Calcified Tissue International最新文献

{"title":"Consensus-Based Recommendations for the Diagnosis, Treatment, and Monitoring of Hypoparathyroidism: Insights from the DACH Region.","authors":"Elena Tsourdi, Karin Amrein, Christian Meier, Markus Ketteler, Michael C Kreissl, Annie Mathew, Tobias Vogelmann, Tino Schubert, Heide Siggelkow","doi":"10.1007/s00223-025-01414-5","DOIUrl":"10.1007/s00223-025-01414-5","url":null,"abstract":"<p><p>Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by low parathyroid hormone (PTH) levels, hypocalcemia, hyperphosphatemia, reduced active vitamin D (1,25-OH2 vitamin D), and hypercalciuria. Due to its rarity, non-specialized physicians often lack experience managing HypoPT. To address this, expert consensus statements were developed for the DACH region (Germany, Austria, Switzerland), considering regional differences and high HypoPT incidence. These statements aim to enhance adherence to guideline recommendations and improve non-specialist knowledge. From December 2023 to April 2024, three rounds of a Delphi consensus survey were conducted with seven DACH-region clinical experts. Consensus was defined as agreement among at least 6 of 7 participants (85%). Experts agreed surgery accounts for 90% of chronic HypoPT cases. Common symptoms include paresthesia, muscle cramps, and fatigue. Albumin-adjusted serum calcium should be measured 12-24 h post-surgically, within 2 weeks, and every 3-6 months thereafter. Key treatment goals are maintaining albumin-adjusted serum calcium in the lower normal range, symptom control, and quality of life. Long-term objectives include avoiding hypo- and hypercalcemia phases and disease-related complications. Failure of calcium and active vitamin D therapy is defined by persistent symptoms, hospitalization, laboratory values outside of the normal range, or medication intolerance. Experts emphasized using HypoPT-specific, validated quality-of-life questionnaires. This consensus provides practical guidance for non-specialists in diagnosing, treating, and monitoring HypoPT, improving care in German-speaking regions.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"107"},"PeriodicalIF":3.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820671","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}

{"title":"Effectiveness of Radiotherapy in Preventing Heterotopic Ossification: A Meta-analysis of Randomized Controlled Trials Beyond Total Hip Arthroplasty.","authors":"Lei Wen, Ge Chen, Changshun Chen, Kun Liu, Zhong Chen","doi":"10.1007/s00223-025-01416-3","DOIUrl":"10.1007/s00223-025-01416-3","url":null,"abstract":"<p><p>Heterotopic ossification (HO) frequently occurs after procedures such as hip replacements, acetabular fractures, and elbow fractures. While radiotherapy (RT) has been a longstanding preventive measure against HO, its efficacy remains controversial, with some studies questioning its effectiveness and noting potential side effects. Previous research has predominantly focused on total hip arthroplasty (THA), leading to a gap in comprehensive evaluation of RT's efficacy and safety across other conditions. This systematic review and meta-analysis were conducted strictly adhering to PRISMA guidelines, utilizing the PICO framework to critically assess randomized clinical trials. A thorough literature search was executed across PubMed, Embase, Cochrane Library, and Web of Science). Methodological integrity was ensured through structured data extraction and quality assessment using validated criteria. The protocol was prospectively registered with INPLASY, ensuring full methodological transparency. A total of seven studies with 933 patients were included in the analysis, comprising 594 patients receiving RT and 339 patients in the control condition. Subgroup analyses included 784 patients undergoing THA and 149 patients receiving other surgical interventions. Overall findings supported RT's efficacy in significantly reducing severe HO formation. Notably, subgroup analysis of patients who underwent non-THA procedures indicated no statistically meaningful reduction in the incidence of mild-to-moderate HO (Brooker I-II) after RT treatment compared to controls. Conversely, an increased risk of nonunion was specifically noted among patients receiving elbow RT. Our meta-analysis strongly supports the preventive effect of RT on HO, especially for high-risk patients and in cases that other treatments, like NSAIDs, are contraindicated or avoided. However, the risk of nonunion in elbow treatments warrants caution. Further prospective randomized controlled trials, particularly focusing on non-hip joints, are necessary to validate these findings.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"106"},"PeriodicalIF":3.2,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815813","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}

