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

Aims. A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 10. 6. cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. Results. Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores – RUST and Allen score – histologically compared to controls. Conclusion. We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659–667

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In our previous research, we have found that melatonin (MEL) affects the osteoporotic process. By balancing bone remoulding, autophagy is involved in age-related bone loss. However, as a regulator of autophagy, whether MEL influences senile osteoporosis via regulating autophagy remains unclear.

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A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process.

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Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture.

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Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation.