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Postmenopausal women with osteopenia received green tea polyphenols (GTP) supplement and/or Tai Chi exercise for 6 months. Bone turnover biomarkers, calcium metabolism, and muscle strength were measured. This study showed that GTP supplementation and Tai Chi exercise increased bone formation biomarkers and improved bone turnover rate. Tai Chi exercise increased serum parathyroid hormone. GTP supplementation, Tai Chi exercise, and the combination of the two all improved muscle strength in postmenopausal women with osteopenia.
This study evaluated the effect of GTP supplementation and Tai Chi (TC) exercise on serum markers of bone turnover (bone-specific alkaline phosphatase, BAP, and tartrate-resistant acid phosphatase, TRAP), calcium metabolism, and muscle strength in postmenopausal osteopenic women.
One hundred and seventy-one postmenopausal osteopenic women were randomly assigned to four groups: (1) placebo (500 mg starch/day), (2) GTP (500 mg GTP/day), (3) placebo + TC (placebo plus TC training at 60 min/session, three sessions/week), and (4) GTP + TC (GTP plus TC training). Overnight fasting blood and urine samples were collected at baseline, 1, 3, and 6 months for biomarker analyses. Muscle strength was evaluated at baseline, 3, and 6 months. One hundred and fifty subjects completed the 6-month study.
Significant increases in BAP level due to GTP intake (at 1 month) and TC (at 3 months) were observed. Significant increases in the change of BAP/TRAP ratio due to GTP (at 3 months) and TC (at 6 months) were also observed. Significant main effect of TC on the elevation in serum parathyroid hormone level was observed at 1 and 3 months. At 6 months, muscle strength significantly improved due to GTP, TC, and GTP + TC interventions. Neither GTP nor TC affected serum TRAP, serum and urinary calcium, and inorganic phosphate.
In summary, GTP supplementation and TC exercise increased BAP and improved BAP/TRAP ratio. TC exercise increased serum parathyroid hormone. GTP supplementation, TC exercise, and the combination of the two all improved muscle strength in postmenopausal women with osteopenia.
Osteoporosis is a degenerative bone disease characterized by low bone mass and micro-structural deterioration of bone tissue leading to fragility and an increased risk for fractures, especially of the hip, spine, and wrist . Postmenopausal women are four times more likely to develop osteoporosis than men because of a decrease in estrogen level after menopause causing decreased bone mineral density (BMD) and deteriorated bone microstructure .
Studies (both cross-sectional and retrospective) have shown that tea and its bioactive component may benefit bone health by maintaining BMD [3–8] and reducing the risk of fracture [9, 10]. Our animal studies [11, 12] have also shown that the osteo-protective effects of tea and its bioactive components may be mediated through enhanced osteoblastic activities and suppressed osteoclastic activities in bone remodeling. A positive correlation [4–7, 13–16], a weak inverse correlation , and no correlation [18–20] between tea drinking and BMD have been reported in published human studies. However, these results were based on cross-sectional or retrospective studies with inconsistent conclusion. Furthermore, no study has ever investigated the effect of tea and its bioactive components on bone biomarkers as well as bone metabolism in postmenopausal women.
Among different categories of tea, green tea seemed to benefit BMD more than others (e.g., white, black tea, and Oolong). Green tea polyphenols (GTP, extract of green tea) has shown its osteo-protective effects via decreasing oxidative stress , increasing activity of antioxidant enzymes , and decreasing expression of proinflammatory mediators  in various rodent bone loss models. In addition, green tea extract has been demonstrated to improve muscle function in mice , and combined tea catechin and treadmill exercise intervention mitigates aging-related degeneration in physical performance of mice . However, limited information is available on the protective effect of consumption of tea or its bioactive components (i.e., GTP) on musculoskeletal health in postmenopausal women.
Tai Chi (TC) exercise, a weight-bearing mind–body exercise with aerobic and muscular fitness activity, has shown its potential to benefit musculoskeletal health [25– 31] in terms of decelerating bone loss , preserving BMD  or improving neuromuscular function . Among the previous studies, there was only one longitudinal study , but that study did not target a high-risk population with osteopenia or osteoporosis. Besides, that study employed a complicated 108-form TC which was difficult to learn for the US population . A cross-sectional study failed to identify the types of regular TC exercise practiced by the women included in the study .
