Pub Date : 2026-03-01Epub Date: 2025-11-30DOI: 10.1016/j.bone.2025.117744
Lauren Lynch , Patrick R. Shea , Natalie Vena , Wendy K. Chung , Elizabeth Shane , Mafo Kamanda-Kosseh , Jordan Barry , Dany El-Najjar , Sanchita Agarwal , Ananya Kondapalli , Ivelisse Colon , Mariana Bucovsky , Adi Cohen
Pregnancy- and lactation-associated osteoporosis (PLO) describes a fragility fracture presentation around pregnancy/lactation. Presentation often includes multiple vertebral fractures, but can also involve hip, sacral/pelvic, or other fractures. Substantial bone structural deficits and low bone formation rate have been documented. Most have no known secondary cause. Many have a history of childhood fracture and/or family history of osteoporosis. These characteristics, together with early onset and disease severity, lead to the hypothesis that genetic factors may contribute to PLO.
We enrolled 110 women with PLO (mean #fractures = 6, vertebral fractures in 88 %) in an exome sequencing (ES) study. Analyses identified rare (<1 % allele frequency in gnomAD) predicted deleterious variants (RPDV) in 33/110 (30 %) women. All were heterozygous; two participants had multiple RPDV. No RPDV in COL1A1/COL1A2 were identified. 28/110 (25 %) had RPDV in genes related to WNT signaling, critical to bone formation: LRP5 (n = 19), LRP6 (n = 6), WNT1 (n = 2) or WNT1&LRP5 (n = 1). Seven had RPDV related to renal/calcium handling (SLC34A1, SLC34A3, SLC9A3), or other osteoporosis mechanisms (PLS3 (n = 3), HGD (n = 1)). Those with RPDV did not differ from those without in terms of BMD, fracture characteristics, and most clinical characteristics.
Among 110 PLO women, exome sequencing analyses identified a potential genetic osteoporosis contribution in 30 %, suggesting that many genetic contributors to PLO have yet to be elucidated. The finding of variants related to WNT signaling in 25 % of the cohort is consistent with the predominantly low bone formation phenotype of PLO and may have implications for prognosis and treatment response.
{"title":"Genetic contributors to osteoporosis in pregnancy and lactation associated osteoporosis (PLO)","authors":"Lauren Lynch , Patrick R. Shea , Natalie Vena , Wendy K. Chung , Elizabeth Shane , Mafo Kamanda-Kosseh , Jordan Barry , Dany El-Najjar , Sanchita Agarwal , Ananya Kondapalli , Ivelisse Colon , Mariana Bucovsky , Adi Cohen","doi":"10.1016/j.bone.2025.117744","DOIUrl":"10.1016/j.bone.2025.117744","url":null,"abstract":"<div><div>Pregnancy- and lactation-associated osteoporosis (PLO) describes a fragility fracture presentation around pregnancy/lactation. Presentation often includes multiple vertebral fractures, but can also involve hip, sacral/pelvic, or other fractures. Substantial bone structural deficits and low bone formation rate have been documented. Most have no known secondary cause. Many have a history of childhood fracture and/or family history of osteoporosis. These characteristics, together with early onset and disease severity, lead to the hypothesis that genetic factors may contribute to PLO.</div><div>We enrolled 110 women with PLO (mean #fractures = 6, vertebral fractures in 88 %) in an exome sequencing (ES) study. Analyses identified rare (<1 % allele frequency in gnomAD) predicted deleterious variants (RPDV) in 33/110 (30 %) women. All were heterozygous; two participants had multiple RPDV. No RPDV in <em>COL1A1</em>/<em>COL1A2</em> were identified. 28/110 (25 %) had RPDV in genes related to WNT signaling, critical to bone formation<em>: LRP5</em> (<em>n</em> = 19), <em>LRP6</em> (<em>n</em> = 6), <em>WNT1</em> (<em>n</em> = 2) or <em>WNT1&LRP5</em> (n = 1). Seven had RPDV related to renal/calcium handling (<em>SLC34A1, SLC34A3, SLC9A3</em>), or other osteoporosis mechanisms (<em>PLS3</em> (<em>n</em> = 3), <em>HGD</em> (<em>n</em> = 1)). Those with RPDV did not differ from those without in terms of BMD, fracture characteristics, and most clinical characteristics.</div><div>Among 110 PLO women, exome sequencing analyses identified a potential genetic osteoporosis contribution in 30 %, suggesting that many genetic contributors to PLO have yet to be elucidated. The finding of variants related to WNT signaling in 25 % of the cohort is consistent with the predominantly low bone formation phenotype of PLO and may have implications for prognosis and treatment response.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117744"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atypical periprosthetic femoral fracture (APFF) is a rare but increasingly recognized complication of hip arthroplasty. Although cemented stems are generally considered protective against fractures, APFFs have also been reported around these implants. However, their clinical and radiographic characteristics remain poorly understood. This multicenter retrospective study aimed to clarify the features of APFFs occurring around cemented stems. Twenty hips from 19 patients were identified, based on the revised criteria of the American Society for Bone and Mineral Research Task Force, without excluding periprosthetic fractures. Fracture location was classified by distance from the stem tip: beyond 25 mm proximally as subtrochanteric type, within 25 mm as stem tip-type, and beyond 25 mm distally as femoral shaft type. Stem tip-type fractures were most common (15 hips, 75 %), followed by femoral shaft type (four hips, 20 %) and subtrochanteric type (one hip, 5 %). All varus aligned stems (four hips) and 83 % of neutrally aligned stems (10 of 12 hips) were stem tip-type fractures. Beaking or flaring of the lateral cortex was present in 76 % (13 of 17 hips) with pre-fracture radiographs. Prodromal pain was reported in 40 % (eight hips) and bisphosphonate use was identified in 94 % (16 of 17 hips) with available medication data. Surgical treatment was performed in 85 % (17 hips), including internal fixation (10 hips) and revision arthroplasty (seven hips); 15 % (three hips) were managed conservatively. Cemented APFFs frequently occur around the stem tip and are often preceded by radiographic changes and symptoms. Early recognition may support timely diagnosis and intervention.
