Bone最新文献

{"title":"SB16 versus reference denosumab in postmenopausal women with osteoporosis: 18-month outcomes of a phase III randomized clinical trial","authors":"Yoon-Sok Chung ,&nbsp;Bente Langdahl ,&nbsp;Rafal Plebanski ,&nbsp;Edward Czerwinski ,&nbsp;Eva Dokoupilova ,&nbsp;Jerzy Supronik ,&nbsp;Jan Rosa ,&nbsp;Andrzej Mydlak ,&nbsp;Rafal Sapula ,&nbsp;Anna Rowińska-Osuch ,&nbsp;Ki-Hyun Baek ,&nbsp;Audrone Urboniene ,&nbsp;Robert Mordaka ,&nbsp;Sohui Ahn ,&nbsp;Young Hee Rho ,&nbsp;Jisuk Ban ,&nbsp;Richard Eastell","doi":"10.1016/j.bone.2024.117371","DOIUrl":"10.1016/j.bone.2024.117371","url":null,"abstract":"<div><h3>Purpose</h3><div>This study evaluated the efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of SB16 versus reference denosumab (DEN) up to 18 months in postmenopausal osteoporosis (PMO) patients, and assessed outcomes after switching from DEN to SB16 compared to those who continued with DEN or SB16.</div></div><div><h3>Methods</h3><div>457 PMO patients were initially randomized, with 407 re-randomized at Month 12 to either continue DEN (DEN+DEN), switch to SB16 (DEN+SB16), or continue SB16 (SB16 + SB16) through Month 18. Efficacy was assessed by the percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck. Safety, PD, PK, and immunogenicity were evaluated throughout the study period.</div></div><div><h3>Results</h3><div>Mean percent changes from baseline in lumbar spine, total hip, and femoral neck BMD at Month 18 were comparable across treatment groups, indicating comparable efficacy between SB16 and DEN. The mean percent change in lumbar spine BMD was 6.8 % (SB16 + SB16), 6.2 % (DEN+SB16), and 6.8 % (DEN+DEN). Total hip BMD increased by 4.4 %, 3.5 %, and 4.0 %, and femoral neck BMD by 3.4 %, 3.1 %, and 2.7 % for SB16 + SB16, DEN+SB16, and DEN+DEN, respectively. Safety profiles were similar among groups, with no new safety concerns identified after switching. Only one patient in the DEN+SB16 group developed non-neutralizing anti-drug antibodies by Month 18, indicating a low immunogenicity risk for SB16.</div></div><div><h3>Conclusion</h3><div>Switching from DEN to SB16 demonstrated comparable efficacy, safety, PD, PK, and immunogenicity in PMO patients relative to those who continued DEN. SB16 was well tolerated over 18 months, demonstrating comparable outcomes to DEN.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117371"},"PeriodicalIF":3.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RANK IVVY motif plays crucial roles in osteoclastogenesis","authors":"Shenyuan Chen ,&nbsp;Zhenqi Shi ,&nbsp;Joel Jules ,&nbsp;Yuyu Li ,&nbsp;Robert A. Kesterson ,&nbsp;Mohamed Halaby Elbahoty ,&nbsp;Ping Zhang ,&nbsp;Xu Feng","doi":"10.1016/j.bone.2024.117367","DOIUrl":"10.1016/j.bone.2024.117367","url":null,"abstract":"<div><div>RANKL and its receptor RANK play a vital role in osteoclastogenesis. RANK primarily recruits TRAFs to promote osteoclastogenesis but also contains an TRAF-independent motif (IVVY^535–538), which mediates osteoclast lineage commitment <em>in vitro</em>. Here, we have developed knockin mice in which inactivating mutations are introduced in the IVVY motif (IV<u>VY</u> to IV<u>AF</u>). Homozygous knockin (RANK^AF/AF) mice are viable and born at the expected Mendelian ratio. Micro-computed tomography (μCT) and histomorphometric analyses of femurs of wild type (RANK^+/+) and RANK^AF/AF mice reveal significant increases in trabecular bone mass in RANK^AF/AF compared to age and sex matched RANK^+/+ mice due to impaired osteoclastogenesis <em>in vivo</em>. Bone marrow macrophages (BMMs) from RANK^AF/AF mice do not form osteoclasts <em>in vitro</em> upon M-CSF and RANKL treatment. RANKL-induced activation of NF-ĸB, ERK, p38 and JNK pathways in RANK^AF/AF BMMs remains intact, but RANKL-induced expression of c-Fos and NFATc1 is impaired in RANK^AF/AF BMMs. Consistent with the crucial role of the IVVY motif in priming BMMs into the osteoclast lineage, RANKL-primed RANK^AF/AF BMMs do not form osteoclasts in response