Osteoporosis and Osteoarthritis: A Bidirectional Mendelian Randomization Study

Yuan, Qing; Chen, S.; Han, M.; Fan, Tianxiang; Zeng, Muhui; Ruan, Guangfeng; Cao, Peihua; Zhang, Y.; Zhu, Zhaohua; Ding, Chao Feng

doi:10.1016/j.joca.2022.02.447

Cited by 2 publications

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“…To be a valuable tool for causal inference in MR studies, genetic variation must satisfy three fundamental criteria: Assumption 1, genetic variation as an instrumental variable must be genuinely associated with exposure (sarcopenia phenotypes); assumption 2, exposure-outcome confounders have no effect on genetic variation; and assumption 3, genetic variation affects outcome through exposure (sarcopenia phenotypes) only, independent of other pathways. Previous studies have shown that KOA and HOA can be affected by obesity [21], insomnia [22], sedentary behavior [23], and bone mineral density [24]. To exclude the potential influence of these factors, this study used MVMR analysis to determine the causal associations of sarcopenia phenotypes with KOA and HOA independent of body mass index (BMI), insomnia, TV watching time, and femoral-neck bone mineral density (FN-BMD).…”

Section: Methodsmentioning

confidence: 99%

Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study

Jin,

Wang,

Jin

et al. 2024

BMC Geriatr

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Background Recent genetic evidence supports a causal role for sarcopenia in osteoarthritis, which may be mediated by the occurrence of obesity or changes in circulating inflammatory protein levels. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between sarcopenia, obesity, circulating inflammatory protein levels, and osteoarthritis. Methods In this study, we used Mendelian randomization analyses to explore the causal relationship between sarcopenia phenotypes (Appendicular lean mass [ALM], Low hand-grip strength [LHG], and usual walking pace [UWP]) and osteoarthritis (Knee osteoarthritis [KOA], and Hip osteoarthritis [HOA]). Univariable Mendelian randomization (UVMR) analyses were performed using the inverse variance weighted (IVW) method, MR-Egger, weighted median method, simple mode, and weighted mode, with the IVW method being the primary analytical technique. Subsequently, the independent causal effects of sarcopenia phenotype on osteoarthritis were investigated using multivariate Mendelian randomization (MVMR) analysis. To further explore the mechanisms involved, obesity and circulating inflammatory proteins were introduced as the mediator variables, and a two-step Mendelian randomization analysis was used to explore the mediating effects of obesity and circulating inflammatory proteins between ALM and KOA as well as the mediating proportions. Results UVMR analysis showed a causal relationship between ALM, LHG, UWP and KOA [(OR = 1.151, 95% CI: 1.087–1.218, P = 1.19 × 10–6, PFDR = 7.14 × 10–6) (OR = 1.215, 95% CI: 1.004–1.470; P = 0.046, PFDR = 0.055) (OR = 0.503, 95% CI: 0.292–0.867; P = 0.013, PFDR = 0.027)], and a causal relationship between ALM, UWP and HOA [(OR = 1.181, 95% CI: 1.103–1.265, P = 2.05 × 10–6, PFDR = 6.15 × 10–6) (OR = 0.438, 95% CI: 0.226–0.849, P = 0.014, PFDR = 0.022)]. In the MVMR analyses adjusting for confounders (body mass index, insomnia, sedentary behavior, and bone density), causal relationships were observed between ALM, LHG, UWP and KOA [(ALM: OR = 1.323, 95%CI: 1.224- 1.431, P = 2.07 × 10–12), (LHG: OR = 1.161, 95%CI: 1.044- 1.292, P = 0.006), (UWP: OR = 0.511, 95%CI: 0.290- 0.899, P = 0.020)], and between ALM and HOA (ALM: OR = 1.245, 95%CI: 1.149- 1.348, P = 7.65 × 10–8). In a two-step MR analysis, obesity was identified to play a potential mediating role in ALM and KOA (proportion mediated: 5.9%). Conclusions The results of this study suggest that decreased appendicular lean mass, grip strength, and walking speed increase the risk of KOA and decreased appendicular lean mass increases the risk of HOA in patients with sarcopenia in a European population. Obesity plays a mediator role in the occurrence of KOA due to appendicular lean body mass reduction.

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Section: Methodsmentioning

confidence: 99%

Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study

Jin,

Wang,

Jin

et al. 2024

BMC Geriatr

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“…A review of published Mendelian randomised studies reveals a negative causal association between sleep duration in sleep behaviour and the risk of developing osteoarthritis of the knee; osteoporosis may be associated with an increased risk of osteoarthritis; and there is a causal association between elevated levels of LDL cholesterol and reduced heel bone density [24][25][26]. In addition, a study based on the NHANES database showed a signi cant positive correlation between the triglyceride glucose index steady-state model assessment and its associated indices and BMD [27]; therefore, this paper uses two-sample bidirectional multivariate mediated Mendelian randomisation to elucidate whether there is a causal relationship between different sleep behaviours and BMD at different sites as well as to discuss whether there is a positive correlation between LDL and triglyceride potential mediating role between sleep behaviour and BMD.…”

Section: Introductionmentioning

confidence: 99%

A causal relationship between sleep behaviour and osteoporosis: a two-sample reverse-mediated Mendelian randomisation study

Wang,

Li,

Liu

2024

Preprint

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Background In recent years, there have been more and more clinical observational studies on sleep behaviour and osteoporosis, but the causal relationship between sleep behaviour and osteoporosis at the genetic level, and whether there are mediating factors between the two is still unclear. Methods From the published GWAS data, seven sleep behaviours were selected as exposure factors: insomnia, sleep time, getting up in the morning, napping during the day, sleep type (early/late rise), narcolepsy and snoring. Bone mineral density of heel (H-BMD), forearm (FA-BMD), lumbar vertebra (LS-BMD) and femoral neck (FN-BMD) were the outcome factors. The causal relationship between low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) was analyzed through Mendelian randomization. Results The results of a two-sample Mendelian randomization study showed that snoring was positively correlated with lumbar bone density (OR = 1.555, 95%CI: 1.189–2.032, P = 0.001). The results of reverse Mendelian randomization showed that lumbar bone density was not the cause of snoring (P = 0.466). Mediating Mendelian randomization studies showed that both LDL cholesterol and triglycerides had mediating effects on sleep behaviour and bone density (OR = 0.92, 95%CI: 0.87–0.98, P = 5.56e-3) (OR = 1.17, 95%CI: 1.09–01.26, P = 3.72e-5). Conclusions Our study shows that snoring is a factor affecting lumbar bone density, and low-density lipoprotein cholesterol and triglyceride play an intermediary role in it. Therefore, correcting snoring and controlling low-density lipoprotein cholesterol and triglyceride index should be included in the clinical regimen for preventing and treating bone mineral density decline.

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Osteoporosis and Osteoarthritis: A Bidirectional Mendelian Randomization Study

Cited by 2 publications

References 0 publications

Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study

Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study

A causal relationship between sleep behaviour and osteoporosis: a two-sample reverse-mediated Mendelian randomisation study

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