Causal associations between insulin-like growth factor binding protein-1 to -7 and osteoporosis: A two-sample Mendelian randomization study

Insulin-like growth factor binding proteins (IGFBPs) are important regulatory factors of bone metabolism. However, the association between IGFBPs and osteoporosis remains a subject of contention in observational studies. We conducted a 2-sample Mendelian randomization (MR) study to assess the causal relationship between IGFBP 1-7 and osteoporosis using publicly available genome-wide association study summary statistics. The IGFBP 1-7 datasets were derived from German cohort studies and were selected at the genome-wide significance level (P < 5 × 10-6). The osteoporosis dataset was obtained from the UK Biobank study and included 484,598 individuals of European ancestry. Inverse variance weighting (IVW) was used as the primary MR method to investigate the causal relationship between exposure and outcome. To make the conclusions more robust and reliable, we used Cochran Q statistics, MR-Egger regression, and leave-one-out analysis as sensitivity analyses. Based on the IVW results, we identified a causal relationship between IGFBP-2 and osteoporosis, in which IGFBP-2 prevented the development of osteoporosis (IVW, P = .006; odds ratio = 0.998; β = -0.0022; 95% confidence interval: 0.996-0.999). However, the study did not show a significant causal relationship between the remaining 6 IGFBPs and osteoporosis (P > .05). In addition, the sensitivity analyses confirmed the findings in our study were robust. This MR study suggests a potential protective role of IGFBP-2 against osteoporosis and that it may serve as a biomarker or therapeutic target, although further research is needed.