Background/Purpose: Osteoarthritis (OA) is the most common form of arthritic disease. It is characterized by pathological changes in both bone and cartilage turnover as well as structure in which subchondral bone remodeling is speculated to be both an initiator and driver of OA. The aim of the current study was to evaluate a biomarker of high localized bone resorption, a-CTX, previously used for bone metastasis. OA patients were characterized by; radiographic knee OA, severity, progression and localized knee bone turnover as assessed by bone scintigraphy, a dynamic and sensitive indicator of symptomatic knee OA. 

Methods: A total of 149 participants (111 women, 38 men) were included who met ACR criteria for symptomatic OA and had the presence of Kellgren Lawrence (K/L) grade 1-4 radiographic OA in at least one knee. Late-phase bone scan images of both knees were obtained 2 hours after administration of ^99mTc-MDP. The intensity of uptake was scored semi-quantitatively and summed for each joint site. Radiographic knee OA severity, based on the summed scoring of osteophytes (OST) and joint space narrowing (JSN) was assessed using the standardized OARSI radiographic atlas. Progression status was determined by calculating the sum of the change score in either JSN or OST between baseline and the 3-year follow-up assessment. The concentrations of urinary a-CTX and CTX-II were determined by ELISA and normalized to creatinine concentration. 

Results: a-CTX was related to OST formation independent of the effects of age, gender, BMI, and HRT (p=0.009). a-CTX did not correlate with severity of knee OA based on OST and JSN, but did correlate with bone turnover assessed by intensity of ^99mTc-MDP uptake in the medial knee compartment. Concentrations of urinary CTX-II were strongly associated with knee OA severity based on osteophyte, intensity of total knee ^99mTc-MDP uptake, and joint space narrowing. 

Conclusion: a-CTX was associated with subchondral bone turnover, and osteophyte formation, both central features of the pathogenesis of OA. CTX-II was correlated to JSN, and burden of disease as previously reported. The significant and strong association of a-CTX to bone turnover in the subchondral region suggests that this marker may be a non-invasive surrogate for active bone turnover in knee OA. Such markers may assist in the identification patients whom may benefit from strong anti-resorptives which inhibit bone and subchondral bone turnover.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/subchondral-bone-turnover-and-osteophyte-formation-are-key-aspects-in-the-progression-of-osteoarthritis-and-may-be-assessed-and-predicted-by-a-ctx/