Pubertal timing, bone acquisition, and risk of fracture throughout life

Endocr Rev. 2014 Oct;35(5):820-47. doi: 10.1210/er.2014-1007. Epub 2014 Aug 25.


Pubertal maturation plays a fundamental role in bone acquisition. In retrospective epidemiological surveys in pre- and postmenopausal women, relatively later menarcheal age was associated with low bone mineral mass and increased risk of osteoporotic fracture. This association was usually ascribed to shorter time exposure to estrogen from the onset of pubertal maturation to peak bone mass attainment. Recent prospective studies in healthy children and adolescents do not corroborate the limited estrogen exposure hypothesis. In prepubertal girls who will experience later menarche, a reduced bone mineral density was observed before the onset of pubertal maturation, with no further accumulated deficit until peak bone mass attainment. In young adulthood, later menarche is associated with impaired microstructural bone components and reduced mechanical resistance. This intrinsic bone deficit can explain the fact that later menarche increases fracture risk during childhood and adolescence. In healthy individuals, both pubertal timing and bone development share several similar characteristics including wide physiological variability and strong effect of heritable factors but moderate influence of environmental determinants such as nutrition and physical activity. Several conditions modify pubertal timing and bone acquisition, a certain number of them acting in concert on both traits. Taken together, these facts should prompt the search for common genetic regulators of pubertal timing and bone acquisition. It should also open epigenetic investigation avenues to pinpoint which environmental exposure in fetal and infancy life, such as vitamin D, calcium, and/or protein supplies, influences both pubertal timing and bone acquisition.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adolescent Development / physiology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Development / genetics
  • Bone Development / physiology*
  • Female
  • Fractures, Bone / epidemiology*
  • Fractures, Bone / genetics
  • Humans
  • Male
  • Middle Aged
  • Puberty / genetics
  • Puberty / physiology*
  • Young Adult