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.