Primary osteoporosis is a global issue, which leads to an increased risk of bone fractures. Osteopenia is considered an initial stage of bone tissue deterioration and a precursor of osteoporosis [1]. Postmenopausal women are considered a high-risk group in terms of osteopenia and primary osteoporosis, because of estrogen deficiency after amenorrhea [2], [3], [4]. Recent investigations have demonstrated that lasting inflammation, whether direct or induced by oxidative stress, has significant negative effects on bone health, which might be associated with postmenopausal osteopenia/osteoporosis [4], [5], [6], [7], [8]. In these conditions, hypo-estrogenism leads to upregulation of inflammatory factors, consisting of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) [1], [2], [3], [9]. Bone remodeling disruption leads to numerous complications, including pain, fracture, deformity, disability, excessive healthcare costs, reduced quality of life, and even early death in postmenopausal women [2], [10], [11]. Hence, timely diagnosis and treatment are necessary to avert osteoporosis ramifications and promote the well-being of postmenopausal women [2], [5]. Bone mineral density (BMD) evaluation is used to diagnose osteopenia and osteoporosis, based on the World Health Organization (WHO) operational definition [12]. The WHO defines osteopenia as a BMD T-score between −1 and −2.5 SDs and osteoporosis as 2.5 SDs or more below the average for youthful healthy adults [13].

Current pharmacological treatments include bisphosphonates, hormone replacement therapy (HRT), human monoclonal antibodies, parathyroid hormone (PTH) analogs, and selective estrogen receptor modulators (SERMs) [10], [11]. The aim of these treatments is the stimulation of bone formation, the deterrence of bone loss, or both [12]. Considering the necessity of long-term use, concerns about the possible ramifications and expenses of the current pharmacological treatments persist. Moreover, there is an increasing demand for non-pharmacological treatments for osteoporosis, including natural products derived from medicinal herbs [3], [6]. Current investigations have shown that these components have lower expenses and side effects, which can be administered alone or combined with therapeutic remedies to ameliorate the complications [3], [4], [6]. Therefore, it is necessary to research novel adjunctive or alternative natural treatments for long-term management of osteoporosis [4], [6].

Curcumin (CUR) is one of the naturally derived compounds, isolated from the turmeric plant (Curcuma longa). Curcumin has been widely explored regarding its antioxidant and anti-inflammatory properties in numerous chronic diseases, which may mitigate the pathogenesis of osteopenia and osteoporosis [14], [15], [16], [17]. Nigella sativa (NS), classified under the Ranunculaceae family, is a plant containing bioactive compounds with numerous pharmacological properties. Thymoquinone (TQ), the major bioactive component of NS, exerts beneficial therapeutic effects. Recent studies have clearly demonstrated the beneficial effects of Nigella sativa on bone health, primarily due to its antioxidant and anti-inflammatory properties [18], [19], [20], [21], [22].

Considering the above-described background, the efficiency of Curcumin and Nigella sativa administration in the management of menopause-related osteopenia or osteoporosis has not been fully investigated based on the latest evidence. Additionally, recent studies have indicated that combination therapy is usually more effective compared to separate treatments due to the synergistic effects of herbal compounds [23], [24]. Hence, this study was conducted to appraise whether administration of Curcumin Nano-micelle, a highly-soluble form, and Nigella sativa, alone and combined, impact serum inflammatory factors in postmenopausal women diagnosed with primary osteopenia or osteoporosis.