Sex Steroids and Osteoarthritis: A Mendelian Randomization Study

Abstract

ObjectiveSex steroids are thought to contribute to the pathogenesis of osteoarthritis (OA). This study investigated the causal role of sex steroids in site- and sex-specific OA and risk of joint replacement surgery using the Mendelian randomization (MR) method.MethodsInstrumental variables for estradiol, dehydroepiandrosterone sulfate, testosterone (T), and dihydrotestosterone (DHT) were selected. We used the inverse variance weighting (IVW) approach as the main MR method to estimate causal effects based on the summary-level data for OA and joint replacement surgery from genome-wide association studies (GWAS).ResultsA positive causal association was observed between serum T level and risks of hip OA (odds ratio [OR]=1.558, 95% confidence interval [CI]: 1.193–2.034; P=0.001) and hip replacement (OR=1.013, 95% CI: 1.008–1.018; P=2.15×10−8). Serum DHT level was also positively associated with the risk of hip replacement (OR=1.011, 95% CI: 1.006–1.015; P=4.03×10−7) and had potential causality with hip OA (OR=1.398, 95% CI: 1.054–1.855; P=0.020).ConclusionsSerum T and DHT levels may play causal roles in the development of hip OA and contribute to the risk of hip replacement, although the underlying mechanisms require further investigation.

Causal Association Between Tea Consumption and Bone Health: A Mendelian Randomization Study

“…The subgroup analysis indicated tea consumption reduced OP risk ( 38 ). In a study in Iran, bone mineral density at the lumbar spine and hip were measured, and it was found that habitual tea consumption was associated with better bone health in women but not in men ( 35 ).…”

“…Therefore, individual SN P could be assessed for their influence on causal associations. The PhenoScanner database (version 2.0) was examined for each SNP ( 30 ) to determine whether existing risk factors have previously been associated with any significant associations ( P < 5 × 10 –8 ): BMI ( 31 , 32 ), previous knee injury ( 32 ), gout ( 33 ), coffee intake ( 12 ) for knee OA; Hip dysplasia ( 34 ), Steroids use ( 35 ), coffee intake ( 11 ) for hip OA; hypertension ( 33 ), diabetes, smoking ( 36 ) for RA; Vitamin D intake, Steroids use, smoking for OP ( 37 ). To rule out potential pleiotropic effects, we evaluated the effect of removing these SNPs from the MR estimations.…”

Osteoarthritis: pathogenic signaling pathways and therapeutic targets

“… 6 , 57 , 58 Several studies showed that OA development could be triggered by the plunge in sex hormone levels in menopausal women. 59 , 60 Besides, compared to male OA patients, female patients were reported to have higher levels of joint inflammation and clinical pain, thinner articular cartilage, and severe physical joint mobilities. 57 , 60 , 61 The potential contributing factors for this gender difference in OA are not fully understood and need further attention in the OA research community.…”

Gender-Related Aspects in Osteoarthritis Development and Progression: A Review

“…The factors that might contribute to their susceptibility include thinner cartilage, tendency to varus malalignment, joint instability, and uneven mechanical loading. Furthermore, OA development can be triggered by the steep decline of sex hormone levels in the menopause [ 13 , 14 ]. Sex-related differences in the onset and progression of OA have been the subject of a number of studies, and there is increasing interest in this topic, with new data constantly brought to the attention of scientists [ 14 , 15 ].…”