The oldest case of osteopetrosis in a human skeleton: exploring the history of rare diseases

Gresky, Julia; Sokiranski, Roman; Witzmann, Florian; Petiti, Emmanuele

doi:10.1016/s2213-8587(20)30307-7

Cited by 12 publications

(7 citation statements)

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“…It was first introduced by Albers-Schoenberg in 1904 [1]. The oldest reported case of OP in a human skeleton dates back to 4620-4456 BCE [2]. This rare hereditary disease is also referred to as Albers-Schönberg disease or marble bone disease.…”

Section: Introductionmentioning

confidence: 99%

Pediatric patient with a bilateral Salter-Harris II fracture and slipped capital femoral epiphysis secondary to autosomal recessive osteopetrosis

et al. 2022

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Treatment of femoral neck fractures secondary to osteopetrosis is an uncertain and puzzled decision. Experience in the treatment, especially in the pediatric population, is scarcely reported. The duration of conservative treatment is prolonged and poses the risks of non-union and development of coxa vara deformity. The recommended treatment is closed reduction and internal fixation; however, surgery on osteopetrotic bone is challenging due to defective bone marrow function, delayed consolidation and higher risk of intraoperative fractures. Slipped capital femoral epiphysis secondary to osteopetrosis is very rarely reported. This article presents the case of a 5-year-old female patient with rapidly deteriorating physical function due to bilateral proximal femoral Salter-Harris type II fractures with associated slippage of the growth plates secondary to confirmed autosomal recessive osteopetrosis. Operative treatment was performed in a tertiary level orthopedic center with closed reduction and internal fixation with cannulated screws. A loss of fixation with coxa vara deformity was seen on the left side 7 months postoperatively with increasing pain. A revision surgery with reosteosynthesis and a valgus osteotomy was thus performed which showed good subjective and objective results 1 year postoperatively with complete bony union.

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Section: Introductionmentioning

confidence: 99%

Pediatric patient with a bilateral Salter-Harris II fracture and slipped capital femoral epiphysis secondary to autosomal recessive osteopetrosis

et al. 2022

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“…Osteopetrosis is a genetic disorder that causes the dysregulation of bone remodeling, resulting in increased BMD in the femur, pelvis, and skull 1 . Typical findings in patients with osteopetrosis include vulnerability to fractures, scoliosis, and sacroiliac joint pain 2 . In this study, we demonstrated that Cotl1 plays a fundamental role in osteoclastogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Osteopetrosis is a genetic skeletal disease primarily caused by abnormal osteoclastogenesis 1 . Autosomal dominant osteopetrosis is the most common disorder, with an incidence of 1 in 20,000 births, whereas autosomal recessive osteopetrosis has an incidence of 1 in 250,000 births and is categorized as a rare disease 2 . Osteopetrosis is characterized by an excessive increase in bone density and susceptibility to fractures, resulting in pain, swelling, and stiffness 1 .…”

Section: Introductionmentioning

confidence: 99%

“…Osteopetrosis is characterized by an excessive increase in bone density and susceptibility to fractures, resulting in pain, swelling, and stiffness 1 . Owing to the increased bone mass, osteopetrosis can cause abnormal syndromes such as macrocephaly, craniofacial dysostosis, and bone marrow failure syndrome 2 . Interrupted alteration of the bone structure is prompted by imbalanced bone remodeling, a metabolic process that maintains healthy bone 3 .…”

Section: Introductionmentioning

confidence: 99%

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Loss of coactosin-like F-actin binding protein 1 (Cotl1) decreases platelet-mediated osteoclastogenesis and causes osteopetrosis phenotypes in mouse

