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1.
Management of Osteoporosis, Fracture and Falls in People with Multiple Sclerosis: Systematic Review of Guidelines.
Grech, L, Laurence, K, Ebeling, PR, Sim, M, Zengin, A
Calcified tissue international. 2024;(3):201-209
Abstract
People with multiple sclerosis (MS) have a higher prevalence of osteoporosis, falls and fractures. Guidelines for MS populations targeting the management of osteoporosis, fracture and falls risk may help reduce the burden of musculoskeletal disease in this population. We aimed to systematically review current guidelines regarding osteoporosis prevention, screening, diagnosis and management in people with MS. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, a systematic review of scientific databases (MEDLINE, CINAHL, Embase and Scopus) was performed (n = 208). In addition, websites from MS organisations and societies were screened for clinical guidelines (n = 28). Following duplicate removal, screening and exclusions (n = 230), in total six guidelines were included in this review. Three of the identified guidelines were specific to managing osteoporosis in MS, while two linked vitamin D to bone health and one was focused on the effect of acute glucocorticoid use for MS exacerbations on bone health. All guidelines were found to contain inadequate recommendations for osteoporosis screening, management and treatment in people with MS given the evidence of higher prevalence of osteoporosis at an earlier age and compounding risk factors in this population. Early diagnosis and treatment of osteoporosis in people with MS is necessary as fractures lead to significant morbidity and mortality. Development of structured clinical guidelines directed at specific healthcare services will ensure screening, appropriate management, and care of bone health in people with MS.
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Vitamin D supplementation and exercise for improving physical function, body composition and metabolic health in overweight or obese older adults with vitamin D deficiency: a pilot randomized, double-blind, placebo-controlled trial.
Mesinovic, J, Rodriguez, AJ, Cervo, MM, Gandham, A, Xu, CLH, Glavas, C, de Courten, B, Zengin, A, Ebeling, PR, Scott, D
European journal of nutrition. 2023;62(2):951-964
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Plain language summary
Overweight and obese older adults are at increased risk for vitamin D deficiency, which is associated with poor metabolic and musculoskeletal health, unfavourable body composition, and attenuated responses to exercise. The aim of this study was to determine whether, compared with placebo, vitamin D3 supplementation (4000 IU/day) taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight or obese older adults with vitamin D deficiency. This study is a 24-week parallel-group, double-blind, placebo-controlled pilot randomised controlled trial. Fifty overweight or obese participants were enrolled for the study, and randomised to either 4000 IU/day of oral vitamin D3 or identical placebo. Results demonstrated that 4000 IU/day vitamin D3 supplementation: - did not affect gait speed when taken with or without exercise, - helped achieve optimal serum 25-hydroxyvitamin D levels and decreased waist circumference (compared with placebo) following multi-modal exercise. - taken alone without exercise reduced stair climb times. However, vitamin D3 supplementation did not have any beneficial effects on other biochemical, body composition or physical function parameters when taken alone or during exercise. Authors conclude that future studies should focus on populations with moderate or severe vitamin D deficiency as they are more likely to experience therapeutic benefits from vitamin D supplementation.
