Pub Date : 2025-09-01Epub Date: 2025-08-15DOI: 10.1016/j.bonr.2025.101871
Michael A. Friedman , Yasmina Zeineddine , Olivier Tuyambaze , Wesam Elhawabri , Ahmed Al Shammary , Louis Stodieck , Virginia L. Ferguson , Henry J. Donahue
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.
{"title":"Simulated microgravity accurately models long-duration spaceflight effects on bone and skeletal muscle in skeletally immature mice","authors":"Michael A. Friedman , Yasmina Zeineddine , Olivier Tuyambaze , Wesam Elhawabri , Ahmed Al Shammary , Louis Stodieck , Virginia L. Ferguson , 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":"2025-09-01","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}
Pub Date : 2025-09-01Epub Date: 2025-07-28DOI: 10.1016/j.bonr.2025.101860
Xiaoqing Lu, Jun Zhu, Bai Zheng, Junsheng Wang
Objective
To evaluate the effect of denosumab combined with proximal femoral nail antirotation (PFNA) surgery in elderly patients with osteoporotic intertrochanteric femoral fractures (ITF Fx).
Design and Setting
This retrospective, comparative study included patients aged ≥65 years with osteoporotic ITF Fx who underwent PFNA fixation at Huai'an Second People's Hospital between July 2021 and July 2023.
Participants
Pain relief (visual analogue scale, VAS), hip function, bone mineral density (BMD), time to fracture healing, refracture rate, and adverse events were compared.
Interventions
This is a retrospective study, without the addition of any intervention measures.
Results
A total of 76 patients were included, with 38 patients in the denosumab + PFNA group and 38 in the PFNA group. The denosumab + PFNA group showed significantly greater improvements in pain relief (1.68 ± 0.93 vs 2.29 ± 0.97, p = 0.014) and BMD T-score (−1.49 ± 0.61 vs −1.98 ± 0.52, p = 0.006) at 12 months compared to the PFNA group. Fracture healing time was significantly shorter in the denosumab + PFNA group (12.37 ± 1.38 vs 13.63 ± 1.34 weeks, p < 0.001), and the refracture rate was significantly lower (2.63 % vs 21.05 %, p < 0.05) than that in the PFNA group. The post-treatment hip function was comparable between the denosumab + PFNA and PFNA groups. Only one case of hypocalcemia was reported in the denosumab + PFNA group (2.63 %).
Conclusion
Denosumab combined with PFNA surgery might have an advantage in pain relief, BMD T-score, and fracture healing, while reducing refracture risk in elderly patients with osteoporotic ITF Fx compared with PFNA surgery alone.
目的评价地诺单抗联合股骨近端钉防旋（PFNA）手术治疗老年骨质疏松性股骨粗隆间骨折（itffx）的疗效。设计和背景：这项回顾性比较研究纳入了2021年7月至2023年7月在淮安市第二人民医院接受PFNA固定的年龄≥65岁的骨质疏松性ITF Fx患者。比较参与者的西班牙缓解（视觉模拟量表，VAS）、髋关节功能、骨密度（BMD）、骨折愈合时间、再骨折率和不良事件。干预措施：这是一项回顾性研究，没有增加任何干预措施。结果共纳入76例患者，其中denosumab + PFNA组38例，PFNA组38例。与PFNA组相比，denosumab + PFNA组在12个月时疼痛缓解（1.68±0.93 vs 2.29±0.97,p = 0.014）和BMD t评分（- 1.49±0.61 vs - 1.98±0.52,p = 0.006）方面的改善显著大于PFNA组。denosumab + PFNA组骨折愈合时间明显缩短(12.37±1.38 vs 13.63±1.34周，p <；0.001)，折射率明显低于(2.63% vs 21.05%, p <；0.05)，高于PFNA组。治疗后髋关节功能在denosumab + PFNA和PFNA组之间具有可比性。denosumab + PFNA组仅报告1例低钙血症（2.63%）。结论与单纯PFNA手术相比，denosumab联合PFNA手术在老年骨质疏松性ITF Fx患者的疼痛缓解、BMD t评分和骨折愈合方面具有优势，同时可降低再骨折风险。
