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Osteopetrosis

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Osteopetrosis. Core disease mechanisms, molecular and cellular pathways, i...

2026-04-02
Asta MONDO:0017198 Model: Asta Scientific Corpus Retrieval 19 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Osteopetrosis. Core disease mechanisms, molecular and cellular pathways, i...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 19
  • Snippets retrieved: 20

Relevant Papers

[1] Molecular Mechanisms of Craniofacial and Dental Abnormalities in Osteopetrosis

  • Authors: Yu Ma, Ya-Li Xu, Yanli Zhang, X. Duan
  • Year: 2023
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/892ca3cdce36f8ff4d5b6e1c76a733568d2bd689
  • DOI: 10.3390/ijms241210412
  • PMID: 37373559
  • PMCID: 10299715
  • Citations: 11
  • Summary: It is found that all 13 types of osteopetrosis have craniomaxillofacial and dental phenotypes, and it is concluded that the telltale craniof facial and dental abnormalities are important for dentists and other clinicians in the diagnosis of osteOPetrosis and other genetic bone diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.510) > Osteopetrosis is a group of genetic bone disorders characterized by increased bone density and defective bone resorption. Osteopetrosis presents a series of clinical manifestations, including craniofacial deformities and dental problems. However, few previous reports have focused on the features of craniofacial and dental problems in osteopetrosis. In this review, we go through the clinical features, types, and related pathogenic genes of osteopetrosis. Then we summarize and describe the characteristics of craniofacial and dental abnormalities in osteopetrosis that have been published in PubMed from 1965 to the present. We found that all 13 types of osteopetrosis have craniomaxillofacial and dental phenotypes. The main pathogenic genes, such as chloride channel 7 gene (CLCN7), T cell immune regulator 1 (TCIRG1), osteopetrosis-associated transmembrane protein 1 (OSTM1), pleckstrin homology domain-containing protein family member 1 (PLEKHM1), and carbonic anhydrase II (CA2), and their molecular mechanisms involved in craniofacial and dental phenotypes, are discussed. We conclude that the telltale craniofacial and dental abnormalities are important for dentists and other clinicians in the diagnosis of osteopetrosis and other genetic bone diseases.

[2] Clinical, genetic aspects and molecular pathogenesis of osteopetrosis

  • Authors: D. Nadyrshina, R. Khusainova
  • Year: 2023
  • Venue: Vavilov Journal of Genetics and Breeding
  • URL: https://www.semanticscholar.org/paper/363334bbbc470c136915249d0e92bc581ecccb7a
  • DOI: 10.18699/VJGB-23-46
  • PMID: 37465191
  • PMCID: 10350861
  • Citations: 7
  • Influential citations: 1
  • Summary: The current state of the art in this field, including clinical and genetic aspects, and the molecular pathogenesis of the osteopetrosis are summarized.
  • Evidence snippets:
  • Snippet 1 (score: 0.406) > Clinical, genetic aspects and molecular pathogenesis of osteopetrosis
  • Snippet 2 (score: 0.402) > Osteopetrosis is a clinically and genetically heterogeneous group of disorders the diagnosis of which is complicated by the presence of different clinical forms and types of inheritance and the absence of a clear correlation between genotype and phenotype. Moreover, the mutations identified to date explain only 70 % of cases of osteopetrosis. The search for the molecular defects responsible for the remaining 30 % of the disease continues. > The study of osteopetrosis is necessary for DNA diagnosis, treatment prescription, and prognosis. The study of os teopetrosis has shed light on little-known aspects of bone tissue cell biology and identified new mechanisms of osteoclast differentiation and function.

[3] Organoids in gastrointestinal diseases: from bench to clinic

  • Authors: Qinying Wang, Fanying Guo, Qinyuan Zhang, Tingting Hu, Yutao Jin et al.
  • Year: 2024
  • Venue: MedComm
  • URL: https://www.semanticscholar.org/paper/9b8880d8b9d45670da950197d7e353794f51d09e
  • DOI: 10.1002/mco2.574
  • PMID: 38948115
  • PMCID: 11214594
  • Citations: 12
  • Summary: A comprehensive and systematical depiction of organoids models is drawn, providing a novel insight into the utilization of organoids models from bench to clinic and clinical adhibition.
  • Evidence snippets:
  • Snippet 1 (score: 0.405) > Organoids models offer a robust platform for investigating the potential mechanisms of GI diseases and evaluating potential therapeutic interventions.By culturing organoids derived from patients' tissues or stem cells, researchers can delve into disease-specific cellular and molecular pathways, encompassing aberrant cell signaling, perturbed immune responses, and dysfunctional metabolic processes.These disease-specific phenotypes enable the study of disease progression, screening of prospective therapeutics, as well as identification of novel drug targets and mechanisms of action for GI diseases in a clinically relevant context.

