Curr Osteoporos Rep 2018 Apr 14. Epub 2018 Apr 14.

Centre of Medical Genetics, University of Antwerp & University Hospital Antwerp, Antwerp, Belgium.

Purpose Of Review: The group of sclerosing bone disorders encompasses a variety of disorders all marked by increased bone mass. In this review, we give an overview of the genetic causes of this heterogeneous group of disorders and briefly touch upon the value of these findings for the development of novel therapeutic agents.

Recent Findings: Advances in the next-generation sequencing technologies are accelerating the molecular dissection of the pathogenic mechanisms underlying skeletal dysplasias. Read More

Bone Res 2018 28;6. Epub 2018 Mar 28.

1Department of Cancer Biology and Genetics and Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH 43210 USA.

Genome-wide association studies (GWASs) have been instrumental in understanding complex phenotypic traits. However, they have rarely been used to understand lineage-specific pathways and functions that contribute to the trait. In this study, by integrating lineage-specific enhancers from mesenchymal and myeloid compartments with bone mineral density loci, we were able to segregate osteoblast- and osteoclast (OC)-specific functions. Read More

Kidney Int 2018 Apr;93(4):1020

Department of Nephrology, University Hospital Limerick, St Nessan's Rd, Dooradoyle, County Limerick, Ireland.

J Hum Genet 2018 Mar 22. Epub 2018 Mar 22.

Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, 108-8639, Japan.

Dysosteosclerosis (DOS) is a form of sclerosing bone disease characterized by irregular osteosclerosis and platyspondyly. Its mode of inheritance is autosomal recessive. SLC29A3 mutations have been reported as the causal gene in two DOS families, however, genetic heterogeneity has been suggested. Read More

Bone 2018 Mar 6. Epub 2018 Mar 6.

Department of Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, MO, USA; Department of Pathology and Immunology, Division of Anatomic and Molecular Pathology, Washington University School of Medicine, St. Louis, MO, USA.

Bone and marrow are the two facets of the same organ, in which bone and hematopoietic cells coexist and interact. Marrow and skeletal tissue influence each-other and a variety of genetic disorders directly targets both of them, which may result in combined hematopoietic failure and skeletal malformations. Other conditions primarily affect one organ with secondary influences on the other. Read More

Bone 2018 May 6;110:343-354. Epub 2018 Mar 6.

Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio - Coppito 2, 67100 L'Aquila, Italy. Electronic address:

Autosomal Dominant Osteopetrosis type 2 (ADO2) is a rare bone disease characterized by dense and brittle bones due to impairment of osteoclast bone resorption. Dominant negative mutations of the CLCN7 gene affect about 70% of ADO2 patients. ADO2 has no cure and our recent work established that it is suitable for gene silencing by a specific small interfering RNA that does not affect the normal mRNA, thus inducing a condition of pseudo-haplosufficiency and rescuing the bone phenotype. Read More

Gastroenterology 2018 Feb 28. Epub 2018 Feb 28.

Enteric Neuroscience Program, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background & Aims: Muscularis propria macrophages lie close to cells that regulate gastrointestinal motor function, including interstitial cells of Cajal (ICC) and myenteric neurons. In animal models of diabetic gastroparesis, development of delayed gastric emptying has been associated with loss of macrophages that express cytoprotective markers and reduced networks of ICC. Mice with long-term diabetes and normal gastric emptying have macrophages that express anti-inflammatory markers and have normal gastric ICC. Read More

Pediatr Blood Cancer 2018 Jun 22;65(6):e27010. Epub 2018 Feb 22.

Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Medical Center, Jerusalem, Israel.

Background: Infantile malignant osteopetrosis (IMO) is an autosomal recessive condition characterized by defective osteoclast activity, with hematopoietic bone marrow transplant being the only available cure. Over the past several years, new conditioning regimes and donor options have emerged, thus extending the possibility of cure to a greater number of patients and improving the outcomes of bone marrow transplant. Here we detail the outcomes of bone marrow transplant in a cohort of 31 patients treated with a combination of fludarabine, treosulphan, thiotepa, and antithymocyte globulin. Read More

J Pediatr Hematol Oncol 2018 Apr;40(3):225-226

Pediatric Hematology/Oncology, NYU Winthrop Hospital, Mineola, New York, NY.

