Purpose: Accumulating evidence implicates parathyroid hormone (PTH) in the development of osteoporosis. However, the causal effect of PTH on bone mineral density (BMD) remains unclear. Thus, this study aimed at exploring the association between the concentrations of serum PTH and BMD.

Methods: The instrumental variables for PTH were selected from a large-scale genome-wide association study (GWAS) [n = 29,155]. Outcomes included BMD of forearm (FA) [n = 8143], femoral neck (FN) [n = 33,297], lumbar spine (LS) [n = 32,735], heel (HL) [n = 394,929] and risk of fractures in these bones (n = 361,194). Furthermore, the BMD of five different age groups; 15 or less [n = 11,807], 15-30 [4180], 30-45 [10,062], 45-60 [18,805] and 60 or more [22,504] were extracted from a GWAS meta-analysis study. The analyses were performed using the two-sample Mendelian randomization (MR) method.

Results: MR analysis revealed that the level of serum PTH were inversely associated with BMD of FA (95% CI: -0.763 to -0.016), FN (95% CI: -0.669 to -0.304) and LS (95% CI: -0.667 to -0.243). A causal relationship between serum PTH levels and BMD was observed in individuals aged 30-45 (95% CI: -0.888 to -0.166), 45-60 (95% CI: -0.758 to -0.232) and over 60 years (95% CI: -0.649 to -0.163).

Main conclusions: This study demonstrated that the concentrations of serum PTH is inversely associated with BMD of several bones. Further analysis revealed a site and age-specific correlations between serum PTH levels and BMD, which implies that the levels of serum PTH contribute to the development of osteoporosis.