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

Abstract

Objective We aimed to characterize severity and occurrence of knee osteoarthritis (OA), and effects of age, sex, body weight, and reproductive status on population-level normal variation in this condition in the baboon, a natural model of human knee OA. Methods 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, weight, 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). Results 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. Conclusions 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.

Osteoarthritic changes in vervet monkey knees correlate with meniscus degradation and increased matrix metalloproteinase and cytokine secretion

“…CT scans demonstrated the typical pathology of osteoarthritis which was accompanied by cartilage and meniscus degeneration subsequently observed during examination of the knee joint tissues. These changes were similar to human osteoarthritis, and consistent with established reports of idiopathic and surgically induced osteoarthritis in non-human primates 2-5, 31 .…”

“…Age-related increases in knee osteoarthritis was identified in Rhesus macaques 10, 32, 33 and Cynomolgus macaques 6 and noted to be more severe in older baboons compared to younger baboons with osteoarthritis changes 31 . Knee arthritis and the development of osteophytes were found to increase with age in nonhuman primates 6, 8, 31, 32, 34 .…”

Animal Models of Osteoarthritis

“…Although experimental models of disease do exist, 85 a major advantage of these species is the development of naturally occurring OA in multiple joints that very closely mimics the onset and progression seen in aging humans. 23,24,55,86,120 Disease severity and age are closely correlated in this model, but the spectrum of disease across ages mimics that seen in humans, with some younger animals affected with moderate disease (particularly young males) and some elderly individuals spared entirely. 55,86 Although the joint biomechanics of nonhuman primates do differ from humans, they are more similar than those of strict quadrupeds.…”

“…100 Macroscopic grading of lesions is also widely reported, either alone or in combination with microscopic scoring, typically utilizing a modification of the Outerbridge classification system. 86 Zebrafish. Although zebrafish do not develop synovial joints as mammals do, they have been widely used as models to study skeletogenesis, and it is in this capacity that they have recently been proposed as a potential model for OA.…”

“…55,120 Additionally, similarities in reproductive physiology allow for the investigation of the effects of hormones/reproductive status on the development of OA. 16,55,86 However, despite these advantages as a model of OA, significant disadvantages related to cost, availability, ethical issues, and public perception do exist and generally preclude the widespread use of these species.…”