High-Dose Treatment With Vitamin A Analogues and Risk for Fractures
Vestergaard P, Rejnmark L, Mosekilde L
Arch Dermatol. 2010;146:478-482
Study Summary
Hypervitaminosis A is known to cause adverse musculoskeletal effects, including bone spur formation, premature epiphyseal closure, diffuse idiopathic skeletal hyperostosis, and osteoporosis. In contrast, the link between oral retinoid drugs (synthetic derivatives of vitamin A, such as etretinate, acitretin, and isotretinoin) and adverse musculoskeletal changes is less clear. Oral retinoids may induce premature epiphyseal closure in children and tendon and ligament calcification in adults. In contrast, oral retinoids do not seem to increase the risk for osteoporosis, with one recent, large study showing no reduction in the bone mineral densities of teenagers undergoing a single course of oral isotretinoin for nodulocystic acne.
Now, in a comprehensive case-control study of the Danish population, Vestergaard and colleagues report no association between oral retinoid use (isotretinoin and acitretin) and the risk for bone fracture. This registry-based analysis included a total of 124,655 patients who sustained bone fractures in 2000, compared with 373,962 randomly selected age- and sex-matched controls. Investigators controlled for confounding variables known to increase the risk for fracture, including use of corticosteroids, alcoholism, and other comorbidities.
This large-scale analysis found no association between oral retinoid use and the risk for fractures, even at high retinoid doses. In addition, investigators saw no increase in fracture risk with longer retinoid courses. This finding held true for both isotretinoin and acitretin.
Viewpoint
In this important case-control study, Vestergaard and colleagues provide compelling evidence that oral retinoid drugs do not increase the risk for fractures, even when administered at higher doses and over longer periods. These results correlate nicely with a recent prospective study showing no reduction in bone mineral density in adolescent patients who took oral isotretinoin for nodulocystic acne.
Should one conclude from these findings that oral retinoids pose no risk for adverse musculoskeletal effects? Clearly not, since Vestergaard and associates' analysis is limited to a single clinical endpoint: fractures. Future studies should focus on other potential adverse effects of chronic oral retinoid use, such as diffuse idiopathic skeletal hyperostosis, dystrophic calcification of tendons and ligaments, and premature epiphyseal closure in children and adolescents.
Abstract