Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study.
In a randomized controlled study, we investigated the effect of treatment with intravenous neridronate in prepubertal children with OI. Our study suggests that quarterly intravenous infusions of the bisphosphonate significantly raise the rate of increase in BMD at both the spine and hip, the projected area of the lumbar vertebrae, and height. These results are associated with a significant decrease in the risk of clinical fractures.


BACKGROUND
Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seem to be the most promising therapy, but randomized, controlled studies are scarce and have never been carried out in prepubertal children.


METHODS
This was a randomized, controlled 3-year clinical trial. The Italian Patients' Society of OI (AsItOI) sent their members affected by any type of OI to two centers at the University of Verona (Italy) to participate in the study. Sixty-four children, 6-11 years of age for boys and 6-9 years of age for girls, with no signs of puberty and who were never treated with bisphosphonates, were randomized to either intravenous neridronate (2 mg/kg infused IV in 30 minutes every 3 months) or no treatment, with a ratio of 2:1. Control patients were given the same bisphosphonate therapy at the end of the first year. BMD and projected bone areas, as measured by DXA, at spine and hip, height, and peripheral fracture incidence, both prospective and retrospective (2 years preceding randomization), were the main outcomes of the study.


RESULTS
At the end of the first year, spine and hip BMD rose by 3.5-5.7% in control patients and by 18-25% (p < 0.001 versus controls) in the active group, respectively. During the following 2 years, the treatment in all patients was associated with BMD increases of 10-25% per year. Height and the DXA-derived projected area of lumbar spine rose during the first year of observation significantly more in the active group than in the control group (<0.01 and <0.05, respectively). Both height and spine projected area continued to rise in the treated patients toward levels found in healthy individuals. During the first year of treatment, 45% of the control patients and 27% of the active group had a nonvertebral fracture, but this difference was not statistically significant (p = 0.2). The total number of fractures was 18 in the 22 control patients and 13 in the active group (relative risk, 0.36; 95% CI, 0.15-0.87; p < 0.05).


CONCLUSIONS
Intravenous neridronate infusions, administered quarterly, significantly increase BMD and lower the risk of clinical fracture in prepubertal children with OI.
Gatti
Davide
D
Department of Rheumatology, University of Verona, Verona, Italy.
Antoniazzi
Franco
F
Prizzi
Rosangela
R
Braga
Vania
V
Rossini
Maurizio
M
Tatò
Luciano
L
Viapiana
Ombretta
O
Adami
Silvano
S
D000469:Alkaline Phosphatase / Q000378:metabolism; D001827:Body Height; D015519:Bone Density; D001842:Bone and Bones; D002648:Child; D004164:Diphosphonates / Q000008:administration & dosage* / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010013:Osteogenesis Imperfecta / Q000188:drug therapy*; D011446:Prospective Studies; D012306:Risk; D013997:Time Factors
D004164:Diphosphonates; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate; D000469:Alkaline Phosphatase