Potential New Treatment for Osteoarthritis

Tuesday, February 23  |  Arthritis Today Magazine

Traditionally, treatment for osteoarthritis has been limited to relieving pain. Scientists have found hope that drugs used to treat osteoporosis may be useful in treating not only osteoarthritis (OA) pain, but cartilage damage as well.

Osteoporosis is a condition in which bone tissue breaks down faster than it is replaced, causing the bones to become brittle and prone to fracture. Bisphosphonates, a class of drugs commonly prescribed for osteoporosis, work by inhibiting cells called osteoclasts that break down bone. Researchers believe they may work similarly for OA, by inhibiting the activity of osteoclasts in the bone beneath the cartilage in affected joints.

In animal studies, bisphophonates have shown to reduce OA progression – as measured by the severity of cartilage damage and bony overgrowth – by as much as 30–40%.

Providing Pain Relief

Limited clinical research suggests bisphosphonates—whether taken orally or injected – may indeed be helpful for both relieving pain and reducing cartilage damage in people with OA, but many questions remain.

In one 2015 study published in Rheumatology International, Italian researchers separated 80 patients with painful knee OA into two groups: one received four weekly injections of the bisphosphonate drug clodronate into the painful knee and the other group received weekly saline injections. (Neither the patients nor the doctors knew which injections they were receiving.) Five weeks after the final injection, researchers compared the two groups and found those who received clodronate had greater improvement on many measures, including pain level, self-reported OA severity, and need for pain-relieving medication.

In a review of earlier investigations, published in 2013 in PLoS1, researchers identified 13 studies with a total of 3,832 participants with OA. They found that eight of the trials reported that bisophophonates improve pain. However the two largest studies of knee OA (using 15-milligram doses of the bisphosphonate drug risedronate) actually showed more improvement among the placebo group than the treatment group. The researchers concluded there is limited evidence that bisphosphosphonates are effective in the treatment of OA pain, but noted limitations of the studies, including differences in duration of bisphosphonate use, the dose and route of administration, and the lack of long-term data on OA joint structure. The authors say more research is needed to determine which patients could benefit most from bisphosphonate treatment.

Beyond Pain Relief

Research has also looked at the effects on cartilage damage of osteoporosis drugs. Scientists have assessed joint space narrowing – a sign of OA progression – and bone marrow lesions, which are predictive of more rapidly progressing OA.

Results of an observational study of 55 patients taking bisphosphonates and 268 nonusers were published in Annals of the Rheumatic Diseases in 2013. Researchers found that treatment with bisphosphonates over a period of two to three years was associated with both a reduction of osteoarthritis pain and less joint space narrowing.

In a 2012 study published in the same journal, researchers compared the effects of a single infusion of zoledronic acid with placebo in 59 people with knee osteoarthritis and bone marrow lesions. They found that after six months, patients taking zoledronic acid not only had reduced pain scores, but magnetic resonance imaging scans showed a reduction in the size of their bone marrow lesions.

Perhaps the most promising news about the potential of osteoporosis drugs for OA comes from a 2013 Belgian study of a drug called strontium ranelate, which is approved in Europe but not the US. Strontium ranelate is a dual-action bone agent, which means it inhibits bone-destroying osteoclasts much like a bisphosphonate while also increasing activity of bone-building cells called osteoblasts.

In the Belgian study, 1,683 patients with knee OA were randomly selected to receive strontium ranelate or placebo. Researchers followed the participants over three years measuring joint damage pain, stiffness and physical function. They found that strontium ranelate was associated with decreases in joint damage, as measured by joint space narrowing, compared to placebo.

Like bisphosphonates, strontium ranelate was effective in reducing pain and improving physical function, suggesting that osteoporosis drugs may indeed hold a role in the treatment of OA. However, further research is needed to determine if and what that role might be.

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