{"title":"Effect of denosumab combination with proximal femoral nail antirotation surgery in elderly patients with intertrochanteric femoral fractures: A comparative study","authors":"Xiaoqing Lu, Jun Zhu, Bai Zheng, Junsheng Wang","doi":"10.1016/j.bonr.2025.101860","DOIUrl":"10.1016/j.bonr.2025.101860","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effect of denosumab combined with proximal femoral nail antirotation (PFNA) surgery in elderly patients with osteoporotic intertrochanteric femoral fractures (ITF Fx).</div></div><div><h3>Design and Setting</h3><div>This retrospective, comparative study included patients aged ≥65 years with osteoporotic ITF Fx who underwent PFNA fixation at Huai'an Second People's Hospital between July 2021 and July 2023.</div></div><div><h3>Participants</h3><div>Pain relief (visual analogue scale, VAS), hip function, bone mineral density (BMD), time to fracture healing, refracture rate, and adverse events were compared.</div></div><div><h3>Interventions</h3><div>This is a retrospective study, without the addition of any intervention measures.</div></div><div><h3>Results</h3><div>A total of 76 patients were included, with 38 patients in the denosumab + PFNA group and 38 in the PFNA group. The denosumab + PFNA group showed significantly greater improvements in pain relief (1.68 ± 0.93 vs 2.29 ± 0.97, <em>p</em> = 0.014) and BMD T-score (−1.49 ± 0.61 vs −1.98 ± 0.52, <em>p</em> = 0.006) at 12 months compared to the PFNA group. Fracture healing time was significantly shorter in the denosumab + PFNA group (12.37 ± 1.38 vs 13.63 ± 1.34 weeks, <em>p</em> < 0.001), and the refracture rate was significantly lower (2.63 % vs 21.05 %, <em>p</em> < 0.05) than that in the PFNA group. The post-treatment hip function was comparable between the denosumab + PFNA and PFNA groups. Only one case of hypocalcemia was reported in the denosumab + PFNA group (2.63 %).</div></div><div><h3>Conclusion</h3><div>Denosumab combined with PFNA surgery might have an advantage in pain relief, BMD T-score, and fracture healing, while reducing refracture risk in elderly patients with osteoporotic ITF Fx compared with PFNA surgery alone.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101860"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144713413","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}
Pub Date : 2025-09-01Epub Date: 2025-07-28DOI: 10.1016/j.bonr.2025.101861
Michaela Tencerova , Biagio Palmisano , Stéphanie Lucas , Camille Attané , Kaisa K. Ivaska , Léa Loisay , Yoshiko M. Ikushima , Drenka Trivanovic , Alessandro Corsi , Adriana Roque , Hongshuai Li , Friederike Behler-Janbeck , Jeroen Geurts , Mara Riminucci , Izabela Podgorski , William P. Cawthorn , Bram C.J. van der Eerden , André J. van Wijnen
Bone marrow adipose tissue (BMAT) is physiologically linked to bone and energy metabolism, endocrine regulation, hematopoiesis and cancer-related processes. A key challenge in the field is that methods for isolating BMAT or bone marrow adipocytes (BMAds) are variable because there are no widely adopted standardized protocols. To generate awareness of this challenge and to establish uniformity in experimental approaches requiring isolation, storage and characterization of BMAT and BMAds, the Biobanking Working Group of the international Bone Marrow Adiposity Society (BMAS) has previously recommended experimental standards. This paper provides an update on this effort and presents current state-of-the-art methods and technical considerations for isolation and characterization of BMAT and BMAds, including currently available high-throughput omics approaches. This review provides a reference point based on the consensus view of BMAS investigators to support studies on biomedical, biological, biochemical and biophysical questions associated with bone marrow adiposity.