{"title":"Atypical periprosthetic femoral fractures around cemented stems: Radiographic features and clinical implications from a multicenter study","authors":"Ken Tashiro , Tomonori Baba , Hiroshi Fujita , Hiroaki Iwase , Hirotsugu Ohashi , Kenichi Oe , Makoto Otsuka , Shintaro Iwai , Suguru Nakamura , Takeru Morimoto , Takeshi Sawaguchi , Yosuke Nagai , Yosuke Otsuki , Youngwoo Kim , Muneaki Ishijima","doi":"10.1016/j.bone.2025.117741","DOIUrl":"10.1016/j.bone.2025.117741","url":null,"abstract":"<div><div>Atypical periprosthetic femoral fracture (APFF) is a rare but increasingly recognized complication of hip arthroplasty. Although cemented stems are generally considered protective against fractures, APFFs have also been reported around these implants. However, their clinical and radiographic characteristics remain poorly understood. This multicenter retrospective study aimed to clarify the features of APFFs occurring around cemented stems. Twenty hips from 19 patients were identified, based on the revised criteria of the American Society for Bone and Mineral Research Task Force, without excluding periprosthetic fractures. Fracture location was classified by distance from the stem tip: beyond 25 mm proximally as subtrochanteric type, within 25 mm as stem tip-type, and beyond 25 mm distally as femoral shaft type. Stem tip-type fractures were most common (15 hips, 75 %), followed by femoral shaft type (four hips, 20 %) and subtrochanteric type (one hip, 5 %). All varus aligned stems (four hips) and 83 % of neutrally aligned stems (10 of 12 hips) were stem tip-type fractures. Beaking or flaring of the lateral cortex was present in 76 % (13 of 17 hips) with pre-fracture radiographs. Prodromal pain was reported in 40 % (eight hips) and bisphosphonate use was identified in 94 % (16 of 17 hips) with available medication data. Surgical treatment was performed in 85 % (17 hips), including internal fixation (10 hips) and revision arthroplasty (seven hips); 15 % (three hips) were managed conservatively. Cemented APFFs frequently occur around the stem tip and are often preceded by radiographic changes and symptoms. Early recognition may support timely diagnosis and intervention.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117741"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145650404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-21DOI: 10.1016/j.bone.2025.117768
Yajun Zhang , Hanwen Cheng , Jiuxu Deng , Bo Chen , Yuyang Ran , Yuhui Kou , Baoguo Jiang
Background
Rat models are widely used in preclinical osteoporosis research to study disease mechanisms and evaluate therapies. Current Micro-CT studies mostly rely on cross-sectional comparisons at a single time point, and there is a lack of standardized reference data across multiple time points. To address this gap, the present study provides standardized reference data from multiple time points using a deep learning-based Micro-CT grayscale analysis, enabling early detection and precise staging of osteoporosis.
Methods
A standardized osteoporosis model was established in ovariectomized Sprague–Dawley rats (n = 32) with a sham-operated group (n = 32). Femurs were harvested at 4, 8, 16, and 24 weeks post-surgery. The proximal 0–250 slice region adjacent to the growth plate was defined as the region of interest (ROI), and six representative slices per femur were analyzed. Voxels within each ROI were classified into four grayscale regions: 0–50 (non-bone), 51–100 (bone–nonbone transition), 101–150 (defined bone), and 151–255 (highly mineralized bone). The percentage areas of the four regions across the six slices (4 × 6 input) were used to train a custom deep learning model. Diagnostic performance for early osteoporosis detection and staging was compared with conventional trabecular parameters.
Results
Both the grayscale-based algorithm and conventional Micro-CT parameters distinguished Sham and OVX rats at 4 weeks, enabling early detection, whereas DXA only detected differences at 16 weeks. In osteoporosis staging within the OVX group, the grayscale-based model achieved higher accuracy (88.4 % ± 6.4 %) than conventional parameters (55.9 % ± 8.4 %, p < 0.05). For single-time-point osteoporosis diagnosis, the grayscale-based algorithm (98.3 % ± 3.4 %) also outperformed conventional parameters (85.3 % ± 3.4 %, p < 0.05).
Conclusion
The grayscale-based deep learning method allows sensitive early detection and more accurate staging of osteoporosis, providing a robust quantitative tool for assessment of osteoporotic progression in OVX rats.