We have reported that GTP supplementation increased bone formation and reduced bone resorption in aged ovariectomized rats, an animal model of postmenopausal osteoporosis [11, 21]. In another study, we found that 6 weeks of TC exercise induced an increase in serum bone formation biomarker (bone-specific alkaline phosphatase, BAP) in healthy elderly participants . Further, postmenopausal women with lower lean muscle mass or strength are at a higher risk for osteoporosis [32–36], while GTP [37–41] and TC [42, 43] may improve muscle strength. Based on these findings, the objective of the present study is to evaluate the effect of GTP supplementation and TC exercise on serum markers of bone turnover, calcium metabolism, and muscle strength in postmenopausal osteopenic women. The hypothesis is that GTP intake and TC exercise alone and in combination would increase bone formation, decrease bone resorption, improve calcium metabolism, and improve muscle strength in postmenopausal women with low bone mass.
This was a 6-month, placebo-controlled and randomized intervention trial to investigate the effects of GTP and TC on relevant primary and secondary outcomes in postmenopausal women with osteopenia. The primary outcome measures included a bone formation biomarker (bone-specific alkaline phosphatase, BAP), and a bone resorption biomarker (tartrate-resistant acid phosphatase, TRAP), while the secondary outcome parameters included calcium metabolism parameters such as serum parathyroid hormone (PTH), serum and urinary calcium (Ca), inorganic phosphate (Pi), creatinine, and muscle strength assessments.
The minimum sample size for assessing primary outcome measures was calculated based on data of bone biomarkers from previous studies [27, 44]. The baseline measurements values for control (placebo) and intervention groups (GTP, Placebo + TC, GTP + TC) were assumed the same as that in the previous study . Intervention groups were expected to exhibit certain percentage changes in outcome measures in the follow-up visits, while the placebo group was expected to exhibit no changes throughout the study. It was further assumed that the correlation between baseline and the follow-up measurements is 0.85 and the correlation between the follow-up measurements is 0.90. Power analysis showed that a sample size yielding a power of approximately 0.85 to 0.9 at α=0.05 for detecting differences in primary outcome measures was 120 participants. With an expected attrition rate of 15% over 24 weeks of intervention, a minimal sample size of 140 participants was needed.
Postmenopausal women were recruited primarily through flyers, local TV, radios, newspaper, municipal community centers, and clinics to participate in this study. The complete study protocol  has been published and only a brief description is provided here.
Of 315 potential participant candidates who showed interest and willingness of participation, 171 were recruited after screening based on the inclusion and exclusion criteria. The inclusion criteria were (1) postmenopausal women (at least 2 years after menopause) with osteopenia (mean lumbar spine and/or hip BMD T-score between 1 and 2.5 standard deviation (SD) below the young normal sex-matched areal BMD of the reference database); (2) normal function of thyroid, liver, and kidney; (3) serum alkaline phosphatase, Ca, and Pi within normal ranges; and (4) serum 25-hydroxy-vitamin D [25(OH)D] ≥20 ng/mL. Women were excluded if they (1) had a disease condition or were on medication known to affect bone metabolism; (2) had a history of cancer except for treated superficial basal or squamous cell carcinoma of the skin; (3) had uncontrolled intercurrent illness or physical condition that would be a contraindication to exercise; (4) had depression, cognitive impairment; or (5) were unwilling to accept randomization. Written informed consent was obtained from all the participants before enrollment. The study was approved by the Texas Tech University Health Sciences Center Institutional Review Board.
To ensure comparable distribution across treatment arms, 171 participants were stratified by a fixed randomization scheme based on age (≥65 or <65 years old), habit of green tea consumption (yes or no), or current usage of estrogen/hormone replacement treatment (yes or no), and randomly assigned into placebo, GTP, Placebo + TC, or GTP + TC group.
Both the study participants and investigators responsible for the day-to-day operation and data analyses were blinded to the placebo or GTP group status. The identity of each treatment was revealed to the investigators and research personnel involved in the collection and analyses of the data only after all analyses have been completed.
