OSTEOPOROSIS IS A TOXIC EFFECT OF LONG-TERM ETRETINATE THERAPY

Background and Design: Osteoporosis has been observed with chronic hyp ervitaminosis A but has not been established as a toxic effect of synt hetic retinoid therapy in humans. This cross-sectional study was desig ned to assess bone mineral density (BMD) during long-term therapy with the retinoids etretinate or isotretinoin. Twenty-four patients were e valuated for osteoporosis with the standard techniques: single- and du al-photon absorptiometry. They received 50 g or more of etretinate (15 patients) or isotretinoin (nine patients) for 2 years or longer for t he treatment of skin diseases (ichthyosis [nine patients], Darier's di sease [six patients], xeroderma pigmentosum [four patients], skin canc er [three patients], or psoriasis [two patients]), In each of the two treatment groups, BMDs (measured in grams per square centimeter) were measured at five standard sites tie, lumbar spine, femoral neck, troch anter, Ward's triangle, and radius) and evaluated against a standardiz ed database to control for age, sex, and weight. In addition, for each measurement site, BMDs (controlled for age, sex, and weight) were com pared between the two groups, as a direct control for each other. Obse rvations: Compared with those of the age-, sex-, and weight-matched co ntrols, the BMD values of the etretinate group were significantly decr eased at four of the five measurement sites: femoral neck (90.6%, P = .0001), Ward's triangle (87.8%, P = .0001), trochanter (87.8%, P = .00 12), and radius (85.0% P = .039). In contrast, the BMDs in the isotret inoin group did not differ from control values except for an elevation at the lumbar spine (P = .039). When the two groups were compared, th e mean BMDs were significantly lower in the etretinate group when meas ured at the lumbar spine, trochanter, and radius (P < .05). Conclusion s: This study identified osteoporosis in patients who received long-te rm therapy with etretinate but not isotretinoin. Prospective studies o f BMD would be useful to further define retinoid-associated osteoporos is.