Bone Problems Start Early with Cystic Fibrosis

PARIS, May 2 -- Cystic fibrosis patients may develop bone density deficits in the first years of life regardless of nutritional status or disease severity, researchers here found.

In a study of 114 children with cystic fibrosis, half had bone mineral density a standard deviation below levels seen in their healthy peers, and nearly a third were more than two standard deviations below.

This was true for children from the youngest age group studied (two to five years) through age 18, and significantly lower than expected in children younger than 6, reported Isabelle Sermet-Gaudelus, M.D., Ph.D., of the Hpital Necker-Enfants Malades, and colleagues.

"We recommend that all children with cystic fibrosis undergo assessment of bone mineral density and body composition early in life to make it possible to target those who need preventive treatment," they wrote in the May 1 issue of the American Journal of Respiratory and Critical Care Medicine.

Low bone mineral density is common among adults with cystic fibrosis, they noted. Contributing factors are thought to include vitamin D deficiency, malnutrition, chronic infection, reduced physical activity, hypogonadism, and delayed puberty.

However, the researchers noted, it was unknown how early in life bone mineral density deficits developed.

So they examined data from children at their outpatient clinic, focusing on the youngest age group. There were 25 children ages two to five, 53 prepubertal children ages six to 10, and 36 adolescents ages 11 to 18.

The control population included 317 children, matched for height, sex and puberty status, who lived in the same geographic area and had normal nutritional status and cardiac renal and hepatic function.

The researchers measured bone mineral density of the lumbar spine using dual-energy x-ray absorptiometry adjusted for height rather than age.

They also assessed disease severity at the time of the bone scan. It was defined by the number of antibiotic courses in the prior year and by pulmonary function.

In the youngest age group, the mean bone density z score was significantly lower compared with controls at -0.96 standard deviations from normal. Among these patients, 52% had "moderately low" z scores (less than -1) and 28% had "low" z scores (less than -2).

There was no difference by bone mineral density score for Pseudomonas aeruginosa colonization, corticosteroid treatment, percentage ideal height for weight, body composition, respiratory function, vitamin D level, prematurity, or birth weight.

Among the other bone mineral density findings the researchers reported:

• Mean z score -0.91 for those ages six to 10.
• Mean z score -1.4 for those ages 11 to 18.
• No significant differences between age groups in mean z score.
• No significant difference in the proportion with a z score less than -2 between groups (28% of those younger than six, 22% of those ages six to 10, and 34% of those 11 to 18).

In a subset of patients with mild pulmonary disease and normal nutritional status, lumbar spine z score was less than -1 in 34% suggesting that at least a component of the bone disease is independent of disease severity and nutritional status and may represent a primary CF bone disease.

In a multivariate analysis, only fat-free mass--a measure of lean muscle and body composition--was significantly correlated with bone mineral density (P=0.006).

"In normal individuals, muscular mass is one of the main factors of bone development and bone mineral density increase," the researchers wrote.

"The mechanism underlying this finding may be the continuous inflammatory and protein catabolic state that simultaneously induces more severe pulmonary disease, greater bone resorption, and low muscle mass," they added.

More than 90% of the children in the age two to five group had growth in the normal range as measured by percentage ideal weight for height. More than 70% of those who completed lung function tests had at least 85% of predicted values for age and sex.

However, body composition was already abnormal among these young children.

Of the 22 with body composition data, the mean fat-free mass z score was -2.1, significantly below normal. Half of those with a normal weight were more than two standard deviations below normal for fat-free mass.

Among older children, growth and body composition measures worsened significantly with age as did the severity of pulmonary disease.

This "hidden loss" of muscle mass among patients who appear to be at a normal weight has also been reported in adults with cystic fibrosis, the researchers noted. .

"This may be of critical importance in young children and adolescents, because undiagnosed reduction of muscular mass may deprive the growing skeleton of one of its main factors of development," they wrote.

Further study is needed to conclusively determine the mechanism underlying the bone mineral density deficits among patients with cystic fibrosis, they concluded.