Bone morphogenetic protein 2 (BMP2) is clinically applied for treating intractable fractures and promoting spinal fusion because of its osteogenic potency. However, adverse effects following the release of supraphysiological doses of BMP2 from collagen carriers are widely reported. Nanoclay gel (NC) is attracting attention as a biomaterial, given the potential for localized efficacy of administered agents. However, the efficacy and mechanism of action of NC/BMP2 remain unclear. This study explored the efficacy of NC as a BMP2 carrier in bone regeneration and the enhancement mechanism. Subfascial implantation of NC containing BMP2 elicited superior bone formation compared with collagen sponge (CS). Cartilage was uniformly formed inside the NC, whereas CS formed cartilage only on the perimeter. Additionally, CS induced a dose-dependent inflammatory response around the implantation site, whereas NC induced a minor response, and inflammatory cells were observed inside the NC. In a rat spinal fusion model, NC promoted high-quality bony fusion compared to CS. In vitro, NC enhanced chondrogenic and osteogenic differentiation of hBMSCs and ATDC5 cells while inhibiting osteoclastogenesis. Overall, NC/BMP2 facilitates spatially controlled, high-quality endochondral bone formation without BMP2-induced inflammation and promotes high-density new bone, functioning as a next-generation BMP2 carrier.

Ossification of the posterior longitudinal ligament (OPLL) is a heterotopic ossification that may cause spinal cord compression. With the recent development of computed tomography (CT) imaging, it is known that patients with OPLL often have complications related to ossification of other spinal ligaments, and OPLL is now considered part of ossification of the spinal ligaments (OSL). OSL is known to be a multifactorial disease with associated genetic and environmental factors, but its pathophysiology has not been clearly elucidated. To elucidate the pathophysiology of OSL and develop novel therapeutic strategies, clinically relevant and validated animal models are needed. In this review, we focus on animal models that have been reported to date and discuss their pathophysiology and clinical relevance. The purpose of this review is to summarize the usefulness and problems of existing animal models and to help further the development of basic research on OSL.

Aims: Nonunion occurs when a fracture fails to heal permanently, often necessitating surgical intervention to stimulate the bone healing response. Current animal models of long-bone nonunion do not adequately replicate human pathological conditions. This study was intended as a preliminary investigation of a novel rat nonunion model using a two-stage surgical intervention, and to evaluate the efficacy of a selective prostaglandin E2 receptor 4 agonist (AKDS001) as a novel nonunion therapeutic agent compared with existing treatments.Methods: Initially, Sprague-Dawley rats underwent intramedullary Kirschner wire (K-wire) fixation of a femoral fracture with the interposition of a 2 mm-thick silicon disc. After three weeks, the silicon disc was removed, and the intramedullary K-wire was replaced with plate fixation while maintaining the 2 mm defect. Contrary to the control group (1) that received no treatment, the following therapeutic interventions were performed at injury sites after freshening: (2) freshening group: no grafting; (3) iliac bone (IB) group: IB grafting; (4) AKDS group: AKDS001-loaded microspheres (MS) combined with IB (0.75 mg/ml); and (5) bone morphogenetic protein (BMP) group: grafting of a BMP-2-loaded collagen sponge (10 μg; 0.10 mg/ml). After six weeks, micro-CT (μCT) and histological analysis was performed.Results: In the control group, the radiological union rate was 0%, and histological findings showed that fracture sites comprised fibrous scar tissue, resembling the histology of human nonunion. The union rates in the freshening, IB, AKDS, and BMP groups were 16.7%, 0%, 62.5%, and 50.0%, respectively. The AKDS group demonstrated a significantly higher union rate than the IB group (p = 0.026). μCT and histological analysis indicated that the quality of newly formed bone was superior in the AKDS group than in the BMP group.Conclusion: We developed a novel long-bone nonunion model. The co-therapy of AKDS001-MS and IB grafting presents a promising new treatment for nonunion.Cite this article: Bone Joint Res 2025;14(3):166–175.

Osteoporosis is characterized by reduced bone mass and structural deterioration, leading to increased fracture risk, particularly in older adults. Parathyroid hormone (PTH) is a widely used anabolic therapy for osteoporosis; however, rapid bone loss after treatment discontinuation presents a significant clinical challenge. Cellular senescence has been implicated in age‐related bone fragility. However, its role in PTH‐induced bone remodeling and post‐treatment bone loss remains unclear. This study aimed to investigate the effects of PTH administration frequency on bone microarchitecture and cellular senescence in young and aged mice. High‐frequency PTH administration improved trabecular bone volume in both age groups, but caused cortical bone thinning, increased porosity, and elevated osteoclast activity in aged mice. PTH induces senescent osteoblast‐lineage‐enriched cell accumulation in aged, but not young mice, accompanied by upregulation of senescence‐associated markers and activation of the mechanistic Target of Rapamycin Complex 1 pathway. Co‐administration of the senolytic agents dasatinib and quercetin during PTH treatment reduced senescent cell burden, improved cortical porosity, and mitigated rapid bone loss after PTH discontinuation in aged mice. These findings indicate that senescent osteoblast‐lineage‐enriched cells contribute to bone fragility and post‐treatment bone loss in aged individuals, suggesting that targeting senescence may enhance the efficacy and sustainability of PTH therapy for osteoporosis.