{"title":"Experimental analysis of bone marrow adipose tissue and bone marrow adipocytes: An update from the bone marrow adiposity society (BMAS)","authors":"Michaela Tencerova , Biagio Palmisano , Stéphanie Lucas , Camille Attané , Kaisa K. Ivaska , Léa Loisay , Yoshiko M. Ikushima , Drenka Trivanovic , Alessandro Corsi , Adriana Roque , Hongshuai Li , Friederike Behler-Janbeck , Jeroen Geurts , Mara Riminucci , Izabela Podgorski , William P. Cawthorn , Bram C.J. van der Eerden , André J. van Wijnen","doi":"10.1016/j.bonr.2025.101861","DOIUrl":"10.1016/j.bonr.2025.101861","url":null,"abstract":"<div><div>Bone marrow adipose tissue (BMAT) is physiologically linked to bone and energy metabolism, endocrine regulation, hematopoiesis and cancer-related processes. A key challenge in the field is that methods for isolating BMAT or bone marrow adipocytes (BMAds) are variable because there are no widely adopted standardized protocols. To generate awareness of this challenge and to establish uniformity in experimental approaches requiring isolation, storage and characterization of BMAT and BMAds, the Biobanking Working Group of the international Bone Marrow Adiposity Society (BMAS) has previously recommended experimental standards. This paper provides an update on this effort and presents current state-of-the-art methods and technical considerations for isolation and characterization of BMAT and BMAds, including currently available high-throughput omics approaches. This review provides a reference point based on the consensus view of BMAS investigators to support studies on biomedical, biological, biochemical and biophysical questions associated with bone marrow adiposity.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101861"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828523","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}
Pub Date : 2025-09-01Epub Date: 2025-08-06DOI: 10.1016/j.bonr.2025.101867
L.H. Sattgast , A.J. Branscum , V.A. Jimenez , N. Newman , K.A. Grant , R.T. Turner , U.T. Iwaniec
{"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 , A.J. Branscum , V.A. Jimenez , N. Newman , K.A. Grant , R.T. Turner , 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}
Pub Date : 2025-09-01Epub Date: 2025-08-18DOI: 10.1016/j.bonr.2025.101872
Maria Sääf , Sigridur Björnsdottir , Mathias Haarhaus , Ellen-Margrethe Hauge , Diana Atanasova , Per Magnusson
Hypophosphatasia (HPP) is a rare inborn-error-of-metabolism caused by mutations in the ALPL 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 ALPL 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.
{"title":"Lifetime follow-up of an adult patient with pediatric-onset hypophosphatasia complicated with advanced chronic kidney disease","authors":"Maria Sääf , Sigridur Björnsdottir , Mathias Haarhaus , Ellen-Margrethe Hauge , Diana Atanasova , 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":"2025-09-01","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}
Pub Date : 2025-09-01Epub Date: 2025-08-08DOI: 10.1016/j.bonr.2025.101869
Orit Mazza , Chemda Gluck , Noa Menkes-Caspi , Robyn Jacob Bornstein , Hagay Amir , Michael Bahar , Amir Haim
Background
Secondary fracture prevention is a well-defined treatment-gap within osteoporosis management. Fracture Liaison Service (FLS) coordinates the management and treatment of patients following a fragility fracture in order to close the care gap. We aim to assess the efficacy of the FLS initiative in the management and treatment of patients following fragility hip fracture in the inpatient rehabilitation setting.
Methods
This is a diagnostic, retrospective cohort study using a deidentified, electronic health record database. In the extraction process, patients with fragility hip fractures were identified. Patients after major trauma or malignancy were excluded. The prevalence of initiation and adherence to anti-osteoporotic treatments, including alendronate, risedronate, zoledronate, denosumab, romosozumab, and teriparatide, was compared between the rehabilitation FLS initiative patients and patients from other hospitals without FLS.
Results
A total of 4,124 patients with fragility hip fractures were identified between 2017 and 2021. The FLS initiative showed significantly higher rates of treatment initiation, with 72.1 % of patients receiving pharmacological therapy following a hip fracture, compared to 45.1 % in hospitals without FLS (p < 0.001). Patients in the FLS group also demonstrated higher rates of good adherence and lower rates of poor adherence (p < 0.001). Denosumab was the most commonly prescribed anti-osteoporotic treatment within the FLS initiative.
