Pub 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":"2025-07-28","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}
Bone allografts are frequently used in many surgical procedures because of their osteoconductive and osteoinductive properties. After being extracted from the donor, the graft is treated with a process that cleans and sterilizes it before being implanted in the patient. While they guarantee the safety of the patient receiving the graft, preservation processes often affect bone properties.
This study aims to measure the effect of a supercritical CO2 process on the microarchitecture and the mechanical properties of trabecular bone at a microscopic scale using microindentation. 7 femoral heads were harvested from patients who had undergone a total hip arthroplasty. 42 cubic samples of 10 mm side from these femoral heads were randomly distributed in 3 groups: frozen at −20 °C, gamma irradiated and frozen at −20 °C, and treated with a supercritical CO2 process including gamma irradiation. All samples were imaged by microtomography and characterized by microindentation to correlate the bone microarchitecture with the mechanical properties at a microscopic scale.
Our results show that the supercritical CO2 process exerts no significant effect on the microarchitecture parameters, indentation elastic modulus, and indentation hardness.
The correlations between the microarchitecture and the mechanical properties revealed that gamma irradiation appears to induce a slight alteration in mechanical properties. However, the process combining a supercritical CO2 treatment and gamma irradiation does not induce any more alterations to the material than gamma irradiation itself. Thus, the supercritical CO2 process has no more impact than gamma irradiation on the mechanical properties of trabecular bone at the microscopic scale.
{"title":"The supercritical CO2 process does not affect the mechanical properties and the microarchitecture of trabecular bone at the microscopic scale: A microindentation and microcomputed tomography study","authors":"Théo Krieger , Virginie Taillebot , Aurélien Maurel-Pantel , Claire Camy , Grégoire Edorh , Matthieu Ollivier , Martine Pithioux","doi":"10.1016/j.bonr.2025.101859","DOIUrl":"10.1016/j.bonr.2025.101859","url":null,"abstract":"<div><div>Bone allografts are frequently used in many surgical procedures because of their osteoconductive and osteoinductive properties. After being extracted from the donor, the graft is treated with a process that cleans and sterilizes it before being implanted in the patient. While they guarantee the safety of the patient receiving the graft, preservation processes often affect bone properties.</div><div>This study aims to measure the effect of a supercritical CO<sub>2</sub> process on the microarchitecture and the mechanical properties of trabecular bone at a microscopic scale using microindentation. 7 femoral heads were harvested from patients who had undergone a total hip arthroplasty. 42 cubic samples of 10 mm side from these femoral heads were randomly distributed in 3 groups: frozen at −20 °C, gamma irradiated and frozen at −20 °C, and treated with a supercritical CO<sub>2</sub> process including gamma irradiation. All samples were imaged by microtomography and characterized by microindentation to correlate the bone microarchitecture with the mechanical properties at a microscopic scale.</div><div>Our results show that the supercritical CO<sub>2</sub> process exerts no significant effect on the microarchitecture parameters, indentation elastic modulus, and indentation hardness.</div><div>The correlations between the microarchitecture and the mechanical properties revealed that gamma irradiation appears to induce a slight alteration in mechanical properties. However, the process combining a supercritical CO<sub>2</sub> treatment and gamma irradiation does not induce any more alterations to the material than gamma irradiation itself. Thus, the supercritical CO<sub>2</sub> process has no more impact than gamma irradiation on the mechanical properties of trabecular bone at the microscopic scale.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101859"},"PeriodicalIF":2.1,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703986","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 : 2025-07-19DOI: 10.1016/j.bonr.2025.101858
Neil P. Sheth , Kelly Krohn , Jared Torkelson , Renaud Winzenrieth , Ludovic Humbert , Leny Pearman , Yamei Wang , John I. Boxberger , Mathias P. Bostrom
Background
Acetabular bone loss in patients with osteoporosis is associated with increased risk of acetabular fragility fractures, significant morbidity, and can increase risk of complications in patients undergoing total hip arthroplasty. The anabolic osteoporosis treatment abaloparatide increases total hip areal bone mineral density (BMD), but its effect on acetabular BMD is unknown.
