Estrogen replacement therapy and worsening of radiographic knee osteoarthritis: The Framingham study

Abstract

Objective. To examine whether estrogen replacement therapy (ERT) prevents worsening of radiographic knee osteoarthritis (OA) in elderly women.Methods. A total of 551 women ages 63-91 years (mean age 71) in the Framingham Study were followed up from biennial examination 18 (1983)(1984)(1985) to examination 22 (1992)(1993). Data on postmenopausal ERT were obtained every 2 years. Subjects were classified into 3 groups according to their estrogen use at biennial examination 18: never users (n = 349), past users (n = 162), and current users (n = 40). Women received anteroposterior weight-bearing knee radiographs at examinations 18 and 22. Using the Kellgren and Lawrence criteria, global radiographic knee OL4 was assessed, (grade range 0-4) and individual radiographic features, such as osteophytes and joint space narrowing, were scored from 0 to 3. Worsening was defined as either development of radiographic 0 . 4 that was not present at baseline (incident OA) or progression of baseline radiographic OA by 2 1 Kellgren and Lawrence grade (progressive OA). Potential confounding factors included age, body mass index, weight change, smoking, knee injury, physical activity level, and bone mineral density at the femoral neck.Results. During 8 years of followup, 17.4% of knee radiographic scores worsened by I grade and 5.8% by 2 or 3 grades among never users of ERT. Among current estrogen users, only 11.7% of knee radiographic scores worsened by 1 grade and none worsened by more than 1 grade. After adjusting for age and other potential confounding factors, the relative risk of incident radiographic knee OA in comparison with never users of estrogen was 0.8 (95% confidence interval [95% CI] 0.5-1.4) in past users and 0.4 (95% CI 0.1-3.0) in current users. Current use of estrogen also showed a trend toward decreased risk of progressive knee 0.4 compared with never use (odds ratio [OR] 0.5, 95% CI 0.1-2.9). When both incident and progressive radiographic knee OA cases were combined, current ERT use had a 60% decreased risk compared with never use (OR Conclusion. This is the first prospective cohort study to examine the effects of ERT on radiographic knee OA. The results indicate that current use of ERT had a moderate, but not statistically significant, protective effect against worsening of radiographic knee OA among elderly white women. These findings corroborate those of cross-sectional studies and point further to a potential benefit of female hormones in OA. 0.4, 95% CI 0.1-1.5).Descriptive epidemiologic studies have shown that the risk of osteoarthritis (OA) is comparable in men and women up to -50 years of age. After this age, however. both the incidence and prevalence of OA increase more rapidly in women than in men (1-5). Clinical studies also have described a "menopausal arthritis" that is characterized by development of rapidly progressive OA in multiple joints of the hand at the time of

Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes

“…Accordingly, estrogen deficiency occurring with menopause has been associated with an increased incidence and severity of OA in women [39]. Postmenopausal women taking estrogen replacement therapy exhibit a reduced risk of hip and knee OA, compared with those not taking it [40,41]. …”

Osteoarthritis associated with estrogen deficiency

“…Unlike observational clinical studies, some radiographic studies have suggested a protective effect of ERT on the radiographic detection of OA or its progression [111-115]. In a cross-sectional study, ERT significantly reduced the risk of radiographic hip OA, particularly in long-term users [111].…”

“…Similarly, an initial cross-sectional analysis of two of the largest studies found an inverse association between ERT use and radiological knee OA, suggesting that ERT may have a chondroprotective effect. However, a subsequent follow-up analysis failed to show significant ERT protection against either the development or progression of radiographic knee OA [112-115]. Additionally, contradictory results were described regarding the association between ERT and the requirement for arthroplasty [116].…”

Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management

“…Approximately 25% of women developed arthralgia within 3 weeks of initiation of leuprolide. Alternatively, estrogen-based therapy is associated with reduced incidence of radiologic knee osteoarthritis and decreased incidence of joint pain/swelling [70-72]. However, this effect has not been seen in all studies of estrogen therapy [73].…”