Exercise ameliorates muscular excessive mitochondrial fission, insulin resistance and inflammation in diabetic rats via irisin/AMPK activation.

This study aimed to investigate the effects of exercise on excessive mitochondrial fission, insulin resistance, and inflammation in the muscles of diabetic rats. The role of the irisin/AMPK pathway in regulating exercise effects was also determined. Thirty-two 8-week-old male Wistar rats were randomly divided into four groups (n = 8 per group): one control group (Con) and three experimental groups. Type 2 diabetes mellitus (T2DM) was induced in the experimental groups via a high-fat diet followed by a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 30 mg/kg body weight. After T2DM induction, groups were assigned as sedentary (DM), subjected to 8 weeks of treadmill exercise training (Ex), or exercise training combined with 8-week cycloRGDyk treatment (ExRg). Upon completion of the last training session, all rats were euthanized and samples of fasting blood and soleus muscle were collected for analysis using ELISA, immunofluorescence, RT-qPCR, and Western blotting. Statistical differences between groups were analyzed using one-way ANOVA, and differences between two groups were assessed using t-tests. Our findings demonstrate that exercise training markedly ameliorated hyperglycaemia, hyperlipidaemia, and insulin resistance in diabetic rats (p < 0.05). It also mitigated the disarranged morphology and inflammation of skeletal muscle associated with T2DM (p < 0.05). Crucially, exercise training suppressed muscular excessive mitochondrial fission in the soleus muscle of diabetic rats (p < 0.05), and enhanced irisin and p-AMPK levels significantly (p < 0.05). However, exercise-induced irisin and p-AMPK expression were inhibited by cycloRGDyk treatment (p < 0.05). Furthermore, the administration of CycloRGDyk blocked the effects of exercise training in reducing excessive mitochondrial fission and inflammation in the soleus muscle of diabetic rats, as well as the positive effects of exercise training on improving hyperlipidemia and insulin sensitivity in diabetic rats (p < 0.05). These results indicate that regular exercise training effectively ameliorates insulin resistance and glucolipid metabolic dysfunction, and reduces inflammation in skeletal muscle. These benefits are partially mediated by reductions in mitochondrial fission through the irisin/AMPK signalling pathway.

Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer's disease.

Neuroinflammation is a pathological hallmark of Alzheimer's disease (AD), characterized by the stimulation of resident immune cells of the brain and the penetration of peripheral immune cells. These inflammatory processes facilitate the deposition of amyloid-beta (Aß) plaques and the abnormal hyperphosphorylation of tau protein. Managing neuroinflammation to restore immune homeostasis and decrease neuronal damage is a therapeutic approach for AD. One way to achieve this is through exercise, which can improve brain function and protect against neuroinflammation, oxidative stress, and synaptic dysfunction in AD models. The neuroprotective impact of exercise is regulated by various molecular factors that can be activated in the same way as exercise by the administration of their mimetics. Recent evidence has proven some exercise mimetics effective in alleviating neuroinflammation and AD, and, additionally, they are a helpful alternative option for patients who are unable to perform regular physical exercise to manage neurodegenerative disorders. This review focuses on the current state of knowledge on exercise mimetics, including their efficacy, regulatory mechanisms, progress, challenges, limitations, and future guidance for their application in AD therapy.

Exercise ameliorating myocardial injury in type 2 diabetic rats by inhibiting excessive mitochondrial fission involving increased irisin expression and AMP-activated protein kinase phosphorylation.

PURPOSE: Though exercise generates beneficial effects on diabetes-associated cardiac damage, the underlying mechanism is largely unclear. Therefore, we prescribed a program of 8-week treadmill training for type 2 diabetes mellitus (T2DM) rats and determined the role of irisin signaling, via interacting with AMP-activated protein kinase (AMPK), in mediating the effects of exercise on myocardial injuries and mitochondrial fission. METHODS: Forty 8-week-old male Wistar rats were randomly divided into groups of control (Con), diabetes mellitus (DM), diabetes plus exercise (Ex), and diabetes plus exercise and Cyclo RGDyk (ExRg). Ex and ExRg rats received 8 weeks of treadmill running, and the rats in the ExRg group additionally were treated with a twice weekly injection of Cyclo RGDyk, an irisin receptor-αV/ß5 antagonist. At the end of the experiment, murine blood samples and heart tissues were collected and analyzed with methods of ELISA, Western blot, real-time quantitative polymerase chain reaction, as well as immunofluorescence staining. RESULTS: Exercise effectively mitigated T2DM-related hyperglycemia, hyperinsulinemia, lipid dysmetabolism, and inflammation, which could be diminished by Cyclo RGDyk treatment. Additionally, exercise alleviated T2DM-induced myocardial injury and excessive mitochondrial fission, whereas the beneficial effects were blocked by the administration of Cyclo RGDyk. T2DM significantly decreased serum irisin concentrations and fibronectin type III domain-containing protein 5 (FNDC5)/irisin gene and protein expression levels in the rat heart, whereas exercise could rescue T2DM-reduced FNDC5/irisin expression. Blocking irisin receptor signaling diminished the exercise-alleviated mitochondrial fission protein expression and elevated AMPK phosphorylation. CONCLUSION: Exercise is effective in mitigating diabetes-related insulin resistance, metabolic dysfunction, and inflammation. Irisin signaling engages in exercise-associated beneficial effects on myocardial injury and excessive mitochondrial fission in diabetes rats involving elevated AMPK phosphorylation.