{"title":"Deep learning-based micro-CT grayscale analysis for early detection and staging of osteoporosis in rats","authors":"Yajun Zhang , Hanwen Cheng , Jiuxu Deng , Bo Chen , Yuyang Ran , Yuhui Kou , Baoguo Jiang","doi":"10.1016/j.bone.2025.117768","DOIUrl":"10.1016/j.bone.2025.117768","url":null,"abstract":"<div><h3>Background</h3><div>Rat models are widely used in preclinical osteoporosis research to study disease mechanisms and evaluate therapies. Current Micro-CT studies mostly rely on cross-sectional comparisons at a single time point, and there is a lack of standardized reference data across multiple time points. To address this gap, the present study provides standardized reference data from multiple time points using a deep learning-based Micro-CT grayscale analysis, enabling early detection and precise staging of osteoporosis.</div></div><div><h3>Methods</h3><div>A standardized osteoporosis model was established in ovariectomized Sprague–Dawley rats (<em>n</em> = 32) with a sham-operated group (n = 32). Femurs were harvested at 4, 8, 16, and 24 weeks post-surgery. The proximal 0–250 slice region adjacent to the growth plate was defined as the region of interest (ROI), and six representative slices per femur were analyzed. Voxels within each ROI were classified into four grayscale regions: 0–50 (non-bone), 51–100 (bone–nonbone transition), 101–150 (defined bone), and 151–255 (highly mineralized bone). The percentage areas of the four regions across the six slices (4 × 6 input) were used to train a custom deep learning model. Diagnostic performance for early osteoporosis detection and staging was compared with conventional trabecular parameters.</div></div><div><h3>Results</h3><div>Both the grayscale-based algorithm and conventional Micro-CT parameters distinguished Sham and OVX rats at 4 weeks, enabling early detection, whereas DXA only detected differences at 16 weeks. In osteoporosis staging within the OVX group, the grayscale-based model achieved higher accuracy (88.4 % ± 6.4 %) than conventional parameters (55.9 % ± 8.4 %, <em>p</em> < 0.05). For single-time-point osteoporosis diagnosis, the grayscale-based algorithm (98.3 % ± 3.4 %) also outperformed conventional parameters (85.3 % ± 3.4 %, p < 0.05).</div></div><div><h3>Conclusion</h3><div>The grayscale-based deep learning method allows sensitive early detection and more accurate staging of osteoporosis, providing a robust quantitative tool for assessment of osteoporotic progression in OVX rats.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117768"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-12-23DOI: 10.1016/j.bone.2025.117769
Polyzois Makras , Maria P. Yavropoulou , Athanasios D. Anastasilakis , Natasha M. Appelman-Dijkstra , John J. Carey , Anda Mihaela Naciu , Julien Paccou , Tim Rolvien , Elizabeth M. Winter , Socrates E. Papapoulos , Willem F. Lems
Purpose
This narrative review explores the therapeutic potential of repurposing medications originally developed or approved for osteoporosis to treat non-osteoporotic conditions. Given their pharmacologic profiles and safety data, these agents offer promising therapeutic alternatives in both rare and common diseases with unmet clinical needs.
Principal results
Evidence from preclinical models, observational data, and randomised trials supports the repositioning of several osteoporosis drugs. Cyclic etidronate has shown efficacy in halting arterial calcification progression in pseudoxanthoma elasticum. Pamidronate has demonstrated symptom improvement in adult chronic nonbacterial osteitis. Neridronate is approved only in Italy for complex regional pain syndrome type I. Denosumab has shown therapeutic effects in Langerhans cell histiocytosis and has structural benefits in erosive hand osteoarthritis and rheumatoid arthritis. Parathyroid hormone analogues (rhPTH [1–84] and teriparatide) improve calcium-phosphate homeostasis in chronic and genetic hypoparathyroidism. Calcilytics, though originally discontinued for osteoporosis, show emerging promise in autosomal dominant hypoparathyroidism. In contrast, zoledronic acid has not demonstrated consistent clinical benefit in knee osteoarthritis. Strontium ranelate, despite showing structure-modifying effects in osteoarthritis, is no longer marketed due to safety concerns. Alendronate and denosumab in fibrous dysplasia yielded mixed results, with concerns about rebound effects after denosumab withdrawal.
Conclusions
Repurposing osteoporosis medications represents a cost-effective, timely strategy to expand treatment options across diverse clinical indications. While promising outcomes have been demonstrated—particularly in rare diseases—rigorous, indication-specific clinical trials are essential to confirm efficacy, safety, and long-term outcomes. The accumulated pharmacologic and clinical experience with these agents offers a strong foundation for their continued exploration beyond osteoporosis.
