Effects of Alcohol and Estrogen Receptor Blockade Using ICI 182,780 on Bone in Ovariectomized Rats.

BACKGROUND: Estrogen signaling is essential for the sexual dimorphism of the skeleton, is required for normal bone remodeling balance in adults, and may influence the skeletal response to alcohol. High levels of alcohol consumption lower bone mass in ovary-intact but not ovariectomized (ovx) rats. However, the extremely rapid rate of bone loss immediately following ovx may obscure the effects of alcohol. We therefore determined (i) whether heavy alcohol consumption (35% caloric intake) influences bone in sexually mature ovx rats with established cancellous osteopenia and (ii) whether ICI 182,780 (ICI), a potent estrogen receptor signaling antagonist, alters the skeletal response to alcohol. METHODS: Three weeks following ovx, rats were randomized into 5 groups, (i) baseline, (ii) control + vehicle, (iii) control + ICI, (iv) ethanol (EtOH) + vehicle, or (v) EtOH + ICI, and treated accordingly for 4 weeks. Dual-energy X-ray absorptiometry, microcomputed tomography, blood measurements of markers of bone turnover, and gene expression in femur and uterus were used to evaluate response to alcohol and ICI. RESULTS: Rats consuming alcohol had lower bone mass and increased fat mass. Bone microarchitecture of the tibia and gene expression in femur were altered; specifically, there was reduced accrual of cortical bone, net loss of cancellous bone, and differential expression of 19/84 genes related to bone turnover. Furthermore, osteocalcin, a marker of bone turnover, was lower in alcohol-fed rats. ICI had no effect on weight gain, body composition, or cortical bone. ICI reduced cancellous bone loss and serum CTX-1, a biochemical marker of bone resorption; alcohol antagonized the latter 2 responses. Neither alcohol nor ICI affected uterine weight or gene expression. CONCLUSIONS: Alcohol exaggerated bone loss in ovx rats in the presence or absence of estrogen receptor blockade with ICI. The negligible effect of alcohol on uterus and limited effects of ICI on bone in alcohol-fed ovx rats suggest that estrogen receptor signaling plays a limited role in the action of alcohol on bone in a rat model for chronic alcohol abuse.

Voluntary Chronic Heavy Alcohol Consumption in Male Rhesus Macaques Suppresses Cancellous Bone Formation and Increases Bone Marrow Adiposity.

BACKGROUND: Chronic heavy alcohol consumption is an established risk factor for bone fracture, but comorbidities associated with alcohol intake may contribute to increased fracture rates in alcohol abusers. To address the specific effects of alcohol on bone, we used a nonhuman primate model and evaluated voluntary alcohol consumption on: (i) global markers of bone turnover in blood and (ii) cancellous bone mass, density, microarchitecture, turnover, and microdamage in lumbar vertebra. METHODS: Following a 4-month induction period, 6-year-old male rhesus macaques (Macaca mulatta, n = 13) voluntarily self-administered water or ethanol (EtOH; 4% w/v) for 22 h/d, 7 d/wk, for a total of 12 months. Control animals (n = 9) consumed an isocaloric maltose-dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3 days prior to sacrifice to label mineralizing bone surfaces. Global skeletal response to EtOH was evaluated by measuring plasma osteocalcin and carboxyterminal collagen cross-links (CTX). Local response was evaluated in lumbar vertebra using dual-energy X-ray absorptiometry, microcomputed tomography, static and dynamic histomorphometry, and histological assessment of microdamage. RESULTS: Monkeys in the EtOH group consumed an average of 2.8 ± 0.2 (mean ± SE) g/kg/d of EtOH (30 ± 2% of total calories), resulting in an average blood EtOH concentration of 88.3 ± 8.8 mg/dl 7 hours after the session onset. Plasma CTX and osteocalcin tended to be lower in EtOH-consuming monkeys compared to controls. Significant differences in bone mineral density in lumbar vertebrae 1 to 4 were not detected with treatment. However, cancellous bone volume fraction (in cores biopsied from the central region of the third vertebral body) was lower in EtOH-consuming monkeys compared to controls. Furthermore, EtOH-consuming monkeys had lower osteoblast perimeter and mineralizing perimeter, no significant difference in osteoclast perimeter, and higher bone marrow adiposity than controls. No significant differences between groups were detected in microcrack density (2nd lumbar vertebra). CONCLUSIONS: Voluntary chronic heavy EtOH consumption reduces cancellous bone formation in lumbar vertebra by decreasing osteoblast-lined bone perimeter, a response associated with an increase in bone marrow adiposity.