Methods
Anatomical landmarks were identified in DXA scans from a random subgroup of postmenopausal women with osteoporosis (PMO) treated with abaloparatide 80 μg/d or placebo (n = 250/group) from the phase 3 ACTIVE trial to virtually place a hemispherical shell model of an acetabular cup and define regions of interest corresponding to DeLee and Charnley zones 1 (R1), 2 (R2), and 3 (R3). Changes in BMD from baseline at 6 and 18 months were calculated. Statistical significance was tested using a mixed model with repeated measures. Local mean changes in BMD were depicted by alignment of DXA scans via intensity-based registration onto a reference scan.
Results
Abaloparatide significantly increased acetabular areal BMD in all three DeLee and Charnley zones at 6 and 18 months versus placebo. Mean BMD increases with abaloparatide were 8.38 % (R1), 7.25 % (R2), and 9.73 % (R3) at 18 months. BMD increases were homogenously distributed throughout the regions. With placebo, localized losses in BMD were noted after 18 months.
Conclusions
Abaloparatide treatment rapidly and progressively increases BMD in acetabular zones in PMO.
{"title":"Abaloparatide effects on BMD in acetabular regions corresponding to DeLee and Charnley zones in women with postmenopausal osteoporosis","authors":"Neil P. Sheth , Kelly Krohn , Jared Torkelson , Renaud Winzenrieth , Ludovic Humbert , Leny Pearman , Yamei Wang , John I. Boxberger , Mathias P. Bostrom","doi":"10.1016/j.bonr.2025.101858","DOIUrl":"10.1016/j.bonr.2025.101858","url":null,"abstract":"<div><h3>Background</h3><div>Acetabular bone loss in patients with osteoporosis is associated with increased risk of acetabular fragility fractures, significant morbidity, and can increase risk of complications in patients undergoing total hip arthroplasty. The anabolic osteoporosis treatment abaloparatide increases total hip areal bone mineral density (BMD), but its effect on acetabular BMD is unknown.</div></div><div><h3>Methods</h3><div>Anatomical landmarks were identified in DXA scans from a random subgroup of postmenopausal women with osteoporosis (PMO) treated with abaloparatide 80 μg/d or placebo (n = 250/group) from the phase 3 ACTIVE trial to virtually place a hemispherical shell model of an acetabular cup and define regions of interest corresponding to DeLee and Charnley zones 1 (R1), 2 (R2), and 3 (R3). Changes in BMD from baseline at 6 and 18 months were calculated. Statistical significance was tested using a mixed model with repeated measures. Local mean changes in BMD were depicted by alignment of DXA scans via intensity-based registration onto a reference scan.</div></div><div><h3>Results</h3><div>Abaloparatide significantly increased acetabular areal BMD in all three DeLee and Charnley zones at 6 and 18 months versus placebo. Mean BMD increases with abaloparatide were 8.38 % (R1), 7.25 % (R2), and 9.73 % (R3) at 18 months. BMD increases were homogenously distributed throughout the regions. With placebo, localized losses in BMD were noted after 18 months.</div></div><div><h3>Conclusions</h3><div>Abaloparatide treatment rapidly and progressively increases BMD in acetabular zones in PMO.</div></div><div><h3>Clinical trial number</h3><div><span><span>NCT01343004</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101858"},"PeriodicalIF":2.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144723965","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 : 2025-07-15DOI: 10.1016/j.bonr.2025.101857
Peter Kannu , Aliya A. Khan , Mira Francis , Jonathan D. Adachi
Family mapping is a useful tool for tracking the inheritance of rare inherited diseases, including hypophosphatasia (HPP), through generations. We show the inheritance of HPP in 6 affected families, describing genetic variants, biochemical hallmarks, and clinical manifestations among family members. Mapping families with HPP is warranted in clinical practice to better understand monitoring needs for potentially affected individuals over time, since manifestations of HPP can arise throughout a patient's lifespan.
