Supervisors: professor Agu Tamm (TÜ sisekliinik) ja professor Kalervo Väänänen (Turu Ülikool, Soome)
Opponent: professor Ingemar Petersson, MD, PhD (Lundi Ülikool, Rootsi)
The globally increasing prevalence of osteoarthritis (OA) calls for more detailed knowledge of the early phases of the disease. OA has long been considered to be a "wear and tear" disease of ageing articular cartilage. Nowadays, OA is viewed as a metabolically active process that may arise from any joint tissue: cartilage, bone or soft tissues. It progresses through molecular and radiographic stages. The investigation of pre-radio¬graphic phases is dependent on serum and/or urinary biomarkers originating from articular tissues as new diagnostic and prognostic tools for early OA management. So far, the systemic evaluation of biomarkers reflecting the synthesis and degradation of cartilage and bone has not been simultaneously addressed. The main objectives of the study were to determine: (i) the prevalence and six-year progression of radiographic knee OA in middle-aged subjects with chronic knee joint complaints, and (ii) the diagnostic and prognostic value of biomarkers for progressive radiographic knee OA. More than half of the middle-aged subjects with chronic knee complaints had early radiographic signs of knee OA. In the majority of cases, the six-year OA progression was based on osteophytosis. The radiographic course of knee OA was heterogeneous and non-continuous, with intermittent periods of progression and stabilization. The changes in biomarker values revealed a certain pattern of metabolic shifts in joint tissues in progressive knee OA. All three studied cartilage markers (COMP, CTx-II and PIIANP) had diagnostic value for progressive osteophytosis, and two of them (COMP and CTx-II) also had prognostic value for progressive osteophytosis and joint space narrowing. At the same time, three of the studied bone markers (PINP, OC and MidOC) had diagnostic value for progressive osteophytosis, and one of them, PINP, demonstrated a predictive value for extensive OA progression. Unexpectedly, the activation of bone metabolism seemed to dominate over that of cartilage. The novel bone marker urinary mid-fragments of osteocalcin (MidOC) turned out to be the strongest risk predictor for progressive osteophytosis. The present study proposed a possible sequence of metabolic events in joint tissues during early OA. We discovered the diagnostic and prognostic potential of several biomarkers for progressive OA.