Pamidronate treatment of less severe forms of osteogenesis imperfecta in children.
BACKGROUND
Bisphosphonate therapy improves bone quality in children with severe osteogenesis imperfecta (OI). Children with milder phenotypes also have prepubertal fractures, bone pain and reduced bone mass, predisposing them to adult osteoporosis.


OBJECTIVE
To evaluate treatment effects of pamidronate in children with mild phenotypes of OI.


METHODS
Open label, 2-year observational study of 18 patients, using pamidronate, with clinical, biochemical and radiological monitoring.


RESULTS
Over 2 years, bone pain decreased from 16 to 1 patient and disturbed sleep from 12 children to 0. Independent mobility improved from 10 to 17 children. Fracture incidence decreased from 1.6 to 0.5 fractures/child/year. Surgical interventions decreased from a mean 1.3 procedures/patient to 0 in the second year of treatment. Growth velocity remained stable at a mean 4.8 cm/year. Mean lumbar vertebral bone mineral density improved by 40.8%, from 0.375 to 0.528 g/cm2 (p <0.0001), z-score from -3.77 to -2.44 (p <0.0001). Mean vertebral height improved by 17.3%, from 15.6 to 18.38 mm (p = 0.07); plasma alkaline phosphatase decreased from 222 to 169 U/l (p = 0.0009) and urinary deoxypyridinoline crosslinks decreased from 26.7 to 21.8 nmol/mmol creatinine (p = 0.21). Two children with vitamin D insufficiency were concurrently treated. A significant association (r = -0.6, p = 0.008) was shown between age at start of treatment and percentage change in BMD after 2 years.


CONCLUSIONS
Pamidronate treatment improves bone quality in children with mild types of OI. It ameliorates clinical symptoms, improves mobility, reduces fracture frequency and thus improves quality of life and in future is likely to reduce the severity and consequences of adult osteoporosis by improved peak bone mass in these children.
Zacharin
Margaret
M
Department of Endocrinology and Diabetes, Royal Children 's Hospital, Melbourne, Australia. margaret.zacharin@rch.org.au
Kanumakala
Shankar
S
D015502:Absorptiometry, Photon; D000293:Adolescent; D000469:Alkaline Phosphatase / Q000097:blood; D001827:Body Height; D001835:Body Weight / Q000502:physiology; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010013:Osteogenesis Imperfecta / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010146:Pain / Q000453:epidemiology / Q000209:etiology; D000077268:Pamidronate; D011627:Puberty / Q000502:physiology
D004164:Diphosphonates; D000469:Alkaline Phosphatase; D000077268:Pamidronate