Trabecular and cortical bone density and architecture in women after 60 days of bed rest using high-resolution pQCT: WISE 2005

Prolonged bed rest is used to simulate the effects of spaceflight and causes disuse-related loss of bone. While bone density changes during bed rest have been described, there are no data on changes in bone microstructure. Twenty-four healthy women aged 25 to 40 years participated in 60 days of strict 6-degree head-down tilt bed rest (WISE 2005). Subjects were assigned to either a control group (CON, n = 8), which performed no countermeasures; an exercise group (EXE, n = 8), which undertook a combination of resistive and endurance training; or a nutrition group (NUT, n = 8), which received a high-protein diet. Density and structural parameters of the distal tibia and radius were measured at baseline, during, and up to 1 year after bed rest by high-resolution peripheral quantitative computed tomography (HR-pQCT). Bed rest was associated with reductions in all distal tibial density parameters (p < 0.001), whereas only distal radius trabecular density decreased. Trabecular separation increased at both the distal tibia and distal radius (p < 0.001), but these effects were first significant after bed rest. Reduction in trabecular number was similar in magnitude at the distal radius (p = 0.021) and distal tibia (p < 0.001). Cortical thickness decreased at the distal tibia only (p < 0.001). There were no significant effects on bone structure or density of the countermeasures (p ≥ 0.057). As measured with HR-pQCT, it is concluded that deterioration in bone microstructure and density occur in women during and after prolonged bed rest. The exercise and nutrition countermeasures were ineffective in preventing these changes.

Bone density and neuromuscular function in older competitive athletes depend on running distance

UNLABELLED: Individuals who are involved in explosive sport types, such as 100-m sprints and long jump, have greater bone density, leg muscle size, jumping height and grip strength than individuals involved in long-distance running. INTRODUCTION: The purpose of this study is to examine the relationship between different types of physical activity with bone, lean mass and neuromuscular performance in older individuals. METHODS: We examined short- (n = 50), middle- (n = 19) and long-distance (n = 109) athletes at the 15th European Masters Championships in Poznań, Poland. Dual X-ray absorptiometry was used to measure areal bone mineral density (aBMD) and lean tissue mass. Maximal countermovement jump, multiple one-leg hopping and maximal grip force tests were performed. RESULTS: Short-distance athletes showed significantly higher aBMD at the legs, hip, lumbar spine and trunk compared to long-distance athletes (p ≤ 0.0012). Countermovement jump performance, hop force, grip force, leg lean mass and arm lean mass were greater in short-distance athletes (p ≤ 0.027). A similar pattern was seen in middle-distance athletes who typically showed higher aBMD and better neuromuscular performance than long-distance athletes, but lower in magnitude than short-distance athletes. In all athletes, aBMD was the same or higher than the expected age-adjusted population mean at the lumbar spine, hip and whole body. This effect was greater in the short- and middle-distance athletes. CONCLUSIONS: The stepwise relation between short-, middle- and long-distance athletes on bone suggests that the higher-impact loading protocols in short-distance disciplines are more effective in promoting aBMD. The regional effect on bone, with the differences between the groups being most marked at load-bearing regions (legs, hip, spine and trunk) rather than non-load-bearing regions, is further evidence in support of the idea that bone adaptation to exercise is dependent upon the local loading environment, rather than as part of a systemic effect.

Bone strength and density via pQCT in post-menopausal osteopenic women after 9 months resistive exercise with whole body vibration or proprioceptive exercise

OBJECTIVES: In order to better understand which training approaches are more effective for preventing bone loss in post-menopausal women with low bone mass, we examined the effect of a nine-month resistive exercise program with either an additional whole body vibration exercise (VIB) or balance training (BAL). METHODS: 68 post-menopausal women with osteopenia were recruited for the study and were randomised to either the VIB or BAL group. Two training sessions per week were performed. 57 subjects completed the study (VIB n=26; BAL n=31). Peripheral quantitative computed tomography (pQCT) measurements of the tibia, fibula, radius and ulna were performed at baseline and at the end of the intervention period at the epiphysis (4% site) and diaphysis (66% site). Analysis was done on an intent-to-treat approach. RESULTS: Significant increases in bone density and strength were seen at a number of measurement sites after the intervention period. No significant differences were seen in the response of the two groups at the lower-leg. CONCLUSIONS: This study provided evidence that a twice weekly resistive exercise program with either additional balance or vibration training could increase bone density at the distal tibia after a nine-month intervention period in post-menopausal women with low bone mass.