Resistance training reduces disability in prostate cancer survivors on androgen deprivation therapy: evidence from a randomized controlled trial.

OBJECTIVES: To investigate whether functionally based resistance exercise could improve strength, physical function, and disability among prostate cancer survivors (PCS) on androgen deprivation therapy (ADT); and to explore potential mediators of changes in outcomes from exercise. DESIGN: Randomized controlled trial. SETTING: Academic medical center. PARTICIPANTS: PCS (N=51; mean age, 70.2y) on ADT. INTERVENTION: PCS were randomized to moderate to vigorous intensity resistance training or stretching (placebo control) for 1 year. MAIN OUTCOME MEASURES: Maximal leg press and bench press strength, objective and self-reported physical function, and self-reported disability. Hierarchical linear modeling was used to test for significant group × time differences adjusting for covariates. RESULTS: Retention in the study was 84%, and median attendance to supervised classes was 84% in the resistance group. No study-related injuries occurred. Maximal leg strength (P=.032) and bench press strength (P=.027) were improved after 1 year of resistance training, whereas little change occurred from stretching. Self-reported physical function improved with resistance training, whereas decreases occurred from stretching (P=.016). Disability lessened more with resistance training than stretching (P=.018). One-year change in leg press strength mediated the relation between groups (resistance or stretching) and 1-year change in self-reported disability (P<.05). CONCLUSIONS: One year of resistance training improved muscle strength in androgen-deprived PCS. Strengthening muscles using functional movement patterns may be an important feature of exercise programs designed to improve perceptions of physical function and disability. Findings from this study contribute to the mounting evidence that exercise should become a routine part of clinical care in older men with advanced prostate cancer.

Active women before/after an intervention designed to restore menstrual function: resting metabolic rate and comparison of four methods to quantify energy expenditure and energy availability.

UNLABELLED: It is hypothesized that exercise-related menstrual dysfunction (ExMD) results from low energy availability (EA), defined as energy intake (EI)--exercise energy expenditure (EEE). When EI is too low, resting metabolic rate (RMR) may be reduced to conserve energy. PURPOSE: To measure changes in RMR and EA, using four methods to quantify EEE, before/after a 6-month diet intervention aimed at restoring menses in women with ExMD; eumenorrheic (Eumen) active controls (n = 9) were also measured. METHODS: Active women with ExMD (n = 8) consumed +360 kcal/d (supplement) for 6 months; RMR was measured 2 times at 0 months/6 months. EI and total energy expenditure (TEE) were estimated using 7-day diet/activity records, with EA assessed using four methods to quantify EEE. RESULTS: At baseline, groups did not differ for age, gynecological age, body weight, lean/fat mass, VO2max, EI and EA, but mean TEE was higher in ExMD (58.3 ± 4.4 kcal/ kgFFM/d; Eumen = 50.6 ± 2.4; p < .001) and energy balance (EB) more negative (-10.3 ± 6.9 kcal/kgFFM/d; Eumen=-3.0 ± 9.7; p = .049). RMR was higher in ExMD (31.3 ± 1.8 kcal/kgFFM/d) vs. Eumen (29.1 ± 1.9; p < .02). The intervention increased weight (1.6 ± 2.0 kg; p = .029), but there were no significant changes in EA (0-month range = 28.2-36.7 kcal/kgFFM/d; 6-month range = 30.0-45.4; p > .05), EB (6 months = -0.7 ± 15.1 kcal/kgFFM/d) or RMR (0 months = 1515 ± 142; 6 months = 1522 ± 134 kcal/d). Assessment of EA varied dramatically (~30%) by method used. CONCLUSIONS: For the ExMD group, EI and weight increased with +360 kcal/d for 6 months, but there were no significant changes in EB, EA or RMR. No threshold EA value was associated with ExMD. Future research should include TEE, EB and clearly quantifying EEE (e.g.,>4 MET) if EA is measured.