Exercise for prevention of falls and fall-related injuries in neurodegenerative diseases and aging-related risk conditions: a meta-analysis.

Introduction: Neurodegenerative diseases often cause motor and cognitive deterioration that leads to postural instability and motor impairment, while aging-associated frailty frequently results in reduced muscle mass, balance, and mobility. These conditions increase the risk of falls and injuries in these populations. This study aimed to determine the effects of exercise on falls and consequent injuries among individuals with neurodegenerative diseases and frail aging people. Methods: Electronic database searches were conducted in PubMed, Cochrane Library, SportDiscus, and Web of Science up to 1 January 2023. Randomized controlled trials that reported the effects of exercise on falls and fall-related injuries in neurodegenerative disease and frail aging people were eligible for inclusion. The intervention effects for falls, fractures, and injuries were evaluated by calculating the rate ratio (RaR) or risk ratio (RR) with 95% confidence interval (CI). Results: Sixty-four studies with 13,241 participants met the inclusion criteria. Exercise is effective in reducing falls for frail aging people (RaR, 0.75; 95% CI, 0.68-0.82) and participants with ND (0.53, 0.43-0.65) [dementia (0.64, 0.51-0.82), Parkinson's disease (0.49, 0.39-0.69), and stroke survivors (0.40, 0.27-0.57)]. Exercise also reduced fall-related injuries in ND patients (RR, 0.66; 95% CI, 0.48-0.90) and decreased fractures (0.63, 0.41-0.95) and fall-related injuries (0.89, 0.84-0.95) among frail aging people. For fall prevention, balance and combined exercise protocols are both effective, and either short-, moderate-, or long-term intervention duration is beneficial. More importantly, exercise only induced a very low injury rate per participant year (0.007%; 95% CI, 0-0.016) and show relatively good compliance with exercise (74.8; 95% CI, 69.7%-79.9%). Discussion: Exercise is effective in reducing neurodegenerative disease- and aging-associated falls and consequent injuries, suggesting that exercise is an effective and feasible strategy for the prevention of falls.

Irisin Regulates Cardiac Responses to Exercise in Health and Diseases: a Narrative Review.

Exercise has been recognized as an important non-pharmacological approach for the prevention, treatment, and rehabilitation of cardiovascular diseases, but the mechanisms of exercise in promoting cardiovascular health remain unclear. Exercise generates cardiac benefits via stimulating muscle to secret hundreds of myokines that directly enter circulation and target heart tissue. Therefore, inter-organ communication between skeletal muscle and heart may be one important regulating pattern, and such communication can occur through secretion of molecules, frequently known as myokines. Irisin, a newly identified myokine, is cleaved from fibronectin type III domain-containing protein 5 (FNDC5) and secreted by the stimulation of exercise. Recently, accumulating evidence focusing on the interaction between irisin and cardiac function has been reported. This review highlights the molecular signaling by which irisin regulates the benefits of exercise on cardiac function both in physiological and pathological process, and discusses the clinical potential of irisin in treating heart diseases. Exercise generates various cardiovascular benefits through stimulating skeletal muscle to secrete irisin. The exercise "hormone" irisin, both produced by exercise or recombinant form, exerts therapeutic effects in a group of cardiovascular disorders including heart failure, myocardial infarction, atherosclerosis and hypertension. However, the molecular mechanisms involved remain ambiguous.This review highlights the most up-to-date findings to bridge the gap between exercise, irisin and cardiovascular diseases, and discusses the potential clinical prospect of irisin.

Irisin at the crossroads of inter-organ communications: Challenge and implications.