Participants in the placebo and the placebo + TC groups received two capsules containing a total of 500 mg medicinal starch daily (one capsule ingested after breakfast and the other after dinner). Participants in the GTP and the GTP + TC groups received two capsules containing a total of 500 mg of GTP daily (one capsule ingested after breakfast and the other after dinner). Medicinal starch and GTP study capsules were supplied by Zhejiang Yuxin Pharmaceutical Co., Ltd., China (US FDA IND number 77,470). Based on our laboratory analysis, the GTP was 99.25% pure, with 46.5% of epigallocatechin-3-gallate (EGCG), 21.25% of epigallocatechin (ECG), 10% of epicatechin (EC), 7.5% of epicatechin-3-gallate (EGC), 9.5% of gallocatechin gallate (GCG), and 4.5% of catechin. In addition, during the 6-month intervention, all participants were supplemented with 500 mg elemental calcium and 200 IU vitamin D (as cholecalciferol) daily.
Participants who are randomized into the TC groups (Placebo + TC and GTP + TC) were expected to attend three 1-h TC exercise group classes each week for 6 months. In each session, in addition to 10 min of warm-up and 5 min of cool-down exercises, the routine of 24-form simplified Yang-style TC was repeated six times during the 45-min training period based on the standard speed of about 7 min per routine . The 24-form simplified Yang-style TC is a TC routine for beginners based on the traditional Yang-style TC long form. It consists of 24 movements of martial application performed slowly and gently while breathing deeply and meditating. The instructor explained and demonstrated how the exercise should be performed, and subjects followed. Participants in non-TC groups (Placebo and GTP groups) were asked to continue their customary activity levels throughout the study period.
Data of medical history, physical activity level, depression (mood), and cognitive function were collected at the time of enrollment. Physical activity level was assessed with Godin Leisure-Time Exercise Questionnaire . Depression level was assessed with Yesavage self-rated Geriatric Depression Score . Cognitive function was assessed with Mini-Mental State Examination .
BMD was measured at baseline for screening purpose by dual energy X-ray absorptiometry (DEXA) (Norland Excel X-Ray Bone Densitometer). At baseline, 1, 3, and 6 months, overnight fasting blood and urine samples were collected. All outcomes were measured at baseline, 1, 3, and 6 months, except for muscle strength assessment (measured at baseline, 3, and 6 months). In addition, at 3 and 6 months, physical activity level was monitored for any deviation from routine physical activity level throughout the study period.
Compliance of GTP or placebo study agents was determined as the amount of capsules ingested divided by the amount a participant should have ingested throughout the study period. Adherence of TC classes was assessed by TC classes attended divided by all those a participant should have attended. In the course of the study, adverse events associated with study agents or TC exercise were self-reported by the participants. In addition, the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were determined monthly in order to monitor liver function.
Serum BAP levels were measured by enzyme-linked immunoassay (Quidel Corporation, San Diego, CA, USA) with intra- and inter-assay CV below 5.2% and 5.0%, respectively. Serum TRAP levels were measured by immunocapture enzyme assay (Quidel Corporation) with intra- and inter-assay CV below 2.2% and 3.0%, respectively. Laboratory blood and urinary chemistry parameters, including serum 25(OH)-D, thyroid stimulating hormone (TSH), intact PTH, AST, ALT, Ca, Pi, and creatinine as well as urinary Ca, Pi, and creatinine were analyzed by a certified diagnostic laboratory (Quest Diagnostic Laboratory, Dallas, TX, USA).
The wall-sit test, also referred to as the wall-slide test, was employed to assess static leg strength and endurance, particularly of the quadriceps and hip extensors [50, 51]. A subject first stood in front of a bench (12″ high) positioned against a vertical smooth wall, with her back facing the wall and feet shoulder-width apart. She then leaned back so that her back and buttock were against the wall. With her hands on the waist, the subject flexed her knees, lowering her torso down the wall to assume a position with both her hips and knees flexed at a 90° angle (measured with a goniometer) without touching the bench. The longest time (seconds) that the subject can continuously hold this position before sitting down on the bench was recorded .
All variables were expressed as mean±standard deviations (SD) or standard error of mean (SEM), unless otherwise indicated. Statistical significance was set at the level of p <0.05. Statistical analyses of data were performed using SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). Differences in baseline characteristics including demographic information (e.g., age and general health) among the groups were evaluated by one-way ANOVA. The percent changes in serum BAP/TRAP ratio and in serum PTH were calculated [(post intervention value-baseline value)/baseline value×100%] for each group. The group membership (Placebo, GTP, Placebo + TC, or GTP + TC) is the main independent variable (i.e., the factor). One-way ANCOVAs were performed to determine the main effects of GTP intake, TC exercise, and their interaction on the primary and secondary outcomes at baseline, 1, 3, and 6 months. Post hoc comparisons (Bonferroni adjustment) were conducted to compare the individual outcome difference between the four groups when ANCOVA showed significance. A mixed model of ANOVA (i.e., a repeated measures model that also includes a factor variable in SPSS) was performed to examine impact of the intervention, time, and their interaction on the primary and secondary outcomes. The between-subject factor is the group membership (i.e., type of intervention received), and the within-subject factor is time (three time points of measurement).
