Skeletal effects of systemic and topical corticosteroids.

Oral corticosteroids are associated with an increased risk of fractures from negative effects on sex steroids and vitamin D with a negative calcium balance, together with negative effects on the bone cells and the bone matrix. However, the increase in fracture risk with oral corticosteroids seems more linked to daily than to cumulative dose. A small daily dose may consequently be more detrimental than a large cumulative dose given as intermittent doses. Topical corticosteroids administered locally in the eyes, ears, in the mouth, on the skin, and rectally are not associated with an increased risk of fractures. Inhaled corticosteroids are not associated with an increased risk of fractures, except at very high doses that are much higher than the doses usually administered. With regard to the prevention of fractures, the use of topical corticosteroids may be preferred over oral administration where feasible. More research is needed to determine practically applicable intermittent dosing regimens for corticosteroids, replacing daily administration, to assess if this can have the same beneficial clinical effect but avoid, or at least reduce, the risk of osteoporosis and fractures.