G Cavati, D Merlotti, P Cardamone, G Dipasquale, L Gennari
{"title":"Bone Disease Associated with Inactivating Aromatase Mutations and its Management.","authors":"G Cavati, D Merlotti, P Cardamone, G Dipasquale, L Gennari","doi":"10.1007/s00223-024-01330-0","DOIUrl":"10.1007/s00223-024-01330-0","url":null,"abstract":"<p><p>Aromatase deficiency (ORPHA:91; OMIM: 613,546) is a rare, autosomal recessive disorder due to loss of function mutations in the CYP19A1 gene, described in both genders with an estimated incidence below 1/1000000. While in female the clinical manifestations generally occur at birth or in early infancy, and mainly involve sexual characteristics, in men clinical signs of aromatase deficiency mostly occur in puberty and especially in late puberty, so that diagnosis is generally established after the second decade due to tall stature, unfused epiphyses and reduced bone mass. Here we review the available information concerning the skeletal and extraskeletal phenotype and the clinical management of bone health in patients with aromatase CYP19A1 gene mutations.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"14"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Helicobacter pylori-Related Chronic Gastritis as a Risk Factor for Lower Bone Mineral Density.","authors":"Izumi Inoue, Noriko Yoshimura, Toshiko Iidaka, Chiaki Horii, Shigeyuki Muraki, Hiroyuki Oka, Hiroshi Kawaguchi, Toru Akune, Takao Maekita, Kanae Mure, Kozo Nakamura, Sakae Tanaka, Satoshi Mochida, Masao Ichinose","doi":"10.1007/s00223-024-01310-4","DOIUrl":"10.1007/s00223-024-01310-4","url":null,"abstract":"<p><p>We evaluated the role of Helicobacter pylori (H. pylori)-related chronic gastritis in the development of osteoporosis in a population-based study. A total of 1690 subjects in the cohort of the Research on Osteoarthritis/ osteoporosis Against Disability (ROAD) were investigated, and the association between gastritis and osteoporosis was evaluated by the presence of serologically assessed H. pylori-related chronic gastritis and its stage, based on H. pylori antibody titer and pepsinogen. The presence of the gastritis was associated with significantly lower bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry and a significant risk of lower BMD was observed in femoral neck (adjusted odds ratio [OR]: 0.78, 95% confidence interval [CI]: 061-0.99). The progression of the gastritis appeared to further increase the risk. In the stage of non-atrophic gastritis, the risk of lower BMD was significantly high, especially in a subgroup with higher gastritis activity in the femoral neck (adjusted OR: 0.61, 95% CI: 0.42-0.89). Meanwhile, in the stage of atrophic gastritis, the highest and significant risk of lower BMD was observed in a subgroup with the most extensive and severe atrophy in femoral neck (adjusted OR: 0.62, 95% CI: 0.42-0.91). These results suggest that H. pylori-related chronic gastritis is involved in the risk of osteoporosis, with higher activity of gastritis and more extensive atrophy leading to further increased risk. The serologically assessed stage of the gastritis could be used to identify a high-risk group for osteoporosis in H. pylori-infected subjects from general population.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"16"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emma-Emilie Knudsen, Chris H Dreyer, Søren Overgaard, Yuan Zhang, Ming Ding
{"title":"Long-Term Natural Hydroxyapatite and Synthetic Collagen Hydroxyapatite Enhance Bone Regeneration and Implant Fixation Similar to Allograft in a Sheep Model of Implant Integration.","authors":"Emma-Emilie Knudsen, Chris H Dreyer, Søren Overgaard, Yuan Zhang, Ming Ding","doi":"10.1007/s00223-024-01309-x","DOIUrl":"10.1007/s00223-024-01309-x","url":null,"abstract":"<p><p>There is an increasing demand for a suitable bone substitute to replace current clinical gold standard autografts or allografts. Majority of previous studies have focused on the early effects of substitutes on bone formation, while information on their long-term efficacies remains limited. This study investigated the efficacies of natural hydroxyapatite (nHA) derived from oyster shells and synthetic hydroxyapatite mixed with collagen (COL/HA) or chitosan (CS/HA) on bone regeneration and implant fixation in sheep. Titanium implants were inserted into critical-size defects in distal femur condyles bilaterally, and circumferential gaps around implants were filled with substitute materials or allografts (as control). 