Metabolomics and physiological analysis of the effect of calcium supplements on reducing bone loss in ovariectomized rats by increasing estradiol levels

Abstract

Background Data from the 2010–2012 Chinese National Nutrition and Health Survey showed that the vast majority of postmenopausal women in China had dual deficiencies in calcium and estrogen. Objective This study aimed to clarify whether calcium supplementation alleviated bone loss caused by calcium restriction combined with estrogen deficiency in rats. Methods Forty-eight female rats aged 9 weeks were assigned to 4 groups and fed a low-calcium diet: sham-operated (SHAM-LC), ovariectomized (OVX-LC), and ovariectomized rats treated with 750 mg/kg (OVX-LC-M) or 2800 mg/kg CaCO3 (OVX-LC-H). CaCO3 or distilled water was administered orally for 13 weeks. Bone mineral density (BMD) and histomorphometry of the femur, serum biochemical parameters, and serum metabolites were analyzed. Results The OVX-LC rats showed a significant increase in body weight and serum levels of lipid markers, a significant decrease in serum estradiol, calcium, phosphorus, and 25(OH)D levels, and deterioration of the femur. At 750 mg/kg and 2800 mg/kg, CaCO3 reduced the deterioration of trabecular bone and increased the trabecular area percentage (Tb.Ar %) and BMD of the femur. Serum estradiol levels increased in a dose-dependent manner after CaCO3 supplementation (p < 0.01). The administration of 2800 mg/kg CaCO3 decreased serum triglyceride and high-density lipoprotein levels (p < 0.05) and decreased the levels of the bone turnover markers osteocalcin, N-telopeptide of type I collagen and β-crosslaps. The results of the metabolomics analysis showed that the glycerophospholipid metabolism pathway was closely related to calcium supplementation, and more DG (44:6 n3), LysoPC (22:2) and PE (P-34:3) and less Cer (d43:0) and PE-NMe2 (46:3) were produced. Conclusions The results clearly indicated that calcium supplementation was beneficial for decreasing bone loss in OVX-LC rats. The present study is the first to show that calcium supplementation increased the estradiol content in OVX-LC rats, and the effect of calcium on bone loss may be partially attributed to the increase in the estrogen level that subsequently induced the changes in metabolite levels, eventually increasing the bone mineral density to a relatively higher level to reduce bone deterioration.

Combined Therapy of Yishen Zhuanggu Decoction and Caltrate D600 Alleviates Postmenopausal Osteoporosis by Targeting FoxO3a and Activating the Wnt/β-Catenin Pathway

“…erefore, PMO rat model was established by ovariectomy. E 2 is a female hormone that decreased in postmenopausal women [33,34], and BMD is a critical parameter of PMO [35]. ELISA showed that the serum E 2 and BMD levels decreased in PMO rats.…”

Applications of Metabolomics in Calcium Metabolism Disorders in Humans

“…It is estimated to be higher (more than 10%) in postmenopausal women [ 69 , 70 ]. Low vitamin D levels as well as together with insufficient calcium intake, estrogen deficiency in postmenopausal women and smoking contribute to osteoporosis [ 39 , 71 ]. The prevalence of osteoporosis and the expenditures associated with its treatment impose a significant socioeconomic burden [ 72 ].…”

“…The main differences in glycerophospholipids metabolism were identified in phosphatidylethanolamines, phosphatidylcholines and ceramides. Additionally, it was found that E2 may affect changes in glycerophospholipids and glycerophospholipid metabolism was considered to be the main potential target pathway of E2 [ 71 ]. Zhao used UPLC-Q-TOF-MS-based lipidomics in combination with metabolomics and provided more detailed information about the lipidomic profiles of and alterations in fatty acids, glycerolipids, glycerophospholipids, sphingolipids and sterols in an ovariectomized mouse model of osteoporosis [ 73 ].…”

Application of metabolomics in osteoporosis research

“…A series of studies found that vitamin D levels can significantly alter amino acids, energy metabolism, levels of sugars and their derivatives, and organic acids in patients with OP, thus affecting the metabolomic outcome of OP ( 77 , 78 ). In addition, different blood calcium levels affected the metabolism of lipids and amino acids such as taurine, glycerophospholipids and glycine, thus causing changes in the metabolomic outcome of OP, which ultimately affected BMD and bone degeneration ( 79 , 80 ). Recent studies have found that temperature increases the total amount of polyamines in the body, and that inhibition of polyamine biosynthesis in the body limited the protective effect on bone ( 81 ).…”