Calcium Supplementation Attenuates Disruptions in Calcium Homeostasis during Exercise.

An exercise-induced decrease in serum ionized calcium (iCa) is thought to trigger an increase in parathyroid hormone (PTH), which can stimulate bone resorption. PURPOSE: The purpose of this study was to determine whether taking a chewable calcium (Ca) supplement 30 min before exercise mitigates disruptions in Ca homeostasis and bone resorption in competitive male cyclists. METHODS: Fifty-one men (18 to 45 yr old) were randomized to take either 1000 mg Ca (CA) or placebo (PL) 30 min before a simulated 35-km cycling time trial. Serum iCa and PTH were measured before and immediately after exercise and a marker of bone resorption (C-terminal telopeptide of type I collagen) was measured before and 30 min after exercise. RESULTS: Serum iCa decreased in both groups from before to after exercise (mean ± SD, CA = 4.89 ± 0.16 to 4.76 ± 0.11 mg·dL, PL = 4.92 ± 0.15 to 4.66 ± 0.22 mg·dL, both P ≤ 0.01); the decrease was greater (P = 0.03) in the PL group. There was a nonsignificant (P = 0.07) attenuation of the increase in PTH by Ca supplementation (CA = 30.9 ± 13.0 to 79.7 ± 42.6 pg·mL, PL = 37.1 ± 14.8 to 111.5 ± 49.4 pg·mL, both P ≤ 0.01), but no effect of Ca on the change in C-terminal telopeptide of type I collagen, which increased in both groups (CA = 0.35 ± 0.17 to 0.50 ± 0.21 ng·mL, PL = 0.36 ± 0.13 to 0.54 ± 0.22 ng·mL, both P ≤ 0.01). CONCLUSION: It is possible that ingesting Ca only 30 min before exercise was not a sufficient time interval to optimize gut Ca availability during exercise. Further studies will be needed to determine whether adequate Ca supplementation before and/or during exercise can fully mitigate the exercise-induced decrease in serum iCa and increases in PTH and bone resorption.

Timing of Ibuprofen Use and Musculoskeletal Adaptations to Exercise Training in Older Adults.

Prostaglandins (PG) increase in bone in response to mechanical loading and stimulate bone formation. Inhibition of cyclooxygenase (COX), the enzyme responsible for PG synthesis, by non-steroidal anti-inflammatory drugs (NSAIDs) impairs the bone formation response to loading in animals when administered before, but not after, loading. The aim was to determine whether the timing of ibuprofen use (400 mg before versus after exercise sessions) is a significant determinant of the adaptive response of BMD to exercise training in older adults. We hypothesized that taking ibuprofen before exercise would attenuate the improvements in total hip and lumbar spine BMD in response to 36 weeks of training when compared with placebo or with ibuprofen use after exercise. Untrained women and men (N=189) aged 60 to 75 years were randomly assigned to 1 of 3 treatment arms: placebo before and after exercise (PP); ibuprofen before and placebo after exercise (IP); and placebo before and ibuprofen after exercise (PI). The difference between groups in the change in BMD was not significant when IP was compared with either PP (hip, -0.5% (-1.4, 0.4); spine, 0.1% (-0.9, 1.2)) or PI (hip, 0.3% (-0.6, 1.2); spine, 0.5% (-0.5, 1.5)). Ibuprofen use appeared to have more adverse effects on BMD in women than men. The study demonstrated that ibuprofen use did not significantly alter the BMD adaptations to exercise in older adults, but this finding should be interpreted cautiously. It had been expected that the inhibition of bone formation by ibuprofen would be as robust in men than women, but this did not appear to be the case and may have limited the power to detect the effects of ibuprofen. Further research is needed to understand whether NSAID use counteracts, in part, the beneficial effects of exercise on bone.

Calcium supplementation and parathyroid hormone response to vigorous walking in postmenopausal women.

