Bone Mineral Density in Postmenopausal Women Does Exercise Training Make a Difference? Larry E. Miller, PhD; Sharon M. Nickols-Richardson, PhD, RD; Warren K. Ramp, PhD; Frank C. Gwazdauskas, PhD; Lawrence H. Cross, PhD; William G. Herbert, PhD THE PHYSICIAN AND SPORTSMEDICINE - VOL 32 - NO. 2 - FEBRUARY 2004 ABSTRACT BACKGROUND: Although postmenopausal women are encouraged to exercise to preserve bone mineral density (BMD), few studies have looked at what type of exercise is most effective. OBJECTIVE: To review current data on the effects of exercise training on BMD in postmenopausal women when measured by dual-energy x-ray absorptiometry (DEXA). METHODS: Thirteen studies met defined inclusion criteria and were analyzed. Length of exercise intervention was annualized, and only one effect at each region of interest (lumbar vertebrae, femoral neck, or distal forearm) per intervention group was recorded. RESULTS: Overall, exercise training had a positive effect on BMD of the lumbar vertebrae and femoral neck. Aerobic exercise alone and in combination with strength training positively affected lumbar vertebrae BMD. Aerobic exercise also preserved BMD at the femoral neck. CONCLUSION: These findings provide support for regular aerobic activity in postmenopausal women to offset age-related declines in BMD. Baby boomers, those born between 1946 and 1964, constitute about 30% of the US population. With continuing increases in life expectancy, osteoporosis prevention and treatment will pose a challenge to physicians for years to come. Exercise is commonly recommended to help prevent osteoporosis in postmenopausal women, yet studies show no consensus on the optimal exercise prescription for preserving bone mass. Several factors make study comparisons difficult. Lack of high-quality studies, inconsistent methods of bone mineral density (BMD) assessment, diverse interventions, and confounding treatments (eg, hormone replacement) contribute to the lack of consensus. The purpose of this study was to review published controlled trials of exercise training effects on BMD in postmenopausal women measured with dual-energy x-ray absorptiometry (DEXA). Several factors influenced these delimitations. First, no reviews have used only DEXA to analyze how much BMD changes with exercise training. DEXA is the gold standard for BMD measurement, because it has a unique combination of versatility, fast scan speeds, minimal radiation exposure, and high precision. Second, much of the published data are from studies that used weak research designs (eg, cross-sectional analysis, observational trials with no controls). Third, this particular cohort was selected because postmenopause is characterized by BMD losses of up to 2.5% per year.1 Although exercise may exert beneficial effects on bone in postmenopausal subjects, BMD may remain stable or even decline because of a high rate of age-related bone loss. The effects of exercise training may be determined by comparing normal age-related BMD declines with BMD changes after an exercise intervention. Although an individual may experience an absolute decrease in BMD after exercise training, a net BMD increase may be realized when compared with a sedentary lifestyle. Synthesis of these results may emphasize the key exercise components that best maintain BMD in postmenopausal women. Methods A computerized search was performed using MEDLINE with the following keywords alone and in combination: bone, bone density, bone mineral density, exercise, training, physical, and activity. Inclusion criteria for eligible studies consisted of: (1) full-length articles published in English-language journals and indexed during or before December 2002, (2) postmenopausal subjects at study onset, (3) a comparative control group, and (4) quantifiable DEXA measures of BMD at the lumbar vertebrae, femoral neck, or distal forearm. Studies that used calcium or vitamin D supplements were included, provided the exercise and control groups were given equal doses. Trials were excluded if they: (1) allowed or administered hormone replacement therapy, (2) included subjects with known cardiac, metabolic, or musculoskeletal disease, or (3) used simultaneous dietary interventions aimed at weight loss. All abstracts were examined by one investigator to exclude irrelevant studies. Full texts of all remaining studies were retrieved to confirm those that met study criteria. Thirteen studies2-14 met all inclusion criteria and were analyzed. In studies that measured BMD at multiple times, only the final measurement was included in the analysis to ensure that each intervention group had only one reported effect for each measurement site. Multiple site-specific effects were reported in studies with more than one exercise group. When multiple regions of interest were reported for the distal forearm, only the most distal site was reported to ensure only one effect per intervention group. Data Analysis The main outcomes of this study were net BMD change (BMD%Δ) and net annualized BMD change (BMD%Δ/yr) at the lumbar vertebrae, femoral neck, and distal forearm. Net BMD change was defined as: BMD%ΔE - BMD%ΔC, where BMD%ΔE was the BMD percent