Reproductive history and osteoarthritis in the Women’s Health Initiative

Wang, A; Zawadzki, Nadine K; Hedlin, Haley; LeBlanc, Erin S.; Budrys, Nicole M.; Horn, Linda Van; Gass, M.L.; Westphal, L.M.; Stefanick, Marcia L.

doi:10.1080/03009742.2020.1751271

Cited by 8 publications

(10 citation statements)

References 39 publications

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“…High BMI is known as a risk factor for OA, but it is unlikely that BMI would explain the casualty found here, as we adjusted our analyses for BMI, and our findings were consistently observed within subgroups of no BMI. However, the assumed relationship between the female hormonal aspects and OA was not clinically significant in another cohort study ( 29 ). Since hormonal reproductive factors are prone to bias due to interference from potential confounders which difficult to be excluded by traditional epidemiology, MR estimates reflect the causality at the genetic level.…”

Section: Discussionmentioning

confidence: 89%

Using genetic instruments to estimate the causal effect of hormonal reproductive factors on osteoarthritis

Wang

Wu²,

Li³

et al. 2022

Front. Public Health

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ObjectivesHormonal reproductive factors have been considered to play an important role in the etiology of osteoarthritis (OA). We performed Mendelian randomization (MR) to examine whether a causal effect existed between them.MethodsMR was performed by using publicly released genome-wide association study (GWAS) summary statistics to estimate the causal associations of three relevant exposures, including age at menarche (AAM), age at natural menopause (ANM) and age at first birth (AFB), with the risk of OA. We employed several MR methods, including inverse-variance weighted (IVW), MR-Egger regression, weighted median and weighted mode, to estimate the causality. We performed a sensitivity analysis by manually pruning pleiotropic variants associated with the known confounder body mass index (BMI).ResultsThe instrumental variables that achieved genome-wide significance, including 349 AAM single nucleotide polymorphisms (SNPs), 121 AAM SNPs, 54 ANM SNPs, and 10 AFB SNPs, were incorporated into the operation. IVW analysis indicated that each additional year in AFB was associated with a decreasing risk of hip and/or knee OA and overall OA (hip and/or knee OA: OR = 0.79, 95% CI: 0.64–0.93, P = 1.33 × 10−3; overall OA: OR = 0.80, 95% CI: 0.68–0.92, P = 1.80 × 10−4). In addition, our results suggested that AAM exerted a causal effect on knee OA in an unfavorable manner (OR = 0.86, 95% CI: 0.76–0.95, P = 1.58 × 10−3). After accounting for the effect of BMI, the causal effect association between AFB and hip and/or knee OA was also examined (IVW: OR = 0.78, 95% CI: 0.66–0.92, P = 3.22 × 10−3).ConclusionOur findings add a growing body of evidence surrounding the unfavorable effects of early AFB on OA risk, suggesting the essential for relevant health problem management in susceptible populations.

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Section: Discussionmentioning

confidence: 89%

Using genetic instruments to estimate the causal effect of hormonal reproductive factors on osteoarthritis

Wang

Wu²,

Li³

et al. 2022

Front. Public Health

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“…Many of the trials previously performed are now quite old. In two of the few recent papers, Wang and colleagues studied the association between self-reported OA and reproductive factors in the WHI Observational Study and Clinical Trial cohorts of 145,965 postmenopausal women, [19]. They observed relationships between, among others, OA and history of hysterectomy, history of unilateral oophorectomy, and evidence of a protective effect of current use of hormonal therapy while a recent paper from Korea [20] reported a study of 4766 CarƟlage:…”

Section: Exogenous Hrt and Oafriend Or Foe?mentioning

confidence: 99%

Osteoarthritis: The importance of hormonal status in midlife women

Dennison

2022

Maturitas

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“…While not currently defined as a separate form of OA, we would also hypothesize that OA arising in post-menopausal females should perhaps be considered a mechanistically unique form of the disease due to the loss of tissue regulation following decline in hormonal involvement. Before the age of 50, the incidence of knee and hip OA is ∼1:1 (F/M), while after age 50 (and the onset of menopause), the incidence is at a minimum >2:1(F/M) [ 37 ], and this is not apparently due to a number of reproductive factors [ 38 ]. However, it could also relate to bone shape which differs between males and females [ [39] , [40] ] and changes over time more in females [ 38 ].…”

Section: Is Oa One Disease or Many?mentioning

confidence: 99%

“…Before the age of 50, the incidence of knee and hip OA is ∼1:1 (F/M), while after age 50 (and the onset of menopause), the incidence is at a minimum >2:1(F/M) [ 37 ], and this is not apparently due to a number of reproductive factors [ 38 ]. However, it could also relate to bone shape which differs between males and females [ [39] , [40] ] and changes over time more in females [ 38 ]. While commonly categorized with other idiopathic cases of OA at present, the post-menopausal cases may represent a unique form of OA based on how it arises in this subset of females.…”

Section: Is Oa One Disease or Many?mentioning

confidence: 99%