Background: Osteoporosis is a debilitating bone ailment characterized by the obvious loss of bone mass and bone microarchitecture impairment. Objective: This study aimed to illuminate the in vivo usefulness of nanotechnology as a treatment for osteoporosis via analyzing the effectiveness of nano-hydroxyapatite (nHa), nano-hydroxy- apatite/chitosan (nHa/C), and nano-hydroxyapatite/silver (nHa/S) in mitigation of osteoporosis in ovariectomized rats. Method: The characterization of the nHa, nHa/C, and nHa/S was carried out using TEM, SEM, FTIR, and Zeta potential measurements. This in vivo study included 48 adult female rats that were randomized into six groups (8 rats/group): (1) Sham-operated control, (2) osteoporotic, (3) nHa, (4) nHa/C, (5) nHa/S, and (6) Fosamax®. Serum osterix level was quantified using ELISA. Femur bone morphogenetic protein 2 and SMAD1 mRNA levels were evaluated by qPCR. The femur bones were scanned by DEXA for measurement of bone mineral density and bone mineral content. In ad-dition, a histopathological examination of femur bones was performed. Results: The present approach denoted that the treatment with nHa, nHa/C, or nHa/S yields a signif-icant rise in serum level of osterix and mRNA levels of bone morphogenetic protein 2 and SMAD1 as well as significant enhancements of bone tissue minerals. Conclusion: The findings affirmed the potency of nHa, nHa/C, and nHa/S as auspicious nanoplat-forms for repairing bone defects in the osteoporotic rat model. The positive effect of the inspected nanoformulations arose from bone formation indicators in serum and tissue, and additionally, the reinforcement of bone density and content, which were verified by the histopathological description of bone tissue sections.