Methodology and implications of knemometry in growth assessment of inhaled glucocorticoids

Abstract

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.

The application of knemometry to measure childhood short‐term growth among the indigenous Shuar of Ecuador

“…Standard deviation in Shuar mean 1-week growth (SD 5 0.75 mm/week) is, for example, 20% greater than reported for healthy Dutch children (SD 5 0.63 mm/week) in one of the most comparable existing studies (Valk et al, 1983a). Although suggestive, additional data are needed to determine if variation in Shuar short-term LL growth is (Hermanussen, 1998;Hermanussen et al, 1988;Wolthers, 2010). However, we note several lines of evidence supporting the results of the present study.…”

Growth suppression caused by corticosteroid eye drops

“…That is in accordance with the present fi ndings of suppressed lower leg growth rates during treatment with fl uorometholone eye drops which were very similar to what we have previously seen in randomised double-blind knemometry studies in children treated with oral prednisolone 5 mg/day and methylprednisolone 60 mg intramuscularly (5, 6) . Short-term lower leg growth rates in schoolchildren with atopic disease and in healthy children have been found to be in the range of approximately 0.30 -0.50 mm/week (3) . Considering the high growth rates after withdrawal of treatment, there is no doubt that growth rates were suppressed by fl uorometholone in all children.…”

“…This probably refl ects the fact that short-term treatment is mostly applied implying that conventional height growth studies have not been possible owing to the relatively poor accuracy of body height measurements requiring observation periods of at least 6 months for reliable results to be obtained. During the past decade short-term knemometry, whereby the length of the lower leg is measured with a technical precision of around 0.10 mm, has been established as a non-invasive method for accurate and highly reproducible assessment of systemic activity of topical glucocorticoids in children (3) . The aim of the present study was to assess whether systemic activity of ocular glucocorticoids in children with allergic conjunctivitis can be detected by short-term growth assessment using the knemometer.…”

It is still an open question whether inhaled glucocorticoid-induced effects may reduce adult height

“…3 Despite having been on the market since the early 1980s for use in children, the potential of inhaled glucocorticoids for suppression of final height, however, has not yet been clarified. This study aimed to answer the question: what happens to adult height in children who present a growth deficit caused by few years’ treatment with inhaled glucocorticoids in childhood?…”