Biochemical markers of bone turnover in girls during puberty

Bone turnover and the rate of bone growth increase dramatically during puberty. A number of new assays for the estimation of bone resorption and formation rates have been developed over recent years, and puberty acts as a convenient model for evaluation of these measurements. The aim of this study was to explore the interrelationships between pubertal development, biochemical markers of bone turnover, insulin-like growth factor I and oestradiol in healthy pubertal girls.

Ninety-one healthy girls (ages 11.6-15.5 years) were studied. All subjects were apparently healthy, and were not taking medications known to influence calcium homeostasis. Breast examination was performed to assess pubertal stage according to Tanner. The adult reference range for biochemical markers of bone turnover was obtained from concurrent studies on 42 healthy premenopausal women ranging in age between 20 and 45 years.

Blood samples were obtained from subjects between 0800 and 1000 h. Urine samples were collected between 1330 and 1600 h. We measured total and bone specific alkaline phosphatase, osteocalcin, and type I procollagen carboxyterminal propeptide as markers of bone formation. Tartrate resistant acid phosphatase, carboxyterminal pyridinoline cross-linked telopeptide, creatinine corrected urinary deoxypyridinoline, immunoreactive urinary pyridinolines, and urinary galactosyl hydroxylysine were measured as markers of bone resorption.

Bone turnover as reflected by each of the markers was maximal in mid puberty (breast Tanner stages II and III) and decreased towards adult levels in late puberty (P < 0.001). However, the magnitude of the mid-pubertal increase differed between markers. In particular, the pubertal increase in levels of bone specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline were higher than the increase shown by the other markers. All markers were significantly lower after the menarche. Circulating insulin-like growth factor I and insulin like growth factor binding protein-3 were not important determinants of pubertal changes in bone turnover. In contrast, there was a significant negative correlation between oestradiol and all markers of bone formation and resorption during puberty.

The greater pubertal increase in levels of bone specific alkaline phosphatase, osteocalcin and urinary deoxypyridinoline suggests that these markers may be relatively more sensitive as indicators of skeletal health during puberty. The differences between markers may reflect differences in the bone specificity of the analytes, or differing mechanisms of production and clearance. The negative correlation between oestradiol and markers of bone resorption and formation suggests that this hormone may be responsible for the reduction in bone turnover in late puberty.