Osteoarthritis in cynomolgus macaques: A primate model of naturally occurring disease

Abstract

The objective of the present study was to determine if naturally occurring osteoarthritis of the knee joints that is similar to the condition in humans develops in cynomolgus macaques. Knee joints from 58 young adult (mean age, 7.4 years) female cynomolgus macaques were studied with x-ray densitometry, high-detail radiography, and histology. The animals studied were subjects in a triad designed to examine the effects of the administration of sex steroids on atherosclerosis; except for a control group, the monkeys had been either ovariectomized or treated with sex steroids for 2 years. Therefore, the data were analyzed to determine if these treatments, both of which can influence bone density, affected the severity of osteoarthritis. There was a high prevalence of osteoarthritic lesions, morphologically similar to those seen in humans. Bone changes were more common and severe than cartilage changes and morphologically appeared to precede the cartilage changes. Treatment with testosterone resulted in increased body weight, body mass index, and bone mineral content in the femur and tibia but did not affect the severity of osteoarthritis. These data indicate that naturally occurring osteoarthritis developed in the knee joints of cynomolgus macaques; these animals may be a useful model for the study of osteoarthritis in humans.

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

“…Most importantly, subchondral bone remodelling in OA progresses from increased bone resorption early on to bone accretion, resulting in sclerosis of this tissue. In a primate model of spontaneous OA, increased osteoid volume is often more severe than cartilage changes [5]. Moreover, in this animal model, the severity of cartilage fibrillation and loss generally exceeds bone changes only in advanced OA.…”

Altered mineralization of human osteoarthritic osteoblasts is attributable to abnormal type I collagen production

“…It is now clear, from both animal models and human studies, that bone is altered in OA, even at sites not involved in mechanical loading, therefore limiting the impact of this aspect on disease onset (34)(35)(36)(37). Moreover, the idea that bone mineral density is increased in patients with OA compared with age-matched individuals, protecting them from osteoporosis and/or fractures, has to be reviewed with current findings that OA bone tissue is sclerotic mainly due to an abundant osteoid matrix that fails to mineralize normally in vivo (2,6,38,39).…”

Osteoarthritis: rationale for a new paradigm shift involving transforming growth factor-β1

“…Indeed, increased subchondral bone activity in OA, as judged by enhanced uptake of technetium labelled diphosphonate, predicts cartilage loss, and cartilage lesions do not progress without signi icant subchondral activity 16 . Alterations of the bony bed precede cartilage changes in the Macacafascicularis primate model of OA 17,18 and in the Dunkin-Hartley guinea pig model 15 . This is associated with intensi ied remodelling of the subchondral bone and increased bone stiffness 19 , which results in the bone no longer being an effective shock absorber 20,21 .…”