Osteoporosis
Osteoporosis is a chronic skeletal disorder characterized by low bone mass, impaired bone microarchitecture, and increased fracture risk. It results from an imbalance between bone resorption and formation, often due to aging, hormonal changes, systemic inflammation, or metabolic dysfunction. With an estimated 1 in 3 women and 1 in 5 men over age 50 affected globally, osteoporosis presents a major public health challenge with substantial morbidity, mortality, and socioeconomic burden.
Current therapies, primarily antiresorptives or anabolic agents, offer partial efficacy, limited durability, or adverse effects with long-term use. New pharmacological strategies are needed to restore healthy bone remodeling while avoiding systemic complications.
The Endocannabinoid System in Bone Remodeling
The endocannabinoid system (ECS) plays a critical regulatory role in skeletal physiology. We were the first to demonstrate that both CB1R and CB2R are expressed in bone tissue, where they influence the activity of osteoblasts and osteoclasts, modulate bone formation and resorption, and affect skeletal response to mechanical and hormonal cues.
Our lab has shown that CB1R activation disrupts bone homeostasis, particularly under metabolic stress conditions such as obesity, diabetes, or postmenopausal bone loss. In contrast, peripheral CB1R blockade or CB2R agonism preserves bone mass, enhances bone strength, and improves trabecular architecture in rodent models. In parallel, we have identified that endocannabinoid-like compounds, such as oleoyl serine, exert anabolic effects on bone by stimulating osteoblast activity and reducing osteoclast-mediated resorption. Building on this discovery, we have developed novel synthetic analogs of oleoyl serine that demonstrate enhanced efficacy and improved pharmacokinetic properties. These next-generation compounds are currently advancing through preclinical development as promising candidates for safer, more effective osteoporosis therapies.
Our Approach
We apply a multi-model, translational framework to study the role of CB1R and other metabolic regulators in skeletal degeneration and repair:
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Chemical- and surgical-induced models of osteoporosis, as well as genetic-induced mouse models [Magel2-null mice; Prader-Willi Syndrome (PWS)], to mimic postmenopausal, age-related or genetic-induced osteoporosis
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Histomorphometric and micro-CT imaging to evaluate bone density, architecture, and mechanical properties
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Serum and tissue biomarker analysis to assess bone turnover, inflammation, and endocrine regulation
We also investigate the link between systemic metabolic dysfunction and bone integrity, highlighting the concept that bone health is deeply interconnected with liver, kidney, and adipose tissue signaling networks.
