/2012 - "The spontaneous mutant op/op mouse has been the conventional model of CSF-1 deficiency and exhibits a pleiotropic phenotype characterized by osteopetrosis, and defects in hematopoiesis, fertility and neural function. "
2.	CalciumIBA 12/01/1965 - "[Study of calcium metabolism in humans with the aid of calcium 45: osteopetrosis and osteopsathyrosis]." 04/01/2014 - "Here we observed that all cases with TCIRG1-dependent osteopetrosis displayed severe osteoid accumulation and decreased calcium content within the mineralized matrix. " 09/07/2007 - "In summary, we found that acidification leading to calcium release from bone during resorption controls osteoclast survival, potentially explaining the increased numbers of osteoclasts in patients with osteopetrosis." 01/01/2007 - "Disorders in calcium removal from bone matrix by osteoclasts cause osteopetrosis. " 01/01/1988 - "Biochemical evidence of disturbed bone metabolism and calcium homeostasis in two types of autosomal dominant osteopetrosis."
3.	Vitamin DFDA LinkGeneric 01/01/1988 - "Serum vitamin D metabolites and nuclear uptake of (3H)-1,25-dihydroxyvitamin D3 in monocytes from patients with autosomal dominant osteopetrosis: a study of two radiological types." 01/01/1992 - "A group of 16 infants, 2 weeks to 11 months old, with malignant osteopetrosis were investigated to examine their vitamin D metabolism and parathyroid function. " 06/01/2000 - "Osteopetrosis is an important differential diagnosis of neonatal rickets and is not excluded by low vitamin D levels." 11/01/1977 - "The following report concerns a case of malignant osteopetrosis associated with hypocalcemic rickets unresponsive to vitamin D. " 06/01/2004 - "Detection of rickets in a child with osteopetrosis is necessary, because treatment of the rickets with vitamin D leads to improvement in activity, decrease in irritability, improvement of appetite, and protects against recurrent respiratory tract infections. "
4.	tartrate-resistant acid phosphatase (TSAP)IBA 03/01/1996 - "Tartrate resistant acid phosphatase synthesis was almost nil in osteopetrotic mice during the first 4 weeks, and thereafter appeared coincidental with spontaneous remission of osteopetrosis at 6 weeks. " 11/01/2012 - "Twelve weeks of OPG-Fc treatment resulted in radiographic and histologic osteopetrosis with no evidence of bone modeling and negative tartrate-resistant acid phosphatase staining, root dentin abnormalities, and TRACP-5b activity suppression. " 08/01/2004 - "In contrast, p21/p27 double knockout mice developed osteopetrosis, with fewer osteoclasts that exhibited lower TRACP activity and abnormal cell morphology present in long bone. " 08/01/2000 - "Similar differences were observed in both types of autosomal dominant osteopetrosis compared with controls concerning tartrate resistant acid phosphatase. " 02/01/1999 - "This age-associated reversal of osteopetrosis was accompanied by the expansion of bone marrow cavities and increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive cells and of macrophages in the bone marrow. "
5.	Superoxides (Superoxide)IBA 09/01/1999 - "Superoxide generation in transformed B-lymphocytes from patients with severe, malignant osteopetrosis." 07/01/1992 - "A defect in leukocytic superoxide formation has been demonstrated in patients with congenital osteopetrosis. " 01/01/1997 - "Since treatment with recombinant interferon-γ-1b (interferon γ-1b, IFNγ-1b) has resulted in increased level of superoxide generation and clinical improvement in chronic granulomatous disease, a similar strategy has been employed using IFNγ-1b to treat patients with osteopetrosis. " 06/15/1995 - "Congenital osteopetrosis is a rare osteosclerotic bone disease characterized by both a defect in osteoclastic function and reduced generation of superoxide by leukocytes. " 01/01/1992 - "We have examined the role of superoxide in bone resorption by stimulating defective superoxide production and bone resorption in patients with osteopetrosis and inhibiting superoxide production and bone resorption in murine calvarial explants. "
6.	Complement System Proteins (Complement)IBA 06/01/1998 - "Bone marrow immunoscintigraphy appears to be an ideal complement to radiograph diagnostics in malignant osteopetrosis. " 07/01/1986 - "Because of their central role in host defense (in inflammatory responses, in antigen presentation, and in immunoregulatory networks), monocyte/macrophage dysfunction may result in one or more pathophysiologic consequences: defects in monocyte maturation, deficiencies in the clearance of physiologic substrates in lysosomal diseases (e.g., Gaucher's disease, mucopolysaccharidoses, osteopetrosis, metachromatic leukodystrophy), decreased synthesis and secretion of mediators (complement component deficiencies), defects in microbicidal activity (chronic granulomatous disease) and defects which are acquired following infection and during chemotherapy (e.g., acquired immune deficiency syndrome)."
