Pamidronate in children with osteogenesis imperfecta: histomorphometric effects of long-term therapy.
BACKGROUND
Intravenous pamidronate treatment is beneficial to children and adolescents with osteogenesis imperfecta (OI), but the effects of prolonged therapy are not well characterized.


OBJECTIVE
The objective of this study was to assess the effect of long-term pamidronate treatment on the bone tissue of children and adolescents with OI.


METHODS
This is an observational study on OI patients receiving iv pamidronate for more than 4 yr.


METHODS
The study was carried out in a pediatric metabolic bone research unit.


METHODS
Patients were 25 moderately to severely affected OI patients (seven girls) aged 1.4-15.3 yr at baseline.


METHODS
Intervention was cyclical iv pamidronate at a dose of 9 mg/kg.yr.


METHODS
Iliac bone biopsy and lumbar spine bone mineral density measures were obtained at treatment start, after 2.7 +/- 0.5 yr (mean +/- sd), and after 5.5 +/- 0.7 yr of therapy.


RESULTS
Average areal bone mineral density increased by 72% in the first half of the observation period, but by only 24% in the second half. Mean cortical width and cancellous bone volume increased by 87 and 38%, respectively, between baseline and the first time point during treatment (P < 0.001 for all changes). Thereafter, cortical width did not change significantly, but there was a trend (P = 0.06) toward higher cancellous bone volume. Average bone formation rate on trabecular surfaces decreased by 70% after pamidronate treatment was initiated and showed a trend (P = 0.08) toward a further decline in the second part of the study interval.


CONCLUSIONS
The gains that can be achieved with pamidronate treatment appear to be largely realized in the first 2-4 yr.
Rauch
Frank
F
Genetics Unit, Shriners Hospital for Children, 1529 Cedar Avenue, Montréal, Québec, Canada H3G 1A6. frauch@shriners.mcgill.ca
Travers
Rose
R
Glorieux
Francis H
FH
D000293:Adolescent; D001706:Biopsy; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010013:Osteogenesis Imperfecta / Q000188:drug therapy* / Q000652:urine; D000077268:Pamidronate; D010455:Peptides / Q000652:urine
D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D000077268:Pamidronate