Bone Reports最新文献

{"title":"High-fat diet induced obesity and anti-activin receptor antibody: Effects on bone properties in mice","authors":"Frederik Duch Bromer ,&nbsp;Andreas Lodberg ,&nbsp;Lykke Sylow ,&nbsp;Michala Carlsson ,&nbsp;Christian Brix Folsted Andersen ,&nbsp;Jesper Skovhus Thomsen ,&nbsp;Annemarie Brüel","doi":"10.1016/j.bonr.2025.101878","DOIUrl":"10.1016/j.bonr.2025.101878","url":null,"abstract":"<div><h3>Aim</h3><div>Weight-loss therapy often results in an unintended loss of muscle and bone mass. Inhibitors of the activin receptor signaling pathway, such as bimagrumab, an anti-activin receptor antibody (αActRIIA/IIB ab), are under investigation to counteract weight-loss induced muscle loss, but their skeletal effects in obesity remain unclear. This study investigates αActRIIA/IIB ab on bone in mice exposed to a high-fat diet (HFD) model of obesity or standard chow.</div></div><div><h3>Materials and methods</h3><div>Male C57BL/6 J mice were stratified into four groups (<em>n</em> = 10/group, standard chow or HFD for 10 weeks ± αActRIIA/IIB ab). αActRIIA/IIB ab (10 mg/kg) was administered twice weekly during the final three weeks. The femur and vertebral body were assessed using DEXA, μCT, mechanical testing, and histomorphometry.</div></div><div><h3>Results</h3><div>HFD did not affect bone density, microstructure, or strength but reduced histological bone formation markers. In standard chow mice, αActRIIA/IIB ab increased trabecular bone volume fraction (BV/TV) and volumetric bone mineral density (vBMD) by 36 %. In HFD mice, the effect of αActRIIA/IIB ab was less pronounced but still increased BV/TV (+16 %) and vBMD (+13 %). For cortical bone, μCT parameters remained largely unaffected by αActRIIA/IIB ab, while the treatment increased periosteal mineralizing bone surfaces in standard chow mice (+217 %), but not in HFD mice.</div></div><div><h3>Conclusions</h3><div>αActRIIA/IIB ab enhanced trabecular bone properties in standard chow-fed mice, but its anabolic effects were blunted in HFD-fed mice. Furthermore, αActRIIA/IIB ab improved cortical histological bone formation markers, while morphology remained unaffected, suggesting a site- or time-specific difference. Thus, αActRIIA/IIB ab holds potential for mitigating weight-loss-associated bone deterioration.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"27 ","pages":"Article 101878"},"PeriodicalIF":2.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent fasting alleviates obesity-associated impairments in bone fracture healing: Exploring the role of gut microbiome","authors":"Honey Hendesi ,&nbsp;Dana A. Godfrey ,&nbsp;Ana Ferreira Ruble ,&nbsp;Aaron M. Tran ,&nbsp;David A. Villani ,&nbsp;Samantha H. Landgrave ,&nbsp;Nur A. Hasan ,&nbsp;Douglas J. Adams ,&nbsp;Michael J. Zuscik","doi":"10.1016/j.bonr.2025.101876","DOIUrl":"10.1016/j.bonr.2025.101876","url":null,"abstract":"<div><div>Intermittent Fasting (IF) is a dietary strategy with metabolic benefits that can reverse certain obesity-related pathologies. This study aimed to investigate whether IF can mitigate delayed bone fracture healing associated with obesity. Using cohorts of mice on high-fat or control diets, we applied either an ad libitum feeding or an alternate-day fasting regimen to animals from both diet groups. We assessed bone healing outcomes by evaluating callus mineralization and adipocyte accumulation within the callus through micro computed tomography (micro-CT), histology, and immunohistochemical analyses. Since IF is known to modulate gut microbiome composition, often associated with improvement in various metabolic and inflammatory processes, particularly in high-fat-fed mice, we also explored the microbial community changes in IF mice through 16S rRNA sequencing of cecal samples. Metabolically, IF led to reduced body weight and improved glucose tolerance in obese mice. Regarding fracture healing outcomes, reduced/delayed mineralization and adipocyte accumulation in fracture callus tissue in the high-fat-fed cohort were significantly attenuated when the high-fat-fed mice were subjected to alternate-day fasting. These benefits of IF were not observed in lean mice fed a control diet. Furthermore, IF significantly altered the gut microbiota of mice on a high-fat diet, including an increased abundance of short-chain fatty acid producing bacteria, known for their positive effect on bone density, and a reduction in various pro-inflammatory taxa. While the mechanistic role remains unknown, these findings suggest that the improved fracture healing observed in obese mice following IF may be associated with alterations in gut microbiome composition and function.