Romosozumab is an anti-sclerostin antibody that increases bone formation and decreases bone resorption. It has been available for patients at high risk of osteoporotic fractures in Japan since 2019. The aim of this study was to clarify the clinical effectiveness and safety of romosozumab following previous treatment with raloxifene. The study had an observational pre–post design and included 62 women with primary osteoporosis. Romosozumab 210 mg was administered subcutaneously every 4 weeks for 12 months in patients who had been previously treated with raloxifene (raloxifene group, n = 12) and in those who were treatment-naïve (treatment-naïve group, n = 50). The incidence of new fractures, safety, and changes in bone mineral density (BMD) and bone turnover markers (BTMs) were recorded. No new fractures occurred in either group. Ten patients (16.1%) in the treatment-naïve group discontinued romosozumab for the following reasons: non-serious adverse events (n = 2, 3.2%), a change to another hospital (n = 1, 1.6%), self-discontinuation (n = 5, 8.1%), and financial constraints (n = 2, 3.2%). The percent changes in spine BMD and total hip BMD at 12 months were respectively +13.5% and + 4.9% in the treatment-naïve group and + 16.0% and + 3.4%, respectively, in the raloxifene group. We did not detect significant differences in the changes in BTMs according to whether there was previous treatment with raloxifene. Prior raloxifene treatment may be well tolerated and may not affect increases in BMD, changes in BTMs, and fracture prevention in romosozumab therapy.
{"title":"Effectiveness of romosozumab following prior raloxifene treatment in primary osteoporosis: An observational study","authors":"Kazuaki Mineta , Toshihiko Nishisho , Masahiko Okada , Mitsuhiro Kamada , Koichi Sairyo","doi":"10.1016/j.bonr.2026.101900","DOIUrl":"10.1016/j.bonr.2026.101900","url":null,"abstract":"<div><div>Romosozumab is an anti-sclerostin antibody that increases bone formation and decreases bone resorption. It has been available for patients at high risk of osteoporotic fractures in Japan since 2019. The aim of this study was to clarify the clinical effectiveness and safety of romosozumab following previous treatment with raloxifene. The study had an observational pre–post design and included 62 women with primary osteoporosis. Romosozumab 210 mg was administered subcutaneously every 4 weeks for 12 months in patients who had been previously treated with raloxifene (raloxifene group, <em>n</em> = 12) and in those who were treatment-naïve (treatment-naïve group, <em>n</em> = 50). The incidence of new fractures, safety, and changes in bone mineral density (BMD) and bone turnover markers (BTMs) were recorded. No new fractures occurred in either group. Ten patients (16.1%) in the treatment-naïve group discontinued romosozumab for the following reasons: non-serious adverse events (<em>n</em> = 2, 3.2%), a change to another hospital (<em>n</em> = 1, 1.6%), self-discontinuation (<em>n</em> = 5, 8.1%), and financial constraints (<em>n</em> = 2, 3.2%). The percent changes in spine BMD and total hip BMD at 12 months were respectively +13.5% and + 4.9% in the treatment-naïve group and + 16.0% and + 3.4%, respectively, in the raloxifene group. We did not detect significant differences in the changes in BTMs according to whether there was previous treatment with raloxifene. Prior raloxifene treatment may be well tolerated and may not affect increases in BMD, changes in BTMs, and fracture prevention in romosozumab therapy.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"28 ","pages":"Article 101900"},"PeriodicalIF":2.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073557","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}
Osteogenesis Imperfecta (OI) is a rare hereditary brittle bone disorder typically caused by COL1A1 and COL1A2 variants impairing type I collagen. However, gross deletions involving COL1A1 are uncommon. Here, we report a family with type I OI harboring a 101-kbp deletion encompassing COL1A1, identified through whole genome analysis. Affected individuals presented mild phenotypes. Breakpoint analysis revealed a 5-bp microhomology-mediated end joining involving an Alu element. This report expands the understanding of genetic mechanisms underlying OI.
