What is the relationship between opioid use and bone demineralization?

From the Guidelines

Opioid use is associated with an increased risk of bone demineralization, which can lead to fractures and osteoporosis, as evidenced by the increased risk of fractures found in clinical evidence reviews 1.

Mechanisms of Bone Demineralization

Opioids can affect bone metabolism by binding to opioid receptors on bone cells, inhibiting osteoblast function, and potentially increasing osteoclast activity.

• Opioids disrupt the endocrine system, suppressing sex hormones like testosterone and estrogen, crucial for maintaining bone density.
• Chronic opioid use often leads to vitamin D deficiency due to poor nutrition and reduced sun exposure, further compromising bone health.
• The sedative effects of opioids may reduce physical activity, eliminating the bone-strengthening benefits of weight-bearing exercise.
• Opioids can cause gastrointestinal issues that interfere with calcium and vitamin D absorption.

Clinical Implications

These combined effects lead to decreased bone mineral density over time, increasing the risk of osteoporosis and fractures in long-term opioid users.

• Patients on chronic opioid therapy should be monitored for bone health.
• They may benefit from calcium and vitamin D supplementation, regular exercise when possible, and periodic bone density testing.
• As noted in the guidelines for prescribing opioids for pain, opioids should not be considered first-line or routine therapy for subacute or chronic pain due to their association with serious harms, including increased risk for fractures 1.
• The management of opioid-induced adverse effects, including those affecting bone health, is integral to opioid pain management, as highlighted in guidelines for adult cancer pain 1.

From the Research

Opioid Use and Bone Demineralization

• Opioid use has been associated with an increased risk of fracture and bone demineralization, with studies suggesting that long-term opioid therapy is a risk factor for low bone mineral density (BMD) 2, 3, 4.
• The exact mechanisms by which opioids affect bone health are not fully understood, but it is thought that opioids may interfere with the endocrine system, leading to changes in hormone levels that can impact bone density 5, 6.
• Specifically, opioids have been shown to cause hypogonadism, which can lead to decreased testosterone levels and subsequently decreased bone density 5, 6.
• Other factors that may contribute to low BMD in opioid users include low body mass index, low testosterone level, methadone or heroin use, and longer duration of heavy alcohol use 2.
• Some studies have also suggested that opioids may have a direct effect on bone cells, inhibiting bone formation and promoting bone resorption 3.

Endocrine Effects of Opioids

• Opioids have been shown to affect multiple endocrine pathways, leading to abnormal levels of different hormones such as testosterone, cortisol, and prolactin (PRL) 5.
• The most commonly reported effect of opioids on the endocrine system is hypogonadism, which occurs in more than half of male opioid users 6.
• Opioids may also cause hypocortisolism, which has been reported in approximately one-fifth of all patients 6.
• The effects of opioids on the somatotropic and hypothalamo-pituitary-thyroid axes are less clear, with some studies suggesting that opioids may have no significant impact on these axes 6.

Clinical Implications

• The increased risk of fracture and bone demineralization associated with opioid use highlights the importance of monitoring bone health in patients taking opioids long-term 2, 3, 4.
• Periodical evaluation of the gonadal and adrenal axes is advisable in patients taking opioids, particularly in those with a history of hypogonadism or hypocortisolism 6.
• Further research is needed to fully understand the effects of opioids on bone health and to develop effective strategies for preventing and treating opioid-related bone disease 3, 6.