Cannabinoid receptors in osteoporosis and osteoporotic pain: a narrative update of review.

Osteoporosis is a skeletal disease with decreased bone mass and alteration in microarchitecture of bone tissue, and these changes put patients in risk of bone fracture. As a common symptom of osteoporosis and complication of osteoporotic fracture, chronic pain is a headache for clinicians. Nonsteroidal anti-inflammatory drugs (NSAIDs), selective COX-2 inhibitors and opioid drugs can temporarily reduce osteoporotic pain but have relevant side effects, such as addiction, tolerability and safety. The review summarized the recent advancements in the study of CB receptors in osteoporosis and osteoporotic pain and related mechanisms.Recent studies indicated the two nociceptive receptors, cannabinoid receptor (CB) and transient receptor potential vanilloid type 1 (TRPV1) channel, are co-expressed in bone cells and play important role in the metabolism of bone cells, suggesting that dualtargeting these 2 receptors/channel may provide a novel approach for osteoporotic pain. In addition, both CB receptor and TRPV1 channel are found to be expressed in the glial cells which play vital role in mediating inflammation, chronic pain and metabolism of bone cells, suggesting a role of glial cells inosteoporotic pain.Multiple-targeting against glial cells, CB receptors and TRPV1 channel may be one effective therapeutic strategy for osteoporotic pain in the future, following the elucidation of the complicated mechanism.