Purpose of the Study
To investigate growth and markers of collagen and bone metabolism in prepubertal children with asthma who were treated with inhaled or oral corticosteroids.
Fifty-six prepubertal children (mean age: 8.32 years; SD: 2.06 years) with stable asthma were divided into four groups for the investigation: inhaled budesonide (n = 19), inhaled beclomethasone dipropionate (n = 20), inhaled steroid and prednisolone (n = 4), and nonsteroid treatment (n = 13).
The investigators measured growth velocity over the 12-month study period and, on a single occasion, determined markers of collagen types I and II synthesis (PINP: aminoterminal propeptides of type I procollagen, PICP: carboxyterminal propeptide of type I procollagen, and PIIINP: animoterminal propeptide of type III procollagen); collagen type I degradation (ICTP: carboxyterminal telopeptide of type I collagen); and bone metabolism (bone-specific alkaline phosphatase and osteocalcin).
Children treated with inhaled steroids had reduced collagen synthesis (PINP, PIIINP) compared with the control subjects (P = .038; P = .045); however, PICP was increased (P = .05). Carboxyterminal telopeptide of type I collagen was reduced in patients treated with inhaled steroids (P < .0005) as compared with nonsteroid-treated patients. Serum osteocalcin, but not bone-specific alkaline phosphatase, was significantly reduced in children treated with inhaled steroids (P < .02). Finally, significant correlation was observed between PIIINP and ICTP and growth velocity.
Collagen turnover is reduced in children with asthma receiving long-term inhaled steroid treatment. Markers of collagen synthesis (eg, PINP, PIIINP) may provide a more accurate reflection of growth disturbance than osteocalcin and bone-specific alkaline phosphatase.
Unless you have been residing on a remote desert island, it would be almost impossible to have missed the US Food and Drug Administration's decision in the fall of 1998 requiring manufacturers of inhaled and intranasal corticosteroids to include in product labels a notice that these drugs may reduce the rate of growth in some children. This timely article by Crowley et al contributes useful data to the longstanding debate about the potential for inhaled corticosteroids to reduce growth rate in some children with asthma. With similar lung function in all study groups, the investigators attributed the impaired growth velocity to side effects from corticosteroids. Hopefully, regular (every 3 to 6 months) and reliable growth velocity measurements, as well as markers of collagen synthesis, will be documented in the long-term natural history investigations currently examining the role of inhaled corticosteroids in the management of children with asthma, even those with mild persistent disease. Although corticosteroids are the most effective antiinflammatory medication for asthma, we must seriously consider the benefit/risk ratio of these medications, especially when multiple routes of administration (ie, inhaled, intranasal, and oral) may exist in the same patient.