[4] New therapeutic targets in rare genetic skeletal diseases

  • Authors: M. Briggs, Peter A. Bell, M. Wright, K. A. Pirog
  • Year: 2015
  • Venue: Expert Opinion on Orphan Drugs
  • URL: https://www.semanticscholar.org/paper/1363107f71ae6d2d60abca471cddf3da5d13644b
  • DOI: 10.1517/21678707.2015.1083853
  • PMID: 26635999
  • PMCID: 4643203
  • Citations: 37
  • Influential citations: 1
  • Summary: An overview of disease mechanisms that are shared amongst groups of different GSDs and potential therapeutic approaches that are under investigation are described to generate critical mass for the identification and validation of novel therapeutic targets and biomarkers.
  • Evidence snippets:
  • Snippet 1 (score: 0.404) > proteins of the cartilage ECM such as type II collagen [50]. However, emerging knowledge suggests that the primary genetic defect may be less important than the cells' response to the expression of the mutant gene product [107]. Moreover, the largely overlooked response of a cell (i.e. chondrocyte) to the abnormal extracellular environment is also important for disease progression as illustrated by several GSDs discussed in this review. > It is important that 'omics'-based approaches and technologies are systematically applied to the study of rare GSDs so that definitive reference profiles and disease signatures are generated for each phenotype. These can then be used in a Systems Biology approach to identify both common and dissimilar pathological signatures and disease mechanisms. This approach is entirely dependent upon relevant in vitro and in vivo models (and also novel 'disease-mechanism phenocopies' [107]) for testing new diagnostic and prognostic tools and for determining the molecular mechanisms that underpin the pathophysiology so that effective therapeutic treatments can be developed and validated. This approach will eventually lead to personalized treatments and care strategies centred on shared disease mechanisms with the use of relevant biomarkers to monitor the efficacy of treatment and disease progression. > It is vital that all relevant stakeholders are involved from the outset in defining the appropriate outcomes of any potential therapeutic regime. The perceptions of a successful therapy can differ widely between the clinical academic community and the relevant patient-support groups and it is vital that there is engagement on all these issues. > In summary, the identification of causative genes and mutations for GSDs over the last 20 years, coupled with the generation and in-depth analysis of a plethora of relevant cell and mouse models, has derived new knowledge on disease mechanisms and suggested potential therapeutic targets. The fast-evolving hypothesis that clinically disparate diseases can share common disease mechanisms is a powerful concept that will generate critical mass for the identification and validation of novel therapeutic targets and biomarkers.

[5] Changes in Serum Proteomic Profiles at Different Stages of Pregnancy Toxemia in Goats

  • Authors: M. Uzti̇mür, C. N. Ünal, Gurler Akpinar
  • Year: 2025
  • Venue: Journal of Veterinary Internal Medicine
  • URL: https://www.semanticscholar.org/paper/4b9c488b5dbd65d7b26fd2ad9aed70e8c4b59942
  • DOI: 10.1111/jvim.70139
  • PMID: 40492724
  • PMCID: 12150350
  • Summary: Understanding the serum proteome profiles of goats with pregnancy toxemia might help identify the proteomes and pathways responsible for the development of this disease and improve diagnosis and treatment.
  • Evidence snippets:
  • Snippet 1 (score: 0.396) > The pathophysiology and progression of this disease are not fully understood. > Traditional biomedical research has focused on the analysis of single genes, proteins, metabolites, or metabolic pathways in diseases. This molecular reductionist approach is based on the assumption that identifying genetic variations and molecular components will lead to new treatments for diseases [13][14][15][16]. However, many diseases are complex and multifactorial, and in order to determine the phenotype of such diseases, it is necessary to understand the changes that occur in more than one gene, pathway, protein, or metabolite at the cellular, tissue, and organismal levels [17][18][19]. Therefore, in recent years, proteomics, as one field of multi-omics technologies, has helped in evaluating the complex pathogenetic mechanisms of different diseases from a broad perspective and has made substantial contributions [20,21]. In veterinary medicine, proteomic analysis of metabolic diseases such as ketosis [16], hypocalcemia [22], and fatty liver [23] in dairy cows has contributed valuable insights for the definition of new pathophysiological pathways and new diagnosis and treatment protocols for these diseases. The proteomic approach can contribute importantly to a broad and detailed understanding of the changes that occur at the organismal level associated with the increase in BHBA concentration in goats with pregnancy toxemia. Our aim was to evaluate the serum protein profiles of goats with SPT or CPT using proteomic techniques to determine the proteomic profiles of these animals and to identify the relevant pathophysiological mechanisms.

