First ever study to modify progression of knee osteoarthritis

Strontium ranelate (Protelos ®) reduced structural progression of osteoarthritis (OA) in knee joints by one third, finds an international phase III study. The trial, presented at the European Congress of Osteoporosis and Osteoarthritis (IOF-ECCEO) meeting in Bordeaux, France, 21 to 24 March, 2012, is the first study ever to have demonstrated a disease modifying effect in OA, with additional benefits shown for pain, function and mobility.

“After years of labouring to manage patients with blunt tools we finally have something that allows us to alter the natural history of the disease,” said Professor Cyrus Cooper, the lead investigator of the trial from the University of Southampton, and University of Oxford. “It could reduce or even eliminate the need for expensive and painful joint surgery.”

Until now the only treatment for OA, which is estimated to affect over one in six people, has been short term symptomatic relief with pain killers.

In the study between April 2006 and February 2011 1,683 patients with knee osteoarthritis, with a mean age of 62.3 years were randomised to receive strontium ranelate 2g/day, (n=566), strontium ranelate 1g/ day (n=558) or placebo (n=559).

The patients, recruited from 98 centres in 18 countries, all had a joint space between 2.5 mm and 5mm. For the primary end point, which was measurement of narrowing of the medial-tibio femoral compartment of the target joint, investigators utilised the SynaFlexer ™ frame, a device ensuring that knees were placed in the same position throughout the trial for measurement standardisation.

At three years results show that in comparison with placebo the space between the joints was 33 % wider (less narrow) for patients receiving the 1g dose (p<0.001) and 23% wider (p=0.012) in those receiving the 2g dose. For the 1g dose the risk of patients reaching >0.5mm loss of joint space width ( a threshold level known to place patients at a fivefold increase in the risk of undergoing joint replacement surgery over the next five years) was reduced by 34% (p=0.049); while for the 2g dose risk was reduced by 44 % (p=0.008).

Furthermore, strontium ranelate 2g significantly reduced the WOMAC score (a global score taking into consideration OA pain, function and mobility) in comparison with placebo (p=0.045), and showed an additional effect on the pain sub score (p=0.025). No statistically significant effect, however, was found for the 1g dose.

“Clearly the 2g dose is needed to obtain the beneficial effects on pain and stiffness,” said Dr Jean-Yves Reginster, who presented the data in the scientific session from the University of Liège, Belgium. This, he added, was the dose used in osteoporosis. For every three years of treatment, he said, the equivalent of a year of joint deterioration could be prevented.

Results also showed that levels of CTX II (a marker of cartilage breakdown) was significantly higher in the urine of patients randomised to placebo. The study revealed no adverse effects on skin reactions or venous thromboevents.Tim Spector, professor of Genetics and Epidemiology at St Thomas’ Hospital, London, commented, “Many patients with OA also have osteoporosis, so one of the exciting aspects is that we could kill two birds with one stone to protect both the joints and the bones.”