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"27 ","pages":"Article 101876"},"PeriodicalIF":2.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of burosumab conversion on calciuria and nephrocalcinosis in children with XLH: A real-world cohort study","authors":"Guido Filler ,&nbsp;Harry Chandrakumaran ,&nbsp;Funmbi Babalola ,&nbsp;Dougenie Emile ,&nbsp;Shih-Han Susan Huang ,&nbsp;Robert Stein","doi":"10.1016/j.bonr.2025.101877","DOIUrl":"10.1016/j.bonr.2025.101877","url":null,"abstract":"<div><h3>Background</h3><div>Burosumab, a monoclonal antibody to fibroblast growth factor 23 (FGF23), is effective for X-linked hypophosphatemic rickets (XLH). Renal effects, particularly calciuria and nephrocalcinosis, remain incompletely characterized.</div></div><div><h3>Methods</h3><div>In this retrospective cohort, 13 children with genetically confirmed XLH (7 females, 6 males; 0.6–16.3 years) were evaluated after conversion from conventional therapy to burosumab. Longitudinal changes in serum phosphate, TmP/GFR, TRP, 1,25(OH)₂D, intact parathyroid hormone (PTH), and urinary calcium/creatinine (Ca:Cr) were assessed. Hypercalciuria was defined using age-specific SI thresholds; Ca:Cr was also expressed as ×ULN (Ca:Cr divided by the age-specific upper limit).</div></div><div><h3>Results</h3><div>Burosumab improved serum phosphate (<em>p</em> &lt; 0.001), TmP/GFR (p &lt; 0.001), and TRP (<em>p</em> = 0.007). Despite normalized phosphate handling, two patients developed de novo nephrocalcinosis. No child was hypercalciuric at washout or Day 14; two had ≥1 episode later. A repeated-measures analysis of log10(×ULN) showed no overall time effect from washout to Day 56 (F(4,29) = 1.66, <em>p</em> = 0.185). A larger decline in PTH correlated with higher Ca:Cr (<em>p</em> &lt; 0.05), whereas 1,25(OH)₂D did not.</div></div><div><h3>Conclusion</h3><div>Burosumab improves phosphate homeostasis in children with XLH, but a minority may develop hypercalciuria and nephrocalcinosis, potentially linked to PTH suppression. Vigilant biochemical and ultrasound monitoring—particularly early after conversion—and consideration of prophylaxis in high-risk cases are advisable.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"27 ","pages":"Article 101877"},"PeriodicalIF":2.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of geranylgeranyl diphosphate synthase inhibitor treatment on osteoblast biology and application in a conditioned media model of myeloma bone disease","authors":"Molly E. Muehlebach ,&nbsp;Sarah A. Holstein","doi":"10.1016/j.bonr.2025.101874","DOIUrl":"10.1016/j.bonr.2025.101874","url":null,"abstract":"<div><div>Myeloma bone disease (MBD) is characterized by tumor-induced osteoclast activation with concomitant suppression of osteoblast activity. Nitrogen bisphosphonates (NBPs), including zoledronic acid (ZA), are a mainstay of MBD treatment, due to their anti-osteoclastic effects secondary to high bone affinity and indirect disruption of protein geranylgeranylation through inhibition of farnesyl diphosphate synthase. The development of geranylgeranyl diphosphate synthase (GGDPS) inhibitors (GGSIs) represents a more selective means of targeting geranylgeranylation. The GGSI RAM2061 has direct anti-myeloma activity in vitro and in vivo, achieves both systemic and skeletal distribution, and has anti-osteoclastic activity. However, the effects of this novel therapy on osteoblast activity or in a setting that recapitulates the MBD milieu have yet to be explored. Exposure to RAM2061 or ZA during MC3T3-E1 differentiation resulted in impairment in osteoblast function, including alkaline phosphatase and mineralization activity, however minimal effects were observed in differentiated MC3T3-E1 cells that were subsequently exposed to drug. To evaluate the impact of RAM2061 on osteoblast or osteoclast activity under MBD-like conditions, JJN3 myeloma cell conditioned media (CM) was collected and added to bone cell cultures in order to simulate osteoclast-activating or osteoblast-inhibitory MBD microenvironments. These studies determined that RAM2061 maintains anti-resorptive effects and osteoblast inhibitory effects in undifferentiated precursors while in the presence of JJN3 CM. However, no appreciable effects were detected in osteoblasts exposed to drug post-differentiation. Overall, these studies contribute to the mechanistic understanding of NBP and GGSI effects in the bone and provide support for the continued investigation of GGSIs in MBD.