PATHOGENESIS OF OSTEOARTHRITIS AND SUBSTANTIATION OF THE USE OF STRONTIUM RANELATE

Abstract

Osteoarthritis (OA) is one of the most common diseases, pain and joint dysfunction being its main symptoms. Although OA is a progressive disease causing disability, rapid progression is observed only in some patients. According to the data obtained by different authors, the progressive course of gonarthrosis is typical of 34–55% patients, which is likely to be attributed to variability of the risk factors of disease progression that every single patient has. As the reasons behind OA progression have been studied more thoroughly, the notion of the disease pathogenesis has recently changed. While articular cartilage lesion was considered to be the main reason and the joint space narrowing and concomitant changes in the subchondral bone (SCB) were regarded as a secondary process SCB is now believed to play the initiating role in disease evolution. It was found that acceleration of metabolic processes in SCB in OA patients causes incomplete mineralization of bone and reduces its biomechanical properties. These data initiated the search for new approaches to therapy for OA. A large number of medications that are potentially able to inhibit disease progression are being actively studied. Special attention is paid to the agents affecting the processes of bone tissue remodeling. In addition to bisphosphonates and calcitonin (whose effectiveness in treating OA has been studied over the past decades), much attention has recently been paid to strontium derivatives, in particular, to strontium ranelate (SR). It has been proved that SR stimulates preosteoblast replication, osteoblast differentiation, type 1 collagen synthesis, and mineralization of bone matrix. Meanwhile, SR inhibits osteoclast differentiation and activity, resulting in the reduction of SCB resorption, which is a potentially significant effect in OA therapy. In addition to its effect on SCB, SR can influence the bone tissue. It wasfound during the studies that SR reliably enhances the formation of bone matrix (namely, synthesis of high molecular weight proteoglycans) both in the normal articular cartilage and in patients with OA. The symptomatic effect of SR has been demonstrated in clinical trials. A reliable deceleration of joint space narrowing in patients who received SR therapy (compared to those who received placebo) has also been proved.

Keywords

• osteoarthritis
• subchondral bone
• joint space narrowing
• strontium ranelate