The physiological functions of organs are intercommunicated occurring through secreted molecules. That exercise can improve the physiological function of organs or tissues is believed by secreting myokines from muscle to target remote organs. However, the underlying mechanism how exercise regulates the inter-organ communications remains incompletely understood yet. A recently identified myokine-irisin, primarily found in muscle and adipose and subsequently extending to bone, heart, liver and brain, provides a new molecular evidence for the inter-organ communications. It is secreted under the regulation of exercise and mediates the intercommunications between exercise and organs. To best our understanding of the regulatory mechanism, this review discusses the recent evidence involving the potential molecular pathways of the inter-organ communications, and the interactions between signalings and irisin in regulating the impact of exercise on organ functions are also discussed.

The Dose-Response Associations of Sugar-Sweetened Beverage Intake with the Risk of Stroke, Depression, Cancer, and Cause-Specific Mortality: A Systematic Review and Meta-Analysis of Prospective Studies.

The associations between sugar-sweetened beverage (SSB) consumption and the risk of stroke, depression, cancer, and cause-specific mortality have not been determined, and the quantitative aspects of this link remain unclear. This meta-analysis therefore conducted a systematic review and dose-response analysis to determine their causal links. The database searches were conducted in PubMed, Cochrane library, Embase, Web of Science up to 10 November 2021. The intervention effects were evaluated by relative risk (RR) with 95% confidences (CI). Thirty-two articles met the inclusion criteria. Higher levels of SSB consumption significantly increased the risk of stroke (RR 1.12, 95% CI 1.03-1.23), depression (1.25, 1.11-1.41), cancer (1.10, 1.03-1.17), and all-cause mortality (1.08, 1.05-1.11) compared with none or lower SSB intake. The associations were dose-dependent, with per 250 mL increment of SSB intake daily increasing the risk of stroke, depression, cancer, and all-cause mortality by RR 1.09 (1.03-1.15), 1.08 (1.06-1.10), 1.17 (1.04-1.32), and 1.07 (1.03-1.11), respectively. The link was curved for depression and cancer risk (pnon-linear < 0.05). Subgroup analysis suggested that higher SSB intake increased ischemic stroke by 10%, CVD-caused mortality by 13%, and cancer-caused mortality by 6.0% than none or lower SSB consumption. It is suggested that SSB accounts for a leading risk factor of stroke, depression, cancer, and mortality, and that the risk rises in parallel with the increment of SSB intake (and is affected by participant characteristics).

Exercise improves bone formation by upregulating the Wnt3a/ß-catenin signalling pathway in type 2 diabetic mice.

BACKGROUND: The bone formation ability of type 2 diabetes is inhibited, and exercise can effectively improve the bone formation of T2DM. However, whether exercise can mediate the Wnt3a/ß-catenin pathway to improve the mechanism of bone formation and metabolism still needs further research. METHODS: A T2DM mouse model was established by a high-fat diet and STZ injection, and the mice were trained with swimming and downhill running exercise. Alizarin red staining is used to observe the changes of the left femoral trabecular bone; micro-CT is used to analyze the trabecular and cortical BMD, BV/TV, BS/BV, BS/TV, Tb.Th, Tb.Sp; the ALP staining of skull was used to observe the changes in ALP activity of bone tissues at the skull herringbone sutures; ALP staining was performed to observe the changes in the number of OBs and ALP activity produced by differentiation; Quantitative PCR was used to detect mRNA expression; Western blot was used to detect protein expression levels. RESULTS: When the Wnt3a/ß-catenin pathway in the bones of T2DM mice was inhibited, the bone formation ability of the mice was significantly reduced, resulting in the degradation of the bone tissue morphology and structure. Swimming caused the significant increase in body weight and Runx2 mRNA expression, while downhill running could significantly decrease the body weight of the mice, while the tibia length, wet weight, and the trabecular morphological structure of the distal femur and the indexes of bone histomorphology were significantly improved by activating the Wnt3a/ß-catenin pathway. CONCLUSIONS: Bone formation is inhibited in T2DM mice, leading to osteoporosis. Downhill running activates the Wnt3a/ß-catenin pathway in the bones of T2DM mice, promotes OB differentiation and osteogenic capacity, enhances bone formation metabolism, and improves the bone morphological structure.

The Efficacy of Brief School-Based Exercise Programs in Improving Pubertal Bone Mass and Physical Fitness: A Randomized Controlled Trial.

