Sonja Kukuljan

Calcium‐ and Vitamin D3‐Fortified Milk Reduces Bone Loss at Clinically Relevant Skeletal Sites in Older Men: A 2‐Year Randomized Controlled Trial

In this 2‐year randomized controlled study of 167 men >50 years of age, supplementation with calcium‐vitamin D3‐fortified milk providing an additional 1000 mg of calcium and 800 IU of vitamin D3 per day was effective for suppressing PTH and stopping or slowing bone loss at several clinically important skeletal sites at risk for fracture.

Effects of resistance exercise and fortified milk on skeletal muscle mass, muscle size, and functional performance in middle-aged and older men: an 18-mo randomized controlled trial

Limited data have suggested that the consumption of fluid milk after resistance training (RT) may promote skeletal muscle hypertrophy. The aim of this study was to assess whether a milk-based nutritional supplement could enhance the effects of RT on muscle mass, size, strength, and function in middle-aged and older men. This was an 18-mo factorial design (randomized control trial) in which 180 healthy men aged 50-79 yr were allocated to the following groups: 1) exercise + fortified milk, 2) exercise, 3) fortified milk, or 4) control. Exercise consisted of progressive RT with weight-bearing impact exercise. Men assigned to the fortified milk consumed 400 ml/day of low-fat milk, providing an additional 836 kJ, 1000 mg calcium, 800 IU vitamin D(3), and 13.2 g protein per day. Total body lean mass (LM) and fat mass (FM) (dual-energy X-ray absorptiometry), midfemur muscle cross-sectional area (CSA) (quantitative computed tomography), muscle strength, and physical function were assessed. After 18 mo, there was no significant exercise by fortified milk interaction for total body LM, muscle CSA, or any functional measure. However, main effect analyses revealed that exercise significantly improved muscle strength ( approximately 20-52%, P < 0.001), LM (0.6 kg, P < 0.05), FM (-1.1 kg, P < 0.001), muscle CSA (1.8%, P < 0.001), and gait speed (11%, P < 0.05) relative to no exercise. There were no effects of the fortified milk on muscle size, strength, or function. In conclusion, the daily consumption of low-fat fortified milk does not enhance the effects of RT on skeletal muscle size, strength, or function in healthy middle-aged and older men with adequate energy and nutrient intakes.

Independent and Combined Effects of Calcium-Vitamin D3 and Exercise on Bone Structure and Strength in Older Men: An 18-Month Factorial Design Randomized Controlled Trial

CONTEXT Exercise and calcium-vitamin D are independently recognized as important strategies to prevent osteoporosis, but their combined effects on bone strength and its determinants remain uncertain. OBJECTIVE To assess whether calcium-vitamin D(3) fortified milk could enhance the effects of exercise on bone strength, structure, and mineral density in middle-aged and older men. DESIGN, SETTING, PARTICIPANTS An 18-month factorial design randomized controlled trial in which 180 men aged 50-79 years were randomized to the following: exercise + fortified milk; exercise; fortified milk; or controls. Exercise consisted of progressive resistance training with weight-bearing impact activities performed 3 d/week. Men assigned to fortified milk consumed 400 ml/d of 1% fat milk containing 1000 mg/d calcium and 800 IU/d vitamin D(3). MAIN OUTCOME MEASURES Changes in bone mineral density (BMD), bone structure, and strength at the lumbar spine (LS), proximal femur, mid-femur, and mid-tibia measured by dual energy x-ray absorptiometry and/or quantitative computed tomography. RESULTS There were no exercise-by-fortified milk interactions at any skeletal site. Main effect analysis showed that exercise led to a 2.1% (95% confidence interval, 0.5-3.6) net gain in femoral neck section modulus, which was associated with an approximately 1.9% gain in areal BMD and cross-sectional area. Exercise also improved LS trabecular BMD [net gain 2.2% (95% confidence interval, 0.2-4.1)], but had no effect on mid-femur or mid-tibia BMD, structure, or strength. There were no main effects of the fortified milk at any skeletal site. CONCLUSION A community-based multi-component exercise program successfully improved LS and femoral neck BMD and strength in healthy older men, but providing additional calcium-vitamin D(3) to these replete men did not enhance the osteogenic response.

Obstacles in the Optimization of Bone Health Outcomes in the Female Athlete Triad

Maintaining low body weight for the sake of performance and aesthetic purposes is a common feature among young girls and women who exercise on a regular basis, including elite, college and high-school athletes, members of fitness centres, and recreational exercisers. High energy expenditure without adequate compensation in energy intake leads to an energy deficiency, which may ultimately affect reproductive function and bone health. The combination of low energy availability, menstrual disturbances and low bone mineral density is referred to as the ‘female athlete triad’. Not all athletes seek medical assistance in response to the absence of menstruation for 3 or more months as some believe that long-term amenorrhoea is not harmful. Indeed, many women may not seek medical attention until they sustain a stress fracture.This review investigates current issues, controversies and strategies in the clinical management of bone health concerns related to the female athlete triad. Current recommendations focus on either increasing energy intake or decreasing energy expenditure, as this approach remains the most efficient strategy to prevent further bone health complications. However, convincing the athlete to increase energy availability can be extremely challenging.Oral contraceptive therapy seems to be a common strategy chosen by many physicians to address bone health issues in young women with amenorrhoea, although there is little evidence that this strategy improves bone mineral density in this population. Assessment of bone health itself is difficult due to the limitations of dual-energy X-ray absorptiometry (DXA) to estimate bone strength. Understanding how bone strength is affected by low energy availability, weight gain and resumption of menses requires further investigations using 3-dimensional bone imaging techniques in order to improve the clinical management of the female athlete triad.

