Daniel W. Barry

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.

BMD Decreases Over the Course of a Year in Competitive Male Cyclists

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.

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.

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.

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.

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.

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.

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.

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 Exercise and Physical Interventions on Bone: Clinical Studies

Perhaps the best evidence that physical activity is essential for the maintenance of bone mass and strength is the rapid and profound loss of bone mineral that occurs during conditions of disuse, such as immobilization, bed rest, and spaceflight. Physical activity throughout the lifespan has the potential to reduce the risk for osteoporotic fracture by augmenting the development of peak bone mass during childhood, maintaining bone mass during early adulthood, and slowing the inevitable loss of bone mass in old age. However, the types and amounts of physical activity needed to optimize skeletal integrity across the lifespan and reduce osteoporotic fracture risk have not been precisely defined. This chapter reviews the clinical evidence that physical activity is associated with reduced fracture risk and that exercise training can increase or slow the decline in bone mineral density (BMD) in adults. The clinical relevance of the key determinants of the response of bone to mechanical loading that have evolved from preclinical studies of animals (e.g., high strain magnitude, high strain rate, few repetitions, unique strain distribution) is discussed. Novel factors that may influence the skeletal adaptation to exercise in humans are also discussed.