Opioid receptor agonists may favorably affect bone mechanical properties in rats with estrogen deficiency-induced osteoporosis

Aleksandra Janas,Joanna Folwarczna

doi:10.1007/s00210-016-1295-6

Aleksandra Janas, Joanna Folwarczna

Open Access

https://doi.org/10.1007/s00210-016-1295-6

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Abstract

The results of epidemiological, clinical, and in vivo and in vitro experimental studies on the effect of opioid analgesics on bone are inconsistent. The aim of the present study was to investigate the effect of morphine (an agonist of opioid receptors), buprenorphine (a partial μ opioid receptor agonist and κ opioid receptor antagonist), and naloxone (an antagonist of opioid receptors) on the skeletal system of female rats in vivo. The experiments were carried out on 3-month-old Wistar rats, divided into two groups: nonovariectomized (intact; NOVX) rats and ovariectomized (OVX) rats. The bilateral ovariectomy was performed 7 days before the start of drug administration. Morphine hydrochloride (20 mg/kg/day s.c.), buprenorphine (0.05 mg/kg/day s.c.), or naloxone hydrochloride dihydrate (2 mg/kg/day s.c.) were administered for 4 weeks to NOVX and OVX rats. In OVX rats, the use of morphine and buprenorphine counteracted the development of osteoporotic changes in the skeletal system induced by estrogen deficiency. Morphine and buprenorphine beneficially affected also the skeletal system of NOVX rats, but the effects were much weaker than those in OVX rats. Naloxone generally did not affect the rat skeletal system. The results confirmed the role of opioid receptors in the regulation of bone remodeling processes and demonstrated, in experimental conditions, that the use of opioid analgesics at moderate doses may exert beneficial effects on the skeletal system, especially in estrogen deficiency.

Highlights

There is a progressive increase in the long-term use of opioid analgesics in the treatment of pain associated with cancer and other diseases, such as degenerative changes in the musculoskeletal system (Cherubino et al 2012)
Bilateral ovariectomy caused a profound decrease in the uterus mass/body mass ratio and increases in the thymus mass/ body mass ratio and body mass gain compared to the NOVX control rats (Table 1)
The effects of drugs acting through opioid receptors on the skeletal system, investigated in the present study, did not confirm the damaging action of opioid analgesics, which might have been expected based on the literature

Summary

Introduction

There is a progressive increase in the long-term use of opioid analgesics in the treatment of pain associated with cancer and other diseases, such as degenerative changes in the musculoskeletal system (Cherubino et al 2012). More and more patients, including the elderly, in whom bone mass physiologically decreases, undergo prolonged exposure to opioid analgesics (agonists, partial agonists and agonist-antagonists of opioid receptors) (Ballantyne 2012). This applies to postmenopausal women who are at increased risk of developing osteoporosis due to estrogen deficiency (Braden et al 2012). The unfavorable effects of opioids on the skeletal system are usually attributed to inhibitory effects

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