Six months of voluntary alcohol consumption in male cynomolgus macaques reduces intracortical bone porosity without altering mineralization or mechanical properties.

Chronic heavy alcohol consumption is a risk factor for low trauma bone fracture. Using a non-human primate model of voluntary alcohol consumption, we investigated the effects of 6 months of ethanol intake on cortical bone in cynomolgus macaques (Macaca fascicularis). Young adult (6.4 ± 0.1 years old, mean ± SE) male cynomolgus macaques (n = 17) were subjected to a 4-month graded ethanol induction period, followed by voluntary self-administration of water or ethanol (4 % w/v) for 22 h/d, 7 d/wk. for 6 months. Control animals (n = 6) consumed an isocaloric maltose-dextrin solution. Tibial response was evaluated using densitometry, microcomputed tomography, histomorphometry, biomechanical testing, and Raman spectroscopy. Global bone response was evaluated using biochemical markers of bone turnover. Monkeys in the ethanol group consumed an average of 2.3 ± 0.2 g/kg/d ethanol resulting in a blood ethanol concentration of 90 ± 12 mg/dl in longitudinal samples taken 7 h after the daily session began. Ethanol consumption had no effect on tibia length, mass, density, mechanical properties, or mineralization (p > 0.642). However, compared to controls, ethanol intake resulted in a dose-dependent reduction in intracortical bone porosity (Spearman rank correlation = -0.770; p < 0.0001) and compared to baseline, a strong tendency (p = 0.058) for lower plasma CTX, a biochemical marker of global bone resorption. These findings are important because suppressed cortical bone remodeling can result in a decrease in bone quality. In conclusion, intracortical bone porosity was reduced to subnormal values 6 months following initiation of voluntary ethanol consumption but other measures of tibia architecture, mineralization, or mechanics were not altered.

A prospective evaluation of balance, gait, and strength to predict falling in women with multiple sclerosis.

OBJECTIVE: To identify measures of balance, gait, and strength that predict falls in women with multiple sclerosis (MS). DESIGN: This prospective study followed participants for 1 year. SETTING: University research laboratories. PARTICIPANTS: A convenience sample of women with MS (N=99). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Balance was assessed with the limits of stability (LOS) test and the Sensory Organization Test. Peak force, torque, and power of knee flexors and extensors as well as hip abductors and adductors were also measured. Temporal-spatial parameters of gait were measured by an instrumented walkway system. For 1 year after baseline assessments, the participants reported their falls. Participants were then classified based on the number of reported falls for use in logistic regression models to predict either people with at least 1 fall or people with at least 2 falls (recurrent fallers). RESULTS: A total of 159 falls were reported by 48% of the participants. Expanded Disability Status Scale scores, leaning forward to the LOS, and standing sway within a visually referenced surround significantly predicted people with at least 1 fall as well as recurrent fallers. Stance-phase asymmetries and base-of-support width during gait, as well as the force and power produced during leg extension or flexion additionally predicted recurrent fallers. The models' overall predictive accuracy ranged from 69% to 85%. CONCLUSIONS: This prospective study confirmed the prevalence and multifactorial nature of falls in this MS sample. In addition to advancing disease status, impaired forward LOS and visually dependent sway (as well as gait asymmetries and leg flexor-extensor weakness for recurrent fallers) predict future falls in women with MS.

A Novel Treatment Combination for Failed Back Surgery Syndrome, With a 41-Month Follow-Up: A Retrospective Case Report.

OBJECTIVE: The purpose of this retrospective case report was to describe chiropractic management of a patient with failed back surgery syndrome. CLINICAL FEATURES: A 45-year-old woman presented 2 years after L4-L5 and L5-S1 fusion surgery with low back and sciatic pain. Her physical exam included a positive straight leg raise and diminished lower-extremity reflexes and muscle strength. The patient's magnetic resonance imaging showed right disc bulging and annular tearing at L2-L3 and L3-L4 disc bulging with foraminal impingement. INTERVENTION AND OUTCOME: A total of 52 treatments were provided over 28 weeks consisting of multidirectional functional decompression (FD) unweighted gait training, core exercises while in FD, strengthening exercises on a vibration platform, and supine spinal FD with vibration and chiropractic spinal manipulative therapy. Over the course of treatment, the patient noted gradual improvement in function (Oswestry Disability Index) and pain (Numeric Rating Scale), with a reduction in pain medications. Follow-up of 41 months posttreatment revealed an Oswestry Disability Index score of 0 and Numeric Rating Scale score of 0, and the patient no longer was using any pain medication. CONCLUSION: After a course of care, the patient in this study reported resolution of symptoms, decrease in pain medications, and improvement of function.