Conclusions
The FLS in the inpatient rehabilitation setting was found to be highly effective in improving time to treatment initiation and adherence rates to prescribe anti-osteoporosis therapy. These findings demonstrate the role of FLS in addressing the osteoporosis treatment gap following fragility hip fracture.
{"title":"Inpatient rehabilitation fracture liaison service (FLS) improves outcomes for secondary prevention of hip fractures","authors":"Orit Mazza , Chemda Gluck , Noa Menkes-Caspi , Robyn Jacob Bornstein , Hagay Amir , Michael Bahar , Amir Haim","doi":"10.1016/j.bonr.2025.101869","DOIUrl":"10.1016/j.bonr.2025.101869","url":null,"abstract":"<div><h3>Background</h3><div>Secondary fracture prevention is a well-defined treatment-gap within osteoporosis management. Fracture Liaison Service (FLS) coordinates the management and treatment of patients following a fragility fracture in order to close the care gap. We aim to assess the efficacy of the FLS initiative in the management and treatment of patients following fragility hip fracture in the inpatient rehabilitation setting.</div></div><div><h3>Methods</h3><div>This is a diagnostic, retrospective cohort study using a deidentified, electronic health record database. In the extraction process, patients with fragility hip fractures were identified. Patients after major trauma or malignancy were excluded. The prevalence of initiation and adherence to anti-osteoporotic treatments, including alendronate, risedronate, zoledronate, denosumab, romosozumab, and teriparatide, was compared between the rehabilitation FLS initiative patients and patients from other hospitals without FLS.</div></div><div><h3>Results</h3><div>A total of 4,124 patients with fragility hip fractures were identified between 2017 and 2021. The FLS initiative showed significantly higher rates of treatment initiation, with 72.1 % of patients receiving pharmacological therapy following a hip fracture, compared to 45.1 % in hospitals without FLS (p < 0.001). Patients in the FLS group also demonstrated higher rates of good adherence and lower rates of poor adherence (p < 0.001). Denosumab was the most commonly prescribed anti-osteoporotic treatment within the FLS initiative.</div></div><div><h3>Conclusions</h3><div>The FLS in the inpatient rehabilitation setting was found to be highly effective in improving time to treatment initiation and adherence rates to prescribe anti-osteoporosis therapy. These findings demonstrate the role of FLS in addressing the osteoporosis treatment gap following fragility hip fracture.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101869"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860811","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}
Pub Date : 2025-09-01Epub Date: 2025-08-15DOI: 10.1016/j.bonr.2025.101873
Fatma F. Mohamed , Aonjittra Phanrungsuwan , Francisco H. Nociti Jr. , Brian L. Foster
Cementocytes reside in the cellular cementum of the apical tooth root and resemble bone osteocytes in their markers, lacunocanalicular network, and response to mineralization defects. However, it is unclear if cementocytes have a role in regulating cellular cementum similar to that of osteocytes in controlling bone formation and resorption. The Dmp1Cre-iDTRfl/fl (Dmp1-DTR) mouse sensitizes Dmp1-expressing cells, including osteocytes and cementocytes, to diphtheria toxin (DT), allowing selective ablation of cell populations. Compared to iDTRfl/fl control (CTR) mice, 1.0 μg/kg intraperitoneal DT administration at 6 and 8 weeks of age increased femur cortical bone porosity and reduced alveolar bone density in Dmp1-DTR mice, validating the model. DT administration eliminated approximately 80 % of alveolar bone osteocytes and 60 % of cementocytes in Dmp1Cre-iDTRfl/fl mice. Mice were subjected to the challenge of unopposed first molar super-eruption, which promotes increased cellular cementum apposition. Maxillary molars were bilaterally extracted at 7 weeks, and effects on cellular cementum accumulation in mandibular first molars were analyzed at 3 weeks post-procedure using micro-computed tomography and histology. DT-directed cementocyte ablation did not alter cellular cementum volume, density, or porosity vs. CTR mice. Immunostaining showed similar distributions between treatment groups of osteopontin (OPN), an extracellular matrix protein associated with axial tooth movement. Localization of DMP1 in cellular cementum and cementocyte networks of Dmp1-DTR mice appeared reduced compared to CTR mice. Within the limits of the study, these results suggest that cementocytes are not essential for new cellular cementum formation under challenge. Further insights into roles for cementocytes require additional in vivo approaches.