{"title":"Multigenerational genetic inheritance and clinical characteristics of the rare disease hypophosphatasia in 6 families: A case series","authors":"Peter Kannu , Aliya A. Khan , Mira Francis , Jonathan D. Adachi","doi":"10.1016/j.bonr.2025.101857","DOIUrl":"10.1016/j.bonr.2025.101857","url":null,"abstract":"<div><div>Family mapping is a useful tool for tracking the inheritance of rare inherited diseases, including hypophosphatasia (HPP), through generations. We show the inheritance of HPP in 6 affected families, describing genetic variants, biochemical hallmarks, and clinical manifestations among family members. Mapping families with HPP is warranted in clinical practice to better understand monitoring needs for potentially affected individuals over time, since manifestations of HPP can arise throughout a patient's lifespan.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101857"},"PeriodicalIF":2.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703987","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 : 2025-07-02DOI: 10.1016/j.bonr.2025.101856
Jean Cassuto , Agnetha Folestad , Jan Göthlin , Henrik Malchau , Johan Kärrholm
Introduction
Angiogenic growth factors are a critical part of bone repair and regeneration in the aftermath of bone trauma. In the current study we monitored the spatiotemporal responses of angiogenic factors and receptors during the process of osseointegration of hip implants.
Materials and methods
Twenty-four patients having undergone primary total hip arthroplasty (THA) due to one-sided osteoarthritis (OA) were monitored during a period of 18 years (Y) by repeated measurements of plasma biomarkers as well as clinical and radiographic variables, the latter two showing all implants of the study to be well anchored throughout the follow-up. Eighty-one healthy donors divided into three gender- and age-matched subgroups and twenty OA patients awaiting THA, served as controls. Plasma was analyzed for vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D, vascular endothelial growth factor receptor 1 (VEGFR1) or sFlt-1, VEGFR2 (KDR/sFlk-1), VEGFR3 (sFlt-4), platelet derived growth factor–BB (PDGF-BB), fibroblast growth factor-2 (FGF-2) and placental growth factor (PIGF). Analysis of biomarkers was done by means of a high-sensitivity and wide dynamic range electrochemiluminescence technique allowing for detection of low levels and minor changes in biomarker levels. Spatiotemporal changes of biomarkers in THA patients during the follow-up were presented in the context of the four phases of endochondral bone repair.
Results
VEGF-A, VEGFR1, PDGF-BB and FGF-2 were significantly higher, whereas VEGF-C was significantly lower in presurgery OA patients versus healthy subjects but were all normalized shortly after implant surgery. VEGF-A, VEGF-C, VEGF-D, VEGFR2, VEGFR3, FGF-2 and PDGF-BB increased sharply 1–2 Y post-implant and reached a peak significantly above healthy control subjects at 5–7 Y after implant insertion before returning to control level 13-15Y post-surgery, except for VEGF-D that returned to control level at 7Y post-implant. VEGFR1 decreased to the level of healthy subjects at 6 W post-THA and remained there throughout the study. PIGF did not differ from healthy subjects at any point during the follow-up.
Conclusion
Increased levels of VEGF-A, VEGFR1, PDGF-BB and FGF-2 and reduced VEGF-C in presurgery OA relative healthy subjects support a cartilage protective or disease-inducing role in osteoarthritis. The concerted increase by all proangiogenic factors of the study, except VEGFR1 and PIGF, at 5 Y post-implant lend strong support to this being the phase of bone repair when blood and lymph vessels invade the avascular calcified hypertrophic cartilage and trigger its remodeling into bone in hip arthroplasty patients.
