Abstract
BackgroundSeveral 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 β-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.MethodsTwenty 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 histopathologyResultsGroup 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).ConclusionA 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.
Highlights
IntroductionMany drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing
Several diseases affect bone healing and physiology
Several diseases, including metabolic, neoplastic and infectious conditions, affect bone healing and bone physiology, and many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing [1]
Summary
Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. Naloxone restored the altered cellular and tissue physiology by removing βendorphins from specific receptors. This is only possible if the circulating Ca concentration is adequate. Several diseases, including metabolic, neoplastic and infectious conditions, affect bone healing and bone physiology, and many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing [1]. It has been suggested that high endorphin levels in situations of stress or pain can alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells [9]. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes
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