The effects of hormone replacement therapy and resistance training on spine bone mineral density in early postmenopausal women.

This study evaluated the additive effects of hormone replacement therapy (HRT) and a 1-year site-specific resistance-training (RT) program involving two free weight exercises (i.e., squat and deadlift) 2 days/week as a strategy to reverse or attenuate bone loss at the lumbar spine in early postmenopausal women. Participants from a group of self-selected HRT or non-HRT (N=141) users were randomly assigned to RT (exercise) or no training, creating four groups: 1) non-HRT plus RT [NHRT plus exercise (n=35)]; 2) HRT plus RT [HRT plus exercise (n=37)]; 3) HRT no resistance training [HRT no exercise (n=35)]; or 4) control [non-HRT no resistance training group (n=34)]. Mean age and months past menopause did not differ between groups (52.1+/-3.0 years and 52.8+/-9.9 months, respectively). Post-menopausal status was confirmed by follicle-stimulating hormone levels > or =40 mIU/mL. Bone mineral density (BMD) of the spine was assessed by Dual Energy X-ray Absorptiometry (Hologic), at baseline and month 12. Data were analyzed using a 4 (experimental condition) x 2 (time) repeated measures multivariate analysis of variance to determine the effects of RT on HRT and non-HRT in early postmenopausal women. The main effects for group (P<0.007), time (P<0.001), and the group by time interaction (P<0.001) were each significant. Control participants experienced an average of -3.6% reduction of BMD at the spine. HRT treatment with no exercise showed bone loss of -0.66%. One year of RT produced increases in spine BMD of +0.43% and +0.70%, respectively for the NHRT plus exercise, and HRT plus exercise groups with no differences between the NHRT and HRT exercise groups. In conclusion, RT alone was as effective as HRT in preventing bone loss at the spine and was more effective than HRT alone in attenuating bone loss at the spine. Moreover, there was no additional benefit in combining HRT with RT for preventing bone loss at the spine in this group of early postmenopausal women.

Relative effects of exercise training and alendronate treatment on skeletal muscle function of ovariectomized rats.

OBJECTIVE: Increased physical activity and bisphosphonate treatment are both effective in reducing the risk of fracture in postmenopausal women. Physical activity reduces the risk of fracture by improving both bone and skeletal muscle strength. The effects of bisphosphonates have primarily been evaluated on bone. In this study the authors investigated the combined effects of increased physical activity and bisphosphonate treatment on skeletal muscle function using an animal model of postmenopausal osteoporosis. DESIGN: Seven-month-old ovariectomized rats were assigned to one of four combinations of physical activity treatment (sedentary or endurance running) and alendronate treatment (vehicle or 0.015 mg/kg alendronate, two treatments per week). After 14 weeks slow (soleus) and fast (extensor digitorum longus) muscles were isolated from each animal and electrically stimulated for evaluation of twitch, low-frequency, and tetanic force and resistance to fatiguing stimulation. RESULTS: Exercise training reduced body mass, increased soleus and extensor digitorum longus muscle mass, increased soleus tetanic force, reduced the twitch contraction time of the soleus and extensor digitorum longus, and facilitated relaxation of the soleus during fatiguing stimulation. Bisphosphonate treatment had no independent effect on muscle function and interacted with training for only a single variable (twitch half-relaxation time). CONCLUSIONS: Endurance training increased muscle mass in ovariectomized rats and had subtle effects on slow and fast muscle function. Alendronate treatment, at a dosage previously shown to improve bone strength in ovariectomized rats, neither blunted nor enhanced these training adaptations and had no independent effect on muscle contractility.

Comparison of 2 Multimodal Interventions With and Without Whole Body Vibration Therapy Plus Traction on Pain and Disability in Patients With Nonspecific Chronic Low Back Pain.