to subsequent <em>Porphyromonas gingivalis</em> (Pg)-stimulation, indicating that the IVVY Motif plays a role in Pg-induced osteoclastogenesis. Mechanistically, RANK IVVY motif mediates Pg-induced osteoclast gene expression by rendering NFATc1 and c-Fos genes responsive to Pg stimulation. Consistently, cell penetrating peptides fused to RANK segments containing the IVVY motif impair Pg-induced osteoclastogenesis by impairing RANKL-activated c-Fos and NFATc1 expression. In conclusion, the RANK IVVY motif plays crucial roles in osteoclastogenesis <em>in vivo</em> and modulates Pg-mediated osteoclast formation <em>in vitro</em>.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117367"},"PeriodicalIF":3.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820422","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}

{"title":"Characteristics of patients with very high fracture risk in a community-dwelling geriatric cohort","authors":"Michaela Rippl,&nbsp;Pauline Grupp,&nbsp;Sebastian Martini,&nbsp;Katharina Müller,&nbsp;Olivia Tausendfreund,&nbsp;Ralf Schmidmaier,&nbsp;Michael Drey","doi":"10.1016/j.bone.2024.117366","DOIUrl":"10.1016/j.bone.2024.117366","url":null,"abstract":"<div><h3>Objective</h3><div>Bone anabolic treatment has been shown to be superior to oral bisphosphonates, especially in osteoporosis patients with a very high fracture-risk. The current German osteoporosis guideline classifies the very high 3-year fracture-risk based upon a novel fracture-risk model. As age is a severe risk-factor, we examined the distribution and associations to geriatric assessment parameters of the very high-risk group in a well-characterized cohort of community-dwelling geriatric patients.</div></div><div><h3>Methods</h3><div>Analyses were based on 166 patients (mean age 82 ± 6 years) taken from MUSAR (MUnich SArcopenia Registry). Fracture-risk was calculated as described in the current German guideline. Thereupon, patients were allocated to the low−/moderate (&lt;5 %), high- (5–10 %) or very high-risk group (&gt;10 %). Associations of geriatric assessment parameters with the group allocation to the fracture-risk group were evaluated by covariate-adjusted linear regression analysis.</div></div><div><h3>Results</h3><div>&gt;80 % of the study population were at an increased fracture-risk. Besides, &gt;50 % were allocated to the very high-risk group. Patients in the very high-risk group showed limitations in all physical performance tests (short physical performance battery (SPPB), gaitspeed, handgrip strength and chair rise test). Also, polypharmacy and a risk for malnutrition (from mini nutritional assessment short form (MNA-SF)), were present. All parameters showed significant associations with group allocation to very high-risk group.</div></div><div><h3>Conclusion</h3><div>Most of the geriatric patients are at a very high-risk for osteoporotic fractures. Also, this group presented several limitations in the comprehensive geriatric assessment highlighting the vulnerability of this group. Clinicians need to reinforce fracture-risk assessment and familiarize with treatment options.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117366"},"PeriodicalIF":3.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of different forms of exercise during the early life on the bone microstructure of ovariectomized mice","authors":"Yuxuan Wang ,&nbsp;Keping Zhang ,&nbsp;Weiwei Gao ,&nbsp;Haiqi Lin ,&nbsp;Tingting Li ,&nbsp;Timon Cheng Yi Liu ,&nbsp;Xiquan Weng ,&nbsp;Yu Yuan","doi":"10.1016/j.bone.2024.117364","DOIUrl":"10.1016/j.bone.2024.117364","url":null,"abstract":"<div><div>Postmenopausal osteoporosis is a type of bone disease with bone loss and deterioration of skeletal function that occurs in women after menopause. Studies have found that early-life exercise can reduce the risk of fractures and decrease the occurrence of osteoporosis, making it a promising approach for preventing and reversing bone loss. In this study, to identify the optimal forms of