14 or 24 weeks post-operatively, the implant-bone blocks were harvested and evaluated using microarchitectural, histomorphometric, and mechanical methods. The nHA and COL/HA groups showed significant bone formation at both 14 and 24 weeks. There was a pronounced increase in bone tissue volume and ingrowth into titanium implant's porous surfaces, significantly enhancing mechanical fixation strength at 24 weeks. CS/HA had a limited ability to induce bone formation and implant fixation. We conclude that nHA and COL/HA revealed long-term effects on enhancing bone formation and implant fixation that were at least as good as allograft after 24 weeks, and both nHA and COL/HA appear to be good alternative materials to bone allograft.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"19"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shu Ran, XiTong Lin, SiQi Wang, ZhuoQi Li, BaoLin Liu
{"title":"Multi-trait Genome-Wide Analysis Identified 20 Novel Loci for Sarcopenia-Related Traits in UK Biobank.","authors":"Shu Ran, XiTong Lin, SiQi Wang, ZhuoQi Li, BaoLin Liu","doi":"10.1007/s00223-024-01312-2","DOIUrl":"10.1007/s00223-024-01312-2","url":null,"abstract":"<p><p>This study aims to identify novel loci associated with sarcopenia-related traits in UK Biobank (UKB) through multi-trait genome-wide analysis. To identify novel loci associated with sarcopenia, we integrated the genome-wide association studies (GWAS) of usual walking pace (UWP) and hand grip strength (HGS) to conduct a joint association study known as multi-trait analysis of GWAS (MTAG). We performed a transcriptome-wide association study (TWAS) to analyze the results of MTAG in relation to mRNA expression data for genes identified in skeletal muscle. Additionally, we utilized Weighted Gene Co-Expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) networks to explore the relationships between the identified genes and hub genes related to sarcopenia. We identified 15 novel loci associated with UWP and 5 novel loci associated with HGS at the genome wide significance level (GWS, <math><mrow><mi>p</mi> <mo><</mo> <mn>5</mn> <mo>×</mo> <msup><mrow><mn>10</mn></mrow> <mrow><mo>-</mo> <mn>8</mn></mrow> </msup> </mrow> </math> ). After TWAS ( <math> <mrow><msub><mi>p</mi> <mrow><mi>TWAS</mi></mrow> </msub> <mo><</mo> <mn>6.659</mn> <mo>×</mo> <msup><mrow><mn>10</mn></mrow> <mrow><mo>-</mo> <mn>6</mn></mrow> </msup> <mo>,</mo> <mn>0.05</mn> <mo>/</mo> <mn>7509</mn></mrow> </math> ), we found two significant genes: PPP1R3A, located at 7q31.1 and associated with HGS, and ZBTB38, located at 3q23 and associated with UWP. 11 identified genes associated with hub genes for sarcopenia were obtained through WGCNA. Our findings offer new insights into biological mechanisms underlying sarcopenia and identify several novel genes related to sarcopenia that warrant in-depth study.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"10"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P R Gokul, C Jarvis, G Kassab, S Armitage, M Z Mughal, D Hughes, R Ramakrishnan
{"title":"Base of Skull & Spinal Canal Narrowing in an Adolescent with Autosomal Recessive Hypophosphatemic Rickets Type 2.","authors":"P R Gokul, C Jarvis, G Kassab, S Armitage, M Z Mughal, D Hughes, R Ramakrishnan","doi":"10.1007/s00223-024-01324-y","DOIUrl":"10.1007/s00223-024-01324-y","url":null,"abstract":"<p><p>Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is an uncommon hereditary form of rickets characterised by chronic renal phosphate loss and impaired bone mineralisation. This results from compound heterozygous or homozygous pathogenic variants in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), a key producer of extracellular inorganic pyrophosphate (PPi) and an inhibitor of fibroblast growth factor23 (FGF23). ENPP1 deficiency impacts FGF23 and increases its activity. Inactivating ENPP1 variants are associated with both Generalised Arterial Calcification of Infancy (GACI) and ARHR2, even within the same family. Both conditions share a deficiency of ENPP1, displaying clinical variability without a clear genotype-phenotype correlation. Whilst pathogenic ENPP1 variants are known to be associated with various phenotypes, including vascular calcification, hearing loss, ossification of the posterior longitudinal ligament (OPLL), and pseudoxanthoma elasticum (PXE), skull changes have not been reported to our knowledge. We present herein a case of a 10-year-old girl with ARHR2, due to compound heterozygous pathogenic ENPP1 variants, who was found to have papilledema on a routine eye test. Neuroimaging revealed enlarged lateral ventricles, compression of the spinal cord at the foramen magnum with Chiari 1 malformation and a retroverted odontoid peg. She underwent two endoscopic third ventriculostomy procedures to manage the hydrocephalus and a further foramen magnum decompression procedure to alleviate her headaches and neck pain concerns. Individuals with ARHR2 may experience alterations at the base of the skull, potentially leading to base of skull narrowing, chronic hydrocephalus, and Chiari malformation.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"20"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christian Krause Anderesen, Issam Al-Najami, Winnie Liu, Eric Orwoll, Lars Folkestad
