The World Health Organization (WHO) defines osteoporosis as bone density equal to or greater than 2.5, and osteopenia as bone density between 1 and 2.5 standard deviations less than the average value of young adults [1]. More than 200 million people worldwide suffer from osteoporosis [2]. Studies show that about 28% of Iranian women over the age of 50 have osteoporosis and 53% have osteopenia [3].

Primary osteoporosis is a highly prevalent disease among women, caused by menopause and ageing [4], and is attributed to estrogen deficiency [5]. The activity of osteoclasts and the rate of bone loss increase due to estrogen deficiency, and if no action is taken to prevent it, it leads to osteopenia and eventually leads to osteoporosis [6].

Osteoporosis can have a profound effect on a person's psychosocial function. Anxiety caused by living with a chronic disease can lead to depression, reduced ability to perform social tasks, reduced independence in daily activities, and ultimately reduced self-esteem and quality of life [7]. Therefore, the assessment of health-related quality of life is considered as an important criterion for the clinical course of patients with osteoporosis [8].

In postmenopausal women diagnosed with osteoporosis, hormone therapy is used in addition to conventional treatments to prevent and treat osteoporosis, but it has serious adverse effects such as thrombosis and atherosclerosis [9]. Therefore, there is an urgent need to conduct research on new methods that can effectively and safely prevent and treat osteoporosis [10]. In addition to synthetic drugs, alternative therapies such as herbal medicines have also been considered by researchers [11].

Curcumin is the main and active ingredient of Curcuma longa L. (turmeric spice), which may be effective in treating joint problems with its anti-inflammatory, anti-catabolic and antioxidant effects [12], [13], [14], [15], [16]. In animal studies, it has been shown that Curcumin can effectively reduce the rate of osteoblasts apoptosis [17] and inhibit bone resorbtion of osteoclasts [18], and the effect is dose-dependent. Also, high dose of Curcumin with standard doses of alendronate can improve bone density parameters and bone circulation biomarkers [19]. In a clinical trial, it has also been shown that the use of Curcumin for 6 months can significantly improve bone mineral density (BMD) and other indices of bone circulation in patients with chronic spinal cord injury [20]. No complications have been reported following the use of appropriate and standard therapeutic doses of Curcumin, but in cases of overdose, gastrointestinal symptoms (abdominal pain) may occur [21].

The main ingredients of the oil extracted from Nigella sativa‎ seed (Nigella sativa L. of the Ranunculaceae family) are linoleic acid (55.6%), oleic acid (23.4%), and palmitic acid (12.5%), which are reported to have antioxidant, anti-inflammatory, antihistamine, and immune system strengthening effects [22]. Thymoquinone in Nigella sativa may also have osteogenesis effects [23]. It has also been reported that Nigella sativa is a safe antiosteoporotic agent with high levels of unsaturated fatty acids, as well as antioxidant and anti-inflammatory properties [24].

With the increase in life expectancy and the increase in the number of elderly people in the world, the negative effects of osteoporosis are significantly increasing. On the other hand, there are very few clinical studies on the effects of Curcumin and Nigella sativa on osteoporosis in humans [20], [25], [26]. Therefore, we decided to investigate the effect of nanomicellar Curcumin and Nigella sativa‎ supplements alone and in combination with each other on parameters of bone density (primary outcome) and quality of life (secondary outcome) of postmenopausal women with primary osteoporosis or osteopenia.