[6] Osteopetrosis: classification, pathomorphology, genetic disorders, clinical manifestations (literature review and clinical case report)

  • Authors: V. Povoroznyuk, N. Dedukh, M. Bystrytska, A. Musiienko
  • Year: 2019
  • Venue: PAIN. JOINTS. SPINE
  • URL: https://www.semanticscholar.org/paper/94ef09cd3e2d2d3ea69b144f9925736d062ade1d
  • DOI: 10.22141/2224-1507.9.2.2019.172125
  • Citations: 3
  • Summary: The paper presents with clinical case report of a patient with marble bone disease and the main pathomorphological changes in the structural organization of bone tissue are presented and features of the state of osteoclasts are shown depending on the mutation of genes controlling their functional activity.
  • Evidence snippets:
  • Snippet 1 (score: 0.395) > Osteopetrosis: classification, pathomorphology, genetic disorders, clinical manifestations (literature review and clinical case report)

[7] Intramedullary Canal-creation Technique for Patients with Osteopetrosis

  • Authors: J. Kent, D. Ferguson
  • Year: 2020
  • Venue: Strategies in Trauma and Limb Reconstruction
  • URL: https://www.semanticscholar.org/paper/438a0b7172b6e8202c22c9941d251bbd31c3d481
  • DOI: 10.5005/jp-journals-10080-1424
  • PMID: 32742432
  • PMCID: 7368361
  • Citations: 2
  • Summary: Fractures and nonunions in patients with osteopetrosis are difficult to manage; and by detailing this technique, a further option is now available for surgeons when deciding upon fixation method.
  • Evidence snippets:
  • Snippet 1 (score: 0.395) > Osteopetrosis is a rare, hereditary condition characterised by hard, brittle, "marble bone" primarily due to osteoclast dysfunction. > The incidence is 1 in 100,000 to 500,000, 1,2 and it occurs in three main forms, namely, infantile, intermediate, and adult onset. These differ by their genetic inheritance and subsequent clinical findings. 3 Infantile is autosomal recessive (AR) and results in bone marrow failure and a significantly decreased life expectancy unless bone marrow transplant is successfully performed. Intermediate is also due to AR inheritance, whereas adult onset has an autosomal dominant pattern and forms a spectrum of severity and clinical findings, including specific orthopaedic manifestations. > The primary underlying defect in all types of osteopetrosis is failure of bone reabsorption. This can occur due to a defect within the osteoclast lineage resulting in decreased acid secretion or osteoclast maturation or with the mesenchymal cells necessary for their correct function. Multiple genes have thus been implicated and there is also evidence of not only osteoclast involvement but also osteoblasts. 4 ysfunctional osteoclast activity is predominantly due to defective chloride channel 7 (ClCN7) and T cell immune regulator 1 (TCIRG1) (116 kD subunit of vacuolar proton pump) genes. 5 hese result in impairment of acidification due to defective proton pumps leading to decreased acid secretion and subsequent bone reabsorption. In addition, defects to receptor activating NF-κ B ligand (RANKL) along with monocyte-macrophage-colonystimulating factor (M-CSF) genes are responsible for inhibiting the maturation of functional, osteoclast formation. 4 Due to the clinical spectrum seen, additional genetic and environmental determinants affecting gene penetrance have also been implicated. > Other specific forms also exist, which are characterised by renal tubular acidosis and cerebral calcification due to carbonic anhydrase isoenzyme II deficiency, which again results in decreased acid secretion, 6 and due to cathepsin K mutation resulting in pycnodysostosis. 7

[8] Molecular and clinical heterogeneity in CLCN7‐dependent osteopetrosis: report of 20 novel mutations

  • Authors: A. Pangrazio, M. Pusch, E. Caldana, A. Frattini, E. Lanino et al.
  • Year: 2010
  • Venue: Human Mutation
  • URL: https://www.semanticscholar.org/paper/24317e48a583ed2e72271145f7b06fe24494fd94
  • DOI: 10.1002/humu.21167
  • PMID: 19953639
  • Citations: 88
  • Influential citations: 5
  • Summary: Preliminary genotype‐phenotype correlations suggest that haploinsufficiency is not the mechanism causing ADO II, and the availability of biochemical assays to characterize ClC‐7 function will help to confirm this hypothesis.
  • Evidence snippets:
  • Snippet 1 (score: 0.388) > The “Osteopetroses” are genetic diseases whose clinical picture is caused by a defect in bone resorption by osteoclasts. Three main forms can be distinguished on the basis of severity, age of onset and means of inheritance: the dominant benign, the intermediate and the recessive severe form. While several genes have been involved in the pathogenesis of the different types of osteopetroses, the CLCN7 gene has drawn the attention of many researchers, as mutations within this gene are associated with very different phenotypes. We report here the characterization of 25 unpublished patients which has resulted in the identification of 20 novel mutations, including 11 missense mutations, 6 causing premature termination, 1 small deletion and 2 putative splice site defects. Careful analysis of clinical and molecular data led us to several conclusions. First, intermediate osteopetrosis is not homogeneous, since it can comprise both severe dominant forms with an early onset and recessive ones without central nervous system involvement. Second, the appropriateness of haematopoietic stem cell transplantation in CLCN7‐dependent ARO patients has to be carefully evaluated and exhaustive CNS examination is strongly suggested, as transplantation can almost completely cure the disease in situations where no primary neurological symptoms are present. Finally, the analysis of this largest cohort of CLCN7‐dependent ARO patients together with some ADO II families allowed us to draw preliminary genotype‐phenotype correlations suggesting that haploinsufficiency is not the mechanism causing ADO II. The availability of biochemical assays to characterize ClC‐7 function will help to confirm this hypothesis. © 2009 Wiley‐Liss, Inc.

