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Cited by 192Bone health and osteoporosis researchBone Metabolism and DiseasesDietary Effects on Health

Effect of Two-Year Caloric Restriction on Bone Metabolism and Bone Mineral Density in Non-Obese Younger Adults: A Randomized Clinical Trial

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Villareal, Dennis T, Fontana, Luigi, Das, Sai Krupa, Redman, Leanne, Smith, Steven R, Saltzman, Edward, Bales, Connie, Rochon, James +5 more·2016·Journal of Bone and Mineral Research
DOI 10.1002/jbmr.2701PMC PMC4834845
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Abstract

Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two-hundred eighteen non-obese (body mass index [BMI] 25.1 ± 1.7 kg/m2), younger (age 37.9 ± 7.2 years) adults were randomly assigned to 25% CR (CR group, n = 143) or ad libitum (AL group, n = 75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone-active hormones, nutrient intake, and physical activity. Body weight (–7.5 ± 0.4 versus 0.1 ± 0.5 kg), fat mass (–5.3 ± 0.3 versus 0.4 ± 0.4 kg), and fat-free mass (–2.2 ± 0.2 versus –0.2 ± 0.2 kg) decreased in the CR group compared with AL (all between group p < 0.001). Compared with AL, the CR group had greater changes in BMD at 24 months: lumbar spine (–0.013 ± 0.003 versus 0.007 ± 0.004 g/cm2; p < 0.001), total hip (–0.017 ± 0.002 versus 0.001 ± 0.003 g/cm2; p < 0.001), and femoral neck (–0.015 ± 0.003 versus –0.005 ± 0.004 g/cm2; p = 0.03). Changes in bone markers were greater at 12 months for C-telopeptide (0.098 ± 0.012 versus 0.025 ± 0.015 μg/L; p < 0.001), tartrate-resistant acid phosphatase (0.4 ± 0.1 versus 0.2 ± 0.1 U/L; p = 0.004), and bone-specific alkaline phosphatase (BSAP) (–1.4 ± 0.4 versus –0.3 ± 0.5 U/L; p = 0.047) but not procollagen type 1 N-propeptide; at 24 months, only BSAP differed between groups (–1.5 ± 0.4 versus 0.9 ± 0.6 U/L; p = 0.001). The CR group had larger increases in 25-hydroxyvitamin D, cortisol, and adiponectin and decreases in leptin and insulin compared with AL. However, parathyroid hormone and IGF-1 levels did not differ between groups. The CR group also had lower levels of physical activity. Multiple regression analyses revealed that body composition, hormones, nutrients, and physical activity changes explained ∼31% of the variance in BMD and bone marker changes in the CR group. Therefore, bone loss at clinically important sites of osteoporotic fractures represents a potential limitation of prolonged CR for extending life span. Further long-term studies are needed to determine if CR-induced bone loss in healthy adults contributes to fracture risk and if bone loss can be prevented with exercise. © 2015 American Society for Bone and Mineral Research.

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  • After long-term calorie restriction, bone mineral density and bone turnover markers show larger changes in patients than in healthy controls advised to continue their current diet.

    “These findings suggest that BMD and markers of bone turnover following long-term calorie restriction show larger changes in patients than in healthy control participants advised to continue their current diet322.”

    From Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies (2018) · cites this paper as [322]

    The Abstract reports greater BMD changes after 24 months of calorie restriction than with an ad libitum diet, and greater changes in several bone-turnover markers at 12 months; at 24 months, only BSAP differed between groups. The Methods (Participants and Study Design; page unavailable) say both groups were healthy volunteers and the controls were advised to continue their current diets, so describing the restriction group as “patients” is misleading. (LLM, conf=0.87)

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Authors
Villareal, D. T., Fontana, L., Das, S. K., Redman, L., Smith, S. R., Saltzman, E., Bales, C., Rochon, J., Pieper, C., Huang, M., Lewis, M., Schwartz, A. V., & for the CALERIE Study Group
Affiliations
  • Michael E. DeBakey VA Medical Center (US)
  • Washington University in St. Louis (US)
  • Tufts University (US)
  • Pennington Biomedical Research Center (US)
  • Duke University (US)
  • University of Vermont (US)
  • University of California, San Francisco (US)
Corresponding author
Villareal, Dennis T
ORCID
Venue
Journal of Bone and Mineral Research
Publisher
Oxford University Press (OUP)
Published
2015-08-31
Volume
31
Issue
1
Pages
40-51
ISSN
  • 0884-0431 (ISSN-L)
  • 1523-4681
DOI
10.1002/jbmr.2701
PMC
PMC4834845
OpenAlex
W2143004711
Cited by
191
References
55
Citations by year
2026: 17 · 2025: 22 · 2024: 24 · 2023: 15 · 2022: 13 · 2021: 18 · 2020: 17 · 2019: 13 · 2018: 23 · 2017: 11 · 2016: 16 · 2015: 2
FWCI
17.89
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Journal of Bone and Mineral Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
Funders
National Institute on Aging
Topics
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
Keywords
caloric restriction, bone mineral density, bone metabolism, bone turnover markers, bone loss, young adults, body composition, fat mass, bone-specific alkaline phosphatase, C-terminal telopeptide, tartrate-resistant acid phosphatase, physical activity, nutrient intake, weight loss, aging, non-obese adults, femoral neck, lumbar spine, hip
MeSH terms
Adult, Aging, Body Weight, Female, Humans, Lumbar Vertebrae, Male, Middle Aged, Osteoporosis, Biomarkers, Bone Density, Caloric Restriction

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