{"title":"VEGF-A, -C, -D, VEGFR1, -2, -3, PDGF-BB and FGF-2 join forces to induce vascular and lymphatic angiogenesis during bone healing of hip implants","authors":"Jean Cassuto , Agnetha Folestad , Jan Göthlin , Henrik Malchau , Johan Kärrholm","doi":"10.1016/j.bonr.2025.101856","DOIUrl":"10.1016/j.bonr.2025.101856","url":null,"abstract":"<div><h3>Introduction</h3><div>Angiogenic growth factors are a critical part of bone repair and regeneration in the aftermath of bone trauma. In the current study we monitored the spatiotemporal responses of angiogenic factors and receptors during the process of osseointegration of hip implants.</div></div><div><h3>Materials and methods</h3><div>Twenty-four patients having undergone primary total hip arthroplasty (THA) due to one-sided osteoarthritis (OA) were monitored during a period of 18 years (Y) by repeated measurements of plasma biomarkers as well as clinical and radiographic variables, the latter two showing all implants of the study to be well anchored throughout the follow-up. Eighty-one healthy donors divided into three gender- and age-matched subgroups and twenty OA patients awaiting THA, served as controls. Plasma was analyzed for vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D, vascular endothelial growth factor receptor 1 (VEGFR1) or sFlt-1, VEGFR2 (KDR/sFlk-1), VEGFR3 (sFlt-4), platelet derived growth factor–BB (PDGF-BB), fibroblast growth factor-2 (FGF-2) and placental growth factor (PIGF). Analysis of biomarkers was done by means of a high-sensitivity and wide dynamic range electrochemiluminescence technique allowing for detection of low levels and minor changes in biomarker levels. Spatiotemporal changes of biomarkers in THA patients during the follow-up were presented in the context of the four phases of endochondral bone repair.</div></div><div><h3>Results</h3><div>VEGF-A, VEGFR1, PDGF-BB and FGF-2 were significantly higher, whereas VEGF-C was significantly lower in presurgery OA patients versus healthy subjects but were all normalized shortly after implant surgery. VEGF-A, VEGF-C, VEGF-D, VEGFR2, VEGFR3, FGF-2 and PDGF-BB increased sharply 1–2 Y post-implant and reached a peak significantly above healthy control subjects at 5–7 Y after implant insertion before returning to control level 13-15Y post-surgery, except for VEGF-D that returned to control level at 7Y post-implant. VEGFR1 decreased to the level of healthy subjects at 6 W post-THA and remained there throughout the study. PIGF did not differ from healthy subjects at any point during the follow-up.</div></div><div><h3>Conclusion</h3><div>Increased levels of VEGF-A, VEGFR1, PDGF-BB and FGF-2 and reduced VEGF-C in presurgery OA relative healthy subjects support a cartilage protective or disease-inducing role in osteoarthritis. The concerted increase by all proangiogenic factors of the study, except VEGFR1 and PIGF, at 5 Y post-implant lend strong support to this being the phase of bone repair when blood and lymph vessels invade the avascular calcified hypertrophic cartilage and trigger its remodeling into bone in hip arthroplasty patients.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101856"},"PeriodicalIF":2.1,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144570851","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 : 2025-06-26DOI: 10.1016/j.bonr.2025.101855
William Woolley , Naomi Chin , S. Michael Yu , Claire Acevedo
Bone fracture risk is clinically assessed with bone mineral density (BMD); however, individuals with normal BMD also experience fractures, highlighting the need for complementary fracture risk assessment tools. While BMD remains the clinical gold standard, it fails to capture bone quality factors that contribute to fragility. Among these, collagen quality is essential for bone toughness, as it allows collagen to dissipate energy via stretching and uncoiling. When collagen is denatured, it loses its ability to deform, increasing fracture risk. This process is particularly relevant in aging, osteoporosis, and metabolic conditions such as diabetes, yet no clinical methods exist to quantify or localize denatured collagen in mineralized bone. This study introduces Collagen Hybridizing Peptide (CHP) as a tool to quantify denatured collagen in cortical bone. Here, we show that CHP fluorescence correlates strongly with collagen denaturation measured by established trypsin-hydroxyproline assay (r2 = 0.99) when applied to mineralized tissue subjected to heat treatment or mechanical loading. Confocal microscopy revealed a 55 % increase in collagen denaturation when tissue strain exceeded the yield point (p< 0.05). Our findings demonstrate that fluorescent CHP localizes high-strain regions to collagen denaturation on bone fracture surfaces, indicating that collagen damage occurs during post-yield failure. This non-destructive technique offers a powerful tool for assessing collagen quality, with potential applications in osteoporosis, diabetic bone fragility, and aging research. By advancing our ability to evaluate bone quality in cortical bone, R-CHP provides new method to study how denatures collagen affects bone resistance to fracture.