{"title":"Risk of Gastrointestinal Diseases in Osteogenesis Imperfecta: A Nationwide, Register-Based Cohort Study.","authors":"Christian Krause Anderesen, Issam Al-Najami, Winnie Liu, Eric Orwoll, Lars Folkestad","doi":"10.1007/s00223-024-01311-3","DOIUrl":"10.1007/s00223-024-01311-3","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is a group of rare genetic disorders most commonly caused by reduced amount of biologically normal collagen type I, a structural component of the gastrointestinal tract and abdominal wall. The risk of gastrointestinal (GI) disease in individuals with OI is not well understood, despite GI complaints being frequently reported by the OI population. To investigate the risk of GI diseases in individuals with OI. A Danish nationwide register-based cohort study utilizing data from the Danish National Patient Register and the Danish National Prescription Register. All individuals registered with an OI diagnosis in Denmark from 1995 through 2018, along with a reference population matched 1:5 based on sex, birth year, and month. Sub-hazard ratios (SHR) for peptic ulcer disease, diverticular disease, gastrointestinal cancers, intestinal obstruction with ileus, constipation, abdominal wall hernia, and other reasons for abdominal discomfort. The study included 864 individuals with OI (472 women) and 4,276 in the reference population (2,332 women). The SHR was significantly increased for ulcer (3.28 [95% CI 2.21-4.28]), constipation (2.67 [1.91-3.74]), and hernia (among women: 1.85 [1.22-2.80]). Higher SHRs were also observed for inflammatory bowel disease, biliary and pancreatic diseases, appendicitis, and unspecified abdominal pain. SHRs were not statistically significantly increased for diverticular disease, gastrointestinal cancers, intestinal obstruction with ileus, kidney stones or hemorrhoid disease. Individuals with OI have a higher risk of peptic ulcer disease, constipation, hernia among women, inflammatory bowel diseases, biliary and pancreatic diseases, appendicitis, and unspecified abdominal pain, compared with the general population.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"15"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chika Akabane, Mitsuo Kimura, Yukio Yamamoto, Nobukata Shimizu, Richard Weinkamer, Wolfgang Wagermaier, Peter Fratzl, Yoichiro Kashiwagi, Keigo Sawada, Shinya Murakami
{"title":"Nanostructural Analysis of Age-Related Changes Affecting Human Dentin.","authors":"Chika Akabane, Mitsuo Kimura, Yukio Yamamoto, Nobukata Shimizu, Richard Weinkamer, Wolfgang Wagermaier, Peter Fratzl, Yoichiro Kashiwagi, Keigo Sawada, Shinya Murakami","doi":"10.1007/s00223-024-01318-w","DOIUrl":"10.1007/s00223-024-01318-w","url":null,"abstract":"<p><p>Human dentin performs its function throughout life, even though it is not remodeled like bone. Therefore, dentin must have extreme durability against daily repetitive loading. Elucidating its durability requires a comprehensive understanding of its shape, structure, and anisotropy at various levels of its structure. However, few studies have examined the nanostructure of dentin as a whole and not much is known about its age-related changes. Our aim is to characterize the mineral particle characteristics of human dentin and age-related changes using synchrotron scanning small- and wide-angle X-ray scattering. 30 molar and premolar teeth extracted from 16 to 77-year-old individuals for orthodontic or periodontal reasons were used. Synchrotron-based X-ray scattering was employed to acquire two-dimensional maps of nanostructural features. These maps revealed a negative gradient of particle size toward the pulp chamber. The preferential orientation of particles was position-dependent, with a higher orientation in the area from the pulp horn to the cusp tip and root region. These patterns were maintained in different tooth types. The mineral particle thickness of the inner crown increased significantly with age. This increase could relate to the filling of tubules and, therefore, likely contribute to the deterioration of the mechanical performance of teeth with age.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"12"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J A Kanis, H Johansson, M Lorentzon, N C Harvey, E V McCloskey
