Orthopedic diseases are referred to as a series of conditions affecting the normal structure and function of the skeletal system. With a wide variety of types and a year-by-year increasing incidence, they have a severe impact on patients' quality of life. Traditional research has made relatively significant progress in understanding the pathogenesis and treating orthopedic diseases, however, it remains constrained by limitations such as low-throughput experimentation, and difficulty in mimicking the complex bone microenvironment. In recent years, high-throughput screening (HTS) technology has been combined with experimental techniques and models (such as microfluidics, omics technologies, 3D bioprinting, artificial intelligence, and organoid models), which can be used to better simulate the real bone microenvironment and predict molecular activity. This combined approach has not only deepened our understanding of the mechanisms of orthopedic diseases, but also broken through the limitations of traditional drug development, which further accelerates drug discovery and clinical translation. This review aims to systematically summarize the research progress and applications of HTS in typical orthopedic diseases, including osteoporosis, osteoarthritis, bone defects, and bone tumors, to promote the development and clinical translation of novel therapeutic strategies for orthopedic disorders, and to provide references and guidance for researchers in orthopedic basic research, drug development, regenerative medicine, and clinical orthopedic practice. Accordingly, this review is intended for orthopedic researchers, clinicians and biomaterial scientists focusing on high-throughput screening and orthopedic therapeutic development.

Musculoskeletal disorders represent a major global health burden and substantially impair the quality of life. Traditional Chinese medicine (TCM), characterized by its multi-component and multi-target therapeutic properties, has been widely used in the prevention and treatment of major musculoskeletal disorders. However, a comprehensive evaluation of the global research landscape and emerging trends in this field remains lacking. Therefore, we retrieved publications related to TCM therapy for major musculoskeletal disorders from the Web of Science Core Collection (WoSCC) published between January 2016 and August 24, 2025, and performed a bibliometric analysis using CiteSpace and VOSviewer to evaluate publication trends, leading countries and institutions, influential journals and authors, co-cited references, and research hotspots. A total of 781 publications were included. The annual number of publications showed a continuous upward trend over the past decade. China contributed the largest number of publications, whereas the United States demonstrated greater academic influence based on average citations. The Journal of Ethnopharmacology and Frontiers in Pharmacology were identified as the leading journals in this field, while Chunyan Yan and Xin-Sheng Yao were the most productive authors. Co-citation and keyword analyses identified osteoporosis, knee osteoarthritis, active compounds, and molecular signaling pathways, particularly NF-κB, as the major research hotspots. Furthermore, citation burst analysis revealed a shift from studies of single herbal medicines toward TCM formulas, accompanied by the increasing application of network pharmacology and molecular docking, highlighting a transition from efficacy-oriented research to mechanism-based investigations. Overall, this study provides a comprehensive overview of the knowledge structure and research trends of TCM for major musculoskeletal disorders. The findings provide valuable references for future research and suggest that muscle diseases and spinal disorders remain underrepresented and deserve greater attention in future investigations.

Osteoporosis (OP) is a metabolic condition primarily affecting older and postmenopausal women. It is characterized by decreased bone mineral density (BMD), reduced strength, and deteriorated bone microarchitecture. This drastically increases the risk of debilitating fragility fractures and chronic discomfort, severely harming quality of life. Current anti-OP medications can slow bone resorption but often fail to target bone tissue directly, resulting in significant systemic toxicity. A promising solution is nanodrug delivery designed to specifically target bones. This approach minimizes adverse effects by precisely transporting therapeutics to the skeletal site. Hydroxyapatite (HAP) is an ideal material for this purpose due to its close resemblance to human bone mineral. HAP-based nanosystems advanced treatment strategy by enhancing bone targeting, improving drug loading capacity, and optimizing release kinetics and biocompatibility. Furthermore, HAP composite scaffolds hold great promise for bone regeneration. Incorporating bioactive molecules and drugs into these composites facilitates the repair of bone defects. This local delivery method provides the necessary biological activity to directly enhance the bone regeneration process. This review explores recent advancements in HAP-based nanosystems for OP, focusing on their therapeutic mechanisms, interactions with bone tissue, clinical applications, underscoring their superior efficacy, and promising future. However, key challenges remain in translating these systems to clinical practice, including large-scale manufacturing, long-term safety evaluation, and the need for well-designed clinical studies to validate their therapeutic potential.

Osteoporotic fracture is the most severe complication of osteoporosis, and impaired bone regeneration and delayed healing after fracture remain major clinical challenges. Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) may play a critical role in promoting bone regeneration after osteoporotic fracture. Enhancing their osteogenic potential and elucidating the underlying mechanisms may contribute to accelerated fracture healing. In this study, resveratrol-stimulated BMSC-derived EVs (Res-EVs) were isolated using differential centrifugation combined with ultracentrifugation. We found that compared with EVs secreted by BMSCs under normal culture conditions (Nor-EVs), Res-EVs significantly enhanced BMSCs osteogenic differentiation capacity. Analysis of miRNA sequencing data identified miR-19a-3p as significantly downregulated and PC-3p-83,608 as significantly upregulated. The reliability of the sequencing data was validated by qPCR results. By transfecting BMSCs with inhibitor and mimic of miR-19a-3p, we found that miR-19a-3p was a negative regulator of osteogenic differentiation. Bioinformatics prediction and dual-luciferase reporter assays confirmed that miR-19a-3p directly targets Raf1. Western blot results indicated that miR-19a-3p regulates osteogenic differentiation of BMSCs by targeting Raf1. In vivo experiments further demonstrated that Res-EVs treatment enhanced repair at osteoporotic fracture sites and increased the expression of RUNX2 and RAF1. Collectively, these findings indicate that Res-EVs promote bone regeneration at osteoporotic bone defect sites in rats, with the miR-19a-3p/Raf1 axis representing a potential underlying mechanism.

