Effect of cannabinoid receptors 1 modulation on osteoporosis in a rat model of different ages.

Osteoporosis is a common health problem. The endocannabinoid pathway has been implicated as an important regulator of bone turnover. Rimonabant is a potent cannabinoid receptor1 (CB1) receptor antagonist with wide therapeutic use as an antiobesity drug that has been withdrawn due to side effects in the form of depression and suicidal attacks. This study investigated whether glucocorticoid induced bone loss is linked to CB1 signaling and whether modulation of CB1 function affects the deleterious effects of glucocorticoid treatment on bone remodeling in rats. Sixty four rats were divided into two main groups: group 1 (G1) consisted of 12-14 month old rats and group 2 (G2) consisted of 3-4 month old rats. Each main group subdivided into four subgroups as follows: (NC1) and (NC2), the negative control groups, (MP1) and (MP2), received methylprednisolone (glucocorticoid), (RIM1) and (RIM2), received rimonabant, (MP + RIM1) and (MP + RIM2) received methylprednisolone with rimonabant. There was a significant decrease in bone mineral density (BMD) and bone mineral content (BMC) of the tibia bones together with a decrease in osteoprotegrin (OPG) expression but with a significant increase in receptor activator of nuclear factor kappa B ligand (RANKL) expression in osteoporotic rats. These parameters were reversed with co-administration of rimonabant with methylprednisolone in young rats, though it increased the severity of osteoporosis in older rats. Image analysis technique revealed that there was a significant improvement in cortical bone thickness (CBT) and mean trabecular bone density (TBD) in young group only after rimonabant either alone or with glucocorticoid. CB1 receptors play age related different roles in bone turnover. So, CB1 antagonist can be used to prevent corticosteroid induced osteoporosis in young age but should be avoided in old age.