title: Parathyroid hormone treatment improves pain and fracture healing in adult hypophosphatasia.
abstract: BACKGROUND
  Adult hypophosphatasia (HPP) is characterized by low serum alkaline phosphatase (S-ALP) and poorly healing fractures due to ALPL gene mutations. Increased S-ALP and fracture repair were reported in two patients treated with teriparatide, PTH 1-34. The effects of full-length PTH 1-84 have not been studied.
  
  
  METHODS
  Two 56- and 64-yr-old sisters (patients 1 and 2) with HPP and with long-standing, painful femur fractures received PTH 1-84 (Preotact, 100 μg/d sc) for 7 and 18 months, respectively. Patient 1 had another treatment 8 months later because of new femur fractures. We characterized the underlying mutation(s) and treatment effects according to S-ALP, bone markers, serum ionized calcium, plasma phosphate (P-Pi), pain, mobility, and fracture healing.
  
  
  RESULTS
  Both patients were compound heterozygotes for a p.G339R and p.E191K ALPL mutation. S-ALP increased significantly, 4.9- and 6.8-fold in patient 1 and 2.7-fold in patient 2. Responses decreased at 6 months but remained higher than basal activity. Serum N-terminal propeptide of type I procollagen and urinary N-telopeptide of type I collagen increased 14- to 19-fold and 9-5-fold in patient 1, respectively, and 9- and 3-fold in patient 2. P-Pi fluctuated in patient 1 and increased in patient 2. Pain and mobility improved promptly. Fractures healed after 7-8 months of treatment in patient 1 and at 15 months in patient 2.
  
  
  CONCLUSIONS
  PTH 1-84 improves pain, mobility, and fracture repair in adult HPP, even after repeat treatment. Residual activity of the p.E191K ALPL gene mutation could explain why PTH can stimulate S-ALP. P-Pi concentrations may modulate the response.
authors.affiliation: Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, P.O. Box 340, FI-00290 Helsinki, Finland. camilla.schalin-jantti@hus.fi
authors.forename: Camilla
authors.initials: C
authors.lastname: Schalin-Jäntti
authors.forename: Etienne
authors.initials: E
authors.lastname: Mornet
authors.forename: Antti
authors.initials: A
authors.lastname: Lamminen
authors.forename: Matti J
authors.initials: MJ
authors.lastname: Välimäki
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D005260:Female; D005264:Femoral Fractures / Q000601:surgery; D050723:Fractures, Bone / Q000188:drug therapy*; D006801:Humans; D007014:Hypophosphatasia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D035781:Siblings; D014945:Wound Healing
chemical_list: D010281:Parathyroid Hormone; C548267:ALPL protein, human; D000469:Alkaline Phosphatase