{"title":"Partial cementocyte ablation does not reduce cellular cementum apposition in a mouse model of molar super-eruption","authors":"Fatma F. Mohamed , Aonjittra Phanrungsuwan , Francisco H. Nociti Jr. , Brian L. Foster","doi":"10.1016/j.bonr.2025.101873","DOIUrl":"10.1016/j.bonr.2025.101873","url":null,"abstract":"<div><div>Cementocytes reside in the cellular cementum of the apical tooth root and resemble bone osteocytes in their markers, lacunocanalicular network, and response to mineralization defects. However, it is unclear if cementocytes have a role in regulating cellular cementum similar to that of osteocytes in controlling bone formation and resorption. The Dmp1Cre-iDTR<sup>fl/fl</sup> (Dmp1-DTR) mouse sensitizes <em>Dmp1</em>-expressing cells, including osteocytes and cementocytes, to diphtheria toxin (DT), allowing selective ablation of cell populations. Compared to iDTR<sup>fl/fl</sup> control (CTR) mice, 1.0 μg/kg intraperitoneal DT administration at 6 and 8 weeks of age increased femur cortical bone porosity and reduced alveolar bone density in Dmp1-DTR mice, validating the model. DT administration eliminated approximately 80 % of alveolar bone osteocytes and 60 % of cementocytes in <em>Dmp1Cre</em>-iDTR<sup>fl/fl</sup> mice. Mice were subjected to the challenge of unopposed first molar super-eruption, which promotes increased cellular cementum apposition. Maxillary molars were bilaterally extracted at 7 weeks, and effects on cellular cementum accumulation in mandibular first molars were analyzed at 3 weeks post-procedure using micro-computed tomography and histology. DT-directed cementocyte ablation did not alter cellular cementum volume, density, or porosity vs. CTR mice. Immunostaining showed similar distributions between treatment groups of osteopontin (OPN), an extracellular matrix protein associated with axial tooth movement. Localization of DMP1 in cellular cementum and cementocyte networks of Dmp1-DTR mice appeared reduced compared to CTR mice. Within the limits of the study, these results suggest that cementocytes are not essential for new cellular cementum formation under challenge. Further insights into roles for cementocytes require additional in vivo approaches.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101873"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860810","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}
Pub Date : 2025-08-06eCollection Date: 2025-09-01DOI: 10.1016/j.bonr.2025.101865
Alyson March, Sandra H Castillo Aguirre, Roman Eliseev, Regine Choe, Danielle S W Benoit
Decellularized bone allografts are used in approximately 1/3 of grafting procedures and are preferred in treating critical-size bone defects, as volumetric constraints limit autografts. However, allografts demonstrate high failure rates, with 60 % of allografts failing within 10-years post-implantation. Allograft failure is linked to poor graft integration, which directly results from lack of periosteum, which surrounds bone and is necessary for successful bone healing. Therefore, a tissue-engineered periosteum (TEP) is a promising approach to recapitulate the missing periosteum and promote allograft healing. We have systematically developed an enzymatically degradable poly(ethylene glycol) (PEG) hydrogel with encapsulated mouse mesenchymal stem cells and osteoprogenitor cells, recapitulating key periosteal paracrine signals and producing improvements in bone allograft healing. While successful TEP-mediated allograft healing has been observed, previous studies have been limited to short-term healing (up to 16-weeks), which has yet to enable the observation of TEP-modified allograft healing resolution. To this end, this study extended evaluation of allograft healing in a murine femur defect model up to 12-months post-implantation. TEP-modified allografts demonstrated improvements in key bone healing outcomes, including graft vascularization and bone callus formation, at early time points (up to 9-weeks post-implantation), but improvements in healing outcomes compared to unmodified allografts were lost after 4-months post-implantation. In addition, unmodified allografts displayed incomplete healing up to 12-months post-implantation, with significant fibrotic tissue, incomplete graft remodeling, and inferior biomechanical strength observed. Given these results, future TEP designs should support long-term healing and graft remodeling to promote resolution of TEP-mediated graft healing in a clinically relevant timeline.
