Mixed effects are not sufficient…

Two major studies, SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis) were first conducted involving more than 6 500 patients showing both post-menopausal osteoporosis and arthrosis of the backbone. A nice surprise: treatment of osteoporosis by strontium ranelate reduced the progression of lumbar arthrosis by 42%. The TROPOS study also showed that in menopausal women receiving strontium ranelate, the excretion in urine of a biological marker reflecting the deterioration of cartilage collagen (the C-telopeptide of collagen II) was significantly reduced, and this was after the third month of treatment. This effect continued during three years of research. In addition, 34 % of patients also saw an end to their back pain…

From these encouraging results, a new stage began: the study of the effects of a molecule a molecule on people suffering from arthrosis, in a separate context to osteoporosis. “At this stage it was decided to analyze whether strontium ranelate made it possible to improve the symptoms and reduce the structural progression of arthrosis of the knee, explains Professor Jean-Yves Reginster.

A Common program

This is how a large multi-centre study, carried out in 98 research canters in 18 different countries and involving 1,683 patients, was set in motion. “The protocol, classic and in perfect conformity with the regulatory European requirements, had no difficulty being approved by the Ethics Committee”, explains the specialist. To the extent that the firm (Servier) which markets the molecule financed the study, a series of precautions were scrupulously followed in order to avoid any later suspicion about the results. In fact, the guidelines published by the European Medicine Agency for the assessment of osteoporosis treatments were respected to the letter, almost to the point of being “copied and pasted”.
 
This retrospective study (an assessment and analysis of the situation, of trends and prospects), carried out as a double blind trial (neither the experimenter nor the volunteer knew the content of the treatment given to the person), made it possible to compare the administration of two doses of strontium ranelate (1 gram per day or 2 grams per day) to a placebo. The entire duration of the study was three years.

The patients included in this study were men and women with arthrosis that was radiographically classed as light to moderate but symptomatic : their pain level was at least 40 on a visual scale for measuring pain composed of a gradation going up to 100. “The group included in this study was composed of 69% women and 31% men. The average age was 62.5 years, and the respective proportion between light and moderate arthrosis was 60-40”, explains Prof. Reginster. All the investigators worked according to the same rules allowing them to include volunteers based on the same criteria.

Clear objectives

“The main assessment criterion of this study was the progression of the most painful joint space narrowing of the internal femorotibial compartment of the knee of the individual” recalls Prof. Reginster. A digitalized radiology technique that was analyzed by a semi-automatic software previously validated by Prof. Roland Chapurlat’s team from Lyon, in the Bone Rheumatology Unit of the Edouard Heriot Hospital, was used to measure this progression of joint space narrowing.  Moreover - and this is one of the particularities of this study, a second analysis, conducted in parallel and totally independent, was conducted in Liège, in the department of Prof. Jean-Yves Reginster. These two radiographic studies of the main criterion yielded similar results. “This high level of agreement confirms the quality of the method used and the result obtained with strontium ranelate”, Confirms Prof. Reginster.