INTRODUCTION: Disruptions in calcium (Ca) homeostasis during exercise may influence skeletal adaptations to exercise training. In young men, vigorous cycling causes increases in parathyroid hormone (PTH) and bone resorption (C-terminal telopeptides of type I collagen [CTX]); responses are attenuated by Ca supplementation. The study aimed to determine whether vigorous walking causes similar increases in PTH and CTX in older women and how the timing of Ca supplementation before and during exercise influences these responses. METHODS: In experiment 1, 10 women (61 ± 4 yr) consumed 125 mL of either a Ca-fortified (1 g·L) or control beverage every 15 min during exercise starting 60 min before and continuing during 60 min of exercise. In experiment 2, 23 women (61 ± 4 yr) consumed 200 mL of a Ca-fortified (1 g·L) or control beverage every 15 min starting 15 min before and continuing during 60 min of exercise. The exercise was treadmill walking at 75%-80% V˙O2peak. RESULTS: In experiment 1, serum ionized Ca decreased in the control condition (P < 0.001), but not with Ca supplementation. PTH increased after exercise on both days (Ca, P = 0.05; control, P = 0.009) but was attenuated by Ca supplementation (8.3 vs 26.1 pg·mL; P = 0.03). CTX increased only on the control day (P = 0.02). In experiment 2, serum ionized Ca decreased on Ca and control days (Ca and control, P < 0.001), but less so on the Ca day (P = 0.04). PTH (Ca and control, P < 0.001) and CTX (Ca, P = 0.02; control P = 0.007) increased on the Ca and control day, and there were no differences in the changes. CONCLUSION: The timing of Ca supplementation may be a key mediator of Ca homeostasis during acute exercise. Further research is necessary to determine how this influences skeletal adaptations to training.

Bone loss over 1 year of training and competition in female cyclists.

OBJECTIVE: To observe changes in hip, spine, and tibia bone characteristics in female cyclists over the course of 1 year of training. DESIGN: Prospective observational study. SETTING: Laboratory. PARTICIPANTS: Female cyclists (n = 14) aged 26-41 years with at least 1 year of competition history and intent to compete in 10 or more races in the coming year. ASSESSMENT OF RISK FACTORS: Women who train and compete in road cycling as their primary sport. MAIN OUTCOME MEASURES: Total body fat-free and fat mass and lumbar spine and proximal femur areal bone mineral density (aBMD) and bone mineral content (BMC) assessments by dual-energy x-ray absorptiometry. Volumetric BMD and BMC of the tibia were measured by peripheral quantitative computed tomography at sites corresponding to 4%, 38%, 66%, and 96% of tibia length. Time points were baseline and after 12 months of training and competition. RESULTS: Weight and body composition did not change significantly over 12 months. Total hip aBMD and BMC decreased by -1.4% ± 1.9% and -2.1% ± 2.3% (P < 0.02) and subtrochanter aBMD and BMC decreased by -2.1% ± 2.0% and -3.3% ± 3.7% (P < 0.01). There was a significant decrease in lumbar spine BMC (-1.1% ± 1.9%; P = 0.03). There were no significant bone changes in the tibia (P > 0.11). CONCLUSIONS: Bone loss in female cyclists was site specific and similar in magnitude to losses previously reported in male cyclists. Research is needed to understand the mechanisms for bone loss in cyclists.

Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels.

