by Kerry Bone, BSc (hons), Dip. Phyto, FNIMH, FNHAA, MCPP

Nonsteroidal anti-inflammatory drugs are the mainstay of the conventional treatment for osteoarthritis and related conditions.

We already have witnessed the 2004 withdrawal from sale of rofecoxib (Vioxx), one of the main COX-2 inhibitors, due to increased cardiac deaths. In addition, recent studies have emerged that raise serious concerns regarding the long-term safety of all NSAIDs in this regard, not just the selective COX-2 inhibitors mentioned above.

Some of the most commonly used non-selective NSAIDs are, in fact, more likely to cause heart attacks than rofecoxib.¹ A case-control study of more than 9,000 people ages 25 to 100 who had suffered their first ever heart attack was published last year in the prestigious British Medical Journal (BMJ). After adjusting for all confounding variables, a significantly increased risk of myocardial infarction was observed for diclofenac (55 percent increase), ibuprofen (24 percent increase), rofecoxib (32 percent increase) and naproxen (27 percent increase). Also, for other nonselective NSAIDs (viewed as a whole), there was a significant 21 percent higher risk of heart attack. The authors concluded that their study suggested enough concerns might exist to warrant a reconsideration of the cardiovascular safety of all NSAIDs.

NSAIDs also have taken a hammering concerning their clinical efficacy. A recent meta-analysis and systematic review of 23 clinical trials involving more than 10,000 patients found that NSAIDs, as a whole (including selective COX-2 inhibitors), were ineffective for long-term pain relief of osteoarthritis of the knee.² The authors of this BMJ study concluded that while NSAIDs can reduce short term pain in osteoarthritis of the knee slightly better than placebo, the long-term use of NSAIDs for this condition is not supported on the current evidence. They added that as serious adverse events are associated with NSAIDs, only limited patient use can be recommended.

Clearly, the message from the current research is that NSAIDs should not be the first option for the treatment of arthritis and muscle pain. One frontline option that is receiving much research attention in Europe is the standardized extract of willow bark. The clinical efficacy of willow bark in pain management already has been demonstrated in several randomized, controlled clinical trials.³ Recent large-scale studies showed that this herbal product, when tested in a clinical setting, had a superior safety and efficacy profile compared to NSAIDs.

Two large-scale observational clinical studies have been presented at recent conferences confirming the safety and efficacy of standardised willow bark extract in the management of osteoarthritis and chronic low back pain. The first study was presented at a Berlin conference in 2004 and involved 922 physicians and 4,731 patients in Germany.⁴ For six to eight weeks or more, patients with arthritis or back pain took various doses of willow bark extract (an average of three tablets per day; see comment below regarding the standardisation of the product used) and rated their pain intensity from 1 to 10, with 10 representing pain of the highest intensity. Most of the patients had previously been taking NSAIDs, but had generally discontinued their use because of either a lack of efficacy or side effects.

"The current disillusionment with COX-2 inhibitors and recent research findings emphasize the advantages of using willow bark extract to manage osteoarthritis and related conditions."

During the observation period, only 15.5 percent needed supplementary antirheumatic drugs in addition to their willow bark. Average pain intensity reduced from 6.4 to 3.7 points in the first four weeks of treatment and had fallen further to 2.7 after eight weeks, with 97 percent of patients reporting a reduction in pain and 18 percent reporting no pain at all. Side effects were judged as minor and occurred in only 1.3 percent of patients. The effects were mainly abdominal pain or allergic skin rash.

The second study was undertaken in Switzerland and involved 204 physicians and 807 patients.⁵ Most patients suffered osteoarthritis (44 percent) or chronic back pain (36 percent). In 69 percent of patients, the problem had existed for more than six months. In 55 percent of patients, the willow bark was prescribed on its own, whereas in 39 percent, it was combined with conventional medications (mainly NSAIDs) that the patients already were taking. The average daily dosage of willow bark extract was 3.4 tablets at the beginning of the study and 2.8 tablets at the end. Throughout the six-to-eight week observation period, mean pain intensity decreased from 6.4 points to 3.3 and at the final visit, 15 percent of patients were pain free. A substantial reduction in physical impairment also was observed. Suspected adverse reactions occurred in 4.5 percent of patients; none of the reactions was rated as serious. More than two-thirds of patients rated the tolerability of the willow bark extract as better than conventional antirheumatic drugs.

The willow bark extract used in the two studies was standardised to contain 60 mg of salicin per tablet. It's important to note that only preparations and doses of willow bark capable of providing this activity will be likely to reproduce the impressive results of these trials. Taken together, these studies show that standardised willow bark is safer and more effective than antirheumatic drugs.

Professor Reinhard Saller, a rheumatologist based in Zurich, recently was interviewed concerning these two studies and his clinical perspective on willow bark extract.⁶ He highlighted the high tolerability demonstrated for willow bark extract in the trials and emphasized that these studies provided useful information concerning its effective dose in a clinical setting. He also observed that the excellent results he had encountered with willow bark in his own practice attested to its anti-inflammatory and analgesic potential. When questioned on the relative value of willow bark extract versus NSAIDs, he suggested that the herbal product had such a large advantage because of its complex of active principles that had an overall modulating effect. The mixture of'actives neither provoked a complete blockage nor a maximal stimulation of biochemical phenomena. This resulted in a broader spectrum of action and a greater tolerability than NSAIDs, which he then advised the patients to use on a limited "as required" basis once they had started willow bark.

Clearly, the message from the current research is that NSAIDs should not be the first option for the treatment of arthritis and muscle pain.

Given the current disillusionment with COX-2 inhibitors, Professor Saller stressed the advantages of using willow bark extract, which had complex and multiple activity.^3,7,8 He felt such treatments gave the body sufficient margin to manoeuvre in its proper use of regulatory mechanisms to influence pathological phenomena. This contrasted with COX-2 inhibitors that actually block important compensatory and regulatory mechanisms in the body, which leads to serious side effects.