The Influence of Pubertal Timing on Bone Mass Acquisition: A Predetermined Trajectory Detectable Five Years before Menarche

Background: Later menarcheal age (MENA) is a risk factor for osteoporosis. It is associated with low peak bone mass (PBM). Like PBM, MENA is under strong genetic influence. We hypothesized that MENA-related bone mass differences could be predetermined before puberty. Methods: We tested this hypothesis in 124 healthy subjects followed from age 7.9 to 20.4 yr with dual-energy x-ray absorptiometry assessment at mean ages of 8.9, 10.0, 12.4, and 16.4 yr. Six sites were measured: radial metaphysis, radial diaphysis, femoral neck, trochanter, femoral diaphysis, and L2-L4. Mean MENA(+/-SD) was 13.0 +/- 1.2 yr. The cohort was segregated by the median of MENA into LATER (14.0 +/- 0.7 yr) and EARLIER (12.1 +/- 0.7 yr) subgroups. Results: At 20.4 +/- 0.6 yr, areal bone mineral density (aBMD) was lower in the LATER than the EARLIER subgroup at all six sites, with a mean difference of -0.31 Z-score (P = 0.022). Lower Z-scores in the LATER than in the EARLIER subgroup were observed at all sites at mean ages of 10.0, 12.4, and 16.4 yr, and before pubertal maturation, i.e. at 8.9 yr with a mean Z-score difference of -0.34 (P = 0.016). From mean age 8.9 to 20.4 yr, a BMD gains of all sites were similar in LATER and EARLIER subgroups, with mean of +301 and +308 mg/cm(2) (P = 0.402), respectively. Conclusions: In prepubertal girls who will experience later menarche, a deficit in a BMD can already be observed before the onset of pubertal maturation, with no further accumulated deficit until PBM compared to girls with earlier menarche. This suggests that shorter estrogen exposure from prepuberty to PBM is not the main factor for increased osteoporosis risk associated with later menarche. Rather common genetic determinants of low bone mass and later puberty could be involved. (J Clin Endocrinol Metab 94: 3424-3431, 2009)