Osteogenesis Imperfecta Types I, III, and IV: Effect of Pamidronate Therapy on Bone and Mineral Metabolism
Frank Rauch,
Horacio Plotkin,
Rose Travers,
Leonid Zeitlin and
Francis H. Glorieux
Genetics Unit, Shriners Hospital for Children and McGill University, Montréal, Québec, Canada H3G 1A6
Address all correspondence and requests for reprints to: Dr. Frank Rauch, Genetics Unit, Shriners Hospital for Children, 1529 Cedar Avenue, Montréal, Québec, Canada H3G 1A6. E-mail: frauch{at}shriners.mcgill.ca.
Cyclical iv therapy with pamidronate improves the clinical coursein children and adolescents with osteogenesis imperfecta (OI).In this study we evaluated the effect of this therapy on boneand mineral metabolism in 165 patients with OI types I, III,and IV (age, 2 wk to 17.9 yr; 86 girls and 79 boys). All patientsreceived iv pamidronate infusions on 3 successive days, administeredat age-dependent intervals of 2–4 months. During the 3d of the first infusion cycle, serum concentrations of ionizedcalcium dropped by 0.14 ± 0.008 mmol (mean ± SE;P < 0.001), and serum PTH levels transiently almost doubled(P < 0.001). At the same time, urinary excretion of the boneresorption marker type I collagen N-telopeptide related to creatinine(uNTX/uCr) decreased by 61–73% (P < 0.001). Two to4 months later, ionized calcium had returned to pretreatmentlevels, and uNTX/uCr remained 30–35% lower than at baseline(P < 0.001). During 4 yr of pamidronate therapy (n = 40 patients),ionized calcium levels remained stable, but PTH levels increasedby about 30% (P < 0.01). uNTX/uCr, expressed as a percentageof the age- and sex-specific mean value in healthy children,decreased from 132 ± 13% (mean ± SE) at baselineto 49 ± 3% after 4 yr of therapy (P < 0.001). In conclusion,serum calcium levels can decrease considerably during and afterpamidronate infusions, requiring close monitoring especiallyat the first infusion cycle. In long-term therapy, bone turnoveris suppressed to levels lower than those in healthy children.The consequences of chronically low bone turnover in childrenwith OI are unknown at present.
This work was supported by the Shriners of North America.
Present address for H.P.: Inherited Metabolic Diseases Section,Children’s Hospital and Department of Pediatrics, Universityof Nebraska, Omaha, Nebraska 68114.
Abbreviations: OI, Osteogenesis imperfecta; Pi, inorganic phosphorus;uCa, urinary excretion of calcium; uCr, urinary excretion ofcreatinine; TRAcP, tartrate-resistant acid phosphatase; uNTX/uCr,urinary excretion of the bone resorption marker type I collagenN-telopeptide related to creatinine.
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