Noor Alhuda Sawalha, Marcos Loreto Sampaio, Dora Liu, Frank Rauch, Kerry Siminoski, Lynda Bonewald, Leanne M Ward
{"title":"Expanding the Autosomal Recessive Hypophosphatemic Rickets Type I Carrier Phenotype and Adult Treatment with Burosumab.","authors":"Noor Alhuda Sawalha, Marcos Loreto Sampaio, Dora Liu, Frank Rauch, Kerry Siminoski, Lynda Bonewald, Leanne M Ward","doi":"10.1007/s00223-026-01490-1","DOIUrl":"https://doi.org/10.1007/s00223-026-01490-1","url":null,"abstract":"","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442747","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":"Prognostic Nutritional Index is a Superior Predictor to Geriatric Nutritional Risk Index for 1-Year Mortality in Older Adult Patients with Proximal Femoral Fractures.","authors":"Shu Yamazaki, Tomohiro Shimizu, Hotaka Ishizu, Shun Shimodan, Kosuke Arita, Yusuke Ohashi, Yutaro Sugawara, Tetsuro Oue, Hiroya Hashizume, Norimasa Iwasaki","doi":"10.1007/s00223-026-01508-8","DOIUrl":"https://doi.org/10.1007/s00223-026-01508-8","url":null,"abstract":"<p><p>This prospective multicenter cohort study aimed to compare the predictive accuracy of the Prognostic Nutritional Index (PNI) and the Geriatric Nutritional Risk Index (GNRI) for 1 year mortality in older adult patients undergoing proximal femoral fracture surgery. We analyzed the data from 252 patients aged ≥ 65 years who underwent surgery. Patients were classified based on their preoperative PNI (cutoff, 40) and GNRI (cutoff, 98). To minimize confounding, 1:1 propensity score matching (PSM) was performed for each index, adjusting for age, sex, body mass index, comorbidities, and inflammatory markers. Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. The overall 1 year mortality rate was 14.7%. After PSM, the low PNI group exhibited a significantly higher mortality rate than the control group (18.9% vs. 3.3%, p < 0.01). Similarly, the low GNRI group had a significantly higher mortality rate than the control group (14.1% vs. 4.2%, p = 0.04). Cox proportional hazards analysis confirmed that both indices were independent predictors of 1 year mortality. Notably, the low-PNI group was significantly younger than the control group yet demonstrated higher mortality. Preoperative PNI and GNRI were associated with 1 year mortality in older adult patients with proximal femoral fractures and remained independent prognostic indicators after adjustment for confounders. These findings suggest that PNI and GNRI may serve as supplementary prognostic markers beyond chronological age and could provide additional information to support multidisciplinary perioperative assessment and shared clinical decision-making in this vulnerable population.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147442719","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}
Letícia Cristina Dias Lima, Isabella Ramos Cavalcante, Felipe Emanuel Oliveira Rocha, Jader Oliva Jorge, Talita Martins, Mila Fernandes Moreira Madeira, Maria José Campagnole-Santos, Soraia Macari, Clésia Cristina Nascentes, Eduardo Henrique Martins Nunes, Celso Martins Queiroz-Junior, Robson Augusto Souza Dos Santos, Paula Rocha Moreira, Marcos Augusto de Sá
{"title":"The Alamandine/MrgprD as a Key Player in Antiresorptive Effects in an Osteoporosis Experimental Model.","authors":"Letícia Cristina Dias Lima, Isabella Ramos Cavalcante, Felipe Emanuel Oliveira Rocha, Jader Oliva Jorge, Talita Martins, Mila Fernandes Moreira Madeira, Maria José Campagnole-Santos, Soraia Macari, Clésia Cristina Nascentes, Eduardo Henrique Martins Nunes, Celso Martins Queiroz-Junior, Robson Augusto Souza Dos Santos, Paula Rocha Moreira, Marcos Augusto de Sá","doi":"10.1007/s00223-025-01465-8","DOIUrl":"https://doi.org/10.1007/s00223-025-01465-8","url":null,"abstract":"<p><p>The renin-angiotensin system plays a key role in bone metabolism. While the classical renin-angiotensin system axis promotes bone resorption, the counter-regulatory axis, including alamandine via MrgprD receptor, favors bone formation. This study evaluated the therapeutic effects of alamandine in a model of osteoporosis. In vitro, alamandine reduced osteoclast activation and size in a MrgprD receptor-dependent manner. In vivo, ovariectomy-induced osteoporosis reduced bone parameters, and alamandine reversed trabecular bone loss in wild-type mice but not in MrgprD knockout mice, demonstrating the essential role of the receptor. Alamandine also reduced serum calcium and phosphorus levels in ovariectomized wild-type mice, with no effect on ovariectomized knockout animals. Furthermore, modulation of iron levels differed between genotypes, suggesting the involvement of ferroptosis-related pathways. Histological analysis revealed an increase in the number of osteoblasts and osteocytes in wild-type mice treated with alamandine, corroborating its role in osteogenic differentiation, possibly via the AMPK/eNOS pathway. In contrast, alamandine exacerbated bone resorption in ovariectomized MrgprD knockout mice, potentially through alternative renin-angiotensin system receptors. In conclusion, alamandine increases bone formation and reduces resorption through MrgprD receptor signaling, highlighting its potential as a therapeutic agent in osteoporosis.