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Does adding exercise or physical activity to pharmacological osteoporosis therapy in patients with increased fracture risk improve bone mineral density and lower fracture risk? A systematic review and meta-analysis.
Schumm, AK, Craige, EA, Arora, NK, Owen, PJ, Mundell, NL, Buehring, B, Maus, U, Belavy, DL
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2023;34(11):1867-1880
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Osteoporosis, a progressive systematic skeletal disease is caused by diminished bone density and strength, which may increase the risk of fragility fractures in the spine, pelvis, femur etc. Women are at greater risk of developing osteoporosis. Osteopenia is an intermediary stage of reduced bone mineral density before progressing into the osteoporosis disease state. Exercise and pharmacological therapies are considered two effective strategies commonly used in the treatment of osteoporosis. Exercise may help to improve bone mineral density, strength and muscle mass and reduce the risk of fractures. This systematic review and meta-analysis of five parallel-arm randomised controlled trials investigated the combined effect of exercise and pharmacological therapy on bone mineral density, bone turnover markers, fractures and fracture healing in patients with osteopenia and osteoporosis. This systematic review and meta-analysis showed a non-significant improvement in bone mineral density in patients with osteopenia and osteoporosis followed by combined pharmacological treatment with exercise. Pharmacological therapy alone showed improvement and maintenance of bone mineral density. There was no evidence for the improvement in fragility fracture healing. Due to the low evidence and high heterogeneity of included studies, further robust studies are required to evaluate the combined effect of exercise and pharmacological therapy in people with systematic skeletal disease. Healthcare professionals can use this study to understand the benefits of pharmacological therapy in improving osteoporosis and osteopenia and the potential of adding exercise as a therapeutic strategy in clinical practice.
Abstract
This prospectively registered systematic review and meta-analysis examines whether exercise (EX) training has an additive effect to osteoanabolic and/or antiresorptive pharmacological therapy (PT) in people with osteoporosis on bone mineral density (BMD), bone turnover markers (BTMs), fracture healing, and fractures. Four databases (inception to 6 May 2022), 5 trial registries, and reference lists were searched. Included were randomized controlled trials comparing the effect of EX + PT vs. PT with regard to BMD, BTM, fracture healing, and fractures. Risk of bias was assessed using the Cochrane RoB2 and certainty of evidence by the GRADE approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate standardized mean differences and 95% confidence intervals. Out of 2593 records, five RCTs with 530 participants were included. Meta-analysis showed with very low certainty evidence and wide confidence intervals that EX + PT compared to PT had larger effect sizes for BMD at 12 months at the hip (SMD [95%CI]: 0.18 [- 1.71; 2.06], n = 3 studies), tibia (0.25 [- 4.85; 5.34], n = 2), lumbar spine (0.20 [- 1.15; 1.55], n = 4), and forearm (0.05 [- 0.35; 0.46], n = 3), but not femoral neck (- 0.03 [- 1.80; 1.75], n = 3). Furthermore, no improvement was revealed for BTM such as bone ALP (- 0.68 [- 5.88; 4.53], n = 3), PINP (- 0.74 [- 10.42; 8.93], n = 2), and CTX-I (- 0.69 [- 9.61; 8.23], n = 2), but with very wide confidence intervals. Three potentially relevant ongoing trials were identified via registries. No data were found for fracture healing or fracture outcomes. It remains unclear whether EX has an additive impact to PT in people with osteoporosis. High-quality, adequately powered, targetted RCTs are required. PROTOCOL REGISTRATION PROSPERO CRD42022336132.
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Mediterranean diet and structural neuroimaging biomarkers of Alzheimer's and cerebrovascular disease: A systematic review.
