As pointed out by Dr Daniell, the increased risk of fractures in older women taking narcotics in our study may, in part, be due to the effects of narcotics on production of endogenous sex steroids, including testosterone and estradiol, and bone turnover. We acknowledge his previous cross-sectional study1 that found lower levels of free testosterone and estradiol in a group of community-dwelling men taking sustained-action oral opioids for nonmalignant pain compared with a sex-matched control group. These effects may lead to lower bone density and decreased muscle strength, though neither low bone density nor impaired neuromuscular function in the older women taking narcotics in our study entirely explained their increased risk of fractures. Prospective studies of the associations between opioid use and changes in sex steroids, markers of bone turnover, and rates of bone loss are needed to demonstrate the causality of these relationships.
Ensrud KE. Opioid Osteoporosis—Reply. Arch Intern Med. 2004;164(3):338. doi:10.1001/archinte.164.3.338-b