Reproductive status and sex show strong effects on knee OA in a baboon model

Abstract

We aimed to characterize severity and occurrence of knee osteoarthritis (OA), and effects of age, sex, body mass, and reproductive status on population-level normal variation in this condition in the baboon, a natural model of human knee OA. We visually inspected articular cartilage of distal right femora of 464 baboons (309 females, 155 males) and assigned an OA severity score (comparable to a modified Outerbridge score) from 1 = unaffected to 4 = advanced OA (eburnation). Presence/absence of osteophytes was recorded. We tested for significant effects of age, sex, body mass, and, in females, reproductive status (pre-, peri-, or post-menopausal) on OA. When appropriate, analyses were repeated on an age-matched subset (153 of each sex). Knee OA was more frequent and severe in older animals (P < 0.0001), but significant age variation was apparent in each severity grade. Sex differences within the younger and older age groups suggest that males develop knee OA earlier, but females progress more quickly to advanced disease. There is a strong relationship between reproductive status and OA severity grade in females (P = 0.0005) with more severe OA in peri- and post-menopausal female baboons, as in humans. Idiopathic knee OA is common in adult baboons. Occurrence and severity are influenced strongly by reproductive status in females, and by sex with regard to patterns of disease progression - providing an animal model to investigate sex-specific variation in OA susceptibility in which the environmental heterogeneity inherent in human populations is vastly reduced.