Knee joint replacement over 5 years in patients with knee osteoarthritis. A long term follow up study in patients of the CL3-12911-018 study.

Osteoarthritis (OA) is thought to be the most prevalent chronic joint disease.
The incidence of OA is markedly rising with the ageing of the population and
the epidemic of obesity. Cartilage degradation and loss, due to biomechanical
and biochemical changes in the joint, are the major degenerative changes of OA.
Pain and loss of function are the main clinical features that lead to
treatment, including non-pharmacological, pharmacological and surgical
approaches (1).

Over the past years, there have been considerable efforts to study new agents
for their potential to improve symptoms and also alter the course of OA by
delaying or reversing the progression of joint structural damage. However, the
ultimate clinically relevant outcome for these structure modifying drugs would
be to prevent or delay the joint replacement surgery.

According to the European guideline on clinical investigation of medicinal
products used in the treatment of osteoarthritis (CPMP/EWP/784/97 Rev.1 dated
20 January 2010), the necessity of joint replacement is a recommended outcome
to evaluate, although this outcome may not be a feasible endpoint within the
frame of a Phase III clinical trial (2).

Knee joint replacement is an invasive procedure in which cartilage, bone and
soft tissues are replaced by artificial materials. It often occurs after OA has
been treated for a long period with drugs (usually analgesics to treat the
pain), physical therapy (specific exercises that may help improve motility and
pain) and salvage surgical procedures (3).

Little data on long-term progression of OA in large cohorts of patients with
knee OA is available in the literature. The Group for the Respect of Ethics and
Excellence in Science (GREES) organised a working group to assess the time to
joint surgery. They concluded that existing data could suggest that criteria
such as lack of progressive joint space narrowing (JSN) is predictive of not
going to surgery (5) .
A study has been designed to evaluate the efficacy of Strontium Ranelate (1g
and 2g per day) on the Joint Space Width (JSW) progression, as assessed by
measuring the mean change in the JSW of the medial femoro-tibial compartment
determined by X-ray. This study numbered CL3-12911-018 study and entitled: *The
efficacy and safety of two doses of Strontium Ranelate (1g and 2g per day)
versus placebo administered orally for 3 years in the treatment of knee
osteoarthritis* started in 2006 and was completed in February 2011.

In order to evaluate the long term outcome of these patients with regards to
knee surgery, a 5 year follow up study will be proposed to all patients with
knee osteoarthritis having participated in the CL3-12911-018 study and having
received at least one year (365 days) of CL3-12911-018 study treatment.
Patients in this long term study will not receive any study drug and will be
followed by their usual practioner, no study exams will be required. The only
requirements for an initial visit will be to inform the patient about the study
and obtain the patient*s informed consent. At all visits, patient*s weight, OA
treatments and knee surgery/procedure history will simply be collected.

To collect data on knee joint replacement procedures or procedures
practiced in the knee (arthroscopy, osteotomy or other) over 5 years in
patients with knee osteoarthritis having participated in the CL3-12911-
018 study and having received at least one year (365 days) of CL3-
12911-018 study treatment (Strontium Ranelate 1g/2g or placebo).

A 5 year international multicentric study in patients who have participated in
the CL3-12911-018 study, having received the study treatment (strontium
ranelate 1g/2g or placebo) for at least one year.
There will be no modification of the medical practice of the participating
investigators and no additional examinations for the patients, medication will
be prescribed solely as a result of a normal clinical evaluation. This study
will not require any extra routine medical examination for the patient.
The study will be divided into the following periods :
-1 inclusion visit (M000)
-5 follow-up phone calls at 12,24,36,48 and 60 months (± 3 months time window
will be allowed)

There are no risks related to this study.