[9] Identification of the first deletion in the LRP5 gene in a patient with Autosomal Dominant Osteopetrosis type I

  • Authors: A. Pangrazio, E. Boudin, E. Piters, G. Damante, N. L. Iacono et al.
  • Year: 2011
  • Venue: Bone
  • URL: https://www.semanticscholar.org/paper/f885e59dcea94368989f9c1e4b66a13d40acf790
  • DOI: 10.1016/j.bone.2011.05.006
  • PMID: 21600326
  • PMCID: 3149657
  • Citations: 33
  • Summary: A patient who presented with a clinical picture of Autosomal Dominant Osteopetrosis type I (ADO I), in whom the first deletion in the LRP5 gene causing increased bone mass was identified, highlighting an increasing molecular heterogeneity in L RP5-related bone diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.387) > At the end of the eighties, Bollerslev and Andersen reviewed a large group of patients affected by Autosomal Dominant Osteopetrosis (ADO) and, on the basis of radiological and biochemical findings, suggested that two different types of ADO existed [1].More recently this clinical observation was supported by the results of molecular investigations in patients, which showed that monoallelic defects in low-density lipoprotein receptor-related protein 5 (LRP5) gene caused human ADO I, in which the long bones and the skull are mainly affected, while mutations in a single allele of the chloride channel 7 (ClCN7) gene were responsible for ADO II, in which an increased rate of bone fractures is reported.Both LRP5 and ClCN7 proteins are involved in signalling pathways or cellular processes which are crucial in bone metabolism as demonstrated by the range of bone diseases arising from different mutations in either encoding gene.In particular, biallelic loss of function mutations in LRP5 are responsible for the autosomal recessive osteoporosis pseudoglioma syndrome (OPPG; MIM 259770) [2][3][4]; on the contrary, monoallelic mutations in LRP5, initially thought to lead to a gain of function of the protein product, cause a range of phenotypes inherited in an autosomal dominant way and characterised by increased bone density.These are endosteal hyperostosis (MIM 144750), osteosclerosis (MIM 144750), dominant osteopetrosis (MIM 607634), van Buchem disease type 2 (VBCH2; MIM 607636) and high bone mass syndrome (HBM; MIM 601884) [4][5][6][7][8][9].In addition, studies in different populations have suggested that LRP5 could be a susceptibility gene for osteoporosis and fracture risk [10,11]. > The specific clinical picture is strongly related to the LRP5 domain affected by the mutation.

[10] Osteoclast Genetic Diseases

  • Authors: A. D. Fattore, A. Teti
  • Year: 2011
  • Venue: Unknown venue
  • URL: https://www.semanticscholar.org/paper/ac91c528442ed639bbef3343b3cb29cc2ea3cb6b
  • DOI: 10.5772/23417
  • Citations: 4
  • Summary: Often osteoclast diseases are monogenic, and in many of them the responsible gene and the respective function have been identified, while for other osteopetrosis, pycnodysostosis and Paget's disease of bone the causative gene has not been isolated or the exact function of the matching protein still remains unknown.
  • Evidence snippets:
  • Snippet 1 (score: 0.383) > Osteopetrosis is a rare (>1:100.000)genetic disorder characterized by an impaired osteoclast function that leads to pathological increase of bone mass and skeletal fragility.It was identified for the first time in 1904 by Albers-Scönberg, who described a patient with generalized sclerosis of the skeleton, suffering from several fractures (Albers-Schönberg, 1904).Subsequently, in 1926, Karshner denominated the syndrome "marble bone disease" or "osteopetrosis" (Karshner, 1926).Impaired bone resorption causes persistence of old bone, increase of bone mass and obstruction of cavities containing vital organs such as the bone marrow and the nervous system.Osteopetrotic patients usually suffer from pathological fractures, short stature and haematological and neural failures (Balemans et al.;2005;Del Fattore et., 2008;Frattini et.;2003;Loria-Cortes et al., 1977).Osteopetrosis is a heterogeneous disorder which includes several forms that differ on the basis of inheritance, severity and secondary clinical features (Balemans et al., 2005).So far, there is no effective cure for osteopetrosis (Del Fattore et al., 2010).Haematopoietic Stem Cell Transplantation (HSCT) is indicated only for some severe forms; however a large rate of unsuccessful engraftment and persistence of irreversible symptoms are frequently observed (Driesses et al., 2003).

