Clinical Problems with Bone Mass Measurement in Pediatrics

The use of densitometry is not only a matter of instruments, but is strongly related to the availability of normative data. The reference databases supplied by the manufacturers are generally not adequate for serious studies. It is essential that the normal reference sample be of adequate size and stratified by sex, age and ethnicity. In studying pediatric patients, the pubertal status must also be considered. Weight and height should also be included in the normal sample (and actually measured in the examined subject) in order to normalize densitometric data for body size. From birth to about 25 years of age (i.e., until the achievement of peak bone mass), the normal reference population must be that of healthy subjects of the same sex and age. BMD comparisons are made in terms of the number of standard deviation (SD) below the average value of the reference population. This index is called the Z-score, and is calculated with the formula: Z-score = Examined subject's

BMD - Average BMD of the reference population/SD of the reference population (39).

In pediatric studies, much more than in adult subjects, the adoption of rigorous protocols for scanning and data analysis is necessary. Regular calibration of the instruments is necessary. The correct positioning (and repositioning) of a patient is a particularly delicate point in order to obtain comparable serial data.

As the skeletal changes in a growing subject are much faster than in adults, and are particularly sensitive to the influence of chronic diseases, the interval between two successive DXA measurements must be adapted to the individual situation, and may be as short as 6 to 12 months.

The simple finding of low bone mass in a child or an adolescent should always be considered a serious warning, but by itself does not allow any diagnosis. Clinical examination, X-rays, biochemical tests, and sometimes also bone biopsy, are needed. Table 2 illustrates the key points in the

Table 2 Initial Diagnostic Workup for Young Patients with Low Bone Mass History

Evaluation of primary disease (if any) History of fractures (familiar and personal) History of drug use (including inhalatory steroids) History of gastrointestinal disorders (diarrhea) Evaluation of lifestyle

Dietary intake of calcium and protein Physical activity (frequency, duration, intensity) Exposure to sunlight (or not) Smoking Examination

Auxological parameters (height, weight, BMI, growth velocity) Pubertal stage

Spine abnormalities (kyphosis, scoliosis) Deformities, trunk/limbs proportion Joint laxity Color of sclerae Pain

Deambulation Basic blood tests Calcium, phosphate Alkaline phosphatase 25-hydroxyvitamin D Parathyroid hormone Basic tests Bone density Wrist X-ray for bone age

Table 3 Most Common Available Bone Biochemical Markers

Formation Serum

Bone specific alkaline phosphatase (BSAP) Osteocalcin (OC)

Carboxyterminal propeptide of type I collagen (PICP) Aminoterminal propeptide of type I collagen (PINP)

Resorption Urine

Hydroxyproline (rarely used now, due to determination problems)

Free and total pyridinolines (Pyd)

Free and total deoxypyridinolines (Dyd)

N-telopeptide of collagen cross-links (NTx)

C-telopeptide of collagen cross-links (CTx)

Serum

Tartrate-resistant acid phosphatase (TRACP) Cross-linked C-telopeptide of type I collagen (ICTP) NTx CTx diagnostic workup. Of note, a recent large study has shown that a low BMD in adolescence is associated with a history of fracture occurrence (40).

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