{"title":"Repurposing osteoporosis medications for other diseases: a narrative review by the European Calcified Tissue Society (ECTS)","authors":"Polyzois Makras , Maria P. Yavropoulou , Athanasios D. Anastasilakis , Natasha M. Appelman-Dijkstra , John J. Carey , Anda Mihaela Naciu , Julien Paccou , Tim Rolvien , Elizabeth M. Winter , Socrates E. Papapoulos , Willem F. Lems","doi":"10.1016/j.bone.2025.117769","DOIUrl":"10.1016/j.bone.2025.117769","url":null,"abstract":"<div><h3>Purpose</h3><div>This narrative review explores the therapeutic potential of repurposing medications originally developed or approved for osteoporosis to treat non-osteoporotic conditions. Given their pharmacologic profiles and safety data, these agents offer promising therapeutic alternatives in both rare and common diseases with unmet clinical needs.</div></div><div><h3>Principal results</h3><div>Evidence from preclinical models, observational data, and randomised trials supports the repositioning of several osteoporosis drugs. Cyclic etidronate has shown efficacy in halting arterial calcification progression in pseudoxanthoma elasticum. Pamidronate has demonstrated symptom improvement in adult chronic nonbacterial osteitis. Neridronate is approved only in Italy for complex regional pain syndrome type I. Denosumab has shown therapeutic effects in Langerhans cell histiocytosis and has structural benefits in erosive hand osteoarthritis and rheumatoid arthritis. Parathyroid hormone analogues (rhPTH [1–84] and teriparatide) improve calcium-phosphate homeostasis in chronic and genetic hypoparathyroidism. Calcilytics, though originally discontinued for osteoporosis, show emerging promise in autosomal dominant hypoparathyroidism. In contrast, zoledronic acid has not demonstrated consistent clinical benefit in knee osteoarthritis. Strontium ranelate, despite showing structure-modifying effects in osteoarthritis, is no longer marketed due to safety concerns. Alendronate and denosumab in fibrous dysplasia yielded mixed results, with concerns about rebound effects after denosumab withdrawal.</div></div><div><h3>Conclusions</h3><div>Repurposing osteoporosis medications represents a cost-effective, timely strategy to expand treatment options across diverse clinical indications. While promising outcomes have been demonstrated—particularly in rare diseases—rigorous, indication-specific clinical trials are essential to confirm efficacy, safety, and long-term outcomes. The accumulated pharmacologic and clinical experience with these agents offers a strong foundation for their continued exploration beyond osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117769"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145835476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-11-29DOI: 10.1016/j.bone.2025.117738
Xiaoyue Sun , Binqian Liu , Zetong Li , Songqin Zhou , Zijun Wang , Jingjing Yu , Qing Nie , Lingxin Zhu
Aseptic craniofacial osteolysis around the implant-bone interface, induced by wear particles, leads to the loosening and failure of dental implants, temporomandibular joint prostheses and internal fixation during maxillofacial reconstruction. Osteoclasts, as terminally differentiated multinucleated giant cells and the exclusive bone resorptive cells, play an important role in this pathological process. The PINK1/Parkin pathway is involved in mitochondrial quality control; however, its effects on osteoclast-mediated physiological bone homeostasis and the therapeutic potential on craniofacial osteolysis remains unexplored. We generated the mutant mice in which Parkin was conditionally deleted in myeloid lineage cells (LysM-Cre/Park2flox/flox; Park2ΔM/ΔM). Unexpectedly, the Park2ΔM/ΔM mice displayed no overall skeletal phenotype. In tandem, upon osteoclastogenic induction, Park2ΔM/ΔM macrophages undergone RANKL-induced osteoclastogenesis normally with compensated increased PINK1 expression. Notably, Mdivi-1 remarkably simultaneously inhibited the PINK1 and Parkin expression, leading to significant attenuated osteoclastogenesis in a concentration-dependent manner. The aseptic titanium particle-induced calvaria erosion model was constructed to simulate craniofacial osteolysis. Importantly, Mdivi-1 effectively alleviated the bone resorption and trabecular structure destruction induced by titanium particles, and blocked the osteoclast accumulation in the lesions. Taken together, Mdivi-1 alleviated titanium particle-induced aseptic craniofacial osteolysis via inhibition of PINK1/Parkin-dependent mitophagy. In summary, while myeloid lineage conditionally deletion of Park2 does not interfere with osteoclast differentiation and physiological bone homeostasis in mice probably due to the compensation by PINK1 expression, Mdivi-1 as the inhibitor of PINK1/Parkin-dependent mitophagy may provide a novel therapeutic strategy towards aseptic craniofacial osteolysis.
{"title":"Mdivi-1 alleviates aseptic craniofacial osteolysis via inhibition of PINK1/Parkin-dependent mitophagy","authors":"Xiaoyue Sun , Binqian Liu , Zetong Li , Songqin Zhou , Zijun Wang , Jingjing Yu , Qing Nie , Lingxin Zhu","doi":"10.1016/j.bone.2025.117738","DOIUrl":"10.1016/j.bone.2025.117738","url":null,"abstract":"<div><div>Aseptic craniofacial osteolysis around the implant-bone interface, induced by wear particles, leads to the loosening and failure of dental implants, temporomandibular joint prostheses and internal fixation during maxillofacial reconstruction. Osteoclasts, as terminally differentiated multinucleated giant cells and the exclusive bone resorptive cells, play an important role in this pathological process. The PINK1/Parkin pathway is involved in mitochondrial quality control; however, its effects on osteoclast-mediated physiological bone homeostasis and the therapeutic potential on craniofacial osteolysis remains unexplored. We generated the mutant mice in which Parkin was conditionally deleted in myeloid lineage cells (<em>LysM-Cre/Park2</em><sup><em>flox/flox</em></sup><em>; Park2</em><sup><em>ΔM/ΔM</em></sup>). Unexpectedly, the <em>Park2</em><sup><em>ΔM/ΔM</em></sup> mice displayed no overall skeletal phenotype. In tandem, upon osteoclastogenic induction, <em>Park2</em><sup><em>ΔM/ΔM</em></sup> macrophages undergone RANKL-induced osteoclastogenesis normally with compensated increased PINK1 expression. Notably, Mdivi-1 remarkably simultaneously inhibited the PINK1 and Parkin expression, leading to significant attenuated osteoclastogenesis in a concentration-dependent manner. The aseptic titanium particle-induced calvaria erosion model was constructed to simulate craniofacial osteolysis. Importantly, Mdivi-1 effectively alleviated the bone resorption and trabecular structure destruction induced by titanium particles, and blocked the osteoclast accumulation in the lesions. Taken together, Mdivi-1 alleviated titanium particle-induced aseptic craniofacial osteolysis <em>via</em> inhibition of PINK1/Parkin-dependent mitophagy. In summary, while myeloid lineage conditionally deletion of <em>Park2</em> does not interfere with osteoclast differentiation and physiological bone homeostasis in mice probably due to the compensation by PINK1 expression, Mdivi-1 as the inhibitor of PINK1/Parkin-dependent mitophagy may provide a novel therapeutic strategy towards aseptic craniofacial osteolysis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"204 ","pages":"Article 117738"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-19DOI: 10.1016/j.bone.2025.117733