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"27 ","pages":"Article 101874"},"PeriodicalIF":2.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Dose-response effects of alcohol on biochemical markers of bone turnover in non-human primates: Effects of species, sex and age of onset of drinking” [Bone Rep. 16 (2021) 101159]","authors":"M.L. Benton ,&nbsp;V.A. Jimenez ,&nbsp;N. Newman ,&nbsp;S.W. Gonzales ,&nbsp;K.A. Grant ,&nbsp;R.T. Turner ,&nbsp;U.T. Iwaniec ,&nbsp;E.J. Baker","doi":"10.1016/j.bonr.2025.101868","DOIUrl":"10.1016/j.bonr.2025.101868","url":null,"abstract":"","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101868"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Multigenerational genetic inheritance and clinical characteristics of the rare disease hypophosphatasia in 6 families: A case series” [Bone Rep. 26 (2025) 1–6 (101857)]","authors":"Peter Kannu ,&nbsp;Aliya A. Khan ,&nbsp;Mira Francis ,&nbsp;Jonathan D. Adachi","doi":"10.1016/j.bonr.2025.101866","DOIUrl":"10.1016/j.bonr.2025.101866","url":null,"abstract":"","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101866"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Between-subject and within-subject variability in measures of biochemical markers of bone turnover in cynomolgus and rhesus macaques” [Bone Rep. 15(2021) 101126]","authors":"L.H. Sattgast ,&nbsp;A.J. Branscum ,&nbsp;V.A. Jimenez ,&nbsp;N. Newman ,&nbsp;K.A. Grant ,&nbsp;R.T. Turner ,&nbsp;U.T. Iwaniec","doi":"10.1016/j.bonr.2025.101867","DOIUrl":"10.1016/j.bonr.2025.101867","url":null,"abstract":"","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101867"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifetime follow-up of an adult patient with pediatric-onset hypophosphatasia complicated with advanced chronic kidney disease","authors":"Maria Sääf ,&nbsp;Sigridur Björnsdottir ,&nbsp;Mathias Haarhaus ,&nbsp;Ellen-Margrethe Hauge ,&nbsp;Diana Atanasova ,&nbsp;Per Magnusson","doi":"10.1016/j.bonr.2025.101872","DOIUrl":"10.1016/j.bonr.2025.101872","url":null,"abstract":"<div><div>Hypophosphatasia (HPP) is a rare inborn-error-of-metabolism caused by mutations in the <em>ALPL</em> gene, resulting in deficient activity of tissue-nonspecific alkaline phosphatase and impaired skeletal mineralization. Affected individuals have a higher prevalence of chronic kidney disease (CKD) than the general population. We report a woman who underwent craniosynostosis surgery in infancy and lost her deciduous teeth prematurely. From age 27, she experienced recurrent foot pain due to multiple metatarsal fractures. Low levels of total alkaline phosphatase (ALP) was noted at 39 years of age, and low activities for the three bone-specific ALP (BALP) isoforms B/I, B1 and B2. Genetic analysis revealed 2 missense variants in the <em>ALPL</em> gene (p.Glu191Lys and p.Gly456Arg) confirming HPP. At age 44, she developed bilateral hip fissures requiring right-sided total hip replacement. Treatment with the parathyroid hormone analogue teriparatide (20 μg/day) was initiated at age 50, leading to increased BALP isoform levels indicating improved mineralization, less bone pain, and no new fractures during 9 months of treatment, which was stopped due to hypercalcemia and hyperphosphatemia. She began peritoneal dialysis at age 55 and received a kidney transplant at age 58. At age 65, seven years post-transplantation, she remained free of new fractures and significant bone pain. This case illustrates the long-term natural history of HPP with progressive skeletal complications across decades, and highlights the potential of short-term teriparatide as a therapeutic option for symptom relief and improved mineralization. It also suggests that kidney transplantation may contribute to improved bone health in HPP with advanced CKD.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101872"},"PeriodicalIF":2.