change observed in the exercise group and BMD%ΔC was the control group. Thus, a BMD%Δ of 1% indicates that exercise preserved 1% more BMD than in controls. Because the length of exercise interventions in the selected studies ranged from 6 to 24 months, BMD%Δ/yr was also reported and defined as: BMD%Δ ÷ intervention length in months X 12. Thus, the 12 multiplier adjusts all BMD outcomes to a 1-year period. All outcomes of the evaluated studies were presented by measurement site. Only measures of BMD between L-1 and L-4 were considered for the lumbar vertebrae. The femoral neck was the only region of interest reported at the proximal femur. The distal forearm included any measure of the radius, ulna, or forearm (ie, radius and ulna combined). The impact of study design differences on BMD%Δ/yr was evaluated with independent-samples t tests with appropriate adjustments made for significant Levene's equality of variance tests. All calculations were performed using Statistical Package for Social Sciences version 11.5 (SPSS, Inc, Chicago). Results are presented as mean ± standard error (SE). The significance level was set at P = 0.05. Results The 13 studies in this review reported 34 effects (lumbar vertebrae = 16, femoral neck = 13, distal forearm = 5), representing 29 groups (exercise = 16, control = 13) consisting of 991 subjects (exercise = 533, control = 458). A description of the exercise modes used for each study is presented in table 1. Selected baseline subject characteristics are shown in table 2. TABLE 1. Description of Exercises Used in the Bone Mineral Density Studies Selected for Meta-Analysis Study Exercise Adami et al2 Press-ups, "flexion on the arms in a prone position," standing or seated volleyball, supinated wrist curls Bassey et al3 50 (5 sets of 10 repetitions) jumps of about 8.5 cm each Brooke-Wavell et al4 Self-selected "brisk" walking Hatori et al5 Group 1: walking at 90% of HRAT; group 2: walking at 110% of HRAT Iwamoto et al6 Brisk walking (30% more steps/day than usual, about 8,000 steps/day) plus straight-leg raises, squats, and back and abdominal exercises Kemmler et al7 Walking/running, jumping sequences, strength training (all major muscle groups) Kerr et al8 Group 1: heavy resistance training (nine exercises); group 2: resistance training with very light weights (nine exercises) plus moderate-intensity cycling Kohrt et al9 Group 1: walking, jogging, stair climbing/descending; group 2: weight lifting (all major muscle groups) plus rowing Kohrt et al10 Walking, jogging, stair climbing/descending Kohrt et al11 Walking, jogging, stair climbing/descending Lord et al12 Aerobic exercises, activities for balance, hand-eye and foot-eye coordination, strengthening exercises Nelson et al13 High-intensity (80% of 1 RM) pneumatic strength training Prince et al14 Walking and weight-bearing exercise at > 60% of HRmax HRAT = heart rate at the anaerobic threshold; 1 RM = one repetition maximum; HRmax = heart rate maximum

TABLE 2. Baseline Characteristics of Subjects in Selected Bone Mineral Density Studies   Exercise Group    Control Group    Variable Size*    Mean ± SE Range Size*    Mean ± SE Range N 16 33 ± 7 8-118 13 35 ± 8 8-116 Age (yr) 16 62 ± 1 55-72 13 63 ± 1 55-72 Body weight (kg) 14 64 ± 2 46-73 11 63 ± 2 46-72 Lumbar vertebrae    BMD (g/cm2) 16 0.911 ± 0.028    0.606-1.091    13 0.906 ± 0.034    0.611-1.117 Femoral neck BMD (g/cm2) 13 0.740 ± 0.024 0.612-0.892 11 0.756 ± 0.027 0.643-0.927 * The number of groups for which values were reported. SE = standard error; BMD = bone mineral density Lumbar vertebrae. Sixteen effects from 13 studies were reported for the lumbar vertebrae. Baseline BMD in the exercise and control groups were similar (P > 0.9). The BMD%Δ and BMD%Δ/yr were significantly greater (P < 0.01) than 0. The annualized BMD changes associated with these effects were 0.9% in the exercise groups and -0.5% in the control groups. Femoral neck. Thirteen effects from 11 studies were reported for the femoral neck. Baseline BMD in the exercise and control groups were similar (P > 0.6). Positive outcomes were shown for BMD%Δ (P = 0.04) while BMD%Δ/yr approached significance (P = 0.06). The annualized BMD changes associated with these effects were 0.7% in the exercise groups and -0.4% in the control groups. Distal forearm. Five effects from three studies were reported for the distal forearm. Baseline BMD was not reported due to disparate measured regions of interest among studies. The exercise groups reported similar (P > 0.3) BMD outcomes at the distal forearm compared with the control groups. The annualized BMD changes associated with these effects were -0.3% in the exercise groups and -0.6% in the control groups. Subgroup analysis. Exercise interventions that used only aerobic exercises resulted in positive effects at the lumbar vertebrae and, albeit weakly, the femoral neck (table 3). Muscular strength training alone resulted in no significant effects at any site. Interventions that used both aerobic and strength exercises showed a positive effect at the lumbar vertebrae only. Small sample size limited the interpretation of this analysis, especially at the distal forearm.