PURPOSE: To examine the effects of three types of school-based exercises on bone health and physical fitness function in Chinese boys and girls. METHODS: One hundred and seventy-four Chinese boys and girls were randomly assigned into four groups: (1) sham exercise (ShEx); (2) high-impact exercise (HiEx); (3) high-impact exercise with various directions (HiExVi); and (4) high-intensity interval exercise (HiInEx). Speed of sound (SOS) and physical fitness parameters were determined before and after six-month intervention. RESULTS: At the end of six-month intervention, participants in all groups show an increment of SOS compared with the baseline (p < 0.05), and the changes were higher in HiEx (mean: 38.878 m/s, 95% CI: 32.885~44.872, p = 0.001) and HiExVi groups (49.317 m/s, 42.737~55.897, p < 0.001) compared with ShEx group (20.049 m/s, 13.751~26.346). Six-month exercise training generated a reduction of percent of body fat (PBF) and waist-hip ratio (WHR) (p < 0.05). The decrease of PBF was greater in HiExVi (-1.222%, -1.820~-0.624, p = 0.012) and HiInEx groups (-1.395%, -1.809~-0.982, p = 0.003), whereas the reduction of WHR was larger in HiEx (-0.026, -0.039~-0.014, p = 0.009), HiExVi (-0.024, -0.036~-0.012, p = 0.021), and HiInEx groups (-0.035, -0.046~-0.024, p < 0.001) compared with ShEx group. Balance function (BLF), vital capacity (VC), standing long jump (SLJ), and sit up (SU) increased in all intervention groups (p < 0.05). The BLF increased in HiEx (6.332 s, 4.136~8.528, p = 0.001), HiExVi (10.489 s, 8.934~12.045, p < 0.001), and HiInEx groups (9.103 s, 7.430~10.776, p < 0.001) showed a greater change than that of ShEx group (1.727 s, 0.684~2.770). The increment of VC (273.049 mL, 199.510~346.587, p < 0.001) and SU (2.537 times/min, 0.639~4.435, p = 0.017) was higher in HiInEx group, whereas the accrual in SLJ was larger in HiExVi (7.488 cm, 4.936~10.040, p = 0.007) compared with ShEx group (58.902 mL, 7.990~109.814; -0.463 times/min, -2.003~1.077; 1.488 cm, -0.654~3.630). CONCLUSION: The brief school-based exercises were effective in improving schoolchildren's health, but they showed different effects, with HiEx mostly improving bone health, HiInEx largely benefiting physical fitness function, and HiExVi enhancing both bone and physical fitness.

Irisin Regulating Skeletal Response to Endurance Exercise in Ovariectomized Mice by Promoting Akt/ß-Catenin Pathway.

Purpose: Thought irisin is recognized as a pivotal modulator for bone formation, its role in regulating skeletal response to exercise training remains unknown. Therefore, we aimed to determine the change of irisin in response to 8-week exercise training and its role in regulating the effects of exercise on bone loss in ovariectomized (Ovx) mice. Methods: Forty 3-month old female C57BL/6 mic were randomly allocated into four groups: (1) Sham-operated (Sham); (2) ovariectomized; (3) Ovx plus 8-week downhill running exercise (Ex); (4) Ovx plus exercise and received twice weekly injection of cyclo RGDyk protein (a putative anti-irisin receptor agents) (ExRg). Results: Ex group showed enhanced cortical and trabecular volumetric bone mineral density (vBMD) (p < 0.05), improved bone microarchitecture, and increased intensity of alkaline phosphatase positive (ALP+) cells compared with Ovx group. However, cyclo RGDyk administration weakened the exercise-related improvement of vBMD, BV/TV, and ALP intensity in bone. Serum estradiol, irisin, and bone alkaline phosphatase were higher, whereas circulating tartrate-resistant acid phosphatase was lower in Ex group compared with Ovx group (p < 0.05). Exercise promoted mRNA expression of fibronectin type III domain-containing protein 5 (FNDC5), Akt and ß-catenin, and enhanced protein levels of FNDC5, the ratio of phosphorylated Akt (p-Akt) to Akt, and ß-catenin (p < 0.05). When irisin pathways were blocked with cyclo RGDyk, increment of Akt, p-Akt/Akt, and ß-catenin in Ex mice were attenuated. Conclusion: It is suggested that irisin plays a potential role in regulating skeletal response to exercise partly through its interaction with Akt/ß-catenin pathways.

Oyster oligopeptide improving cyclophosphamide-induced partial androgen deficiency of the aging male by promotion of testosterone synthesis.

