High levels of serum prostaglandin E2 in children with osteogenesis imperfecta are reduced by neridronate treatment.
Prostaglandin E2 (PGE2) is an activator of bone remodeling, and increase levels of PGE2 are found in several disorders characterized by chronic inflammation. Bisphosphonates are used in the treatment of osteogenesis imperfecta (OI), an inherited disorder characterized by bone fragility and low bone mass. We evaluated the serum PGE2 (ng/mL) level in 16 children affected by OI (11 with mild and 5 with severe forms) at basal time and during treatment with neridronate. The levels of PGE2 in mild and severe forms were increased at basal time compared with controls (13.14 +/- 4.2 versus 0.72 +/- 0.05, p < 0.01; 15.1 +/- 1.5 versus 0.72 +/- 0.05, p < 0.01, respectively) and showed a significant decrease after the second (T1) cycle of treatment (mild: 4.97 +/- 5.0 versus 13.14 +/- 4.2, p < 0.01; severe: 5.32 +/- 4.5 versus 15.1 +/- 1.5, p < 0.01) with a further significant decrease after the fourth (T2) cycle. The high basal PGE2 levels in OI, a noninflammatory disorder, could be explained by stress-induced release mediated by inducible cyclooxygenase-2-catalyzed pathway. The reduction obtained by treatment with bisphosphonates could be attributed to a direct pharmacological effect since these drugs has been reported to modulate the release of proinflammatory mediators.
D'Eufemia
Patrizia
P
Department of Pediatrics, University La Sapienza, 00161 Rome, Italy. patdeufemia@inwind.it
Finocchiaro
Roberto
R
Celli
Mauro
M
Zambrano
Anna
A
Tetti
Martina
M
Villani
Ciro
C
Persiani
Pietro
P
Mari
Emanuela
E
Zicari
Alessandra
A
D001842:Bone and Bones / Q000187:drug effects; D002384:Catalysis; D002648:Child; D002675:Child, Preschool; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000097:blood*; D004164:Diphosphonates / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation; D008297:Male; D008954:Models, Biological; D010013:Osteogenesis Imperfecta / Q000097:blood* / Q000188:drug therapy*
D004164:Diphosphonates; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate; D051546:Cyclooxygenase 2; D015232:Dinoprostone