Effect of fenretinide on bone mineral density and metabolism in women withearly breast cancer

Prolonged administration of natural or synthetic retinoids has been associa ted with significant skeletal abnormalities, including osteoporosis. We stu died the effects of the synthetic retinoid fenretinide (N-4-hydroxyphenylre tinamide, or 4-HPR) administered for a mean of 40 months on bone mineral de nsity and metabolism in 66 consecutive women with early breast cancer belon ging to a secondary prevention trial. The mean (+/-SD) bone mineral density at the distal and ultradistal forearm were, respectively, 0.61 +/- 0.08 an d 0.30 +/- 0.05 g/cm(2) in 33 treated women and 0.62 +/- 0.07 and 0.29 +/- 0.07 g/cm(2) in 33 control women (p = ns for both). Also, no significant di fference was observed in markers of bone formation such as bone alkaline ph osphatase and osteocalcin, nor in urinary bone resorption markers such as c alcium, hydroxyproline, and type I bone collagen cross-linked N-telopeptide (NTx). However, a border-line higher excretion of urinary calcium and NTx was found in the 4-HPR group after adjustment for menopausal status. We con clude that prolonged administration of 4-HPR is not associated with signifi cant alterations of bone mineral density of the forearm. However, a trend t owards an increase in bone resorption markers suggests the need for further assessment at different skeletal sites.