Abstract
PURPOSE Vitamin D supplementation may have non-skeletal health benefits and enhance exercise responsiveness, particularly in those with low vitamin D levels. We determined whether, compared with placebo, vitamin D supplementation taken prior to and during a 12-week exercise program improves physical function, body composition or metabolic health, in overweight and obese older adults with vitamin D deficiency. METHODS Fifty overweight or obese older adults (mean ± SD age: 60 ± 6 years; BMI 30.6 ± 5.7 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] < 50 nmol/L) were recruited. Participants were randomly allocated to receive either vitamin D3 (4000 IU/day) or matching placebo for 24 weeks. Between weeks 12 and 24, all participants completed multi-modal exercise three days per week while continuing with vitamin D/placebo. Mean changes in physical function (primary outcome: gait speed), body composition and biochemical parameters at weeks 12 and 24 were compared between groups. RESULTS Vitamin D supplementation, with or without exercise, had no effect on gait speed. From baseline to week 12, vitamin D supplementation increased serum 25(OH)D levels (placebo: 2.5 ± 14.7 nmol/L; treatment: 43.4 ± 18.4 nmol/L; P < 0.001) and reduced stair climb times (placebo: 0.3 ± 1.0 s; treatment: - 0.2 ± 1.0 s; P = 0.046). From 12 to 24 weeks, vitamin D supplementation combined with exercise decreased waist circumference (placebo: 1.3 ± 7.3 cm; treatment: - 3.0 ± 6.1 cm; P = 0.02) and waist-to-hip ratio (placebo: 0.01 ± 0.05; treatment: - 0.03 ± 0.05; P = 0.01) relative to placebo. Vitamin D supplementation, with or without exercise, had no effect on other physical function, body composition or metabolic health outcomes. CONCLUSION Vitamin D supplementation had no effect on most physical function, body composition or metabolic health parameters when taken alone, or during exercise, in overweight or obese older adults with vitamin D deficiency. Vitamin D-related improvements in stair climb times and waist circumference suggest that future trials should explore the effects of vitamin D on muscle power, and its effects on body composition when combined with exercise, in populations with moderate or severe vitamin D deficiency.
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Sustainability of a 12-month lifestyle intervention delivered by community health workers in reducing blood pressure in Nepal: 5-year follow-up of the COBIN open-label, cluster randomised trial.
Thapa, R, Zengin, A, Neupane, D, Mishra, SR, Koirala, S, Kallestrup, P, Thrift, AG
The Lancet. Global health. 2023;(7):e1086-e1095
Abstract
BACKGROUND The sustainability and scalability of limited-duration interventions in low-income and middle-income countries remain unclear. We aimed to investigate the sustainability in reduction of blood pressure through a 12-month lifestyle intervention led by community health workers to reduce blood pressure in Nepal, 4 years after the intervention ceased. METHODS The Community-Based Intervention for Control of Hypertension in Nepal (COBIN) trial was a non-blinded, cluster-randomised trial done in Kaski, Nepal. Adults aged 25-65 years were eligible. People were excluded if they declined consent, were severely ill, unlikely to be in the community throughout the intervention, or pregnant. During the 12-month intervention, female community health volunteers (FCHVs) visited participants in the intervention groups and provided lifestyle counselling and blood pressure measurement every 4 months. At the end of the 12-month intervention, systolic blood pressure was significantly lower in the intervention group than in the usual care group in all cohorts, ranging from -2·3 mm Hg (95% CI -3·8 to -0·8) lower in those with normal blood pressure to -4·9 mm Hg (-7·8 to -2·0) in the hypertensive cohort. The primary outcome for this follow-up study was a mean change in systolic blood pressure from baseline to follow-up at 60 months. We did an intention-to-treat analysis. FINDINGS Between April 1, 2015, and Dec 31, 2015, 1638 participants were recruited in COBIN (939 [57·3%] assigned to intervention and 699 [42·7%] assigned to usual care). Of the 1468 (89·6%) who completed the 12-month assessments, we followed up 1352 (92·1%) participants at 60 months, between Oct 11, 2020, and May 5, 2022. 964 (71·3%) participants were women and 388 (28·7%) were men. From baseline to 60 months, the mean systolic blood pressure increased by 10·4 mm Hg (95% CI 9·1-11·6) in the intervention group and 6·0 mm Hg (4·6-7·5) in the usual care group (adjusted mean difference 4·1 mm Hg [2·2 to 5·8]). INTERPRETATION Lifestyle counselling and blood pressure monitoring by community health workers is effective in substantially reducing blood pressure while adults are being monitored in a trial but, following cessation of the intervention, this benefit is not maintained in the long term, with potential for harm. This finding could have important implications for funders and research communities to regularly target participants for education and follow-up at an optimal timepoint to reduce any likelihood of harm. FUNDING Monash University (Melbourne, VIC, Australia) and the Jayanti Memorial Trust (Kathmandu, Nepal). TRANSLATION For the Nepali translation of the abstract see Supplementary Materials section.
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4.
Medication and bone health in multiple sclerosis: A systematic review and meta-analysis.