Gregory, S, Pullen, H, Ritchie, CW, Shannon, OM, Stevenson, EJ, Muniz-Terrera, G
Experimental gerontology. 2023;172:112065
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Nearly a million people in the UK have Alzheimer's disease, the most common type of dementia. Mediterranean diet (MedDiet) adherence is associated with healthy brain ageing, a reduced stroke risk, and a lower incidence of dementia. Seven studies were included in this review to evaluate the effects of MedDiet on hippocampal volume and white matter hyperintensity volume, predictors of stroke and dementia. This systematic review did not reveal any associations between MedDiet adherence and hippocampal volume. However, there was a significant negative relationship between MedDiet adherence and white matter hyperintensity volume in two of the studies included. It is necessary to conduct more robust studies to investigate the associations between MedDiet adherence and structural brain imaging findings and understand the mechanisms behind dementia and other cerebrovascular diseases. This study could provide healthcare professionals with valuable information about the effects of increased MedDiet adherence on brain health, including its potential to delay neurodegenerative disease progression.
Expert Review
Conflicts of interest:
None
Take Home Message:
Due to inconclusive results on the associations between MedDiet adherence and AD and cerebrovascular related structural neuroimaging findings, specific recommendations for the MedDiet cannot be made on the basis of this study until further research has been completed.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background:
Changes in hippocampal volume (HV) and white matter intensity volume (WMIV) have been identified as structural neuroimaging biomarkers of neurodegenerative disease such as Alzheimer’s Disease (AD) and Cerebrovascular disease (CVD) respectively. Evidence has shown adherence to the Mediterranean Diet (MedDiet) has been associated with reduced risk for strokes. This review evaluated the MedDiet in relation to HV and WMIV.
Methods:
The review followed PRISMA guidelines and was registered on PROSPERO. Literature searching resulted in seven studies published between 2012 and 2022, which met the inclusion criteria. Six studies analysed cross-sectional data and one analysed longitudinal data. The NIH Quality Assessment Tool for Observational and Cross-Sectional Studies was used to assess risk of bias.
Overall, the studies were rated as low-risk of bias with details of the research question, participant group exposure and outcome variables included. Due to moderate to high heterogeneity in some studies, a meta-analysis was deemed unsuitable and narrative synthesis was conducted to present the results.
Results:
Mean participant age ranged from 53.19 to 80.3 years and volunteers were healthy or had subjective cognitive decline and a few participants had dementia (n=46).
Hippocampal Volume:
Four studies included 20,077 participants and found no significant associations between MedDiet adherence and hippocampal volume. All four studies were cross-sectional from larger cohort studies. To establish causative relationships longitudinal and RCT trials are required.
White Matter Hyperintensity Volumes:
Four studies included 1938 participants. Two studies found a significant negative association between MedDiet and WMHV, demonstrating higher Mediterranean Scores were associated with lower level of WHMV. The other two studies found no significant associations.
Although the review methodology with a piloted search strategy was considered a key strength, the lack of meta-analysis as planned in the a priori protocol, due to minimal eligible studies and high heterogeneity was a limitation as well as the restriction of brain imaging outcomes.
Conclusion:
Overall, these results are inconclusive on the associations between the MedDiet and HV and WMHV, and identify a gap in the knowledge, therefore further research such as RCT’s remains a priority to further understand the impact diet may have on neuroimaging markers of AD and CVD.
Clinical practice applications:
There were no significant associations between MedDiet adherence and HV, which was surprising given the evidence stating adherence to the MedDiet is associated with a lower incidence of dementia and stroke. However all four studies were cross-sectional studies and in order to detect causal associations, longitudinal and RCT’s are needed. Two studies did show a significant association between higher MedDiet adherence and lower WMHV, whereas two studies reported no significant associations.
Caution needs to be taken when recommending the MedDiet specifically for a reduction in HV and WMHV until further research has been undertaken.
Considerations for future research:
Future research should consider:
- larger cohorts and participants from the Mediterranean region where lifelong adherence to the MedDiet is more likely.
- looking at other risk factors to include obesity, lack of activity, poor sleep quality and stress.
- evaluating different socio-economic status, which has been shown to impact dietary behaviour.
- alternative imaging outcomes such as cortical thinning, PET amyloid and tau.
- . gold standard for methodology in particular dietary analysis and scanning and outcome derivation.
