Obesity is traditionally viewed to be beneficial to bone health because of well-established positive effect of mechanical loading conferred by body weight on bone formation, despite being a risk ...factor for many other chronic health disorders. Although body mass has a positive effect on bone formation, whether the mass derived from an obesity condition or excessive fat accumulation is beneficial to bone remains controversial. The underline pathophysiological relationship between obesity and bone is complex and continues to be an active research area. Recent data from epidemiological and animal studies strongly support that fat accumulation is detrimental to bone mass. To our knowledge, obesity possibly affects bone metabolism through several mechanisms. Because both adipocytes and osteoblasts are derived from a common multipotential mesenchymal stem cell, obesity may increase adipocyte differentiation and fat accumulation while decrease osteoblast differentiation and bone formation. Obesity is associated with chronic inflammation. The increased circulating and tissue proinflammatory cytokines in obesity may promote osteoclast activity and bone resorption through modifying the receptor activator of NF-κB (RANK)/RANK ligand/osteoprotegerin pathway. Furthermore, the excessive secretion of leptin and/or decreased production of adiponectin by adipocytes in obesity may either directly affect bone formation or indirectly affect bone resorption through up-regulated proinflammatory cytokine production. Finally, high-fat intake may interfere with intestinal calcium absorption and therefore decrease calcium availability for bone formation. Unraveling the relationship between fat and bone metabolism at molecular level may help us to develop therapeutic agents to prevent or treat both obesity and osteoporosis. Obesity, defined as having a body mass index ≥ 30 kg/m2, is a condition in which excessive body fat accumulates to a degree that adversely affects health. The rates of obesity rates have doubled since 1980 and as of 2007, 33% of men and 35% of women in the US are obese. Obesity is positively associated to many chronic disorders such as hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, and certain cancers. It is estimated that the direct medical cost associated with obesity in the United States is ~$100 billion per year.Bone mass and strength decrease during adulthood, especially in women after menopause. These changes can culminate in osteoporosis, a disease characterized by low bone mass and microarchitectural deterioration resulting in increased bone fracture risk. It is estimated that there are about 10 million Americans over the age of 50 who have osteoporosis while another 34 million people are at risk of developing the disease. In 2001, osteoporosis alone accounted for some $17 billion in direct annual healthcare expenditure. Several lines of evidence suggest that obesity and bone metabolism are interrelated. First, both osteoblasts (bone forming cells) and adipocytes (energy storing cells) are derived from a common mesenchymal stem cell and agents inhibiting adipogenesis stimulated osteoblast differentiation and vice versa, those inhibiting osteoblastogenesis increased adipogenesis. Second, decreased bone marrow osteoblastogenesis with aging is usually accompanied with increased marrow adipogenesis. Third, chronic use of steroid hormone, such as glucocorticoid, results in obesity accompanied by rapid bone loss. Fourth, both obesity and osteoporosis are associated with elevated oxidative stress and increased production of proinflammatory cytokines. At present, the mechanisms for the effects of obesity on bone metabolism are not well defined and will be the focus of this review.
Cao discusses the study of Sharma et al in which they investigated the acute changes in concentrations of the circulating bone resorption marker, C-terminal cross-linking telopeptide of type 1 ...collagen (CTX), in response to either calcium in the form of high-calcium skim milk or calcium carbonate in a randomized crossover study design with 77 nonoverweight and overweight or obese postmenopausal women. The finding from Sharma et al that circulating concentrations of CTX in overweight or obese postmenopausal women are similarly responsive to dietary calcium intake compared with nonobese women has important implications for bone metabolism. Most forms of bone loss reflect increased bone resorption relative to bone formation, especially in postmenopausal women, who are susceptible to bone loss due to the decrease in estrogen after menopause.
Weight reduction through caloric restriction (CR) or exercise can have opposite effects on bone. This study investigated the effects of comparable weight reduction through CR and/or exercise on body ...composition and bone structure in an obese rat model. Male 6‐week‐old rats were fed either a normal‐fat diet for 6 months or a high‐fat (HF) diet for 3 months and then started on different CR or exercise regimens for an additional 3 months. Compared to HF conditions, rats given HF diet plus CR at 8% (HF+8CR), HF diet plus CR at 16% (HF+16CR), or HF+8CR plus exercise (HF+Ex+8CR) had lower fat mass. In addition, HF+8CR rats had lower serum tartrate‐resistant acid phosphatase and bone volume/total volume at distal femur (P < 0.05), and HF+16CR rats had lower serum insulin growth factor 1, osteocalcin, tartrate‐resistant acid phosphatase, and bone volume/total volume at distal femur and 2nd lumbar vertebrae, compared to regimens that included exercise. These data indicate that while CR (e.g., HF+8CR) was detrimental to bone structure, combined with exercise CR (e.g., HF+Ex+8CR) was effective in decreasing adiposity and mitigating bone structural deterioration associated with weight reduction in obese rats.
This study investigated the effects of comparable weight reduction achieved through caloric restriction and/or exercise on adiposity, bone structure, and related bone biomarkers. The working hypothesis was that caloric restriction combined with exercise is more effective that caloric restriction alone in reducing adiposity and mitigating bone structural deterioration in weight reduction in high‐fat diet‐induced obesity in rodents.
Obesity induced by a high-fat (HF) diet increases bone resorption and/or decreases bone formation, resulting in reduced bone mass and strength in various animal models. Studies showed that Ca intake ...is a modifiable factor for osteoporosis and obesity. This study investigated whether Ca deficiency affects bone structure and adiposity in ovariectomized (OVX) rats fed a HF diet. We hypothesized that Ca deficiency further decreases bone mass and increases fat mass in HF-fed OVX rats. Forty-seven OVX at 6-month-old were randomly assigned to four groups in a 2 × 2 factorial design: normal-fat (NF, 10% fat as energy) or HF (45% fat as energy) diet with either low Ca (LC, 1 g/4057 kcal) or normal Ca (NC, 6 g/4057 kcal). In addition, 12 sham-operated rats at 6 months old were fed a NFNC diet as a control for the OVX procedure. Rats were fed the respective diet for 4 months. Dietary Ca content did not affect body weight, fat mass, lean mass, food intake, energy intake, and serum cytokines. Compared to NC, LC resulted in lower tibial bone volume/total volume (BV/TV,
< 0.01), connectivity density (
< 0.01), trabecular number (Tb.N,
= 0.01), bone mineral density (BMD,
< 0.01), and femur weight (
< 0.01), femur content of Ca (
< 0.01), Cu (
= 0.03), Zn (
< 0.01), and greater trabecular separation (Tb.Sp,
< 0.01) at proximal tibia indicating bone structure deterioration. Compared to rats on the NF diet, animals fed the HF had lower BV/TV (
= 0.03) and Tb.N (
< 0.01) with greater body weight (
< 0.01), fat mass (
< 0.01), Tb.Sp (
= 0.01), the content of Ca, Cu, and Zn in the femur, and serum leptin (
< 0.01). There were no significant interactions between Ca and fat for body composition and bone structural parameters. Compared to Sham, OVX resulted in greater body weight and fat mass. The trabecular bone structure of the tibia, but not the cortical bone, was significantly impaired by the OVX procedure. These data indicate that inadequate Ca intake and a high-fat diet have independent negative effects on bone structure and that Ca deficiency does not affect adiposity in OVX rats.
Obesity-derived body mass may be detrimental to bone health through not well-defined mechanisms. In this study we determined changes in bone structure and serum cytokines related to bone metabolism ...in diet-induced obese mice. Mice fed a high-fat diet (HFD) had higher serum tartrate-resistant acid phosphatase (TRAP) and leptin but lower osteocalcin concentrations than those fed the normal-fat diet. The HFD increased multinucleated TRAP-positive osteoclasts in bone marrow compared to the control diet. Despite being much heavier, mice fed the HFD had lower femoral bone volume, trabecular number, and connectivity density and higher trabecular separation than mice on the control diet. These findings suggest that obesity induced by a HFD increases bone resorption that may blunt any positive effects of increased body weight on bone.
Background:
Circadian clock genes are expressed in bone and biomarkers of bone resorption and formation exhibit diurnal patterns in animals and humans. Disruption of the diurnal rhythms may affect ...the balance of bone turnover and compromise the beneficial effects of exercise on bone.
Objective:
This study investigated whether the time of day of exercise alters bone metabolism in a rodent model. We hypothesized that exercise during the active phase results in greater bone mass than exercise during the rest phase in older female rats.
Methods:
Fifty-five, female 12-month-old Sprague Dawley rats were randomly assigned to four treatment groups (
n
= 13–14/group). Rats were subjected to no exercise or 2 h of involuntary exercise at 9 m/min and 5 days/wk for 15 weeks using motor-driven running wheels at Zeitgeber time (ZT) 4–6 (rest phase), 12–14 (early active phase), or 22–24 (late active phase). ZT 0 is defined as light on, the start of the rest phase. A red lamp was used at minimal intensity during the active, dark phase exercise period, i.e., ZT 12–14 and 22–24. Bone structure, body composition, and bone-related cytokines in serum and gene expression in bone were measured. Data were analyzed using one-way ANOVA followed by Tukey-Kramer
post hoc
contrasts.
Results:
Exercise at different ZT did not affect body weight, fat mass, lean mass, the serum bone biomarkers, bone structural or mechanical parameters, or expression of circadian genes. Exercise pooled exercise data from different ZT were compared to the No-Exercise data (
a priori
contrast) increased serum IGF-1 and irisin concentrations, compared to No-Exercise. Exercise increased tibial bone volume/total volume (
p
= 0.01), connectivity density (
p
= 0.04), and decreased structural model index (
p
= 0.02). Exercise did not affect expression of circadian genes.
Conclusion:
These data indicate that exercise is beneficial to bone structure and that the time of day of exercise does not alter the beneficial effect of exercise on bone in older female rats.
Intake of total fat is linked to obesity and inversely associated with bone density in humans. Epidemiologic and animal studies show that long-chain n–3 (ω-3) PUFAs supplied as fish oil (FO) are ...beneficial to skeletal health.
This study tested the hypothesis that increasing dietary FO would decrease adiposity and improve bone-related outcomes in growing obese mice.
Male C57BL/6 mice at 6 wk old were assigned to 6 treatment groups and fed either a normal-fat diet (3.85 kcal/g and 10% energy as fat) or a high-fat diet (HF; 4.73 kcal/g and 45% energy as fat) containing either 0%, 3%, or 9% energy as FO (0FO, 3FO, and 9FO, respectively) ad libitum for 6 mo. Bone structure, body composition, and serum bone-related cytokines were measured.
The HF diet increased the expression of the adipose tissue tumor necrosis factor α (Tnfa) and serum concentrations of leptin and tartrate-resistant acid phosphatase (TRAP), and decreased serum concentrations of osteocalcin and bone-specific alkaline phosphatase (P < 0.05). FO decreased fat mass (P < 0.05), serum TRAP (P < 0.05), and adipose tissue Tnfa expression (P < 0.01). Bone content of long-chain n–3 PUFAs was increased and n–6 PUFAs were decreased with the elevation in dietary FO content (P < 0.01). Compared with mice fed 9FO, animals fed 3FO had higher femoral bone volume/total volume (25%), trabecular number (23%), connectivity density (82%), and bone mass of second lumbar vertebrae (12%) and lower femoral trabecular separation (-19%). Mice fed the 3FO HF diet had 42% higher bone mass than those fed the 0FO HF diet.
These data indicate increasing dietary FO ≤3% energy can decrease adiposity and mitigate HF diet–induced bone deterioration in growing C57BL/6 mice possibly by reducing inflammation and bone resorption. FO at 9% diet energy had no further beneficial effects on bone of obese mice.
The purpose of this work was to determine the effects of varying levels of dietary protein on body composition and muscle protein synthesis during energy deficit (ED). A randomized controlled trial ...of 39 adults assigned the subjects diets providing protein at 0.8 (recommended dietary allowance; RDA), 1.6 (2X‐RDA), and 2.4 (3X‐RDA) g kg–1 d–1 for 31 d. A 10‐d weight‐maintenance (WM) period was followed by a 21 d, 40% ED. Body composition and postabsorptive and postprandial muscle protein synthesis were assessed during WM (d 9‐10) and ED (d 30‐31). Volunteers lost (P<0.05) 3.2 ± 0.2 kg body weight during ED regardless of dietary protein. The proportion of weight loss due to reductions in fat‐free mass was lower (P<0.05) and the loss of fat mass was higher (P<0.05) in those receiving 2X‐RDA and 3X‐RDA compared to RDA. The anabolic muscle response to a protein‐rich meal during ED was not different (P>0.05) from WM for 2X‐RDA and 3X‐RDA, but was lower during ED than WM for those consuming RDA levels of protein (energy × protein interaction, P<0.05). To assess muscle protein metabolic responses to varied protein intakes during ED, RDA served as the study control. In summary, we determined that consuming dietary protein at levels exceeding the RDA may protect fat‐free mass during short‐term weight loss.—Pasiakos, S. M., Cao, J. J., Margolis, L. M., Sauter, E. R., Whigham, L. D., McClung, J. P., Rood, J. C., Carbone, J. W., Combs, G. F., Jr., Young, A. J. Effects of high‐protein diets on fat‐free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J. 27, 3837–3847 (2013). www.fasebj.org
Purpose of Review
Consumption of high-protein diets is increasingly popular due to the benefits of protein on preserving lean mass and controlling appetite and satiety. The paper is to review recent ...clinical research assessing dietary protein on calcium metabolism and bone health.
Recent Findings
Epidemiological studies show that long-term, high-protein intake is positively associated with bone mineral density and reduced risk of bone fracture incidence. Short-term interventional studies demonstrate that a high-protein diet does not negatively affect calcium homeostasis. Existing evidence supports that the negative effects of the acid load of protein on urinary calcium excretion are offset by the beneficial skeletal effects of high-protein intake.
Summary
Future research should focus on the role and the degree of contribution of other dietary and physiological factors, such as intake of fruits and vegetables, in reducing the acid load and further enhancing the anabolic effects of protein on the musculoskeletal system.
Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Such findings may relate to roles of Se in ...antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Elucidation of the mechanisms by which Se supports these cellular processes can lead to a better understanding of the role of this nutrient in normal bone metabolism. This article reviews the current knowledge concerning the molecular functions of Se relevant to bone health.
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