Alendronate sodium nanoemulsion ameliorates postmenopausal osteoporosis: hematological and histopathological evidence from an ovariectomized rat model

Background Osteoporosis is a chronic metabolic bone disease with a significant global health burden, particularly among postmenopausal women. This study aimed to evaluate the effect of alendronate sodium nanoemulsion (ALN-NE) on hematological parameters and femoral bone histopathological changes in an ovariectomized (OVX) rat model of postmenopausal osteoporosis. Methods Thirty-six adult female Sprague-Dawley rats were randomly allocated into six groups ( n = 6 per group): Sham (negative control), OVX (disease control), OVX + ALN (1 mg/kg; reference control), OVX + ALN-NE 0.2%, OVX + ALN-NE 0.4%, and OVX + ALN-NE 0.6%. ALN-NE was prepared and characterized by Zetasizer analysis. Treatments were administered orally by gavage three times per week for eight consecutive weeks post-ovariectomy. Key endpoints included hematological parameters (RBC, WBC, Hb, LYM) and femoral bone histopathological assessment using H&E staining. Results Zetasizer analysis confirmed concentration-dependent size increases (70.00–534.0 nm) and favorable zeta potential values (-21.9 to -41.1 mV). The OVX group demonstrated severe histopathological bone lesions and hematological dysregulation. The 0.6% ALN-NE group showed significant reduction in WBC and restoration of Hb and LYM compared to the OVX group ( P < 0.05), showing more pronounced hematological improvements than conventional ALN in the parameters assessed. Conclusion ALN-NE, particularly at 0.6%, showed promising hematological and bone microarchitectural improvements over conventional alendronate following eight weeks of treatment in an OVX rat model, supporting its potential as a next-generation delivery platform for postmenopausal osteoporosis. These findings warrant further investigation incorporating bone-specific outcomes such as BMD and micro-CT analysis.