OBJECTIVE: The purpose of this secondary data analysis was to compare the effect of 2 multimodal exercise-based physical therapy interventions (one with and one without whole-body vibration [WBV] therapy plus traction) on pain and disability in patients with nonspecific chronic low back pain (NSCLBP). METHODS: We conducted a secondary analysis of data from 2 distinct samples. One sample was from the Focus on Therapeutic Outcomes Inc. (FOTO) group (n = 55, age 55.1 ± 19.0 years), and the other was the Illinois Back Institute (IBI) (n = 70, age 47.5 ± 13.4 years). Both groups of patients had NSCLBP for more than 3 months and a pain numeric rating scale (NRS) score of ≥7. Both groups received treatment consisting of flexibility or stretching exercises, core stability training, functional training, and postural exercises and strengthening exercises. However, the IBI group also received WBV plus traction. NSCLBP was measured before and after therapeutic trials using the NRS for pain and Oswestry Disability Index (ODI). RESULTS: The NRS scores were significantly improved in both groups, decreasing by 2 points in the FOTO group and by 5 points in the IBI group. The ODI scores were significantly improved in both groups; the FOTO group score improved by 9 points and the IBI group improved by 22 points. CONCLUSIONS: The results of this preliminary study suggest that NPS and ODI scores statistically improved for both NSCLBP groups receiving multimodal care. However, the group that included WBV therapy plus traction in combination with multimodal care had greater clinical results. This study had several limitations making it difficult to generalize the results from this study sample to the entire population.

Twelve months of voluntary heavy alcohol consumption in male rhesus macaques suppresses intracortical bone remodeling.

Chronic heavy alcohol consumption is a risk factor for cortical bone fractures in males. The increase in fracture risk may be due, in part, to reduced bone quality. Intracortical (osteonal) bone remodeling is the principle mechanism for maintaining cortical bone quality. However, it is not clear how alcohol abuse impacts intracortical bone remodeling. This study investigated the effects of long-duration heavy alcohol consumption on intracortical bone remodeling in a non-human primate model. Following a 4-month induction period, male rhesus macaques (Macaca mulatta, n=21) were allowed to voluntarily self-administer water or alcohol (4% ethanol w/v) for 22h/d, 7 d/wk for 12months. Control monkeys (n=13) received water and an isocaloric maltose-dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3days prior to sacrifice for determination of active mineralization sites. Animals in the alcohol group consumed 2.7±0.2g alcohol/kg/d (mean±SE) during the 12months of self-administration, resulting in a mean daily blood alcohol concentration of 77±9mg/dl from samples taken at 7h after the start of a daily session. However, blood alcohol concentration varied widely from day to day, with peak levels exceeding 250mg/dl, modeling a binge-drinking pattern of alcohol consumption. The skeletal response to alcohol was determined by densitometry, microcomputed tomography and histomorphometry. Significant differences in tibial bone mineral content, bone mineral density, and cortical bone architecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and polar moment of inertia) in the tibial diaphysis were not detected with treatment. However, cortical porosity was lower (1.8±0.5 % versus 0.6±0.1 %, p=0.021) and labeled osteon density was lower (0.41±0.2/mm(2)versus 0.04±0.01/mm(2), p<0.003) in alcohol-consuming monkeys compared to controls, indicating a reduced rate of intracortical bone remodeling. In concordance, plasma CTx was lower (2.5±0.3ng/ml versus 1.7±0.1ng/ml, p=0.028) in the alcohol group. These results suggest that chronic heavy alcohol consumption may negatively impact bone health, in part, by suppressing intracortical bone remodeling.

Resistance Exercise Reduces Body Fat and Insulin During Androgen-Deprivation Therapy for Prostate Cancer.