CONTEXT: Aging in men is associated with reduced testosterone (T) levels and physiological changes leading to frailty, but the benefits of T supplementation are inconclusive. OBJECTIVE: We studied the effects of T supplementation with and without progressive resistance training (PRT) on functional performance, strength, and body composition. DESIGN, SETTING, AND PARTICIPANTS: We recruited 167 generally healthy community-dwelling older men (66 ± 5 years) with low-normal baseline total T levels (200-350 ng/dL). INTERVENTION: Subjects were randomized to placebo or transdermal T gel [2 doses targeting either a lower (400-550 ng/dL) or higher (600-1000 ng/dL) T range] and to either PRT or no exercise for 12 months. MAIN OUTCOME MEASURE: The primary outcome was functional performance, whereas secondary outcomes were strength and body composition. RESULTS: A total of 143 men completed the study. At 12 months, total T was 528 ± 287 ng/dL in subjects receiving any T and 287 ± 65 ng/dL in the placebo group. In the PRT group, function and strength were not different between T- and placebo-treated subjects, despite greater improvements in fat mass (P = .04) and fat-free mass (P = .01) with T. In the non-PRT group, T did not improve function but improved fat mass (P = .005), fat-free mass (P = .03), and upper body strength (P = .03) compared with placebo. There were fewer cardiovascular events in the T-treated groups compared with placebo. CONCLUSIONS: T supplementation was well tolerated and improved body composition but had no effect on functional performance. T supplementation improved upper body strength only in nonexercisers compared with placebo.

Increasing dietary fat elicits similar changes in fat oxidation and markers of muscle oxidative capacity in lean and obese humans.

In lean humans, increasing dietary fat intake causes an increase in whole-body fat oxidation and changes in genes that regulate fat oxidation in skeletal muscle, but whether this occurs in obese humans is not known. We compared changes in whole-body fat oxidation and markers of muscle oxidative capacity differ in lean (LN) and obese (OB) adults exposed to a 2-day high-fat (HF) diet. Ten LN (BMI = 22.5±2.5 kg/m², age = 30±8 yrs) and nine OB (BMI = 35.9±4.93 kg/m², 38±5 yrs, Mean±SD) were studied in a room calorimeter for 24hr while consuming isocaloric low-fat (LF, 20% of energy) and HF (50% of energy) diets. A muscle biopsy was obtained the next morning following an overnight fast. 24h respiratory quotient (RQ) did not significantly differ between groups (LN: 0.91±0.01; OB: 0.92±0.01) during LF, and similarly decreased during HF in LN (0.86±0.01) and OB (0.85±0.01). The expression of pyruvate dehydrogenase kinase 4 (PDK4) and the fatty acid transporter CD36 increased in both LN and OB during HF. No other changes in mRNA or protein were observed. However, in both LN and OB, the amounts of acetylated peroxisome proliferator-activated receptor γ coactivator-1-α (PGC1-α) significantly decreased and phosphorylated 5-AMP-activated protein kinase (AMPK) significantly increased. In response to an isoenergetic increase in dietary fat, whole-body fat oxidation similarly increases in LN and OB, in association with a shift towards oxidative metabolism in skeletal muscle, suggesting that the ability to adapt to an acute increase in dietary fat is not impaired in obesity.

Acute calcium ingestion attenuates exercise-induced disruption of calcium homeostasis.

PURPOSE: Exercise is associated with a decrease in bone mineral density under certain conditions. One potential mechanism is increased bone resorption due to an exercise-induced increase in parathyroid hormone (PTH), possibly triggered by dermal calcium loss. The purpose of this investigation was to determine whether calcium supplementation either before or during exercise attenuates exercise-induced increases in PTH and C-terminal telopeptide of Type I collagen (CTX; a marker of bone resorption). METHODS: Male endurance athletes (n = 20) completed three 35-km cycling time trials under differing calcium supplementation conditions: 1) 1000 mg of calcium 20 min before exercise and placebo during, 2) placebo before and 250 mg of calcium every 15 min during exercise (1000 mg total), or 3) placebo before and during exercise. Calcium was delivered in a 1000-mg·L(-1) solution. Supplementation was double-blinded, and trials were performed in random order. PTH, CTX, bone-specific alkaline phosphatase (BAP; a marker of bone formation), and ionized calcium (iCa) were measured before and immediately after exercise. RESULTS: CTX increased and iCa decreased similarly in response to exercise under all test conditions. When compared with placebo, calcium supplementation before exercise attenuated the increase in PTH (mean ± SE: 55.8 ± 15.0 vs 74.0 ± 14.2 pg·mL(-1), P = 0.04); there was a similar trend (58.0 ± 17.4, P = 0.07) for calcium supplementation during exercise. There were no effects of calcium on changes in CTX, BAP, and iCa. CONCLUSIONS: Calcium supplementation before exercise attenuated the disruption of PTH. Further research is needed to determine the effects of repeated increases in PTH and CTX on bone (i.e., exercise training) and whether calcium supplementation can diminish any exercise-induced demineralization.