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389637","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":"Macrophage Metabolic Reprogramming-Related Osteoimmunity in Osteoporosis.","authors":"Kejia Zhou, Zhenpeng Wang, Mei Zhang","doi":"10.1007/s00223-026-01477-y","DOIUrl":"https://doi.org/10.1007/s00223-026-01477-y","url":null,"abstract":"<p><p>Osteoporosis is a disease characterized by increased bone turnover and decreased bone mass, closely associated with suppressed osteogenesis, enhanced osteoclastogenesis, and immune-metabolic dysregulation. Studies in osteoimmunology have shown that immune dysregulation can disrupt bone homeostasis through multiple signaling pathways and metabolic interactions between immune cells and bone cells. Macrophages, as key players in osteoimmunity, dynamically alter their metabolism in specific environments, integrating environmental signals to exhibit context-specific functions. Among the primary metabolic phenotypes, classically activated macrophages (M1) mainly promote bone resorption, while alternatively activated macrophages (M2) primarily facilitate osteogenesis. These effects are mainly achieved through inflammatory pathways, macrophage-driven osteoclastogenesis, and efferocytosis. Dysregulation of macrophage metabolic reprogramming in osteoimmunity can lead to diseases such as osteoporosis. The link between metabolic reprogramming and epigenetic modifications is a research hotspot in immune-metabolic diseases, and targeting macrophage metabolic reprogramming has shown potential therapeutic benefits for osteoporosis. This review discusses the impact of macrophage metabolic reprogramming-related osteoimmune pathways on osteoporosis.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282413","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}
Francisco Mônico Moreira, Virgínia Amorin Fróes de Moraes, Carolina Dos Santos Santinoni, Graziela Garrido Mori
{"title":"Extracellular Vesicles for Treatment of Bone Resorption-Related Diseases in Animal Models: Systematic Review.","authors":"Francisco Mônico Moreira, Virgínia Amorin Fróes de Moraes, Carolina Dos Santos Santinoni, Graziela Garrido Mori","doi":"10.1007/s00223-025-01474-7","DOIUrl":"10.1007/s00223-025-01474-7","url":null,"abstract":"<p><p>This systematic review aimed to analyze the usefulness of EV therapy in controlling bone resorption-related diseases in animal models. The study was conducted following the PRISMA guidelines. The search was conducted until November 2025 using PubMed/MEDLINE, Scopus, Cochrane Library, and OpenGrey databases to respond to the PICO question: Would therapy with EVs be efficient for the treatment of bone resorption-related diseases in vivo? The primary and secondary outcomes were the control of bone resorption and the molecular mechanisms involved, respectively. The risk of bias was examined according to the criteria of SYRCLE's RoB tool. A total of 1031 studies were reviewed, and after applying the eligibility criteria and excluding duplicates, 38 articles were included in the results. The usefulness of EVs in controlling bone resorption was established in the majority of studies. Increased levels of osteoprotegerin (OPG) and decreased levels of the pro-inflammatory cytokines, receptor activator of nuclear factor-kB ligand (RANKL), tartrate-resistant acid phosphatase (TRAP), and osteoclasts were reported. The studies also showed enhanced levels of alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteocalcin (OCN), contributing to increased bone density. EV is a promising treatment for bone resorption-related diseases in vivo. Further studies are needed to assess safety, optimal dosing, and ideal source cells, in order to confirm the findings and support potential investigations in humans.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":"34"},"PeriodicalIF":3.2,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12913318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212086","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}
Nathália Dantas Duarte, Fábio Roberto de Souza Batista, Marcelly Braga Gomes, Laura Gabriela Macedo, Naara Gabriela Monteiro, Gabriel Mulinari-Santos, Pedro Henrique Silva Gomes-Ferreira, Paulo Noronha Lisboa-Filho, Luiz Meirelles, Roberta Okamoto