7.	SteroidsIBA 07/01/1986 - "These patients provide further evidence for the efficacy of steroids in juvenile osteopetrosis, and the combination with the low calcium, high phosphate diet described offers a potentially effective alternative treatment to marrow transplantation, both for the haematological and skeletal complications of the disorder."
8.	beta-apocarotenoid-14',13'-dioxygenase (ADO)IBA 08/01/2013 - "Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. " 10/01/2009 - "In this study we analysed the imaging patterns in two families containing five members with asymptomatic and uncomplicated autosomal dominant osteopetrosis (ADO II), and we report new and uncommon radiological manifestations. " 07/01/2005 - "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. " 01/01/2015 - "Osteopetrosis (OP) is hereditary X-linked, autosomal recessive (ARO), or autosomal dominant (ADO) skeletal disease. " 12/01/2014 - "Autosomal dominant osteopetrosis (ADO) is a sclerotic bone disorder due to failure of osteoclasts. "
9.	HormonesIBA 07/01/1956 - "[Marmoreal osteopetrosis in a prostate patients; radiologic and humoro-endocrine research; antagonism between genital hormones and parathyroids]." 09/01/1993 - "Studies of these mutations have revealed that osteopetrosis is a complex, heterogeneous disorder in its expression, etiology, and response to treatment by bone marrow transplantation or by hormone/growth factor therapy. " 01/01/2003 - "The study gives a further biochemical description of two different forms of autosomal dominant osteopetrosis (ADO) in relation to murine counterparts, with special attention to osteoblast function and the recent discovery of LRP5 gene mutations in ADO I. Patients and controls were investigated for markers of bone formation and resorption at baseline and following stimulation with thyroid hormone. " 07/01/1993 - "Comparison of the present results of the cellular examination in two patients with GTHR, with the results obtained in other families with altered peripheral thyroid hormone sensitivity, suggest that the classic GTHR (phenotype: normal or with goitre) is linked to impaired thyroid hormone stimulated glucose uptake, whereas in patients with osteopetrosis, the thyroid hormone insensitivity seems located at the mitochondrial level (impaired thyroid hormone stimulated oxygen consumption." 01/01/1991 - "Decreased thyroid hormone-stimulated oxygen consumption and glucose uptake in mononuclear blood cells from patients with autosomal dominant osteopetrosis type I."