AIM: The aim of this study was to investigate the effect of oyster oligopeptide (OOP) at different doses on testosterone secretion and its regulating mechanism in partial androgen deficiency syndrome of aging male. METHODS: The cyclophosphamide-induced partial androgen deficiency syndrome of the aging male rats were treated with a low, medium and high dose of OOP for 6 weeks. RESULTS: Cyclophosphamide could decrease levels of total testosterone and luteinizing hormone in serum, and testosterone and glutathione peroxidase in testis, and increase malondialdehyde, and downregulate the mRNA expression of steroidogenic acute regulatory protein, steroidogenic acute regulatory-related lipid transfer domain 7 and P450 cholesterol side chain cleavage enzyme in testis (P < 0.05). All these changes were reversed by OOP co-administration with different doses, although, OOP at a low dose did not increase serum testosterone, luteinizing hormone and testicular glutathione peroxidase levels. CONCLUSIONS: OOP treatment with different doses can effectively reduce oxidative stress in testicular tissue, promote the synthesis of testosterone and then prevent the formation of partial androgen deficiency syndrome of the aging male, with optimal effect at medium dose. Geriatr Gerontol Int 2021; 21: 268-275.

The efficacy and safety of exercise for prevention of fall-related injuries in older people with different health conditions, and differing intervention protocols: a meta-analysis of randomized controlled trials.

BACKGROUND: Whether exercise prevents fall-related injuries in different health conditions and with different training protocols is still unclear. This study aimed to determine the effect of exercise on fall-related injuries by participant characteristics and divergent exercise protocols. The safety and compliance of exercise were also examined. METHODS: Electronic database searches were conducted in PubMed, Web of Science, and EMBASE for randomised controlled trials that evaluated the influence of exercise on fall-induced injuries in older people. RESULTS: Twenty-five trials met the inclusion criteria. Exercise significantly reduced the risk of fall-related injuries in older adults, risk ratio (RR) 0.879 [95% confidence interval (CI) 0.832-0.928]. Among the injuries, events needing medical care or resulting fractures were also decreased by exercise intervention, with RR 0.681 (0.562-0.825) and 0.561 (0.366-0.860), respectively. When analysis was stratified by participant characteristics and exercise protocols, we found that participants at high risk of falling, or with osteoporosis, were sensitive to exercise intervention. Combined exercise protocols and balance training were the most effective exercise types in reducing fall-related injuries. Exercise-associated beneficial effects were even significant in very old people (≥80 years) and across the duration of interventions (< 6 months, 6 to 12 months and ≥ 12 months). Exercise only generated a very low injury rate per participant year (0.002, 95% CI 0-0.05) and showed relatively good compliance of exercise (as reported in the included papers) (78.5, 95% CI 72.8-84.2%). CONCLUSIONS: Exercise is effective in preventing fall-induced injuries across a variety of baseline participant characteristics and exercise protocols. Exercise was associated with a low injury rate and had a good compliance, suggesting it is a feasible approach to managing fall-related injuries.

Icariin Treatment Enhanced the Skeletal Response to Exercise in Estrogen-Deficient Rats.

Estrogen deficiency frequently leads to a fall in estrogen receptor- (ER) numbers and then reduces the skeletal response to mechanical strain. It, however, is still unclear whether phytoestrogen administration will enhance the effects of exercise on the estrogen-deficient bone loss. This study aimed to determine the effect of Icariin treatment on the response of osteogenic formation to exercise in ovariectomized (OVX) rats. Thirty-two 3-month old female Sprague-Dawley rats were randomly allocated into four groups: (1) Sham-operated (SO); (2) OVX; (3) OVX plus exercise (EX); and (4) OVX plus exercise and Icariin (EI). After 8-week interventions, the rats were killed and samples were collected for bone morphometry, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. EI interventions showed a greater improvement for the OVX-induced bone loss and the elevated serum tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) compared with EX only. Both EX and EI interventions bettered the OVX-related reduction of BV/TV and trabecular number and thickness, and decreased the enlargement of trabecular bone separation (Tb. Sp); the improvement for BV/TV and Tb. Sp was greater in EI group. Furthermore, EX and EI treatment significantly increased the number of ALP+ cells and mineralized nodule areas compared with OVX group; the change was higher in EI group. Additionally, in comparison to OVX rats, the protein and mRNA expression of -catenin, phosphorylated-Akt (p-Akt) or Akt, ER, and Runt-related transcription factor 2 (Runx2) in osteoblasts were elevated in EX and EI intervention rats, with greater change observed in EI group. The upregulated -catenin and Akt mRNA levels in EX and EI groups was depressed by ICI182780 treatment, and the difference in -catenin and Akt mRNA levels between EX and EI groups was no longer significant. Conclusively, the combination of Icariin and exercise significantly prevent OVX-induced bone loss and increase osteoblast differentiation and the ability of mineralization compared with exercise alone; the changes might be regulated partly by ER/Akt/-catenin pathway.

