Synergistic effects of platelet-rich plasma and teriparatide on osteoporotic fracture healing in OVX rats

To evaluate the combined efficacy of locally injected platelet-rich plasma (PRP) and systemically administered teriparatide (PTH) on fracture healing in osteoporotic rats. Thirty female Sprague-Dawley rats underwent ovariectomy (OVX) to induce osteoporosis, followed by a left femoral osteotomy with Kirschner wire fixation. Rats were randomized into five groups (n = 6 per group): Sham, Model (OVX + Fx), PRP (local injection of 0.3 mL autologous PRP biweekly), PTH (subcutaneous teriparatide 10 µg/kg/day), and Combination (PRP + PTH). Healing was assessed 6 weeks post-treatment via serum ELISA (measuring osteocalcin (OCN), platelet-derived growth factor (PDGF), transforming growth factor-beta 1 (TGF-β1)), radiography, biomechanical testing (ultimate load, stiffness), histology (H&E staining), and micro-computed tomography (BV/TV, Tb.Th, Tb.N, Tb.Sp). The Combination group exhibited significantly higher serum levels of OCN, PDGF, and TGF-β1 compared to the monotherapy groups (P < 0.05). Radiographic evaluation indicated nearly complete fracture bridging at 6 weeks in the Combination group, with superior mineralization density observed as early as 4 weeks. Biomechanically, the Combination group demonstrated the greatest increase in ultimate load (135.7%) compared to the Model group, surpassing the improvements seen with either PRP (90.5%) or PTH (78.6%) monotherapy. Micro-CT analysis confirmed the highest bone volume fraction (BV/TV) in the Combination group (0.337 ± 0.017), significantly greater than in the PRP (0.280 ± 0.012) and PTH (0.263 ± 0.015) groups. H&E staining revealed optimal trabecular continuity and minimal adipocyte infiltration in the Combination group. PRP (promoting local callus augmentation) and PTH (enhancing systemic mineralization) demonstrated complementary actions. Their combination synergistically restored bone microarchitecture and biomechanical strength in osteoporotic fractures, yielding outcomes superior to those achieved with monotherapies.