exercise during early life to optimize bone health and provide suggestions for promoting bone health through exercise training during early life, we conducted different forms of exercise interventions including ladder climbing, treadmill running, combined training, and whole-body vibration (WBV) on adolescent mice for 8 weeks and observed the accumulation of bone mass and arrangement of bone microstructure in adult mice. After removing the ovaries bilaterally, the mice were resting for 22 weeks to simulate the bone loss condition observed in postmenopausal women. We examined the resistance of the bone microstructure to degradation in response to exercise during early life and characterized the specific effects of different forms of exercise on countering bone microstructure deterioration. Our findings demonstrate that early-life exercise exerts long-term beneficial effects on bone health. All four forms of early-life exercise can delay bone loss due to decreased estrogen and improve the bone microstructure to varying degrees, with resistance and vibration training demonstrating superior protective benefits.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117364"},"PeriodicalIF":3.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793031","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}

{"title":"Clinical challenges in bone tissue engineering - A narrative review","authors":"Amir Human Hoveidaei ,&nbsp;Mehdi Sadat-Shojai ,&nbsp;Sara S. Nabavizadeh ,&nbsp;Reza Niakan ,&nbsp;Amirhosein Shirinezhad ,&nbsp;SeyedArad MosalamiAghili ,&nbsp;Sean Tabaie","doi":"10.1016/j.bone.2024.117363","DOIUrl":"10.1016/j.bone.2024.117363","url":null,"abstract":"<div><div>Bone tissue engineering (BTE) has emerged as a promising approach to address large bone defects caused by trauma, infections, congenital malformations, and tumors. This review focuses on scaffold design, cell sources, growth factors, and vascularization strategies, highlighting their roles in developing effective treatments. We explore the complexities of balancing mechanical properties, porosity, and biocompatibility in scaffold materials, alongside optimizing mesenchymal stem cell delivery methods. The critical role of growth factors in bone regeneration and the need for controlled release systems are discussed. Vascularization remains a significant hurdle, with strategies such as angiogenic factors, co-culture systems, and bioprinting under investigation. Mechanical challenges, tissue responses, and inflammation management are examined, alongside gene therapy's potential for enhancing osteogenesis and angiogenesis via both viral and non-viral delivery methods. The review emphasizes the impact of patient-specific factors on bone healing outcomes and the importance of personalized approaches. Future directions are described, emphasizing the necessity of interdisciplinary cooperation to advance the field of BTE and convert laboratory results into clinically feasible solutions.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117363"},"PeriodicalIF":3.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788095","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}

{"title":"Inhibiting autophagy further promotes Ginkgolide B's anti-osteoclastogenesis ability","authors":"Haoying Xu ,&nbsp;Zijie Zhou ,&nbsp;Fuli Wen ,&nbsp;Hong Sun ,&nbsp;Jianming Hou","doi":"10.1016/j.bone.2024.117348","DOIUrl":"10.1016/j.bone.2024.117348","url":null,"abstract":"<div><div>Excessive osteoclast activity could cause skeletal diseases including osteoporosis. Additionally, autophagy plays an initial role in osteoclast differentiation and function. Ginkgolide B (GB), a key compound in <em>Ginkgo biloba</em>, improves bone mass and suppresses mature osteoclast formation <em>in vitro</em>. This study examines the role of GB role in regulating osteoclast formation <em>via</em> autophagy. Using murine bone marrow-derived macrophages <em>in vitro</em>, we explored GB's effects on autophagy and osteoclast formation. We