The effects of cigarette smoking on the associations between sitting time and all-cause mortality: a meta-analysis.

BACKGROUND: Sedentary behavior is recognized as an independent risk factor for mortality, but it remains unclear whether cigarette smoking will aggravate the detrimental effects of prolonged sitting on mortality. This study examined the impact of cigarette smoking on the relationship between sitting time and all-cause mortality in adults. METHODS: Electronic database searches were conducted in PubMed, Web of Science, and the EMBASE up to 1 June 2017. Prospective studies that reported sitting time, percent of current smokers, and all-cause mortality were included. Data were extracted independently by two authors. RESULTS: Ten prospective studies met the inclusion criteria. These studies included 850990 adults who were followed up for 2-15.7 years, during which 64 781 died (7.6%). Generally, during follow-up sitting time showed a dose-response relationship with all-cause mortality, with each 1 h increment of sitting time per day accounting for hazard ratio (HR) of mortality 1.02 (95%CI, 1.02-1.03). The relationship remained significant when stratified by the quartiles of smoking populations (≤8.4%, 8.5%-12.6%, 12.7%-27.9%, and ≥28.0%), and the risk of sitting time-related mortality increased parallel to the increment of the percent of smoking populations, with HRs 1.02 (95%CI, 1.02-1.03), 1.03 (95%CI, 1.02-1.03), 1.04 (95%CI, 1.03-1.04) and 1.06 (95%CI, 1.06-1.06), respectively. The associations between the risk of prolonged sitting-related mortality and the percent of smoking populations were linear (P = 0.032). CONCLUSIONS: Cigarette smoking significantly aggravated the detrimental effects of sitting time on all-cause mortality. Our findings provided further evidence on the harmful effects of smoking combing prolonged sitting on adult health.

The Effectiveness of Combined Exercise Interventions for Preventing Postmenopausal Bone Loss: A Systematic Review and Meta-analysis.

Study Design Systematic review and meta-analysis. Background It remains unclear whether exercise combining different types of physical activities (combined exercise interventions) would effectively preserve postmenopausal women's bone mineral density (BMD) at different sites. Objective To examine the impact of combined exercise interventions on lumbar spine, femoral neck, total hip, and total body BMD in postmenopausal women. Methods An electronic database search was conducted in PubMed, EMBASE, SPORTDiscus, and Web of Science up to January 1, 2016. Randomized controlled trials that conducted combined exercise interventions and reported BMD values in postmenopausal women were included. Two authors independently extracted the data from individual studies. The primary end point was the change in BMD values from baseline to follow-up. The effect sizes were estimated by the standardized mean difference (SMD) methods using fixed-effects models. Results Eleven randomized controlled trials including 1061 postmenopausal women met the inclusion criteria. The levels of between-study heterogeneity were relatively low (I2<50%). Exercise integrating different physical activities significantly increased lumbar spine (SMD, 0.170; 95% confidence interval [CI]: 0.027, 0.313; P = .019), femoral neck (SMD, 0.177; 95% CI: 0.030, 0.324; P = .018), total hip (SMD, 0.198; 95% CI: 0.037, 0.359; P = .016), and total body (SMD, 0.257; 95% CI: 0.053, 0.461; P = .014) BMD. Combined exercise interventions generated a beneficial effect on femoral neck BMD (SMD, 0.219; 95% CI: 0.034, 0.404; P = .020) in groups with women aged younger than 60 years, and significantly improved lumbar spine BMD (SMD, 0.349; 95% CI: 0.064, 0.634; P = .016) in groups with women aged 60 years or older. Conclusion Our findings suggest that combined exercise interventions appear to be effective in preserving postmenopausal women's BMD at the lumbar spine, femoral neck, total hip, and total body. Level of Evidence Therapy, level 1a. J Orthop Sports Phys Ther 2017;47(4):241-251. Epub 3 Mar 2017. doi:10.2519/jospt.2017.6969.

Exercise interventions and prevention of fall-related fractures in older people: a meta-analysis of randomized controlled trials.

