Materials and Methods: The study protocol will be implemented in two phases. The first phase is a cross-sectional study aiming at determining the prevalence of primary osteoporosis and its risk factors, especially cellular-molecular factors in 528 postmenopausal women aged 50-65 years in Tabriz, Iran through simple random sampling. The second phase is a triple-blind factorial randomized controlled clinical trial. In this phase, patients with primary osteoporosis, identified with dual-energy X-ray absorptiometry, will be randomly divided into equal four groups of 30 individuals in a triple-blind factorial randomized controlled trial. The four group included N. sativa oil soft capsules (one capsule 1000 mg/d) and placebo- curcumin nanomicelles, curcumin nanomicelles soft capsules (one capsule 80 mg/d) and placebo-N. sativa, N. sativa oil, and curcumin nanomicelles soft capsules, and both placebos for six months.

Results: The prevalence of primary osteoporosis and its relationship with several parameters will be determined in phase 1, including socio-demographic-obstetric-medical characteristics, anthropometric indices, body composition, lifestyle, osteoporosis-related microRNAs, inflammatory and oxidative biomarkers, bone turnovers, and some gene polymorphisms. Finally, changes in mean bone mineral density (BMD), bone turnovers, inflammatory and oxidative biomarkers, and osteoporosis-related microRNAs will be evaluated in phase 2.

Conclusions: The present study can significantly contribute to the prognosis of the disease and the selection of an appropriate herbal supplement given the cost-effectiveness of herbal compounds as pharmaceutical adjuvants.