Deleterious Effect of Late Menarche on Distal Tibia Microstructure in Healthy 20-Year-Old and Premenopausal Middle-Aged Women

Abstract

Late menarche is a risk factor for fragility fractures. We hypothesized that pubertal timing-dependent alterations in bone structural components would persist from peak bone mass to menopause, independent of premenopausal bone loss. We studied the influence of menarcheal age (MENA) on femoral neck BMD (FN aBMD) by DXA and microstructure of distal tibia by HR-pQCT in healthy young adult (YAD; 20.4 +/- 0.6 [SD] yr, n = 124) and premenopausal middle-aged (PREMENO; 45.8 +/- 3.4 yr, n = 120) women. Median of MENA was 13.0 +/- 1.2 and 13.1 +/- 1.7 yr in YAD and PREMENO, respectively. In YAD and PREMENO (n = 244), FN aBMD (R = -0.29, p = 0.013), as well as total volumetric BMD (Dtot; R = -0.23, p = 0.006) and cortical thickness (Ct.Th; R = -0.18, p = 0.011) of distal tibia were inversely correlated to MENA. After segregation by the median of MENA in EARLY and LATE subgroups, the significant influences of both MENA (p = 0.004) and chronological age (p < 0.0001) were observed for FN aBMD and trabecular bone volume fraction of the distal tibia with similar differences in T-scores between LATE and EARLY subgroups in YAD (-0.36 and -0.31 T-scores) and PREMENO (-0.35 and -0.42 T-scores) women. Ct.Th was negatively influenced by MENA, whereas trabecular thickness (Tb.Th) was negatively influenced by chronological age. There was a striking inverse relationship between cross-sectional area and Ct.Th (R = -0.57, p < 0.001). In conclusion, the negative influence of late menarcheal age at weight-bearing sites as observed by the end of skeletal growth remains unattenuated a few years before menopause and is independent of premenopausal bone loss. Alterations in both bone mineral mass and microstructural components may explain the increased risk of fragility fractures associated with later menarcheal age.