Figure 1 shows the study flow chart with details of the participants. A total of 171 subjects were recruited and 150 subjects completed the study. Seven (16%) participants in the Placebo arm, eight (17%) in the GTP arm, five (12%) in the Placebo + TC arm, and one (3%) in the GTP + TC arm withdrew before the end of the study due to accidental fall at home (one subject), relocation (two subjects), time conflicts (six subjects), lost to follow-up (five subjects), and lost interest (seven subjects). Baseline characteristics were similar among all treatment groups (Table 1). No statistically significant differences between the subjects who withdrew from the study and those who completed the study were observed in any parameter. Based on the results of pill count, the compliance rate was 89% for both GTP and placebo capsules. The adherence rate for TC classes was 83%. Neither GTP supplementation nor TC exercise affected serum ALT and AST activity (indicators of liver function) throughout the study (data not shown). No adverse event due to study treatment was reported by the participants.
Overall, mix-ANOVA model did not find a significant impact of the intervention when intervention, time, and their interaction were included in one model. However, separate one-way and two-way ANCOVA revealed some significant findings at different time points.
Data of bone turnover biomarkers are exhibited in Table 2. One-way ANOVA revealed no significant difference among the four groups at baseline in terms of serum BAP and serum TRAP (p>0.05). Based on two-way ANCOVA results, significant main effects of GTP intake and TC exercise were found on serum BAP. GTP groups (GTP and GTP + TC) had higher serum BAP values at 1 month (p=0.03), while TC groups (Placebo + TC and GTP + TC) had higher BAP values at 3 months (p=0.04) (Table 2). However, neither GTP supplementation nor TC exercise had any effect on serum TRAP levels (bone resorption biomarker) at any time point (p>0.05). No changes in serum BAP and TRAP were observed due to TC and GTP at 6 months. No interaction effect between GTP supplementation and TC exercise was observed in serum BAP and TRAP at any time point.
Figure 2 displays the results of the changes in the BAP/TRAP ratio. Similar to the results for individual bone biomarkers, GTP groups (GTP and GTP + TC groups) demonstrated higher values for the percent change in BAP/TRAP ratio at 3 months compared to the non-GTP groups (Placebo and Placebo + TC groups) (p=0.011). TC exercise groups (Placebo + TC and GTP + TC groups) also demonstrated higher values for the percent change in BAP/TRAP ratio at 6 months compared to the non-TC groups (Placebo and GTP groups) (p=0.011). No interaction effect between GTP and TC on the change of BAP/TRAP ratio was observed at any time point.
Table 3 presents the data of serum/urinary Ca, Pi, and creatinine. One-way ANOVA showed no significant difference among the four treatment groups in serum and urinary Ca and Pi at the baseline. Neither GTP nor TC affected serum/urinary calcium, inorganic phosphate, or creatinine. Figure 3 shows the percent change in serum intact PTH from baseline to 6 months. There was no significant difference among all four groups at the baseline (p>0.05). Two-way ANCOVA showed that TC exercise (Placebo + TC and GTP + TC groups) induced a significant elevation in the percent change in serum intact PTH levels at 1 month (p=0.009) and 3 months (p=0.035) than those in the non-TC groups (Placebo and GTP groups) (Fig. 3). No interaction was observed between GTP intake and TC exercise in the change in serum intact PTH levels.
One-way ANOVA analysis revealed no difference in static leg strength/endurance measured by wall-sit test, at the baseline among the four treatment groups. Figure 4 exhibits the data of muscle strength during the 6-month study. Based on one-way ANOVA analysis, at 6 months, the Placebo group showed no statistically significant change in muscle strength, while all three treatments (GTP, Placebo + TC, and GTP + TC) significantly improved participants’ static leg strength/endurance as shown by the longer wall-sit time duration (p<0.001 for the Placebo + TC group, p<0.001 for the GTP group, and p=0.001 for the GTP + TC group).