Whole-body vibration versus proprioceptive training on postural control in post-menopausal osteopenic women

BACKGROUND: To prevent falls in the elderly, especially those with low bone density, is it necessary to maintain muscle coordination and balance. The aim of this study was to examine the effect of classical balance training (BAL) and whole-body vibration training (VIB) on postural control in post-menopausal women with low bone density. METHODS: Sixty-eight subjects began the study and 57 completed the nine-month intervention program. All subjects performed resistive exercise and were randomized to either the BAL- (N=31) or VIB-group (N=26). The BAL-group performed progressive balance and coordination training and the VIB-group underwent, in total, four minutes of vibration (depending on exercise; 24-26Hz and 4-8mm range) on the Galileo Fitness. Every month, the performance of a single leg stance task on a standard unstable surface (Posturomed) was tested. At baseline and end of the study only, single leg stance, Romberg-stance, semi-tandem-stance and tandem-stance were tested on a ground reaction force platform (Leonardo). RESULTS: The velocity of movement on the Posturomed improved by 28.3 (36.1%) (p<0.001) in the VIB-group and 18.5 (31.5%) (p<0.001) in the BAL-group by the end of the nine-month intervention period, but no differences were seen between the two groups (p=0.45). Balance tests performed on the Leonardo device did not show any significantly different responses between the two groups after nine months (p≥0.09). CONCLUSIONS: Strength training combined with either proprioceptive training or whole-body vibration was associated with improvements in some, but not all, measures of postural control in post-menopausal women with low bone density. The current study could not provide evidence for a significantly different impact of whole-body vibration or balance training on postural control.

Vibration or balance training on neuromuscular performance in osteopenic women

Maintaining neuromuscular function in older age is an important topic for aging societies, especially for older women with low bone density who may be at risk of falls and bone fracture. This randomized controlled trial investigated the effect of resistive exercise with either whole-body vibration training (VIB) or coordination/balance training (BAL) on neuromuscular function (countermovement jump, multiple 1-leg hopping, sit-to-stand test). 68 postmenopausal women with osteopenia or osteoporosis were recruited for the study. 57 subjects completed the 9-month, twice weekly, intervention period. All subjects conducted 30 min of resistance exercise each training day. The VIB-group performed additional training on the Galileo vibration exercise device. The BAL-group performed balance training. An "intent-to-treat" analysis showed greater improvement in the VIB-group for peak countermovement power (p=0.004). The mean [95% confidence interval] effect size for this parameter was a  + 0.9[0.3 to 1.5] W/kg greater change in VIB than BAL after 9 months. In multiple 1-leg hopping, a significantly better performance in the VIB-group after the intervention period was seen on a "per-protocol" analysis only. Both groups improved in the sit-to-stand test. The current study provides evidence that short-duration whole-body vibration exercise can have a greater impact on some aspects of neuromuscular function in post-menopausal women with low bone density than proprioceptive training.

Greater association of peak neuromuscular performance with cortical bone geometry, bone mass and bone strength than bone density : a study in 417 older women

BACKGROUND: We evaluated which aspects of neuromuscular performance are associated with bone mass, density, strength and geometry. METHODS: 417 women aged 60-94years were examined. Countermovement jump, sit-to-stand test, grip strength, forearm and calf muscle cross-sectional area, areal bone mineral content and density (aBMC and aBMD) at the hip and lumbar spine via dual X-ray absorptiometry, and measures of volumetric vBMC and vBMD, bone geometry and section modulus at 4% and 66% of radius length and 4%, 38% and 66% of tibia length via peripheral quantitative computed tomography were performed. The first principal component of the neuromuscular variables was calculated to generate a summary neuromuscular variable. Percentage of total variance in bone parameters explained by the neuromuscular parameters was calculated. Step-wise regression was also performed. RESULTS: At all pQCT bone sites (radius, ulna, tibia, fibula), a greater percentage of total variance in measures of bone mass, cortical geometry and/or bone strength was explained by peak neuromuscular performance than for vBMD. Sit-to-stand performance did not relate strongly to bone parameters. No obvious differential in the explanatory power of neuromuscular performance was seen for DXA aBMC versus aBMD. In step-wise regression, bone mass, cortical morphology, and/or strength remained significant in relation to the first principal component of the neuromuscular variables. In no case was vBMD positively related to neuromuscular performance in the final step-wise regression models. CONCLUSION: Peak neuromuscular performance has a stronger relationship with leg and forearm bone mass and cortical geometry as well as proximal forearm section modulus than with vBMD.