TABLE 3. Effects of Exercise Mode on Bone Mineral Density in Postmenopausal Women in Selected Studies   Aerobic    Strength    Combination    Site Size*   BMD%Δ    BMD%Δ/yr    Size*   BMD%Δ    BMD%Δ/yr    Size*   BMD%Δ    BMD%Δ/yr    Lumbar vertebrae 8 1.1 ± 0.4†    1.3 ± 0.5†    4 0.5 ± 0.9    0.7 ± 0.8    4 2.0 ± 0.6†    1.9 ± 0.6† Femoral neck 6 1.8 ± 0.8‡ 1.7 ± 0.9‡ 4 1.2 ± 1.0 0.8 ± 1.0 3 0.2 ± 0.9 0.2 ± 0.9 Distal forearm    3 0.1 ± 0.1 0.1 ± 0.1 1 -0.3 -0.2 1 1.2 1.3 *The number of groups for which values were reported. †Effect vs control group: P ≤ 0.05. ‡Effect vs control group: P ≤ 0.10. BMD%Δ = percent change in bone mineral density (exercise vs control group); BMD%Δ/yr = annualized percent change in bone mineral density (exercise vs control group) Study design affects BMD responsiveness to exercise interventions. Thus, the impact of several variables on BMD%Δ/yr was assessed (table 4). Studies with small sample size (≤ 40 subjects in exercise group) and high exercise compliance (≥ 80%) resulted in high BMD%Δ/yr at the lumbar vertebrae and femoral neck. Furthermore, nonrandomized studies and interventions with longer exercise duration (≥ 40 min/session) showed weak positive effects on femoral neck BMD. Subgroup analysis was not performed for the distal forearm because of insufficient sample size.

TABLE 4. Study Design Variables in Selected Studies on Net Annualized Bone Mineral Density in Postmenopausal Women   Lumbar Vertebrae    Femoral Neck    Variable Subgroup    Size*    BMD%Δ/yr    P       Size*    BMD%Δ/yr    P       Randomized study   Yes No 11 5 1.3 ± 0.5 1.4 ± 0.3 0.97       8 5 0.4 ± 0.5 2.3 ± 0.9 0.08 Sample size (exercise group) ≤ 40 > 40 8 8 2.1 ± 0.5 0.6 ± 0.3 0.02 5 8 2.8 ± 0.9 0.1 ± 0.3 0.01 Calcium supplementation Yes No 10 6 1.0 ± 0.4 1.9 ± 0.7 0.22 9 4 1.3 ± 0.6 0.6 ± 1.1 0.52 Intervention length (mo)† ≥ 12 < 12 9 7 1.1 ± 0.5 1.2 ± 0.3 0.89 8 5 0.7 ± 0.6 1.9 ± 0.9 0.27 Frequency (sessions/wk) ≥ 3 < 3 7 9 1.3 ± 0.4 1.4 ± 0.6 0.91 8 5 1.4 ± 0.7 0.6 ± 0.8 0.47 Duration (min) ≥ 40 < 40 9 7 1.7 ± 0.3 0.9 ± 0.7 0.34 8 5 1.9 ± 0.7 -0.1 ± 0.5 0.06 Supervision Full None or partial   12 4 1.4 ± 0.4 1.3 ± 0.8 0.92 10 3 1.4 ± 0.6 0.0 ± 0.5 0.29 Compliance (%) ≥ 80 < 80 8 6 1.6 ± 0.4 0.4 ± 0.3 0.06 7 6 2.0 ± 0.8 0.1 ± 0.4 0.07 Attrition (%) ≥ 15 < 15 7 7 0.9 ± 0.6 1.8 ± 0.6 0.29 6 5 0.1 ± 0.5 1.9 ± 1.0 0.17 * The number of groups for which values were reported. † Nonannualized bone mineral density percent change reported. BMD%Δ/yr = percent change in bone mineral density per year (exercise vs control group) Discussion These results suggest that the lumbar vertebrae and femoral neck respond positively to exercise training in postmenopausal women. Exercisers maintained BMD just over 1% more than controls. Subgroup analysis revealed positive effects on lumbar vertebrae BMD with aerobic training alone and in combination with strength training, but not with strength training alone. Positive effects at the femoral neck were observed with aerobic exercise only. No significant effects were noted at the distal forearm with exercise training. Although most studies reported no difference between BMD%Δ in the exercise and control groups, many of these studies were plagued by low sample sizes, making statistical significance more difficult to detect. Meta-analytic techniques combine all studies to calculate an effect size. Thus, the resulting larger sample size yields a more precise estimate of the true population effect and makes it easier to detect group differences if they, in fact, exist. Trabecular bone has a greater metabolic rate than cortical bone and may be more responsive to exercise and pharmacologic interventions. The lumbar vertebrae are composed of about 66% trabecular bone, and the femoral neck is about 25%; however, the distal forearm is only 5% to 25% trabecular bone, depending on the measurement site.15 Not surprisingly, BMD changes with exercise training were greatest at the lumbar vertebrae and least at the distal forearm. Another possible reason for the lack of effect at the distal forearm was the small sample size. Also, two9,11 of the five reported effects were measured in treatment groups that