Stimulation of osteoclast formation and bone resorption by glucocorticoids: Synergistic interactions with the calcium regulating hormones parathyroid hormone and 1,25(OH)2-vitamin D3

• Osteoporosis is a significant health problem, with skeletal fractures increasing morbidity and mortality. Excess glucocorticoids (GC) represents the leading cause of secondary osteoporosis. The first phase of glucocorticoid-induced osteoporosis is increased bone resorption. In this Chapter, in vitro studies of the direct glucocorticoid receptor (GR) mediated cellular effects of GC on osteoclasts to affect bone resorption and indirect effects on osteoblast lineage cells to increase the RANKL/OPG ratio and stimulate osteoclastogenesis and bone resorption are reviewed in detail, together with detailed descriptions of in vivo effects of GC in different portions of the skeleton in research animals and humans. Brief sections are devoted to contrasting functions of GC in osteonecrosis, vitamin D formation, in vitro and in vivo bone resorptive actions dependent on vitamin D receptor and vitamin D toxicity, as well as the molecular basis of GR action. Included are also more detailed assessments of the interactions of GC with the major calcium regulating hormones, 1,25(OH)2-vitamin D3 and parathyroid hormone, describing the in vitro increases in RANKL/OPG ratios, osteoclastogenesis and synergistic bone resorption that occurs when GC is combined with either 1,25(OH)2-vitamin D3 or parathyroid hormone. Additionally, a molecular basic for the synergistic interaction of GC with 1,25(OH)2-vitamin D3 is provided along with a suggested molecular basic for the interaction between GC and parathyroid hormone.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Bone resorption

Glucocorticoid

Osteoclast

Osteoporosis

Parathyroid hormone

Vitamin D

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