also assessed bone loss prevention in an ovariectomized (OVX) mouse model using GB combined with an autophagy inhibitor. Tartrate-resistant acid phosphatase staining was used to observe osteoclast formation. Autophagy-related proteins and intracellular microtubule associated protein 1 light chain 3 beta puncta were observed using western blotting and immunofluorescence. The impact of GB on OVX mice was evaluated using micro-computed tomography and hematoxylin and eosin staining. GB directly promoted autophagy in osteoclast precursors (OCPs), but inhibited osteoclast differentiation by reducing receptor activator of nuclear factor kappa B ligand (RANKL)-induced autophagy. GB inhibits the phosphorylation of RANKL downstream signaling pathways, such as Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). Anisomycin (ANI), a JNK activator, reversed GB's inhibitory effects on RANKL-induced autophagy and osteoclastogenesis. Inhibiting autophagy using 3-Methyladenine (3-MA) or small interfering RNA significantly suppressed osteoclast differentiation both <em>in vitro</em> and <em>in vivo</em>. Our findings suggested that GB inhibits osteoclast formation by decreasing JNK phosphorylation and autophagy under RANKL stimulation. Interestingly, GB also directly promotes autophagy in OCPs. Thus, GB markedly reduces osteoclast differentiation and prevents bone loss, with its anti-osteoclastogenesis effect being enhanced by 3-MA. Accordingly, inhibiting GB-induced direct autophagy could further increase its therapeutic effect on bone disease resulting from excessive osteoclast activity.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117348"},"PeriodicalIF":3.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775615","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}

{"title":"LncRNA H19 promotes osteoclast differentiation by sponging miR-29c-3p to increase expression of cathepsin K","authors":"Huazhi Li ,&nbsp;Fu Zheng ,&nbsp;Anqi Tao ,&nbsp;Tong Wu ,&nbsp;Xinxin Zhan ,&nbsp;Hongyi Tang ,&nbsp;Xinyu Cui ,&nbsp;Zeyun Ma ,&nbsp;Cuiying Li ,&nbsp;Jiuhui Jiang ,&nbsp;Yixiang Wang","doi":"10.1016/j.bone.2024.117340","DOIUrl":"10.1016/j.bone.2024.117340","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis is a prevalent metabolic bone disease. Osteoporotic fractures can lead to severe functional impairment and increased mortality. Long noncoding RNA <em>H19</em> has emerged as a pivotal player in bone remodeling, serving both as a biomarker and a regulator. While previous research has elucidated <em>H19</em>'s role in promoting osteogenic differentiation through diverse mechanisms, its involvement in osteoclast differentiation remains largely unknown.</div></div><div><h3>Methods</h3><div>In this study, we used lentiviral vectors to stably overexpress or knockdown <em>H19</em> in RAW264.7 cell lines. Quantitative reverse polymerase chain reaction, Western blot, tartrate resistant acid phosphatase staining and bone resorption assay were performed to assess the level of osteoclast differentiation and bone resorption capacity. And fluorescence in situ hybridization, dual-luciferase reporter and RNA immunoprecipitation were used to explore the specific mechanism of <em>H19</em> regulating osteoclast differentiation in vitro. Then, ovariectomized osteoporosis models in wild type mice and <em>H19</em> knockout mice were conducted. And micro-CT analysis, HE staining, and immunohistochemistry were performed to verify the mechanism of <em>H19</em> regulating osteoclast differentiation in vivo. Bone marrow derived monocytes and bone mesenchymal stem cells were extracted from mice and assayed for osteoclastic and osteogenic-related assays, respectively.</div></div><div><h3>Results</h3><div>In vitro, <em>H19</em> promoted osteoclast differentiation and bone resorption of RAW264.7 cells, while miR-29c-3p inhibited them. Both <em>H19</em> and <em>cathepsin K</em> were the target genes of <em>miR-29c-3p</em>. In vivo, <em>H19</em> knockout mice have increased femur bone mineral density, decreased osteoclast formation, and reduced <em>cathepsin K</em> expression. <em>MiR-29c-3p</em> agomir could increase bone mineral density in osteoporotic mice on the premise of <em>H19</em> knockout.