| Vitamin D a group of fat-soluble secosteroids which is involved in the metabolism and balance of calcium and phosphate.Vitamin D metabolites1α,25-(OH)2D plays important roles in this biological effects through modulating its receptor VDR,and single nucleotide polymorphisms(SNPs)on VDR and the vitamin D metabolic procedures significantly influenced the circulating vitamin D in human body.Previous observational or experimental studies have investigated the associations between vitamin D and the bone mineral density(BMD),but their results were inconsistent.This study evaluated the correlation between 25(OH)D levels and BMD in Chinese elderly population.Samples were collected from four areas of China,including Beijing,Shanghai,Guangzhou and Gansu.The basic information of 7,175 elderly Chinese individuals(average age 63.5 years)who met the inclusion criteria were collected,their lumbar BMD,femoral BMD,and serum bone metabolism biomarkers were recorded.Four SNPs related to 25(OH)D levels(rs10741657,rs12785878,rs2282679,rs6013897)were detected.The single-sample two-stage Mendelian randomization(MR)method was used to evaluate the correlation between 25(OH)D levels with genetic susceptibility and BMD of the lumbar spine and femur.Chi-square test was used to compare the differences in lumbar spine BMD,femur BMD and serum bone metabolism biomarkers in samples.Linear regression was used to evaluate the relationship between the body mass index(BMI)and the lumbar spine BMD and femur BMD of the elderly Chinese individuals.There are significant differences in the lumbar spine BMD,femur BMD and serum bone metabolism biomarkers among the elderly from four areas.The BMD of the lumbar spine and femur of the elderly in China is positively correlated with their BMIs.Every increase in BMI(kg/m~2)by one unit will increase the BMD of lumbar spine by 0.014g/cm~2 and the BMD of femur by 0.013g/cm~2.The results of Mendelian randomization analysis showed that the high genetic susceptibility of 25(OH)D levels is not associated with the lumbar spine BMD(β=-0.078,se = 0.046;P =0.792),femoral BMD(β=-0.021,se = 0.048;P = 0.281)and biomarkers related to bone metabolism.The MR-Egger and weighted median MR analysis models gave similar results.There are significant differences in BMD and bone metabolism-related biomarkers in the elderly Chinese from different regions.The high genetic susceptibility of 25(OH)D levels is not associated with the lumbar and femoral BMD and bone metabolism-related biomarkers in the Chinese elderly.Fibroblast growth factor 23(FGF23),a phosphoric hormone that inhibits calcitriol synthesis,is associated with the metabolism of serum phosphate and vitamin D,studies suggested that it may involve in the regulation of bone mineral density(BMD);however,whether this association is causal remains unclear.In this study,we conducted a two sample Mendelian Random(MR)analysis to investigate whether the FGF23 levels was causally associated with BMD change in adults.Five single nucleotide polymorphisms(SNPs)significantly associated with FGF23 were selected as instruments variables(IVs)in our two-sample MR study(rs17216707,rs11741640,rs9925837,rs2769071 and rs17479566).The relationship between FGF23 level with high genetic susceptibility(n = 16,624)and adult lumbar spine BMD(n =28,498),femur BMD(n = 8,143),femoral neck BMD(n = 32,735),heel BMD(n = 265,753)and biomarkers of bone turnover were examined.Summary-level data on adult lumbar spine BMD,femur BMD,femoral neck BMD,heel BMD and bone turnover biomarkers were obtained from the genome-wide association(GWAS)research database.The two-sample MR analysis showed that for every 1-unit increase in the log-transformed blood FGF23 level(pg/m L),there would be decreased levels of adult heel BMD(β =-0.201,se = 0.084,P = 0.016)and femoral neck BMD(β =-0.286,se = 0.126,P = 0.022),indicative of a causal relationship based on the inverse variance weighting method.However,FGF23 levels were not correlated with adult lumbar spine BMD(β =-0.166,se = 0.193,P = 0.389),and forearm BMD(β =-0.186,se = 0.366,P = 0.610).Moreover,the two-sample MR analysis suggested that there was no evidence for associations between FGF23 and serum calcium,phoshpate,magnesium,25(OH)D and creatinine levels.This study suggests that there may be a causal relationship between blood FGF23 levels and BMD of the heel and femoral neck in adults;however,further investigations are necessary to determine whether FGF23 may be a potential biomarker or therapeutic target for bone mineralization disorders. |
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