{"title":"Long-term tissue engineered periosteum-mediated allograft healing is hindered due to persistent fibrosis and limited allograft remodeling.","authors":"Alyson March, Sandra H Castillo Aguirre, Roman Eliseev, Regine Choe, Danielle S W Benoit","doi":"10.1016/j.bonr.2025.101865","DOIUrl":"10.1016/j.bonr.2025.101865","url":null,"abstract":"<p><p>Decellularized bone allografts are used in approximately 1/3 of grafting procedures and are preferred in treating critical-size bone defects, as volumetric constraints limit autografts. However, allografts demonstrate high failure rates, with 60 % of allografts failing within 10-years post-implantation. Allograft failure is linked to poor graft integration, which directly results from lack of periosteum, which surrounds bone and is necessary for successful bone healing. Therefore, a tissue-engineered periosteum (TEP) is a promising approach to recapitulate the missing periosteum and promote allograft healing. We have systematically developed an enzymatically degradable poly(ethylene glycol) (PEG) hydrogel with encapsulated mouse mesenchymal stem cells and osteoprogenitor cells, recapitulating key periosteal paracrine signals and producing improvements in bone allograft healing. While successful TEP-mediated allograft healing has been observed, previous studies have been limited to short-term healing (up to 16-weeks), which has yet to enable the observation of TEP-modified allograft healing resolution. To this end, this study extended evaluation of allograft healing in a murine femur defect model up to 12-months post-implantation. TEP-modified allografts demonstrated improvements in key bone healing outcomes, including graft vascularization and bone callus formation, at early time points (up to 9-weeks post-implantation), but improvements in healing outcomes compared to unmodified allografts were lost after 4-months post-implantation. In addition, unmodified allografts displayed incomplete healing up to 12-months post-implantation, with significant fibrotic tissue, incomplete graft remodeling, and inferior biomechanical strength observed. Given these results, future TEP designs should support long-term healing and graft remodeling to promote resolution of TEP-mediated graft healing in a clinically relevant timeline.</p>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"101865"},"PeriodicalIF":2.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-01Epub Date: 2025-05-15DOI: 10.1016/j.bonr.2025.101851
Fjorda Koromani , Jiawei Li , Hiroshi Hagino , Richard Eastell , Annegreet Vlug , Ling Wang , Hua Yue , Yong-Chan Ha , Steven Cummings , Salvatore Minisola , Claus-C. Glüer , Ling Oei , the East Meets West Action Group of the European Calcified Tissue Society
Osteoporotic vertebral fractures (VFs) are among the most common and clinically significant manifestations of skeletal fragility, contributing substantially to morbidity, disability, and future fracture risk worldwide. Yet, their recognition and management remain inconsistent across regions. To explore differences and similarities in the prevalence, diagnosis, management, and prevention of vertebral fractures, the East Meets West (EmW) Action Group of the European Calcified Tissue Society convened a multi-country exchange among clinical and research experts from Europe, the USA, and East Asia. This report summarizes the discussions and synthesizes current knowledge on the topic. Evidence from China, South Korea, Japan, and Germany shows a wide range in reported VF prevalence and incidence, largely influenced by differences in population aging, imaging access, and diagnostic adjudication methods. While lateral spine radiographs remain the standard for detection in both research and clinical care, variable use of quantitative morphometry (QM), semi-quantitative (SQ), and algorithm-based qualitative (ABQ) methods limits comparability. MRI remains the gold standard for assessing fracture acuity, but is not feasible for widespread screening. VFA via DXA is gaining popularity, although underutilized in several settings. Despite the availability of effective pharmacologic treatments, including bisphosphonates, denosumab, and anabolic agents, treatment rates following VF remain suboptimal across all countries studied. None of the countries currently has a nationwide vertebral fracture screening program, although fracture liaison services (FLS) and AI-assisted imaging offer promising pathways forward. The lack of a universally accepted definition and gold standard for VF adjudication continues to hamper clinical decision-making and data harmonization. This report highlights the need for greater international consensus on diagnostic criteria, improved integration of vertebral fracture screening into clinical workflows, and the development of targeted strategies to close treatment gaps and reduce the global burden of vertebral fractures.
