The unsolved case of &amp;ldquo;bone-impairing analgesics&amp;rdquo;: the endocrine effects of opioids on bone metabolism

Coluzzi, Flaminia; Pergolizzi, Joseph V.; Raffa, Robert B.; Mattia, Consalvo

doi:10.2147/tcrm.s79409

Cited by 59 publications

(35 citation statements)

References 58 publications

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“…FGF23, a fibroblast growth factor that is highly expressed in bone, reduces levels of activated vitamin D [64] and thus leads to reduced bone mineral density and a higher risk of fracture [65]. Interestingly, long-term use of opioid analgesics has been associated with bone loss [66].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Opioid Cessation

Cox

Sherva

Lunetta

et al. 2020

JCM

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The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Opioid Cessation

Cox

Sherva

Lunetta

et al. 2020

JCM

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“…While these findings were encouraging, the adverse psychoactive effects caused by activation of cannabinoid receptors, in particular Cnr1, in the brain may limit the development of these agents for cancer treatment. This and the fact that long-term use of analgesics such as opiates is often associated with excessive bone loss [166] encouraged the development and testing of selective Cnr2 for the reduction of cancer-induced pain [23,[167][168][169][170][171].…”

Section: Regulation Of Cancer-induced Bone Pain By Cnr2mentioning

confidence: 99%

Emerging therapeutic targets in cancer induced bone disease: A focus on the peripheral type 2 cannabinoid receptor

Marino

Idris

2017

Pharmacological Research

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Skeletal complications are a common cause of morbidity in patients with primary bone cancer and bone metastases. The type 2 cannabinoid (Cnr2) receptor is implicated in cancer, bone metabolism and pain perception. Emerging data have uncovered the role of Cnr2 in the regulation of tumour-bone cell interactions and suggest that agents that target Cnr2 in the skeleton have potential efficacy in the reduction of skeletal complications associated with cancer. This review aims to provide an overview of findings relating to the role of Cnr2 receptor in the regulation of skeletal tumour growth, osteolysis and bone pain, and highlights the many unanswered questions and unmet needs. This review argues that development and testing of peripherally-acting, tumour-, Cnr2-selective ligands in preclinical models of metastatic cancer will pave the way for future research that will advance our knowledge about the basic mechanism(s) by which the endocannabinoid system regulate cancer metastasis, stimulate the development of a safer cannabis-based therapy for the treatment of cancer and provide policy makers with powerful tools to assess the science and therapeutic potential of cannabinoid-based therapy. Thus, offering the prospect of identifying selective Cnr2 ligands, as novel, alternative to cannabis herbal extracts for the treatment of advanced cancer patients.

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“…A balanced and early multimodal pain therapy including opioids, as necessary, even in case of acute pain, improve the functional capacity of patients and helps to prevent neurological alterations, which seem to contribute in a significant way in causing irreversible pain chronic syndromes (50). When treating OP related pain opioid-associated androgen deficiency (OPIAD) syndrome should be considered, as this could be related with an increased risk of OP; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses >100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density (51).…”

Section: Clinical Aspectsmentioning

confidence: 99%

Bone pain mechanism in osteoporosis: a narrative review

Mattia

Coluzzi

Celidonio

et al. 2016

ccmbm

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SummaryBone pain in elderly people dramatically affects their quality of life, with osteoporosis being the leading cause of skeletal related events. Peripheral and central mechanisms are involved in the pathogenesis of the nervous system sensitization. Osteoporosis in the elderly has been associated with increased density of bone sensory nerve fibers and their pathological modifications, together with an over-expression of nociceptors sensitized by the lowering pH due to the osteoclastic activity. The activation of Nmethyl-D-aspartate (NMDA) receptors and the microglia, as a response to a range of pathological conditions, represent the leading cause of central sensitization. Unfortunately, osteoporosis is named the "silent thief" because it manifests with painful manifestation only when a fracture occurs. In the management of patients suffering from bone pain, both the nociceptive and the neuropathic component of chronic pain should be considered in the selection of the analgesic treatment.

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The unsolved case of “bone-impairing analgesics”: the endocrine effects of opioids on bone metabolism

Cited by 59 publications

References 58 publications

Genome-Wide Association Study of Opioid Cessation

Genome-Wide Association Study of Opioid Cessation

Emerging therapeutic targets in cancer induced bone disease: A focus on the peripheral type 2 cannabinoid receptor

Bone pain mechanism in osteoporosis: a narrative review

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