{"title":"Osteogenesis Imperfecta with a gross deletion including the COL1A1 gene, induced by Alu-driven microhomology-mediated end joining","authors":"Kenichi Yamamoto , Hirofumi Nakayama , Yusaku Ito , Masaya Hattori , Takaaki Shimada , Ikumi Ueda , Takeshi Ishimi , Chieko Yamada , Yukako Nakano , Makoto Fujiwara , Takuo Kubota , Yasuhisa Ohata , Yasuji Kitabatake","doi":"10.1016/j.bonr.2026.101901","DOIUrl":"10.1016/j.bonr.2026.101901","url":null,"abstract":"<div><div>Osteogenesis Imperfecta (OI) is a rare hereditary brittle bone disorder typically caused by <em>COL1A1</em> and <em>COL1A2</em> variants impairing type I collagen. However, gross deletions involving <em>COL1A1</em> are uncommon. Here, we report a family with type I OI harboring a 101-kbp deletion encompassing <em>COL1A1</em>, identified through whole genome analysis. Affected individuals presented mild phenotypes. Breakpoint analysis revealed a 5-bp microhomology-mediated end joining involving an Alu element. This report expands the understanding of genetic mechanisms underlying OI.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"28 ","pages":"Article 101901"},"PeriodicalIF":2.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073559","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 : 2026-01-16DOI: 10.1016/j.bonr.2026.101898
Wei Huang , Pin Pan , Kunpeng Liu , Yang Xu , Shuyi Cheng , Hanyang Wang , Longxu Han , Yinyu Qi , Lu Ren , Jianjun Chu
Objective
This study aimed to develop and evaluate a deep learning model based on the Vision Transformer (ViT) architecture for the automatic classification of hip X-ray images into three categories: normal bone mass, osteopenia, and osteoporosis. The goal was to explore the model's potential for early screening and auxiliary diagnosis of osteoporosis.
Methods
A total of 3016 hip anteroposterior X-ray images were retrospectively collected from Hefei Hospital Affiliated to Anhui Medical University and affiliated community clinics. After standard preprocessing and extraction of proximal femur regions of interest (ROI), the dataset was split into training and internal validation sets in an 8:2 ratio. A pretrained ViT model was fine-tuned for the three-class classification task and compared with conventional convolutional neural networks (ResNet50 and InceptionV3). Performance was assessed using accuracy, area under the ROC curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Additionally, the model was further validated using an external dataset to assess its generalizability.
Results
On the internal validation set, the ViT model achieved an overall classification accuracy of 97.0%. The AUCs for osteoporosis, osteopenia, and normal bone mass were 99.6%, 99.4%, and 99.9%, respectively. The PPV were 96.9%, 94.1% and 100%;The NPV were 97.9%, 98.5% and 99.2%. On the external validation set, the ViT model achieved an overall classification accuracy of 89.4%. The AUCs for osteoporosis, osteopenia, and normal bone mass were 96.5%, 91.6%, and 98.4%, respectively. The PPV were 83.5%, 90.2% and 91.3%;The NPV were 94.5%, 91.3% and 96.4%. The model demonstrated high sensitivity, specificity, PPV, and NPV across all classes, and outperformed both ResNet50 and InceptionV3 in overall diagnostic performance and classification stability.
Conclusion
The ViT-based deep learning model showed excellent performance in classifying bone mineral density using hip X-rays, with high accuracy and generalizability. Relying on routine X-ray images, this method provides a cost-effective and efficient tool for osteoporosis screening, with strong potential for clinical implementation in primary care settings.