PURPOSE/OBJECTIVES: To determine whether exercise could reduce biomarkers of cancer progression in prostate cancer survivors (PCSs) on androgen-deprivation therapy (ADT). DESIGN: Randomized, controlled trial. SETTING: Oregon Health and Science University School of Nursing. SAMPLE: 51 PCSs randomized to one year of resistance and impact training or a stretching control group. METHODS: The authors investigated changes in body composition and cancer-related biomarkers, and the influence of age and fat loss on changes in biomarkers. MAIN RESEARCH VARIABLES: Body composition (total fat, trunk fat, and lean mass), insulin, insulin-like growth factor-1, and sex hormone-binding globulin. FINDINGS: In the 36 PCSs with baseline and 12-month data, total fat (p = 0.02) and trunk fat (p = 0.06) mass decreased in the training group compared to gains in controls. Loss of total and trunk fat each mediated the relationship between groups and one-year change in insulin (p < 0.05). Age moderated the insulin response to exercise where insulin reductions were smaller with increasing age (p = 0.03). CONCLUSIONS: Resistance and impact exercise may reduce body fat among PCSs undergoing ADT, in turn exerting an insulin-lowering effect. IMPLICATIONS FOR NURSING: Nurses should counsel PCSs to exercise to reduce the risk of obesity and associated conditions, including cancer progression.

The association between hormone therapy use and changes in strength and body composition in early postmenopausal women.

OBJECTIVE: To prospectively examine potential differences in upper- and lower-body muscle strength, lower-body power, lean muscle mass, total body fat, intra-abdominal fat, and energy expenditure (METS) variables in early postmenopausal women. Measurements were taken at baseline and 12 months. DESIGN: Prospective, 1-year non-randomized [self-selected hormone therapy (HT) and non-HT-replaced], longitudinal study with participation from 136 normally active, early [14.2 +/- 9.8 mo past menopause (51.1 +/- 3.0 y) mean age +/- SD] postmenopausal women. Total body fat mass, lean mass, and bone mass were assessed by dual-energy x-ray absorptiometry (Hologic), METS (6-mo activity recall questionnaire) upper- and lower-body peak force by isokinetic dynamometry (KinCom 500H, Chattex Corp.), and leg power by the Bassey Power Rig (Nottingham, UK). RESULTS: We observed no significant differences in central adipose tissue, total fat mass, lean muscle mass, strength, or lower limb power. However, estrogen did promote a maintenance affect in bone mineral density at the spine and total hip and an increase in greater trochanter bone mineral density (P < 0.01) in the estrogen-replaced group. CONCLUSION: Our findings suggest that HT does not play a role in either increasing or maintaining strength, lean muscle mass, lower limb power, or the attenuation of increases in total body or abdominal fat, at least in this group of postmenopausal women during the initial years of menopause

Morphological and functional characteristics of skeletal muscle fibers from hormone-replaced and nonreplaced postmenopausal women.

We tested the hypothesis that cross-bridge mechanisms of contraction differed in early postmenopausal women who did or did not receive hormone replacement therapy (HRT). Vastus lateralis biopsies were obtained from 17 postmenopausal women (49-57 years old), 8 of whom were on HRT for the previous 24 +/- 5 months and 9 of whom were never on HRT. Electrophoresis and enzyme histochemistry revealed that fiber myosin heavy chain (MHC) isoform distribution, the cross-sectional area (CSA) of slow and fast fibers, and the relative CSA occupied by each, were similar for HRT and non-HRT groups. Single permeabilized fibers containing type IIa MHC had greater Ca(2+)-activated peak specific force, unloaded shortening velocity, and peak power than fibers containing type I MHC, but in all cases the values for HRT and non-HRT groups were similar. In this cross-sectional study, we found no evidence that Ca(2+)-activated fiber function, MHC isoform distribution, or relative CSA occupied by slow and fast fibers differed between HRT and non-HRT groups.

Concurrent validity of the BOD POD and dual energy x-ray absorptiometry techniques for assessing body composition in young women.

The purpose of this study was to determine the concurrent validity of the BOD POD (BP) (Life Measurement Instruments) and Dual Energy X-Ray Absorptiometry (DXA) Elite 4500A (Hologic, Inc.) techniques for assessing the body fat percentage of young women. The participants were forty-three white college-aged women (19.4 +/- 1.4 years) with a BMI of 23.4 +/- 2.3. Both body composition analyses were completed on the same day and were taken within 10 minutes of each other. Body fat percentage was estimated to be 24.3 (SE = 1.1) and 23.8 (SE = 0.8) using the BP and DXA techniques, respectively. Exact matches, in terms of body fat percentage, were obtained for 10 of the 43 participants (23.3%). In conclusion, our data supports the concurrent validity of the BP and DXA techniques for assessing body fat in young women.

