Methodology and implications of knemometry in growth assessment of inhaled glucocorticoids.
When validated recommendations for standardization and measurement procedures are used short-term assessment of lower leg growth by knemometry is a highly accurate and reproducible method for assessment of systemic activity of inhaled glucocorticoids. Crossover and parallel designs applying consistent measurement intervals can be used. Crossover designs with a single-blind run in and washout and double-blind active periods are as sensitive as designs using randomized placebo periods. In populations of children, short-term knemometry appears to be capable of defining specific glucocorticoids, application devices and doses that do not suppress long-term height growth. Although no specific cut-off level can be identified in individuals from the available randomized, double-blind short-term knemometry and intermediate-term height growth rate studies, good evidence have been provided that if the short-term lower leg growth suppression in populations of children is higher than approximately 25%, the risk of intermediate-term growth suppression becomes significant with a mean height growth rate retardation in the range of approximately 0.5-1.5 cm during the first year of treatment. Short-term knemometry should be performed as an integral part of the safety assessments of new inhaled glucocorticoids and inhalation devices in children with asthma, before intermediate-term height growth evaluations are initiated.
Wolthers
O D
OD
Asthma and Allergy Clinic, Children's Clinic Randers, Randers, Denmark. akk.odws@dadlnet.dk
D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology*; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D048788:Growth and Development / Q000187:drug effects; D006801:Humans; D007867:Leg Bones / Q000033:anatomy & histology* / Q000187:drug effects / Q000254:growth & development; D008991:Monitoring, Physiologic / Q000379:methods / Q000639:trends; D016037:Single-Blind Method
D005938:Glucocorticoids