</div></div><div><h3>Conclusions</h3><div><em>H19</em> upregulates <em>cathepsin K</em> expression through sponging <em>miR-29c-3p, w</em>hich promoting osteoclast differentiation and enhancing bone resorption. This underscores the potential of <em>H19</em> and <em>miR-29c-3p</em> as promising biomarkers for osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117340"},"PeriodicalIF":3.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphology and spatial distribution of cortical bone canals: Evaluation of shape parameters, lacunarity, and fractal dimension in the human irradiated mandible","authors":"Karin Berria Tomazelli ,&nbsp;Bianca Carla Bianco ,&nbsp;Barbara Rech de Castro ,&nbsp;Isabela Ramos ,&nbsp;Vithória Rabelo Zimmer ,&nbsp;Priscila Barbosa Ferreira Soares ,&nbsp;Liliane Janete Grando ,&nbsp;Gustavo Davi Rabelo","doi":"10.1016/j.bone.2024.117349","DOIUrl":"10.1016/j.bone.2024.117349","url":null,"abstract":"<div><div>This study aimed to assess the spatial distribution of cortical bone canals' network through the analysis of lacunarity (Lac), fractal dimension (FD), and canal morphological parameters in the mandible (IR group, n = 7) of human patients under radiotherapy in comparison with non-irradiated younger (yC group, n = 8) and older (oC group, n = 8) individuals. Patients who underwent mandibular surgery were selected to have bone fragments removed during surgery, and undecalcified histological slides were analyzed by phase-contrast microscopy by two operators. The following morphological parameters were assessed in the Haversian canal (Ca): area (Ca·Ar, μm²), perimeter (Ca·Pm, μm), and circularity (Ca.c, #). Binary images were obtained by manually segmenting canals for Lac and FD analysis through box-counting. A total of 273 canals were segmented in the IR group, 284 in the yC group, and 60 in the oC group. Higher values for canal area and perimeter (p &lt; 0.0001) were found for oC (7871 μm² and 358.9 μm, respectively), followed by IR (2958 μm² and 212.9 μm, respectively), and yC (1286 μm² and 135.8 μm, respectively). Canal circularity was lower for oC (p &lt; 0.0001). Lac and FD did not differ when comparing irradiated individuals with the younger and older individuals. In conclusion, cortical canals are morphologically different when comparing younger and older individuals with patients exposed to ionizing radiation. Alterations on Haversian canals after radiotherapy could have clinical implications, mostly related to vascularization. Lac and FD were reliable parameters in assessing the spatial organization of the canals within the matrix.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117349"},"PeriodicalIF":3.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756047","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}

{"title":"Association of Glucagon-like peptide-1 receptor agonists use with fracture risk in type 2 diabetes: A meta-analysis of randomized controlled trials","authors":"Yuan Zhang ,&nbsp;Guanhua Chen ,&nbsp;Weimin Wang ,&nbsp;Donghui Yang ,&nbsp;Dalong Zhu ,&nbsp;Yali Jing","doi":"10.1016/j.bone.2024.117338","DOIUrl":"10.1016/j.bone.2024.117338","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporosis (OP) and fractures.</div></div><div><h3>Purpose</h3><div>The aim of this study was to analyze the available evidence on the effect of GLP-1 RAs on fracture risk in patients with type 2 diabetes.</div></div><div><h3>Methods</h3><div>A systematic search based on PubMed, Embase and Web of Science databases was performed to collect relevant literature published until May 2024 on the application of GLP-1 RAs in T2DM patients. Data were extracted from each study for comparative analysis, and meta-analysis was performed using R software to calculate relative risk (RR) and 95 % confidence intervals (CI) for dichotomous variables. Two subgroup analyses were also performed.