Biomarker-calibrated protein intake and bone health in the Women's Health Initiative clinical trials and observational study

Am J Clin Nutr. 2014 Apr;99(4):934-40. doi: 10.3945/ajcn.113.076786. Epub 2014 Feb 19.


Background: The effects of dietary protein on bone health are controversial.

Objective: We examined the relation between protein intake with fracture and bone mineral density (BMD) within the Women's Health Initiative (WHI).

Design: This prospective analysis included 144,580 women aged 50-79 y at baseline in the WHI clinical trials (CTs) and observational study (OS) that recruited participants in 1993-1998 with follow-up through 2011. Self-reported clinical fractures were collected semiannually through the original end of the trials (WHI CTs) and annually (WHI OS) by questionnaires. Hip fracture was adjudicated by a central review of radiology reports. BMDs for total body, hip, and spine were measured at baseline and 3 and 6 y in 9062 women at 3 WHI clinics by using dual-energy X-ray absorptiometry. Protein intake was assessed via food-frequency questionnaire and calibrated by using biomarkers of energy and protein intakes. Associations between protein intake and fracture were estimated by using Cox proportional hazards regression, and the relation between protein intake and BMD was estimated by using linear regression.

Results: Median biomarker-calibrated protein intake was 15% of energy intake. Per 20% increase in calibrated protein intake (percentage of energy), there was no significant association with total fracture (HR: 0.99; 95% CI: 0.97, 1.02) or hip fracture (HR: 0.91; 95% CI: 0.84, 1.00), but there was an inverse association with forearm fracture (HR: 0.93; 95% CI: 0.88, 0.98). Each 20% increase in calibrated protein intake was associated with a significantly higher BMD for total body (mean 3-y change: 0.003 g/cm²; 95% CI: 0.001, 0.005 g/cm²) and hip (mean 3-y change: 0.002 g/cm²; 95% CI: 0.001, 0.004 g/cm²).

Conclusions: Higher biomarker-calibrated protein intake within the range of usual intake was inversely associated with forearm fracture and was associated with better maintenance of total and hip BMDs. These data suggest higher protein intake is not detrimental to bone health in postmenopausal women.

Trial registration: NCT00000611.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Arm Bones
  • Biomarkers / urine
  • Bone Density
  • Bone and Bones / metabolism*
  • Cohort Studies
  • Confounding Factors, Epidemiologic
  • Dietary Proteins / adverse effects
  • Dietary Proteins / metabolism
  • Dietary Proteins / therapeutic use*
  • Female
  • Follow-Up Studies
  • Hip Fractures / epidemiology
  • Hip Fractures / etiology
  • Hip Fractures / prevention & control
  • Humans
  • Incidence
  • Middle Aged
  • Nitrogen / urine
  • Osteoporosis, Postmenopausal / etiology
  • Osteoporosis, Postmenopausal / metabolism
  • Osteoporosis, Postmenopausal / physiopathology
  • Osteoporosis, Postmenopausal / prevention & control*
  • Osteoporotic Fractures / epidemiology
  • Osteoporotic Fractures / etiology
  • Osteoporotic Fractures / prevention & control*
  • Proportional Hazards Models
  • United States / epidemiology


  • Biomarkers
  • Dietary Proteins
  • Nitrogen

Associated data