Timing of ibuprofen use and bone mineral density adaptations to exercise training.

Prostaglandins (PGs) are essential signaling factors in bone mechanotransduction. In animals, inhibition of the enzyme responsible for PG synthesis (cyclooxygenase) by nonsteroidal anti-inflammatory drugs (NSAIDs) blocks the bone-formation response to loading when administered before, but not immediately after, loading. The aim of this proof-of-concept study was to determine whether the timing of NSAID use influences bone mineral density (BMD) adaptations to exercise in humans. Healthy premenopausal women (n = 73) aged 21 to 40 years completed a supervised 9-month weight-bearing exercise training program. They were randomized to take (1) ibuprofen (400 mg) before exercise, placebo after (IBUP/PLAC), (2) placebo before, ibuprofen after (PLAC/IBUP), or (3) placebo before and after (PLAC/PLAC) exercise. Relative changes in hip and lumbar spine BMD from before to after exercise training were assessed using a Hologic Delphi-W dual-energy X-ray absorptiometry (DXA) instrument. Because this was the first study to evaluate whether ibuprofen use affects skeletal adaptations to exercise, only women who were compliant with exercise were included in the primary analyses (IBUP/PLAC, n = 17; PLAC/PLAC, n = 23; and PLAC/IBUP, n = 14). There was a significant effect of drug treatment, adjusted for baseline BMD, on the BMD response to exercise for regions of the hip (total, p < .001; neck, p = .026; trochanter, p = .040; shaft, p = .019) but not the spine (p = .242). The largest increases in BMD occurred in the group that took ibuprofen after exercise. Total-hip BMD changes averaged -0.2% +/- 1.3%, 0.4% +/- 1.8%, and 2.1% +/- 1.7% in the IBUP/PLAC, PLAC/PLAC, and PLAC/IBUP groups, respectively. This preliminary study suggests that taking NSAIDs after exercise enhances the adaptive response of BMD to exercise, whereas taking NSAIDs before may impair the adaptive response.

When energy balance is maintained, exercise does not induce negative fat balance in lean sedentary, obese sedentary, or lean endurance-trained individuals.

Fat oxidation during exercise is increased by endurance training, and evidence suggests that fat oxidation during exercise is impaired in obesity. Thus the primary aim of this study was to compare the acute effects of exercise on 24-h fat oxidation and fat balance in lean sedentary [LS, n = 10, body mass index (BMI) = 22.5 +/- 6.5 kg/m(2)], lean endurance-trained (LT, n = 10, BMI = 21.2 +/- 1.2 kg/m(2)), and obese sedentary (OS, n = 7, BMI = 35.5 +/- 4.4 kg/m(2)) men and women. Twenty-four-hour energy expenditure and substrate oxidation were measured under sedentary (control; CON) and exercise (EX) conditions while maintaining energy balance. During EX, subjects performed 1 h of stationary cycling at 55% of aerobic capacity. Twenty-four-hour fat oxidation did not differ on the CON or EX day in LS (43 +/- 9 vs. 29 +/- 7 g/day, respectively), LT (53 +/- 8 vs. 42 +/- 5 g/day), or OS (58 +/- 7 vs. 80 +/- 9 g/day). However, 24-h fat balance was significantly more positive on EX compared with CON (P < 0.01). Twenty-four-hour glucose, insulin, and free fatty acid (FFA) profiles were similar on the EX and CON days, but after consumption of the first meal, FFA concentrations remained below fasting levels for the remainder of the day. These data suggest that when exercise is performed with energy replacement (i.e., energy balance is maintained), 24-h fat oxidation does not increase and in fact, may be slightly decreased. It appears that the state of energy balance is an underappreciated factor determining the impact of exercise on fat oxidation.