{"title":"Effect of Oral Semaglutide on Volumetric BMD and Bone Microarchitecture in Overweight/Obese Individuals with Type 2 Diabetes.","authors":"Liza Das, Sanjay Kumar Bhadada, Durairaj Arjunan, Ajay Duseja","doi":"10.1007/s00223-025-01417-2","DOIUrl":"https://doi.org/10.1007/s00223-025-01417-2","url":null,"abstract":"<p><p>Obesity, type 2 diabetes, and therapeutic weight loss are all associated with impaired bone quantity and microarchitecture. Glucagon-like peptide receptor analogs (GLP1RAs) have direct beneficial effects on bone microarchitecture, in preclinical settings. This study aimed to evaluate the net impact of GLP1RA on microarchitecture in overweight/obese type 2 diabetes individuals. It was an interventional, paired-sample cohort study with oral semaglutide in consecutive type 2 diabetes patients with overweight/obesity and metabolic-dysfunction associated steatotic liver disease. Oral semaglutide was initiated at 3 mg daily, with escalation to 14 mg at the end of 12 weeks. Bone turnover markers (P1NP, β-CTX) were estimated by electrochemiluminescence and body composition by DXA. Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed using HRpQCT (XtremeCT II, Scanco Medical). There were 36 patients (44% males) with a mean (± SD) age of 50.8 ± 10.1 years, mean BMI of 34.3 ± 6.2 kg/m² and median duration of diabetes being 7 (IQR 2-13) years. At 52 weeks, there was an increase in tibial total vBMD (317.4 ± 47.4 vs. 331.6 ± 52.7 mg HA/cm³, p = 0.06) and cortical vBMD at both radius and tibia (trend towards significance). Trabecular vBMD and trabecular bone volume fraction at radius were also increased. Males showed significantly increased tibial total and cortical vBMD, and trabecular bone volume fraction, but there was no significant change in females. There were no significant differences in bone microarchitecture based on steatosis or fibrosis reduction. Oral semaglutide improves vBMD in overweight/obese type 2 diabetes, despite a significant reduction in body weight.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"105"},"PeriodicalIF":3.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803610","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":"Expanding the Genotypic and Phenotypic Spectrum of P3H1 Related Osteogenesis Imperfecta.","authors":"Erdem Kındış, Enise Avcı Durmuşaliğlu, Elif Eviz","doi":"10.1007/s00223-025-01418-1","DOIUrl":"https://doi.org/10.1007/s00223-025-01418-1","url":null,"abstract":"<p><p>Osteogenesis Imperfecta (OI) is a genetically heterogeneous disorder with a clinical spectrum ranging from mild to severe. Biallelic P3H1 (OMIM*610339) variants are generally associated with a severe recessive phenotype. This study reports six individuals from three families with phenotypic variability and two novel variants, aiming to expand the phenotypic and genotypic spectrum of P3H1-related OI. The six patients from three unrelated families exhibited varying severity of P3H1-related OI. In Family 1, three siblings, all homozygous for the recurrent c.446 T > G (p.Leu149Arg) variant, showed marked phenotypic differences. One presented with a deforming phenotype, while the other two had milder forms with fewer fractures and little to no skeletal deformity. In Family 2, the affected individual had neonatal fractures and was compound heterozygous for a novel splice-site variant (c.1171-2_1171-1delinsC) and a missense change previously classified as variant of uncertain significance (VUS) (c.1224G > C; p.Lys408Asn). The variants were segregated confirming compound heterozygosity. In Family 3, two siblings with neonatal fractures were homozygous for a novel 58 bp deletion in exon 15 (c.2112_2169del; p.Glu708AlafsTer21), with both parents identified as carriers. This study expands the P3H1 genotypic spectrum with two novel variants and provides evidence supporting reclassification of c.1224G > C as likely pathogenic based on the updated PM3 criterion. It highlights phenotypic variability in patients with the same variant and suggests mild phenotypes may be seen in patients with certain P3H1 variants.