{"title":"Local Delivery of Genistein in Peri-Implant Defects Enhances Osseointegration in Ovariectomized Rats.","authors":"Nathália Dantas Duarte, Fábio Roberto de Souza Batista, Marcelly Braga Gomes, Laura Gabriela Macedo, Naara Gabriela Monteiro, Gabriel Mulinari-Santos, Pedro Henrique Silva Gomes-Ferreira, Paulo Noronha Lisboa-Filho, Luiz Meirelles, Roberta Okamoto","doi":"10.1007/s00223-026-01496-9","DOIUrl":"10.1007/s00223-026-01496-9","url":null,"abstract":"<p><strong>Background: </strong>Estrogen deficiency, a key factor in osteoporosis, may influence peri-implant healing, which requires cautious and individualized planning for dental implant placement. Functionalizing biomaterials with bioactive molecules, such as soy-derived isoflavone, could enhance their osteoconductive potential.</p><p><strong>Objective: </strong>Investigate the performance of genistein in the functionalization of bioactive glass and deproteinized bovine bone by sonochemistry on peri-implant bone repair in ovariectomized rats.</p><p><strong>Methods: </strong>In total, 50 female rats were divided into five groups (n = 10): blood clot (CLOT); bioactive glass (BG); bioactive glass functionalized with genistein (BG + GEN); deproteinized bovine bone (BO); and deproteinized bovine bone functionalized with genistein (BO + GEN). Thirty days after ovariectomy, implants were placed in the tibia of the rats. Calcein and alizarin were administered at 14 and 24 days post-surgery, respectively. The rats were euthanized 28 days after implant placement for analysis.</p><p><strong>Results: </strong>BO + GEN showed the highest removal torque (5.4 Ncm), significantly higher than BO (2.3 Ncm; p < 0.05), followed by BG + GEN (4.2 Ncm), BG (3.3 Ncm), and CLOT (2.1 Ncm). BG + GEN and BO + GEN upregulated the bone markers (RANKL, OPG, OCN, IBSP) (p < 0.05). Micro-CT revealed higher bone volume percentage (BV/TV) in BO + GEN (11.67%) and BG + GEN (10.51%) versus their controls (p < 0.05). Trabecular separation (Tb.Sp) was significantly reduced in BO + GEN compared to BG (p < 0.05).</p><p><strong>Conclusion: </strong>These findings suggest that genistein can potentiate the osteoconductive properties of clinically used biomaterials, enhancing peri-implant bone repair in ovariectomized rats.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":"33"},"PeriodicalIF":3.2,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12913274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212128","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":"Dual Osteoprotective Actions of the Kefir Peptide KFP-1: Enhancement of Bone Formation and Suppression of Bone Resorption in Cells and Murine Models.","authors":"Min-Che Tung, Gary Ro-Lin Chang, Min-Yu Tu, Hueng-Chuen Fan, Chih-Ching Yen, Abdulkadir Cidem, I-Chien Chen, Chuan-Mu Chen","doi":"10.1007/s00223-026-01487-w","DOIUrl":"10.1007/s00223-026-01487-w","url":null,"abstract":"<p><p>KFP-1, a kefir-fermented peptide, promotes osteoblast differentiation and bone formation while inhibiting osteoclast differentiation and bone resorption. We also confirmed the bioaccessibility of KFP-1 in bone tissue and its overall benefits for bone health. Kefir is a dairy beverage rich in bioactive peptides with diverse health benefits. We identified a kefir-fermented peptide, KFP-1 (TEVPAINTIASAEPTVH), which enhances intestinal calcium absorption and may modulate bone remodeling. This study investigated the effects of KFP-1 on osteoblast and osteoclast gene expression and differentiation in BMMSCs, MC3T3-E1, BMMs, and Raw264.7 cells. Using iodine-125 labeling, we tracked KFP-1 distribution in mice following oral and intravenous administration, and evaluated its osteoprotective effects in AKR1A1 knockout (AKR1A1-KO) osteoporotic mice. KFP-1 upregulated osteogenic markers (ALP, Col1a1, OCN, OPG, RUNX2, OSX, BMP-2, β-catenin) and promoted osteoblast differentiation and mineralization, while downregulating osteoclastic markers (CTK, CTR, DC-STAMP, TRAP, c-Fos, c-Src, NFATc1) and inhibiting osteoclast differentiation and resorption via the inhibition of NFATc1, c-Fos, and c-Jun nuclear translocation and attenuation of RANKL-induced p38 MAPK, JNK, ERK, and NF-κB signaling. Biodistribution analysis showed KFP-1 reached femur and tibia at approximately 0.4% (oral) and 1% (intravenous) of the administered dose. In AKR1A1-KO mice, oral KFP-1 prevented bone loss, with additional calcium supplementation further improving cortical bone mechanical properties. These findings highlight KFP-1's dual action in promoting bone formation and inhibiting bone resorption, supporting its potential as a therapeutic adjuvant or functional food ingredient for osteoporosis prevention and bone health.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"117 1","pages":"32"},"PeriodicalIF":3.2,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12913355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212091","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}