Arch Orthop Trauma Surg 2018 Feb 10. Epub 2018 Feb 10.

Department of Orthopaedic Surgery, National Hospital Organization Fukuyama Medical Center, 4-14-17, Okinogami-cho, Fukuyama, Hiroshima, 720-8520, Japan.

Introduction: Osteopetrosis is a clinical syndrome characterized by the failure of osteoclasts to resorb bone. Affected patients usually suffer from repetitive fractures due to this pathological state. Surgical treatment of these fractures is often complicated by the difficulty of working with the extremely hard and brittle bones. Read More

Joint Bone Spine 2018 Mar 1. Epub 2018 Mar 1.

Service de rhumatologie, CHU de Rennes, hôpital Sud, 16, boulevard de Bulgarie, BP 90347, 35203 Rennes cedex 2, France; Inserm UMR 991, 35043 Rennes, France; Université Rennes 1, faculté de médecine, 35043 Rennes, France.

A finding of high bone mineral density (BMD) from routine dual-energy X-ray absorptiometry (DXA) screening is not uncommon. No consensus exists about the definition of high BMD, and T-score and/or Z-score cutoffs of ≥+2.5 or ≥+4 have been suggested. Read More

Histochem Cell Biol 2018 Apr 1;149(4):325-341. Epub 2018 Feb 1.

Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8549, Japan.

The bone is an essential organ for locomotion and protection of the body, as well as hematopoiesis and mineral homeostasis. In order to exert these functions throughout life, bone tissue undergoes a repeating cycle of osteoclastic bone resorption and osteoblastic bone formation. The osteoclast is a large, multinucleated cell that is differentiated from monocyte/macrophage lineage cells by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). Read More

Am J Physiol Cell Physiol 2018 Jan 31. Epub 2018 Jan 31.

Physiology and Biophysics, SUNY: The University at Buffalo, United States.

The SLC4 family Cl-HCO exchangers (AE1, AE2, and AE3) and Na/HCO cotransporters (NBCe1, NBCe2, NBCn1, and NBCn2) contribute to a variety of vital physiological processes including pH regulation and epithelial fluid secretion. Accordingly, their dysfunction can have devastating effects. Disorders such as epilepsy, hemolytic anemia, glaucoma, hearing loss, osteopetrosis and renal tubular acidosis are all genetically linked to SLC4-family gene loci. Read More

Chin Med J (Engl) 2018 Feb;131(3):354-356

Department of Ophthalmology, Beijing Children's Hospital, National Center for Children's Health, National Key Discipline of Pediatrics, Capital Medical University, Beijing 100045, China.

Curr Drug Targets 2018 Jan 22. Epub 2018 Jan 22.

Laboratory of Endocrinology and Metabolism, Department of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041. China.

Background: High bone mass (HBM) disorders are a group of clinically and genetically heterogeneous bone diseases characterized by increased bone density on radiographs, due to progressive bone overgrowth or impaired bone resorption, or both. Some HBM cases are secondary to other diseases, such as chronic hepatitis C virus infection. Despite the great advance in gene diagnostic technology, the majority of HBM individuals remain undiagnosed. Read More

Cell Death Differ 2018 Jan 22. Epub 2018 Jan 22.

Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.

Reorganization of the podosome into the sealing zone is crucial for osteoclasts (OCLs) to resorb bone, but the underlying mechanisms are unclear. Here, we show that tuberous sclerosis complex 1 (TSC1) functions centrally in OCLs to promote podosome organization and bone resorption through mechanistic target of rapamycin complex 1 (mTORC1) and the small GTPases Rac1/Cdc42. During osteoclastogenesis, enhanced expression of TSC1 downregulates mTORC1 activity. Read More

J Biomed Res 2018 Jan;32(1):68-76

Department of Neurological Surgery, University of California-Davis Medical Center, Sacramento, CA 95817, USA.