{"title":"Fluorescent collagen hybridizing peptide for quantifying collagen denaturation in cortical bone","authors":"William Woolley , Naomi Chin , S. Michael Yu , Claire Acevedo","doi":"10.1016/j.bonr.2025.101855","DOIUrl":"10.1016/j.bonr.2025.101855","url":null,"abstract":"<div><div>Bone fracture risk is clinically assessed with bone mineral density (BMD); however, individuals with normal BMD also experience fractures, highlighting the need for complementary fracture risk assessment tools. While BMD remains the clinical gold standard, it fails to capture bone quality factors that contribute to fragility. Among these, collagen quality is essential for bone toughness, as it allows collagen to dissipate energy via stretching and uncoiling. When collagen is denatured, it loses its ability to deform, increasing fracture risk. This process is particularly relevant in aging, osteoporosis, and metabolic conditions such as diabetes, yet no clinical methods exist to quantify or localize denatured collagen in mineralized bone. This study introduces Collagen Hybridizing Peptide (CHP) as a tool to quantify denatured collagen in cortical bone. Here, we show that CHP fluorescence correlates strongly with collagen denaturation measured by established trypsin-hydroxyproline assay (r<sup>2</sup> = 0.99) when applied to mineralized tissue subjected to heat treatment or mechanical loading. Confocal microscopy revealed a 55 % increase in collagen denaturation when tissue strain exceeded the yield point (<em>p</em> <em><</em> 0.05). Our findings demonstrate that fluorescent CHP localizes high-strain regions to collagen denaturation on bone fracture surfaces, indicating that collagen damage occurs during post-yield failure. This non-destructive technique offers a powerful tool for assessing collagen quality, with potential applications in osteoporosis, diabetic bone fragility, and aging research. By advancing our ability to evaluate bone quality in cortical bone, R-CHP provides new method to study how denatures collagen affects bone resistance to fracture.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101855"},"PeriodicalIF":2.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501282","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 : 2025-06-13DOI: 10.1016/j.bonr.2025.101854
Chiho Kadota-Watanabe , Jinsook Suh , Zhenqing Liu , Eric Yin , Kate Lindsey , Isabelle Lao-Ngo , Byron Zhao , Jonathan H. Wu , In Won Chang , Reuben H. Kim , Ophir D. Klein , Christine Hong
p75NTR has emerged as a key regulator of skeletal development and bone homeostasis. To define its role, we characterized skeletal phenotypes in global and mesenchyme-specific p75NTR knockout mouse models. Global deletion of p75NTR resulted in postnatal growth retardation, decreased trabecular and cortical bone mass, and impaired growth plate architecture—hallmarks of an osteoporotic phenotype that persisted into adulthood. Conditional deletion of p75NTR in mesenchymal progenitor cells using Prx1-Cre recapitulated these skeletal deficits, confirming a cell-autonomous role in bone development. In vitro, bone marrow stromal cells (BMSCs) derived from p75NTR-deficient mouse exhibited diminished osteogenic differentiation capacity, reduced mineralization, and downregulation of key osteogenic genes. Transcriptomic profiling revealed significant suppression of the NGF-MAPK/AP-1 signaling axis in p75NTR-deficient BMSCs. Functional studies demonstrated that loss of p75NTR reduced JNK pathway activation and downstream epigenetic regulators, including Kdm4b and its target gene Dlx5. Overexpression of Kdm4b rescued mineralization defects and restored osteogenic gene expression in p75NTR-deficient BMSCs, establishing a mechanistic link between p75NTR signaling and osteoblast differentiation. These findings define the NGF–p75NTR–JNK–KDM4B–Dlx5 axis as a central regulatory pathway in postnatal bone growth and osteogenesis. Given the critical role of p75NTR in skeletal development and bone homeostasis, targeted modulation of this signaling cascade may represent a promising therapeutic approach for treating osteoporosis and other bone disorders.