participated in only lower-body exercises, such as walking, jogging, and stair climbing. Wolff's law states that changes in bone function are followed by changes in internal architecture and external conformation. The magnitude of bone strain (the amount of relative change in bone length under mechanical loading) may be responsible for these alterations. Thus, one would expect no change in BMD in a bone that undergoes no loading. Although studies incorporating only strength exercises showed no effect on BMD, the real benefits of a strength-training regimen in postmenopausal women cannot be discounted. Muscle weakness has been shown to increase fall risk,16,17 and falls are a major cause of osteoporotic fractures at the femoral neck and distal forearm. Thus, an exercise regimen consisting of aerobic and strength training may be adopted by postmenopausal women to reduce the likelihood of fracture. Several reviews have been conducted in the last few years on exercise training and BMD in postmenopausal women, although none have been published with BMD measured with DEXA only. Kelley18,19 showed positive effects of aerobic exercise on BMD of the lumbar vertebrae and the hip. Kelley et al20 also demonstrated positive effects of resistance training on BMD at the lumbar vertebrae, femur, and forearm. Wallace and Cumming21 concluded that impact and nonimpact exercise both have a positive effect on lumbar vertebrae BMD in postmenopausal women; however, conclusions about effects at the hip were unclear because of insufficient sample size. Wolff et al22 determined that exercise training in postmenopausal women prevented bone loss of about 1% per year at the lumbar vertebrae and femoral neck. Finally, Berard et al23 determined that exercise programs for postmenopausal women were effective in preventing bone loss at the lumbar vertebrae but not at the femur or forearm. This review is consistent with previous studies that show that lumbar vertebrae respond to exercise interventions; however, reports of the femoral neck and distal forearm response are conflicting. Reporting outcomes of exercise training as BMD%Δ and BMD%Δ/yr has certain limitations. The BMD%Δ measure in this study was confounded by large differences in periods of exposure to the exercise interventions (6 to 24 months). Although greater effects may be anticipated with longer interventions, this was not the case. The strong relationship of exercise intervention length with subject compliance (r = -0.60, P < 0.001) and attrition (r = 0.68, P < 0.001) diminished the potential for greater effects with long-term training. Using the BMD%Δ/yr formula attempts to correct for disparate intervention lengths. However, because the longest reviewed trial lasted only 24 months, it should not be assumed that BMD%Δ/yr implies a constant linear effect over an infinite period. Studies with longer exercise training interventions that maximize subject compliance and limit attrition are necessary to determine a true long-term benefit on BMD. DEXA has some inherent limitations that may affect the BMD outcomes reported in exercise training studies. For example, let us assume that an exercise intervention results in a 5% increase in trabecular BMD and no change in cortical BMD at a particular region of interest. If this site consists of 10% trabecular bone (eg, the one-third distal forearm), DEXA will show a BMD increase of only 0.5%. Furthermore, BMD changes resulting from exercise training are often less than the sensitivity of what DEXA can detect. In this review, the mean BMD%Δ across all sites was 1.4%; however, the mean coefficient of variation for DEXA reported for the studies averaged 1.5%. Despite high sensitivity in comparison to many biomedical modalities, effects of this magnitude obtained with DEXA are clearly too small to provide convincing evidence for the recommendation of exercise training for bone mass maintenance in postmenopausal women. Beyond DEXA Although DEXA is the current gold standard for BMD measurement, other tools hold promise for future bone health assessment. Quantitative computed tomography (QCT) can measure volumetric BMD and differentiate between trabecular and cortical bone