Park,

Yun,

Jin

et al. 2023

Preprint

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BACKGROUNDSOsteopetrosis, a rare skeletal disease, is characterized by an increased bone mass resulting from impaired bone remodeling process. Platelet is the major bone-healing blood component involved in the regulation of bone resorption, particularly in the removal of compromised bones. Several actin-associated proteins contribute to the orchestration of actin ring formation in osteoclasts closely related to bone resorption. However, the role of coactosin-like F-actin binding protein 1 (Cotl1) in actin ring formation and platelet-mediated bone resorption mechanisms remains unclear.METHODSWhole-mountin situRNA hybridization was performed to detect cotl1 expression pattern in zebrafish.cotl1gene knockdown zebrafish using morpholino oligonucleotides and platelet marker-expressing transgenic zebrafish were investigated for finding the phenotypic clues.Cotl1knockout (Cotl1-/-) mice were generated usingCre/loxPrecombination systems.In siliconetwork analysis of the differentially expressed genes between bone marrow samples of wild type andCotl1-/-mice was conducted. Primary-cultured monocytes fromCotl1-/-mice were examined for osteoclast differentiation and mRNA and protein expression patterns.Cotl1-/-mice underwent hematological examination and bone phenotype assessments including micro-CT, bone density, histology, immunohistochemistry, electron microscopy, and mechanical testing. Genetic association of SNPs in humanCOTL1gene with estimated bone mineral density was analyzed.RESULTSZebrafishcotl1mRNA was highly expressed in the caudal hematopoietic tissue region. Knockdown ofcotl1in zebrafish embryos decreased the expression ofc-myb, a marker of hematopoietic stem cells (HSCs). Notably, the platelet receptor CD41 was reduced in the HSCs ofcotl1-depleted zebrafish andCotl1-/-mice showed reduced platelet production with platelet surface markers of CD41 and CD61. Significantly reduced osteoclast differentiation and bone resorption pit, and impaired actin ring formation were observed in the primary myocytes fromCotl1-/-mice. Structural and histological analyses of the femur revealed sclerotic bone phenotypes inCotl1-/-mice. Mechanical assessment ofCotl1-/-mouse femoral bones revealed osteopetrotic phenotypes. Association analysis of genetic variants inCOTL1gene in subjects from the UK Biobank suggested thatCOTL1is susceptible to bone density in humans.CONCLUSIONSOur results provide insights into the role of Cotl1 in platelet-mediated osteoclastogenesis and the novel finding that the loss ofCotl1-/-mice causes osteopetrosis phenotypes.Clinical PerspectiveWhat Is New?Deficiency of Cotl1 decreased platelet production in zebrafish and mice.Absence of Cotl1 disrupted the actin ring formation which is crucial for osteoclast differentiation in bone remodeling process.Cotl1knockout mice displayed sclerotic bone phenotypes and increased bone density that are representative characteristics of osteopetrosis.Genetic variants inCOTL1gene in subjects from the UK Biobank are significantly associated with bone density.What Are the Clinical Implications?The current findings suggest that Cotl1 plays a fundamental role in platelet production-mediated osteoclastogenesis during bone remodeling, providing valuable insights into novel strategies for bone health maintenance.Cotl1 may be a promising target for novel therapeutic strategies for the treatment and/or prevention of impaired osteoclastogenesis-mediated bone diseases such as osteopetrosis and osteoporosis.

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“…The first case ever recorded of marble bone disease has been dated back as early as 350 AD [ 2 ]. Since its original discovery in 1904 by German Radiologist Albers-Schonberg, studies have shown that there is a strong genetic component to this disease process.…”

Section: Introductionmentioning

confidence: 99%

Managing Osteopetrosis in the Complex Polytrauma Orthopedic Patient

Sabacinski¹,

Booth²,

Bramer³

2022

Cureus

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Osteopetrosis is a genetic illness defined by defective osteoclasts that are incapable of absorbing adequate amounts of bone. This exceedingly rare disorder has been linked to multiple genetic mutations that have a direct impact on osteoclast function. Osteopetrosis causes bones to become brittle with large amounts of cortical bone formation making patients susceptible to pathologic fractures, pancytopenia, and cranial neuropathies among other sequelae. Known as the "marble bone disease," this condition can range from as severe as causing death in newborn infants to as mild as an incidental finding of increased cortical thickening in a trauma patient. This case demonstrates an incidental finding of osteopetrosis in a trauma patient who suffered from significant injuries as a result of a high-velocity trauma. The patient was the pedestrian in a car vs pedestrian accident and suffered from a central cord syndrome in his cervical spine, a right humerus fracture, a left subtrochanteric femur fracture, a right tibia fracture, and a right fibula fracture. This case report illustrates the complexity of dealing with a polytrauma patient with osteopetrosis and reviews the literature on the approach to fracture fixation in osteopetrotic individuals. This paper will also discuss current medication recommendations and the current standard of care for optimizing patients with osteopetrosis as well as genetic counseling.

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The oldest case of osteopetrosis in a human skeleton: exploring the history of rare diseases

Cited by 12 publications

References 6 publications

Pediatric patient with a bilateral Salter-Harris II fracture and slipped capital femoral epiphysis secondary to autosomal recessive osteopetrosis

Pediatric patient with a bilateral Salter-Harris II fracture and slipped capital femoral epiphysis secondary to autosomal recessive osteopetrosis

Loss of coactosin-like F-actin binding protein 1 (Cotl1) decreases platelet-mediated osteoclastogenesis and causes osteopetrosis phenotypes in mouse

Managing Osteopetrosis in the Complex Polytrauma Orthopedic Patient

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