{"title":"p75NTR regulates postnatal skeletal development via NGF-responsive JNK signaling","authors":"Chiho Kadota-Watanabe , Jinsook Suh , Zhenqing Liu , Eric Yin , Kate Lindsey , Isabelle Lao-Ngo , Byron Zhao , Jonathan H. Wu , In Won Chang , Reuben H. Kim , Ophir D. Klein , Christine Hong","doi":"10.1016/j.bonr.2025.101854","DOIUrl":"10.1016/j.bonr.2025.101854","url":null,"abstract":"<div><div>p75<sup>NTR</sup> has emerged as a key regulator of skeletal development and bone homeostasis. To define its role, we characterized skeletal phenotypes in global and mesenchyme-specific <em>p75</em><sup><em>NTR</em></sup> knockout mouse models. Global deletion of <em>p75</em><sup><em>NTR</em></sup> resulted in postnatal growth retardation, decreased trabecular and cortical bone mass, and impaired growth plate architecture—hallmarks of an osteoporotic phenotype that persisted into adulthood. Conditional deletion of <em>p75</em><sup><em>NTR</em></sup> in mesenchymal progenitor cells using Prx1-Cre recapitulated these skeletal deficits, confirming a cell-autonomous role in bone development. In vitro, bone marrow stromal cells (BMSCs) derived from <em>p75</em><sup><em>NTR</em></sup>-deficient mouse exhibited diminished osteogenic differentiation capacity, reduced mineralization, and downregulation of key osteogenic genes. Transcriptomic profiling revealed significant suppression of the NGF-MAPK/AP-1 signaling axis in <em>p75</em><sup><em>NTR</em></sup>-deficient BMSCs. Functional studies demonstrated that loss of <em>p75</em><sup><em>NTR</em></sup> reduced JNK pathway activation and downstream epigenetic regulators, including <em>Kdm4b</em> and its target gene <em>Dlx5</em>. Overexpression of <em>Kdm4b</em> rescued mineralization defects and restored osteogenic gene expression in <em>p75</em><sup><em>NTR</em></sup>-deficient BMSCs, establishing a mechanistic link between p75<sup>NTR</sup> signaling and osteoblast differentiation. These findings define the NGF–p75<sup>NTR</sup>–JNK–KDM4B<em>–Dlx5</em> axis as a central regulatory pathway in postnatal bone growth and osteogenesis. Given the critical role of p75<sup>NTR</sup> in skeletal development and bone homeostasis, targeted modulation of this signaling cascade may represent a promising therapeutic approach for treating osteoporosis and other bone disorders.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"26 ","pages":"Article 101854"},"PeriodicalIF":2.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322046","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 : 2025-05-29DOI: 10.1016/j.bonr.2025.101853
Lothar Seefried, Franca Genest
Purpose
Hypophosphatasia (HPP) is a rare disease characterized by skeletal and nonskeletal manifestations that can increase patient disability. The 6-Minute Walk Test (6MWT) is frequently used to assess mobility in patients with HPP, although the test is laborious to conduct in clinical practice. The purpose of the current study was to determine correlations between time to complete the 6MWT, time to complete the Chair-Rise Test (CRT), and scores on the Lower Extremity Functional Scale (LEFS) in adults with HPP.
Methods
Pearson correlations between time to complete outcomes on the 6MWT and CRT, time to complete the 6MWT and scores on the LEFS, and time to complete the CRT and scores on the LEFS were calculated using de-identified data from adults with HPP who had first onset of symptoms in childhood. All patients were enrolled in the previously conducted, observational EmPATHY study.
Results
Pearson correlation analyses showed inverse correlations between 6MWT and CRT outcomes (r = −0.584) and between CRT and LEFS outcomes (r = −0.596) and a direct correlation between 6MWT and LEFS outcomes (r = 0.808).
Conclusions
Time to complete the 6MWT was correlated with time to complete the CRT and scores on the LEFS in adults with HPP. CRT and LEFS may be suitable, expeditious options to amend or substitute 6MWT when assessing functional status in patients with HPP.