{"title":"Intelligent identification of osteoporosis on hip X-rays using vision transformer","authors":"Wei Huang , Pin Pan , Kunpeng Liu , Yang Xu , Shuyi Cheng , Hanyang Wang , Longxu Han , Yinyu Qi , Lu Ren , Jianjun Chu","doi":"10.1016/j.bonr.2026.101898","DOIUrl":"10.1016/j.bonr.2026.101898","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to develop and evaluate a deep learning model based on the Vision Transformer (ViT) architecture for the automatic classification of hip X-ray images into three categories: normal bone mass, osteopenia, and osteoporosis. The goal was to explore the model's potential for early screening and auxiliary diagnosis of osteoporosis.</div></div><div><h3>Methods</h3><div>A total of 3016 hip anteroposterior X-ray images were retrospectively collected from Hefei Hospital Affiliated to Anhui Medical University and affiliated community clinics. After standard preprocessing and extraction of proximal femur regions of interest (ROI), the dataset was split into training and internal validation sets in an 8:2 ratio. A pretrained ViT model was fine-tuned for the three-class classification task and compared with conventional convolutional neural networks (ResNet50 and InceptionV3). Performance was assessed using accuracy, area under the ROC curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Additionally, the model was further validated using an external dataset to assess its generalizability.</div></div><div><h3>Results</h3><div>On the internal validation set, the ViT model achieved an overall classification accuracy of 97.0%. The AUCs for osteoporosis, osteopenia, and normal bone mass were 99.6%, 99.4%, and 99.9%, respectively. The PPV were 96.9%, 94.1% and 100%;The NPV were 97.9%, 98.5% and 99.2%. On the external validation set, the ViT model achieved an overall classification accuracy of 89.4%. The AUCs for osteoporosis, osteopenia, and normal bone mass were 96.5%, 91.6%, and 98.4%, respectively. The PPV were 83.5%, 90.2% and 91.3%;The NPV were 94.5%, 91.3% and 96.4%. The model demonstrated high sensitivity, specificity, PPV, and NPV across all classes, and outperformed both ResNet50 and InceptionV3 in overall diagnostic performance and classification stability.</div></div><div><h3>Conclusion</h3><div>The ViT-based deep learning model showed excellent performance in classifying bone mineral density using hip X-rays, with high accuracy and generalizability. Relying on routine X-ray images, this method provides a cost-effective and efficient tool for osteoporosis screening, with strong potential for clinical implementation in primary care settings.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"28 ","pages":"Article 101898"},"PeriodicalIF":2.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023103","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}
We report a case of a 64-year-old woman who developed a 4-parts shoulder fracture-dislocation with peripheral nerve injury by the displaced fragment, during abaloparatide treatment. Following shoulder hemiarthroplasty, bone union at the greater tuberosity was achieved on postoperative day 16, with remodelling completed at 6 months postoperatively. This course was exceptionally favourable. Factors potentially contributing to the early bone union progression may include the coincidental administration of abaloparatide prior to trauma and the presence of peripheral nerve injury.
{"title":"Rapid fracture healing of the greater tuberosity fragment after shoulder hemiarthroplasty in a patient with daily abaloparatide injection: A case report","authors":"Itsuo Joko , Mio Uchida , Masahito Hino , Shunsuke Miyaoka , Manabu Tanaka , Kazuo Kasuga , Nobuyuki Shimojo , Shigeharu Uchiyama","doi":"10.1016/j.bonr.2026.101899","DOIUrl":"10.1016/j.bonr.2026.101899","url":null,"abstract":"<div><div>We report a case of a 64-year-old woman who developed a 4-parts shoulder fracture-dislocation with peripheral nerve injury by the displaced fragment, during abaloparatide treatment. Following shoulder hemiarthroplasty, bone union at the greater tuberosity was achieved on postoperative day 16, with remodelling completed at 6 months postoperatively. This course was exceptionally favourable. Factors potentially contributing to the early bone union progression may include the coincidental administration of abaloparatide prior to trauma and the presence of peripheral nerve injury.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"28 ","pages":"Article 101899"},"PeriodicalIF":2.6,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022353","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 : 2026-01-05DOI: 10.1016/j.bonr.2026.101897
Maria E. Aguirre-Flores , Leah E. Tokach , Eric Cheang , Gregory Trahan , Dennis A. Webster , Adrienne L. Watson , Daniel F. Carlson , David R. Deyle
Osteogenesis imperfecta (OI) comprises a group of disorders that lead to bone fragility. The most common forms are caused by pathogenic variants in COL1A1 and COL1A2. There are many different animal models OI from zebrafish to dogs, with murine models being the most used model. In this brief study, we describe the successful generation of the first large animal porcine model of OI Type I carrying a clinically relevant pathogenic variant, c.757C>T (p.Arg253Ter). These pigs exhibited classic features of OI Type I including blue sclera, low bone mass, and bone fragility. This model is more genetically and physiologically similar to humans and will be useful in studying the skeletal and extra-skeletal symptoms associated with OI.