Corentin Serra , Romain Monchaux , Benjamin Salmon , Lara Nokovitch , Natacha Kadlub , Jean Boisson
The vascularization of bone still holds several unknowns, crucial to future developments in reconstructive surgery: both for bone transplantation and decellularized allograft. This study introduces a novel method to analyze pressure-dependent vascular territories in the human mandible, with direct implications for the optimization of decellularization by perfusion protocols. Traditional anatomical approaches have struggled to delineate perfusion territories due to the complexity of multiple arterial inputs and the dynamic nature of blood flow. Our methodology integrates pressure-controlled perfusion with 3D imaging to map vascular distribution within the mandibular bone under varying perfusion pressures. We conducted controlled perfusions on human cadaveric mandibles, progressively increasing pressure while monitoring the expansion of perfused territories using contrast-enhanced cone beam computed tomography. A custom segmentation pipeline allowed for the reconstruction of pressure maps detailing the minimal pressure required to perfuse different regions of the mandible. Our results demonstrate a low-pressure anastomosis of the maxillary artery to the facial artery through the mental artery, suggesting the equivalence of intraosseous territories, followed by a radial perfusion pattern from the inferior alveolar artery, with increasing resistance at the cortical bone. Perfusion saturation was achieved at approximately 100–125 hPa, in accordance with physiological arterial pressures. Furthermore, cortical bone exhibited higher perfusion thresholds than cancellous bone, emphasizing differential vascular resistance across bone structures.
These findings suggest that pressure-driven perfusion analysis can provide crucial insights into bone vascularization. By optimizing pressure parameters, it may be possible to achieve more effective decellularization by perfusion in massive bone allografts, improving graft integration and long-term viability. This study also underscores the need for pressure-controlled anatomical studies, as perfusion territories vary significantly with applied pressure, challenging traditional static angiosoma models. Future research should explore the applicability of these findings in living tissues and refine decellularization techniques based on controlled perfusion dynamics.
{"title":"Influence of pressure on mandibular angiosomes: What implications for decellularization?","authors":"Corentin Serra , Romain Monchaux , Benjamin Salmon , Lara Nokovitch , Natacha Kadlub , Jean Boisson","doi":"10.1016/j.bone.2025.117733","DOIUrl":"10.1016/j.bone.2025.117733","url":null,"abstract":"<div><div>The vascularization of bone still holds several unknowns, crucial to future developments in reconstructive surgery: both for bone transplantation and decellularized allograft. This study introduces a novel method to analyze pressure-dependent vascular territories in the human mandible, with direct implications for the optimization of decellularization by perfusion protocols. Traditional anatomical approaches have struggled to delineate perfusion territories due to the complexity of multiple arterial inputs and the dynamic nature of blood flow. Our methodology integrates pressure-controlled perfusion with 3D imaging to map vascular distribution within the mandibular bone under varying perfusion pressures. We conducted controlled perfusions on human cadaveric mandibles, progressively increasing pressure while monitoring the expansion of perfused territories using contrast-enhanced cone beam computed tomography. A custom segmentation pipeline allowed for the reconstruction of pressure maps detailing the minimal pressure required to perfuse different regions of the mandible. Our results demonstrate a low-pressure anastomosis of the maxillary artery to the facial artery through the mental artery, suggesting the equivalence of intraosseous territories, followed by a radial perfusion pattern from the inferior alveolar artery, with increasing resistance at the cortical bone. Perfusion saturation was achieved at approximately 100–125 hPa, in accordance with physiological arterial pressures. Furthermore, cortical bone exhibited higher perfusion thresholds than cancellous bone, emphasizing differential vascular resistance across bone structures.</div><div>These findings suggest that pressure-driven perfusion analysis can provide crucial insights into bone vascularization. By optimizing pressure parameters, it may be possible to achieve more effective decellularization by perfusion in massive bone allografts, improving graft integration and long-term viability. This study also underscores the need for pressure-controlled anatomical studies, as perfusion territories vary significantly with applied pressure, challenging traditional static angiosoma models. Future research should explore the applicability of these findings in living tissues and refine decellularization techniques based on controlled perfusion dynamics.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117733"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-04DOI: 10.1016/j.bone.2025.117709
Annabel R. Bugbird , Lauren A. Burt , Danielle E. Whittier , Steven K. Boyd
