MAPK inhibition and growth hormone: a promising therapy in XLH

X-linked hypophosphatemia (XLH) leads to growth retardation and bone deformities, which are not fully avoided by conventional treatment with phosphate and vitamin D analogs. Pediatric patients have been treated with growth hormone (GH), and recent findings suggest that blocking fibroblast growth factor 23 actions may be the most effective therapy, but its effects on growth are not known. We here report the effect of MAPK inhibition alone or associated with GH on growth and growth plate and bone structure of young Hyp (the XLH animal model) mice. Untreated Hyp mice were severely growth retarded and had marked alterations in both growth plate structure and dynamics as well as defective bone mineralization. GH accelerated growth and improved mineralization and the cortical bone, but it failed in normalizing growth plate and trabecular bone structures. MAPK inhibition improved growth and rickets and, notably, almost normalized the growth plate organization. The administration of a MAPK pathway inhibitor plus ...