{"title":"Development of a large porcine model of osteogenesis imperfecta type I","authors":"Maria E. Aguirre-Flores , Leah E. Tokach , Eric Cheang , Gregory Trahan , Dennis A. Webster , Adrienne L. Watson , Daniel F. Carlson , David R. Deyle","doi":"10.1016/j.bonr.2026.101897","DOIUrl":"10.1016/j.bonr.2026.101897","url":null,"abstract":"<div><div>Osteogenesis imperfecta (OI) comprises a group of disorders that lead to bone fragility. The most common forms are caused by pathogenic variants in COL1A1 and COL1A2. There are many different animal models OI from zebrafish to dogs, with murine models being the most used model. In this brief study, we describe the successful generation of the first large animal porcine model of OI Type I carrying a clinically relevant pathogenic variant, c.757C>T (p.Arg253Ter). These pigs exhibited classic features of OI Type I including blue sclera, low bone mass, and bone fragility. This model is more genetically and physiologically similar to humans and will be useful in studying the skeletal and extra-skeletal symptoms associated with OI.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"28 ","pages":"Article 101897"},"PeriodicalIF":2.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022354","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 : 2026-01-05DOI: 10.1016/j.bonr.2025.101896
Gang-Qing Yao, Meiling Zhu, Karl Insogna
Single daily doses of parathyroid hormone (PTH) are an established anabolic therapy for osteoporosis. The actions of PTH in bone are modulated by interactions between osteoblasts and osteoclasts. Colony-stimulating factor 1 (CSF1) exists in both soluble (sCSF1) and membrane-bound (mCSF1) isoforms, with distinct roles in skeletal remodeling identified for each isoform. To investigate the specific role of mCSF1 in PTH-induced bone anabolism, we treated mCSF1 knockout (KO) and wild-type (WT) mice with single daily doses of hPTH (1–34) for 4 weeks. Both genotypes exhibited increased bone mineral density and trabecular bone volume in response to PTH, but KO mice demonstrated significantly greater bone density gains. Histomorphometric analysis demonstrated enhanced osteoblast activity in KO mice, with no significant differences in osteoclast numbers or in the bone resorption marker carboxyterminal cross-linked telopeptide of type 1 collagen (serum CTx), compared to WT. These findings indicate that mCSF1 constrains the anabolic effects of PTH, likely by modulating osteoblast activity, and that its absence enhances bone formation without disrupting resorptive processes. Targeting mCSF1 may therefore represent a strategy to amplify the skeletal benefits of anabolic therapies without impairing bone turnover.
{"title":"Selective deletion of the membrane-bound isoform of CSF1 in vivo augments the anabolic response to PTH without impairing bone resorption","authors":"Gang-Qing Yao, Meiling Zhu, Karl Insogna","doi":"10.1016/j.bonr.2025.101896","DOIUrl":"10.1016/j.bonr.2025.101896","url":null,"abstract":"<div><div>Single daily doses of parathyroid hormone (PTH) are an established anabolic therapy for osteoporosis. The actions of PTH in bone are modulated by interactions between osteoblasts and osteoclasts. Colony-stimulating factor 1 (CSF1) exists in both soluble (sCSF1) and membrane-bound (mCSF1) isoforms, with distinct roles in skeletal remodeling identified for each isoform. To investigate the specific role of mCSF1 in PTH-induced bone anabolism, we treated mCSF1 knockout (KO) and wild-type (WT) mice with single daily doses of hPTH (1–34) for 4 weeks. Both genotypes exhibited increased bone mineral density and trabecular bone volume in response to PTH, but KO mice demonstrated significantly greater bone density gains. Histomorphometric analysis demonstrated enhanced osteoblast activity in KO mice, with no significant differences in osteoclast numbers or in the bone resorption marker carboxyterminal cross-linked telopeptide of type 1 collagen (serum CTx), compared to WT. These findings indicate that mCSF1 constrains the anabolic effects of PTH, likely by modulating osteoblast activity, and that its absence enhances bone formation without disrupting resorptive processes. Targeting mCSF1 may therefore represent a strategy to amplify the skeletal benefits of anabolic therapies without impairing bone turnover.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"28 ","pages":"Article 101896"},"PeriodicalIF":2.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022355","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 : 2026-01-02DOI: 10.1016/j.bonr.2025.101895
Joanna Veres , Eduardo A.C. Almeida , Jeannie Bailey , Grace D. O'Connell
The unique mechanical unloading induced by spaceflight is associated with a very high incidence rate of chronic back pain and general degradation of tissues associated with the spinal column (i.e., bone, skeletal muscle, intervertebral disc, and cartilage). Despite the well documented phenomena of spinal damage following microgravity conditions, there is not a clear timeline of the pathways that leads to bulk tissue damage and back pain. This is both due to the majority of work in the field focusing on assessing the impact of microgravity on a single component or tissue, as well as in doing so at a narrow scale (e.g., genetic, cellular, morphologic, etc.). This review paper surveyed the literature to assemble a multiscale timeline for the pathway of degeneration due to mechanical unloading for key tissues of the spinal column. In doing so, we aim to clarify the cascading, multiscale, degenerative pathway caused by spaceflight conditions that manifest into bulk tissue atrophy and pain. This work also covers potential avenues of investigation to mitigate the deleterious effects of prolonged mechanical unloading on the spine.
{"title":"The effect of spaceflight on tissues of the spinal column","authors":"Joanna Veres , Eduardo A.C. Almeida , Jeannie Bailey , Grace D. O'Connell","doi":"10.1016/j.bonr.2025.101895","DOIUrl":"10.1016/j.bonr.2025.101895","url":null,"abstract":"<div><div>The unique mechanical unloading induced by spaceflight is associated with a very high incidence rate of chronic back pain and general degradation of tissues associated with the spinal column (i.e., bone, skeletal muscle, intervertebral disc, and cartilage). Despite the well documented phenomena of spinal damage following microgravity conditions, there is not a clear timeline of the pathways that leads to bulk tissue damage and back pain. This is both due to the majority of work in the field focusing on assessing the impact of microgravity on a single component or tissue, as well as in doing so at a narrow scale (e.g., genetic, cellular, morphologic, etc.). This review paper surveyed the literature to assemble a multiscale timeline for the pathway of degeneration due to mechanical unloading for key tissues of the spinal column. In doing so, we aim to clarify the cascading, multiscale, degenerative pathway caused by spaceflight conditions that manifest into bulk tissue atrophy and pain. This work also covers potential avenues of investigation to mitigate the deleterious effects of prolonged mechanical unloading on the spine.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"28 ","pages":"Article 101895"},"PeriodicalIF":2.6,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073558","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 : 2025-12-12DOI: 10.1016/j.bonr.2025.101894
