| Summary: | Caffeine (1,3,7-trimethylxanthine) is a naturally occurring plant xanthine alkaloid present in many commonly consumed beverages worldwide, including tea, coffee, and cocoa. Although moderate caffeine intake is generally considered to exert positive effects on human health, its effect on bone metabolism remains controversial. The aim of this study was to systematically evaluate the pharmacological effect of long-term administration of caffeine on ovariectomy-induced postmenopausal osteoporosis in female rats. A sham operation or ovariectomy was performed to establish the ovariectomy rat model. The ovariectomized (OVX) rats were divided into five subgroups: OVX with vehicle (model), OVX with raloxifene hydrochloride (RLX, positive control; 4 mg/kg body weight/day), and OVX with low-, medium-, and high-dose caffeine (9.6, 19.2, and 38.4 mg/kg of body weight/day, respectively). Their corresponding treatments were administered intragastrically for 13 weeks. In-vivo studies showed that treatment with caffeine effectively improved the lipid profiles and increased the concentration of calcium in the serum of OVX rats. Medium- or high-dose treatment with caffeine significantly decreased the activities of alkaline and acid phosphatases in OVX rats. In addition, treatment with caffeine (at any dose) did not adversely affect organ weights, organ coefficients, femoral length, bone mineral density, biomechanical properties, or bone microarchitecture in OVX rats. Collectively, our study demonstrated that caffeine did not exert a damaging effect on the skeletal system of OVX rats.
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