Muscle forces or gravity: what predominates mechanical loading on bone?

Most mechanical forces acting on the skeleton are generated either through impact with the ground (i.e., gravitational loading) or through muscle contractions (i.e., muscle loading). If one of these conduits for activating mechanotransduction in bone is more effective than the other with respect to developing or maintaining bone strength, this would have important clinical implications for prescribing physical activity for the prevention or treatment of osteoporosis. This section of the symposium considered whether there is evidence from studies of humans that the effectiveness of physical activity to preserve bone health is dependent on whether the activities stimulate the skeleton primarily through gravitational or muscle loading. Conclusive evidence is lacking, but several lines of research suggest that physical activities that involve impact forces, and therefore generate both gravitation and muscle loading, are most likely to have beneficial effects on bone metabolism and reduce fracture risk.

Exercise and the preservation of bone health.

Exercise is generally accepted as having favorable effects on bone health and, subsequently, a reduction in fracture risk. In the absence of large randomized controlled trials of the potential benefits of exercise on fracture risk, support for this belief comes from cross-sectional studies and interventional studies using surrogate endpoints such as bone mineral density and falls. In this review, we discuss the characteristics of exercise programs that provide an osteogenic stimulus. The goals and benefits of exercise on bone across the age spectrum are discussed. Where there is a paucity of human data, animal studies examining the roles of variables such as exercise intensity, frequency, duration, and mode in shaping the response of bone to exercise are discussed. The effects of disuse and the limited response of bone to remobilization are described. The rapid and dramatic decrease in bone mineral density observed in the early period after heart or lung transplantation is discussed, as are the available data on the benefits of exercise on bone in this population. For cardiopulmonary rehabilitation programs to improve bone health, they should include not just weight-supported activities (eg, cycling) but also weight-bearing activities (eg, walking, resistance exercise). Although the optimal exercise routine for bone health is unknown, components of an osteogenic program are discussed.

BMD decreases over the course of a year in competitive male cyclists.

UNLABELLED: Male cyclists have been found to have low BMD in cross-sectional studies. Changes in BMD values over 1 yr of training and competition were studied in 14 male cyclists. BMD decreased significantly at the total hip, neck, trochanter, and shaft regions but not the lumbar spine. This first prospective study of cyclists showed a decrease in BMD over the course of 1 yr. INTRODUCTION: Cross-sectional studies have shown that some endurance athletes, and cyclists in particular, have low BMD. Whether vigorous cycle training is causally related with low BMD remains unknown. MATERIALS AND METHODS: Changes in BMD values over 1 yr of training and competition were studied in 14 male road cyclists, 27-44 yr of age. Subjects were randomized to receive 1500 (500 mg with meals) or 250 mg of supplemental calcium citrate daily. BMD measurements were obtained at pre-, mid-, post-, and off-season time points over 1 yr. Dermal calcium loss during exercise was estimated using a patch collection technique to examine calcium loss as a potential mediator of changes in BMD. RESULTS: Using paired t-tests, BMD was found to decrease significantly from pre- to off-season at the total hip, neck, shaft, and trochanter regions (relative changes of -1.5 +/- 2.1%, -0.7 +/- 2.1%, -0.9 +/- 2.1%, and -1.0 +/- 1.2%, respectively, all p < 0.05). The 1.0 +/- 1.2% decrease in BMD at the lumbar spine failed to reach statistical significance (p = 0.079). There were no differences in changes in BMD between the calcium supplementation groups. The 2-h dermal calcium loss was estimated at 136.5 +/- 60.5 mg. Higher dermal calcium losses were associated with lower baseline BMD values at the total hip, neck, and shaft (all p < 0.05), but were not significantly associated with changes in BMD. CONCLUSIONS: This study suggests that high intensity cycle training may adversely affect BMD. Excessive dermal calcium loss during exercise may be a contributing factor, but mechanisms remain to be elucidated.

