Osteoarthritis (OA) is the most common chronic degenerative joint disease which causes substantial joint pain, deformity and loss of activities of daily living. Currently, there are over 500 million OA cases worldwide, and there is an urgent need to identify biomarkers for early detection, and monitoring disease progression in patients without obvious radiographic damage to the joint. We have used regression modelling to describe the association of 19 of the currently available biomarkers (predictors) with key radiographic and clinical features of OA (outcomes) in one of the largest and best characterised OA cohort (NIH Osteoarthritis Initiative). We demonstrate that of the 19 currently available biomarkers only 4 (serum Coll2-1 NO2, CS846, COMP and urinary CTXII) were consistently associated with established radiographic and/or clinical features of OA. These biomarkers are independent of one another and provide additional predictive power over, and above established predictors of OA such as age, gender, BMI and race. We also show that that urinary CTXII had the strongest and consistent associations with clinical symptoms of OA as well as radiographic evidence of joint damage. Accordingly, urinary CTXII may aid in early diagnosis of OA in symptomatic patients without radiographic evidence of OA.

Osteoarthritis (OA) and osteoporosis (OP) are historically considered to be inversely correlated but there may be an overlap between the pathophysiology of the two diseases. This study aimed to investigate the subchondral bone microarchitecture and matrix mineralization, and the association between them in OA and OP in relation to the degree of cartilage degeneration. Fifty-six osteochondral plugs were collected from 16 OA femoral heads. They were graded on a regional basis according to the stages of cartilage degeneration, as evaluated by a new macroscopic and a modified microscopic grading system. Twenty-one plugs were collected from seven femoral heads with OP. Plugs were scanned by microcomputed tomography and the microarchitectural and mineral properties were obtained for both subchondral plate and trabecular bone. Microarchitecture and material and apparent densities of subchondral bone in OP were similar to regions with early cartilage degeneration but different from regions with advanced cartilage degradation in OA femoral heads. Subchondral trabecular bone was more mineralized than subchondral plate in both OP and OA, and this compartmental difference varied by severity of cartilage degradation. Furthermore, the relationship among trabecular bone volume fraction, tissue mineral density, and apparent bone density was similar in OP and different stages of OA. Subchondral bone microarchitecture and mineral properties in OP are different from OA in a regionalized manner in relation to stages of cartilage degeneration. Both regional and compartmental differences at structural, material, and cellular levels need to be studied to understand the transition of OA subchondral bone from being osteoporotic to sclerotic.

Aim: To identify prognostic biomarker(s) for knee osteoarthritis (OA) in the Osteoarthritis Initiative (OAI) cohort. Methods: Multilevel regression was used to determine the association between baseline biomarkers and change in biomarkers from baseline to 24 months with clinical and radiographic OA progression over 48 months of follow-up. Results: Higher values of baseline urinary CTXII were consistently associated with an increased risk of OA disease progression outcomes: Kellgren & Lawrence grade (odds ratio [OR]: 1.15, 95% CI: 1.03–1.28); medial joint space narrowing (OR: 1.06, 95% CI: 1.02–1.10); lateral osteophytes (OR: 1.05, 95% CI: 1.01–1.10); joint space width (regression coefficient: -0.005, 95% CI: -0.008–0.001); and Western Ontario and McMaster Universities Arthritis Index pain scores (OR: 1.02, 95% CI: 1.01–1.04). Changes in serum PIIANP and serum COMP over 24 months were associated with clinical disease progression. Conclusion: Urinary CTXII showed stronger associations with radiographic OA and appears to be a reliable prognostic marker, while changes in other biomarkers were found in early symptomatic OA, supporting the phasic nature of OA.