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 hypothetized that MENA-related bone mass differences could be pre-determined before puberty.

Methods: We tested this hypothesis in 124 healthy subjects followed from 7.9 to 20.4 yr with DXA assessment at mean ages of 8.9, 10.0, 12.4, 16.4 yr. Six sites were measured: Radial Metaphysis, Radial Diaphysis, Femoral Neck, Trochanter, Femoral Diaphysis, L2-L4. Mean MENA (±SD) was 13.0±1.2 yr. The cohort was segregated by the median of MENA in LATER (14.0±0.7 yr) and EARLIER (12.1±0.7 yr).

Results: At 20.4±0.6 yr, areal bone mineral density (aBMD) was lower in LATER than EARLIER at all 6 sites with mean difference of -0.31 Z-score (P=0.022). Lower Z-scores in LATER than EARLIER were observed at all sites at mean age of 10.0, 12.4 and 16.4 yr, and before pubertal maturation, i.e. at 8.9 yr with mean Z-score difference of -0.34 (P=0.016). From mean age 8.9 to 20.4 yr aBMD gains of all sites were similar in LATER and EARLIER with mean of +301 and +308 mg/cm² (P=0.402), respectively.

Conclusions: In prepubertal girls who will experience later menarche a deficit in aBMD can already be observed before the onset of pubertal maturation, with no further accumulated deficit until PBM compared to girls with earlier menarche. It 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.