Voluntary Wheel Running Partially Compensates for the Effects of Global Estrogen Receptor-α Knockout on Cortical Bone in Young Male Mice.

Estrogen receptor-α knockout (ERKO) in female, but not male, mice results in an impaired osteogenic response to exercise, but the mechanisms behind this ability in males are unknown. We explored the main and interactive effects of ERKO and exercise on cortical geometry, trabecular microarchitecture, biomechanical strength, and sclerostin expression in male mice. At 12 weeks of age, male C57BL/6J ERKO and WT animals were randomized into two groups: exercise treatment (EX) and sedentary (SED) controls, until 22 weeks of age. Cortical geometry and trabecular microarchitecture were measured via µCT; biomechanical strength was assessed via three-point bending; sclerostin expression was measured via immunohistochemistry. Two-way ANOVA was used to assess sclerostin expression and trabecular microarchitecture; two-way ANCOVA with body weight was used to assess cortical geometry and biomechanical strength. ERKO positively impacted trabecular microarchitecture, and exercise had little effect on these outcomes. ERKO significantly impaired cortical geometry, but exercise was able to partially reverse these negative alterations. EX increased cortical thickness regardless of genotype. There were no effects of genotype or exercise on sclerostin expression. In conclusion, male ERKO mice retain the ability to build bone in response to exercise, but altering sclerostin expression is not one of the mechanisms involved.

Soy Protein Isolate Suppresses Bone Resorption and Improves Trabecular Microarchitecture in Spontaneously Hyperphagic, Rapidly Growing Male OLETF Rats.

BACKGROUND: Traditionally, milk proteins have been recommended for skeletal health; recently, soy proteins have emerged as popular alternatives. Excess adiposity appears detrimental to skeletal health, as obese adolescents have increased fracture rates compared with healthy controls. However, soy protein effects on skeletal health during excess adiposity remain unknown. OBJECTIVE: The study objective was to examine the effects of isocaloric diets containing milk protein isolate (MPI), soy protein isolate (SPI), or a 50/50 combination (MIX) as the sole protein source on metabolic health indicators and bone outcomes in rapidly growing, hyperphagic, male Otsuka Long Evans Tokushima Fatty (OLETF) rats. METHODS: OLETF rats, aged 4 wk, were randomly assigned to 3 treatment groups (MPI, SPI, or MIX, n = 20 per group) and provided with access to experimental diets ad libitum for 16 wk. RESULTS: Body mass did not differ between the groups, but SPI had lower percentage body fat than MPI (P = 0.026). Insulin was lower in MPI than in MIX (P = 0.033) or SPI (P = 0.044), but fasting blood glucose was not different between the groups. SPI significantly reduced serum cholesterol compared with MPI (P = 0.001) and MIX (P = 0.002). N-terminal propeptide of type I collagen (P1NP) was higher in MIX than MPI (P = 0.05); C-terminal telopeptide of type 1 collagen (CTx) was higher in MPI than SPI (P < 0.001) and MIX (P < 0.001); the P1NP to CTx ratio was significantly higher in SPI and MIX than in MPI (P < 0.001). Trabecular separation was reduced in SPI compared with MPI (P = 0.030) and MIX (P = 0.008); trabecular number was increased in SPI compared with MIX (P = 0.038). No differences were seen in cortical geometry and biomechanical properties. CONCLUSIONS: In the context of excess adiposity, soy- and milk-based proteins have comparable effects on cortical bone geometry and biomechanical properties, whereas soy-based proteins favorably affect the trabecular microarchitecture, and the combination of both proteins may offer additional benefits to bone remodeling in rapidly growing male OLETF rats.

Soy protein improves tibial whole-bone and tissue-level biomechanical properties in ovariectomized and ovary-intact, low-fit female rats.

BACKGROUND: Osteoporosis and related fractures, decreased physical activity, and metabolic dysfunction are serious health concerns for postmenopausal women. Soy protein might counter the negative effects of menopause on bone and metabolic health due to the additive or synergistic effects of its bioactive components. OBJECTIVE: To evaluate the effects of ovariectomy (OVX) and a soy-protein diet (SOY) on bone outcomes in female, low-capacity running (LCR) rats selectively bred for low aerobic fitness as a model of menopause. METHODS: At 27 weeks of age, LCR rats (N = 40) underwent OVX or sham (SHAM) surgery and were randomized to one of two isocaloric and isonitrogenous plant-protein-based dietary treatments: 1) soy-protein (SOY; soybean meal); or, 2) control (CON, corn-gluten meal), resulting in four treatment groups. During the 30-week dietary intervention, animals were provided ad libitum access to food and water; body weight and food intake were measured weekly. At completion of the 30-week intervention, body composition was measured using EchoMRI; animals were fasted overnight, euthanized, and blood and hindlimbs collected. Plasma markers of bone formation (osteocalcin, OC; N-terminal propeptide of type I procollagen, P1NP) and resorption (tartrate-resistant acid phosphatase, TRAP5b; C-terminal telopeptide of type I collagen, CTx) were measured using ELISA. Tibial trabecular microarchitecture and cortical geometry were evaluated using µCT; and torsional loading to failure was used to assess cortical biomechanical properties. Advanced glycation end-product (AGE) content of the femur was measured using a fluorimetric assay, and was expressed relative to collagen content measured by a colorimetric OH-proline assay. Two-factor ANOVA or ANOVCA was used to test for significant main and interactive effects of ovarian status (OV STAT: OVX vs. SHAM) and DIET (SOY vs. CON); final body weight was included as a covariate for body-weight-dependent cortical geometry and biomechanical properties. RESULTS: OVX had significantly greater CTx than SHAM; SOY did not affect bone turnover markers. OVX adversely affected trabecular microarchitecture as evidenced by reduced BV/TV, trabecular thickness (Tb.Th), trabecular number (Tb.N), and connectivity density (Conn.D), and by increased trabecular separation (Tb.Sp) and structural model index (SMI). SOY increased BV/TV only in ovary-intact animals. There was no effect of OVX or SOY on tibial cortical geometry. In SHAM and OVX rats, SOY significantly improved whole-bone strength and stiffness; SOY also increased tissue-level stiffness and tended to increase tissue-level strength (p = 0.067). There was no effect of OVX or SOY on AGE content. CONCLUSION: Soy protein improved cortical bone biomechanical properties in female low-fit rats, regardless of ovarian hormone status.

Obesity and type 2 diabetes, not a diet high in fat, sucrose, and cholesterol, negatively impacts bone outcomes in the hyperphagic Otsuka Long Evans Tokushima Fatty rat.

BACKGROUND: Obesity and type 2 diabetes (T2D) increase fracture risk; however, the association between obesity/T2D may be confounded by consumption of a diet high in fat, sucrose, and cholesterol (HFSC). OBJECTIVE: The study objective was to determine the main and interactive effects of obesity/T2D and a HFSC diet on bone outcomes using hyperphagic Otuska Long Evans Tokushima Fatty (OLETF) rats and normophagic Long Evans Tokushima Otsuka (LETO) controls. METHODS: At 8weeks of age, male OLETF and LETO rats were randomized to either a control (CON, 10 en% from fat as soybean oil) or HFSC (45 en% from fat as soybean oil/lard, 17 en% sucrose, and 1wt%) diet, resulting in four treatment groups. At 32weeks, total body bone mineral content (BMC) and density (BMD) and body composition were measured by dual-energy X-ray absorptiometry, followed by euthanasia and collection of blood and tibiae. Bone turnover markers and sclerostin were measured using ELISA. Trabecular microarchitecture of the proximal tibia and geometry of the tibia mid-diaphysis were measured using microcomputed tomography; whole-bone and tissue-level biomechanical properties were evaluated using torsional loading of the tibia. Two-factor ANOVA was used to determine main and interactive effects of diet (CON vs. HFSC) and obesity/T2D (OLETF vs. LETO) on bone outcomes. RESULTS: Hyperphagic OLEFT rats had greater final body mass, body fat, and fasting glucose than normophagic LETO, with no effect of diet. Total body BMC and serum markers of bone formation were decreased, and bone resorption and sclerostin were increased in obese/T2D OLETF rats. Trabecular bone volume and microarchitecture were adversely affected by obesity/T2D, but not diet. Whole-bone and tissue-level biomechanical properties of the tibia were not affected by obesity/T2D; the HFSC diet improved biomechanical properties only in LETO rats. CONCLUSIONS: Obesity/T2D, regardless of diet, negatively impacted the balance between bone formation and resorption and trabecular bone volume and microarchitecture in OLETF rats.

Exercise initiated after the onset of insulin resistance improves trabecular microarchitecture and cortical bone biomechanics of the tibia in hyperphagic Otsuka Long Evans Tokushima Fatty rats.

The present study extends our previous findings that exercise, which prevents the onset of insulin resistance and type 2 diabetes (T2D), also prevents the detrimental effects of T2D on whole-bone and tissue-level strength. Our objective was to determine whether exercise improves bone's structural and material properties if insulin resistance is already present in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF rat is hyperphagic due to a loss-of-function mutation in cholecystokinin-1 receptor (CCK-1 receptor), which leads to progressive obesity, insulin resistance and T2D after the majority of skeletal growth is complete. Because exercise reduces body mass, which is a significant determinant of bone strength, we used a body-mass-matched caloric-restricted control to isolate body-mass-independent effects of exercise on bone. Eight-wk old, male OLETF rats were fed ad libitum until onset of hyperglycemia (20weeks of age), at which time they were randomly assigned to three groups: ad libitum fed, sedentary (O-SED); ad libitum fed, treadmill running (O-EX); or, sedentary, mild caloric restriction to match body mass of O-EX (O-CR). Long-Evans Tokushima Otsuka rats served as the normophagic, normoglycemic controls (L-SED). At 32weeks of age, O-SED rats had T2D as evidenced by hyperglycemia and a significant reduction in fasting insulin compared to OLETFs at 20weeks of age. O-SED rats also had reduced total body bone mineral content (BMC), increased C-terminal telopeptide of type I collagen (CTx)/tartrate resistant acid phosphatase isoform 5b (TRAP5b), decreased N-terminal propeptide of type I procollagen (P1NP), reduced percent cancellous bone volume (BV/TV), trabecular number (Tb.N) and increased trabecular separation (Tb.Sp) and structural model index (SMI) of the proximal tibia compared to L-SED. T2D also adversely affected biomechanical properties of the tibial diaphysis, and serum sclerostin was increased and ß-catenin, runt-related transcription factor 2 (Runx2) and insulin-like growth factor-I (IGF-I) protein expression in bone were reduced in O-SED vs. L-SED. O-EX or O-CR had greater total body bone mineral density (BMD) and BMC, and BV/TV, Tb.N, Tb.Sp, and SMI compared to O-SED. O-EX had lower CTx and CR greater P1NP relative to O-SED. O-EX, not O-CR, had greater cortical thickness and area, and improved whole-bone and tissue-level biomechanical properties associated with a 4-fold increase in cortical bone ß-catenin protein expression vs. O-SED. In summary, EX or CR initiated after the onset of insulin resistance preserved cancellous bone volume and structure, and EX elicited additional benefits in cortical bone.

Exercise improves femoral whole-bone and tissue-level biomechanical properties in hyperphagic OLETF rats.

An often-overlooked comorbidity of type 2 diabetes (T2D) is increased fracture risk. Since traditional T2D therapies focus solely on glucose homeostasis, there is an increased need for effective treatment strategies that improve both metabolic and bone health. The current study evaluated if previously reported protective effects of exercise (EX) on cortical bone geometry and biomechanical properties are due to the prevention of obesity compared with obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats or the unique skeletal effects of exercise. Four-week-old male OLETF rats were randomly assigned to 1 of 3 groups, each fed a standard rodent chow diet until 40 weeks of age: ad libitum-fed sedentary (O-SED), ad libitum-fed EX (O-EX), or a control group body-weight-matched to the O-EX group by caloric restriction (O-CR). Ad libitum-fed sedentary Long-Evans Tokushima Otsuka (L-SED) rats were used as a lean control. EX or CR prevented the excess body mass accumulation and elevated HbA1c observed in O-SED. Total-body bone mineral density was greater in O-EX than O-CR, but similar to L-SED and O-SED. O-EX and O-CR had lower osteocalcin and TRAP5b than O-SED and L-SED. EX or CR prevented the ∼3-fold increase in CTx in O-SED versus L-SED. EX increased femoral cortical mass accumulation and expansion at the mid-diaphysis compared with O-CR. EX or CR significantly increased tissue-level stiffness and strength compared with O-SED and L-SED, but O-EX had greater whole-bone stiffness than all other groups. In summary, EX has distinct advantages over CR for improving bone biomechanical properties in hyperphagic OLETF rats.

Insulin-Stimulated Bone Blood Flow and Bone Biomechanical Properties Are Compromised in Obese, Type 2 Diabetic OLETF Rats.

Type 2 diabetes (T2D) increases skeletal fragility and fracture risk; however, the underlying mechanisms remain to be identified. Impaired bone vascular function, in particular insulin-stimulated vasodilation and blood flow is a potential, yet unexplored mechanism. The purpose of this study was to determine the effects of T2D on femoral biomechanical properties, trabecular microarchitecture, and insulin-stimulated bone vasodilation by comparison of hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats with normoglycemic control OLETF rats. Four-week old, male OLETF rats were randomized to two groups: type 2 diabetes (O-T2D) or normoglycemic control (O-CON). O-T2D were allowed ad libitum access to a rodent chow diet and O-CON underwent moderate caloric restriction (30% restriction relative to intake of O-T2D) to maintain normal body weight (BW) and glycemia until 40 weeks of age. Hyperphagic O-T2D rats had significantly greater BW, body fat, and blood glucose than O-CON. Total cross-sectional area (Tt.Ar), cortical area (Ct.Ar), Ct.Ar/Tt.Ar, and polar moment of inertia of the mid-diaphyseal femur adjusted for BW were greater in O-T2D rats versus O-CON. Whole-bone biomechanical properties of the femur assessed by torsional loading to failure did not differ between O-T2D and O-CON, but tissue-level strength and stiffness adjusted for BW were reduced in O-T2D relative to O-CON. Micro-computed tomography (µCT) of the distal epiphysis showed that O-T2D rats had reduced percent bone volume, trabecular number, and connectivity density, and greater trabecular spacing compared with O-CON. Basal tibial blood flow assessed by microsphere infusion was similar in O-T2D and O-CON, but the blood flow response to insulin stimulation in both the proximal epiphysis and diaphyseal marrow was lesser in O-T2D compared to O-CON. In summary, impaired insulin-stimulated bone blood flow is associated with deleterious changes in bone trabecular microarchitecture and cortical biomechanical properties in T2D, suggesting that vascular dysfunction might play a causal role in diabetic bone fragility. © 2017 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Serum sclerostin decreases following 12months of resistance- or jump-training in men with low bone mass.

PURPOSE: We previously reported that 12months of resistance training (RT, 2×/wk, N=19) or jump training (JUMP, 3×/wk, N=19) increased whole body and lumbar spine BMD and increased serum bone formation markers relative to resorption in physically active (≥4h/wk) men (mean age: 44±2y; median: 44y) with osteopenia of the hip or spine. The purpose of this secondary analysis was to examine the effects of the RT or JUMP intervention on potential endocrine mediators of the exercise effects on bone, specifically IGF-I, PTH and sclerostin. METHODS: Fasting blood samples were collected after a 24-h period of no exercise at baseline and after 12months of RT or JUMP. IGF-I, PTH and sclerostin were measured in serum by ELISA. The effects of RT or JUMP on IGF-I, PTH and sclerostin were evaluated using 2×2 repeated measures ANOVA (time, group). This study was conducted in accordance with the Declaration of Helsinki and was approved by the University of Missouri IRB. RESULTS: Sclerostin concentrations in serum significantly decreased and IGF-I significantly increased after 12months of RT or JUMP; while PTH remained unchanged. CONCLUSION: The beneficial effects of long-term, progressive-intensity RT or JUMP on BMD in moderately active men with low bone mass are associated with decreased sclerostin and increased IGF-I.

Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a primary cause of diabetic nephropathy, retinopathy and neuropathy and poor bone blood flow is associated with bone loss. Therefore, we also hypothesize that dysfunction of the bone vascular endothelium contributes to the bone fragility observed in T2D. The most important consequence of our-dual hypothesis is the public health significance. Namely, identification of the proximal cause of T2D and associated bone complications allows pursuit of the appropriate therapeutic target to treat and prevent T2D. If our hypothesis that reduced bone blood flow is an early event in the pathogenesis of T2D and diabetic bone fragility is correct, then the endothelium of the bone vasculature should be a therapeutic target.

Effectiveness of resistance training or jumping-exercise to increase bone mineral density in men with low bone mass: A 12-month randomized, clinical trial.

PURPOSE: To examine the effects of 12 mo of resistance training (RT, 2×/wk, N=19) or jump training (JUMP, 3×/wk, N=19) on bone mineral density (BMD) and bone turnover markers (BTM) in physically active (≥ 4h/wk) men (mean age: 44 ± 2 y; median: 44 y) with osteopenia of the hip or spine. METHODS: Participants rated pain and fatigue following each RT or JUMP session. All participants received supplemental calcium (1200 mg/d) and vitamin D (10 µg/d). BMD was measured at 0, 6, and 12 mo using DXA scans of the whole body (WB), total hip (TH) and lumbar spine (LS). BTM and 25 OHD were measured by ELISA. The effects of RT or JUMP on BMD and BTM were evaluated using 3x2 repeated measures ANOVA (time, group). This study was conducted in accordance with the Declaration of Helsinki and was approved by the University of Missouri IRB. RESULTS: At baseline, 36 of 38 participants were vitamin D sufficient (25OHD >50 nmol/L); at 12 mo, all participants were 25OHD sufficient. 25OHD did not differ between groups. WB and LS BMD significantly increased after 6 months of RT or JUMP and this increase was maintained at 12 mo; TH BMD increased only in RT. Osteocalcin increased significantly after 12 mo of RT or JUMP; CTx decreased significantly after 6 mo and returned to baseline concentrations at 12 mo in both RT and JUMP. Pain and fatigue ratings after RT or JUMP sessions were very low at 0, 6, and 12 mo. CONCLUSION: RT or JUMP, which appeared safe and feasible, increased BMD of the whole body and lumbar spine, while RT also increased hip BMD, in moderately active, osteopenic men.

Obesity-related changes in bone structural and material properties in hyperphagic OLETF rats and protection by voluntary wheel running.

PURPOSE: To examine how the development of obesity and the associated insulin resistance affect bone structural and material properties, and bone formation and resorption markers in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model. METHODS: This was a 36-week study of sedentary, hyperphagic, male OLETF rats (OLETF-SED), exercise-treated OLETF rats (OLETF-EX) and sedentary non-hyperphagic controls (LETO-SED) with data collection at 13, 20, and 40 weeks of age (n = 5-8 animals per group per timepoint). RESULTS: Body mass and fat (%) were significantly greater in OLETF-SED versus controls. OLETF-SED were insulin resistant at 13 and 20 weeks, with overt diabetes by 40 weeks. At 13weeks, OLETF-SED had lower total body BMC and BMD and serum P1NP compared with LETO-SED. Differences in total body BMC and BMD between OLETF-SED and LETO-SED persisted at 20 weeks, with reductions in total and cortical BMD of the tibia. OLETF-SED also had lesser femur diameter, cross-sectional area, polar moment of area, and torque at fracture than LETO-SED. By 40 weeks, OLETF-SED had elevated bone resorption and reduced intrinsic bone strength. OLETF-EX did not show the excessive weight gain, obesity, insulin resistance or diabetes observed in OLETF-SED. OLETF-EX had greater BMD than OLETF-SED, and structural and material properties of the femur were significantly increased in OLETF-EX relative to OLETF-SED and LETO-SED. CONCLUSIONS: The negative skeletal effects of excessive adiposity and insulin resistance were evident early in the progressive obesity with lasting negative impacts on intrinsic and extrinsic bone strength. Exercise protected against obesity-associated skeletal changes with marked benefits on the biomechanical properties of bone.

Physical Activity-Associated Bone Loading During Adolescence and Young Adulthood Is Positively Associated With Adult Bone Mineral Density in Men.

Physical activity during growth increases bone mass and strength; however, it remains unclear whether these benefits persist. The purpose of this study was to determine: (a) if bone loading during adolescence (13-18 years) or young adulthood (19-29 years) in men is associated with greater bone mineral density (BMD) in adulthood; (b) if current participation in high-impact activity (ground reaction force>4×body weight) and/or resistance training is associated with greater BMD; and, (c) if continuous participation in a high-impact activity from adolescence to adulthood is associated with greater BMD. Apparently healthy, physically active men aged 30 to 65 years (n=203) participated in this cross-sectional study. Exercise-associated bone loading was estimated based on ground reaction forces of historical physical activity. Current BMD was measured using dual-energy X-ray absorptiometry. Participants were grouped based on current participation in a high-impact activity (n=18), resistance training (n=57), both (n=14), or neither (n=114); groups were compared by two-way analysis of covariance. Bone loading during adolescence and young adulthood were significant, positive predictors of BMD of the whole body, total hip, and lumbar spine, adjusting for lean body mass and/or age in the regression models. Individuals who currently participate in a high-impact activity had greater lumbar spine BMD than nonparticipants. Men who continuously participated in a high-impact activity had greater hip and lumbar spine BMD than those who did not. In conclusion, physical activity-associated bone loading both during and after skeletal growth is positively associated with adult bone mass.

The effects of improved metabolic risk factors on bone turnover markers after 12 weeks of simvastatin treatment with or without exercise.

OBJECTIVE: Emerging evidence supports an association between metabolic risk factors and bone turnover. Statins and exercise independently improve metabolic risk factors; however whether improvements in metabolic risk factor affects bone turnover is unknown. The purpose of the present study was to: 1) evaluate the relationship between metabolic risk factors and bone turnover; and 2) determine if improvements in metabolic risk factors after 12 weeks of statin treatment, exercise or the combination affect bone turnover. METHODS: Fifty participants with ≥2 metabolic syndrome defining characteristics were randomly assigned to one of three groups: statin (STAT: simvastatin, 40 mg/day), exercise (EX: brisk walking and/or slow jogging, 45 minutes/day, 5 days/week), or the combination (STAT+EX). Body composition and whole body bone mineral density were measured with dual energy X-ray absorptiometry. Serum markers of bone formation (bone specific alkaline phosphatase, BAP; osteocalcin, OC), resorption (C-terminal peptide of type I collagen, CTX) and metabolic risk factors were determined. Two-factor (time, group) repeated-measures ANCOVA was used to examine changes of metabolic risk factors and bone turnover. General linear models were used to determine the effect of pre-treatment metabolic risk factors on post-treatment bone turnover marker outcomes. RESULTS: Participants with ≥4 metabolic syndrome defining characteristics had lower pre-treatment OC than those with 3 or fewer. OC was negatively correlated with glucose, and CTX was positively correlated with cholesterol. STAT or STAT+EX lowered total and LDL cholesterol. The OC to CTX ratio decreased in all groups with no other significant changes in bone turnover. Higher pre-treatment insulin or body fat predicted a greater CTX reduction and a greater BAP/CTX increase. CONCLUSION: Metabolic risk factors were negatively associated with bone turnover markers. Short-term statin treatment with or without exercise lowered cholesterol and all treatments had a small effect on bone turnover.

Iron and the endurance athlete.

Iron is a trace mineral that is highly significant to endurance athletes. Iron is critical to optimal athletic performance because of its role in energy metabolism, oxygen transport, and acid-base balance. Endurance athletes are at increased risk for suboptimal iron status, with potential negative consequences on performance, because of the combination of increased iron needs and inadequate dietary intake. This review paper summarizes the role of iron in maximal and submaximal exercise and describes the effects of iron deficiency on exercise performance. Mechanisms that explain the increased risk of iron deficiency in endurance athletes, including exercise-associated inflammation and hepcidin release on iron sequestration, are described. Information on screening athletes for iron deficiency is presented, and suggestions to increase iron intake through diet modification or supplemental iron are provided.

Physical activity and bone health.

Osteoporosis and related fractures cause significant morbidity and mortality worldwide and result in enormous costs to affected individuals and society. Lifestyle choices across the lifespan impact osteoporosis and fracture risk. Physical activity is a viable strategy for the prevention and treatment of low bone mass.

One bout of exercise alters free-living postprandial glycemia in type 2 diabetes.

PURPOSE: Elevated postprandial glycemic (PPG) excursions are significant risk factors for cardiovascular disease in type 2 diabetes patients. In this study, we tested if and for how many meals a single bout of exercise would reduce PPG responses to subsequent meals in type 2 diabetes (T2D) patients using a continuous glucose monitor system (CGMS). METHODS: We recruited nine sedentary (<30 min·wk(-1) of exercise) individuals with T2D (mean ± SD; body mass index = 36.0 ± 1.1 kg·m(-2), age = 60.3 ± 1.0 yr, HbA1c = 6.3% ± 0.2%). The subjects consumed a eucaloric diet (51% carbohydrate, 31% fat, and 18% protein) consisting of three meals, identical in composition, for a 2-d period while wearing a continuous glucose monitor system in two different conditions (exercise [EX], one 60-min bout at 60%-75% of heart rate reserve performed before breakfast), vs a sedentary [SED] condition). We quantified 24-h average glucose, PPG area under the curve (AUC; 4-h glucose AUC after meals), and PPG-2 h (2 h postprandial glucose). RESULTS: EX significantly reduced average [glucose] during the first 24-h period (P = 0.03). EX caused a reduction in PPG-AUC (P = 0.02) for all of the meals during the 2 d (main effect between conditions). A comparison between the EX and the SED conditions at each meal revealed that EX reduced PPG-AUC after the second meal of day 1 (lunch) (P = 0.04). PPG-2 h was not significantly different between EX and SED. CONCLUSIONS: Although a single EX bout does lower 24-h average [glucose], it only significantly lowered PPG-AUC at the second meal after the bout, suggesting that daily exercise may be needed to most effectively improve PPG at the advent of exercise training in T2D patients.

Effects of current exercise and diet on late-life cognitive health of former college football players.

OBJECTIVE: To determine the relative influence of current exercise and diet on the late-life cognitive health of former Division I collision-sport collegiate athletes (ie, football players) compared with noncollision-sport athletes and non-athletes. METHODS: Graduates (n = 400) of a Midwestern university (average age, 64.09 years; standard deviation, 13.32) completed a self-report survey to assess current demographics/physical characteristics, exercise, diet, cognitive difficulties, and physical and mental health. RESULTS: Former football players reported more cognitive difficulties, as well as worse physical and mental health than controls. Among former football players, greater intake of total and saturated fat and cholesterol and lower overall diet quality were significantly correlated with cognitive difficulties; current dietary intake was not associated with cognitive health for the noncollision-sport athletes or nonathletes. Hierarchical regressions predicting cognitive difficulties indicated that income was positively associated with fewer cognitive difficulties and predicted 8% of the variance; status as a former football player predicted an additional 2% of the variance; and the interaction between being a football player and total dietary fat intake significantly predicted an additional 6% of the total variance (total model predicted 16% of variance). Greater intake of dietary fat was associated with increased cognitive difficulties, but only in the former football players, and not in the controls. Prior participation in football was associated with worse physical and mental health, while more frequent vigorous exercise was associated with higher physical and mental health ratings. CONCLUSION: Former football players reported more late-life cognitive difficulties and worse physical and mental health than former noncollision-sport athletes and nonathletes. A novel finding of the present study is that current dietary fat was associated with more cognitive difficulties, but only in the former football players. These results suggest the need for educational interventions to encourage healthy dietary habits to promote the long-term cognitive health of collision-sport athletes.

Acute response of plasma markers of bone turnover to a single bout of resistance training or plyometrics.

The time course of changes in plasma bone turnover markers following an acute bout of resistance training (RT) or plyometrics (PLY) has not been well characterized. This study is the first to compare the acute response of bone formation and resorption markers to a single bout of RT or PLY. Using a partially randomized, cross-over study design, 12 recreationally active men, aged 43 ± 5 yr, each completed four exercise trials: RT (Fed/Fasted) and PLY (Fed/Fasted). In addition to the RT and PLY trials, 5 of the original 12 participants also completed a fasted, no-exercise control trial to examine time-of-day variation. For each trial, blood was drawn immediately before exercise (PRE), immediately following exercise, and 15 min, 30 min, 1 h, 2 h, and 24 h following PRE for determination of plasma bone-specific alkaline phosphatase (BAP), osteocalcin (OC), tartrate-resistant acid phosphatase 5b (TRAP5b), COOH-terminal telopeptide of type I collagen (CTX), testosterone, parathyroid hormone, and cortisol. A one-factor repeated-measures ANOVA was performed for each trial to detect changes in bone markers during the 2 h following RT or PLY. TRAP5b transiently decreased during the 2 h following all exercise trials (main effect for time, P < 0.05), but returned to PRE concentrations 2 h postexercise. BAP, CTX, and OC remained unchanged, except for reductions in BAP and CTX following PLY-Fasted and PLY-Fed, respectively. During the control trial, BAP decreased, while TRAP5b, CTX, and OC remained unchanged. In general, plasma hormone concentrations decreased during the 2 h following PLY or RT, and cumulative decreases in TRAP5b during the 2 h following exercise were positively correlated with cumulative decreases in parathyroid hormone. The results of the present study suggest that the timing of the measurement of bone turnover markers relative to the last exercise bout is important for detection of exercise-associated changes in bone turnover markers, as the markers returned to preexercise values within 2 h of RT or PLY.

Bone loading during young adulthood predicts bone mineral density in physically active, middle-aged men.

BACKGROUND: Physical activity during growth induces skeletal adaptations that increase bone strength; however, it remains unclear whether these benefits persist into middle age. OBJECTIVE: We sought to determine if bone loading during adolescence (ages 13-18 years) or young adulthood (ages 19-29 years) in men is associated with greater bone mineral density (BMD) and reduced risk of low bone density in adulthood. We also sought to determine if participation in high-impact activities (ie, those that produce a ground reaction force [GRF] > 4 times the individual's body weight] during adolescence and/or young adulthood has a lasting positive effect on adult BMD. METHODS: Eighty-six, apparently healthy, physically active men (aged 30-60 years) participated in this cross-sectional study. Bone loading during adolescence, young adulthood, and adulthood were calculated based on GRFs of the reported physical activities. Whole body, lumbar spine, total hip, and femoral neck BMD were assessed using dual-energy x-ray absorptiometry (DXA). Multiple linear regression was used to examine relationships between BMD and bone loading, including body weight and/or age as covariates; logistic regression was used to predict low bone density for age. Participants were grouped based on participation in high-impact activity (never [n = 42], adolescence only [n = 19], or both adolescence and young adulthood [n=23]), and BMDs were compared. RESULTS: Bone loading during young adulthood, but not adolescence, was a significant positive predictor of adult BMD, with the full models explaining 33.4%, 31.7%, 44.6%, and 50.6% of the variance in whole body, lumbar spine, total hip, and femoral neck BMD, respectively. Ten participants (11.6%) had low bone density for age based on z scores of the hip or spine. Body weight and lean body mass, but not bone loading, were associated with reduced risk of low bone density for age. Individuals who participated in high-impact activity during both adolescence and young adulthood had greater BMD at all measured sites compared with those participated only during adolescence. CONCLUSION: The results of the study support a lifelong exercise prescription for bone health to preserve the skeletal benefits of activity derived from activity during adolescence and young adulthood.

Bone formation is increased to a greater extent than bone resorption during a cycling stage race.

This study examined the effects of participation in the Tour of Southland, a 6-day bicycle race, on serum markers of bone turnover in 5 elite male cyclists. During the race, energy intake matched expenditure. Osteocalcin was increased approximately 300% on days 1-5; and C-terminal telopeptide of type I collagen was elevated (43%) on day 3. Participation in a cycling stage race does not appear to have deleterious effects on bone turnover.