Osteopenia associated with renal transplantation remains a problem in the cyclosporine era. The loss of vertebral bone in our subjects was due to an imbalance in bone remodeling consistent with a toxic effect of glucocorticoids.

Quarles, L. Darryl. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab 285: E1-E9, 2003;10.1152/ajpendo.00016.2003.-There is evidence for a hormone/enzyme/extracellular matrix protein cascade involving fibroblastic growth factor 23 (FGF23), a phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX), and a matrix extracellular phosphoglycoprotein (MEPE) that regulates systemic phosphate homeostasis and mineralization. Genetic studies of autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia (XLH) identified the phosphaturic hormone FGF23 and the membrane metalloprotease PHEX, and investigations of tumorinduced osteomalacia (TIO) discovered the extracellular matrix protein MEPE. Similarities between ADHR, XLH, and TIO suggest a model to explain the common pathogenesis of renal phosphate wasting and defective mineralization in these disorders. In this model, increments in FGF23 and MEPE, respectively, cause renal phosphate wasting and intrinsic mineralization abnormalities. FGF23 elevations in ADHR are due to mutations of FGF23 that block its degradation, in XLH from indirect actions of inactivating mutations of PHEX to modify the expression and/or degradation of FGF23 and MEPE, and in TIO because of increased production of FGF23 and MEPE. Although this model is attractive, several aspects need to be validated. First, the enzymes responsible for metabolizing FGF23 and MEPE need to be established. Second, the physiologically relevant PHEX substrates and the mechanisms whereby PHEX controls FGF23 and MEPE metabolism need to be elucidated. Finally, additional studies are required to establish the molecular mechanisms of FGF23 and MEPE actions on kidney and bone, as well as to confirm the role of these and other potential "phosphatonins," such as frizzled related protein-4, in the pathogenesis of the renal and skeletal phenotypes in XLH and TIO. Unraveling the components of this hormone/enzyme/extracellular matrix pathway will not only lead to a better understanding of phosphate homeostasis and mineralization but may also improve the diagnosis and treatment of hypo-and hyperphosphatemic disorders. phosphatonin; Hyp; X-linked hypophosphatemia; rickets; osteomalacia; hypophosphatemia OUR UNDERSTANDING OF HORMONAL REGULATION of phosphate homeostasis is rapidly expanding. The classical parathyroid hormone (PTH)/vitamin D axis is not sufficient to account for the physiological complexity of renal phosphate handling and bone mineralization (58). Rather, there is emerging evidence for other phosphaturic hormones, collectively called phosphatonins (35), as well as other local factors regulating the mineralization process in hypophosphatemic disorders, referred to as minhibins (57,78). Studies of two inherited hypophosphatemic disorders, autosomal dominant hypophosphatemic rickets (ADHR) (2), and X-linked hypophosphatemia (XLH) (70), and the sporadic tumorinduced osteomalacia (TIO, also called oncogenic oste...