Causal relationship of serum nutritional factors with osteoarthritis: a Mendelian randomization study

Abstract

Objectives OA is the most common form of arthritis worldwide and has a major impact on the quality of life among the older population. This study aimed at determining the potential causal effects of several serum nutritional factors on OA. Methods A total of seven serum nutritional factors were identified from genome-wide association studies. Summary statistics for OA were obtained from UK Biobank (194 153 for women and 166 988 for men) and a large genome-wide association studies meta-analysis based on the European population (455 221, 393 873 and 403 124 for overall, hip and knee OA, respectively). Two-sample Mendelian randomization approach was used to estimate the causal association between the selected nutritional factors and the risk of OA. Results The Mendelian randomization analyses suggested that serum calcium levels were inversely associated with overall OA (95% CI, 0.595, 0.850), hip OA (95% CI, 0.352, 0.799) and knee OA (95% CI, 0.461, 0.901). Serum retinol levels were also inversely associated with hip OA (95% CI, 0.257, 0.778). Moreover, sex-specific associations were observed between serum calcium levels (95% CI, 0.936, 0.998), iron levels (95% CI, 1.000, 1.012), selenium levels (95% CI, 0.923, 0.999) and OA in women. Conclusion In this study, an inverse causal association between serum calcium levels and OA was established. Serum retinol levels were inversely associated with hip OA. In addition, we provide evidence for the causal effect of serum calcium, iron and selenium on the risk of OA in women.

An Updated Mendelian Randomization Analysis of the Association Between Serum Calcium Levels and the Risk of Alzheimer’s Disease

“…The 14 serum calcium SNPs were identified by a GWAS using 61,079 individuals of European descent ( O’seaghdha et al, 2013 ). These 14 serum calcium SNPs, especially the 8 SNPs at the genome-wide significance threshold, have been widely used as the potential instrumental variables to evaluate the association of serum calcium with other human complex diseases or phenotypes ( Larsson et al, 2017 , 2019 ; Xu et al, 2017 ; Meng et al, 2020 ; Wang Y. et al, 2020 ; Qu et al, 2021 ; Sun et al, 2021 ; Young et al, 2021 ; Yuan et al, 2021 ). Detailed information about these 14 SNPs is presented in Supplementary Table 1 .…”

Health Effects of Calcium: Evidence From Mendelian Randomization Studies

“…As for other musculoskeletal diseases, a causal association between higher genetically predicted serum calcium levels and lower risk of osteoarthrosis (Odds ratio (OR): 0.67; P = 0.0044) was reported in a phenome-wide MR analysis 34 . A two-sample MR study found that serum calcium levels were also inversely associated with the risk of overall osteoarthritis (OR: 0.712; P = 1.84 × 10 −4 ), although this significant association was only detected in women (OR: 0.967; P = 0.038) 35 . Similar findings were found in a recent MR where a negative causal effect of higher serum calcium on localized osteoarthritis was reported (OR: 0.87, P = 0.021) 36 .…”

“…Interestingly, this association was not supported by a meta-analysis published in 2015 where the authors used data from 7 RCTs (n= 51,111) and found no increased risk in calcium-treated patients for myocardial infarction in elderly women 44 . A large RCT involving women aged 50-79 years (n= 35,983) found no association between calcium plus vitamin D supplements and risk of heart failure 45 .…”

Causal Relationship Between Parathyroid Hormone and the Risk of Osteoarthritis: A Mendelian Randomization Study

“…Another MR analyses conducted by Qu et al (2020) showed that serum calcium levels were inversely associated with overall OA [OR 0.712, 95% CI (0.595, 0.850)]. According to a 48-month follow-up study, frequent milk consumption may be associated with reduced OA progression in women partially through elevated dietary calcium intake ( Lu et al, 2014 ).…”