The prevalence and age of onset of psychiatric disorders in Australian men

OBJECTIVE: Given the burden of common psychiatric disorders and their consequent service and planning requirements, it is important to have a thorough knowledge of their distribution and characteristics in the population. Thus, we aimed to report the prevalence and age of onset of mood, anxiety and substance-use disorders in an age-stratified representative sample of Australian men. METHOD: Psychiatric disorders (mood, anxiety and substance-use disorders) were diagnosed utilising a structured clinical interview (Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Non-Patient Edition) for 961 men aged 24-98 years enrolled in the Geelong Osteoporosis Study. The lifetime and current prevalence of these disorders was determined from the study population and standardised to 2006 census data for Australia. RESULTS: Approximately one in three men (28.8%, 95% confidence interval [CI] = [26.8%, 30.8%]) reported a lifetime history of any psychiatric disorder, with mood disorders (18.2%, 95% CI = [15.2%, 21.2%]) being more prevalent than anxiety (7.2%, 95% CI = [5.0%, 9.4%]) and substance-use disorders (12.9%, 95% CI = [9.7%, 16.0%]). Approximately 8.7% (95% CI = [7.5%, 10.0%]) were identified as having a current disorder, with 3.8% (95% interquartile range [IQR] = [2.2%, 5.4%]), 2.4% (95% CI = [1.1%, 3.8%]) and 3.4% (95% CI = [1.8%, 4.9%]) meeting criteria for current mood, anxiety and substance-use disorders, respectively. The median age of onset for mood disorders was 37.5 years (IQR = 27.0-48.0 years), 25.0 years (IQR = 20.0-40.3 years) for anxiety and 22.0 years (IQR = 18.0-34.3 years) for substance-use disorders. CONCLUSION: This study reports the lifetime and current prevalence of psychiatric disorders in the Australian male population. These findings emphasise the extent of the burden of these disorders in the community.

Falls and depression in men: a population-based study

The link between falls and depression has been researched in the elderly; however, little information is available on this association in younger adults, particularly men. This study sought to investigate the link between major depressive disorder (MDD) and falls in a population-based sample of 952 men (24-97 years). MDD was diagnosed utilizing the Structured Clinical Interview for DSM-IV-TR Research Version, Non-Patient edition, and categorized as 12-month/past/never. Body mass index and gait were measured; falls, smoking status, psychotropic medication use, and alcohol intake were self-reported as part of the Geelong Osteoporosis Study 5-year follow-up assessment. Thirty-four (3.6%) men met criteria for 12-month MDD, and 110 (11.6%) for past MDD. Of the 952 men, 175 (18.4%) reported falling at least once during the past 12 months. Fallers were older (66 [interquartile range: 48-79] vs. 59 [45-72] years, p = .001) and more likely to have uneven gait (n = 16, 10% vs. n = 31, 4%, p = .003) than nonfallers. Participants with 12-month MDD had more than twice the odds of falling (age-adjusted odds ratio: 2.22, 95% confidence interval [1.03, 4.80]). The odds of falling were not associated with past depression (p = .4). Further adjustments for psychotropic drug use, gait, body mass index, smoking status, blood pressure, and alcohol did not explain these associations. Given the 2.2-fold greater likelihood of falling associated with depression was not explained by age or psychotropic drug use, further research is warranted.

Effects of depression and serotonergic antidepressants on bone: mechanisms and implications for the treatment of depression

Osteoporosis is a chronic skeletal disease marked by microarchitectural deterioration of the bone matrix and depletion of bone mineral density (BMD), with a consequent increased risk for fragility fractures. It has been frequently associated with depression, which is also a chronic and debilitating disorder with high prevalence. Selective serotonin reuptake inhibitors (SSRIs), first-line agents in the pharmacological treatment of mood and anxiety disorders, have also been shown to negatively affect bone metabolism. SSRIs are the most prescribed antidepressants worldwide and a large number of persons at risk of developing osteoporosis, including older patients, will receive these antidepressants. Therefore, a proper musculoskeletal evaluation of individuals who are being targeted for or using SSRIs is a priority. The aim of this article is to review the evidence regarding the effects of depression and serotonergic antidepressants on bone and its implications for clinical care.

Patients presenting with fractures are likely to be vitamin D deficient: are we getting enough sun?

