Fractures in Healthy Females Followed from Childhood to Early Adulthood Are Associated with Later Menarcheal Age and with Impaired Bone Microstructure at Peak Bone Mass

Background: Whether fractures observed in healthy children are associated with microstructural alterations and strength deficit that persists by the end of the growth period is not established. Considering the importance of pubertal timing in bone development, we also quantified the fracture risk related to later menarcheal age (MENA). Participants and Methods: We followed 124 healthy girls from mean +/- SD age 7.9 +/- 0.5 to 20.4 +/- 0.6 yr. Fractures, MENA, and radius areal bone mineral density (aBMD) were recorded at regular intervals. At a mean age of 20.4 yr, microstructural and strength variables of the distal radius were determined by high-resolution peripheral computerized tomography and micro-finite element analysis. Results: Sixty-one fractures occurred in 42 subjects. At 20.4 yr, subjects with fractures had lower aBMD at radial diaphysis (P = 0.005) and metaphysis (P = 0.008), lower distal radius trabecular volumetric density (vBMD) (P = 0.010) and thickness (P = 0.014), and reduction in stiffness (P = 0.013), failure load (P = 0.013), and apparent modulus (P = 0.046). Odds ratios revealed an increased risk of fracture for a 1-SD reduction in radial aBMD diaphysis [1.97 (P = 0.006)] and metaphysis [1.97 (P = 0.008)] and distal radius trabecular vBMD [1.89 (P = 0.011)], thickness [1.97 (P = 0.017)], stiffness [2.02 (P = 0.014)], failure load [2.00 (P = 0.014)], and apparent modulus [1.79 (P = 0.043)]. MENA occurred at a later age in subjects with fractures (P = 0.003). For MENA 1 SD (1.2 yr) later, the increase of fracture risk was 2.1 (P = 0.002). Conclusions: In healthy young women, low trabecular vBMD and thickness in the distal radius are associated with reduced bone strength and increased fracture risk during growth. This study also documents that later pubertal timing is associated with increased incidence of fracture during childhood and adolescence. (J Clin Endocrinol Metab 97: 4174-4181, 2012)