Osteoporotic bone defects pose a threat to the lives of senior citizens, leading to prolonged hospitalization and increased cardiovascular risks due to imbalances in the bone tissue microenvironment. This study established a multifunctional composite system integrating ultrasound-responsive microsphere carriers and photocrosslinkable hydrogel substrates. The microsphere with PVP/ALG (1 : 1) group exhibited ultrasound‑responsive behavior; such feature was not detected for PVP/ALG = 3 : 1 and PVP/ALG = 1 : 3. Systematic investigations regarding the influence of coagulation bath variation on the cross-linking behavior and resultant properties of sodium alginate remain scarce. In this work, we fabricated risedronate (Ris)-loaded ultrasound-responsive microspheres (MS) and incorporated these microspheres into a photopolymerized vancomycin (Van)-loaded GelMA hydrogel system for the repair of osteoporotic bone defects. This work firstly explored the formation and characterization of ALG/PVP composite microspheres prepared in anhydrous ethanol medium. While the cross-linking bath is converted from an absolute ethanol-calcium solution to an aqueous calcium ion solution, sodium alginate microspheres prepared by electrostatic spraying exhibit optically visible responsive performance, presenting a frog-egg-like morphology, and possess ultrasound responsive characteristics. The GelMA@Van/MS@Ris hydrogel exhibits a loose and porous structure, with a 14-day degradation rate of 41.94%, enabling effective sustained release of the loaded vancomycin and risedronate. The GelMA@Van/MS@Ris hydrogel exhibits excellent biocompatibility and osteogenesis, which enhances alkaline phosphatase expression and promotes calcium deposition. In RT-PCR experiments, the GelMA@Van/MS@Ris group showed 1.61-, 1.40-, 2.45-, and 2.38-fold up-regulations in the gene expression levels of Col 1, Alp, Ocn, and Runx2 compared to the GelMA/MS group. In in vivo experiments, GelMA@Van/MS@Ris effectively promotes bone tissue regeneration under osteoporotic pathological conditions. The bone index of GelMA@Van/MS@Ris is 1.73 times that of GelMA/MS. Collectively, this work provides a feasible strategy for constructing bioactive scaffold materials with integrated antibacterial, controlled-release, and osteogenic functions, offering new insights for the development of biomaterials in bone tissue engineering.

Osteoporosis in men is under-recognized and under-treated despite a substantial disease burden and poorer fracture-related outcomes than in women. Secondary osteoporosis is highly prevalent in men, making the identification and management of underlying causes essential. Bone mineral density (BMD) and fracture risk are influenced by sex-specific patterns of skeletal growth and age-related bone loss, with men typically exhibiting greater cortical thickness, larger bone size, and trabecular thinning rather than loss of trabecular number. Although randomized controlled trials in men are fewer than in postmenopausal women, bisphosphonates, denosumab, teriparatide, abaloparatide, and romosozumab have all been shown to significantly increase BMD. Fracture outcome data remain limited; however, reductions in vertebral fracture risk have been demonstrated for zoledronate, alendronate, risedronate, denosumab, and teriparatide. Treatment should be individualized according to fracture risk, comorbidities, and patient preferences. In men at very high fracture risk, osteoanabolic therapy should be considered as first-line treatment, followed by antiresorptive therapy to consolidate and maintain BMD gains. Goal-directed (treat-to-target) management, including long-term maintenance therapy, and careful discontinuation strategies, particularly following denosumab, is essential for optimizing long-term skeletal health. This narrative review and position statement by The ECTS Clinical Action Group provides an updated overview of current and emerging treatment options and offers practical, evidence-based recommendations for the long-term management of osteoporosis in men.

Senile osteoporosis (SOP) creates a hostile peri-implant microenvironment characterized by impaired osteogenesis, excessive bone resorption, and persistent oxidative stress, leading to poor osseointegration. Here, we developed a dual-functional titanium surface (Ti-Ta@RS) co-modified with a thioctic acid derivative and risedronate sodium to simultaneously regulate oxidative stress and osteoclast activity. Ti-Ta@RS improved the physicochemical properties of the titanium surface and significantly enhanced BMSC viability, migration, spreading, and osteogenic differentiation under senescence-associated conditions, as evidenced by increased ALP activity, collagen deposition, mineralization, and osteogenesis-related protein expression. Moreover, Ti-Ta@RS effectively reduced intracellular oxidative stress and inhibited RANKL-induced osteoclastogenesis, demonstrating its dual regulatory effects on the pathological SOP microenvironment. In vivo, Ti-Ta@RS markedly promoted peri-implant bone formation, improved trabecular microarchitecture, and enhanced osseointegration in senile osteoporotic rats. Transcriptomic analysis further suggested that these beneficial effects were associated with the regulation of extracellular matrix remodeling, calcium signaling, and cell cycle-related pathways. Collectively, these findings demonstrate that Ti-Ta@RS effectively rebalances the pathological SOP microenvironment by integrating antioxidative regulation with local anti-resorptive activity, thereby providing a promising surface-engineering strategy for enhancing implant osseointegration under senile osteoporotic conditions.