Priyesh Patel , Sirion Aksornthong , Svetlana V. Komarova
Osteogenesis imperfecta (OI) is a rare genetic disorder most often caused by mutations in genes that encode collagen type I. OI collagen-I differs from healthy collagen-I due to the underlying mutation and altered post-translational modifications (PTMs). The objective of this study was to use knowledge synthesis to quantify the levels of selected PTMs, hydroxylysine (HYL), hydroxyproline (HYP) and glycosylation (GLY) in OI collagen-I. A systematic search in Medline, Ovid and Web of Science, identified 701 studies reporting on PTM outcomes for OI patients with collagen-I mutation. We excluded animal studies, and reports for OI patients with mutations other than in collagen-I. After screening, we included 36 qualitative studies and 25 quantitative studies for meta-analysis. All qualitative studies reported that OI collagen-I was overmodified. Meta-analysis of studies with quantitative data was performed using normalized mean difference as a study-level effect size and a random-effects model with the Hunter and Smith with sample size correction. The hydroxylysine dataset included 150 patients across 20 studies and had an effect size of 0.33 (confidence interval (CI) 0.21, 0.45). HYL levels were higher in bone-derived collagen-I than in fibroblast- or dentine-derived. The hydroxyproline dataset included 141 patients across 17 studies and had an effect size of 0.00 (CI: −0.02, 0.02). The glycosylation dataset included 17 patients across 5 studies and had an effect size of 0.55 (CI: 0.38, 0.71). Patients with the most severe form of OI (type 2) had the highest levels of collagen-I HYL and GLY. Our study provides new insights into collagen-I pathophysiology in OI, generating new hypotheses regarding the role of PTM in mediating disease presentation in different tissues and overall severity.
成骨不全症（Osteogenesis imperfecta， OI）是一种罕见的遗传性疾病，通常是由编码i型胶原蛋白的基因突变引起的。成骨不全症的胶原- i不同于健康的胶原- i，主要是由于潜在的突变和翻译后修饰（PTMs）的改变。本研究的目的是利用知识合成来量化OI胶原- i中选定的PTMs、羟赖氨酸（HYL）、羟脯氨酸（HYP）和糖基化（GLY）的水平。在Medline， Ovid和Web of Science上进行了系统搜索，确定了701项关于i型胶原突变成骨不全患者PTM结果的研究。我们排除了动物研究，以及伴有i型胶原蛋白以外突变的成骨不全患者的报告。筛选后，我们纳入36项定性研究和25项定量研究进行meta分析。所有定性研究均报告成骨不全症胶原蛋白i被过度修饰。对具有定量数据的研究进行荟萃分析，使用归一化平均差作为研究水平效应大小，并使用Hunter和Smith进行样本大小校正的随机效应模型。羟赖氨酸数据集包括20项研究中的150例患者，效应值为0.33（置信区间（CI） 0.21, 0.45）。骨源性胶原i中的HYL水平高于成纤维细胞或牙本质源性胶原i。羟脯氨酸数据集包括17项研究中的141例患者，效应值为0.00 （CI:−0.02,0.02）。糖基化数据集包括5项研究中的17例患者，效应值为0.55 （CI: 0.38, 0.71）。最严重的成骨不全（2型）患者的胶原- i HYL和GLY水平最高。我们的研究为i型胶原蛋白在成骨不全症中的病理生理学提供了新的见解，提出了关于PTM在不同组织中介导疾病表现和整体严重程度中的作用的新假设。
{"title":"Post-translational modifications of collagen type I in osteogenesis imperfecta: Systematic review and meta-analysis","authors":"Priyesh Patel , Sirion Aksornthong , Svetlana V. Komarova","doi":"10.1016/j.bonr.2025.101894","DOIUrl":"10.1016/j.bonr.2025.101894","url":null,"abstract":"<div><div>Osteogenesis imperfecta (OI) is a rare genetic disorder most often caused by mutations in genes that encode collagen type I. OI collagen-I differs from healthy collagen-I due to the underlying mutation and altered post-translational modifications (PTMs). The objective of this study was to use knowledge synthesis to quantify the levels of selected PTMs, hydroxylysine (HYL), hydroxyproline (HYP) and glycosylation (GLY) in OI collagen-I. A systematic search in Medline, Ovid and Web of Science, identified 701 studies reporting on PTM outcomes for OI patients with collagen-I mutation. We excluded animal studies, and reports for OI patients with mutations other than in collagen-I. After screening, we included 36 qualitative studies and 25 quantitative studies for meta-analysis. All qualitative studies reported that OI collagen-I was overmodified. Meta-analysis