in the vertebral bodies. The limitations of standard QCT systems (eg, high cost of equipment, lack of versatility, and greater radiation exposure) may be overcome by using peripheral QCT (pQCT), which has the same abilities as QCT but measures BMD at the forearm and calcaneus. Thus, an area of predominantly cortical bone may demonstrate a change in trabecular density with exercise training, whereas DEXA would likely show no change. In fact, Adami et al2 measured BMD at the distal radius with pQCT and DEXA before and after a 6-month exercise regimen. BMD did not change when measured with DEXA, but volumetric trabecular BMD decreased 2.6% when assessed with pQCT. Thus, DEXA may not be the most appropriate tool to assess the effects of exercise training on bone health. The bending stiffness of long bones in vivo is a stronger predictor of breaking strength than BMD.24 Mechanical response tissue analysis (MRTA), a technique that measures bending stiffness, involves positioning a probe over the ulna or tibia where a low-frequency, transcutaneous vibration is applied. The probe contains an impedance sensor that relays force and acceleration data to a signal analyzer. Then, a microprocessor fits the data to a prediction model to estimate bending stiffness. Although efforts are underway to increase the technical performance of MRTA,25 the current test-retest reliability is not sufficient for clinical use. Clinical Implications DEXA, the current gold standard for BMD measurement and osteoporosis detection, is a clinical tool that is widely used to predict fracture risk and monitor the effects of pharmacologic treatment. Aerobic training is associated with modest BMD increases in lumbar vertebrae and the femoral neck and appears to yield greater effects on BMD than strength training. Aerobic exercise and strength training have distinct beneficial health effects and, in combination, may slow postmenopausal bone loss, reduce risk of falls that give rise to fracture, and enhance quality of life and overall physical fitness. The evidence from the 13 studies does not support a recommendation for a specific exercise protocol to preserve BMD, because the exercise interventions varied markedly from one study to another. Despite the strong inverse relationship between BMD and fracture risk, the effects of exercise training on fracture risk are unknown, because no prospective studies to examine this relationship have been conducted. The long follow-up period required, an anticipated high rate of attrition, and the enormous sample size required to detect differences between low fracture incidences limit prospective randomized studies. Most evidence recommends pharmacologic intervention as the first line of defense in osteoporosis treatment, because BMD losses throughout menopause are greater than any bone-preserving effects of exercise. Although specific exercise prescriptions should be formulated on a case-by-case basis, physicians may incorporate these general findings with their personal recommendations for pharmacologic therapy and fall risk reduction to provide a comprehensive osteoporosis prevention program for their postmenopausal patients. References Pouilles JM, Tremollieres F, Ribot C: Effect of menopause on femoral and vertebral bone loss. J Bone Miner Res 1995;10(10):1531-1536 Adami S, Gatti D, Braga V, et al: Site-specific effects of strength training on bone structure and geometry of ultradistal radius in postmenopausal women. J Bone Miner Res 1999;14(1):120-124 Bassey EJ, Rothwell MC, Littlewood JJ, et al: Pre- and postmenopausal women have different bone mineral density responses to the same high-impact exercise. J Bone Miner Res 1998;13(12):1805-1813 Brooke-Wavell K, Jones PR, Hardman AE: Brisk walking reduces calcaneal bone loss in post-menopausal women. Clin Sci (Lond) 1997;92(1):75-80 Hatori M, Hasegawa A, Adachi H, et al: The effects of walking at the anaerobic threshold level on vertebral bone loss in postmenopausal women. Calcif Tissue Int 1993;52 (6):411-414 Iwamoto J, Takeda T, Otani T, et al: Effect of increased physical activity on bone mineral density in postmenopausal osteoporotic women. Keio J Med 1998;47(3):157-161 Kemmler