New insights into the biology of glucocorticoid-induced osteoporosis

Glucocorticoid (GC) use results in rapid bone loss and elevated fracture risk. The excess bone fragility from GC treatment is multi-factorial. GCs alter calcium and phosphorus metabolism, which can result in elevation of parathyroid hormone (PTH) and early stimulation of osteoclast activity and bone remodeling, followed by a delayed but sustained reduction in osteogenesis, osteoblast activity and osteocyte metabolism. The changes in bone cell viability with GCs results in reduction of localized and whole bone strength. New data reveal that GC use may influence mineral metabolism through FGF23. The altered perilacunar mineralization around GC-treated osteocytes may be secondary to increased FGF23 production. In addition, low doses of GCs can induce self-preservation of osteocytes through the molecular mechanisms of autophagy, while higher doses of GCs induce osteocyte apoptosis. Osteocytic autophagy may allow for cell survival and then, with withdrawal of GCs, for the repair of lost bone tissue. Currently, both antiresorptive and anabolic agents are prescribed to prevent or treat GC-induced bone loss. Additional studies are needed to further explore whether current treatments used for GC-induced bone loss alter osteocyte metabolism and how this influences localized and whole bone strength. IBMS BoneKEy. 2011 May;8(5):229236. 2011 International Bone & Mineral Society Introduction – The Clinical Importance of Glucocorticoid-Induced Bone Loss Glucocorticoids (GCs) are frequently used in clinical medicine to treat non-infectious inflammatory diseases. However, GC use results in rapid trabecular bone loss and a high incident fracture risk. Epidemiologic studies show 50% of rheumatoid arthritis patients treated with chronic GCs will suffer an osteoporotic fracture; baseline data from randomized clinical trials show a prevalence of vertebral fracture of 30% (1-6). Other studies show that both old and young, men and women, and all ethnic groups studied lose bone mass with GC treatment, making this an important public health problem (7). Because patients treated with GCs may require treatment for a long period of time, thereby increasing their risk of fractures, there is a medical need to understand the biology of GC-induced bone loss so that clinicians can effectively prevent and treat this disease. The observational data from GC clinical studies shows that the initiation of GC treatment is associated with a change in bone metabolism, which in turn leads to a rapid reduction in bone mass at sites rich in trabecular bone, e.g., the vertebra and femur, with incident vertebral fracture risk elevated within 1 year of initiating GC treatment (8-10). Nevertheless, the loss of trabecular mass and architecture do not entirely explain the increase in fracture risk, as individuals treated with GCs frequently experience fractures at higher BMDs than women with postmenopausal osteoporosis (9). The Biology of GC-Induced Bone Loss GC treatment results in changes in bone remodeling (8;11). Observations of surface and biochemically-based turnover in clinical studies of glucocorticoid-induced osteoporosis show a reduction in trabecular IBMS BoneKEy. 2011 May;8(5):229-236 http://www.bonekey-ibms.org/cgi/content/full/ibmske;8/5/229 doi: 10.1138/20110511