<div><h3>Introduction:</h3><div>A previously developed <em>phenotyping</em> model groups common combinations of bone characteristics into three primary phenotypes: <em>healthy</em>, <em>low volume</em>, and <em>low density</em> from high resolution peripheral quantitative computed tomography (HR-pQCT). While these phenotypes have been characterized in cross-sectional cohorts, their longitudinal progression and transitions with aging remains unknown. Therefore, the aim of this study was to investigate how bone microarchitecture phenotypes evolves over time, identify common transitional patterns, and examine their association with fracture risk.</div></div><div><h3>Methods:</h3><div>Our cohort included 606 adult male and female participants from a longitudinal population study. HR-pQCT scans of the distal radius and tibia were acquired at two visits. Bone phenotypes, defined as <em>healthy</em>, <em>low volume</em>, and <em>low density</em>, were determined at baseline and follow-up. Transitional patterns in phenotypes were examined by age group and sex, and further analyzed in relation to average bone size based on cross-sectional area. The relative contributions of sex and bone size to phenotype transitions were evaluated using nested linear regression models.</div></div><div><h3>Results:</h3><div>The average age of participants was 60.4 ± 16.2 years, with a mean follow-up duration of 6.76 ± 1.78 years. Phenotype membership remained relatively stable over the follow-up time but exhibited an average transitional pattern from the <em>healthy</em> phenotype in younger adults (18–40 years), to <em>low volume</em> (40–60 years), and eventually to <em>low density</em> (60+ years), particularly among females. When stratified by bone size, individuals with larger bones tended to follow an average trajectory from <em>healthy</em> to <em>low density</em>, whereas those with smaller bones typically transitioned from <em>healthy</em> to <em>low volume</em> to <em>low density</em>. Although sex and bone size were strongly correlated (R<span><math><mrow><msup><mrow></mrow><mrow><mn>2</mn></mrow></msup><mo>=</mo></mrow></math></span> 0.43), and showed similar transitional patterns, sex remained a significant predictor of phenotype membership even after adjusting for bone size (p <span><math><mo><</mo></math></span> 0.001).</div></div><div><h3>Conclusion:</h3><div>These findings demonstrate that the bone phenotype model provides a dynamic, interpretable framework for monitoring skeletal health over time, capturing age-, sex-, and size-related trajectories, and offering potential for individualized bone health assessment.</div></div><div><h3>Lay Summary:</h3><div>We investigated the longitudinal progression of bone phenotypes, categorized as <em>healthy</em>, <em>low volume</em>, and <em>low density</em>, in adult males and females. Phenotype transitions were analyzed by age, sex, and average bone size. Most individuals followed an average trajectory from <em>
{"title":"Bone size and sex are key determinants of the longitudinal bone phenotype trajectory in aging males and females","authors":"Annabel R. Bugbird , Lauren A. Burt , Danielle E. Whittier , Steven K. Boyd","doi":"10.1016/j.bone.2025.117709","DOIUrl":"10.1016/j.bone.2025.117709","url":null,"abstract":"<div><h3>Introduction:</h3><div>A previously developed <em>phenotyping</em> model groups common combinations of bone characteristics into three primary phenotypes: <em>healthy</em>, <em>low volume</em>, and <em>low density</em> from high resolution peripheral quantitative computed tomography (HR-pQCT). While these phenotypes have been characterized in cross-sectional cohorts, their longitudinal progression and transitions with aging remains unknown. Therefore, the aim of this study was to investigate how bone microarchitecture phenotypes evolves over time, identify common transitional patterns, and examine their association with fracture risk.</div></div><div><h3>Methods:</h3><div>Our cohort included 606 adult male and female participants from a longitudinal population study. HR-pQCT scans of the distal radius and tibia were acquired at two visits. Bone phenotypes, defined as <em>healthy</em>, <em>low volume</em>, and <em>low density</em>, were determined at baseline and follow-up. Transitional patterns in phenotypes were examined by age group and sex, and further analyzed in relation to average bone size based on cross-sectional area. The relative contributions of sex and bone size to phenotype transitions were evaluated using nested linear regression models.</div></div><div><h3>Results:</h3><div>The average age of participants was 60.4 ± 16.2 years, with a mean follow-up duration of 6.76 ± 1.78 years. Phenotype membership remained relatively stable over the follow-up time but exhibited an average transitional pattern from the <em>healthy</em> phenotype in younger adults (18–40 years), to <em>low volume</em> (40–60 years), and eventually to <em>low density</em> (60+ years), particularly among females. When stratified by bone size, individuals with larger bones tended to follow an average trajectory from <em>healthy</em> to <em>low density</em>, whereas those with smaller bones typically transitioned from <em>healthy</em> to <em>low volume</em> to <em>low density</em>. Although sex and bone size were strongly correlated (R<span><math><mrow><msup><mrow></mrow><mrow><mn>2</mn></mrow></msup><mo>=</mo></mrow></math></span> 0.43), and showed similar transitional patterns, sex remained a significant predictor of phenotype membership even after adjusting for bone size (p <span><math><mo><</mo></math></span> 0.001).</div></div><div><h3>Conclusion:</h3><div>These findings demonstrate that the bone phenotype model provides a dynamic, interpretable framework for monitoring skeletal health over time, capturing age-, sex-, and size-related trajectories, and offering potential for individualized bone health assessment.</div></div><div><h3>Lay Summary:</h3><div>We investigated the longitudinal progression of bone phenotypes, categorized as <em>healthy</em>, <em>low volume</em>, and <em>low density</em>, in adult males and females. Phenotype transitions were analyzed by age, sex, and average bone size. Most individuals followed an average trajectory from <em>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117709"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-16DOI: 10.1016/j.bone.2025.117731
Rongjie Lin , Yiqing Huang , Zhenbin Chen , Xi Zeng , Yao Wang , Shaohuang Weng , Yu Cheng , Min Chen
Osteomyelitis (OM) is a severe bone-destructive disease characterized by infection and inflammation. Transcriptomic analysis of datasets GSE18043 and GSE30119 identified CTLA4 as a key regulator associated with immune modulation and osteogenic differentiation. Subsequent bioinformatic and immune infiltration analyses revealed that CTLA4 expression correlated with increased anti-inflammatory macrophage infiltration and activation of the Wnt/β-catenin signaling pathway of osteoblasts. Functionally, CTLA4-Ig promoted osteogenic differentiation, enhanced matrix mineralization, and upregulated osteogenic markers in MC3T3-E1 cells, while concurrently inhibiting osteoclast formation and bone resorption activity. In a Staphylococcus aureus-induced rat OM model, histological and immunohistochemical analyses further confirmed enhanced osteoblast activity and reduced osteoclast presence in the CTLA4-Ig treated group. CTLA4-Ig administration preserved bone structural integrity by modulating the inflammatory microenvironment, characterized by reduced expression of pro-inflammatory cytokines, increased levels of anti-inflammatory cytokines, enhanced osteogenic regeneration, and a reduction in bacterial burden. Collectively, these findings established CTLA4-Ig as a dual-action modulator that promoted bone regeneration while inhibiting bone destruction, offering a promising therapeutic strategy for OM.