The present study is the first to assess GTP supplementation and TC exercise for their individual and conjugate effects on bone turnover biomarkers, calcium metabolism, and muscle strength in postmenopausal women with osteopenia.
We observed elevated BAP level in GTP and TC groups, respectively, at earlier time points during the intervention. Higher values of BAP, an indicator of increased bone formation, were observed after 1 month in the GTP supplemented group. This finding appears to be consistent with our previous animal study that GTP supplementation enhanced bone formation activity in ovariectomized rats, a model of postmenopausal osteoporosis . The ability of GTP to increase an index of bone formation demonstrated in our study also agrees with GTP’s effect on osteoblastic activity suggested in in vitro studies [53–56].
In terms of impact of TC exercise on BAP, higher values of BAP observed after 3 months in the TC exercise groups agree with a previous study in an elderly population . TC exercise involves shifting body weight so slowly that almost the entire body weight is supported alternately by one of the legs at all times during the exercise. As a result, a significant weight-bearing condition is created [27, 57] which may induce mechanical loading in bone, thus stimulating new bone formation. The disappearance of the effects of GTP and TC on BAP level after 6 months may be related to the bone adaptation to GTP or TC after a long intervention period.
In addition to individual bone biomarkers, the ratio of bone formation to resorption biomarkers (BAP/TRAP in this study) has been also used as an indicator of the state of bone turnover to evaluate the effect of exercises [58–60] and dietary supplements [61, 62] on bone metabolism. An increased BAP/TRAP ratio, which could result from an increase in bone formation or a decrease in bone resorption, indicates a state of bone turnover to increase bone formation due to the intervention . On the other hand, a decreased BAP/TRAP ratio, which could result from a decrease in bone formation or an increase in bone resorption, indicates a state of bone turnover to increase bone resorption caused by the intervention . In this study, the increased BAP/TRAP ratio at 3 and 6 months by GTP intake and TC exercise, respectively, are due to increased bone formation rather than decreased bone resorption (see Table 2). Therefore, such an increase in the BAP/TRAP ratio suggests that GTP intake and TC exercise increased bone formation.
In this study, we also noticed that all treatment groups, including placebo, demonstrated an increase in BAP/TRAP ratio during the study period. In the present study, all participating subjects were provided with calcium plus vitamin D supplement daily throughout the study period, as described in section “Study intervention”. According to the reported data, the average calcium intake for our target population was about 700–800 mg daily [64, 65]. After taking the 500 mg of calcium provided by the study, our subjects would have taken 1,200–1,300 mg of calcium daily, compared to the recommended dietary allowance (RDA) (1,200 mg). Similarly, the vitamin D supplementation we provided was to ensure that all subjects had received the total RDA of vitamin D after that received from diet and sun exposure. Adequate calcium plus vitamin D intake is essential for bone activities in order to study the effect of dietary supplements and exercise on bone health [66, 67]. The increase of the BAP/TRAP ratio in the placebo group may be due to the supplementation of calcium plus vitamin D during the study.
PTH plays a key role in the changes of bone markers. PTH has been shown to play dual roles in the skeleton, anabolic and catabolic, in terms of stimulation of osteoblast and osteoclast differentiation, number, and activity . Continuous administration of PTH can induce bone loss, where intermittent administration of PTH has been shown to increase cancellous bone volume  probably due to a stimulatory effect of local growth factors, such as insulinlike growth factors and transforming growth factor-beta . In the present study, the findings that higher serum PTH level at TC exercise group was observed at 1 and 3 months in postmenopausal osteopenic women agrees with previous studies that different exercise forms including TC were related to raised serum PTH level [27, 57, 71, 72]. We also noticed that after 6 months, there was no difference in the change of PTH relative to baseline among four treatment groups, possibly because the bone cells may have adapted to stimuli (GTP intake or TC exercise in the present study) after a long period of time. It is not clear why TC exercise resulted in a higher serum PTH at 1 and 3 months and whether and how such transient increases in serum PTH would affect bone quality. These issues may need to be investigated in future studies.