BACKGROUND: 25-Hydroxyvitamin D serves a crucial role in bone metabolism through its role on osteoclast and osteoblastic function. To assess the implication of vitamin D and its relationship to bone fracture and fracture force, we have examined vitamin D levels in patients requiring inpatient fracture management. METHODS: We performed serological testing of vitamin D levels, calcium, parathyroid hormone and liver function tests on patients admitted to our rural institution in southeastern Australia for inpatient fracture management. All participants completed a questionnaire designed to screen for potential contributing factors to bony fragility. Demographic data were also obtained including age, gender and body mass index. Fracture location and the type of inpatient management as well as the force of injury were included in our analysis. RESULTS: We recruited 100 patients to the study, with a median age of 72 (range 22-98) of whom 66 were women. Most had low-energy fractures (79%), treated by internal fixation (73%) or arthroplasty (9%) with 18 treated non-operatively. The majority of the patients were at best vitamin D insufficient, <75 nmol/L (77%), and 38% were vitamin D deficient (<50 nmol/L). Only 14 patients had a formal diagnosis of osteoporosis at presentation, with 63 patients claiming daily sun exposure in line with recommendations for vitamin D sufficiency. CONCLUSIONS: Our data suggest that the prevalence of vitamin D insufficiency and deficiency is common in patients presenting with fractures in southeastern Australia and is not confined to elderly patients. All patients with fractures should be assessed for vitamin D levels and treated in accordance with vitamin D deficiency guidelines.

Pro-inflammatory dietary intake as a risk factor for CVD in men: a 5-year longitudinal study

Convincing evidence has identified inflammation as an initiator of atherosclerosis, underpinning CVD. We investigated (i) whether dietary inflammation, as measured by the 'dietary inflammatory index (DII)', was predictive of 5-year CVD in men and (ii) its predictive ability compared with that of SFA intake alone. The sample consisted of 1363 men enrolled in the Geelong Osteoporosis Study who completed an FFQ at baseline (2001-2006) (excluding participants who were identified as having previous CVD). DII scores were computed from participants' reported intakes of carbohydrate, micronutrients and glycaemic load. DII scores were dichotomised into a pro-inflammatory diet (positive values) or an anti-inflammatory diet (negative values). The primary outcome was a formal diagnosis of CVD resulting in hospitalisation over the 5-year study period. In total, seventy-six events were observed during the 5-year follow-up period. Men with a pro-inflammatory diet at baseline were twice as likely to experience a CVD event over the study period (OR 2·07; 95 % CI 1·20, 3·55). This association held following adjustment for traditional CVD risk factors and total energy intake (adjusted OR 2·00; 95 % CI 1·03, 3·96). This effect appeared to be stronger with the inclusion of an age-by-DII score interaction. In contrast, SFA intake alone did not predict 5-year CVD events after adjustment for covariates (adjusted OR 1·40; 95 % CI 0·73, 2·70). We conclude that an association exists between a pro-inflammatory diet and CVD in Australian men. CVD clinical guidelines and public health recommendations may have to expand to include dietary patterns in the context of vascular inflammation.

DNA methylation and the social gradient of osteoporotic fracture: a conceptual model

INTRODUCTION: Although there is a documented social gradient for osteoporosis, the underlying mechanism(s) for that gradient remain unknown. We propose a conceptual model based upon the allostatic load theory, to suggest how DNA methylation (DNAm) might underpin the social gradient in osteoporosis and fracture. We hypothesise that social disadvantage is associated with priming of inflammatory pathways mediated by epigenetic modification that leads to an enhanced state of inflammatory reactivity and oxidative stress, and thus places socially disadvantaged individuals at greater risk of osteoporotic fracture. METHODS/RESULTS: Based on a review of the literature, we present a conceptual model in which social disadvantage increases stress throughout the lifespan, and engenders a proinflammatory epigenetic signature, leading to a heightened inflammatory state that increases risk for osteoporotic fracture in disadvantaged groups that are chronically stressed. CONCLUSIONS: Our model proposes that, in addition to the direct biological effects exerted on bone by factors such as physical activity and nutrition, the recognised socially patterned risk factors for osteoporosis also act via epigenetic-mediated dysregulation of inflammation. DNAm is a dynamic modulator of gene expression with considerable relevance to the field of osteoporosis. Elucidating the extent to which this epigenetic mechanism transduces the psycho-social environment to increase the risk of osteoporotic fracture may yield novel entry points for intervention that can be used to reduce individual and population-wide risks for osteoporotic fracture. Specifically, an epigenetic evidence-base may strengthen the importance of lifestyle modification and stress reduction programs, and help to reduce health inequities across social groups. MINI ABSTRACT: Our conceptual model proposes how DNA methylation might underpin the social gradient in osteoporotic fracture. We suggest that social disadvantage is associated with priming of inflammatory signalling pathways, which is mediated by epigenetic modifications, leading to a chronically heightened inflammatory state that places disadvantaged individuals at greater risk of osteoporosis.