{"title":"Conflating the Operational Definition of Osteoporosis with Intervention Thresholds.","authors":"J A Kanis, H Johansson, M Lorentzon, N C Harvey, E V McCloskey","doi":"10.1007/s00223-024-01336-8","DOIUrl":"10.1007/s00223-024-01336-8","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"22"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lotte Steyaert, Karel David, Jeroen Breckpot, Marleen Renard, Vincent Vander Poorten, Brigitte Decallonne
{"title":"The Delicate Balancing of Pros and Cons in the Surgical Management of Hyperparathyroidism in a Young Female with Germline Variant in the CDC73 Gene.","authors":"Lotte Steyaert, Karel David, Jeroen Breckpot, Marleen Renard, Vincent Vander Poorten, Brigitte Decallonne","doi":"10.1007/s00223-024-01334-w","DOIUrl":"10.1007/s00223-024-01334-w","url":null,"abstract":"<p><p>Hyperparathyroidism-jaw tumor syndrome is a rare form of syndromic primary hyperparathyroidism. We describe a young female with a history of common precursor B acute lymphoblastic leukaemia who was diagnosed with overt primary hyperparathyroidism due to a pathogenic CDC73 variant (c.25C > T). This patient posed several challenging management aspects: the development of nephrocalcinosis, the risk for parathyroid carcinoma, and persistent hyperparathyroidism after two selective parathyroidectomies, leading to the decision to perform a total parathyroidectomy. The latter resulted in permanent complete hypoparathyroidism, with subsequent difficult medical therapy. This case report illustrates the challenge to identify the optimal treatment of parathyroid disease in the context of hyperparathyroidism-jaw tumor syndrome, balancing the risks of hyperparathyroidism and parathyroid carcinoma against the burden of permanent hypoparathyroidism at young age.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"21"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11698747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia P Machado, Marcelo M Pinheiro, Domingos C Chula, Rafaela Ceron, Francisco I Pinheiro, Varlei A Serrato, Valderílio F Azevedo, Carolina A Moreira
{"title":"Low Bone Turnover, Mineralization Impairment, and Cortical Alterations in Patients with Axial Spondyloarthritis: A Histomorphometric Study.","authors":"Natalia P Machado, Marcelo M Pinheiro, Domingos C Chula, Rafaela Ceron, Francisco I Pinheiro, Varlei A Serrato, Valderílio F Azevedo, Carolina A Moreira","doi":"10.1007/s00223-024-01314-0","DOIUrl":"10.1007/s00223-024-01314-0","url":null,"abstract":"<p><p>Patients with radiographic axial spondyloarthritis (r-axSpA) experience a higher prevalence of fragility fractures, though the pathophysiology of osteoporosis associated with this disease remains poorly understood. The objective of this study was to evaluate the histomorphometric data in r-axSpA patients. Male r-axSpA patients up to 55 years old were enrolled in this cross-sectional study. Clinical, lab, and imaging data, including spine X-Ray to evaluate vertebral fractures and new bone formation, as well as dual-energy X-ray absorptiometry (DXA) at spine, hip, and forearm and trabecular bone score (TBS), were performed in all patients. Transiliac histomorphometry was also underwent in all patients, and data were compared with 21 male cadavers' material. A total of 21 patients were included, with a mean age of 45.8 years, long disease duration (median 17.5 years), mostly white (66.7%) and positive for HLA-B27 (90.5%). The prevalence of DXA abnormalities and low TBS (≤ 1.338) was 42.8% and 57.1%, respectively. There was higher osteoid trabecular thickness (p = 0.027) and cortical bone changes, including reduced thickness (p = 0.031) and increased porosity (p = 0.015) in r-axSpA patients. In addition, a pattern of cortical trabecularization was observed in 52.3%. Dynamic evaluation revealed a longer mineralization lag time (p = 0.0074) and lower mineralized surface (p = 0.0029) and bone formation rate (p = 0.0074) in patients compared to reference values. Our results showed a pattern of low trabecular remodeling, bone mineralization impairment, as well as cortical thickness and porosity abnormalities in men with r-axSpA. These findings may impact future treatment of bone fragility in this disease.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"17"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}