{"title":"CTLA4-Ig sustains osteogenic potential and inhibits osteoclastogenesis in Staphylococcus aureus osteomyelitis","authors":"Rongjie Lin , Yiqing Huang , Zhenbin Chen , Xi Zeng , Yao Wang , Shaohuang Weng , Yu Cheng , Min Chen","doi":"10.1016/j.bone.2025.117731","DOIUrl":"10.1016/j.bone.2025.117731","url":null,"abstract":"<div><div>Osteomyelitis (OM) is a severe bone-destructive disease characterized by infection and inflammation. Transcriptomic analysis of datasets GSE18043 and GSE30119 identified CTLA4 as a key regulator associated with immune modulation and osteogenic differentiation. Subsequent bioinformatic and immune infiltration analyses revealed that CTLA4 expression correlated with increased anti-inflammatory macrophage infiltration and activation of the Wnt/β-catenin signaling pathway of osteoblasts. Functionally, CTLA4-Ig promoted osteogenic differentiation, enhanced matrix mineralization, and upregulated osteogenic markers in MC3T3-E1 cells, while concurrently inhibiting osteoclast formation and bone resorption activity. In a <em>Staphylococcus aureus</em>-induced rat OM model, histological and immunohistochemical analyses further confirmed enhanced osteoblast activity and reduced osteoclast presence in the CTLA4-Ig treated group. CTLA4-Ig administration preserved bone structural integrity by modulating the inflammatory microenvironment, characterized by reduced expression of pro-inflammatory cytokines, increased levels of anti-inflammatory cytokines, enhanced osteogenic regeneration, and a reduction in bacterial burden. Collectively, these findings established CTLA4-Ig as a dual-action modulator that promoted bone regeneration while inhibiting bone destruction, offering a promising therapeutic strategy for OM.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117731"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-09DOI: 10.1016/j.bone.2025.117711
Alibek Zhakubayev , Kathleen A. Grant , Lara H. Sattgast , Russell T. Turner , Urszula T. Iwaniec , Mary Lauren Benton
Alcohol abuse is a risk factor for atraumatic fractures. Our previous work using a non-human primate model of voluntary ethanol consumption showed that chronic ethanol intake for 6 months to 2.5 years decreased global bone turnover and tibial cortical porosity but did not result in changes in distal tibia cancellous architecture. However, bone remodeling varies among skeletal sites. Here, we extended this analysis to include 3 additional cancellous bone compartments (distal femur metaphysis, distal femur epiphysis, lumbar vertebra). Specifically, we applied a machine learning framework to data from 155 monkeys (100 ethanol and 55 controls) to identify the bone features associated with chronic ethanol use. In concordance with our prior findings, we did not find that ethanol consumption resulted in population-level changes in cancellous bone architecture. These findings support the concept that ethanol consumption similarly decreases bone formation and bone resorption across sites, resulting in minimal changes in bone remodeling balance.
{"title":"Ethanol consumption has minimal effects on cancellous bone architecture in femur and lumbar vertebra in two species of non-human primates","authors":"Alibek Zhakubayev , Kathleen A. Grant , Lara H. Sattgast , Russell T. Turner , Urszula T. Iwaniec , Mary Lauren Benton","doi":"10.1016/j.bone.2025.117711","DOIUrl":"10.1016/j.bone.2025.117711","url":null,"abstract":"<div><div>Alcohol abuse is a risk factor for atraumatic fractures. Our previous work using a non-human primate model of voluntary ethanol consumption showed that chronic ethanol intake for 6 months to 2.5 years decreased global bone turnover and tibial cortical porosity but did not result in changes in distal tibia cancellous architecture. However, bone remodeling varies among skeletal sites. Here, we extended this analysis to include 3 additional cancellous bone compartments (distal femur metaphysis, distal femur epiphysis, lumbar vertebra). Specifically, we applied a machine learning framework to data from 155 monkeys (100 ethanol and 55 controls) to identify the bone features associated with chronic ethanol use. In concordance with our prior findings, we did not find that ethanol consumption resulted in population-level changes in cancellous bone architecture. These findings support the concept that ethanol consumption similarly decreases bone formation and bone resorption across sites, resulting in minimal changes in bone remodeling balance.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117711"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-11DOI: 10.1016/j.bone.2025.117728
Lewis Weeda , Saiuj Bhat , Katie Wang , Ben Chia , Nick Calvert , Hannah Seymour , Revathy Manickavasagar , Lucy Kilshaw
Aims
Hip fracture patients have significant morbidity and mortality, with worse outcomes in end-stage kidney disease (ESKD) patients receiving dialysis. This study evaluates and quantifies the risk of mortality and complications in dialysis patients undergoing surgery for hip fractures.
