Osteoporosis is a condition characterized by weak bones. With reduced bone density, bones may fracture easily and oftentimes lead to deforming the physical structure of the body. Approximately 4.74 million Australians over 50 have osteoporosis or poor bone health and the number is growing due to the aging population.
Abnormalities in the bone remodeling cycle, particularly an imbalance in the ratio of bone forming to bone mineralizing cells, is thought to cause osteoporosis. The endocannabinoid system acts to maintain homeostasis and balance the bone cycle.
This image is a simplification for website aesthetics only. For more information please refer to the clinical studies referenced below.
Osteoclasts – bone reabsorbing cells
Osteoblasts –bone forming cells
Simplified Bone Remodeling Cycle
- Following chemical stimuli, damage, or mechanical stress, mature osteoclasts migrate to the site requiring bone reabsorption. Osteoclast formation in mediated by a number of cytokines. The amount of bone resorbed is dependent on the number, size, and life span of the newly formed osteoclasts.
- Mature osteoclasts undergo apoptosis and are removed by phagocytes. This is termed the reversal phase.
- New bone is laid down by the osteoblasts that originate from bone marrow. Bone formation is initiated by chemotactic transforming growth factor beta (TGFβ) as well as bone matrix proteins such as collagen type 1
- The remaining mature osteoblasts are either buried within the matrix as osteocytes or converted to lining cells in the quiescent state.
The Endocannabinoid System and Osteoporosis
- CB1 and CB2 receptors are known to be found in the skeleton
- CB1 receptors are found on nerve fibers innervating bone as well as cells in the bone marrow
- CB1 receptors are also found on osteoblasts, osteoclasts and bone marrow derived adipocytes
- Osteoclasts, osteoblasts and osteocytes also express CB2 receptors at significantly higher levels than those reported for CB1
The way in which activation and inactivation of the endocannabinoid system affects bone density and its application to osteoporosis is not so straight forward. Several mouse models have been used to test this interaction. In each test researchers found that the CB-deficient mice, lacking either CB1, CB2 or both, exhibited higher bone density than their wild-type counterparts. While this suggests that CB inactivation may be useful as a preventative measure, interestingly, each group of CB deficient mice showed an increase in age related osteoporosis. Like its role in other systems of the body the endocannabinoid system plays an important modulatory role in the bone cycle. Up-regulation of this system may prove helpful for prevention of osteoporosis in older patients or others with a predisposition to it. It is important to note that these studies are all based on animal models and the extent to which the results translate to humans still requires further research.
Bab, I., Zimmer, A., & Melamed, E. (2009). Cannabinoids and the skeleton: from marijuana to reversal of bone loss. Annals of medicine, 41(8), 560-567.
Idris, A. I., Sophocleous, A., Landao-Bassonga, E., Canals, M., Milligan, G., Baker, D., … & Ralston, S. H. (2009). Cannabinoid receptor type 1 protects against age-related osteoporosis by regulating osteoblast and adipocyte differentiation in marrow stromal cells. Cell Metabolism, 10(2), 139-147.
Idris, A. I., & Ralston, S. H. (2010). Cannabinoids and bone: friend or foe?.Calcified tissue international, 87(4), 285-297.
Kogan, N. M., Melamed, E., Wasserman, E., Raphael, B., Breuer, A., Stok, K. S., … & Bab, I. (2015). Cannabidiol, a Major Non‐Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts. Journal of Bone and Mineral Research.