Cahyadi, M, Mesinovic, J, Chim, ST, Ebeling, P, Zengin, A, Grech, L
Journal of managed care & specialty pharmacy. 2023;(12):1331-1353
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Abstract
BACKGROUND People with multiple sclerosis (MS) are often prescribed medications associated with adverse effects on bone health. However, it is unclear whether these medications incur decreases in areal bone mineral density (aBMD) and higher fracture risk in this population. OBJECTIVE To investigate the effects of commonly used medications on aBMD and fracture risk among people with MS. METHODS MEDLINE, Embase, Scopus, CINAHL, and Web of Science were searched from their inception until February 5, 2023. We included randomized controlled trials as well as cross-sectional, retrospective, and prospective studies investigating whether glucocorticoids, immunomodulators, antidepressants, anticonvulsants, anxiolytics, opioids, or antipsychotics influenced aBMD or fracture risk in people with MS. Data were pooled using random effects meta-analyses to determine hazard ratios (HRs) and 95% CIs. RESULTS We included 22 studies (n = 18,193). Six studies were included in the meta-analyses of glucocorticoid use and aBMD, whereas 2 studies were included in the medication use and fracture risk meta-analyses. No studies assessed the effect of antidepressants, anxiolytics, anticonvulsants, opioids, and antipsychotics on aBMD, and no studies assessed the effect of immunomodulators on fracture risk. Glucocorticoid use was significantly negatively associated with femoral neck aBMD (correlation = -0.21 [95% CI = -0.29 to -0.13]), but not with lumbar spine aBMD (correlation = -0.21 [95% CI = -0.50 to 0.12]). There were no differences in fracture risk between users of glucocorticoids (HR = 1.71 [95% CI = 0.04 to 76.47]), antidepressants (HR = 1.84 [95% CI = 0.09 to 38.49]), or anxiolytics (HR = 2.01 [95% CI = 0.06 to 64.22]), compared with nonusers. CONCLUSIONS The available evidence is insufficient to support a relationship between greater fracture risk for people with MS taking glucocorticoid, antidepressant, or anxiolytic medication, compared with nonusers, and it is unclear whether these medications are associated with bone loss in people with MS, beyond that in the general population. Additional high-quality studies with homogenous methodology exploring how medications influence aBMD and fracture risk in people with MS are required.
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Exercise attenuates bone mineral density loss during diet-induced weight loss in adults with overweight and obesity: A systematic review and meta-analysis.
Mesinovic, J, Jansons, P, Zengin, A, de Courten, B, Rodriguez, AJ, Daly, RM, Ebeling, PR, Scott, D
Journal of sport and health science. 2021;(5):550-559
Abstract
BACKGROUND Weight-loss-induced fat loss improves cardiometabolic health in individuals with overweight and obesity; however, weight loss can also result in bone loss and increased fracture risk. Weight-loss-induced bone loss may be attenuated with exercise. Our aim was to compare changes in bone mineral density (BMD) in adults with overweight and obesity who undertook diet-induced weight loss alone or in combination with exercise. METHODS We included randomized controlled trials (RCTs) in adults with overweight or obesity (aged ≥18 years; body mass index ≥25 kg/m2) that prescribed diet-induced weight loss alone or in combination with supervised exercise, and measured any bone structural parameters. Risk of bias was assessed using the Cochrane Risk of Bias tool. Random-effects meta-analyses determined mean changes and net mean differences (95% confidence intervals (95%CIs)) in the percentage of areal BMD (aBMD) change between groups. RESULTS We included 9 RCTs. Diet-induced weight loss led to significant losses in femoral neck aBMD (mean change: -1.73% (95%CI: -2.39% to -1.07%), p < 0.001) and total hip aBMD (-2.19% (95%CI: -3.84% to -0.54%), p = 0.009). Femoral neck aBMD losses were significantly greater in the diet-induced weight loss group compared to the exercise plus diet-induced weight loss group (net difference: -0.88% (95%CI: -1.73% to -0.03%)); however, there were no differences in aBMD changes at any other skeletal site: total hip (-1.96% (95%CI: -4.59% to 0.68%)) and lumbar spine (-0.48% (95%CI: -1.81% to 0.86%)). aBMD changes did not differ significantly according to exercise modality (resistance exercise, aerobic exercise, or a combination of the two) during diet-induced weight loss. CONCLUSION Diet-induced weight loss led to greater femoral neck bone loss compared to diet-induced weight loss plus exercise. Bone loss at the total hip and lumbar spine was not attenuated by exercise during diet-induced weight loss. The lack of consistent skeletal benefits may be due to the insufficient duration and/or training intensities of most exercise interventions. Additional RCTs with appropriate, targeted exercise interventions should be conducted.
