Chronic Δ9-Tetrahydrocannabinol Inhalation Following Osteoporosis Results in Bone Deficits

Background: Osteoporosis, a debilitating bone disease characterized by low bone mineral density, poses a large burden on the population. Current pharmacological treatment options are limited, with antiresorptive drugs being the current first-line option. Recent research has shown that the endocannabinoid system, modulated by endocannabinoids and phytocannabinoids, may influence bone remodeling. As the prevalence of cannabis use and research into its medicinal potential continues to increase, its therapeutic potential has emerged. Objective: To investigate the role of Δ9-tetrahydrocannabinol (THC) inhalation in treating osteoporosis in a rodent model. Methods: Adult female Sprague-Dawley rats underwent ovariectomy (OVX) to induce osteoporosis. Four weeks post-OVX, rats received either THC or Air treatment via inhalation for 8 weeks. A control group of age-matched rats received sham surgery. Rats were then euthanized at 38 weeks old, and hindlimb samples were collected for caliper, microCT, and biomechanical analyses. Results: OVX Air-treated rats showed significantly decreased trabecular bone volume, trabecular bone volume fraction, trabecular separation, trabecular tissue mineral density, trabecular number, and connective density compared to sham surgery controls. Compared with Air controls, OVX rats treated with THC showed increased endosteal volume (20%; p < 0.05). THC-treated rats also showed decreased trabecular bone mineral density (2%; p < 0.005) and trabecular thickness (14%; p < 0.05). Conclusions: Chronic inhaled THC worsened key aspects of trabecular bone microarchitecture. Results do not support use of THC vapor as a therapeutic agent for osteoporosis and suggest THC may adversely affect bone quality in estrogen-deficient states. Further research is needed to evaluate dose-dependent effects and to distinguish the skeletal impacts of different cannabinoid components.