3,496 results match your criteria Osteopetrosis

Sorting Nexin 10 as a Key Regulator of Membrane Trafficking in Bone-Resorbing Osteoclasts: Lessons Learned From Osteopetrosis.

Front Cell Dev Biol 2021 20;9:671210. Epub 2021 May 20.

Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.

Bone homeostasis is a complex, multi-step process, which is based primarily on a tightly orchestrated interplay between bone formation and bone resorption that is executed by osteoblasts and osteoclasts (OCLs), respectively. The essential physiological balance between these cells is maintained and controlled at multiple levels, ranging from regulated gene expression to endocrine signals, yet the underlying cellular and molecular mechanisms are still poorly understood. One approach for deciphering the mechanisms that regulate bone homeostasis is the characterization of relevant pathological states in which this balance is disturbed. Read More

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A critical review of the anthropological and paleopathological literature on osteopetrosis as an ancient rare disease (ARD).

Int J Paleopathol 2021 Jun 31;33:280-288. Epub 2021 May 31.

Department of Natural Sciences, German Archaeological Institute, Berlin, Germany.

Objective: A reappraisal of the available evidence of osteopetrosis in the archaeological record as first step in promoting new approaches to rare diseases in paleopathology.

Materials And Methods: Three different approaches are combined: a survey of the last 50 years of bioarchaeological publications; an online search addressing six of the more widely used search engines; macroscopic and radiographic analyses of the human remains from the Neolithic site of Palata 2 (Italy).

Results: The combined results of the literature survey and the online search identified six cases of osteopetrosis. Read More

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CSF1R-dependent macrophages control postnatal somatic growth and organ maturation.

PLoS Genet 2021 Jun 3;17(6):e1009605. Epub 2021 Jun 3.

Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, Qld, Australia.

Homozygous mutation of the Csf1r locus (Csf1rko) in mice, rats and humans leads to multiple postnatal developmental abnormalities. To enable analysis of the mechanisms underlying the phenotypic impacts of Csf1r mutation, we bred a rat Csf1rko allele to the inbred dark agouti (DA) genetic background and to a Csf1r-mApple reporter transgene. The Csf1rko led to almost complete loss of embryonic macrophages and ablation of most adult tissue macrophage populations. Read More

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Genetically Modified Ferritin Nanoparticles with Bone-Targeting Peptides for Bone Imaging.

Int J Mol Sci 2021 May 3;22(9). Epub 2021 May 3.

Bionanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Daejeon 34141, Korea.

Bone homeostasis plays a major role in supporting and protecting various organs as well as a body structure by maintaining the balance of activities of the osteoblasts and osteoclasts. Unbalanced differentiation and functions of these cells result in various skeletal diseases, such as osteoporosis, osteopetrosis, and Paget's disease. Although various synthetic nanomaterials have been developed for bone imaging and therapy through the chemical conjugation, they are associated with serious drawbacks, including heterogeneity and random orientation, in turn resulting in low efficiency. Read More

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Identification of novel mutation in RANKL by whole-exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis.

Mol Genet Genomic Med 2021 May 30:e1727. Epub 2021 May 30.

Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Background: Osteopetrosis is a rare form of skeletal dysplasia characterized by increased bone density that leads to bone marrow failure, compressive neuropathy, and skeletal dysmorphism. Molecular diagnosis is essential as it guides treatment and prognosis. We report Thai siblings with an ultra-rare form of osteopetrosis. Read More

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A novel mutation in TNFRSF11A gene causes pediatric osteopetrosis: case report.

BMC Surg 2021 May 28;21(1):269. Epub 2021 May 28.

Department of Otolaryngology, Head & Neck Surgery, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610091, China.

Background: Osteopetrosis is a rare inherited bone disorder affected individual by osteoclast disfunction and increasing bone density. Surgery was taken for histological examination of the specimen and evidence of malignancy was not found. Finally, X-ray and gene detection lead to the diagnosis. Read More

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Metabolic Bone Diseases in the Pediatric Population.

Semin Musculoskelet Radiol 2021 Feb 21;25(1):94-104. Epub 2021 May 21.

Department of Clinical and Experimental Medicine, Foggia University School of Medicine, Foggia, Italy.

Bone plays an important role in regulating mineral balance in response to physiologic needs. In addition, bone is subject to a continuous remodeling process to maintain healthy bone mass and growth. Metabolic bone diseases are a heterogeneous group of diseases caused by abnormalities of bone mass, mineral structure homeostasis, bone turnover, or bone growth. Read More

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February 2021

Characterization of unique functionalities in c-Src domains required for osteoclast podosome belt formation.

J Biol Chem 2021 May 18:100790. Epub 2021 May 18.