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Falls, fractures, and areal bone mineral density in older adults with sarcopenic obesity: A systematic review and meta-analysis.
Gandham, A, Mesinovic, J, Jansons, P, Zengin, A, Bonham, MP, Ebeling, PR, Scott, D
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2021;(5):e13187
Abstract
Sarcopenia and obesity are common conditions in older adults that may have differing effects on falls and fracture risk. This systematic review and meta-analysis aimed to determine whether older adults with sarcopenic obesity have increased risk of falls and fractures or lower bone mass compared with older adults with sarcopenia, obesity, or neither condition. Twenty-six studies (n = 37,124) were included in the systematic review and 17 (n = 31,540) were included in the meta-analysis. Older adults with sarcopenic obesity had lower femoral neck areal bone mineral density (aBMD) compared with those with obesity alone but had higher femoral neck aBMD compared with counterparts with sarcopenia alone (both P < 0.05). Older adults with sarcopenic obesity had higher nonvertebral fracture rates (incidence rate ratio: 1.88; 95% confidence intervals: 1.09, 3.23; based on two studies), compared with those with sarcopenia alone, and also had higher falls risk compared with controls (risk ratio: 1.30; 95% confidence intervals: 1.10, 1.54) and obesity alone (risk ratio: 1.17; 95% confidence intervals: 1.01, 1.36). In conclusion, this systematic review and meta-analysis has demonstrated that older adults with sarcopenic obesity are at increased risk of adverse musculoskeletal outcomes compared with individuals with obesity, sarcopenia, or neither condition. These data support the need for developing interventions to improve bone health and physical function in this population.
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Sarcopenia and type 2 diabetes mellitus: a bidirectional relationship.
Mesinovic, J, Zengin, A, De Courten, B, Ebeling, PR, Scott, D
Diabetes, metabolic syndrome and obesity : targets and therapy. 2019;:1057-1072
Abstract
The incidence and prevalence of metabolic and musculoskeletal diseases are increasing. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, inflammation, advanced glycation end-product accumulation and increased oxidative stress. These characteristics can negatively affect various aspects of muscle health, including muscle mass, strength, quality and function through impairments in protein metabolism, vascular and mitochondrial dysfunction, and cell death. Sarcopenia is a term used to describe the age-related loss in skeletal muscle mass and function and has been implicated as both a cause and consequence of T2DM. Sarcopenia may contribute to the development and progression of T2DM through altered glucose disposal due to low muscle mass, and also increased localized inflammation, which can arise through inter- and intramuscular adipose tissue accumulation. Lifestyle modifications are important for improving and maintaining mobility and metabolic health in individuals with T2DM and sarcopenia. However, evidence for the most effective and feasible exercise and dietary interventions in this population is lacking. In this review, we discuss the current literature highlighting the bidirectional relationship between T2DM and sarcopenia, highlight current research gaps and treatments, and provide recommendations for future research.
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Ethnic differences in bone health.
Zengin, A, Prentice, A, Ward, KA
Frontiers in endocrinology. 2015;:24
Abstract
There are differences in bone health between ethnic groups in both men and in women. Variations in body size and composition are likely to contribute to reported differences. Most studies report ethnic differences in areal bone mineral density (aBMD), which do not consistently parallel ethnic patterns in fracture rates. This suggests that other parameters beside aBMD should be considered when determining fracture risk between and within populations, including other aspects of bone strength: bone structure and microarchitecture, as well as muscle strength (mass, force generation, anatomy) and fat mass. We review what is known about differences in bone-densitometry-derived outcomes between ethnic groups and the extent to which they account for the differences in fracture risk. Studies are included that were published primarily between 1994 and 2014. A "one size fits all approach" should definitely not be used to understand better ethnic differences in fracture risk.