Structure modification in osteoarthritis

For decades, the traditional pharmacological management of osteoarthritis (OA) has been mainly symptomatic, despite a lack of evidence of its influence on the duration of the disease and its progression. However, in recent years several sets of guidelines, recommendations or points to consider have been issued by regulatory authorities or scientific groups regarding requirements for the registration of drugs to be used in the treatment of OA. The ideal outcomes currently include pain and function assessment for symptom-modifying drugs, and joint-space narrowing (JSN) assessed by plain radiography for structure-modifying compounds. Taking advantage of these more precise recommendations, several chemical entities have been carefully investigated for the management of OA.

This article provides a summary of the available evidence demonstrating that some compounds can effectively interfere with the structural progression of the disease.

Avocado/Soybean Unsaponifiables
The unsaponifiable part of avocado (A) and soybean (S) oils (ASU) mixed in a ratio of 1:2 (A1:S2) has been investigated in the treatment of connective tissues, including in OA, for several years. A pilot randomised, double-blind, placebo-controlled trial with follow-up over two years failed to demonstrate a structural effect of ASU in 163 patients with painful hip OA.1 However, in a post hoc analysis a significant difference was detected in the subgroup with a baseline joint-space width (JSW) smaller than 2.45mm: joint space loss was halved in the treated group (-0.43±0.51mm) compared with the placebo group (-0.86±0.62mm; p=0.01). This finding suggests that ASU may have a structure-modifying effect in patients with severe hip OA.

Chondroitine Sulphate
Chondroitine sulphate (CS) is a major component of the extra-cellular matrix from many connective tissues, including – but not limited to – cartilage, bone, skin, ligaments and tendons. In the articular cartilage, the high content of CS in the aggrecan plays a major role in creating considerable osmotic swelling pressure, which expands the matrix and places the collagen network under tension. In a pilot double-blind study, JSW measurement on digitalised radiographs of the extended knees was used to compare the effects of CS 800mg/day and a placebo in patients with knee OA.2 There were 23 patients in each group. After one year, JSW was unchanged in the treated group but had decreased by 0.4mm in the placebo group (p<0.005). No significant difference was found for JSW at the narrowest site. The small number of patients for whom end-point values were available (12 in the placebo group and 14 in the CS group) limits the relevance of the results.

Another study randomised a total of 120 patients with symptomatic knee OA into two groups receiving either 800mg CS or placebo per day for two periods of three months during one year.3 Radiological progression was assessed as a secondary outcome by automatic measurement of medial femoro-tibial JSW on weight-bearing X-rays of both knees. Radiological progression at month 12 showed significantly decreased JSW in the placebo group, with no change in the CS group.