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


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.


CONCLUSIONS
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.
Genetics Unit, Shriners Hospital for Children, and McGill University, Montréal, Quebec, Canada H3G 1A6. frauch@shriners.mcgill.ca
Frank
F
Rauch
Abdallah
A
Husseini
Peter
P
Roughley
Francis H
FH
Glorieux
Pierre
P
Moffatt
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005136:Eye Proteins / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009414:Nerve Growth Factors / Q000097:blood* / Q000235:genetics; D010013:Osteogenesis Imperfecta / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics; D015843:Serpins / Q000097:blood* / Q000235:genetics; D000099174:Pigment Epithelium-Derived Factor
D015415:Biomarkers; D005136:Eye Proteins; D009414:Nerve Growth Factors; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C506231:PHEX protein, human