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of biomechanical properties of ex vivo human femoral cortical bone using Raman spectroscopy and machine learning algorithms","authors":"Mustafa UNAL ,&nbsp;Ramazan UNLU ,&nbsp;Sasidhar UPPUGANTI ,&nbsp;Jeffry S. NYMAN","doi":"10.1016/j.bonr.2025.101870","DOIUrl":"10.1016/j.bonr.2025.101870","url":null,"abstract":"<div><div>This study applied Raman spectroscopy (RS) to ex vivo human cadaveric femoral mid-diaphysis cortical bone specimens (<em>n</em> = 118 donors; age range 21–101 years) to predict fracture toughness properties via machine learning (ML) models. Spectral features, together with demographic variables (age, sex) and structural parameters (cortical porosity, volumetric bone mineral density), were fed into support vector regression (SVR), extreme tree regression (ETR), extreme gradient boosting (XGB), and ensemble models to predict fracture-toughness metrics such as crack-initiation toughness (K_init) and energy-to-fracture (J-integral). Feature selection was based on Raman-derived mineral and organic matrix parameters, such as ν₁Phosphate (PO₄)/CH₂-wag, ν₁PO₄/Amide I, and others, to capture the complex composition of bone. Our results indicate that ensemble models consistently outperformed individual models, with the best performance for crack initiation toughness (K_init) prediction being achieved using the ensemble approach. This yielded a coefficient of determination (R²) of 0.623, root-mean squared error (RMSE) of 1.320, mean absolute error (MAE) of 1.015, and mean percentage absolute error (MAPE) of 0.134. For prediction of the overall energy to propagate a crack (J-integral), the XGB model achieved an R² of 0.737, RMSE of 2.634, MAE of 2.283, and MAPE of 0.240. This study highlights the importance of incorporating mineral quality properties (MP) and organic matrix properties (OMP) for enhanced prediction accuracy. This work represents the first-ever study combining Raman spectroscopy with other clinical and structural features to predict fracture toughness of human cortical bone, demonstrating the potential of artificial intelligence (AI) and ML in advancing bone research. Future studies could focus on larger datasets and more advanced modeling techniques to further improve predictive capabilities.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101870"},"PeriodicalIF":2.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulated microgravity accurately models long-duration spaceflight effects on bone and skeletal muscle in skeletally immature mice","authors":"Michael A. Friedman ,&nbsp;Yasmina Zeineddine ,&nbsp;Olivier Tuyambaze ,&nbsp;Wesam Elhawabri ,&nbsp;Ahmed Al Shammary ,&nbsp;Louis Stodieck ,&nbsp;Virginia L. Ferguson ,&nbsp;Henry J. Donahue","doi":"10.1016/j.bonr.2025.101871","DOIUrl":"10.1016/j.bonr.2025.101871","url":null,"abstract":"<div><div>Spaceflight (SF) and disuse result in decreases in bone and skeletal muscle volume that increase fracture risk. Hindlimb unloading (HLU) has been widely used to model the effects of microgravity. However, the effects of SF and HLU on bone and skeletal muscle have not been directly compared during long-duration SF. We examined the effects of five weeks of SF and HLU in the femurs of female Balb/c mice. For the first time, SF and HLU were directly compared using mice of the same age, strain, sex, and duration as a mission to the ISS. We hypothesized that HLU would accurately model SF, resulting in similar bone and skeletal muscle loss. Ten-week old female Balb/c mice were assigned to baseline, vivarium control, habitat control, and SF groups (n = 10/group). A separate cohort of 10-week female Balb/c mice were placed in HLU or control (n = 10/group). Femoral cortical area increased from baseline in all groups except HLU. The magnitudes of increases were lower in the SF and HLU groups. Similar effects were seen in trabecular bone. Femoral ultimate force decreased in SF and HLU groups, compared to control groups. Gastrocnemius and quadriceps mass was lower in SF and HLU mice than in control mice. HLU resulted in greater bone loss than SF, possibly due to differences in housing conditions. HLU effectively models long-duration effects of SF on the musculoskeletal system, highlighting its utility for studying astronaut health risks and developing countermeasures.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101871"},"PeriodicalIF":2.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}