Division of Bone and Mineral Research, Oral medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School and Endocrine Unit, MGH, Boston, Massachusetts, USA. Electronic address:

Deletion of c-Src, a ubiquitously expressed tyrosine kinase, results in osteoclast dysfunction and osteopetrosis, in which bones harden into "stone". In contrast, deletion of the genes encoding other members of the Src family kinase (SFK) fails to produce an osteopetrotic phonotype. This suggests that c-Src performs a unique function in the osteoclast that cannot be compensated for by other Src family kinases. Read More

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Managing challenging pain and irritability in mutation-related infantile malignant osteopetrosis.

BMJ Case Rep 2021 May 19;14(5). Epub 2021 May 19.

Pediatrics, Al Adan Hospital, Al Ahmadi Health District, Kuwait.

Osteopetrosis describes a heterogeneous group of diseases characterised by increased bone density due to impaired osteoclast. The malignant infantile autosomal recessive (MIOP) form caused by mutations in is the most severe form of osteopetrosis. Children with this phenotype exhibit multisystemic complications, of which the neuropathic manifestations are the most severe. Read More

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Surgical management of chronic osteomyelitis with benign osteopetrosis: A case report.

Ann Med Surg (Lond) 2021 May 20;65:102296. Epub 2021 Apr 20.

Oral and Maxillofacial Surgery Department, CHU Ibn Rochd, B.P 2698, Casablanca, Morocco.

Introduction: Osteopetrosis is a rare genetic bone disease caused by a functional abnormality of the osteoclasts. Until now there is no codified management for the complications of this pathology and few cases cited in the literature.

Presentation Of Case: a 19-year-old adult followed in our maxillofacial surgery department in the IBN ROCHD University Hospital for chronic osteomyelitis complicating mandibular osteopetrosis with skin fistulas. Read More

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A Rare Case of Osteoclast-poor Osteopetrosis (RANKL Mutation) with Recurrent Osteomyelitis of Mandible: A Case Report.

Int J Clin Pediatr Dent 2020 Nov-Dec;13(6):717-721

Department of Oral and Maxillofacial Surgery, Nair Hospital Dental College, Mumbai, Maharashtra, India.

Osteopetrosis (OP) is a group of rare genetic bone disorders. Osteoclast-poor form of osteopetrosis is much rarer in humans and represents a small percentage of the total cases of autosomal recessive osteopetrosis presenting with impaired bone remodeling due to defective osteoclastic activity and is characterized by distinctive increase in bone density and high bone fragility. Reduction in marrow spaces with decreased vasculature to the bone owing to increased bone mass makes the bones vulnerable for varied infections resulting in osteomyelitis. Read More

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An SNX10-dependent mechanism downregulates fusion between mature osteoclasts.

J Cell Sci 2021 May 11;134(9). Epub 2021 May 11.

Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.

Homozygosity for the R51Q mutation in sorting nexin 10 (SNX10) inactivates osteoclasts (OCLs) and induces autosomal recessive osteopetrosis in humans and in mice. We show here that the fusion of wild-type murine monocytes to form OCLs is highly regulated, and that its extent is limited by blocking fusion between mature OCLs. In contrast, monocytes from homozygous R51Q SNX10 mice fuse uncontrollably, forming giant dysfunctional OCLs that can become 10- to 100-fold larger than their wild-type counterparts. Read More

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Autosomal recessive osteopetrosis: mechanisms and treatments.

Dis Model Mech 2021 May 10;14(5). Epub 2021 May 10.

San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.

Autosomal recessive osteopetrosis (ARO) is a severe inherited bone disease characterized by defective osteoclast resorption or differentiation. Clinical manifestations include dense and brittle bones, anemia and progressive nerve compression, which hamper the quality of patients' lives and cause death in the first 10 years of age. This Review describes the pathogenesis of ARO and highlights the strengths and weaknesses of the current standard of care, namely hematopoietic stem cell transplantation (HSCT). Read More

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The genotypic and phenotypic spectrum of pycnodysostosis in Saudi Arabia: Novel variants and clinical findings.

Am J Med Genet A 2021 May 8. Epub 2021 May 8.

Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Pycnodysostosis is characterized by short stature, osteosclerosis, acro-osteolysis, increased tendency of fractures, and distinctive dysmorphic features. It is a rare autosomal recessive disease caused by biallelic CTSK mutations. The clinical details of 18 patients from Saudi Arabia were reviewed. Read More

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Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7-related osteopetrosis.

J Bone Miner Res 2021 Apr 27. Epub 2021 Apr 27.

BIH Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Human induced pluripotent stem cells (hiPSCs) hold great potential for modeling human diseases and the development of innovative therapeutic approaches. Here, we report on a novel, simplified differentiation method for forming functional osteoclasts from hiPSCs. The three-step protocol starts with embryoid body formation, followed by hematopoietic specification, and finally osteoclast differentiation. Read More

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Case report of osteomyelitis of the mandible in osteopetrosis and management considerations.

