Abstract
We investigated the beneficial effects and underlying mechanisms of Zhuanggu Guanjie (ZGGJ) pill in osteoporosis in vitro and in vivo. Bone marrow macrophages from 4–6-week-old mice were cultured in the presence of macrophage colony-stimulating factor (15 ng/mL) and receptor activator of nuclear factor-κB ligand (30 ng/mL). Osteoclast differentiation was determined by quantification of tartrate-resistant acid phosphatase activity. Gelatin zymography was used to detect the activity of matrix metalloproteinases in osteoclasts. Ovariectomized rats were administered orally with estradiol valerate or ZGGJ for 8 weeks. Blood was collected to measure serum indices. Tibiae were harvested to carry out bone microcomputed tomography scanning, histomorphological analysis, and bone strength determination. ZGGJ inhibited tartrate-resistant acid phosphatase activity, matrix metalloproteinase 9 expression, and bone resorption in vitro. At doses of 0.55, 1.1, and 2.2 g/kg, ZGGJ exerted significant osteoprotective effects including inhibition of bone turnover markers and improved tibia bone strength in ovariectomized rats. Microcomputed tomographic analysis showed that ZGGJ improved the trabecular architecture with increased connectivity density and trabecular thickness and decreased trabecular spacing. These results revealed that ZGGJ prevents bone loss induced by ovariectomy in rats and that inhibition of bone resorption is involved in the bone-protective effects of ZGGJ.
Highlights
Osteoporosis is characterized by a systemic decrease in bone mass and impairment of microarchitecture resulting in fragility fractures, which is a common disease in the aging population, especially postmenopausal women [1]
Serum tartrateresistant acid phosphatase (TRAP) and RANKL of the model group were significantly higher than those of the control group, and their activities in rats of the Zhuanggu Guanjie (ZGGJ) groups were lower than those in the model group, which tended to be normal (Figure 4). These results suggest that ZGGJ inhibits bone resorption in rats
This study evaluated the effects of ZGGJ on osteoporosis in vitro and in vivo
Summary
Osteoporosis is characterized by a systemic decrease in bone mass and impairment of microarchitecture resulting in fragility fractures, which is a common disease in the aging population, especially postmenopausal women [1]. Hormone replacement therapy is the first-line therapy for prevention and treatment of osteoporosis in postmenopausal women because of estrogen deficiency during menopause, leading to bone loss. Hormone replacement therapy has adverse effects after long-term use, such as increased risks of breast cancer and cardiovascular events [2]. There are several effective modalities for osteoporosis treatment, continuous efforts are being made to develop novel agents that improve outcomes and minimize the risks of adverse events. In China, traditional Chinese medicines (TCMs) comprising herbal formulas are a growing alternative to prevent osteoporosis [3]. TCMs are attracting the attention of researchers worldwide because of their active and effective properties and lower reported side effects compared with synthetic drugs [4]
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