Elevated bone turnover markers predict bone mineral density accrual in adolescents with 21-hydroxylase deficiency

Context Prognostic biomarkers for monitoring bone health in adolescents with 21-hydroxylase deficiency (21OHD) are needed. Objectives To assess associations between concentrations of baseline bone turnover markers (BTMs) including osteocalcin (OC) and type-I collagen C-terminal telopeptide (CTX) and changes in lumbar spine bone mineral density (LSBMD) in adolescents with classic 21OHD. Designs and patients A retrospective-prospective study of 33 adolescents with classic 21OHD who had baseline data for LSBMD, bone age (BA), and BTM concentrations. Methods BTM concentrations were converted into z-scores according to BA. We measured LSBMD at the follow-up study visit and calculated the annual percentage change in LSBMD (% increment LSBMD). Results At baseline, participants (55% female, 79% Tanner 5) had mean (+/- SD) age of 14.6 +/- 3.6 years, BA 16.7 +/- 2.9 years, and average glucocorticoid (GC) dose 17.3 +/- 5.6 mg/m(2)/day of hydrocortisone equivalent. The mean follow-up duration was 14.4 +/- 5.6 months. Median (Q1-Q3) % increment LSBMD was 3.6% (0-8.5)/year. % increment LSBMD was similar among genders or 21OHD subtypes. Prednisolone versus hydrocortisone replacement resulted in lower % increment LSBMD (p = .004). % increment LSBMD was increased across tertiles of CTX z-score (p = .014). % increment LSBMD correlated negatively with GC dose (p = .01) and positively with CTX and OC z-scores (p < .01). In regression analyses, only CTX z-score positively associated with % increment LSBMD (p = .003), adjusting for sex, BA, body mass index, testosterone, 25-hydroxyvitamin D, and GC type and dose. Conclusions Higher GC dose and the use of prednisolone were associated with decreased LSBMD accrual in adolescents with 21OHD. CTX z-score independently associated with LSBMD accrual, suggesting its potential for prognostic bone biomarker.

Automated summary

This study evaluated the associations between prognostic biomarkers and bone mineral density changes in adolescents with 21-hydroxylase deficiency. The results showed that higher glucocorticoid dose and the use of prednisolone were associated with decreased bone mineral density accrual. Additionally, CTX z-score independently associated with bone mineral density accrual.