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

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/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??g/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.

SUBMITTER: Villareal DT

PROVIDER: S-EPMC4834845 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Villareal Dennis T DT Fontana Luigi L Das Sai Krupa SK Redman Leanne L Smith Steven R SR Saltzman Edward E Bales Connie C Rochon James J Pieper Carl C Huang Megan M Lewis Michael M Schwartz Ann V AV

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20150924 1

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 ...[more]

PMID: 26332798

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Project description:Weight loss therapy of older adults with obesity is limited by weight loss-induced decrease in bone mineral density (BMD), which could exacerbate ongoing age-related bone loss and increase the risk for fractures. Therefore, it is recommended that weight loss therapy of older adults with obesity should include an intervention such as regular exercise to reduce the concomitant bone loss. However, the most appropriate exercise types to combine with weight loss therapy in this older population is unknown. In a randomized controlled trial, we performed a head-to-head comparison of aerobic or resistance exercise, or both, during matched ~10% weight loss in 160 older adults with obesity. We measured changes in BMD (total hip, femoral neck, trochanter, intertrochanter, one-third radius, lumbar spine) and bone markers. Changes between groups were analyzed using mixed-model repeated measures analyses of variance. After 6?months of intensive lifestyle interventions, BMD decreased less in the resistance group (-0.006?g/cm2 [-0.7%]) and combination group (-0.012?g/cm2 [-1.1%]) than in the aerobic group (-0.027?g/cm2 [-2.6%]) (p = 0.001 for between-group comparisons). Serum C-telopeptide, procollagen type 1?N-propeptide, and osteocalcin concentrations increased more in the aerobic group (33%, 16%, and 16%, respectively) than in the resistance group (7%, 2%, and 0%, respectively) and combination group (11%, 2%, and 5%, respectively) (p = 0.004 to 0.048 for between-group comparisons). Multiple regression analyses revealed that the decline in whole body mass and serum leptin were the independent predictors of the decline in hip BMD (multiple R = 0.45 [p?<?.001]). These findings indicate that compared with aerobic exercise, resistance and combined aerobic and resistance exercise are associated with less weight loss-induced decrease in hip BMD and less weight loss-induced increase in bone turnover. Therefore, both resistance and combined aerobic and resistance exercise can be recommended to protect against bone loss during weight loss therapy of older adults with obesity. (LITOE ClinicalTrials.gov number NCT01065636.) © 2019 American Society for Bone and Mineral Research. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.

Project description:BackgroundChronic metabolic acidosis leads to bone mineral loss and results in lower bone mineral density (BMD), which is a risk factor for osteoporosis-related fractures. The effect of low-level metabolic acidosis on bone density in the general population is unknown.Study designCross-sectional study.Setting & participants9,724 nationally representative adults 20 years or older in NHANES (National Health and Nutrition Examination Survey) 1999-2004.FactorSerum bicarbonate level.OutcomesLumbar and total BMD, as well as low lumbar and total bone mass, defined as 1.0 SD below the sex-specific mean value of young adults.MeasurementsBMD was measured by dual-energy x-ray absorptiometry and serum bicarbonate was measured in all participants.ResultsBoth men and women with lower serum bicarbonate levels were more likely to be current smokers and had higher body mass index and estimated net endogenous acid production. There was a significant linear trend across quartiles of serum bicarbonate with lumbar BMD in the total population, as well as in sex-specific models (P=0.02 for all 3 models, P=0.1 for interaction). For total BMD, a significant association was seen with serum bicarbonate level for women but not men (P=0.02 and P=0.1, respectively; P=0.8 for interaction), and a significant association was seen for postmenopausal women but not premenopausal women (P=0.02 and P=0.2, respectively; P=0.5 for interaction). Compared with women with serum bicarbonate levels <24mEq/L, those with serum bicarbonate levels ≥27mEq/L had 0.018-g/cm(2) higher total BMD (95% CI, 0.004-0.032; P=0.01) and 31% lower odds of having low total bone mass (OR, 0.68; 95% CI, 0.46-0.99; P=0.049).LimitationsCross-sectional study using a single measurement of serum bicarbonate. Subgroup differences are not definitive.ConclusionsLower serum bicarbonate levels are associated with lower BMD in US adults. Further studies should examine whether serum bicarbonate levels should be incorporated into the diagnostic assessment and management of osteoporosis.

Dataset Information

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

Publications

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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