[This corrects the article DOI: 10.1093/jbmrpl/ziag006.].

Sacral insufficiency fractures are an underrecognized source of atraumatic lumbopelvic pain in elderly osteoporotic patients and may evade diagnosis when initial radiographs are inconclusive. We describe an elderly osteoporotic woman who presented to an outpatient spine clinic with atraumatic low back and hip girdle/groin pain, without radicular symptoms or neurologic deficit. After failure of four weeks of conservative treatment, MRI confirmed bilateral sacral insufficiency fractures, and CT-guided bilateral sacroplasty was performed for persistent axial pain. The procedure was complicated by immediate severe right L5-S1 radicular pain, with MRI and CT demonstrating cement extravasation into the right S1 neural foramen, posterior epidural space, cephalad to the L5 vertebral body, and caudally within the sacral canal. Conservative management with pharmacologic therapy, rehabilitation, and a single right L5 and S1 transforaminal epidural steroid injection resulted in gradual symptom resolution. Spine surgery was consulted, but operative intervention was deferred because symptoms improved and no neurologic deficit developed. This case highlights both the diagnostic complexity of sacral insufficiency fractures and the importance of prompt recognition of cement migration after sacroplasty, while supporting nonoperative management in selected patients without neurologic deficit.

Bone health is maintained by a balance between bone formation and bone resorption. Lycopene, a lipophilic carotenoid and an acyclic isomer of beta-carotene, functions as an antioxidant and may improve bone health via multiple pathways, including the suppression of inflammatory cytokines, stimulation of osteoblast activity, regulation of the wingless-related integration site (Wnt)/β-catenin pathway, and modulation of the receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway. Our understanding of the mechanisms involved in bone remodeling has improved with the discovery of the RANK/RANKL/OPG pathway. Elevated RANKL/RANK signaling promotes osteoclastogenesis and consequently bone resorption, while inhibition of this pathway may prevent bone resorption. This review summarizes current evidence on the impact of lycopene on bone health via the RANK/RANKL/OPG signaling pathway, a key regulator of bone remodeling.

Secondary osteoporosis is a major but frequently under-recognized contributor to skeletal fragility, particularly in men, premenopausal women, patients with fragility fractures at unexpectedly preserved bone mineral density, and individuals with rapid bone loss or inadequate response to standard therapy. Endocrine disorders are among the leading causes because they affect bone remodeling, mineral metabolism, sex steroid signaling, glucocorticoid pathways, insulin-like growth factor activity, and parathyroid hormone regulation. Management requires both correction of the underlying endocrine disorder and pharmacological treatment of skeletal fragility according to fracture risk. This review provides a clinically oriented and guideline-informed synthesis of endocrine-related secondary osteoporosis, with a focus on disease-specific skeletal phenotypes, diagnostic red flags, and targeted management strategies. Particular emphasis is placed on the concept of bone quality as a major determinant of fracture risk and on the limitations of conventional tools such as BMD and FRAX in this setting. We propose a practical clinical framework that integrates endocrine phenotype, vertebral imaging, trabecular bone score, and biochemical assessment into fracture-risk stratification and therapeutic decision-making. This approach supports a shift from a purely densitometric model toward a mechanism-based strategy, enabling improved identification of high- and very-high-risk patients and facilitating the appropriate use of anabolic and antiresorptive therapies.

Osteoporotic vertebral fractures (OVF) represent a growing clinical challenge due to population aging and the increasing prevalence of osteoporosis. Surgical management of OVF differs substantially from that of traumatic vertebral fractures in younger patients and requires careful consideration of fracture morphology, stability, and patient-related factors. A wide range of surgical techniques is currently available, yet clear treatment algorithms remain limited. A non-systematic narrative review of the literature was performed using PubMed, Scopus, and Google Scholar, supplemented by manual reference screening. The review focuses on contemporary surgical strategies for thoracic and lumbar OVF, with particular emphasis on fracture morphology as defined by the AO Spine-DGOU Osteoporotic Fracture (OF) classification and its implications for treatment selection. Minimally invasive cement augmentation techniques, including vertebroplasty and kyphoplasty, are primarily indicated for stable fracture patterns and provide effective pain relief and early mobilization. Posterior fixation strategies range from short-to long-segment constructs, with stability increasing as construct length increases, particularly in osteoporotic bone. Cement augmentation of pedicle screws significantly improves implant anchorage and reduces mechanical complications. Hybrid stabilization, combining posterior instrumentation with vertebral body augmentation, offers circumferential stabilization with favourable mid-term outcomes and reduced invasiveness compared with combined anterior-posterior surgery. Combined anterior-posterior reconstruction remains the most biomechanically robust option for selected patients with severe instability, neurological deficits, or structural collapse, although its use is limited by patient frailty and surgical morbidity. Surgical treatment of osteoporotic vertebral fractures encompasses a spectrum of techniques tailored to fracture morphology, biomechanical demands, and patient condition. Cement augmentation is suitable for less unstable fractures, whereas posterior fixation-often augmented or combined with hybrid strategies-is preferred in more complex patterns. Individualized treatment selection based on fracture classification and patient factors remains essential to optimize outcomes while minimizing complications.