title: Teriparatide Treatment in Patients With WNT1 or PLS3 Mutation-Related Early-Onset Osteoporosis: A Pilot Study.
abstract: We previously identified 2 Finnish families with dominantly inherited, low-turnover osteoporosis caused by mutations in WNT1 or PLS3.
  
  
  
  This prospective, longitudinal, uncontrolled study was undertaken to evaluate whether these patients respond to teriparatide.
  
  
  
  We recruited 6 adults (median age, 54 years); 3 with a WNT1 missense mutation, c.652T>G, and 3 with a PLS3 splice mutation, c.73-24T>A, to receive teriparatide 20 μg daily for 24 months. Five patients had previously used bisphosphonates.
  
  
  
  Outcome measures included lumbar spine and hip bone mineral density (BMD) by dual-energy X-ray absorptiometry, distal radius peripheral quantitative computed tomography, spinal radiography, serum bone turnover markers, paired iliac crest biopsies.
  
  
  
  All patients showed increases in formation markers procollagen type 1 amino-terminal propeptide (90% to 398%) and osteocalcin (50% to 280%) and in resorption markers cross-linked C-terminal telopeptide of type I collagen (58% to 457%) and tartrate-resistant acid phosphatase 5b (20% to 68%) in first 6 months. Lumbar spine BMD increased 5.2% to 7.9% in 5 patients and femoral neck BMD 2.6% to 7.8% in 4 patients in 24 months. Distal radius cortical volumetric BMD decreased 5.4% to 26.1%. In histomorphometric analyses, osteoid indices increased more consistently in patients with WNT1 vs PLS3 mutation. Eroded surface decreased 44% to 100% in all patients. Adipocyte number increased in 5 patients studied.
  
  
  
  Patients with WNT1 or PLS3 mutation-related osteoporosis responded to teriparatide treatment. Future studies are needed to evaluate whether observed changes translate to fracture resistance.
authors.affiliation: Department of Orthopaedics and Traumatology, Helsinki University Central Hospital and Helsinki University, Jorvi Hospital, 00029 Espoo, Finland.
authors.forename: Ville-Valtteri
authors.initials: VV
authors.lastname: Välimäki
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland.|Folkhälsan Institute of Genetics, 00290 Helsinki, Finland.|Department of Molecular Medicine and Surgery, Karolinska Institutet, and Department of Clinical Genetics, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Renata
authors.initials: R
authors.lastname: Pereira
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland.|Department of Endocrinology, Institute of Medicine, Sahlgrenska University Hospital and University of Gothenburg, SE-413 45 Gothenburg, Sweden.
authors.forename: Christine
authors.initials: C
authors.lastname: Laine
authors.affiliation: Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Katherine
authors.initials: K
authors.lastname: Wesseling-Perry
authors.affiliation: Institute of Biomedicine, Department of Cell Biology and Anatomy, University of Turku, 20520 Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Määttä
authors.affiliation: Department of Orthopaedics and Traumatology, Helsinki University Central Hospital and Helsinki University, Töölö Hospital, 00029 Helsinki, Finland.|Dextra Sports and Trauma Clinic, 00350 Helsinki, Finland; and.
authors.forename: Mikko
authors.initials: M
authors.lastname: Kirjavainen
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland.|Folkhälsan Institute of Genetics, 00290 Helsinki, Finland.
authors.forename: Heli
authors.initials: H
authors.lastname: Viljakainen
authors.affiliation: Division of Endocrinology, Department of Medicine, Helsinki University Central Hospital, 00029 Helsinki, Finland.
authors.forename: Matti J
authors.initials: MJ
authors.lastname: Välimäki
mesh_terms: D015502:Absorptiometry, Photon; D017668:Age of Onset; D000368:Aged; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016723:Bone Remodeling; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010024:Osteoporosis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics*; D017063:Outcome Assessment, Health Care; D010384:Pelvic Bones / Q000000981:diagnostic imaging; D010865:Pilot Projects; D011446:Prospective Studies; D011884:Radius / Q000000981:diagnostic imaging; D019379:Teriparatide / Q000008:administration & dosage / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed; D051155:Wnt1 Protein / Q000235:genetics*
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C495247:WNT1 protein, human; D051155:Wnt1 Protein; C026742:plastin; D019379:Teriparatide