Loss of estrogen and physical inactivity has been considered important contributors to loss of muscle mass and strength in postmenopausal women . Recent studies suggested that postmenopausal women with lower lean muscle mass or strength at legs and trunk would be at a higher risk for osteoporosis and should be a target for preventive measures [32–36]. The present results showed that after 6 months of GTP supplementation, TC exercise, or their combined intervention, the static leg muscle strength/endurance in postmenopausal osteopenic women significantly improved. The positive impacts of green tea on muscle have been reported in rodent models [37–41]. Green tea extract has been shown to improve muscle health by reducing or delaying muscle necrosis in mdx mice, a model of muscular dystrophy [37–39]. Recent studies showed that combined tea catechin and exercise intervention palliates aging-related degeneration in physical performance and energy metabolism by improving mitochondrial function in skeletal muscle in mice  and enhances endurance capacity in maturing mdx mice possibly due to increased skeletal muscle lipid oxidation by green tea extract along with exercise . Further, our findings that TC exercise improved muscle strength is supported by other studies reporting that regular TC practitioners had better muscle strength and endurance capacity than sedentary controls [42, 43], possibly because TC’s movements of the lower limbs put more demand on ankle dorsiflexors , knee extensors , and knee muscle activation . Therefore, TC exercise may provide bone protection by improving neuromuscular function in postmenopausal women .
We recognize the following limitations in the present study: (1) The number of subjects in each group was not equal. (2) The amount of dietary calcium intake for each subject was not available. However, there may be an interaction between calcium and treatments (GTP and/or TC). (3) Bone remodeling is a slow process, and the time required to complete a bone remodeling cycle may increase with age. Therefore, BMD could not be justified as an outcome in the present short-term study where changes in BMD were not expected to be detectable, although BMD is considered more closely related to clinical implication of the treatments than the biomarkers measured in this study. In addition, we have noticed that in the present study, the effects of GTP and TC on bone biomarkers were transient and none of the changes were significant at the 6-month time point. A long-term study is therefore recommended that measures BMD as the primary outcome using DEXA. In addition, evaluation of bone microstructure including volumetric BMD, stress–strain index, and bone geometry using advanced peripheral quantitative computed tomography (pQCT) can further elucidate the clinical impact of GTP supplementation, TC exercise, and their combined treatment.
The results of this study showed that both GTP supplementation and TC exercise increased bone formation biomarkers and improved bone turnover rate. TC exercise increased serum parathyroid hormone levels. GTP supplementation, TC exercise, and the combination of the two all improved muscle strength in postmenopausal women with osteopenia.
This study was supported by the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health under grant 1R21AT003735-01A1. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM or the National Institutes of Health. We gratefully acknowledge the study participants; without them, this study would not have been possible. We would like to thank Dr. Jay Magaziner (University of Maryland, MD) for their advice. We also thank Mary J. Flores, Raul Y. Dagda, and Marisela Dagda for their assistance in data collection. Clinical trial number: NCT00625391.
Partial results were presented at the Annual Meeting of American Society for Bone and Mineral Research.
Conflicts of interest None.
C.-L. Shen, Department of Pathology, Texas Tech University Health Sciences Center, BB 198, 3601 4th street, Lubbock, TX 79430-9097, USA. Department of Laboratory Science and Primary Care, Texas Tech University Health Sciences Center, Lubbock, TX, USA. Laura W. Bush Institute for Women’s Health, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
M.-C. Chyu, Department of Pathology, Texas Tech University Health Sciences Center, BB 198, 3601 4th street, Lubbock, TX 79430-9097, USA. Healthcare Engineering, Texas Tech University, Lubbock, TX 79409, USA. Department of Health, Exercise, and Sport Sciences, Texas Tech University, Lubbock, TX 79409, USA. Department of Mechanical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
J. K. Yeh, Applied Bench Core Laboratory, Winthrop-University Hospital, Mineola, NY 11501, USA.
Y. Zhang, Laura W. Bush Institute for Women’s Health, Texas Tech University Health Sciences Center, Lubbock, TX, USA. Department of Community and Family Medicine, Texas Tech University, Lubbock, TX 79409, USA.
B. C. Pence, Department of Pathology, Texas Tech University Health Sciences Center, BB 198, 3601 4th street, Lubbock, TX 79430-9097, USA.
C. K. Felton, Department of Obstetrics and Gynecology, Texas Tech University, Lubbock, TX 79409, USA.
J.-M. Brismée, Rehabilitation Sciences, Texas Tech University, Lubbock, TX 79409, USA.
B. H. Arjmandi, Department of Nutrition, Food & Exercise Sciences, Florida State University, Tallahassee, FL 32303, USA.
S. Doctolero, Clinical Research Center, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
J.-S. Wang, Department of Environmental Health Science, University of Georgia, Athens, GA 30602, USA.