Dunkin Hartley guinea pigs develop spontaneous, age-related osteoarthr
itis (OA) of the knee and other joints, Histologic changes are observe
d beginning at 3 months of age, Disease severity increases with age, a
nd at 18 months moderate to severe OA is observed. A study was underta
ken to assess the morphologic and biochemical changes of 22-month-old
animals, and to compare them with values in a-month-old guinea pigs. B
iochemical indices characteristic of OA, from tibial cartilage, indica
ted an increase in proteoglycan content from 233 +/- 2 mu g/mg (mean /- SEM) at 2 months of age to 365 +/- 6 mu g/mg at 22 months. Collagen
concentration in cartilage decreased from 364 +/- 2 mu g/mg at 2 mont
hs to 223 +/- 3 mu g/mg at 22 months. Proteoglycan fragments found in
synovial fluid measured 4.6 +/- 1 mu g/ml at 2 months and increased to
37 +/- 2 mu g/ml at 22 months. Radiographic changes observed at 22 mo
nths included marginal osteophytes of the tibia and femur, sclerosis o
f the subchondral bone of the tibial plateau, femoral condyle cysts, a
nd calcification of the collateral ligaments, Histologic evaluation re
vealed severe OA, with a Mankin score of 10.7 +/- 0.5 in 22-month-old
animals. In contrast, 2-month-old animals had no histologic or radiogr
aphically detectable lesions. The results of the study reported here i
ndicate that the lesions observed in this model are similar to those o
f human OA. Spontaneous development of OA in guinea pigs is amenable t
o the study of the pathogenesis of OA and to the evaluation of potenti
al disease-modifying agents.