Methods
A systematic review of studies investigating complications after surgery for hip fractures in ESKD patients receiving dialysis was performed across various databases. Mortality (30-day or longer) was the primary outcome.
Results
Thirty studies encompassing 23,024 dialysis patients were included, most of which had a low risk of bias (n = 26; 87 %). Thirty-day (RR 2.2; CI 95 %: 1.5, 3.2 and HR 2.3; CI 95 %: 1.7, 3.0) and overall mortality (RR 1.9; CI 95 %: 1.6, 2.2) were two-fold greater in dialysis patients. There was also an increased risk of surgical site infection (RR 1.6. CI 95 %: 1.3, 2.0), major adverse cardiac events (RR 1.9. CI 95 %: 1.3, 3.0), and sepsis (RR 1.9. CI: 1.5, 2.2) in this cohort compared to a non-dialysis cohort.
Conclusion
Patients receiving dialysis experience approximately two-fold greater mortality after hip fracture surgery compared to patients not receiving dialysis. Dialysis patients face higher rates of complications after surgery, notably wound infection, major adverse cardiac events, and sepsis. Results from this study provide quantitative estimates for perioperative counselling of patients alongside families. While some tools aid in predicting post-operative outcomes, further research may refine risk stratification in this cohort. Additional evidence is required to establish evidence-based models of care that optimise the peri-operative health of dialysis patients.
目的：髋部骨折患者具有显著的发病率和死亡率，终末期肾病（ESKD）患者接受透析治疗的预后更差。本研究评估和量化透析患者髋部骨折手术的死亡率和并发症的风险。方法：通过不同的数据库对接受透析的ESKD患者髋部骨折术后并发症的研究进行系统回顾。死亡率（30天或更长）是主要结局。结果：纳入了30项研究，包括23,024例透析患者，其中大多数具有低偏倚风险（n = 26;87 %）。透析患者的30天死亡率（RR 2.2; CI 95 %:1.5,3.2和HR 2.3; CI 95 %:1.7,3.0）和总死亡率（RR 1.9; CI 95 %:1.6,2.2）高出两倍。手术部位感染的风险也增加（RR为1.6）。CI 95 %:1.3,2.0)，主要心脏不良事件（RR 1.9）。CI 95 %:1.3,3.0)和脓毒症(RR 1.9。CI: 1.5, 2.2)，与非透析组相比。结论：与未接受透析的患者相比，接受透析的患者髋部骨折术后死亡率大约高出两倍。透析患者术后并发症发生率较高，特别是伤口感染、主要心脏不良事件和败血症。本研究的结果为患者及其家属围手术期咨询提供了定量估计。虽然一些工具有助于预测术后结果，但进一步的研究可能会完善该队列的风险分层。需要更多的证据来建立循证护理模式，以优化透析患者的围手术期健康。
{"title":"Complications following hip fracture surgery in end-stage kidney disease patients receiving dialysis: A systematic review and meta-analysis of cohort studies","authors":"Lewis Weeda , Saiuj Bhat , Katie Wang , Ben Chia , Nick Calvert , Hannah Seymour , Revathy Manickavasagar , Lucy Kilshaw","doi":"10.1016/j.bone.2025.117728","DOIUrl":"10.1016/j.bone.2025.117728","url":null,"abstract":"<div><h3>Aims</h3><div>Hip fracture patients have significant morbidity and mortality, with worse outcomes in end-stage kidney disease (ESKD) patients receiving dialysis. This study evaluates and quantifies the risk of mortality and complications in dialysis patients undergoing surgery for hip fractures.</div></div><div><h3>Methods</h3><div>A systematic review of studies investigating complications after surgery for hip fractures in ESKD patients receiving dialysis was performed across various databases. Mortality (30-day or longer) was the primary outcome.</div></div><div><h3>Results</h3><div>Thirty studies encompassing 23,024 dialysis patients were included, most of which had a low risk of bias (<em>n</em> = 26; 87 %). Thirty-day (RR 2.2; CI 95 %: 1.5, 3.2 and HR 2.3; CI 95 %: 1.7, 3.0) and overall mortality (RR 1.9; CI 95 %: 1.6, 2.2) were two-fold greater in dialysis patients. There was also an increased risk of surgical site infection (RR 1.6. CI 95 %: 1.3, 2.0), major adverse cardiac events (RR 1.9. CI 95 %: 1.3, 3.0), and sepsis (RR 1.9. CI: 1.5, 2.2) in this cohort compared to a non-dialysis cohort.</div></div><div><h3>Conclusion</h3><div>Patients receiving dialysis experience approximately two-fold greater mortality after hip fracture surgery compared to patients not receiving dialysis. Dialysis patients face higher rates of complications after surgery, notably wound infection, major adverse cardiac events, and sepsis. Results from this study provide quantitative estimates for perioperative counselling of patients alongside families. While some tools aid in predicting post-operative outcomes, further research may refine risk stratification in this cohort. Additional evidence is required to establish evidence-based models of care that optimise the peri-operative health of dialysis patients.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117728"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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