of studies with quantitative data was performed using normalized mean difference as a study-level effect size and a random-effects model with the Hunter and Smith with sample size correction. The hydroxylysine dataset included 150 patients across 20 studies and had an effect size of 0.33 (confidence interval (CI) 0.21, 0.45). HYL levels were higher in bone-derived collagen-I than in fibroblast- or dentine-derived. The hydroxyproline dataset included 141 patients across 17 studies and had an effect size of 0.00 (CI: −0.02, 0.02). The glycosylation dataset included 17 patients across 5 studies and had an effect size of 0.55 (CI: 0.38, 0.71). Patients with the most severe form of OI (type 2) had the highest levels of collagen-I HYL and GLY. Our study provides new insights into collagen-I pathophysiology in OI, generating new hypotheses regarding the role of PTM in mediating disease presentation in different tissues and overall severity.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"28 ","pages":"Article 101894"},"PeriodicalIF":2.6,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788336","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 : 2025-12-05DOI: 10.1016/j.bonr.2025.101893
Justyna J. Miszkiewicz , Karen M. Cooke , Holly E. Reid , Julien Louys
Secondary osteons are fundamental products of bone metabolic processes. They accumulate, crowd, and superimpose over themselves over the lifespan of the individual and capture significant biological, environmental, and even social information. They are crucial in biomedical research as a reflection of bone health and disease. Because bone preserves after death, secondary osteons offer a window into past human and animal lives. They are arguably one of very few biological traits that have been examined across multiple disciplines that work with modern and ancient samples. Here, we review articles indexed in PubMed that examine secondary osteons but span beyond biomedicine, such as palaeontology and bioarchaeology. We aim to identify commonalities and differences across these disciplines to highlight potential for exchange of existing complementary data and future collaborative avenues. We find that 9 % of articles reporting new secondary osteon data (622 obtained) represent archaeological or fossil material. The key shared positive outcome across these disciplines has been data and histology images that provide insights into age, sex, behaviour, species discrimination, and anatomical variation. The main limitations of using ancient samples are the unknown and thus estimated demographic information of human and animal remains studied, and artifacts of taphonomy and bioerosion seen in bone histology that originate from post-mortem, burial, and diagenetic processes, which are not present in biomedical samples. We conclude that a histological analysis of secondary osteons can be a versatile tool in different fields of bone research and encourage transdisciplinary collaboration to better improve our knowledge of bone remodelling processes.
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Pub Date : 2025-12-01DOI: 10.1016/j.bonr.2025.101890
David Castro Corredor , Luis Ángel Calvo Pascual
Objective
To evaluate the real-world effectiveness of Romosozumab in postmenopausal women with severe osteoporosis and to identify baseline clinical and biochemical predictors of clinically meaningful bone mineral density (BMD) gains (≥10 %, used for exploratory classification) using an explainable machine-learning approach.
Methods
We conducted a retrospective, observational multicentre study across seven hospitals in Castilla-La Mancha, Spain. Postmenopausal women aged ≥50 years who initiated romosozumab between May 2023 and November 2024 for severe osteoporosis or high fracture risk were included. Lumbar-spine, femoral-neck, and total-hip BMD were assessed by dual-energy X-ray absorptiometry (DXA) at baseline and 12 months. Baseline biochemical variables included serum P1NP, CTX, PTH, vitamin D, calcium, phosphate, alkaline phosphatase, and creatinine. Predictors of a ≥ 10 % BMD gain were examined using elastic-net logistic regression combined with SHapley Additive exPlanations (SHAP) for model interpretability.
