Glucocorticoids, osteocytes, and skeletal fragility: The role of bone vascularity

Abstract

Glucocorticoid administration is required for many inflammatory and autoimmune diseases, but use of these drugs is associated with skeletal side effects including bone loss, fractures, and osteonecrosis. Fractures often occur without a reduction in bone mineral density, strongly suggesting that glucocorticoid excess adversely affects other aspects of bone strength. Although the primary effects of glucocorticoid excess on the skeleton are directly on bone cells, a vascular connection between these cells and the loss of bone strength appears likely. This review examines this connection and how it may explain the greater decline in bone strength than loss of bone mass that occurs with glucocorticoid excess.

Mechanism of Glucocorticoid-Induced Osteoporosis: An Update

“…Glucocorticoids also decrease intestinal calcium absorption thus further predisposing to osteoporosis. Recently, effects of glucocorticoids on decreasing bone vasculature, has also been implicated as a potential mechanism for glucocorticoid effects on bone [126]. There also seems to be an agedependence of glucocorticoid effects on bone.…”

Bmp2 gene in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells

“…During aging or glucocorticoid treatment, bone angiogenesis is reduced and brittleness in bone is increased (Weinstein, 2010;Weinstein et al, 2010). VegfA overexpression in bone marrow leads to formation of new bone and associated blood vessels (Maes et al, 2010a).…”

Glucocorticoids, Inflammation, and Bone

“…Some studies have shown that glucocorticoidinduced fractures tend to be multiple and occur at BMD values that are higher than in patients with other kinds of osteoporosis. The adverse effects on bone of excess glucocorticoid may, therefore, be partly due to abnormalities that are not related to the decline in bone mass [ 121,176 ] .…”

“…Within the fi rst year, BMD is reduced by 6-12% and by about 3% in each subsequent year of additional treatment. The relative risk of fracture escalates by as much as 75% within the fi rst 3 months after initiation of steroid therapy [ 163,176 ] . Up to 50% of patients develop vertebral fractures if under prolonged treatment with systemic glucocorticoids [ 27,41,50,115 ] .…”