Subchondral Pathology Independently Associated With Knee Osteoarthritis

An association has been identified between subchondral pathology and knee osteoarthritis (OA), according to a study recently published in Arthritis & Rheumatology. This association was independent of synovitis or chondropathy. However, bone pain associated with knee OA may be linked with osteoclast density and elevated osteochondral channel nerve growth factor expression.

This study included 62 participants, half of whom had symptomatic chondropathy and had donated tibial plateau during total knee replacement surgery. The other half had chondropathy without symptoms or knee pain, but died due to an unrelated cause. The study researchers compared the 2 groups in terms of OA histopathology, subchondral osteoclasts positive for tartrate-resistant acid phosphatase, synovitis, and CD68 and nerve growth factor immunoreactivity. To measure nerve growth factor expression, the percentage of osteochondral channels presenting with nerve growth factor-immunoreactive cells were calculated. Chi-square or Mann-Whitney U tests were used to compare variables, while adjustments for synovitis and age were performed using logistic regression.

The 2 groups showed similar subchondral bone densities, Mankin scores, subchondral plate area, and percentages of fibrovascular marrow replacement. The symptomatic group had higher synovitis scores than the asymptomatic group, which persisted after age adjustments (adjusted odds ratio 2.75; 95% CI, 1.35-6.20; P =.01). Symptomatic participants also showed higher subchondral bone osteoclast densities (P =.02; after adjustment for age and synovitis score, P =.04) and osteochondral channel nerve growth factor (P <.01; after adjustment, P =.01).

Osteoclasts, chondrocytes, and subchondral mononuclear cells displayed nerve growth factor-like immunoreactivity. Synovitis score did not correlate significantly with osteochondral pathology. Around 28% of the allocation to either group was explained by combined subchondral osteoclast density, osteochondral channel nerve growth factor expression, and synovitis score.

Limitations to this study included potential unreported knee pain in the asymptomatic group, age-based differences between the 2 groups, and limited scope of pain mechanisms in the symptomatic group.

The study researchers conclude that “increased [nerve growth factor] expression appears as a key [feature] associated with subchondral bone pain in knee OA, and could contribute to the previously observed association between osteoclasts and OA pain. Our data support a heterogeneous model of OA pain, with discrete contributions from different compartments in the joint. Different treatments could benefit pain from synovitis or from subchondral pathology, necessitating the development of biomarkers to help target treatments to those who will most benefit.”

Two authors report financial associations with Pfizer.

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Reference

Aso K, Shahtaheri SM, Hill R, Wilson D, McWilliams DF, Walsh DA. Associations of symptomatic knee OA with histopathologic features in subchondral bone [published online January 21, 2019]. Arthritis Rheumatol. doi:10.1002/art.40820