Dose-response relationships between energy availability and bone turnover in young exercising women

J Bone Miner Res. 2004 Aug;19(8):1231-40. doi: 10.1359/JBMR.040410. Epub 2004 Apr 19.


To help refine nutritional guidelines for military servicewomen, we assessed bone turnover after manipulating the energy availability of 29 young women. Bone formation was impaired by less severe restrictions than that which increased bone resorption. Military servicewomen and others may need to improve their nutrition to avoid these effects.

Introduction: We determined the dose-response relationship between energy availability (defined as dietary energy intake minus exercise energy expenditure) and selected markers of bone turnover in 29 regularly menstruating, habitually sedentary, young women of normal body composition.

Materials and methods: For 5 days in the early follicular phase of two menstrual cycles separated by at least 2 months, subjects expended 15 kcal/kgLBM/day in supervised exercise at 70% of aerobic capacity and consumed controlled amounts of a clinical dietary product in balanced (45 kcal/kgLBM/day) and one of three restricted (either 10, 20, or 30 kcal/kgLBM/day) energy availability treatments in random order. Blood was sampled at 10-minute intervals, and urine was collected for 24 h. Samples were assayed for plasma osteocalcin (OC), serum type I procollagen carboxy-terminal propeptide (PICP), and urinary N-telopeptide (NTX).

Results: NTX concentrations (p < 0.01) and indices of bone resorption/formation uncoupling (Z(NTX-OC) and Z(NTX-PICP); both p < 10(-4)) were increased by the 10 kcal/kgLBM/day treatment. OC and PICP concentrations were suppressed by all restricted energy availability treatments (all p < 0.05). PICP declined linearly (p < 10(-6)) with energy availability, whereas most of the suppression of OC occurred abruptly between 20 and 30 kcal/kgLBM/day (p < 0.05).

Conclusions: These dose-response relationships closely resembled those of particular reproductive and metabolic hormones found in the same experiment and reported previously: similar relationships were observed for NTX and estradiol; for PICP and insulin; and for OC, triiodothyronine (T3), and insulin-like growth factor (IGF)-I. The uncoupling of bone resorption and formation by severely restricted energy availability, if left to continue, may lead to irreversible reductions in BMD, and the suppression of bone formation by less severe restrictions may prevent young women from achieving their genetic potential for peak bone mass. More prolonged experiments are needed to determine the dose-response relationships between chronic restrictions of energy availability and bone turnover.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Bone Resorption / metabolism
  • Bone and Bones / metabolism*
  • Collagen / metabolism
  • Collagen / urine
  • Collagen Type I
  • Energy Intake / physiology*
  • Energy Metabolism / physiology
  • Exercise / physiology*
  • Exercise Test
  • Female
  • Food, Formulated
  • Humans
  • Military Personnel
  • Osteocalcin / blood
  • Osteocalcin / metabolism
  • Osteogenesis / physiology
  • Peptide Fragments / blood
  • Peptide Fragments / metabolism
  • Peptides / metabolism
  • Peptides / urine
  • Procollagen / blood
  • Procollagen / metabolism
  • Regression Analysis


  • Collagen Type I
  • Peptide Fragments
  • Peptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • procollagen type I carboxy terminal peptide
  • Osteocalcin
  • Collagen