Effects of lifetime loading history on cortical bone density and its distribution in middle-aged and older men

We have reported previously that long-term participation of weight-bearing exercise is associated with increased QCT-derived cortical bone size and strength in middle-aged and older men, but not whole bone cortical volumetric BMD. However, since bone remodeling and the distribution of loading-induced strains within cortical bone are non-uniform, the aim of this study was to examine the effects of lifetime loading history on cortical bone mass distribution and bone shape in healthy community dwelling middle-aged and older men. We used QCT to assess mid-femur and mid-tibia angular bone mass distribution around its center (polar distribution), the bone density distribution through the cortex (radial distribution), and the ratio between the maximum and minimum moments of inertia (I(max)/I(min) ratio) in 281 men aged 50 to 79 years. Current (>50 years) and past (13-50 years) sport and leisure time activity was assessed by questionnaire to calculate an osteogenic index (OI) during adolescence and adulthood. All men were then categorized into a high (H) or low/non impact (L) group according to their OI scores in each period. Three contrasting groups were then formed to reflect weight-bearing impact categories during adolescence and then adulthood: H-H, H-L and L-L. For polar bone mass distribution, bone deposition in the anterolateral, medial and posterior cortices were 6-10% greater at the mid-femur and 9-24% greater at mid-tibia in men in the highest compared to lowest tertile of lifetime loading (p<0.01-<0.001). When comparing the influence of contrasting loading history during adolescence and adulthood, there was a graded response between the groups in the distribution of bone mass at the anterior-lateral and posterior regions of the mid-tibia (H-H>H-L>L-L). For radial bone density distribution, there were no statistically significant effects of loading at the mid-femur, but a greater lifetime OI was associated with a non-significant 10-15% greater bone density near the endocortical region of the mid-tibia. In conclusion, a greater lifetime loading history was associated with region-specific adaptations in cortical bone density.

1 H-NMR analysis of the human urinary metabolome in response to an 18-month multi-component exercise program and calcium-vitamin-D 3 supplementation in older men

The musculoskeletal benefits of calcium and vitamin-D3 supplementation and exercise have been extensively studied, but the effect on metabolism remains contentious. Urine samples were analyzed by (1)H-NMR spectroscopy from participants recruited for an 18-month, randomized controlled trial of a multi-component exercise program and calcium and vitamin-D3 fortified milk consumption. It was shown previously that no increase in musculoskeletal composition was observed for participants assigned to the calcium and vitamin-D3 intervention, but exercise resulted in increased bone mineral density, total lean body mass, and muscle strength. Retrospective metabolomics analysis of urine samples from patients involved in this study revealed no distinct changes in the urinary metabolome in response to the calcium and vitamin-D3 intervention, but significant changes followed the exercise intervention, notably a reduction in creatinine and an increase in choline, guanidinoacetate, and hypoxanthine (p < 0.001, fold change > 1.5). These metabolites are intrinsically involved in anaerobic ATP synthesis, intracellular buffering, and methyl-balance regulation. The exercise intervention had a marked effect on the urine metabolome and markers of muscle turnover but none of these metabolites were obvious markers of bone turnover. Measurement of specific urinary exercise biomarkers may provide a basis for monitoring performance and metabolic response to exercise regimes.

Independent and Combined Effects of Exercise and Calcium on Bone Structural and Material Properties in Older Adults

Whole bone strength is determined by the combination of the mass, macro- and micro- structure, and intrinsic material properties of bone. Bone strength decreases with aging because of an imbalance in bone remodeling, so that the balance between the volume of bone resorbed and the volume formed in the basic multicellular unit is negative. This leads to a reduction in bone density and cortical thickness, with accompanying increases in periosteal and endosteal areas. Any factor that influences bone remodeling (disease, drugs, or lifestyle factors) will therefore impact upon whole bone strength. Regular weight-bearing exercise and adequate nutrition, particularly calcium and vitamin D, are two widely recommended strategies that have been shown to independently have positive effects on bone in older adults. However, the mechanism by which exercise and calcium–vitamin D influence bone is different; exercise has a site-specific modifying effect, whereas nutrition has a permissive, generalized effect that act systematically to influence bone remodeling. There is no evidence that excess intakes will result in greater skeletal gains. However, it has been suggested that the beneficial effects of exercise on bone may be dependent on adequate calcium (or nutrient) intake. Early research suggested that there may be a threshold of calcium (∼1,000 mg/day) needed to optimize the skeletal response to loading. However, current data from a limited number of studies using state-of-the-art imaging techniques [(p)QCT] indicate that additional calcium or calcium and vitamin D does not enhance the effects of exercise on bone structural or material properties in older adults with adequate calcium intakes or sufficient circulating vitamin D levels. It is more likely that additional calcium may only promote exercise-induced osteogenesis in older adults in a state of nutritional calcium insufficiency. However, further studies are still needed using three-dimensional bone imaging technology to increase our understanding of the structural based by which exercise and/or nutrition influence whole bone strength.