Glucocorticoid-induced Osteoporosis: From Pathogenesis to Treatment
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Glucocorticoid-induced osteoporosis(GIO) is the most common type of secondary osteoporosis. However, the mechanism responsible for GIO and the appropriate treatment for this problem remain poorly understood. The pathogenesis of GIO can be explained by a traditional model and a scientific model of bone cells. According to the traditional model, glucocorticoids decrease intestinal calcium absorption and increase urinary calcium excretion, and the negative calcium balance induces secondary hyperparathyroidism. In the more recent scientific model of bone cells, glucocorticoids stimulate osteoclast cells directly and increase osteoclast cell activity and survival during early accelerated bone loss this activity induces high bone turnover and rapid bone loss. Glucocorticoids suppress osteoblast cell activity directly and suppress osteoblast cell activity indirectly by osteoclast-mediated osteoblast recruitment during late decelerated continuous sustained bone loss. This results in low bone turnover and slow bone loss. A more detailed action mechanism of glucocorticoids in osteoblasts may include: (1) Runx2 expression, (2) PPAR gamma expression, and (3) Wnt/β-catenin signaling. Glycogen synthase kinase-3β(GSK3β) also plays a role in osteoblast apoptosis. Traditional general guidelines and life style modifications for GIO are: (1) doses of glucocorticoids as low as possible (2) duration of steroid administration as short as possible (3) topical rather than systemic glucocorticoid treatment, if possible (4) smoking cessation (5) reduction of alcohol; (6) weight -bearing exercise (7) adequate amounts of calcium and vitamin D intake (8) and the prevention of falls. Medical treatment options for GIO are sex hormones, calcitonin, bisphosphonate, and parathyroid hormone. In some studies, estrogen/progestin therapy in postmenopausal women and testosterone therapy in hypogonadal men have shown a beneficial effect on bone mineral density(BMD) of the spine. Calcitonin treatment may have the additional benefit of relieving the pain associated with vertebral fractures. Bisphosphonates reduce early accelerated bone loss, prevents bone resorption by inflammatory cytokines, and demonstrates anti-apoptotic effects on osteoblasts and osteocytes. In many studies, bisphosphonates have shown significant increase in the BMD of the spine and reduction of the risk of vertebral fractures in GIO. Parathyroid hormone(PTH) might be a better treatment option than bisphosphonate therapy, because PTH (1) targets osteoblasts, (2) increases osteoblast recruitment, activity, and survival, and (3) does not suppress osteoclasts. PTH treatment significantly increased lumbar spine BMD and total hip BMD and prevented vertebral fractures compared to alendronate therapy in patients with GIO. Future therapy targeting osteoblasts include: (1) the GSK3β inhibitor, (2)Dickkopf antibody, (3) Sclerostin antibody.
Abstract
Glucocorticoid-induced osteoporosis(GIO) is the most common type of secondary osteoporosis. However, the mechanism responsible for GIO and the appropriate treatment for this problem remain poorly understood. The pathogenesis of GIO can be explained by a traditional model and a scientific model of bone cells. According to the traditional model, glucocorticoids decrease intestinal calcium absorption and increase urinary calcium excretion, and the negative calcium balance induces secondary hyperparathyroidism. In the more recent scientific model of bone cells, glucocorticoids stimulate osteoclast cells directly and increase osteoclast cell activity and survival during early accelerated bone loss this activity induces high bone turnover and rapid bone loss. Glucocorticoids suppress osteoblast cell activity directly and suppress osteoblast cell activity indirectly by osteoclast-mediated osteoblast recruitment during late decelerated continuous sustained bone loss. This results in low bone turnover and slow bone loss. A more detailed action mechanism of glucocorticoids in osteoblasts may include: (1) Runx2 expression, (2) PPAR gamma expression, and (3) Wnt/β-catenin signaling. Glycogen synthase kinase-3β(GSK3β) also plays a role in osteoblast apoptosis. Traditional general guidelines and life style modifications for GIO are: (1) doses of glucocorticoids as low as possible (2) duration of steroid administration as short as possible (3) topical rather than systemic glucocorticoid treatment, if possible (4) smoking cessation (5) reduction of alcohol; (6) weight -bearing exercise (7) adequate amounts of calcium and vitamin D intake (8) and the prevention of falls. Medical treatment options for GIO are sex hormones, calcitonin, bisphosphonate, and parathyroid hormone. In some studies, estrogen/progestin therapy in postmenopausal women and testosterone therapy in hypogonadal men have shown a beneficial effect on bone mineral density(BMD) of the spine. Calcitonin treatment may have the additional benefit of relieving the pain associated with vertebral fractures. Bisphosphonates reduce early accelerated bone loss, prevents bone resorption by inflammatory cytokines, and demonstrates anti-apoptotic effects on osteoblasts and osteocytes. In many studies, bisphosphonates have shown significant increase in the BMD of the spine and reduction of the risk of vertebral fractures in GIO. Parathyroid hormone(PTH) might be a better treatment option than bisphosphonate therapy, because PTH (1) targets osteoblasts, (2) increases osteoblast recruitment, activity, and survival, and (3) does not suppress osteoclasts. PTH treatment significantly increased lumbar spine BMD and total hip BMD and prevented vertebral fractures compared to alendronate therapy in patients with GIO. Future therapy targeting osteoblasts include: (1) the GSK3β inhibitor, (2)Dickkopf antibody, (3) Sclerostin antibody.
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