Factors Associated with Low Bone Density in Opioid Substitution Therapy Patients: A Systematic Review

Abstract

Background: Long-term opioid therapy is a risk factor for low bone mineral density (BMD). However, other factors may also contribute to low BMD. Several studies have examined the variables that might contribute to low BMD in patients receiving opioid replacement therapy (OST). However, to our knowledge, there was no systemic review conducted to address this particular issue. Thus, we reviewed the articles on the factors associated with low BMD in the population of opioid use disorder receiving substitution therapy. Methods: The articles that examined correlates or risk factors of low BMD in OST population were retrieved from OVID, SCOPUS, and PUBMED from inception until July 2020 by two independent investigators. Results: A total of 429 articles from three databases were retrieved initially. After screening based on eligibility criteria, five articles were included in the final analysis. The risk factors or correlates found to be significantly associated with low BMD in the OST population include male gender, low body mass index, low testosterone level, methadone or heroin use, and longer duration of heavy alcohol use. The review limitations include small sample sizes and inconsistent definition of variables. Conclusion: OST patients should be screened for BMD and its associated factors. Guidelines and training of practitioners involving in the OST service should be provided to increase the detection of low BMD in the OST population.

Two Weeks of Continuous Opioid Treatment in an Adenine-Induced Mouse Model of Chronic Kidney Disease Exacerbates the Bone Inflammatory State and Increases Osteoclasts

“…As opioids have been widely used and misused over many years, epidemiological studies demonstrate connections to reduced bone mass[ 28 – 33 ] and elevated fracture risk with long-term use [ 34 ]. For example, individuals with an opioid use disorder are 4.13 × more likely to fracture than those without [ 35 ].…”

“…We previously have shown similar phenotypes in male and female C57Bl/6 mice with adenine-induced CKD [ 25 ], but the impact of opioids in the context of CKD may vary between sexes. In humans, the impact of long-term opioid exposure on bone appears to be stronger in males vs. females [ 30 , 33 , 45 ]. Additionally, 25 days of sustained morphine administration in mice impacted the bone of male mice, but not female mice [ 19 ].…”

How Do Drugs Affect the Skeleton? Implications for Forensic Anthropology

“…However, as it would appear that it inhibits osteoblastic activity and certain hormones such as gonadotropinreleasing hormone (GnRH) [41,42], it has been shown that opioids can induce osteoporosis and thus increase osteoporosis risk fracture [43]. This reduction in bone density and thus leading to osteoporosis has been demonstrated in some human and non-human experimental studies [44], although other factors, leading to this lower bone mass density, need to be considered [45]. The risk of fracture in morphine users also increases, especially in common osteoporotic fractures such as those found at the hip, spine, and forearm; a risk increased by loss of postural balance and falls due to side effects of the drug [46].…”

20- Deoxyingenol attenuate morphine-induced hippocampus neurotoxicity and memory impairments in rats

“…It also indicates that opioids can affect hippocampal-dependent memory [ 2 ]. Learning and memory disorders caused by morphine addiction are related to the imbalance of HCN1 and HCN2 subunits in CA1 region [ 3 ].CA1 neural network plays an integrated role in memory [ 4 ].Additionally, long-term use of opioids can lead to blocked nerve formation, decreased bone density, and changes in the synaptic transmission process [ 5 , 6 ]. Related studies reveal that chronic use of morphine causes oxidative stress, apoptosis, and changes in autophagy in different brain regions, like the hippocampus [ 7 ].…”