Glucocorticoid-induced osteoporosis: pathophysiology and therapy

Abstract

Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. Fractures, which are often asymptomatic, may occur in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Vertebral fractures occur early after exposure to glucocorticoids, at a time when bone mineral density (BMD) declines rapidly. Fractures tend to occur at higher BMD levels than in women with postmenopausal osteoporosis. In human subjects, the early rapid decline in BMD is followed by a slower progressive decline in BMD. Glucocorticoids have direct and indirect effects on the skeleton. The primary effects are on osteoblasts and osteocytes. Glucocorticoids impair the replication, differentiation and function of osteoblasts and induce the apoptosis of mature osteoblasts and osteocytes. These effects lead to a suppression of bone formation, a central feature in the pathogenesis of GIO. Glucocorticoids also favor osteoclastogenesis and as a consequence increase bone resorption. Bisphosphonates are effective in the prevention and treatment of GIO. Anabolic therapeutic strategies are under investigation.

Effects of propranolol on the development of glucocorticoid-induced osteoporosis in male rats

“…In humans, it occurs in two phases: a rapid, early phase in which bone mineral density is reduced possibly due to increased bone resorption, and a slower, progressive phase in which bone mineral density decreases due to impaired bone formation [9]. However, low-dose prednisone was reported to decrease bone formation markers and to decrease the bone resorption marker free urinary deoxypyridinoline in postmenopausal women, indicating the possibility of inhibition of bone resorption [38].…”

“…At present, bisphosphonates (antiresorptive drugs) are considered to be the first line option for the treatment of glucocorticoid-induced osteoporosis [9][10][11]. However, because the dominant bone-damaging mechanism in glucocorticoid-induced osteoporosis is the inhibition of bone formation, we decided to study effects of propranolol, a drug that should stimulate bone formation and inhibit bone resorption.…”

“…Glucocorticoid-induced osteoporosis is the most frequently occurring type of secondary osteoporosis [9,40]. For the treatment of glucocorticoid-induced osteoporosis, usually bisphosphonates, which are antiresorptive agents, are used [10,11,40].…”

Glucocorticoids maintain human osteoclasts in the active mode of their resorption cycle

“…This effect on bone for a long time has been ascribed mainly to impairment of osteoblasts (OBs), the cells responsible for bone formation. Accordingly, the strong negative effects of GCs on bone-formation rates and OB survival are well documented, (1,2) and the latter effect also was extended to osteocytes. (3) However, lack of bone formation and function of OB lineage cells cannot be responsible alone for some of the most important effects that GCs have on bone.…”

Prevention of glucocorticoid‐induced bone loss in mice by inhibition of RANKL

“…Profound, rapid-onset bone loss and fragility fractures are frequent and severe complications of systemic glucocorticoid therapy. In fact, glucocorticoidinduced osteoporosis is the most common cause of secondary osteoporosis and affects up to 50% of patients receiving long-term glucocorticoid therapy (2,3). Bone loss in glucocorticoid-induced osteoporosis is most pronounced in trabecular bone and in the cortical shell of the vertebral body, typically leading to vertebral compression fractures.…”