[11] Zebrafish Models for Human Skeletal Disorders

  • Authors: M. Marí-Beffa, Ana B. Mesa-Román, Ivan Duran
  • Year: 2021
  • Venue: Frontiers in Genetics
  • URL: https://www.semanticscholar.org/paper/965c289599ff2b38e8ba04136ce390d3cacd7356
  • DOI: 10.3389/fgene.2021.675331
  • PMID: 34490030
  • PMCID: 8418114
  • Citations: 29
  • Summary: This article reviews the state-of-art of this “aquarium to bedside” approach describing the models according to the list provided by the Nosology Committee and intends to stimulate research in the appropriate direction to efficiently meet the actual needs of clinicians.
  • Evidence snippets:
  • Snippet 1 (score: 0.380) > Skeletal disorders are a heterogeneous group of rare hereditary diseases with many different skeletal symptoms and molecular mechanisms of disease (Krakow and Rimoin, 2010). These diseases are characterized by skeletal defects that appear during development and/or growth, the dysplasia, or at late stages and/or adulthood. These disorders may also show symptoms in other organs. Although skeletal disorders are considered rare diseases, they affect around 1.5% of births and emerge as a primary scientific objective in modern countries. Due to the available data that arise from whole genome (Wheway et al., 2015) or exome (Bamshad et al., 2011) sequencing of patients and genomewide association studies (GWASs) (Kemp et al., 2017), sufficient information is being screened for the genotype/phenotype characterization of many of these diseases. > During the last 50 years, these disorders have been subjected to a continuous revision by a Nosology Committee of the International Skeletal Dysplasia Society. This committee periodically provides a classification of them according to anatomical or physiological symptoms and genomic data, the Nosology and Classification of Genetic Skeletal Disorders (NCGSD). In the last version (Mortier et al., 2019), 461 skeletal diseases were classified in 42 groups, and 437 genes were assigned as causative of 425 of them. The anatomical features used to classify these diseases range from the tissue (chondrodysplasia or osteodysplasia) or cell affected (i.e., osteoclasts dysfunction in osteopetrosis), the severity of phenotype (achondroplasia vs. hypochondroplasia), specific genotype/phenotype relationships (FGFR3 chondrodysplasia and collagenopathies), cell functions affected (i.e., ciliopathies or cohesinopathies), or even the specific cell pathologies involved (i.e., ER-cell stress). In the NCGSD-2019, single pathogenic gene variants may be associated with several disease groups, and various phenotypes in turn may be assigned to more than one gene mutation.

[12] Clinical and Radiological Findings of Autosomal Dominant Osteopetrosis Type II: A Case Report

  • Authors: P. Kant, N. Sharda, R. Bhowate
  • Year: 2013
  • Venue: Case Reports in Dentistry
  • URL: https://www.semanticscholar.org/paper/12e1ce3d699dee9f05c9997505a68aa245960ed6
  • DOI: 10.1155/2013/707343
  • PMID: 24260721
  • PMCID: 3821930
  • Citations: 17
  • Influential citations: 1
  • Summary: The clinical and radiographic features of a 35-year-old female patient with autosomal dominant osteopetrosis type II who exhibited features of chronic generalised periodontitis, and the radiographs revealed generalised osteosclerosis and hallmark radiography features of ADO type II, that is, “bone-within-bone appearance” and “Erlenmeyer-flask deformity.”
  • Evidence snippets:
  • Snippet 1 (score: 0.380) > The term osteopetrosis is derived from the Greek word "osteo" meaning bone and "petros" meaning stone. Osteopetrosis is referred to as "marble bone disease" and "Albers-Schönberg disease", after the German radiologist credited with the first description of the condition in 1904 [1]. Osteopetrosis comprises a clinically and genetically heterogeneous group of conditions that share the hallmark of increased bone density on radiographs. The increase in bone density results from abnormalities in osteoclast differentiation or function [2]. In healthy bone, a steady state is achieved in which production of bone by cells called osteoblasts is balanced by bone resorption by osteoclasts. Dysfunctional osteoclasts that are observed in osteopetrosis result in bony overgrowth, leading to bones that are abnormally dense and brittle. It is believed that osteoclasts fail to release the necessary lysosomal enzymes for bone resorption into the extracellular space [3,4]. > Defects in different genes have been described that lead to a phenotype with osteopetrosis, and mutations in at least 10 genes have been identified as causative in humans. These defects include mutations in the gene encoding carbonic anhydrase II, the proton pump gene, and the chloride channel gene [5,6]. Recently, the immune response has been incriminated in the pathogenesis of various metabolic bone diseases, including osteopetrosis. Both cytotoxic T lymphocyte-associated antigen 4 and programmed death-1, a newly identified immunoregulatory receptor, have been shown to negatively regulate immune responses and to affect osteoclastogenesis and bone remodeling [7]. > This disease has been reported in three clinical forms: (1) malignant infantile form with poor prognosis and autosomal recessive inheritance, (2) benign/adult osteopetrosis with autosomal dominant inheritance and with fewer symptoms, (3) autosomal recessive intermediate form with clinical manifestations similar to malignant form and lowest incidence rate [8][9][10].