Dietary intervention restored menses in female athletes with exercise-associated menstrual dysfunction with limited impact on bone and muscle health.

Exercise-related menstrual dysfunction (ExMD) is associated with low energy availability (EA), decreased bone mineral density (BMD), and increased risk of musculoskeletal injury. We investigated whether a 6-month carbohydrate-protein (CHO-PRO) supplement (360 kcal/day, 54 g CHO/day, 20 g PRO/day) intervention would improve energy status and musculoskeletal health and restore menses in female athletes (n = 8) with ExMD. At pre/post-intervention, reproductive and thyroid hormones, bone health (BMD, bone mineral content, bone markers), muscle strength/power and protein metabolism markers, profile of mood state (POMS), and energy intake (EI)/energy expenditure (7 day food/activity records) were measured. Eumenorrheic athlete controls with normal menses (Eumen); n = 10) were measured at baseline. Multiple linear regressions were used to evaluate differences between groups and pre/post-intervention blocking on participants. Improvements in EI (+382 kcal/day; p = 0.12), EA (+417 kcal/day; p = 0.17) and energy balance (EB; +466 kcal/day; p = 0.14) were observed with the intervention but were not statistically significant. ExMD resumed menses (2.6 ± 2.2-months to first menses; 3.5 ± 1.9 cycles); one remaining anovulatory with menses. Female athletes with ExMD for >8 months took longer to resume menses/ovulation and had lower BMD (low spine (ExMD = 3; Eumen = 1); low hip (ExMD = 2)) than those with ExMD for <8 months; for 2 ExMD the intervention improved spinal BMD. POMS fatigue scores were 15% lower in ExMD vs. Eumen (p = 0.17); POMS depression scores improved by 8% in ExMD (p = 0.12). EI, EA, and EB were similar between groups, but the intervention (+360 kcal/day) improved energy status enough to reverse ExMD despite no statistically significant changes in EI. Similar baseline EA and EB between groups suggests that some ExMD athletes are more sensitive to EA and EB fluctuations.

Exploring physical activity in women with multiple sclerosis: associations with fear of falling and underlying impairments.

OBJECTIVE: The aim of this study was to conduct an exploratory analysis of fear of falling (FoF), balance, gait, and strength impairments and future physical activity in women with multiple sclerosis. DESIGN: This prospective study followed a convenience sample of 99 women with multiple sclerosis for 1 yr. The participants were assessed on FoF and perceived mental health by questionnaire. Objective measures included Limits of Stability, the Sensory Organization Test, and the Functional Ambulation Profile. Strength was quantified by knee extensor power asymmetry. Activity-specific metabolic equivalent values were used to determine minutes per week of moderate and vigorous physical activity. RESULTS: Future physical activity most strongly associated with baseline FoF (R = 0.09, P < 0.01), and baseline FoF associated with limits of stability and lower extremity strength asymmetry (R = 0.21, P < 0.001). Follow-up FoF is best predicted by initial levels of FoF independent of intervening falls (ß = 3.26, P < 0.001). CONCLUSIONS: Future physical activity of women with multiple sclerosis was best predicted by FoF independent of physical and mental functioning. Increased FoF was associated with greater lower extremity strength asymmetry and decreased limits of stability rather than with the experience of falls.

Skeletal response to resistance and impact training in prostate cancer survivors.

INTRODUCTION: Androgen deprivation therapy (ADT) is associated with significant bone loss and an increase in fracture risk among prostate cancer survivors (PCS). We investigated whether impact + resistance training could stop ADT-related declines in bone mineral density (BMD) among PCS on ADT. METHODS: We randomized 51 PCS (mean age, 70.2 yr) currently prescribed ADT to participate in 1 yr of impact + resistance training (Prevent Osteoporosis with Impact + Resistance (POWIR)) or in an exercise placebo program of stretching exercise (FLEX). Outcomes were proximal femur (total hip, femoral neck, and greater trochanter) and spine (L1-L4) BMD (g·cm) and bone turnover markers (serum osteocalcin (ng·mL) and urinary deoxypyrodinoline cross-links (nmol·mmol Cr)). RESULTS: Retention in the 1-yr study was 84% and median attendance to supervised classes was 84% in POWIR and 74% in FLEX. No study-related injuries were reported. There were no significant differences between groups for average L1-L4 BMD or for BMD at any hip site. When examining individual vertebrae, POWIR has a significant effect on preservation of BMD (-0.4%) at the L4 vertebrae compared with losses (-3.1%) in FLEX (P = 0.03). CONCLUSION: Impact + resistance training was a safe and acceptable form of exercise for older PCS on ADT. Among our limited sample, POWIR did not appear to have a clinically meaningful effect on hip or spine BMD, but some evidence of skeletal adaptation to resistance + impact training in an androgen-deprived state was apparent. Future studies need to be conducted on a larger sample of patients and should consider modifications to POWIR that could further enhance loading across the spine and at the hip to preserve BMD at these clinically relevant sites.

