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The Effect of Opiates on Bone Formation and Bone Healing

  • Skeletal Biology and Regulation (MR Forwood and A Robling, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

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.

Recent Findings

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.

Summary

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.

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Abbreviations

5AR:

5 alpha reductase

AD :

Alzheimer’s disease

BDL:

Bile duct ligated

cAMP:

3′,5′-cyclic adenosine monophosphate

CI:

Confidence interval

CNCP:

Chronic non-cancer pain

CNS:

Central nervous system

DHT:

Dihydrotestosterone

FSH:

Follicle stimulating hormone

GnRH:

Gonadotropin-releasing hormone

H2O2 :

Hydrogen peroxide

hFOB:

Human fetal osteoblast

HPG:

Hypothalamus-pituitary-gonadal (axis)

HR:

Hazard ratio

ICU:

Intensive care unit

IL-6:

Interleukin-6

IL-10:

Interleukin-10

KOR :

Kappa-opioid receptor

LH:

Luteinizing hormone

met-enk:

Methionine-enkephalin

MMT:

Methadone maintenance therapy

MOR:

mu-opioid receptor

NPY:

Neuropeptide Y

NSAIDs:

Nonsteroidal anti-inflammatory drugs

OA:

Osteoarthritis

OGF:

Opioid growth factor

OGFR:

Opioid growth factor receptor

OGF-OGFR:

Opioid growth factor-opioid growth factor receptor (pathway)

OPIAD:

Opioid-induced androgen deficiency

OR:

Odds ratio

PAMORA:

Peripheral acting mu-opioid receptor antagonist

PKA:

Protein kinase A

RANKL:

Receptor activator of nuclear factor kappa-Β ligand

ROS:

Reactive oxygen species

Runx2:

Runt-related transcription factor 2

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

US:

United States of America

VIP:

Vasoactive intestinal peptide

VIP/NPY:

Vasoactive intestinal peptide/neuropeptide Y

Vs:

Versus

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Authors and Affiliations

  1. Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Corso della Repubblica 79, 04100, Latina, Italy

    Flaminia Coluzzi, Maria Sole Scerpa & Marco Centanni

  2. Unit of Anaesthesia, Intensive Care Medicine and Pain Therapy, AUSL Latina c/o ICOT, Latina, Italy

    Flaminia Coluzzi & Maria Sole Scerpa

  3. Endocrinology Unit, Santa Maria Goretti Hospital, AUSL Latina, Latina, Italy

    Marco Centanni

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  1. Flaminia Coluzzi
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  2. Maria Sole Scerpa
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  3. Marco Centanni
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Correspondence to Flaminia Coluzzi.

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Coluzzi, F., Scerpa, M.S. & Centanni, M. The Effect of Opiates on Bone Formation and Bone Healing. Curr Osteoporos Rep 18, 325–335 (2020). https://doi.org/10.1007/s11914-020-00585-4

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