[13] TNF receptor-associated factors: promising targets of natural products for the treatment of osteoporosis

  • Authors: Xicheng Yang, Lili Zhao, YinQuan Pang
  • Year: 2025
  • Venue: Frontiers in Physiology
  • URL: https://www.semanticscholar.org/paper/d9021ed6a69cee708a998f67bb9fb923ec06671b
  • DOI: 10.3389/fphys.2025.1527814
  • PMID: 40496246
  • PMCID: 12148923
  • Citations: 2
  • Summary: The mechanisms by which natural compounds modulate TRAF signaling in osteoclastogenesis and osteoblastogenesis are explored, providing insights into their potential for osteoporosis treatment.
  • Evidence snippets:
  • Snippet 1 (score: 0.380) > Understanding the intricacies of these cellular and molecular mechanisms is crucial for unraveling the pathophysiology of bone disorders like osteoporosis and developing targeted therapeutic interventions to mitigate their impact. Yang et al. 10.3389/fphys.2025.1527814 3 Pathophysiology of osteoporosis > Osteoporosis is a complex skeletal disorder indicative of reduced BMD and deterioration of bone microarchitecture, causing enhanced bone fragility and susceptibility to fractures. The pathophysiology of osteoporosis involves a disruption in the delicate balance between osteoclastic bone resorption and osteoblastic bone formation within the process of bone remodeling.

[14] Key Triggers of Osteoclast-Related Diseases and Available Strategies for Targeted Therapies: A Review

  • Authors: Haidi Bi, Xing Chen, Song Gao, Xiao-Long Yu, Jun Xiao et al.
  • Year: 2017
  • Venue: Frontiers in Medicine
  • URL: https://www.semanticscholar.org/paper/e47a465d11867900c3c32555435e8795987deb20
  • DOI: 10.3389/fmed.2017.00234
  • PMID: 29326938
  • PMCID: 5742334
  • Citations: 126
  • Influential citations: 2
  • Summary: The aim of this review is to provide an updated summary of the current progress in research involving osteoclast-related diseases and of the development of targeted inhibitors of osteOClast formation.
  • Evidence snippets:
  • Snippet 1 (score: 0.376) > Osteopetrosis is a metabolic bone disease characterized by increased bone mass caused by polygenic disorders. Disorders in osteoclast formation and loss of osteoclast function are the main reasons for decreased bone resorption and increased bone mass. Recent studies have suggested that decreased bone resorption could be caused by abnormalities in the RANKL/RANK/OPG system, lack of c-Fos protein, and mutations in M-CSF, while mutations in the vacuolar (H + )-ATPase (V-ATPase) subunit, loss of CLC-7 chloride channels, and a shortage of cathepsin K are the most common reasons for osteopetrosis caused by bone resorption disorders. Bone marrow transplantation and the subsequent differentiation of hematopoietic stem cells from the implanted new bone marrow into mature and functioning osteoclasts is a treatment option for osteopetrosis.

[15] “Bridging the Gap” Everything that Could Have Been Avoided If We Had Applied Gender Medicine, Pharmacogenetics and Personalized Medicine in the Gender-Omics and Sex-Omics Era

  • Authors: D. Gemmati, K. Varani, B. Bramanti, R. Piva, G. Bonaccorsi et al.
  • Year: 2019
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/8b07704baf9c61d095539dcdb4ba800a11209bbb
  • DOI: 10.3390/ijms21010296
  • PMID: 31906252
  • PMCID: 6982247
  • Citations: 92
  • Influential citations: 3
  • Summary: The description and critical discussion of some key selected multidisciplinary topics considered as paradigmatic of sex/gender differences and sex/ gender inequalities will allow to draft and design strategies useful to fill the existing gap and move forward.
  • Evidence snippets:
  • Snippet 1 (score: 0.365) > A large number of studies have considered pathologies affecting bone, which are numerous and extremely heterogeneous. Bone is a highly dynamic tissue, constantly undergoing to catabolic and anabolic processes to maintain its flexibility and adapt to the demands of the organism for growth, mechanical loading and mineral balance [178]. Bone homeostasis is due to the opposite and complementary action of bone-forming cells (osteoblasts, OBs) and bone-resorbing cells (osteoclasts, OCs). Their synergy is implemented in a functional anatomic structure known as the basic multicellular unit (BMU) [179,180]. A considerable body of literature describes the effects of imbalances in the formation or resorption of bone, which may give rise to various diseases characterized by different levels of bone-remodelling cycle impairment, like osteoporosis, Paget's disease and osteopetrosis [178,181]. The knowledge on the mechanisms underlying the formation and maintenance of bone is rapidly increasing, as well as the development of target therapeutic strategies against bone pathologies and skeletal degeneration [178,182,183]. However, extensive investigations are hampered by the limited accessibility of bone tissue, its mineralized nature, as well as by the complexity of the molecular aspects of bone turnover processes. As a result, not much work has been done to explore the role of sex/gender in the pathophysiology, diagnosis, prognosis, and treatment of bone diseases. Many critical issues remain open and further research is needed to address emerging new challenges in this field, and to identify relevant therapeutic targets. > Currently, the most relevant approach to this complex thematic considers the numerous variables that may affect the physio-pathological bone microenvironment, namely:

[16] Osteosynthesis of an intertrochanteric fracture on osteopetrosis A case report

  • Authors: K. Tabbak, M.A. Kharroube, F. Lamnaouar, C. Elkassimi, A. Rafaoui et al.
  • Year: 2024
  • Venue: International Journal of Surgery Case Reports
  • URL: https://www.semanticscholar.org/paper/731f0b9b3e442ef6a7daa7d78cf68abfc00e50b0
  • DOI: 10.1016/j.ijscr.2024.109568
  • PMID: 38513419
  • PMCID: 10972786
  • Summary: Open reduction and anatomic plate fixation remain effective management modalities for trochanteric fractures in osteopetrosis patients as some principles are respected with better consolidation of the osteoporotic fracture.
  • Evidence snippets:
  • Snippet 1 (score: 0.365) > The name osteopetrosis is derived from the Greek language. 'Osteo' means bone, and 'petrosis' means stone. Therefore, the disease is often referred to colloquially as "marble bone disease." The disease was originally described by a radiologist in Germany, Dr. Albers-Schonberg, in 1904. Bone with abnormally increased density is the key radiographic finding. This increased density is secondary to osteoclast dysfunction and leads to the affected bones being abnormally brittle [4]. > Osteopetrosis is a rare group of bone disorders characterized by osteoclast dysfunction that causes an increase in bone density, impaired remodelling, and thus bone fragility. Intraosteoclast deficiency of the enzyme carbonic anhydrase, as well as at least 10 gene mutations-most importantly, the chloride channel gene CLCN7-have been associated with this disease. Patterns include an autosomal recessive form, osteopetrosis congenita, which carries a poor prognosis with death, usually in infancy. The autosomal dominant form, osteopetrosis tarda, is usually asymptomatic and is found in adults. Malignant variants, known as marble bone disease, are diagnosed in childhood and manifest as recurrent bony fractures, short stature, skull thickening, sensorineural hearing loss, psychomotor retardation, and distal renal tubular acidosis. Bony pain, osteomyelitis, and degenerative joint disease frequently occur [5]. > Healing and fracture remodelling in osteopetrotic patients are unpredictable. The healing response is variable [6]. > The histologic features of bone callus after a traumatic fracture in a patient with osteopetrosis are presented. The fracture callus develops in stages that are apparently normal. The tissue is initially rich in boneforming cells and vessels. One year later, however, unlike mature osteopetrotic bone, the tissue shows no Haversian organization [7]. > Management must be individualized. Decisions on whether to operate, mobilize, and allow normal daily activities must be made on a case-by-case basis, as there are no fixed guidelines for management.

[17] Metabolic bone disorders and the promise of marine osteoactive compounds

  • Authors: A. Carletti, P. Gavaia, M. L. Cancela, V. Laizé
  • Year: 2023
  • Venue: Cellular and Molecular Life Sciences: CMLS
  • URL: https://www.semanticscholar.org/paper/e71c875a4a92972d503f33ab03044e3d3db6181e
  • DOI: 10.1007/s00018-023-05033-x
  • PMID: 38117357
  • PMCID: 10733242
  • Citations: 14
  • Summary: The marine osteoactive compounds currently identified and spotted the groups of marine organisms with potential for MOC production are inventoried and the availability of in vivo screening and validation tools for the study of MOCs are briefly examined.
  • Evidence snippets:
  • Snippet 1 (score: 0.365) > These pathologies are characterized by a vast group of rare, primary monogenic disorders gathered under the name osteopetrosis, also known as the marble bone disease. Osteopetrosis is characterized by a defective bone resorption, increased bone mass and high BMD, and is associated with bone fragility and an increased risk of fractures, and, in some cases, with defective bone marrow, kidney, and nervous and immune systems [50]. There are two prevalent forms of osteopetrosis, which are distinguishable based on their inheritance modality. A more prevalent, milder, and typically late-onset form (arising late during childhood) known as autosomal dominant osteopetrosis (ADO), and a more rare, aggressive and early-onset form (arising early after birth) associated with severe phenotypes and poor prognosis, known as autosomal recessive osteopetrosis (ARO) [50]. ARO can be subdivided into osteoclast-poor and osteoclast-rich forms, depending on whether the mutation at the origin of the disease affects a gene linked to osteoclast differentiation or resorptive function [50]. In addition, a rare form of X-linked osteopetrosis (XLO) has also been described [51]. > Mutations in genes that are central to osteoclast function have been associated with the etiology of osteopetrosis, in particular those involved in the acidification of bone microenvironment (TCIRG1, CNCL7), degradation of the extracellular matrix (CTSK), and cell differentiation (RANK, RANKL, CSF1R, NEMO, RELA) [52]. There are currently no pharmaceutics to efficiently treat osteopetrosis, and therapeutic approaches are only aimed at managing symptoms and relieve pain, e.g., supplementation of vitamin D and calcium in patients with hypercalcemic seizures, transfusion of red blood cells and platelets in patients with bone marrow failure, transplantation of hematopoietic stem cells in patient suffering from the most severe forms of osteopetrosis [50]. > What is on the menu?

