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Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system


Petrizzi, Lucio; Mariscoli, Massimo; Valbonetti, Luca; Varasano, Vincenzo; Langhoff, Jens D; von Rechenberg, Brigitte (2007). Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system. BMC Musculoskeletal Disorders, 8:43.

Abstract

BACKGROUND: Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxone is a pure opioid antagonist. Morphine-induced osteocalcin inhibition was abolished when osteoblasts were incubated with naloxone. Naloxone restored the altered cellular and tissue physiology by removing beta-endorphins from specific receptors. However, this is only possible if the circulating Ca concentration is adequate. The aim of the present study was to evaluate the efficacy of parenteral naloxone administration in inducing fast mineralization and callus remodelling in a group of sheep with a standardised bone lesion.
METHODS: Twenty ewes were randomly assigned to 4 treatment groups. Group A acted as control, group B received a solution of calcium gluconate, group C a solution of naloxone, and group D a solution of calcium gluconate and naloxone. A transverse hole was drilled in the left metacarpus, including both cortices, then parenteral treatment was administered intramuscularly, daily for four weeks. Healing was evaluated by weekly radiographic examination for eight weeks. For quantitative evaluation, the ratio of the radiographic bone density between the drill area and the adjacent cortical bone was calculated. After eight weeks the sheep were slaughtered and a sample of bone was collected for histopathology
RESULTS: Group D showed a higher radiographic ratio than the other groups. Sheep not treated with naloxone showed a persistently lower ratio in the lateral than the medial cortex (P < 0.01). Histopathology of bone samples showed more caverns and fewer osteoblasts in group D than in the other groups (P </= 0.001).
CONCLUSION: A low-dose parenteral regimen of naloxone enhances mineralization and remodelling of the callus in healing cortical defects in sheep, especially if associated with calcium gluconate.

BACKGROUND: Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxone is a pure opioid antagonist. Morphine-induced osteocalcin inhibition was abolished when osteoblasts were incubated with naloxone. Naloxone restored the altered cellular and tissue physiology by removing beta-endorphins from specific receptors. However, this is only possible if the circulating Ca concentration is adequate. The aim of the present study was to evaluate the efficacy of parenteral naloxone administration in inducing fast mineralization and callus remodelling in a group of sheep with a standardised bone lesion.
METHODS: Twenty ewes were randomly assigned to 4 treatment groups. Group A acted as control, group B received a solution of calcium gluconate, group C a solution of naloxone, and group D a solution of calcium gluconate and naloxone. A transverse hole was drilled in the left metacarpus, including both cortices, then parenteral treatment was administered intramuscularly, daily for four weeks. Healing was evaluated by weekly radiographic examination for eight weeks. For quantitative evaluation, the ratio of the radiographic bone density between the drill area and the adjacent cortical bone was calculated. After eight weeks the sheep were slaughtered and a sample of bone was collected for histopathology
RESULTS: Group D showed a higher radiographic ratio than the other groups. Sheep not treated with naloxone showed a persistently lower ratio in the lateral than the medial cortex (P < 0.01). Histopathology of bone samples showed more caverns and fewer osteoblasts in group D than in the other groups (P </= 0.001).
CONCLUSION: A low-dose parenteral regimen of naloxone enhances mineralization and remodelling of the callus in healing cortical defects in sheep, especially if associated with calcium gluconate.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Veterinary Clinic > Equine Department
Dewey Decimal Classification:570 Life sciences; biology
630 Agriculture
Language:English
Date:2007
Deposited On:11 Feb 2008 12:11
Last Modified:03 May 2016 17:44
Publisher:BioMed Central
ISSN:1471-2474
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1186/1471-2474-8-43
Official URL:http://www.biomedcentral.com/content/pdf/1471-2474-8-43.pdf
PubMed ID:17518998
Permanent URL: http://doi.org/10.5167/uzh-25

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