Lack of circulating pigment epithelium-derived factor is a marker of osteogenesis imperfecta type VI

J Clin Endocrinol Metab. 2012 Aug;97(8):E1550-6. doi: 10.1210/jc.2012-1827. Epub 2012 Jun 5.

Abstract

Background: Osteogenesis imperfecta (OI) type VI is a rare autosomal recessive bone fragility disorder that is caused by inactivating mutations in SERPINF1, the gene that encodes pigment-epithelium derived factor (PEDF). Determining PEDF serum levels might facilitate the diagnosis of OI type VI.

Objective: The objective of the study was to assess whether lack of circulating PEDF is a specific marker of OI type VI and to evaluate whether PEDF serum levels are influenced by other metabolic bone diseases.

Materials and methods: Serum PEDF concentrations were measured in 12 patients with OI type VI (aged 2.7-31 yr) as well as in 96 children and adolescents with OI types I, III, and IV; in 26 young patients with hypophosphatemic rickets; and in 19 healthy controls.

Results: Circulating PEDF was undetectable in all 12 patients with OI type VI but was measurable for the other 141 study participants. No significant differences in serum PEDF concentrations were found between the diagnostic groups other than OI type VI. Treatment with bisphosphonates (in OI types I, III, and IV) and with phosphate and calcitriol (in hypophosphatemic rickets) did not have a detectable influence on serum PEDF. In patients with OI types I, III, and IV, serum creatinine, body mass index z-score, and OI severity were significant predictors of PEDF serum levels.

Conclusion: Determining PEDF serum concentration helps to diagnose OI type VI but does not seem to provide information on the activity of bone turnover or mineralization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Eye Proteins / blood*
  • Eye Proteins / genetics
  • Female
  • Humans
  • Male
  • Nerve Growth Factors / blood*
  • Nerve Growth Factors / genetics
  • Osteogenesis Imperfecta / blood*
  • Osteogenesis Imperfecta / diagnosis
  • Osteogenesis Imperfecta / drug therapy
  • PHEX Phosphate Regulating Neutral Endopeptidase / genetics
  • Serpins / blood*
  • Serpins / genetics

Substances

  • Biomarkers
  • Eye Proteins
  • Nerve Growth Factors
  • Serpins
  • pigment epithelium-derived factor
  • PHEX Phosphate Regulating Neutral Endopeptidase
  • PHEX protein, human