[18] Exocrine Pancreatic Dysfunction in Diabetes: An Observational Study

  • Authors: Ipsita Ghosh, M. Basu, Beatrice Anne, P. Mukhopadhyay, Sujoy Ghosh
  • Year: 2021
  • Venue: Indian Journal of Endocrinology and Metabolism
  • URL: https://www.semanticscholar.org/paper/a9b7ca8756816322c0ff72ee6d085c2237512950
  • DOI: 10.4103/ijem.IJEM_822_20
  • PMID: 34386397
  • PMCID: 8323623
  • Citations: 2
  • Summary: The pancreatic enzyme replacement therapy (PERT) with mixed meals to evaluate changes in glycemic state have yielded variable results.
  • Evidence snippets:
  • Snippet 1 (score: 0.365) > Osteopetrosis (Marble bone disease or Albers-Schönberg disease or Osteitis Condensans Generalisata) is a rare heterogeneous group of metabolic bone disease in which there is impaired osteoclastic function of bone resorption resulting sclerotic bones. Osteopetrosis is categorized by clinical severity and inheritance pattern into milder or benign autosomal dominant form of adult to severe or malignant, autosomal recessive form of infants, and autosomal recessive intermediate form. [1] There is defect in acidification of bones in osteopetrosis due to three mutations. First, the most common is defect in the A3 subunit of the osteoclast vacular H+-ATPase proton pump and the two other are CLCN7 and carbonic anhydrase II defect. [2] The excessive osseous tissue in sclerotic bones compromise marrow spaces, that is responsible for cytopenias and extramedullary hematopoiesis. Anemia in osteopetrosis is leukoerythroblastic in type. Constricted cranial foraminas leads to multiple cranial nerve palsies. Rickets is a paradoxical complication of infantile osteopetrosis because of impaired osteoclastic function to maintain normal calcium phosphorus balance in extra cellular fluid, despite markedly total positive calcium balance as majority of total body calcium is sequestrated in skeleton tissue. This fall in calcium is further exacerbated by inadequate dietary intake of calcium or poor absorption from gastrointestinal tract. Persistence hypocalcemia and hypophosphatemia is responsible for decreased mineralization of newly formed chondroid and osteoid bones in osteopetrorickets. [3] motopoietic stem cell transplantation (HSCT) is reserved for severe infantile osteopetrosis. It is important to detect and treat underlying rickets in these patients for proper and adequate response of HSCT. Corticosteroids and splenectomy have benefited in some patients with hematological complications but not in all cases. The host osteoclasts cells can be stimulated

[19] Genetics and Epigenetics of Bone Remodeling and Metabolic Bone Diseases

  • Authors: L. Otòn-Gonzalez, C. Mazziotta, M. Iaquinta, E. Mazzoni, Riccardo Nocini et al.
  • Year: 2022
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/eba8f239e766b5289526ae96336548df534f650a
  • DOI: 10.3390/ijms23031500
  • PMID: 35163424
  • PMCID: 8836080
  • Citations: 65
  • Influential citations: 5
  • Summary: The genetics and epigenetics of the bone remodeling process are summarized and described and the current findings behind the genetics of metabolic bone diseases are reported.
  • Evidence snippets:
  • Snippet 1 (score: 0.361) > Osteopetrosis, also known as Marble bone disease or Albers-Schönberg disease, is a rare genetic, heritable condition that causes increased bone density [45]. Osteopetrosis may be caused by mutations in at least 10 genes. Genetically and clinically, osteopetrosis is very heterogeneous, therefore, accurate molecular classification is relevant for prognosis and treatment [196]. The disease progresses as the bones grow; the cavities of the marrow are filled with compact bone which results in a reduced amount of marrow, which in turn reduces the bone's capacity to produce red blood cells. This can lead to severe anemia. Three forms of osteopetrosis can be distinguished based on the pattern of inheritance: (i) autosomal recessive, (ii) autosomal dominant, and (iii) X-linked. The first, which accounts for the most severe forms, is caused by biallelic mutations in TCIRG1, CLCN7, OSTM1, SNX10, and PLEKHM1 genes, encoding for proteins involved in the acidification of the resorption lacunae and/or in vesicular transport and loss-of-function mutations leading to osteoclast-rich osteopetrosis. Furthermore, mutations in RANKL and its receptor RANK are associated with osteoclast-poor autosomal recessive, where osteoclastogenesis is blocked [197,198]. The second osteopetrosis form can be type I or II; both differ in the presentation of clinical features and genetic mutations located in the LRP5 and CLCN7 genes, respectively. Type I derives from enhanced osteoblast activity due to reduced LRP5 affinity for the extracellular antagonists SOST and dikkopf-1 (DKK-1) and consequent increased Wnt canonical signaling [199], while the most common cause of type 2 is the presence of inactivating mutations in the chloride channel 7 (CLCN7) gene, which results in ineffective, osteoclast-mediated bone resorption [200].

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