Fenretinide prevents the development of osteoporosis in Cftr-KO mice.

Background: The most recently described phenotype associated with Cystic Fibrosis (CF) is reduced bone mineral density which results in osteopenia and osteoporosis. The etiology of the early onset of osteoporosis in CF patients has remained to be established. It has been suggested that inadequate nutritional absorption of essential fatty acids may play a role in the altered bone metabolism. In this study, we characterized the protective effect of fenretinide [N-(4-hydroxyphenyl) retinamide], a vitamin A derivative, on the early onset of osteoporosis in cystic fibrosis transmembrane conductance regulator knockout (Cftr-KO) mice.

Methods: Using micro-computed-tomography we examined the effect of fenretinide on the bone composition and architecture in a Cftr-KO mouse model which was then confirmed with histological analyses. Plasma fatty acids were quantified using thin layer chromatography-ELISA method.

Results: Twice-weekly treatments with fenretinide, over four weeks dramatically increased trabecular bone volume compared to controls. This increase in bone volume was also related to an increased concentration of ceramide in the plasma resulting in the down regulation of phospholipid-bound AA in Cftr-KO mice.

Conclusions: To our knowledge, this is the first time that fenretinide's protective effect against osteoporosis has been demonstrated. The results of this study strongly suggest that fenretinide has potential to be used as a prophylaxis by preventing the early onset of osteoporosis.