The Effect of Opiates on Bone Formation and Bone Healing

Opioids have been shown to be associated with an increased risk of fracture. The purpose of this paper is to review recent research into the effects of opioids on bone formation and bone healing in animal models and in human studies.

Most opioids, such as morphine and fentanyl, negatively affected bone remodeling and bone healing in animal models. Conversely, remifentanil has been recently shown to promote in vitro osteoblast differentiation and to inhibit differentiation and maturation of osteoclasts, therefore reducing bone resorption. According to the possible negative role of opioids in bone healing, opioid antagonists have been shown to enhance bone mineralization, suggesting a possible therapeutic role in the future for osteoporosis. Other neuropeptides, such as the vasoactive intestinal peptide (VIP) and the neuropeptide Y (NPY), have been proved to promote osteogenesis. The increased risk of fractures among opioid users may be related to their central nervous system side effects or to the reduced bone density, partly due to their endocrine effects, and partly to their direct activity on bone cells. Clinical data strongly suggested a potential negative effect of opioids in bone healing. The risk of nonunion fracture is significantly increased in opioid users, and bone mass density was reduced in patients under long-term opioid treatment. The direct effects of opioids on bone remodeling appears evident from these reports. Not all opioids have the same potential for negatively impacting bone healing. Opioid antagonists may increase bone density and could represent a possible future treatment for low bone mass density pathologies. However, further trials are warranted to clarify the clinical relevance of these emerging findings from animal studies.