Longitudinal Effects of Prolonged Opioid Use on Cortical Bone Remodeling in a Rabbit Model

The misuse and addiction to opioids (and synthetic opioids) is a serious public health crisis nationwide that has become an epidemic. The overall yearly cost to the United States government for opioid abuse-related healthcare, law enforcement, and education/prevention programs has been estimated at $78.5 billion. This crisis afflicts millions of Americans and costs our healthcare system billions. Current evidence suggests that opioids upset the balance of bone remodeling towards more destruction and less formation of bone. Experimental studies have been limited by the fact that small laboratory animals traditionally used in bone research (mice and rats) do not exhibit spontaneous cortical bone remodeling, making them a poor choice of animal model for this subject. The current proposal seeks to develop a longitudinal model for studying the effects of prolonged opioid exposure on cortical bone remodeling in an animal which remodels its cortical bone in a manner comparable to humans, the rabbit. Given the limited data available related to the longitudinal impact of opioid abuse on bone remodeling, we must further understandings of the underlying biological processes to improve the applicability of histological age-estimation methods and scientific standards within the field of forensic anthropology. An innovative 3D Xray imaging technique (micro-CT), combined with dynamic histomorphometry, will allow us to describe how analgesic drugs, particularly morphine and fentanyl, affect microscopic structures of cortical bone used in histological age estimation methods in forensic anthropology. Male New Zealand White rabbits will be divided into three groups of seven animals each: morphine, fentanyl, and control. Repeated Measures ANOVA tests will be employed to compare histological parameters conventionally quantified to estimate age-at-death, between the two opioid groups and controls, spanning four time points. The implications are critical given that many of the skeletal remains examined by forensic anthropologists come from marginalized backgrounds with substance abuse issues and overall poor health. Thus, histological methods developed on healthy cases may not be useful in the assessment of such individuals, resulting in severely compromised age-at-death estimates. Although micro-CT imaging is not available to all forensic anthropologists, the ultimate goal of this work is to discover the true impact of opioid abuse on bone microstructure and prepare new and accessible guidelines for routine microscopic analysis. Knowledge gained from the proposed work will provide the basis for developing powerful new histological aging techniques that can be applied to unknown individuals from the regrettably growing pool of victims of opioid abuse. This project contains a research and/or development component, as defined in applicable law, and complies with Part 200 Uniform Requirements - 2 CFR 200.210(a)(14). CA/NCF