{"title":"Correlations between 6-minute walk test, chair-rise test, and lower extremity functional scale among patients with hypophosphatasia","authors":"Lothar Seefried, Franca Genest","doi":"10.1016/j.bonr.2025.101853","DOIUrl":"10.1016/j.bonr.2025.101853","url":null,"abstract":"<div><h3>Purpose</h3><div>Hypophosphatasia (HPP) is a rare disease characterized by skeletal and nonskeletal manifestations that can increase patient disability. The 6-Minute Walk Test (6MWT) is frequently used to assess mobility in patients with HPP, although the test is laborious to conduct in clinical practice. The purpose of the current study was to determine correlations between time to complete the 6MWT, time to complete the Chair-Rise Test (CRT), and scores on the Lower Extremity Functional Scale (LEFS) in adults with HPP.</div></div><div><h3>Methods</h3><div>Pearson correlations between time to complete outcomes on the 6MWT and CRT, time to complete the 6MWT and scores on the LEFS, and time to complete the CRT and scores on the LEFS were calculated using de-identified data from adults with HPP who had first onset of symptoms in childhood. All patients were enrolled in the previously conducted, observational EmPATHY study.</div></div><div><h3>Results</h3><div>Pearson correlation analyses showed inverse correlations between 6MWT and CRT outcomes (<em>r</em> = −0.584) and between CRT and LEFS outcomes (<em>r</em> = −0.596) and a direct correlation between 6MWT and LEFS outcomes (<em>r</em> = 0.808).</div></div><div><h3>Conclusions</h3><div>Time to complete the 6MWT was correlated with time to complete the CRT and scores on the LEFS in adults with HPP. CRT and LEFS may be suitable, expeditious options to amend or substitute 6MWT when assessing functional status in patients with HPP.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101853"},"PeriodicalIF":2.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167867","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 : 2025-05-20DOI: 10.1016/j.bonr.2025.101852
Sema Ertan Birsel , Ekrem Demirci , Ali Seker , Kadriye Yasemin Usta Ayanoğlu , Emir Oncu , Fatih Ciftci
Hip displacement is a significant concern in children with cerebral palsy (CP), necessitating accurate and timely assessment to prevent long-term complications. This study developed a support vector machine (SVM) model to classify hip conditions using migration percentage (MP) measurements obtained from 176 hips across 88 anteroposterior pelvic radiographs. MP values were categorized into three groups: normal (MP ≤ 30 %), risky (30 % < MP ≤ 60 %), and dislocated (MP > 60 %). The SVM model was evaluated using stratified k-fold cross-validation, with accuracy, precision, recall, and F1-scores as key metrics. Its classifications were compared to manual evaluations performed by an orthopedic resident and a pediatric orthopedic surgeon. The model achieved an overall accuracy of 92.898 %, surpassing the consistency and reliability of manual assessments, particularly in identifying dislocated hips. Statistical analysis showed no significant differences between the model's MP measurements and those of the clinicians, validating its effectiveness. This study highlights the potential of SVM models to enhance diagnostic accuracy, reduce variability in evaluations, and support clinical decision-making. Future research should expand the dataset and incorporate advanced machine learning models to further improve diagnostic precision.
{"title":"Machine learning-assisted classification of hip conditions in pediatric cerebral palsy patients using migration percentage measurements","authors":"Sema Ertan Birsel , Ekrem Demirci , Ali Seker , Kadriye Yasemin Usta Ayanoğlu , Emir Oncu , Fatih Ciftci","doi":"10.1016/j.bonr.2025.101852","DOIUrl":"10.1016/j.bonr.2025.101852","url":null,"abstract":"<div><div>Hip displacement is a significant concern in children with cerebral palsy (CP), necessitating accurate and timely assessment to prevent long-term complications. This study developed a support vector machine (SVM) model to classify hip conditions using migration percentage (MP) measurements obtained from 176 hips across 88 anteroposterior pelvic radiographs. MP values were categorized into three groups: normal (MP ≤ 30 %), risky (30 % < MP ≤ 60 %), and dislocated (MP > 60 %). The SVM model was evaluated using stratified k-fold cross-validation, with accuracy, precision, recall, and F1-scores as key metrics. Its classifications were compared to manual evaluations performed by an orthopedic resident and a pediatric orthopedic surgeon. The model achieved an overall accuracy of 92.898 %, surpassing the consistency and reliability of manual assessments, particularly in identifying dislocated hips. Statistical analysis showed no significant differences between the model's MP measurements and those of the clinicians, validating its effectiveness. This study highlights the potential of SVM models to enhance diagnostic accuracy, reduce variability in evaluations, and support clinical decision-making. Future research should expand the dataset and incorporate advanced machine learning models to further improve diagnostic precision.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"25 ","pages":"Article 101852"},"PeriodicalIF":2.1,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144099602","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 : 2025-05-15DOI: 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":"2025-05-15","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}
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