10.	BB Form Creatine KinaseIBA 07/01/1992 - "Elevated serum levels of creatine kinase BB in autosomal dominant osteopetrosis type II--a family study." 08/01/2000 - "Creatine kinase-BB in mammalian osteopetrosis is related to osteoclastic number and size, where it probably reflects the differentiation and maturation of inactive bone resorbing cells. " 08/01/2000 - "Although creatine kinase-BB was unchanged in Type 1 autosomal dominant osteopetrosis at baseline and after stimulation, the rodent counterparts characterized by small osteoclasts, microphthalmic and osteopetrotic mice and toothless rats, had significantly decreased levels. " 08/01/2000 - "Creatine kinase-BB was increased markedly in Type 2 autosomal dominant osteopetrosis and in the incisors absent rat, both characterized by large numbers of giant osteoclasts, and did not change significantly after stimulation. " 08/01/2000 - "Recently, high blood levels of creatine kinase-BB have been reported in some human forms, suggesting it as a marker of osteopetrosis. "

Therapies and Procedures

1.	Bone Marrow Transplantation (Transplantation, Bone Marrow) 04/01/2012 - "In eight patients with infantile osteopetrosis which could be cured by bone marrow transplantation, the study identified by homozygosity mapping in distantly related consanguineous pedigrees a missense mutation in a highly conserved residue in the SNX10 gene. " 03/15/1990 - "The osteopetrosis of mi/mi mice can be cured by bone marrow transplantation from congenic normal (+/+) mice, and therefore, the cause of the osteopetrosis is attributed to a defect of osteoclasts. " 06/01/1986 - "No differences were found between mutant and normal bone from this stock or from two other osteopetrotic rat stocks, incisors-absent and osteopetrosis, known to be cured by bone marrow transplantation. " 04/01/1980 - "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." 07/01/1999 - "A nine-month-old female patient suffering from malignant osteopetrosis was evaluated by light and transmission electron microscopic study before and following allogeneic bone marrow transplantation (BMT). "
2.	Transplants (Transplant) 07/01/2000 - "Here, we report the good outcome of two cases of mild AR osteopetrosis with a follow-up of 5 and 6 years, respectively, after an HLA-identical sibling transplant undergone at 5 and 12 years of age, respectively. " 01/01/1984 - "Recent demonstrations that not all children with congenital osteopetrosis are cured by bone marrow transplants from HLA-matched donors suggest that the oplop mouse mutation may be a useful model system in which to develop alternate treatments." 05/01/2003 - "Bone marrow transplant has been used with cure for infantile malignant osteopetrosis. " 04/01/1997 - "[Value of in vitro study of osteoclast precursors in the case of severe infantile osteopetrosis treated by bone marrow graft]." 07/01/2015 - "Autosomal recessive osteopetrosis (ARO) is the most severe form and is often fatal within the first years of life; early hematopoietic stem cell transplant (HSCT) remains the only curative treatment for ARO. "
3.	Transplantation (Transplant Recipients) 03/01/2008 - "So far, the only cure for children with severe osteopetrosis is allogeneic hematopoietic stem cell (HSC) transplantation but without a matching donor this form of therapy is far from optimal. " 06/01/1981 - "Our studies indicate that marrow transplantation will correct osteopetrosis but that permanent reconstitution necessitates sustained engraftment of marrow precursors of cells with osteoclastic activity." 07/09/2015 - "We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. " 12/01/2013 - "After transplantation, a donor chimerism of 97-98% was obtained, and by 15 weeks mild osteopetrosis had developed in recipients of cells from osteopetrotic mice. " 09/01/2010 - "In summary, nonablative neonatal transplantation leading to engraftment of only a small fraction of normal cells rapidly reverses severe osteopetrosis in the oc/oc mouse model."
4.	Arthroplasty 04/01/2010 - "However, many intraoperative and postoperative challenges need to be overcome when performing arthroplasty in patients with osteopetrosis, and few studies have focused on the longer-term outcomes.This" 01/01/2015 - "Total Hip and Knee arthroplasty in a patient with osteopetrosis: a case report and review of the literature." 12/01/2014 - "Autosomal dominant type I osteopetrosis is related with iatrogenic fractures in arthroplasty." 09/01/2012 - "Total knee arthroplasty in osteopetrosis using patient-specific instrumentation." 09/01/2011 - "Bipolar hip arthroplasty for subtrochanteric femoral nonunion in an adult with autosomal dominant osteopetrosis type II."
5.	Decompression 12/01/2000 - "The efficacy of optic nerve decompression in patients with osteopetrosis is still controversial. " 12/01/2000 - "The purpose of this study is to report that visual deterioration in osteopetrosis can be completely reversed by early optic nerve decompression. " 04/01/2011 - "To the authors' knowledge, this report represents the first described case of extreme posterior fossa calvarial thickening from autosomal dominant osteopetrosis with associated Chiari I malformation (CM-I) requiring posterior fossa decompression and extradural decompression. " 12/01/2000 - "Progressive loss of vision associated with osteopetrosis can be prevented by optic nerve decompression in the early stage of visual deterioration. " 12/01/2000 - "Complete visual recovery in osteopetrosis by early optic nerve decompression."