Elsevier

Joint Bone Spine

Volume 70, Issue 4, August 2003, Pages 257-262
Joint Bone Spine

Review
Estrogens, cartilage, and osteoarthritis

https://doi.org/10.1016/S1297-319X(03)00067-8Get rights and content

Abstract

A role for estrogens in osteoarthritis is consistent with the larger increases in women than in men in the incidence and prevalence of hip, knee, and finger osteoarthritis after 50 years of age. Furthermore, hormone replacement therapy for the menopause seems to be associated with a decrease in the prevalence of symptoms and radiological alterations related to hip and knee osteoarthritis. The two estrogen receptors alpha and beta (ERα and Erβ) have been identified in normal and osteoarthritic cartilage, indicating that cartilage can respond to estrogens. Finally, in vivo experiments in animals and in vitro studies have shed light on the mechanisms by which estrogens may influence chondrocyte metabolism.

Introduction

That estrogens may play a role in osteoarthritis was first suggested over three-quarters of a century ago, by Cecil and Archer [1], who described “arthritis of the menopause” as rapid development of hand and knee osteoarthritis coinciding with cessation of menses. Epidemiological observations provided support for a link between estrogen deprivation and osteoarthritis development by showing that the age-related increases in the incidence and prevalence of hip, knee, and finger osteoarthritis were larger in men than in women before 50 years of age but subsequently became larger in women. This gender difference widened with advancing age [2], [3], [4], [5]. Furthermore, hip and knee osteoarthritis were more likely to be progressive in women than in men. Finally, hip and knee osteoarthritis were more often symptomatic in postmenopausal women than in same-age men [4], [6].

Many studies are now available, although their results are often conflicting. However, studies of the prevalence and incidence of osteoarthritis in postmenopausal women with and without hormone replacement therapy (HRT) have provided strong support for a beneficial effect of estrogens in osteoarthritis. Subsequently, the identification of the two estrogen receptors alpha and beta (ERα and Erβ) in chondrocytes provided further evidence that the cartilage is sensitive to estrogens [7]. Finally, several in vitro studies and in vivo animal experiments confirmed that chondrocytes respond to estrogens and also provided insight into the mechanisms by which estrogens may influence chondrocyte metabolism.

Section snippets

Osteoarthritis, menopause, and hysterectomy

No association has been found between the duration of estrogen exposure and osteoarthritis: age at menarche and age at menopause are not correlated with the prevalence of osteoarthritis [8], [9], [10]. In two studies of gynecological risk factors for osteoarthritis, Spector et al. [11] found a significant association with hysterectomy. The first study found that hysterectomy was significantly more prevalent among cases with osteoarthritis than among controls without the disease (odds ratio

Estrogen receptors and cartilage

There is general agreement that estrogens cannot act on their target tissues unless they bind to a specific protein, the estrogen receptor [33], of which two isoforms have been cloned, alpha (ERα) and beta (ERβ). ERα was isolated in 1986 [34], [35] and ERβ 10 years later from a rat prostate cDNA library [36], [37], [38], [39]. The identification of this second receptor led to a radical change in concepts about the mechanism of action of estrogens. Estrogen receptors are nuclear proteins

Effects of estrogens in vivo in animals and in vitro

No genes directly transactivated by 17β estradiol in chondrocytes have been identified to date. However, several studies have found incontrovertible evidence that estrogens have effects on chondrocytes both in vivo and in vitro.

In vivo in animals, intraarticular estrogen injections had dose-dependent effects: supraphysiological dosages of 17β estradiol induced histological osteoarthritis, whereas lower dosages had no effect [57]. A study of joint cartilage from ewes showed decreased resistance

Conclusions

Epidemiological studies of a potential role for estrogens in osteoarthritis showed two very different findings. First, estrogen deprivation at the menopause seems to be associated with increases in the frequency of knee, hip, and finger osteoarthritis and in the severity of hip osteoarthritis. Second, HRT for the menopause may decrease the incidence and progression of hip and knee osteoarthritis.

Differences across studies in evaluation criteria (symptomatic vs. structural osteoarthritis,

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