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Osteoarthritis (OA) is the most common disease of the joints and is a very common cause of disability. In contrast with rheumatoid arthritis, there is presently no disease-modifying drug for OA (DMOAD) available, which slows down the progression of joint deterioration in combination with pain relieve.

Evidence is accumulating, that anti-osteoporosis drugs, which act on bone, may be also effective DMOADs through interaction between cartilage and bone. Fortunately, zoledronate appears to be a readily available, well tolerated candidate DMOAD. Several in vitro studies, animal studies, observational studies and randomized clinical trials suggest that zoledronate may be an effective DMOAD for knee OA.

As OA is heterogeneous disease, it is achievable that bone-targeted treatment, such as zoledronate, is more effective in a subset of patients with increased metabolic activity of the bone (in contrast to patients with prominent synovitis or cartilage loss with very little bony features).

Therefore, the aim of the present study is to investigate whether semi-annual treatment with zoledronate reduces both cartilage degradation and pain in patients with knee OA with active bone metabolism indicated by BML on MRI.

This is the first study that is specifically designed (and as such properly powered) to study the effects of zoledronate on both cartilage loss and pain in a prospective double-blind, placebo-controlled fashion in a subgroup of OA patients with active bone metabolism.

If zoledronat proves to be an effective DMOAD, joint replacement may be postponed and revision surgery may be postponed or prevented.

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