Abstract

Osteoarthritis (OA) is the most common form of arthritis and the prevalence is increasing. The need for effective preventive and treatment measures are therefore urgent. OA is characterized by progressive degeneration of articular cartilage, synovitis and changes to the subchondral bone characterized by increased turnover, thinning of the trabecular structures, sclerosis of the subchondral plate, osteophytes and bone marrow lesions. Pain in OA is associated with synovitis and increased subchondral bone turnover. Based on these observations it has been suggested that drugs that either inhibit synovitis or bone turnover may have beneficial effects on already existing OA and/or be able to prevent the development of OA.

Several antiresorptive therapies are available for the treatment of osteoporosis. Bisphosphonates, strontium ranelate and calcitonin have been investigated in clinical studies for their effect on progression of OA.

The effects of bisphosphonates on OA have been investigated in two long-term prospective studies with effect on OA as primary endpoint. The BRISK study included 284 women with mild to moderate knee OA treated with risedronate (RIS) 15 mg daily for 12 months. Treatment with RIS resulted in improvement of the WOMAC index, particularly of physical function, and improvement in patient global assessment. Subsequently, a larger study, KOSTAR, was undertaken. 2483 patients with mild to moderate knee OA were included and randomized to different doses of RIS or placebo. Overall, no improvement in signs and symptoms of OA was observed and progression of OA was unaffected by treatment allocation. Serum levels of CTX-II were dose dependently decreased. Posthoc analyses revealed that more pronounced suppression of CTX-II was associated with less progression of the disease. A subgroup analysis of patients with progressive disease demonstrated that RIS preserves structural integrity of the subchondral bone.

The effect of strontium ranelate (SR) on OA has been investigated in the TROPOS study, a study designed to examine the effect of SR on fracture prevention. SR reduced serum levels of CTX-II, a marker of cartilage degradation with 15-20% and deterioration of spinal OA with 42%. Back pain was reduced but there was no effect on health-related quality of life.

Calcitonin has been demonstrated to reduce serum levels of CTX-II and improve functional disability despite no change in pain in patients with knee OA over 3 months.

In order to further investigate the potential of antiresorptive treatments in prevention or treatment of OA, future research should be focused on 1. developing clinical relevant animal models, 2. identifying the pathogenic mechanisms that can be modified by intervention and 3. targeting pharmacological intervention towards those mechanisms in the right patients at the right time.