Background: This meta-analysis aimed to determine whether exercise interventions were effective in preventing fall-related fractures in older people. The treatment effects on rate of falls, leg strength and balance were also examined. Methods: An electronic database search was conducted in PubMed, EMBASE, the Cochrane library and PEDro up to 1 September 2015. Randomized controlled trials (RCTs) that conducted exercise interventions and reported fall-related fracture data in older people were included. The primary outcome was the treatment effects on fall-related fractures determined by relative risk (RR) and 95% confidence interval (CI). The treatment effects on falls, leg strength and balance were also reported using rate ratio (RaR) with 95% CI and standardized mean difference (SMD) with 95% CI, respectively. Random effects models were used for meta-analysis. Results: Fifteen studies including 3136 participants met the inclusion criteria. Exercise had a beneficial effect on reduction of fall-related fractures, with pooled estimates of RR 0.604 (95% CI 0.453 - 0.840, P = 0.003, I 2 = 0%). The rate of falls (RaR 0.856, 95% CI 0.778 - 0.941, P = 0.001, I 2 = 45%) and leg strength (SMD 0.613, 95% CI 0.119 - 1.107, P = 0.015, I 2 = 76.7%) were also potentially affected by exercise interventions. These only had a marginally beneficial effect on balance (SMD 0.468, 95% CI -0.011 - 0.947, P = 0.055, I 2 = 93.6%). Conclusions: Our findings implied that exercise interventions were effective in preventing fall-related fractures and reducing risk factors of fall-related fractures in older people.

Upregulated Cellular Expression of IL-17 by CD4+ T-Cells in Osteoporotic Postmenopausal Women.

AIM: The study aimed to investigate cellular expression of IL-17 by CD4+ T-cells in osteoporotic postmenopausal women. METHODS: We enrolled 25 postmenopausal women with osteoporosis (PostMO) and 25 postmenopausal women with normal bone mineral density measurements (PostM) to examine the production of IL-17, tumor necrosis factor α (TNFα) and receptor activator of nuclear factor x03BA;-B ligand (RANKL) by CD4+ T-cells and IL-17, RORx03B3;t, TNFα and RANKL mRNA levels in CD4+ T-cells. Circulating concentrations of IL-17 along with IL-6, TNFα, RANKL and osteoprotegerin (OPG) were also determined. RESULTS: Osteoporotic postmenopausal women had higher serum concentrations of IL-17 (3.7 ± 1.3 vs. 2.5 ± 1.1 ng/ml, p = 0.042), IL-6 (158 ± 56 vs. 105 ± 39 pg/ml, p = 0.044), TNFα (138 ± 41 vs. 74 ± 11 pg/ml, p < 0.001) and OPG (1.7 ± 0.4 vs. 1.3 ± 0.4 ng/ml, p = 0.039) than healthy controls. The IL-17-producing CD4+ T-cells were higher in the PostMO group than in the PostM group (7.1 ± 2.4 vs. 4.9 ± 1.4%, p = 0.0015). Additionally, osteoporotic postmenopausal women had greater mRNA levels of IL-17 (3.5 ± 2.9 vs. 1.2 ± 1.0%, p = 0.019) and RORx03B3;t (5.7 ± 2.5 vs. 2.2 ± 1.0%, p < 0.001) in CD4+ T-cells than in healthy controls. CONCLUSIONS: Our findings implied that the upregulated production of IL-17 may play an important role in regulating bone loss in osteoporotic postmenopausal women.

Effects of Oestrogen Treatment on Skeletal Response to Exercise in the Hips and Spine in Postmenopausal Women: A Meta-Analysis.

BACKGROUND: It is recognized that low oestrogen status impairs the skeletal response to mechanical loading in elderly women; therefore, oestrogen administration is expected to increase the osteogenic response to mechanical strain. OBJECTIVES: This meta-analysis aimed to evaluate the combined effects of hormone replacement therapy (HRT) and exercise on femoral neck and lumbar spine bone mineral density (BMD) in postmenopausal women, in comparison with the effects of exercise-only intervention. METHODS: A systematic literature search was conducted in PubMed, Embase, SPORTDiscus and ProQuest up to May 1, 2014, to ascertain the influence of oestrogen administration and exercise on BMD in postmenopausal women. The study quality and potential publication bias of the included trials were evaluated. The primary end point was the change in BMD from baseline to follow-up. The effect sizes were estimated in terms of the standardized mean difference (SMD). Subgroup analysis was conducted on the basis of exercise categories. RESULTS: Six studies with a total of 764 postmenopausal women (aged between 51.8 ± 2.9 and 68.0 ± 3.0 years) met the inclusion criteria. The included studies had low and high levels of heterogeneity of hip outcomes (I2 = 0.0 %) and spine outcomes (I2 = 80.8%), respectively. Fixed- and random-effects models were used for calculating the effect size estimates. The pooled effect sizes associated with the combined interventions of HRT and exercise were significant for femoral neck BMD (SMD 0.220, 95% confidence interval [CI] 0.011-0.429, p = 0.039) and lumbar spine BMD (SMD 0.729, 95% CI 0.186-1.273, p = 0.009) in comparison with the exercise-only intervention. The mixed loading exercise programmes were sensitive to HRT in preventing postmenopausal bone loss in the spine (SMD 1.073, 95% CI 0.140-2.005, p = 0.024) in comparison with single-mode exercise. CONCLUSIONS: Our findings indicate that oestrogen treatment significantly increases the skeletal response to exercise training in both the hips and the spine in postmenopausal women, which implies that the combination of oestrogen administration and exercise may generate greater effects.

