New developments in osteoarthritis. Sex differences in magnetic resonance imaging-based biomarkers and in those of joint metabolism

Sex differences have been noted in the prevalence, incidence, and severity of osteoarthritis (OA) for many years [1-3]. The incidence of knee, hip, and hand OA is higher in women than men and in women increases dramatically around the time of menopause [3,4], prompting many investigations into the roles of estrogen and other hormones as possible explanatory factors. Results of clinical and epidemiologic studies have been conflicting [5-7], with some showing a protective effect for estrogen or hormone replacement therapy (HRT) on radiographic knee and hip OA [8,9] or progression to joint replacement [10] but no effect on joint symptoms [11]. Differences in study results can be ascribed to differences in (a) study populations and study designs; (b) distribution of, or confounding by, other risk factors such as age, race/ethnicity, body mass index (BMI), and smoking; and (c) joints affected by OA and definitions used to define OA [3] and statistical methodology. A recent systematic review of 17 studies illustrates this point. There was no clear association between sex hormones and hand, knee, or hip OA in women, but study heterogeneity precluded combining them into a single analysis [6]. For example, radiographic OA can be defined by overall radiographic scoring, such as the Kellgren-Lawrence system (grades 0 to 4) [12], or by individual radiographic features, such as osteophytes or joint space narrowing [13]. Other definitions may incorporate joint-specific symptoms with or without accompanying radiographic OA. With these multiple methods of examining sex differences in OA, it is no wonder that the issue is far from settled.One way to examine the basis of sex differences in OA is to examine sex differences in the individual components of the joint through magnetic resonance imaging (MRI) and joint metabolism biomarkers. Structural features of OA can be examined using overall grading [14] or, more commonly, by individual features, such as cartilage thickness or volume,