{"title":"The prevention of osteoporotic vertebral fractures in eastern and in western countries","authors":"Fjorda Koromani , Jiawei Li , Hiroshi Hagino , Richard Eastell , Annegreet Vlug , Ling Wang , Hua Yue , Yong-Chan Ha , Steven Cummings , Salvatore Minisola , Claus-C. Glüer , Ling Oei , the East Meets West Action Group of the European Calcified Tissue Society","doi":"10.1016/j.bonr.2025.101851","DOIUrl":"10.1016/j.bonr.2025.101851","url":null,"abstract":"<div><div>Osteoporotic vertebral fractures (VFs) are among the most common and clinically significant manifestations of skeletal fragility, contributing substantially to morbidity, disability, and future fracture risk worldwide. Yet, their recognition and management remain inconsistent across regions. To explore differences and similarities in the prevalence, diagnosis, management, and prevention of vertebral fractures, the East Meets West (EmW) Action Group of the European Calcified Tissue Society convened a multi-country exchange among clinical and research experts from Europe, the USA, and East Asia. This report summarizes the discussions and synthesizes current knowledge on the topic. Evidence from China, South Korea, Japan, and Germany shows a wide range in reported VF prevalence and incidence, largely influenced by differences in population aging, imaging access, and diagnostic adjudication methods. While lateral spine radiographs remain the standard for detection in both research and clinical care, variable use of quantitative morphometry (QM), semi-quantitative (SQ), and algorithm-based qualitative (ABQ) methods limits comparability. MRI remains the gold standard for assessing fracture acuity, but is not feasible for widespread screening. VFA via DXA is gaining popularity, although underutilized in several settings. Despite the availability of effective pharmacologic treatments, including bisphosphonates, denosumab, and anabolic agents, treatment rates following VF remain suboptimal across all countries studied. None of the countries currently has a nationwide vertebral fracture screening program, although fracture liaison services (FLS) and AI-assisted imaging offer promising pathways forward. The lack of a universally accepted definition and gold standard for VF adjudication continues to hamper clinical decision-making and data harmonization. This report highlights the need for greater international consensus on diagnostic criteria, improved integration of vertebral fracture screening into clinical workflows, and the development of targeted strategies to close treatment gaps and reduce the global burden of vertebral fractures.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101851"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144105356","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}
Pub Date : 2025-06-01Epub Date: 2025-04-28DOI: 10.1016/j.bonr.2025.101847
Shejil KUMAR , Courtney STREETER , Michelle M. MCDONALD , Roderick J. CLIFTON- BLIGH , Matti L. GILD , Christian M. GIRGIS
The optimal osteoanabolic strategy in denosumab (Dmab)-users remains uncertain. In treatment-naïve patients, Dmab/teriparatide (TPTD) combinations result in dramatic bone mineral density (BMD) gains at the spine and hip. However, BMD outcomes with combination Dmab/TPTD have not been investigated in patients on established Dmab.
We retrospectively reviewed patients with osteoporosis at two Sydney centers between 2013 and 2023. Eligible patients were managed with Dmab immediately before ≥12-months TPTD. Patients were grouped according to whether TPTD was added to ongoing Dmab (combination) or Dmab was withheld during TPTD (sequence). BMD outcomes were assessed during TPTD.