W, Engelke K, Lauber D, et al: Exercise effects on fitness and bone mineral density in early postmenopausal women: 1-year EFOPS results. Med Sci Sports Exerc 2002;34(12):2115-2123 Kerr D, Ackland T, Maslen B, et al: Resistance training over 2 years increases bone mass in calcium-replete postmenopausal women. J Bone Miner Res 2001;16(1):175-181 Kohrt WM, Ehsani AA, Birge SJ Jr: Effects of exercise involving predominantly either joint-reaction or ground-reaction forces on bone mineral density in older women. J Bone Miner Res 1997;12(8):1253-1261 Kohrt WM, Ehsani AA, Birge SJ Jr: HRT preserves increases in bone mineral density and reductions in body fat after a supervised exercise program. J Appl Physiol 1998;84(5):1506-1512 Kohrt WM, Snead DB, Slatopolsky E, et al: Additive effects of weight-bearing exercise and estrogen on bone mineral density in older women. J Bone Miner Res 1995;10(9):1303-1311 Lord SR, Ward JA, Williams P, et al: The effects of a community exercise program on fracture risk factors in older women. Osteoporos Int 1996;6(5):361-367 Nelson ME, Fiatarone MA, Morganti CM, et al: Effects of high-intensity strength training on multiple risk factors for osteoporotic fractures: a randomized controlled trial. JAMA 1994;272(24):1909-1914 Prince R, Devine A, Dick I, et al: The effects of calcium supplementation (milk powder or tablets) and exercise on bone density in postmenopausal women. J Bone Miner Res 1995;10(7):1068-1075 Mundy GR: Bone remodeling, in Favus MJ (ed): Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Philadelphia, Lippincott Williams & Wilkins, 1999, pp 30-38 Skelton DA, Kennedy J, Rutherford OM: Explosive power and asymmetry in leg muscle function in frequent fallers and non-fallers aged over 65. Age Ageing 2002;31(2):119-125 Wolfson L, Judge J, Whipple R, et al: Strength is a major factor in balance, gait, and the occurrence of falls. J Gerontol A Biol Sci Med Sci 1995;Nov(50 spec no.):64-67 Kelley G: Aerobic exercise and lumbar spine bone mineral density in postmenopausal women: a meta-analysis. J Am Geriatr Soc 1998;46(2):143-152 Kelley GA: Aerobic exercise and bone density at the hip in postmenopausal women: a meta-analysis. Prev Med 1998;27(6):798-807 Kelley GA, Kelley KS, Tran ZV: Resistance training and bone mineral density in women: a meta-analysis of controlled trials. Am J Phys Med Rehabil 2001;80(1):65-77 Wallace BA, Cumming RG: Systematic review of randomized trials of the effect of exercise on bone mass in pre- and postmenopausal women. Calcif Tissue Int 2000;67(1):10-18 Wolff I, van Croonenborg JJ, Kemper HC, et al: The effect of exercise training programs on bone mass: a meta-analysis of published controlled trials in pre- and postmenopausal women. Osteoporos Int 1999;9(1):1-12 Berard A, Bravo G, Gauthier P: Meta-analysis of the effectiveness of physical activity for the prevention of bone loss in postmenopausal women. Osteoporos Int 1997;7(4):331-337 Roberts SG, Hutchinson TM, Arnaud SB, et al: Noninvasive determination of bone mechanical properties using vibration response: a refined model and validation in vivo. J Biomech 1996;29(1):91-98 Miller LE: Reliability of Mechanical Response Tissue Analysis in Composite and Human Tibiae, dissertation. Blacksburg, VA, Virginia Polytechnic Institute and State University, 2003 Dr Miller is a research associate, Dr Nickols-Richardson is an associate professor, Dr Ramp is an adjunct professor, and Dr Herbert is a professor in the department of human nutrition, foods, and exercise; Dr Gwazdauskas is a professor in the department of dairy science; and Dr Cross is a professor emeritus in the educational research and evaluation program, all at the Virginia Polytechnic Institute and State University in Blacksburg, Virginia. Address correspondence to Larry E. Miller, PhD, 1786 S Ax Handle Way, Flagstaff, AZ 86001; e-mail to millerle@vt.edu. Disclosure information: Drs Miller, Nickols-Richardson, Ramp, Gwazdauskas, Cross, and Herbert disclose no significant relationship with any manufacturer of any commercial product mentioned in this article. No drug is mentioned in this article for an unlabeled use. 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