Effect of Two-Year Caloric Restriction on Bone Metabolism and Bone Mineral Density in Non-Obese Younger Adults: A Randomized Clinical Trial.
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/m(2) ), 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/cm(2) ; p < 0.001), total hip (-0.017 ± 0.002 versus 0.001 ± 0.003 g/cm(2) ; p < 0.001), and femoral neck (-0.015 ± 0.003 versus -0.005 ± 0.004 g/cm(2) ; 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.
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.|Baylor College of Medicine and Center for Translational Research on Inflammatory Diseases (CTRID), Michael E DeBakey VA Medical Center, Houston, TX, USA.
Dennis T
DT
Villareal
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.|Department of Clinical and Experimental Sciences, University Medical School, Brescia, Italy.|CEINGE Biotecnologie Avanzate, Napoli, Italy.
Luigi
L
Fontana
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
Sai Krupa
SK
Das
Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Leanne
L
Redman
Pennington Biomedical Research Center, Baton Rouge, LA, USA.|Translational Research Institute for Metabolism and Diabetes, Florida Hospital and Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA.
Steven R
SR
Smith
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
Edward
E
Saltzman
Durham VA Medical Center and Duke University Medical Center, Durham, NC, USA.|Duke Clinical Research Institute, Durham, NC, USA.
Connie
C
Bales
Duke Clinical Research Institute, Durham, NC, USA.|Rho Federal Systems, Chapel Hill, NC, USA.
James
J
Rochon
Duke Clinical Research Institute, Durham, NC, USA.
Carl
C
Pieper
Duke Clinical Research Institute, Durham, NC, USA.
Megan
M
Huang
University of Vermont, Burlington, VT, USA.
Michael
M
Lewis
University of California, San Francisco, San Francisco, CA, USA.
Ann V
AV
Schwartz
D000328:Adult; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D015519:Bone Density; D031204:Caloric Restriction / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000209:etiology
D015415:Biomarkers
BONE-FAT INTERACTIONS; BONE-MUSCLE INTERACTIONS; DXA; FRACTURE PREVENTION; NUTRITION