Diagnosis and Management of Osteopetrosis: Consensus Guidelines From the Osteopetrosis Working Group

Wu, Calvin; Econs, Michael J.; DiMeglio, Linda A.; Insogna, Karl L.; Levine, Michael A.; Orchard, Paul J.; Miller, Weston P.; Petryk, Anna; Rush, Eric T.; Shoback, Dolores; Ward, Leanne M.; Polgreen, Lynda E.

doi:10.1210/jc.2017-01127

Cited by 193 publications

(194 citation statements)

References 75 publications

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“…Autosomal recessive osteopetrosis is a lethal genetic disease whose main symptoms are caused by OCL dysfunction. The only treatment currently available for ARO is hematopoietic stem cell transplantation, a highly-invasive procedure that is not suitable for all patients and which does not completely reverse the damage caused by the initial failure in bone resorption Tolar et al, 2004;Wu et al, 2017). These facts, together with the rare occurrence of ARO and its heterogeneous genetic basis, make development of accurate mouse model systems for ARO essential for clarifying its cellular and molecular bases, and for developing alternative approaches for diagnosis and therapy.…”

Section: Discussionmentioning

confidence: 99%

“…A key feature among these is massive, early-onset, and widespread osteopetrosis that is caused by dysfunctional OCLs. Additional similarities include missing and impacted teeth, occasional osteomyelitis, stunted growth, failure to thrive, and a significantly reduced lifespan Tolar et al, 2004;Wu et al, 2017).…”

Section: The Snx10 R51q Mutation Leads To a Unique Form Of Aro That Cmentioning

confidence: 99%

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R51Q SNX10 induces osteopetrosis by promoting uncontrolled fusion of monocytes to form giant, non-functional osteoclasts

Barnea

Stein

Winograd‐Katz

et al. 2018

Preprint

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In this study we report on the establishment and characterization of a novel knock-in mouse model that is homozygous for the R51Q mutation in the sorting nexin 10 (SNX10) protein. This mutation leads to massive, early-onset, and widespread osteopetrosis in the mutant mice, similar to that observed in humans who are homozygous for this mutation. The diseased mice exhibit multiple additional characteristics of the corresponding human osteopetrosis, including missing and impacted teeth, occasional osteomyelitis, stunted growth, failure to thrive, and a significantly-reduced lifespan. The phenotype of homozygous R51Q SNX10 osteoclasts is unique and defines a novel form of ARO that combines both lack of bone-resorbing activity and reduced cell numbers in vivo. Furthermore, mutant osteoclasts grown on bone develop a giant cell morphology, reaching sizes that are up to three orders of magnitude larger than osteoclasts from wild-type or heterozygous mice. These large osteoclasts display poor survival in vitro, which may account for their fewer numbers in vivo. Electron microscopy studies indicate that homozygous mutant osteoclasts exhibit severely impaired ruffled borders and are incapable of resorbing bone, providing a clear cellular basis for the osteopetrotic phenotype. We propose that the R51Q SNX10 mutation directly causes osteoporosis by affecting both osteoclast formation and function.We further conclude that the maximal size of osteoclasts is determined by an active and geneticallyregulated mechanism in which SNX10 participates, and that it is disrupted by the R51Q SNX10 mutation.

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Section: Discussionmentioning

confidence: 99%

Section: The Snx10 R51q Mutation Leads To a Unique Form Of Aro That Cmentioning

confidence: 99%

R51Q SNX10 induces osteopetrosis by promoting uncontrolled fusion of monocytes to form giant, non-functional osteoclasts

Barnea

Stein

Winograd‐Katz

et al. 2018

Preprint

View full text Add to dashboard Cite

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“…Our patient presented with osteomyelitis of the right femur at the age of 9 years, followed by an osteomyelitis of the left ischiopubic ramus a few months later. X-rays at that time showed generalized increased bone density (Figure 1 Given the known evolution in osteopetrosis patients with biallelic SNX10 mutations 7,9 (Table S1) and the massive impact of the chronic bone pain on the patient's quality of life, allogeneic hematopoietic stem cell transplantation (HSCT) was offered to the patient after discussion in a multidisciplinary setting. 9,10 The patient received a genoidentical bone marrow transplantation from her brother at the age of 14.3 years without major complications.…”

Section: Intermediate Autosomal Recessive Osteopetrosis With a Large mentioning

confidence: 99%

Intermediate autosomal recessive osteopetrosis with a large noncoding deletion in SNX10: A case report

Baer

Schaefer

Michot

et al. 2019

Pediatric Blood & Cancer

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“…14,19 Osteopetrosis can affect the skull, causing thickening of the cranial vault, stenosis of the skull base foramina, and stenosis of the IAC. 14 The diagnosis of osteopetrosis can be made based on radiographic evidence of parallel bands of dense bone giving a "bone within bone" appearance on CT. 20 HCI and hyperostosis frontalis interna are diseases caused by thickening of cancellous bone within the inner table of the calvarium. 17,18,21 Patients with HCI and hyperostosis frontalis interna often present with intracranial hypertension, atrophy of the cerebrum due to compression, hypercalcemia, and abnormal electroencephalograms.…”

Section: Clinical Presentation and Evaluationmentioning

confidence: 99%

Internal Acoustic Canal Stenosis Due to Hyperostosis

Goodarzi

Toussi

Garza

et al. 2019

J Neurol Surg B Skull Base

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Background Exostoses and osteomas are benign, insidious lesions of the bone involving the internal acoustic canal (IAC). We present two cases of IAC exostoses managed with surgical decompression and review the clinical outcomes of previously reported cases in the literature. Methods A comprehensive search was conducted using PubMed Central, Web of Science Core Collection, and Google Scholar databases to identify previous reports of IAC exostoses and osteomas. A total of 26 reported cases were identified, and patient presenting symptoms, management strategies, and response to surgery was obtained when available. Results Of the 13 patients who underwent surgical decompression, 8 patients had resolution of vertigo symptoms, 10 patients had improvement of tinnitus symptoms, and all patients maintained some level of serviceable hearing. Conclusion IAC exostoses and osteomas are rare lesions that lead to insidious onset of debilitating symptoms from vestibulocochlear nerve dysfunction. Although the role of surgical decompression remains unclear, it appears that patients presenting with vertigo have more favorable response to surgical decompression as compared with those presenting with tinnitus and sensorineural hearing loss.

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Diagnosis and Management of Osteopetrosis: Consensus Guidelines From the Osteopetrosis Working Group

Abstract: Scarcity of published studies on osteopetrosis reduce the ability to develop evidence-based guidelines for the management of these patients. Expert opinion-based guidelines for this rare condition are nevertheless important to enable improved care.

Cited by 193 publications

References 75 publications

R51Q SNX10 induces osteopetrosis by promoting uncontrolled fusion of monocytes to form giant, non-functional osteoclasts

R51Q SNX10 induces osteopetrosis by promoting uncontrolled fusion of monocytes to form giant, non-functional osteoclasts

Intermediate autosomal recessive osteopetrosis with a large noncoding deletion in SNX10: A case report

Internal Acoustic Canal Stenosis Due to Hyperostosis

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