Risedronate sodium is a widely used bisphosphonate for the treatment of osteoporosis and other metabolic bone disorders. This study aimed to evaluate the bioequivalence and safety of a test formulation of risedronate sodium 35 mg tablets compared with the reference formulation in healthy Chinese participants under fasting conditions. A randomized, open-label, single-dose, three-period, partial replicate crossover study was conducted in healthy participants. Forty-five participants were enrolled and 38 completed the study. Plasma concentrations of risedronic acid were measured using a validated liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters were calculated using non-compartmental analysis. Bioequivalence was assessed using the reference-scaled average bioequivalence approach. The geometric mean values of Cmax, AUC0-t, and AUC0-∞ for the test formulation were 28.50 ng/mL, 115.40 h.ng/mL, and 129.60 h.ng/mL, respectively, compared with 26.67 ng/mL, 107.01 h.ng/mL, and 119.03 h.ng/mL for the reference formulation. The geometric mean ratios for Cmax, AUC0-t, and AUC0-∞ were 1.1077, 1.0894, and 1.0897, respectively, all within the predefined acceptance range. For the primary pharmacokinetic parameters, the point estimate of the test/reference mean ratios were within 0.80-1.25 and the upper bounds of the one-sided 95% confidence intervals for the RSABE criteria were below zero. Both formulations were generally well tolerated, and no serious adverse events were reported. These findings demonstrate that the test and reference formulations of risedronate sodium 35 mg tablets are bioequivalent under fasting conditions and exhibit comparable safety profiles. Clinical Trial Registration: CTR20201946.

Osteosarcoma faces the challenges of limited drug delivery and an immunosuppressive tumor microenvironment. M1 macrophages, a type of tumor-associated macrophage, play a pivotal role in shaping tumor immune responses. A dual enzyme-mimicking nanozyme coordinated to risedronate sodium and encapsulated in a sodium alginate gel (RZRSA) was developed to enhance the radiosensitivity of osteosarcoma. After intratumoral injection, RZRSA formed a calcium alginate hydrogel in osteosarcoma owing to the presence of Ca[2+]. Because of its peroxidase-like activity, RZRSA generated abundant toxic hydroxyl radicals in the presence of intratumoral H2O2 overexpression. Moreover, the hypoxia status of tumors was alleviated by the catalase-mimicking property of RZRSA by transforming H2O2 into O2, thereby improving the efficacy of radiotherapy. The Ru elements in RZRSA augmented the energy decomposition of ionizing irradiation in tumor regions. These properties contributed to magnifying the oxidative stress in the tumor microenvironment, which promoted M1-like polarization to kill tumor cells. In addition, radiosensitization by RZRSA triggered a robust immunogenic cell death effect and promoted dendritic cell maturation. This innovative design of RZRSA provides a promising strategy for targeted osteosarcoma treatment.

This study evaluated the structural, electronic, pharmacokinetic, and receptor-binding properties of three bisphosphonate derivatives, alendronate, risedronate, and zoledronate, to investigate their therapeutic relevance in osteoporosis and breast cancer. Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d,p) level showed that risedronate exhibited the highest kinetic stability (ΔE = 6.7468 eV), whereas zoledronate displayed greater chemical reactivity (ΔE = 2.9669 eV) and the strongest nonlinear optical response (β = 1.20 × 10[-30] esu). ADMET analysis indicated acceptable safety profiles for all compounds, although high polarity and low lipophilicity may limit oral bioavailability. Molecular docking against 11 breast cancer- and bone metabolism-related targets revealed favorable binding affinities, particularly for zoledronate and risedronate. Zoledronate showed strong interactions with ESR2, VEGFR/KDR, GGPS1, and FPPS, whereas risedronate exhibited notable affinity for BRCA2 and MMP9. Bioinformatics analyses identified significant dysregulation of GGPS1, FDPS, TNFSF11, ESR1, MMP9, and BRCA2 in breast cancer tissues, while survival analysis linked elevated FDPS, MMP9, and BRCA2 expression to poor prognosis. Network analyses highlighted pathways related to mevalonate metabolism, hormone signaling, angiogenesis, extracellular matrix remodeling, and the RANK/RANKL/OPG axis. These findings support the potential repurposing of bisphosphonates, particularly zoledronate, for breast cancer-associated bone disease.