Acute effects of 2 hours of moderate-intensity cycling on serum parathyroid hormone and calcium.

Previous studies have found that serum parathyroid hormone (PTH) increases in response to relatively short (<60 minutes), intense bouts of exercise, possibly as a result of decreases in serum calcium. Whether longer, less intense exercise also stimulates an increase in PTH is not known. The effects of 2 hours of moderate-intensity cycling on serum PTH and calcium were investigated in 20 competitive male cyclists, aged 22-45 years. Serum concentrations of PTH and calcium were measured before and after exercise. Dermal calcium loss was estimated using patch collections and loss of sweat. There were increases in PTH from 40.6 +/- 15.6 to 69.5 +/- 25.5 pg/mL (P < 0.001) and in serum calcium from 9.3 +/- 0.3 to 9.6 +/- 0.5 mg/dL (mean +/- standard deviation, P = 0.001) in response to exercise. Contraction of plasma volume explained the rise in calcium but not PTH. Dermal calcium loss was estimated at 138.0 +/- 71.9 mg for the 2-hour exercise bout. Neither the change in serum calcium nor the dermal calcium loss was significantly related to the increase in PTH. The study demonstrated that prolonged exercise stimulates PTH secretion. The effects of such transient increases in PTH on bone metabolism are not known.

Patient and physician perceptions of timely access to care.

BACKGROUND: Timeliness of care is 1 of 6 dimensions of quality identified in Crossing the Quality Chasm. We compared patient and physician perceptions of appropriate timing of visits for common medical problems. METHODS: This study was conducted at 2 internal medicine clinics at the University of Colorado Health Sciences Center. Adult patients and companions, and outpatient General Internists were surveyed. The survey contained 11 clinical scenarios of varying urgency. Respondents indicated how soon the patient in each scenario should be seen. Responses ranged from that day to 1 to 3 months. Responses were analyzed using the Mann-Whitney U test. RESULTS: Two hundred and sixty-two patients and 46 of 61 physicians responded. For 8 of the 11 scenarios patients felt they should be seen significantly earlier than physicians. Scenarios involving chronic knee and stomach pain, routine diabetes care, and hyperlipidemia generated the greatest differences. Patients and physicians agreed on the urgency of scenarios concerning wheezing in an asthmatic, an ankle injury, and acute pharyngitis. CONCLUSIONS: Patients expected to be seen sooner than physicians thought necessary for many common chronic medical conditions, but are in agreement about timeliness for some acute problems. Understanding patient expectations may help physicians respond to requests for urgent evaluation of chronic conditions.

Clinical and laboratory diagnosis of acute renal failure.

Acute renal failure (ARF) is defined in general terms as an abrupt decrease in renal function sufficient enough to result in retention of nitrogenous waste and disrupt fluid and electrolyte homeostasis. There is no consensus regarding a quantifiable definition of ARF. Prompt evaluation of ARF is vital because ARF can be the end result of diverse processes which can often be reversed or attenuated through therapy directed at the underlying condition. Evaluation begins with careful review of the patient's history, previous medical records, physical examination, urinalysis, and available laboratory data. Routine urine chemical indices, calculation of the fractional excretion of sodium, and examination of the urine sediment are valuable in characterizing the cause of ARF. When this evaluation fails to yield a diagnosis, further testing may be required to evaluate intravascular volume status or diagnose a systemic disorder or glomerular cause of ARF. Response to therapeutic trials may provide a diagnosis. When a diagnosis cannot be made with reasonable certainty through this evaluation renal biopsy should be considered.