The total cohort (N = 23; 11 = combination, 12 = sequence) had mean age 77 ± 7 years and were predominantly female (87 %). Overall, prior vertebral (52 %) and non-vertebral fractures (2.4 ± 1.5) were prevalent and pre-TPTD BMD T-scores (SD) low at lumbar spine (−2.4 ± 1.2) and total hip (−2.2 ± 0.6). Median Dmab exposure was 5-doses (IQR 3–11), median overall antiresorptive exposure was 6-years (IQR 4–11) and majority (>90 %) received 18-months TPTD. Groups were similar in age, sex, Dmab and overall antiresorptive exposure, fracture prevalence, DXA interval and pre-TPTD BMD values. Combination Dmab/TPTD was associated with significant lumbar spine BMD gains (+0.080 g/cm2 ± 0.059 g/cm2, p = 0.004; +9.8 %). No significant BMD change occurred during sequential Dmab/TPTD (+0.026 g/cm2 ± 0.049 g/cm2, p = 0.107; +3.5 %). Combination Dmab/TPTD resulted in greater lumbar spine BMD gains (p = 0.039). Hip and femoral neck BMD remained stable in both groups.
In this retrospective study, significant lumbar spine BMD gains occurred during combined Dmab/TPTD in patients on established Dmab. These results warrant prospective controlled studies to further inform optimal osteoanabolic strategies in Dmab-users.
{"title":"Combination or sequential teriparatide for osteoporosis treatment in denosumab-users: real-world bone mineral density outcomes","authors":"Shejil KUMAR , Courtney STREETER , Michelle M. MCDONALD , Roderick J. CLIFTON- BLIGH , Matti L. GILD , Christian M. GIRGIS","doi":"10.1016/j.bonr.2025.101847","DOIUrl":"10.1016/j.bonr.2025.101847","url":null,"abstract":"<div><div>The optimal osteoanabolic strategy in denosumab (Dmab)-users remains uncertain. In treatment-naïve patients, Dmab/teriparatide (TPTD) combinations result in dramatic bone mineral density (BMD) gains at the spine and hip. However, BMD outcomes with combination Dmab/TPTD have not been investigated in patients on <em>established</em> Dmab.</div><div>We retrospectively reviewed patients with osteoporosis at two Sydney centers between 2013 and 2023. Eligible patients were managed with Dmab immediately before ≥12-months TPTD. Patients were grouped according to whether TPTD was added to ongoing Dmab (<em>combination</em>) or Dmab was withheld during TPTD (<em>sequence</em>). BMD outcomes were assessed during TPTD.</div><div>The total cohort (<em>N</em> = 23; 11 = combination, 12 = sequence) had mean age 77 ± 7 years and were predominantly female (87 %). Overall, prior vertebral (52 %) and non-vertebral fractures (2.4 ± 1.5) were prevalent and pre-TPTD BMD T-scores (SD) low at lumbar spine (−2.4 ± 1.2) and total hip (−2.2 ± 0.6). Median Dmab exposure was 5-doses (IQR 3–11), median overall antiresorptive exposure was 6-years (IQR 4–11) and majority (>90 %) received 18-months TPTD. Groups were similar in age, sex, Dmab and overall antiresorptive exposure, fracture prevalence, DXA interval and pre-TPTD BMD values. Combination Dmab/TPTD was associated with significant lumbar spine BMD gains (+0.080 g/cm<sup>2</sup> ± 0.059 g/cm<sup>2</sup>, <em>p</em> = 0.004; +9.8 %). No significant BMD change occurred during sequential Dmab/TPTD (+0.026 g/cm<sup>2</sup> ± 0.049 g/cm<sup>2</sup>, <em>p</em> = 0.107; +3.5 %). Combination Dmab/TPTD resulted in greater lumbar spine BMD gains (<em>p</em> = 0.039). Hip and femoral neck BMD remained stable in both groups.</div><div>In this retrospective study, significant lumbar spine BMD gains occurred during combined Dmab/TPTD in patients on established Dmab. These results warrant prospective controlled studies to further inform optimal osteoanabolic strategies in Dmab-users.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101847"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879309","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}
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