While management of appendicular fractures has been well described in the setting of osteopetrosis, there is limited information on managing fractures of the axial spine. Here we present an osteopetrotic patient with multiple traumatic multiple, comminuted, unstable cervical spinal fractures managed with non-operative stabilization, and provide a review of the pathophysiology, genetic characteristics, and special considerations that must be explored when determining operative versus non-operative management of spinal injury in osteopetrosis. A PubMed query was performed for English articles in the literature published up to June 2016, and used the following search terms alone and in combination: "osteopetrosis", "spine", "fractures", "osteoclasts", and "operative management". Read More

Ther Adv Chronic Dis 2018 Jan 24;9(1):51-60. Epub 2017 Nov 24.

University College Dublin, Belfield, Dublin, 4, Ireland.

In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the classification system for osteogenesis imperfecta (OI) and the resultant increase in therapeutic options available for management of OI. Bisphosphonates remain the most widely used intervention for OI, although the effect on fracture rate reduction is equivocal. Read More

Curr Osteoporos Rep 2018 Feb;16(1):13-25

Humanitas Clinical and Research Institute, via Manzoni 113, 20089, Rozzano, MI, Italy.

Purpose Of Review: The term osteopetrosis refers to a group of rare skeletal diseases sharing the hallmark of a generalized increase in bone density owing to a defect in bone resorption. Osteopetrosis is clinically and genetically heterogeneous, and a precise molecular classification is relevant for prognosis and treatment. Here, we review recent data on the pathogenesis of this disorder. Read More

Childs Nerv Syst 2018 May 11;34(5):991-994. Epub 2018 Jan 11.

Department of Neurosurgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Introduction: There are very few reports in the literature associating in hydrocephalus in osteopetrosis. As a complication of shunt procedure, there are two reports on shunt malfunction due to osseous overgrowth at the burr hole in patients with osteopetrosis. We herein report a case of osteopetrosis with hydrocephalus that was successfully treated with endoscopic third ventriculostomy (ETV). Read More

Front Med (Lausanne) 2017 20;4:234. Epub 2017 Dec 20.

Department of Orthopaedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Center of Jiangxi Province, Nanchang, China.

Osteoclasts, the only cells with bone resorption functions , maintain the balance of bone metabolism by cooperating with osteoblasts, which are responsible for bone formation. Excessive activity of osteoclasts causes many diseases such as osteoporosis, periprosthetic osteolysis, bone tumors, and Paget's disease. In contrast, osteopetrosis results from osteoclast deficiency. Read More

J Bone Miner Res 2018 Jan 3. Epub 2018 Jan 3.

Institut de Recherches Cliniques de Montréal (IRCM), Montréal, Québec, Canada.

Ostm1 mutations are responsible for the most severe form of osteopetrosis in human and mice. To gain insight into Ostm1 cellular functions, we engineered a conditional in-frame deletion of the Ostm1 transmembrane domain and generated the first Ostm1 mouse model with a human mutation. Systemic targeting of Ostm1 loss of transmembrane domain produced osteopetrosis, as in the null Ostm1 gl/gl mouse. Read More

Blood Adv 2017 Jan 30;1(4):279-281. Epub 2016 Dec 30.

Center for Childhood Cancer and Blood Diseases, The Research Institute.

HCT prior to onset of neurologic symptoms in children with OSTM1 osteopetrosis does not halt neurologic progression. Read More

Bone 2017 Dec 29. Epub 2017 Dec 29.

Department of Pathology, School of Medicine, University of Alabama at Birmingham, 1825 University Blvd., Birmingham, AL 35294, USA. Electronic address:

The tooth root is essential for normal tooth physiological function. Studies on mice with mutations or targeted gene deletions revealed that osteoclasts (OCs) play an important role in tooth root development. However, knowledge on the cellular and molecular mechanism underlying how OCs mediate root formation is limited. Read More

Ann N Y Acad Sci 2017 Dec;1410(1):93-106

Mineralized Tissue Laboratory, Hospital for Special Surgery, New York, New York.

Bone quality encompasses all the characteristics of bone that, in addition to density, contribute to its resistance to fracture. In this review, we consider changes in architecture, porosity, and composition, including collagen structure, mineral composition, and crystal size. These factors all are known to vary with tissue and animal ages, and health status. Read More

J Hip Preserv Surg 2017 Dec 23;4(4):269-275. Epub 2017 Aug 23.

Clinica Orthopedica, Ospedale di Portogruaro, 30026 Portogruaro, Italy.

