Short-Acting Opioids Raise Fracture Risk

Abstract

Bruce Jancin is with the Denver bureau of Elsevier Global Medical News. DENVER — Elderly patients who are placed on short-acting opioids for arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on long-acting opioids, according to a large study. The increased risk was particularly strong during the first 2 weeks of therapy, when it was almost sevenfold in patients on short-acting opioids, such as propoxyphene or oxycodone, as in patients started on nonsteroidal anti-inflammatory drugs (NSAID) or long-acting opioids, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk associated with short-acting opioid therapy dropped but remained about three times that with NSAID therapy, Matthew Miller, MD, ScD, reported at the annual meeting of the American Public Health Association. The fracture risk during the first 2 weeks on long-acting opioids didn't differ significantly from that in patients who were placed on NSAIDs. Over 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on long-acting opioids than in those on NSAIDs. In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on short-acting opioids, added Dr. Miller, associate director of the Harvard Injury Control Research Center, Boston. “Our findings indicate that opioids increase the risk of fractures among older patients with arthritis and suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed. These results have the potential to change clinical practice in the elderly, said Dr. Miller. At present, short-acting opioids are prescribed far more often than long-acting ones. <Our findings, if borne out in other databases, could help inform safer prescribing practices consonant with the latest American Geriatrics Society guidelines on the pharmacological management of pain in older persons, which recommend that all patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life due to pain should be considered for opioid therapy,” he said. His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with opioid analgesics, and 4,874 who started on NSAIDs. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months. Not surprisingly, patients who were started on opioids tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on long-acting opioids, and 1.6 in the NSAID group. The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids. A dose effect was evident. Patients on low-doseoopioids hada 2.2 times the fracture risktofdihose onan NSAIDs, after adjustment for comorbid conditions and other potentially confounding variables. Patients on moderate-dose opioids had 4.6 times the-risk. And those on high-dose opioid therapy had a 5.1-foldinisk. Among high-dose opioid users, a patient who was placed on a short-acting opioid had an adjusted risk of fracture d.1 times that of someone on a high-dose, long-acting opioid. Asked why he thought short-acting opioids were prescribed 13 times as frequentlytas long-acting ones in the study population, Dr. Miller reid his impression is that many physicians believe that if they prescribe a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous. “It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream. Yet 90% of the drugs that we're prescribing when we're prescribing opioids in an elderly population are short-acting drugs, raising the question of whether we're putting people at unnecessary risk,” Dr. Miller said. The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use. Dr. Miller declared having no relevant financial interests.