</div></div><div><h3>Results</h3><div>A total of 44 randomized controlled trials (RCTs) involving 47,823 patients were analyzed. There were 292 incident fracture cases (138 in GLP-1 RAs group and 154 in control group). The pooled RR for fractures in patients treated with GLP-1RAs compared with those treated with placebo or other anti-diabetic drugs was 0.77 (95 % CI: 0.61–0.96). Subgroup analyses showed that the beneficial effect was dependent on the period of treatment with GLP-1 RAs, only treated for &gt;78 weeks were effective in reducing the risk of fractures in patients with T2DM (RR 0.77; 95 % CI: 0.61–0.96). Furthermore, subgroup analyses showed that liraglutide treatment was associated with a significant reduction in fracture risk (RR 0.42; 95 % CI: 0.21–0.85). However, other GLP-1 RAs did not present benefits over other anti-diabetic drug treatments.</div></div><div><h3>Conclusion</h3><div>GLP-1 RAs could reduce the risk of fracture in T2DM patients, and the beneficial effect was interrelated to the period of treatment. Liraglutide could significantly reduce the risk of fracture in T2DM patients compared to placebo and other anti-diabetic drugs. Due to the limited nature of contemporary research, further studies are needed to develop a clear clinical consensus.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117338"},"PeriodicalIF":3.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741722","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}

{"title":"Bone remodelling after scaphoid fractures: HR-pQCT, clinical and laboratory data from a prospective 1-year follow-up study","authors":"Stefan Benedikt ,&nbsp;Kerstin Stock ,&nbsp;Lukas Horling ,&nbsp;Gernot Schmidle ,&nbsp;Michael Schirmer ,&nbsp;Gerald Degenhart ,&nbsp;Michael Blauth ,&nbsp;Claudia Lamina ,&nbsp;Johannes Dominikus Pallua ,&nbsp;Rohit Arora","doi":"10.1016/j.bone.2024.117337","DOIUrl":"10.1016/j.bone.2024.117337","url":null,"abstract":"<div><h3>Introduction</h3><div>The exact mechanisms of bone remodelling after scaphoid fractures are not fully understood. Blood supply may lead to delayed consolidation and non-unions as challenging long-term problems. The aim of this study was to follow-up the microstructure during the scaphoid bone remodelling process using High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) and compare the results with clinical and laboratory data.</div></div><div><h3>Patients and methods</h3><div>In this monocentric, prospective, controlled, clinical trial 39 patients with an unilateral conservatively treated scaphoid fracture at the level of the waist or the distal pole were followed up over one year (2, 4, 6, 12, 26 and 52 weeks after trauma). Fracture healing was monitored by clinical examination, blood bone remodelling markers and HR-pQCT.</div></div><div><h3>Results</h3><div>The HR-pQCT showed significant changes in trabecular number, trabecular thickness, trabecular separation and bone mineral density until the 52 week follow-up. Complete bony consolidation on HR-pQCT was evident in half of the fractures at 12 weeks and in all fractures at 52 weeks after trauma. None of the patients developed a non-union. Carboxy-terminal collagen crosslinks as resorption marker showed significant changes until the 52 week follow-up.</div></div><div><h3>Conclusion</h3><div>This study shows detailed clinical, laboratory and radiologic changes during follow-up of uncomplicated fracture healing of conservative scaphoids. Bony consolidation is highly variable and can take up to one year after fracture. Larger studies are warranted, as HR-pQCT might provide detailed microstructural information to better predict fracture healing processes, thus acting as a high-resolution and low-radiation alternative to standard conventional CT.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117337"},"PeriodicalIF":3.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}