MaryFran Sowers

Osteoarthritis is the most common form of arthritis, affecting millions of people in the United States. It is a complex disease whose etiology bridges biomechanics and biochemistry. Evidence is growing for the role of systemic factors (such as genetics, dietary intake, estrogen use, and bone density) and of local biomechanical factors (such as muscle weakness, obesity, and joint laxity). These risk factors are particularly important in weight-bearing joints, and modifying them may present opportunities for prevention of osteoarthritis-related pain and disability. Major advances in management to reduce pain and disability are yielding a panoply of available treatments ranging from nutriceuticals to chondrocyte transplantation, new oral anti-inflammatory medications, and health education. This article is part 1 of a two-part summary of a National Institutes of Health conference. The conference brought together experts on osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. Part 1 focuses on a new understanding of what osteoarthritis is and on risk factors that predispose to disease occurrence. It concludes with a discussion of the impact of osteoarthritis on disability.

The objective of this study was to describe the time of onset and offset of bone mineral density (BMD) loss relative to the date of the final menstrual period (FMP); the rate and amount of BMD decline during the 5 years before and the 5 years after the FMP; and the independent associations between age at FMP, body mass index (BMI), and race/ethnicity with rates of BMD loss during this time interval. The sample included 242 African American, 384 white, 117 Chinese, and 119 Japanese women, pre- or early perimenopausal at baseline, who had experienced their FMP and for whom an FMP date could be determined. Loess-smoothed curves showed that BMD loss began 1 year before the FMP and decelerated (but did not cease) 2 years after the FMP, at both the lumbar spine (LS) and femoral neck (FN) sites. Piecewise, linear, mixed-effects regression models demonstrated that during the 10-year observation period, at each bone site, the rates and cumulative amounts of bone loss were greatest from 1 year before through 2 years after the FMP, termed the transmenopause. Postmenopausal loss rates, those occurring between 2 and 5 years after the FMP, were less than those observed during transmenopause. Cumulative, 10-year LS BMD loss was 10.6%; 7.38% was lost during the transmenopause. Cumulative FN loss was 9.1%; 5.8% was lost during the transmenopause. Greater BMI and African American heritage were related to slower loss rates, whereas the opposite was true of Japanese and Chinese ancestry.

The Tecumseh Community Health Study provides an opportunity to investigate the role of obesity in the etiology of osteoarthritis. This longitudinal study, conducted in Tecumseh, Michigan, began in 1962 with baseline examinations of clinical, biochemical, and radiologic characteristics. A 1985 reexamination of the cohort characterized osteoarthritis status in 1,276 participants, 588 males and 688 females, who were aged 50-74 years at this follow-up. Baseline obesity, as measured by an index of relative weight, was found to be significantly associated with the 23-year incidence of osteoarthritis of the hands among subjects disease free at baseline. Greater baseline relative weight was also associated with greater subsequent severity of osteoarthritis of the hands. The difference between baseline and follow-up weight values was not significantly associated with the incidence of osteoarthritis of the hands. Furthermore, there was no evidence that development of osteoarthritis subsequently led to increased incidence of obesity.

Osteoarthritis (OA) appears to be a mechanically driven but chemically mediated disease process in which there is attempted (or aberrant) repair. Well established risk factors for OA include aging, obesity, gender, and, in selected subgroups, congenital anomalies. This review addresses less well established risk factors for OA that can impact joints through their effect on systemic metabolism rather than their contribution to local joint geometry and structure. These systemic risk factors include obesity; bone and bone density; nutrients, particularly those that function as antioxidants; and genetic factors. There is great opportunity for new prevention and intervention strategies as we expand our understanding of the role of these systemic risk factors.

Using 1990-1995 data, the authors examined the influence of post-challenge maternal glucose concentration on pregnancy outcome in 1,157 nondiabetic US gravidas. After control for potential confounding variables and comparing gravidas with lower glucose concentrations (<99 mg/dl) with the others, they found that mean birth weight increased by 50 g and 200 g with glucose concentrations of 99-130 mg/dl and >130 mg/dl, respectively. Increased maternal glucose concentration also was associated with an increased risk of large-for-gestation fetuses (p for trend < 0.001) and a decreased risk of fetal growth restriction (p for trend < 0.05). The association between glucose and gestation was inverse and significantly shortened when glucose concentrations were higher. Maternal complications increased twofold or more with high glucose concentrations and included cesarean section and clinical chorioamnionitis. Chorioamnionitis in combination with high maternal glucose concentration increased the risk of very preterm delivery almost 12-fold. These observations extend Pedersen's hypothesis-that high concentrations of maternal glucose give rise to increased nutrient transfer to the fetus and increase fetal growth, beyond the model of maternal diabetes (Acta Endocrinol 1954;16:330-42). They raise the question of whether higher, but seemingly normal maternal glucose concentration predisposes to or is a marker for placental inflammation and infection.