Results
Fifty-eight women were analysed (mean ± SD age 71.7 ± 10.0 years; BMI 26.1 ± 4.8 kg/m2; mean age at menopause 47.3 ± 6.0 years). Mean 12-month BMD increases were + 15,35 % at the lumbar spine, +12,42 % at the femoral neck, and + 8,62 % at the total hip. The proportion achieving a ≥ 10 % gain was 39 %, 38.1 %, and 31.7 %, respectively. SHAP analysis identified consistent predictors of response: lower baseline BMD, higher phosphate levels, and younger age at menopause were associated with greater gains, whereas elevated PTH and alkaline phosphatase predicted a reduced response. Patients who had not received corticosteroids or NSAIDs in the six months prior to treatment initiation, typically for pain or inflammation, also showed greater increases in BMD.
Conclusions
Romosozumab was effective and well-tolerated in routine clinical practice, yielding meaningful and site-specific gains in BMD. Explainable machine-learning analysis identified physiologically coherent and consistent clinical predictors of ≥10 % response.
{"title":"Predictors of clinically meaningful bone mineral density gains with romosozumab: An explainable machine leaning analysis of a real-world cohort","authors":"David Castro Corredor , Luis Ángel Calvo Pascual","doi":"10.1016/j.bonr.2025.101890","DOIUrl":"10.1016/j.bonr.2025.101890","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the real-world effectiveness of Romosozumab in postmenopausal women with severe osteoporosis and to identify baseline clinical and biochemical predictors of clinically meaningful bone mineral density (BMD) gains (≥10 %, used for exploratory classification) using an explainable machine-learning approach.</div></div><div><h3>Methods</h3><div>We conducted a retrospective, observational multicentre study across seven hospitals in Castilla-La Mancha, Spain. Postmenopausal women aged ≥50 years who initiated romosozumab between May 2023 and November 2024 for severe osteoporosis or high fracture risk were included. Lumbar-spine, femoral-neck, and total-hip BMD were assessed by dual-energy X-ray absorptiometry (DXA) at baseline and 12 months. Baseline biochemical variables included serum P1NP, CTX, PTH, vitamin D, calcium, phosphate, alkaline phosphatase, and creatinine. Predictors of a ≥ 10 % BMD gain were examined using elastic-net logistic regression combined with SHapley Additive exPlanations (SHAP) for model interpretability.</div></div><div><h3>Results</h3><div>Fifty-eight women were analysed (mean ± SD age 71.7 ± 10.0 years; BMI 26.1 ± 4.8 kg/m<sup>2</sup>; mean age at menopause 47.3 ± 6.0 years). Mean 12-month BMD increases were + 15,35 % at the lumbar spine, +12,42 % at the femoral neck, and + 8,62 % at the total hip. The proportion achieving a ≥ 10 % gain was 39 %, 38.1 %, and 31.7 %, respectively. SHAP analysis identified consistent predictors of response: lower baseline BMD, higher phosphate levels, and younger age at menopause were associated with greater gains, whereas elevated PTH and alkaline phosphatase predicted a reduced response. Patients who had not received corticosteroids or NSAIDs in the six months prior to treatment initiation, typically for pain or inflammation, also showed greater increases in BMD.</div></div><div><h3>Conclusions</h3><div>Romosozumab was effective and well-tolerated in routine clinical practice, yielding meaningful and site-specific gains in BMD. Explainable machine-learning analysis identified physiologically coherent and consistent clinical predictors of ≥10 % response.</div></div>","PeriodicalId":9043,"journal":{"name":"Bone Reports","volume":"27 ","pages":"Article 101890"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620177","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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