Moderate alcohol intake lowers biochemical markers of bone turnover in postmenopausal women.

OBJECTIVE: Epidemiological studies indicate that higher bone mass is associated with moderate alcohol consumption in postmenopausal women. However, the underlying cellular mechanisms responsible for the putative beneficial effects of alcohol on bone are unknown. Excessive bone turnover, combined with an imbalance whereby bone resorption exceeds bone formation, is the principal cause of postmenopausal bone loss. This study investigated the hypothesis that moderate alcohol intake attenuates bone turnover after menopause. METHODS: Bone mineral density was determined by dual-energy x-ray absorptiometry in 40 healthy postmenopausal women (mean ± SE age, 56.3 ± 0.5 y) who consumed alcohol at 19 ± 1 g/day. Serum levels of the bone formation marker osteocalcin and the resorption marker C-terminal telopeptide (CTx) were measured by immunoassay at baseline (day 0) and after alcohol withdrawal for 14 days. Participants then consumed alcohol and were assayed on the following morning. RESULTS: Bone mineral density at the trochanter and total hip were positively correlated to the level of alcohol consumption. Serum osteocalcin and CTx increased after abstinence (4.1 ± 1.6%, P = 0.01 and 5.8 ± 2.6%, P = 0.02 compared with baseline, respectively). Osteocalcin and CTx decreased after alcohol readministration, compared with the previous day (-3.4 ± 1.4%, P = 0.01 and -3.5 ± 2.1%, P = 0.05, respectively), to values that did not differ from baseline (P > 0.05). CONCLUSIONS: Abstinence from alcohol results in increased markers of bone turnover, whereas resumption of alcohol reduces bone turnover markers. These results suggest a cellular mechanism for the increased bone density observed in postmenopausal moderate alcohol consumers. Specifically, the inhibitory effect of alcohol on bone turnover attenuates the detrimental skeletal consequences of excessive bone turnover associated with menopause.

Transitional shifts in exercise behavior among women with multiple sclerosis.

BACKGROUND: While physical activity is recommended to reduce symptomology associated with multiple sclerosis (MS) little has been done to explore the potential usefulness of theoretical models of exercise behavior change in individuals with MS. Based on the success of the transtheoretical model of exercise behavior change (TTM) in the general population and early promising results in those with MS, the TTM was tested in a sample of women with MS over a 1-year period, to examine its usefulness and the effect of TTM constructs on MS-related symptoms. METHODS: This was a longitudinal study conducted over a 1-year period. Ambulatory women (N=86) with MS completed questionnaires assessing exercise behavior, TTM constructs, MS-related quality of life, pain, and fatigue at baseline and after 1 year. After categorization into transitional shift patterns reflecting naturally occurring exercise behavior change over the year, a series of mixed-design analyses of variance were conducted to examine TTM predictions and the relationship of the transitional shift patterns to MS-related quality of life, pain, and fatigue. RESULTS: Significant interactions between transitional shift patterns and time (P < .05) indicated that changes in behavioral and cognitive processes of change and in self-efficacy were consistent with TTM predictions. Significant differences (P < .05) between the transitional shift groups in pain and fatigue in expected directions were also found. CONCLUSIONS: Results supported the TTM proposed relationships, indicating the model's potential for motivating individuals with MS to increase their physical activity. Findings also support the notion that physical activity is useful in reducing MS-related symptoms and that lifestyle types of physical activity may be as useful as structured exercise in bringing about these outcomes.