Proximal femoral fracture and coxarthrosis are the most common orthopaedic problems of osteopetrosis. Fracture fixation is difficult and one-third fail, with total hip replacement as the final solution. There is little reported experience about how to deal with this particular type of bone and what has been published to date is surprisingly non-specific. Read More

BMC Med Genet 2017 12 13;18(1):148. Epub 2017 Dec 13.

Institute of Biomedical and Genetic Engineering, 24-Mauve area, G-9/1, Islamabad, 44000, Pakistan.

Background: Osteopetrosis is a rare inherited bone disorder mainly described as an increased bone density caused by defective osteoclastic bone resorption. To date, genetic variants of eleven genes have been reported so far to be associated with different types of osteopetrosis. However, malignant infantile osteopetrosis, a lethal form of the disease, is mostly (50%) caused by mutation(s) in TCIRG1 gene. Read More

J Endocrinol 2018 Feb 30;236(2):57-68. Epub 2017 Nov 30.

Skeletal Biology LaboratorySchool of Biological and Population Health Sciences, Oregon State University, Corvallis, Oregon, USA

Impaired resorption of cartilage matrix deposited during endochondral ossification is a defining feature of juvenile osteopetrosis. Growing, leptin-deficient mice exhibit a mild form of osteopetrosis. However, the extent to which the disease is (1) self-limiting and (2) reversible by leptin treatment is unknown. Read More

Acta Orthop Belg 2016 Dec;82(4):907-912

Osteopetrosis is a rare hereditary condition which may have autosomal recessive or autosomal dominant inheritance. Patients tend to present most commonly with fractures but involvement of cranial nerves and hematopoetic system is not uncommon. Patients with infantile and intermediate type tend to present more often with problems other than orthopaedic problems. Read More

Rev Bras Hematol Hemoter 2017 Oct - Dec;39(4):372-374. Epub 2017 Jul 21.

King George's Medical University, Lucknow, India.

J Bone Miner Res 2018 Apr 26;33(4):691-703. Epub 2018 Jan 26.

Department of Pathology, University of Alabama, Birmingham, AL, USA.

CCAAT/enhancer-binding protein α (C/ebpα) is critical for osteoclastogenesis by regulating osteoclast (OC) lineage commitment and is also important for OC differentiation and function in vitro. However, the role of C/ebpα in postnatal skeletal development has not been reported owing to lethality in C/ebpα mice from hypoglycemia within 8 hours after birth. Herein, we generated conditional knockout mice by deleting the C/ebpα gene in monocyte via LysM-Cre to examine its role in OC differentiation and function. Read More

Int J Osteoarchaeol 2017 Sep-Oct;27(5):853-866. Epub 2017 Jun 30.

School of Archaeology and Ancient HistoryUniversity of LeicesterLeicesterUK.

The term avian osteopetrosis is used to describe alterations to the skeletal elements of several species of domestic bird, most typically the chicken, Gallus gallus (L. 1758). Such lesions are routinely identified in animal bones from archaeological sites due to their distinctive appearance, which is characterised by proliferative diaphyseal thickening. Read More

J Bone Miner Res 2018 Mar 11;33(3):517-533. Epub 2017 Dec 11.

Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.

Extracellular vesicles (EVs) are newly appreciated regulators of tissue homeostasis and a means of intercellular communication. Reports have investigated the role of EVs and their cargoes in cellular regulation and have tried to fine-tune their biotechnological use, but to date very little is known on their function in bone biology. To investigate the relevance of EV-mediated communication between bone cells, we isolated EVs from primary mouse osteoblasts and assessed membrane integrity, size, and structure by transmission electron microscopy (TEM) and fluorescence-activated cell sorting (FACS). Read More

Avicenna J Med Biotechnol 2017 Oct-Dec;9(4):205-208

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Osteopetrosis is a group of genetically heterogonous diseases and the main feature of that is increased bone density due to osteoclast's abnormality. It has three clinical forms based on inheritance pattern, severity and age of onset: the dominant benign form (ADO), the intermediate form (IRO) and the recessive severe form (ARO). One of the recently discovered genes for ARO form is that accounts for 4% of affected persons by this type. Read More

J Pathol 2018 Mar 29;244(3):271-282. Epub 2018 Jan 29.

Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.

Osteoclast lineage commitment and differentiation have been studied extensively, although the mechanism by which transcription factor(s) control osteoclast terminal differentiation, activation, and function remains unclear. CCAAT/enhancer-binding protein α (C/ebpα) has been reported to be a key regulator of osteoclast cell lineage commitment, yet C/ebpα's roles in osteoclast terminal differentiation, activation and function, and bone homeostasis, under physiological or pathological conditions, have not been studied because newborn C/ebpα-null mice die within several hours after birth. Furthermore, the function of C/ebpα in osteoclast terminal differentiation, activation, and function is largely unknown. Read More

FASEB J 2018 Feb 4;32(2):875-887. Epub 2018 Jan 4.

Department of Orthopaedics, Brown University Alpert Medical School, Rhode Island Hospital, Providence, Rhode Island, USA.

Activation of the RAS/ERK and its downstream signaling components is essential for growth factor-induced cell survival, proliferation, and differentiation. The Src homology-2 domain containing protein tyrosine phosphatase 2 (SHP2), encoded by protein tyrosine phosphatase, non-receptor type 11 ( Ptpn11), is a positive mediator required for most, if not all, receptor tyrosine kinase-evoked RAS/ERK activation, but differentially regulates the PI3K/AKT signaling cascade in various cellular contexts. The precise mechanisms underlying the differential effects of SHP2 deficiency on the PI3K pathway remain unclear. Read More

Stem Cell Res 2017 Oct 24;24:51-54. Epub 2017 Jul 24.

Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland. Electronic address:

Pathogenic sequence variants in the Sorting Nexin 10 (SNX10) gene have been associated with autosomal recessive osteopetrosis (ARO) in human. In this study, an induced pluripotent stem cell (iPSC) line (ARO-iPSC1-11) was generated from an ARO patient carrying the homozygous c.212+1G>T mutation in SNX10, using a retroviral-based reprogramming protocol. Read More

Calcif Tissue Int 2018 Jan 10;102(1):41-52. Epub 2017 Oct 10.

Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestr. 59, 22529, Hamburg, Germany.

The main hallmark of high bone mass (HBM) disorders is increased bone mineral density, potentially visible in conventional radiographs and quantifiable by other radiographic methods. While one of the most common forms of HBM is CLCN7-related autosomal dominant osteopetrosis type II (ADO II), there is no consensus on diagnostic thresholds. We therefore wanted to assess whether CLCN7-osteopetrosis patients differ from benign HBM cases in terms of (1) bone mineral density, (2) bone structure, and (3) microarchitectural abnormalities. Read More

PLoS One 2017 5;12(10):e0185956. Epub 2017 Oct 5.

Department of Pediatrics, University of Colorado Denver, The Anschutz Medical Campus, Aurora, Colorado, United States of America.

The cytokine interferon-γ (IFN-γ) is approved as a drug to treat chronic granulomatous disease (CGD) and osteopetrosis and is also used in hyperimmunoglobulin E syndromes. Patients with CGD have defects in proteins of the NOX2 NADPH oxidase system. This leads to reduced production of microbicidal ROS by PMNs and recurrent life threatening infections. Read More

Pathologe 2018 Mar;39(2):164-171

Institut für Osteologie und Biomechanik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland.

Osteopetrosis is a rare inherited bone disorder characterized by increased bone density owing to failure in bone resorption by the osteoclasts. The disease is genetically and histologically heterogeneous with a wide spectrum of microscopic findings. The histology varies from cases with a total absence of osteoclasts to bone biopsies characterized by high numbers of enlarged multinucleated osteoclasts on a background of sclerotic cancellous bone with or without additional defect of mineralization of the bone matrix. Read More

Postgrad Med 2017 Nov 11;129(8):934-942. Epub 2017 Oct 11.

a Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.

Objectives: Defects in the chloride channel 7 (CLCN7) gene lead to autosomal dominant osteopetrosis type II (ADOII, OPTA2 MIM 166600) and autosomal recessive osteopetrosis, autosomal recessive 4 (ARO, OPTB4 MIM 611490). The objective of the present study was to expand the mutational spectrum and analyze the correlation between mutational sites and clinical phenotypes.

