Facial skin aging is a potential osteoporosis-associated marker: evidence from both observational and genetic studies

Facial skin aging (FSA) is a very easily observable indicator of aging, but whether FSA is associated with osteoporosis is still unknown.

Based on the individual-level datasets from UK Biobank, this study calculated the PhenoAge (an accurate aging parameter), genetic risk score (GRS) and PhenoAge_advance, and performed multiple linear correlation analyses and Cox regression analyses. Based on the summary data from genome-wide association Studies (GWAS), linkage disequilibrium regression (LDSC), pleiotropic analysis under composite null hypothesis (PLACO) and Mendelian randomization (MR) analysis were performed to reveal shared genetic components and infer causal effects, respectively.

Higher degrees of FSA were associated with lower eBMD (p < 0.001), and FSA was positively associated with the risks of osteoporosis (HR = 1.852, p < 0.001) and fracture (HR = 1.501, p < 0.001). However, FSA was not genetically associated as well as causally associated with all studied osteoporosis-related traits. In addition, we found significant phenotypic and genetic correlations between FSA and PhenoAge (rp = -0.137, p < 0.05) as well as between PhenoAge and fractures (rg = 0.092, p < 0.05).

FSA, PhenoAge and osteoporosis are three aging-related parameters that coexist with aging, and the aging process is accompanied by FSA and osteoporosis. FSA may serve as a marker for the onset of osteoporosis. These findings provide clues for early detection of bone loss in at-risk populations and for OP diagnosis using accurate clinical tools.