GLASGOW, SCOTLAND (FRONTLINE MEDICAL NEWS) – Adverse events ranging from major trauma to osteoporosis to death from any cause occurred at significantly higher rates among people who were prescribed opioids long term for musculoskeletal pain in comparison to those who used a single prescription, in a large retrospective matched cohort study.

The analysis of almost 200,000 patient records from 190 primary care practices held within the U.K. Clinical Practice Research Datalink found that use of opioids to control pain for more than 3 months was associated with an increased risk for major trauma and almost doubled the risk of overdose of nonopioid drugs, compared with short-term use.

The absolute risk for major trauma, which included bone fracture, joint dislocation, ligament or tendon rupture, or head trauma, was 387.4 per 10,000 person-years with long-term opioid use and 269.7 per 10,000 person-years for short-term opioid use, with a hazard ratio (HR) of 1.26 and a 95% confident interval (CI) of 1.20 to 1.33. The absolute risk for overdose with drugs other than opioids was 37.7 and 12.9 per 10,000 person-years, respectively (HR 2.03; 95% CI 1.63-2.53).

Long-term use of opioids led to a significant increase in the risk of accidental poisoning (HR 4.12; 95% CI 1.66-10.19) and becoming newly addicted (HR 2.76; 95% CI 1.76-4.35) in comparison with short-term opioid use. The risk of addiction significantly rose with long-term users of nonopioid drugs (HR 2.16; 95% CI 1.78-2.62), compared with short-term users.

Other risks included an increase in falls (HR 1.20; 95% CI 1.14-1.25) and new cases of osteoporosis (HR 1.65; 95% CI 1.52-1.79), incident depression (HR 1.45; 95% CI 1.37-1.53), new gastric (HR 1.38; 95% CI 1.20-1.60) and nongastric (1.33; 95% CI 1.21-1.45) gastrointestinal bleeding, incident iron deficiency anemia (HR 1.22; 95% CI 1.12-1.33), and death from any cause (HR 1.20; 95% CI 1.12-1.29).

There was no increase in the risk for attempted suicide or self-harm, however, nor in a couple of control outcomes (new cases of eczema or psoriasis) that were tested.

“Long-term users [of opioids] appear to be a very vulnerable group at high risk of experiencing quite a lot of adverse events,” said Dr. John Bedson of Keele (England) University who presented the findings at the British Society for Rheumatology annual conference. “So GPs [general practitioners], naturally, need to be actively managing these patients and … as this is in the very early stages of prescribing, they need to be assessing the benefit and whether there is a need to carry on taking these medications and stop them if appropriate.”

The use of opioids in patients with musculoskeletal conditions has been increasing in the past 10 years, particularly the use of more potent and long-acting opioids, Dr. Bedson observed. He noted that of all the adults who newly present with musculoskeletal conditions in the United Kingdom – estimated to be 20% of all primary care consulters annually – one in seven will be prescribed an opioid analgesic. In fact, as it was noted during the discussion, U.K. clinicians are now often opting to use opioids over nonsteroidal anti-inflammatory drugs (NSAIDs) to avoid gastrointestinal bleeding.

While there has been some evidence obtained on the risks associated with long-term opioid use in the United States, there has not been data on the risks in a U.K. population. With differing health systems, guidelines, and practices between the two countries, the aim of the retrospective matched cohort study was to compare the adverse event profiles of long- and short-term opioids users over a period of 12 months in a U.K. primary care practice population.

Between 2002 and 2013 there were 98,140 patients with musculoskeletal conditions who had been prescribed opioids and had received two or more further opioid prescriptions within a 90-day period. These were the long-term opioid users; they were matched according to age, gender, and practice to 98,140 short-term opioid users who were patients with musculoskeletal conditions who did not fulfill the criteria for the long-term definition. The median age of patients was 61 years and 41% were male.

Numerous covariates were taken into account, including previous adverse events in the 15 months prior to the start of follow-up, smoking status, alcohol consumption, body mass index, where patients lived and their socioeconomic status, the presence of any comorbidities, and the coprescription of NSAIDs.

Further research into how and why patients on long-term opioids experience more adverse effects needs to be conducted, Dr. Bedson noted, adding that causality had not been found in this study. The next step would be to look at the morphine equivalent doses of the opioids used to see if that had an effect.

But how does the risk compare to long-term use of NSAIDs? Has the preference for opioids been mistaken as being safer?

“The problem is that we have started using these drugs and we don’t know if they work,” Dr. Bedson said. “So we are now at the point of identifying more and more risks, but do they do any good? So I think the jury is still out, and I think GPs have very little else to use at the moment because of the worries over anti-inflammatories, but from an anecdotal point of view I think people are beginning to swing back to using them again.”

Dr. Bedson had no conflicts of interest to disclose.