Antiresorptive agents increase the effects of exercise on preventing postmenopausal bone loss in women: a meta-analysis.

BACKGROUND AND OBJECTIVES: It remains unknown whether the combination of antiresorptive agents and exercise would generate additive effects on bone mineral density (BMD) in postmenopausal women, though their separate roles in preventing bone loss have been well established. This meta-analysis aimed to evaluate the combined impact of antiresorptive treatment and exercise on the lumbar spine and femoral neck BMD in postmenopausal women compared with an exercise-only intervention. METHODS: A systematic literature search of PubMed, EMBASE, SportDiscus and ProQuest up to Jun 2014 was conducted to identify the influence of antiresorptive agents and exercise on BMD in postmenopausal women. The study quality of the included trials was evaluated. The effect sizes were estimated by calculating the standardized mean difference (SMD). Subgroup analyses were conducted by pharmacological regimens and exercise categories. RESULTS: Nine studies with a total of 1,248 postmenopausal women met the inclusion criteria. The heterogeneity between the studies was evident at the spine (I² = 78.7%) and hip (I² = 41.7%) measurements; random-effects models were used in the data analysis. The pooled effect sizes associated with the combined interventions of antiresorptive agents and exercise were significant at the lumbar spine BMD (SMD = 0.511, 95% CI = 0.118-0.904, p = 0.011). Combining hormone replacement therapy (HRT) and exercise training generated greater beneficial effects on lumbar spine (SMD = 0.729, 95% CI = 0.186-1.273, p = 0.009) and femoral neck BMD (SMD = 0.220, 95% CI = 0.0110-429, p = 0.039) than the exercise-only intervention. Impact exercise was sensitive to antiresorptive agents in preventing postmenopausal bone loss both at the spine (SMD = 1.252, 95%CI = 0.465-2.039, p = 0.002) and hips (SMD = 0.414, 95%CI = 0.106-0.723, p = 0.008). CONCLUSIONS: Our findings indicate that antiresorptive agents significantly increase the impact of exercise on the prevention of bone loss in postmenopausal women, which implies that the combination of antiresorptive agents and exercise may generate additive effects.

Efficiency of jumping exercise in improving bone mineral density among premenopausal women: a meta-analysis.

BACKGROUND: Jumping exercise is frequently regarded as an optimum strategy for increasing pubertal bone growth, but its role in promoting or preserving adult bone mineral density (BMD) is still undefined. OBJECTIVES: This meta-analysis aimed to evaluate the evidence for the influence of jumping exercise on BMD in premenopausal women and to define the effectiveness of high-impact exercise in improving or maintaining female bone health. METHODS: We searched MEDLINE, PubMed, EMBASE, SPORTDiscus, Google Scholar and BIOSIS up to 1 September 2013 for jumping exercise influence on BMD in premenopausal women. The search terms used were 'jumping', 'skipping', 'brief exercise', 'high impact', 'bone density', 'BMD', 'femoral neck', 'lumbar spine', and 'trochanter', and the search was limited to females. Six papers met the search criteria. RESULTS: Six studies on BMD in the femoral neck (Q = 2.63, p = 0.854, I (2) = 0.0 %), trochanter (Q = 2.10, p = 0.10, I (2) = 0.0 %) and lumbar spine (Q = 1.17, p = 0.979, I (2) = 0.0 %) were highly homogenous in determining skeletal responses to jumping exercise. Jumping exercise significantly increased BMD in the femoral neck {weighted mean difference (WMD) [fixed effect] = 0.017 g/cm(2), 95 % confidence interval (CI) 0.014-0.20, p < 0.001} and trochanter (WMD [fixed effect] = 0.021, 95 % CI 0.018-0.024, p < 0.001). However, the lumbar spine seemed to benefit less from such high-impact exercise (p = 0.181). Visual inspection of the plots implicated some degree of asymmetry, indicating a slightly positive treatment effect at the femoral neck and trochanter sites. CONCLUSIONS: Based on meta-analysis of existing studies, the sensitivity of skeletal response to jumping exercise in premenopausal women is significant and site-specific, with significant benefit from high-impact exercise noted, especially at the hip.