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"104"},"PeriodicalIF":3.2,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783599","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":"Impacts of Nonenzymatic Glycation Crosslinks in Bone Matrix on the Mechanosensitivity of Osteocyte.","authors":"Cong-Jin Liu, Xiao Yang, Jing-Wen Shi, Chang-Yang Shi, Xin-Tong Wu, Fei-Xiang Lu, Yu-Bo Fan, Lian-Wen Sun","doi":"10.1007/s00223-025-01411-8","DOIUrl":"https://doi.org/10.1007/s00223-025-01411-8","url":null,"abstract":"<p><p>The products of nonenzymatic glycation (NEG) are a key contributor to various types of osteoporosis, as they affect both the physical properties of bone matrix and the function of osteoblasts and osteoclasts. However, their impact on the mechanosensitivity of osteocytes remains poorly understood. Osteocytes are embedded in lacunar-canalicular system (LCS), and their processes have abundant connections with canalicular matrix to amplify their membrane strain. Thus, we mainly studied the effects of NEG crosslinks in bone matrix on the connections between bone matrix and osteocyte processes, as well as the responses of osteocyte to the mechanical stimulation. To develop the nonenzymatic glycation crosslinked bone matrix in different degrees, we used two concentrations of D-ribose (0.1M and 0.4M) to incubate the decalcified bovine bone slices. Then the osteocyte-like cells (MLO-Y4) were seeded onto these bone slices, and the cell morphology, the mechanical properties of cell processes, the F-actin cytoskeleton, the expression of mechanical sensing elements (integrin αVβ3 and perlecan), were detected to explore the changes in mechanotransduction structure. Followed by, the intracellular Ca²⁺ responses of osteocytes were detected after applying mechanical stimulation to the cell processes. Finally, osteocalcin (OCN) and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) were detected explore the changes in osteocyte function. Results showed that the PEN content increased significantly in 0.1M group and 0.4M group compared to CON group, the hardness of bone also significantly increased in two groups; the expression of integrin αVβ3, as well as the intracellular calcium responses to local mechanical stimulation were higher in 0.1M group; the F-actin intensity, integrin αVβ3 and PLN intensity were lower in 0.4M group. The OCN expression decreased significantly in 0.1M group and 0.4M group compared to CON group. These revealed a glycation threshold may exist to influence osteocyte mechanosensitivity: the low levels of NEG crosslinks could promote the connections of osteocyte processes and bone matrix via these special mechanical sensing elements, as well as the responses of osteocyte to the local mechanical stimulation, although the high levels of NEG crosslinks disrupted this functional connectivity. However, both of these two levels of NEG crosslinks had negative effects on the ability of osteocytes regulating the bone remodeling. This study offered novel insights into the mechanism of glycation-driven bone fragility and therapeutic strategies to counteract age-related and other forms of osteoporosis.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"103"},"PeriodicalIF":3.2,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768447","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":"The Role of Heparan Sulfate in Bone Repair and Regeneration.","authors":"Yuehua Li, Lei Zheng, Wenjie Cheng, Bozhi Hou, Raymond Chung Wen Wong","doi":"10.1007/s00223-025-01413-6","DOIUrl":"10.1007/s00223-025-01413-6","url":null,"abstract":"<p><p>Heparan sulfate (HS) is synthesized in majority of cells in the human body and is typically released as an extension of polysaccharide chains, which then covalently bind to the protein core of proteoglycans to form heparan sulfate proteoglycans (HSPG). Research has shown that HS plays a crucial role in various cellular pathways of bone repair and regeneration and this review aims to summarize the role of HS in the above process. We found that the specific role of HS in bone repair and regeneration may depend on its location by analyzing the published research. Compared to cell surface HS, research on extracellular matrix (ECM) HS is limited. The current research suggests that HS can prevent the formation of blood clots after bone fracture and has a dual role in inflammation. ECM HS promotes soft callus formation and mineralization, while cell surface HS has inhibitory effects.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"102"},"PeriodicalIF":3.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697726","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}

