Carlos R Ferreira, Dillon Kavanagh, Ralf Oheim, Kristin Zimmerman, Julian Stürznickel, Xiaofeng Li, Paul Stabach, R Luke Rettig, Logan Calderone, Colin MacKichan, Aaron Wang, Hunter A Hutchinson, Tracy Nelson, Steven M Tommassini, Simon von Kroge, Imke A K Fiedler, Ethan R Lester, Gilbert W Moeckel, Björn Busse, Thorsten Schinke, Thomas O Carpenter, Michael A Levine, Mark C Horwowitz, Demetrios T Braddock
Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and Autosomal Recessive Hypophosphatemic Rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc...
January 19, 2021: Journal of Bone and Mineral Research