Depression is a risk factor for incident coronary heart disease in women: an 18-year longitudinal study

BACKGROUND: According to a recent position paper by the American Heart Association, it remains unclear whether depression is a risk factor for incident Coronary Heart Disease (CHD). We assessed whether a depressive disorder independently predicts 18-year incident CHD in women. METHOD: A prospective longitudinal study of 860 women enrolled in the Geelong Osteoporosis Study (1993-2011) was conducted. Participants were derived from an age-stratified, representative sample of women (20-94 years) randomly selected from electoral rolls in South-Eastern Australia. The exposure was a diagnosis of a depressive disorder using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. Outcomes data were collected from hospital medical records: (1) Primary outcome: a composite measure of cardiac death, non-fatal Myocardial Infarction or coronary intervention. (2) Secondary outcome: any cardiac event (un/stable angina, cardiac event not otherwise defined) occurring over the study period. RESULTS: Seven participants were excluded based on CHD history. Eighty-three participants (9.6%) recorded ≥1 cardiac event over the study period; 47 had a diagnosis that met criteria for inclusion in the primary analysis. Baseline depression predicted 18-year incidence, adjusting for (1) anxiety (adj. OR:2.39; 95% CIs:1.19-4.82), plus (2) typical risk factors (adj. OR:3.22; 95% CIs:1.45-6.93), plus (3) atypical risk factors (adj. OR:3.28; 95% CIs:1.36-7.90). This relationship held when including all cardiac events. No relationship was observed between depression and recurrent cardiac events. CONCLUSION: The results of this study support the contention that depression is an independent risk factor for CHD incidence in women. Moreover, the strength of association between depression and CHD incidence was of a greater magnitude than any typical and atypical risk factor.

Statin and aspirin use and the risk of mood disorders among men

Background: There is a growing understanding that depression is associated with systemic inflammation. Statins and aspirin have anti-inflammatory properties. Given these agents have been shown to reduce the risk of a number of diseases characterized by inflammation, we aimed to determine whether a similar relationship exists for mood disorders (MD).

Methods: This study examined data collected from 961 men (24–98 years) participating in the Geelong Osteoporosis Study. MD were identified using a semistructured clinical interview (SCID-I/NP). Anthropometry was measured and information on medication use and lifestyle factors was obtained via questionnaire. Two study designs were utilized: a nested case-control and a retrospective cohort study.

Results: In the nested case-control study, exposure to statin and aspirin was documented for 9 of 142 (6.3%) cases and 234 of 795 (29.4%) controls (P < .001); after adjustment for age, exposure to these anti-inflammatory agents was associated with reduced likelihood of MD (OR 0.2, 95%CI 0.1–0.5). No effect modifiers or other confounders were identified. In the retrospective cohort study of 836 men, among the 210 exposed to statins or aspirin, 6 (2.9%) developed de novo MD during 1000 person-years of observation, whereas among 626 nonexposed, 34 (5.4%) developed de novo MD during 3071 person-years of observation. The hazard ratio for de novo MD associated with exposure to anti-inflammatory agents was 0.55 (95%CI 0.23–1.32).

Conclusions: This study provides both cross-sectional and longitudinal evidence consistent with the hypothesis that statin and aspirin use is associated with a reduced risk of MD.

First, do no harm: managing the metabolic impacts of androgen deprivation in men with advanced prostate cancer

Androgen deprivation therapy (ADT) is a standard systemic treatment for men with prostate cancer. Men on ADT may be elderly and have comorbidities that are exacerbated by ADT, such as cardiovascular disease, diabetes, obesity, sedentary lifestyle and osteoporosis. Studies on managing the impacts of ADT have focused on men with non-metastatic disease, where ADT is given for a limited duration. However, some men with advanced or metastatic prostate cancer will achieve long-term survival with palliative ADT and therefore also risk morbidity from prolonged ADT. Furthermore, ADT is continued during the use of other survival-prolonging therapies for men with advanced disease, and there is a general trend to use ADT earlier in the disease course. As survival improves, management of the metabolic effects of ADT becomes important for maintaining both quality and quantity of life. This review will outline the current data, offer perspectives for management of ADT complications in men with advanced prostate cancer and discuss avenues for further research.