{"title":"Bone Mineral Density During Treatment with The Janus Kinase Inhibitor Baricitinib in Patients with Rheumatoid Arthritis: A Monocentric Observational Study.","authors":"Nils Schulz, Thomas Asendorf, Pascal van Wijnen, Tim Wilhelmi, Ulf Müller-Ladner, Uwe Lange, Philipp Klemm","doi":"10.1007/s00223-025-01410-9","DOIUrl":"10.1007/s00223-025-01410-9","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is associated with systemic bone loss and thus an established risk factor for osteoporosis. Janus kinase inhibitors (JAKi) have shown osteo-protective effects. However, clinical data on the effects of baricitinib on bone mineral density (BMD) remain limited. Therefore, we investigated the effects of a 1-year treatment with baricitinib on BMD in RA patients. Patients with active RA beginning treatment with baricitinib were included. BMD was measured at the lumbar spine and femoral neck using Dual-Energy X-Ray Absorptiometry (DXA). Disease activity was assessed using DAS28-CRP and cDAI. The primary endpoint was the change in BMD after 12 months. Secondary endpoints evaluated changes in disease activity, prednisolone dose and alkaline phosphatase (AP) levels and its relation to BMD. A total of 46 RA patients were recruited, of whom 26 completed the study. Overall, BMD remained stable. Non-responders to baricitinib (based on DAS28-CRP) showed a significant decline in spine BMD (- 2.12%, p = 0.039), while responders showed stable BMD. The between-group difference in spine BMD (p = 0.008) and T-score (p = 0.012) was significant. Demographic and clinical characteristics did not differ significantly between groups. Disease activity (DAS28-CRP: p = 0.003; cDAI: p = 0.007), prednisolone dose (p = 0.006), and AP levels (p = 0.03) all improved significantly. Under baricitinib, BMD loss appeared stabilized in RA patients. Non-responders to baricitinib experienced a significant loss of BMD with a significant difference to responders raising the question if seen effects are achieved by controlling disease activity or if there is an additional explicit JAKi effect on bone metabolism. Trial registration number: DRKS00020780, date: 13.3.2020.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"101"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688945","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":"Identification of a Novel Gene ARNT2 for Osteogenic Differentiation of Mesenchymal Stem Cells.","authors":"Mina Ding, Zhiwei Hu, Ke Pei, Junyuan Hu, Yan Liao, Cheguo Cai, Jian V Zhang","doi":"10.1007/s00223-025-01407-4","DOIUrl":"10.1007/s00223-025-01407-4","url":null,"abstract":"<p><p>The balance between adipogenesis and osteogenesis in mesenchymal stem cells (MSCs) is pivotal for the maintenance of bone homeostasis. However, the genes responsible for regulating this balance are still not fully understood. This investigation sought to explore and identify novel genes that influence MSC differentiation into adipogenic and osteogenic lineages, thereby enhancing bone formation. Four datasets from the Gene Expression Omnibus (GEO) database were utilized: three focused on osteogenic differentiation (GSE73087, GSE18043, GSE114117), and one on adipogenic differentiation (GSE37836). Differentially expressed genes (DEGs) during both osteogenic and adipogenic differentiation processes were analyzed using the limma R package. A sum of 471 common differentially expressed genes (CDEGs) were found in MSC osteogenesis, comprising 240 elevated and 231 reduced genes. Similarly, in MSCs adipogenesis, 204 elevated genes and 459 reduced genes were identified. Fourteen hub genes were found to overlap between the CDEGs associated with MSC osteogenesis and DEGs linked to adipogenic differentiation. Notably, the expression of aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) was elevated during osteogenesis but reduced during adipogenesis. Overexpression of ARNT2 enhanced the expression of osteogenic markers in MSCs, while its suppression led to a decrease in osteogenic marker expression. Protein-protein interaction network analysis revealed that ARNT2 interacts with Hypoxia inducible factor 1 subunit alpha (HIF1A), B-cell lymphoma 6 (BCL6), Ubiquitin-specific-processing protease 7 (USP7), and Single-minded homolog 2 (SIM2), which are implicated in the regulation of MSCs osteogenesis. In summary, fourteen hub genes were identified as potential regulators in the osteo-adipogenic differentiation of MSCs. Among them, ARNT2 was confirmed to promote osteogenesis in MSCs and exhibited potential as a therapeutic target for bone-related diseases.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"100"},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658530","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}