Int J Surg Case Rep 2021 Apr 23;81:105813. Epub 2021 Mar 23.

Department of Maxillofacial and Oral Surgery, University Hospital of Dijon, 2 boulevard du Maréchal de Lattre de Tassigny, BP 77908, 21079, Dijon cedex, France; CIC-EC 1432 (Centre d'Investigation clinique - Epidémiologie clinique) - Pr QUANTIN Catherine, Chirurgie endocrinienne, Dr GOUDET Pierre, France.

Introduction And Importance: Osteopetrosis is a poorly known and probably underdiagnosed pathology. It is caused by various genetic abnormalities resulting in osteoclast dysfunction. Functional and aesthetic consequences have a major impact on the patient's quality of life. Read More

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Pediatric Scaphoid Fracture Associated with Osteopetrosis: A Case Report.

JBJS Case Connect 2021 04 13;11(2). Epub 2021 Apr 13.

Department of Orthopaedic Surgery, Maimonides Medical Center, Brooklyn, New York.

Case: A 12-year-old boy with osteopetrosis sustained a scaphoid waist fracture, which has not previously been reported with this condition. Healing was successfully achieved with percutaneous cannulated compression screw fixation, albeit with prolonged healing as is typical for this condition.

Conclusion: A lack of osteoclastic remodeling predisposes patients with osteopetrosis to fractures, commonly in long bones. Read More

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T-cell replete haploidentical transplantation with reduced post-transplant cyclophosphamide in six children with infantile osteopetrosis.

Bone Marrow Transplant 2021 Apr 6. Epub 2021 Apr 6.

Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

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Osteopetrorickets in An Infant with Coexistent Congenital Cytomegalovirus Infection.

Balkan J Med Genet 2020 Nov 23;23(2):107-110. Epub 2021 Mar 23.

Hematology-Oncology Unit, 2nd Pediatric Department, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Osteopetrosis refers to a group of rare hereditary disorders characterized by generalized skeletal densification due to limited bone resorption by osteoclasts. The infantile autosomal recessive form represents the most malignant one with onset early in infancy and life expectancy less than 1-2 years without therapy. Frequently, osteopetrosis is complicated by rickets, a condition called osteopetrorickets. Read More

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November 2020

How rare is rare? A literature survey of the last 45 years of paleopathological research on ancient rare diseases.

Int J Paleopathol 2021 Jun 1;33:94-102. Epub 2021 Apr 1.

German Archaeological Institute, Department of Natural Sciences, Berlin, Germany.

Objective: This paper aims to provide a quantitative estimation of the representation of diseases defined as rare today in the bioarchaeological literature and to outline the reasons for this.

Materials: A 45-year bibliometric study of publications in seven bioarchaeological journals, along with two journals and editorial groups of broader scientific focus.

Methods: Analyses of distribution patterns of the search hits and diachronic trends for achondroplasia, autosomal-dominant osteopetrosis, osteogenesis imperfecta, and osteopoikilosis, compared to those for tuberculosis as control measure of coverage. Read More

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Chronic paronychia in cats with patellar fracture and dental anomaly syndrome.

J Feline Med Surg 2021 Mar 24:1098612X21998612. Epub 2021 Mar 24.

Langford Small Animal Hospital, Langford House, University of Bristol, Bristol, UK.

Case Series Summary: The aim of this case series was to describe the clinical features and treatment of paronychia in cats diagnosed with patellar fracture and dental anomaly syndrome (PADS). Clinical records, photographs, microbiology, cytology and histopathology reports were collected, and follow-up was obtained. Five cats with paronychia were included. Read More

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Further expanding the mutational spectrum of brain abnormalities, neurodegeneration, and dysosteosclerosis: A rare disorder with neurologic regression and skeletal features.

Am J Med Genet A 2021 06 22;185(6):1888-1896. Epub 2021 Mar 22.

Department of Medical Genetics, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Colony stimulating factor 1 receptor (CSF1R, MIM# 164770) encodes a tyrosine-kinase receptor playing an important role in development of osteoclasts and microglia. Heterozygous CSF1R variants have been known to cause hereditary diffuse leukoencephalopathy with spheroids (HDLS, MIM# 221820), an adult-onset leukoencephalopathy characterized by loss of motor functions and cognitive decline. Recently, a new phenotype characterized by brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) with biallelic CSF1R pathogenic variants in the etiology has been described. Read More

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Insertion Mutation in Tnfrsf11a Causes a Paget's Disease-Like Phenotype in Heterozygous Mice and Osteopetrosis in Homozygous Mice.

J Bone Miner Res 2021 Mar 16. Epub 2021 Mar 16.

Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Early onset familial Paget's disease of bone (EoPDB), familial expansile osteolysis, and expansile skeletal hyperphosphatasia are related disorders caused by insertion mutations in exon 1 of the TNFRSF11A gene, which encodes receptor activator of nuclear factor κB (RANK) protein. To understand the mechanisms underlying these disorders, we developed a mouse model carrying the 75dup27 mutation which causes EoPDB. Mice heterozygous for the mutation (Tnfrsf11a ) developed a PDB-like disorder with focal osteolytic lesions in the hind limbs with increasing age. Read More

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Neurodegeneration Upon Dysfunction of Endosomal/Lysosomal CLC Chloride Transporters.

Front Cell Dev Biol 2021 23;9:639231. Epub 2021 Feb 23.

Institute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.

The regulation of luminal ion concentrations is critical for the function of, and transport between intracellular organelles. The importance of the acidic pH in the compartments of the endosomal-lysosomal pathway has been well-known for decades. Besides the V-ATPase, which pumps protons into their lumen, a variety of ion transporters and channels is involved in the regulation of the organelles' complex ion homeostasis. Read More

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February 2021

SNX10 gene mutation in infantile malignant osteopetrosis: A case report and literature review.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Jan;46(1):108-112

Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha 410013, China.

A case of SNX10 gene mutation in a patient with infantile malignant osteopetrosis (IMO) was admitted to Department of Pediatrics, Third Xiangya Hospital, Central South University. The patient had the symptom of anemia, hepatosplenomegaly and growth retardation. The X-ray examination suggested extensive increase of bone density throughout the body, which was clinically diagnosed as IMO. Read More

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January 2021

Further understanding on osteopetrotic femoral fractures: a case report and literature review.

BMC Surg 2021 Mar 6;21(1):117. Epub 2021 Mar 6.

Department of Orthopaedics, First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China.

Background: Osteopetrosis is a genetic disease characterized by defects in osteoclast formation and function. There were a few cases of subtrochanteric femur fractures treated with dynamic hip screw (DHS) in patients with osteopetrosis, but unfortunately the healing outcome was rather poor.

Case Presentation: We present our experience for treating a patient with intermediate autosomal recessive osteopetrosis (IRO) suffering from subtrochanteric femur fracture. Read More

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Pax5 Negatively Regulates Osteoclastogenesis through Downregulation of Blimp1.

Int J Mol Sci 2021 Feb 20;22(4). Epub 2021 Feb 20.

Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Korea.

Paired box protein 5 (Pax5) is a crucial transcription factor responsible for B-cell lineage specification and commitment. In this study, we identified a negative role of Pax5 in osteoclastogenesis. The expression of Pax5 was time-dependently downregulated by receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) stimulation in osteoclastogenesis. Read More

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February 2021

Differentiation of Human Induced Pluripotent Stem Cells (hiPSCs) into Osteoclasts.

I-Ping Chen

Bio Protoc 2020 Dec 20;10(24):e3854. Epub 2020 Dec 20.

Department of Oral Health and Diagnostic Sciences, School of Dental Medicine, University of Connecticut Health, Farmington, CT, USA.

Defects in bone resorption by osteoclasts result in numerous rare genetic bone disorders as well as in some common diseases such as osteoporosis or osteopetrosis. The use of hiPSC-differentiated osteoclasts opens new avenues in this research field by providing an unlimited cell source and overcoming obstacles such as unavailability of human specimens and suitable animal models. Generation of hiPSCs is well established but efficient differentiation of hiPSCs into osteoclasts has been challenging. Read More

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December 2020

The French multicentre elevated bone mass study: prevalence and causes.

Osteoporos Int 2021 Mar 2. Epub 2021 Mar 2.

Rheumatology Unit, MABlab ULR 4490, Lille University Hospital, CHRU Lille, rue Emile Laine, 59037, Lille, France.

The purpose of this multicentric study was to evaluate the prevalence and causes of Elevated Bone Mass (EBM) in patients who underwent DXA scanning over a 10-year period. The prevalence of EBM was 1 in 100. The main causes of EBM were degenerative spine disorders and renal osteodystrophy. Read More

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Hematopoietic stem cell transplantation in a patient with osteopetrosis and mutation in CLCN7: long-term follow-up.

Bol Med Hosp Infant Mex 2021 Mar 2. Epub 2021 Mar 2.

Departamento de Laboratorio Clínico. Hospital Infantil de México Federico Gómez, Mexico City, Mexico.

Introduction: Osteopetrosis is a rare hereditary bone dysplasia characterized by insufficient osteoclast activity that results in increased bone mineral density. Hematopoietic stem cell transplantation (HSCT) can reverse skeletal abnormalities and restore hematopoiesis.

Clinical Case: We present the case of a 3-year and 2-month-old male patient with the diagnosis of osteopetrosis. Read More

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