Liu L, et al. - Given the effect of blood metabolites on the development of osteoporosis remains elusive, researchers assessed the link between blood metabolites and osteoporosis. They found that blood metabolites moderately impacted the variations of bone mineral density (BMD). In addition, several candidate blood metabolites for osteoporosis were identified.

Methods

• This study included the discovery samples including 2286 unrelated white subjects and the replication samples including 3143 unrelated white subjects from the Framingham Heart Study (FHS).
• Using dual-energy X-ray absorptiometry, researchers measured bone mineral density (BMD).
• They carried out genome-wide single nucleotide polymorphism (SNP) genotyping using Affymetrix Human SNP Array 6.0 (for discovery samples) and Affymetrix SNP 500K and 50K array (for FHS replication samples).
• From a reported whole-genome sequencing study, they obtained the SNP sets significantly related to blood metabolites.
• From the genotype data of the metabolite-associated SNP sets, they calculated the genetic risk score of the metabolite for each subject.
• They also performed Pearson correlation analysis to assess the potential impact of blood metabolites on the variations in bone phenotypes; 10,000 permutations were conducted to calculate the empirical P value and false discovery rate.

Results

• Analysis of a total of 481 blood metabolites was carried out.
• Multiple blood metabolites that were found to be related to hip BMD were: 1,5-anhydroglucitol (P_discovery < 0.0001; P_replication=0.0361), inosine (P_discovery=0.0018; P_replication=0.0256), theophylline (P_discovery=0.0048; P_replication=0.0433, gamma-glutamyl methionine (P_discovery=0.0047; P_replication=0.0471), 1-linoleoyl-2-arachidonoyl-GPC (18:2/20:4n6; P_discovery=0.0018; P_replication=0.0390), and X-12127 (P_discovery=0.0002; P_replication = 0.0249).