{"title":"Effect of A Patient Reminder Program on Adherence in Postmenopausal Women with Osteoporosis Receiving Oral Bisphosphonate Treatment: A Randomized Clinical Control Trial.","authors":"U Stumpf, I Kyvernitakis, K Horas, P Hadji","doi":"10.1007/s00223-025-01405-6","DOIUrl":"10.1007/s00223-025-01405-6","url":null,"abstract":"<p><p>Poor adherence to oral bisphosphonate therapy remains a major challenge in the treatment of osteoporosis, substantially reducing therapeutic efficacy. While reminder interventions have been proposed as a method to enhance adherence, evidence remains limited. This study aimed to evaluate the impact of written and verbal reminders on medication adherence compared to standard patient care over a 12-month period in a real-world clinical setting. In this randomized controlled study, 180 postmenopausal women diagnosed with osteoporosis were assigned to one of three groups: standard care (control), written reminder, or verbal reminder. Interventions were administered at five standardized time points. Adherence was defined as intake of ≥80% of prescribed weekly doses (≥42 out of 52 doses) and a ≥35% reduction in serum C-terminal telopeptide of type I collagen (CTX) levels from baseline to 12 months. No significant differences in adherence rates were observed between groups: 53.2% in the control group, 52.0% in the written reminder group, and 52.7% in the verbal reminder group (χ² = 0.014; p = 0.993). Changes in bone mineral density and serum CTX levels were also comparable across groups. The implementation of standardized written or verbal reminder strategy did not result in a statistically significant improvement in adherence to oral bisphosphonate therapy. Further studies are needed to investigate the reasons for low adherence to treatment.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"99"},"PeriodicalIF":3.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648674","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}

{"title":"Blockade of Gi Signaling Enhances the Anabolic Effect of Parathyroid Hormone in Female Mice.","authors":"Liping Wang, Lalita Wattanachanya, Vikrant Piprode, Robert A Nissenson","doi":"10.1007/s00223-025-01409-2","DOIUrl":"10.1007/s00223-025-01409-2","url":null,"abstract":"<p><p>Intermittent administration of parathyroid hormone (PTH) produces potent anabolic effects on bone. These anabolic effects appear to be mediated by activation of the Gs-cyclic AMP system initiated by the PTH1 receptor (PTHR1) in osteoblast lineage cells. Gs-mediated cyclic AMP production can be inhibited by activation of Gi signaling, and we have previously demonstrated that Gi signaling in osteoblasts suppresses bone formation and thereby plays a prominent role in the bone loss associated with aging in female mice. It is not clear whether this increased Gi signaling with aging dampens the anabolic response to intermittent PTH (iPTH) administration. To address this possibility, we determined the effect of inducible blockade of Gi signaling in osteoblasts on the anabolic response to PTH in 4-month-old female mice. Blockade of Gi signaling was achieved by tetracycline-regulated expression of pertussis toxin (PTX) driven by a Col1(2.3) promoter. We found that the expression of PTX potentiated the anabolic effect of iPTH on the trabecular bone, both at the distal femur and L4 lumbar vertebra. In addition, the ability of PTH to promote cortical bone thickness and strength was evident only in mice expressing PTX. These novel results demonstrate that endogenous Gi signaling in osteoblasts limits the anabolic action of iPTH on the skeleton of adult female mice. Strategies that suppress osteoblast Gi signaling could provide an effective adjunct to iPTH therapy in the treatment of postmenopausal osteoporosis.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"98"},"PeriodicalIF":3.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641893","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}