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Skeletal changes through the lifespan—from growth to senescence

Key Points

  • Both peak bone mass attained during childhood and adolescent growth, and bone loss associated with senescence are major determinants of bone mass and fracture risk late in life

  • Incidence of distal forearm fractures increases markedly around the time of puberty and children who sustain these fractures in the setting of mild, but not moderate, trauma have systemic skeletal deficits that persist into young adult life

  • With ageing, cortical bone at multiple skeletal sites remains fairly stable in both sexes until mid-life, when estrogen deficiency in women and gradual sex steroid deficiency in men begins to drive cortical bone loss

  • By contrast, substantial trabecular bone loss occurs in both sexes during young adult life, in conditions of sex steroid sufficiency

  • Cortical porosity is increasingly recognized as an important component of bone 'quality' that increases markedly with age; changes in cortical porosity are not captured by dual-energy X-ray absorptiometry

  • Assessment of cortical porosity might help identify individuals at increased risk of fracture from the large group of patients with osteopenia, in whom assessment of fracture risk remains most ambiguous

Abstract

Age-related fragility fractures are an enormous public health problem. Both acquisition of bone mass during growth and bone loss associated with ageing affect fracture risk late in life. The development of high-resolution peripheral quantitative CT (HRpQCT) has enabled in vivo assessment of changes in the microarchitecture of trabecular and cortical bone throughout life. Studies using HRpQCT have demonstrated that the transient increase in distal forearm fractures during adolescent growth is associated with alterations in cortical bone, which include cortical thinning and increased porosity. Children with distal forearm fractures in the setting of mild, but not moderate, trauma also have increased deficits in cortical bone at the distal radius and in bone mass systemically. Moreover, these children transition into young adulthood with reduced peak bone mass. Elderly men, but not elderly women, with a history of childhood forearm fractures have an increased risk of osteoporotic fractures. With ageing, men lose trabecular bone primarily by thinning of trabeculae, whereas the number of trabeculae is reduced in women, which is much more destabilizing from a biomechanical perspective. However, age-related losses of cortical bone and increases in cortical porosity seem to have a much larger role than previously recognized, and increased cortical porosity might characterize patients at increased risk of fragility fractures.

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Figure 1: Bone mineral accrual during adolescence.
Figure 2: Incidence of distal forearm fractures in residents of Olmsted County, MN, USA.
Figure 3: HRpQCT-resolved bone microarchitecture of the distal radius.
Figure 4: Bone microstructural changes in adolescents with distal forearm fractures.
Figure 5: Age-related changes in cortical and trabecular vBMD.
Figure 6: Cortical porosity and risk of distal forearm fractures.

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Acknowledgements

The authors acknowledge support from the NIH (grants AG004875 and AR027065 to S.K.) and a Mayo Clinical and Translational Science Award (UL1 TR000135 to the Mayo Foundation).

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J.N.F. and S.K. researched data for the article, provided substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Sundeep Khosla.

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Farr, J., Khosla, S. Skeletal changes through the lifespan—from growth to senescence. Nat Rev Endocrinol 11, 513–521 (2015). https://doi.org/10.1038/nrendo.2015.89

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