Abstract
Previous studies have demonstrated an association between adherence to the Mediterranean diet (MedDiet) and better cognitive performance, lower incidence of dementia and lower Alzheimer's disease biomarker burden. The aim of this systematic review was to evaluate the evidence base for MedDiet associations with hippocampal volume and white matter hyperintensity volume (WMHV). We searched systematically for studies reporting on MedDiet and hippocampal volume or WMHV in MedLine, EMBASE, CINAHL and PsycInfo. Searches were initially carried out on 21st July 2021 with final searches run on 23rd November 2022. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Of an initial 112 papers identified, seven papers were eligible for inclusion in the review reporting on 21,933 participants. Four studies reported on hippocampal volume, with inconclusive or no associations seen with MedDiet adherence. Two studies found a significant association between higher MedDiet adherence and lower WMHV, while two other studies found no significant associations. Overall these results highlight a gap in our knowledge about the associations between the MedDiet and AD and cerebrovascular related structural neuroimaging findings.
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The impact of nutrition on tendon health and tendinopathy: a systematic review.
Hijlkema, A, Roozenboom, C, Mensink, M, Zwerver, J
Journal of the International Society of Sports Nutrition. 2022;19(1):474-504
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Tendinopathy, which involves persistent tendon pain and loss of function related to mechanical loading, is common in athletes as well as in the general population. The aim of this study was to evaluate the impact of nutrition on the prevention and treatment of tendinopathy in a general human population. This study is a systematic review of nineteen studies. The number of people included in these studies ranged from 50 to 80,106. Results show that: - there wasn’t an association between any of the dietary parameters and Achilles tendon thickness. - despite inconsistent findings on the risk and severity of tendinopathy in humans, there is evidence that alcohol may inhibit collagen synthesis through toxic effects. - collagen seems to be beneficial in the treatment of tendinopathy, but conclusions about optimal dosage, timing, duration, and type of collagen supplementation cannot be drawn yet. - many other nutrients may contribute to collagen synthesis or may have anti-inflammatory effects, so most dietary supplements used in the different studies contained multiple substances. Authors conclude it is impossible to draw definitive conclusions and formulate dietary recommendations on the prevention and treatment of tendinopathy.
Abstract
BACKGROUND Tendinopathy is a painful condition that is prevalent in athletes as well as the general human population, and whose management is challenging. OBJECTIVE This systematic review aimed to evaluate the impact of nutrition on the prevention and treatment of tendinopathy. METHODS Searches were conducted in PubMed, EMBASE, Web of Science, and SPORTDiscus without restriction to year of publication. Studies examining the impact of exposure to nutrient intake in an adult human population on 1) prevalence/incidence of tendinopathy, 2) clinical outcomes of tendinopathy, 3) structural changes in the tendon by imaging modalities. Experimental and observational study designs written in English, Dutch, or German were eligible. RESULTS Nineteen studies met the inclusion criteria. The effects of the habitual diet were investigated in one study. Four studies examined the effects of exposure to alcohol. Alcohol consumption can be a potential risk factor associated with Achilles tendinopathy and rotator cuff tears, although findings were inconsistent. The use of dietary supplements was examined in fourteen studies. Among these, collagen-derived peptides were most often part of the supplements evaluated. Combining training and dietary supplements seems to induce better clinical and functional outcomes in tendinopathy. CONCLUSION This review demonstrates the paucity of high-quality studies and a wide variety among studies regarding nutrients, tendon location, study population, and reported outcome measures. Individual studies showed promising clinical implications for the use of dietary supplements, particularly those containing collagen-derived peptides. However, giving any definitive dietary recommendations on the prevention and treatment of tendinopathy remains elusive.
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Resistance Training Prevents Muscle Loss Induced by Caloric Restriction in Obese Elderly Individuals: A Systematic Review and Meta-Analysis.
Sardeli, AV, Komatsu, TR, Mori, MA, Gáspari, AF, Chacon-Mikahil, MPT
Nutrients. 2018;10(4)
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Caloric restriction (55% carbohydrate, 15% protein, 30% fat) is associated with increased lifespans and the attenuation of the harmful effects of aging. Furthermore, it has been shown that resistance training increases lean body mass, promotes strength, and attenuates muscle loss and function in elderly people. The aim of the study is to determine the level of lean body mass that can be preserved when resistance training is associated with caloric restriction interventions in elderly obese humans. The study is a meta-analysis, based on data from randomised-controlled trials. The participants were older adults or elderly people with a mean age > 57 year. Results indicate that caloric restriction associated with resistance training prevents 93% lean body mass loss induced by caloric restriction. Authors conclude that caloric restriction with resistance training almost stopped caloric restriction induced lean body mass loss completely.
