Reversible Deterioration in Hypophosphatasia Caused by Renal Failure With Bisphosphonate Treatment

• DOI: 10.1002/jbmr.2495
• Publication Date: 2015-03-04T11:42:19Z
• Authors: Tim Cundy; Toshimi Michigami; Kanako Tachikawa; Michael Dray; John F Collins; Eleftherios P Pas...; Sonja Gamsjaeger; Andreas Roschger; Nadja Fratzl-Zelman; Paul Roschger; Klaus Klaushofer
• Keywords: Hypophosphatasia

ABSTRACT Hypophosphatasia is an inborn error of metabolism caused by mutations in the ALPL gene. It characterized low serum alkaline phosphatase (ALP) activity and defective mineralization bone, but phenotype varies greatly severity depending on degree residual enzyme activity. We describe a man with compound heterozygous ALPL, no previous bone disease, who suffered numerous disabling fractures after he developed progressive renal failure (for which eventually needed dialysis treatment) was prescribed alendronate treatment. A biopsy showed marked osteomalacia osteoblast numbers elevated pyrophosphate concentrations at mineralizing surfaces. In vitro testing that one mutation, T117H, produced ALP protein almost activity; second, G438S, normal activity, its inhibited raising media phosphate concentration, suggesting retention (attributable to uremia) could have contributed phenotypic change, although pathogenic effect bisphosphonate treatment also likely. Alendronate discontinued and, while suitable kidney donor sought, patient treated for 6 months teriparatide, significantly reduced osteomalacia. Eighteen successful transplantation, free symptoms scintigraphic lesions had resolved. third hyperosteoidosis plentiful new formation rate. This case illustrates how pharmacological (bisphosphonate physiologic (renal failure) changes “environment” can dramatically affect genetic disorder. © 2015 American Society Bone Mineral Research.