title: Bone mineral density in sclerosteosis; affected individuals and gene carriers.
abstract: BACKGROUND
  Sclerosteosis is an autosomal recessive sclerosing bone disorder due to deficiency of sclerostin, a protein secreted by the osteocytes that inhibits bone formation. In the present study we assessed the effect of variable expression of the genetic defect on bone mineral density (BMD) in patients and carriers of the determinant gene.
  
  
  METHODS
  We studied 25 individuals (seven patients and 18 phenotypically normal heterozygotes). BMD was measured by dual x-ray absorptiometry at the lumbar spine, total hip, and distal forearm, and lateral radiographs of the skull were obtained.
  
  
  RESULTS
  Individuals with sclerosteosis had markedly increased BMD at all skeletal sites (Z-score ranges: lumbar spine, +7.73 to +14.43; total hip, +7.84 to +11.51; forearm, +4.44 to +9.53). In heterozygotes, BMD was above the mean value of healthy age-matched individuals at all skeletal sites and had a wide range of normal and clearly increased values. Skull radiographs showed the typical hyperostotic changes in affected individuals and mild or no changes in heterozygotes.
  
  
  CONCLUSIONS
  Heterozygous carriers of sclerosteosis have BMD values consistently higher than the mean of healthy subjects without any of the bone complications encountered in homozygotes. This finding suggests that the production and/or activity of sclerostin can be titrated in vivo, leading to variable increases in bone mass without any unwanted skeletal effects, a hypothesis of obvious significance for the development of new therapeutics for osteoporosis.
authors.affiliation: Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, South Africa.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Gardner
authors.forename: Rutger L
authors.initials: RL
authors.lastname: van Bezooijen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mervis
authors.forename: Neveen A T
authors.initials: NA
authors.lastname: Hamdy
authors.forename: Clemens W G M
authors.initials: CW
authors.lastname: Löwik
authors.forename: Herman
authors.initials: H
authors.lastname: Hamersma
authors.forename: Peter
authors.initials: P
authors.lastname: Beighton
authors.forename: Socrates E
authors.initials: SE
authors.lastname: Papapoulos
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000172:deficiency*; D002648:Child; D002675:Child, Preschool; D005808:Genes, Recessive; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D008159:Lumbar Vertebrae / Q000378:metabolism; D008875:Middle Aged; D011859:Radiography; D012886:Skull / Q000000981:diagnostic imaging
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human