Abstract
It remains unclear as to what extent resistance training (RT) can attenuate muscle loss during caloric restriction (CR) interventions in humans. The objective here is to address if RT could attenuate muscle loss induced by CR in obese elderly individuals, through summarized effects of previous studies. Databases MEDLINE, Embase and Web of Science were used to perform a systematic search between July and August 2017. Were included in the review randomized clinical trials (RCT) comparing the effects of CR with (CRRT) or without RT on lean body mass (LBM), fat body mass (FBM), and total body mass (BM), measured by dual-energy X-ray absorptiometry, on obese elderly individuals. The six RCTs included in the review applied RT three times per week, for 12 to 24 weeks, and most CR interventions followed diets of 55% carbohydrate, 15% protein, and 30% fat. RT reduced 93.5% of CR-induced LBM loss (0.819 kg [0.364 to 1.273]), with similar reduction in FBM and BM, compared with CR. Furthermore, to address muscle quality, the change in strength/LBM ratio tended to be different (p = 0.07) following CRRT (20.9 ± 23.1%) and CR interventions (−7.5 ± 9.9%). Our conclusion is that CRRT is able to prevent almost 100% of CR-induced muscle loss, while resulting in FBM and BM reductions that do not significantly differ from CR.
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Efficacy of exercise for treating overweight in children and adolescents: a systematic review.
Atlantis, E, Barnes, EH, Singh, MA
International journal of obesity (2005). 2006;30(7):1027-40
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The global number of overweight and obese children/adolescents is increasing at an alarming rate. This systematic review and meta-analysis aimed to assess the impact of exercise for overweight children/adolescents. Fourteen randomised controlled trials (RCTs) were included in the analysis. Overall the reduction in average body weight and central obesity was not significant. However, it was found that exercise did significantly reduce body fat percentage by 0.6% in studies that involved more exercise (more than 3 days a week) for children with an average age of 12. When results were grouped by exercise amount, it was found that higher amounts had greater effect. Additionally, trials with longer intervention length saw greater effects. None of the trials reached the level of exercise recommended for children by UK/US guidelines (at least 60 minutes a day). The author suggested further studies of longer duration in this area are required to clarify exercise amount response.
Abstract
BACKGROUND Overweight prevalence among children/adolescents is increasing, while adult obesity may potentially cause a decline in life expectancy. More exercise is uniformly recommended, although treatment efficacy remains unclear. OBJECTIVE To determine the efficacy of exercise alone for treating overweight in children/adolescents. DESIGN A systematic review and meta-analysis of randomized trials published in English were completed following multiple database searches performed on December 10, 2004. Studies of isolated or adjunctive exercise/physical activity treatment in overweight/obese children or adolescents which reported any overweight outcome were included. Literature searches identified 645 papers which were manually searched, of which 45 were considered for inclusion, of which 13 papers which reported 14 studies were included (N=481 overweight boys and girls, aged approximately 12 years). Two reviewers independently identified relevant papers for potential inclusion and assessed methodological quality. Principal measures of effects included the mean difference (MD) (between treatment and control groups), the weighted MD (WMD), and the standardized MD (SMD). RESULTS Few studies were of robust design. The pooled SMD was -0.4 (-0.7, -0.1, P=0.006) for percent body fat, and -0.2 (-0.6, 0.1, P=0.07) for central obesity outcomes, whereas the pooled WMD was -2.7 kg (-6.1 kg, 0.8 kg, P=0.07) for body weight, all of which favored exercise. Pooled effects on body weight were significant and larger for studies of higher doses, whereas nonsignificant and smaller effects were seen for studies of lower doses of exercise (155-180 min/weeks vs 120-150 min/weeks). CONCLUSIONS Based on the small number of short-term randomized trials currently available, an aerobic exercise prescription of 155-180 min/weeks at moderate-to-high intensity is effective for reducing body fat in overweight children/adolescents, but effects on body weight and central obesity are inconclusive. Recommendations for future study designs are discussed.