Methods: Seven affected individuals from unrelated Chinese families were clinically examined. Read More

J Clin Diagn Res 2017 Aug 1;11(8):SJ01-SJ02. Epub 2017 Aug 1.

Professor, Department of Paediatrics, North DMC Medical College and Hindu Rao Hospital, Delhi, India.

Bone 2017 Dec 20;105:253-261. Epub 2017 Sep 20.

Orthopaedic Research Laboratories, Boston Children's Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA. Electronic address:

Dominant negative mutations in CLCN7, which encodes a homodimeric chloride channel needed for matrix acidification by osteoclasts, cause Albers-Schönberg disease (also known as autosomal dominant osteopetrosis type 2). More than 25 different CLCN7 mutations have been identified in patients affected with Albers-Schönberg disease, but only one mutation (Clcn7) has been introduced in mice to create an animal model of this disease. Here we describe a mouse with a different osteopetrosis-causing mutation (Clcn7). Read More

Anesth Essays Res 2017 Jul-Sep;11(3):797-801

Anesthesiology, Critical Care and Pain Management Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Osteopetrosis is a rare genetic disorder of osteoclast dysfunction leading to anatomical and physiological disorders. We present the anesthesia management for the femur fracture of a 4-year-old girl with malignant infantile type of osteopetrosis. She had a ventriculoperitoneal shunt, impaired motion, visual disturbance, growth failure, facial deformity, heart murmur of moderate tricuspid regurgitation, and left ventricular heart failure, with splenomegaly and severe anemia. Read More

World Neurosurg 2017 Dec 1;108:991.e1-991.e5. Epub 2017 Sep 1.

King Khalid University Hospital, King Saud University, Saudi Arabia; Department of Neurosurgery, Stanford University, Stanford, California, USA. Electronic address:

Background: Osteopetrosis is a heterogeneous group of uncommon congenital disorders that causes bony sclerosis and remodeling. Patients who are symptomatic can show significant neurologic consequences with the involvement of cranial nerves and symptoms of increased intracranial pressure (ICP).

Case Description: We report an unusual case of a 26-year-old woman with an autosomal-dominant type of osteopetrosis who presented with headache and severe visual deterioration, both attributed to increased ICP. Read More

Reumatol Clin 2017 Aug 21. Epub 2017 Aug 21.

Servicio de Radiodiagnóstico, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, España.

Hum Genome Var 2017 17;4:17036. Epub 2017 Aug 17.

Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Osteopetrosis is a heritable disorder of the skeleton that is characterized by increased bone density on radiographs caused by defects in osteoclast formation and function. Mutations in >10 genes are identified as causative for this clinically and genetically heterogeneous disease in humans. We report two novel missense variations in a compound heterozygous state in the gene, detected through targeted exome sequencing, in a 15-year-old Japanese female with intermediate autosomal recessive osteopetrosis. Read More

Medicine (Baltimore) 2017 Aug;96(33):e7777

Department of Orthopaedics, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.

Rationale: Osteopetrosis is a rare disease that predominantly occurs in descendants of inbreeding families. In the case of fractures happen in patients with osteopetrosis, the choice between operative or conservative treatment is still controversial. Open reduction and internal fixation (ORIF) is a conventional treatment for fractures, and it possesses more applicability than conservative treatment. Read More

Acta Pharmacol Sin 2017 Nov 17;38(11):1456-1465. Epub 2017 Aug 17.

Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Human autosomal recessive osteopetrosis (ARO), also known as infantile malignant osteopetrosis, is a rare genetic bone disorder that often causes death. Mutations in T-cell immune regulator 1 (TCIRG1) are a frequent cause of human ARO. Six additional genes (TNFSF11, TNFRSF11A, CLCN7, OSTM1, SNX10, PLEKHM1) were also found to be associated with human ARO. Read More

Childs Nerv Syst 2017 Dec 31;33(12):2181-2186. Epub 2017 Jul 31.

Departement of Neuro-ophtalmology, Lille University Hospital, Lille, France.

Purpose: Osteopetrosis (OP) is a rare skeletal disease, which can affect the skull base and calvaria. A multidisciplinary approach is mandatory and patient may need neurosurgical care. Few observations have been published, and optimal management of OP is not established yet. Read More