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The Efficacy of Nitrates for Bone Health: A Systematic Review and Meta-Analysis of Observational and Randomized Controlled Studies.
Liu, W, Meng, Z, Wang, G
Frontiers in endocrinology. 2022;:833932
Abstract
BACKGROUND Although some studies have found that nitrates were beneficial for bone health, the findings are inconsistent. To assess the efficacy of nitrates for bone health, we conducted a meta-analysis. METHODS PubMed, EMBASE databases, Cochrane Library for relevant articles published before December 2021 were searched. All observational and randomized controlled studies that reporting bone mineral density (BMD), fractures with nitrates use were included. A meta-analysis was performed to calculate risk ratios (RRs) for fractures, change differences for bone mineral density. RESULTS Four cohort studies and two case-control studies examining the association between nitrates use and fractures were identified. The nitrates use was not associated with any fracture risk (RR = 0.97; 95% CI, 0.94-1.01; I2 = 31.5%) and hip fracture (RR = 0.88; 95% CI, 0.76-1.02; I2 = 74.5%). Subgroup analyses revealed no differences in fracture risk, whereas two cohort studies revealed a reduced risk of hip fracture (RR = 0.71, 95% CI, 0.58-0.86, I2 = 0.0%). There were no statistically significant differences in BMD percent changes at lumbar spine (WMD = -0.07, 95% CI,-0.78-0.65; I2 = 0.0%), total hip (WMD = -0.42, 95% CI,-0.88-0.04; I2 = 0.0%), femoral neck (WMD = -0.38, 95% CI,-1.02-0.25; I2 = 0.0%), or total body (WMD = -0.17, 95% CI,-0.51-0.17; I2 = 0.0%) in two randomized controlled trials (RCTs) compared with a placebo. Another two RCTs compared nitrates with alendronate. Nitrates were comparable to alendronate in increasing bone mineral density at lumbar spine (WMD = 0.00, 95% CI,-0.01-0.02; I2 = 0.0%). Besides, the most common adverse effect was headache, contributing to low adherence to therapy. CONCLUSION Our meta-analysis showed no association between nitrates use and fractures in observational studies. The results of RCTs on the usage of nitrates and their effects on BMD were inconsistent. High-quality, long-term studies are needed to clarify the efficacy of nitrates for bone health.
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Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials.
Li, Q, Yang, G, Xu, H, Tang, S, Lee, WY
BMC complementary medicine and therapies. 2021;(1):214
Abstract
BACKGROUND The results from clinical trials have revealed that the effects of resveratrol supplementation on bone mineral density (BMD) and bone biomarkers are inconsistent. Our objective was to determine the effects of resveratrol supplementation on BMD and serum bone biomarkers. METHODS PubMed, Cochrane library, EMBASE, Web of science and Scopus were searched up to August 24, 2020. Two reviewers independently performed the articles search and screen according to defined selection criteria. The study quality of the randomized controlled trials (RCTs) was evaluated with the Cochrane scoring system. Heterogeneity among studies was examined by Cochrane Q test. Retrieved data were pooled after mean differences (MD) were computed between two groups for BMD and serum biomarkers. Subgroup analyses were performed to evaluate a potential difference in terms of dose of resveratrol and intervention duration. Sensitivity analysis was executed by omitting studies with imputed values in order to evaluate the influence of these studies on the overall results. RESULTS Ten eligible studies involving 698 subjects were included in this meta-analysis with 401 participants receiving resveratrol and 297 receiving placebo. Supplementation of resveratrol had no statistically significant effects on areal bone mineral density (aBMD) at lumbar spine (MD: -0.02, 95% CI: - 0.05, 0.01, p = 0.26, I2 = 6%), total hip BMD (MD: -0.01, 95% CI: - 0.04, 0.02, p = 0.65, I2 = 0%), and whole body BMD (MD: 0.00, 95% CI: - 0.02, 0.02, p = 0.74, I2 = 0%). Supplementation of resveratrol also did not result in significant change in bone serum markers, including serum alkaline phosphatase (ALP), bone alkaline phosphatase (BAP), osteocalcin (OCN), procollagen I N-terminal propeptide (PINP), C-terminal telopeptide of type I collagen (CTX) and parathyroid hormone (PTH). Subgroup analysis showed the effect of resveratrol supplementation on BMD and serum bone markers were similar in trails of different doses, intervention duration, and pathological conditions of the participants. CONCLUSION Resveratrol supplementation did not show any significant effect on BMD or serum bone markers with the current evidence. Further investigation with more well-organized multicentre randomized trial is warranted.
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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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Effects of dairy products on bone mineral density in healthy postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.
Shi, Y, Zhan, Y, Chen, Y, Jiang, Y
Archives of osteoporosis. 2020;(1):48
Abstract
PURPOSE To investigate the effects of dairy products on bone mineral density (BMD) in healthy postmenopausal women. METHODS The EMBASE, Cochrane Library, Medline, and Web of Science databases were systematically searched for relevant studies. The pooled standardized mean difference (SMD) with its 95% confidence interval (CI) was used as the effect size. Subgroup analysis and Begg's test were conducted. RESULTS Six studies with a total of 618 participants were included in the meta-analysis. Milk was the main dairy product used in the trials. There was a significant association between dairy product consumption and BMD of the lumbar spine (SMD 0.21, 95% CI 0.05-0.37, P = 0.009), femoral neck (SMD 0.36, 95% CI 0.19-0.53, P < 0.001), total hip (SMD 0.37, 95% CI 0.20-0.55, P < 0.001), and total body (SMD 0.58, 95% CI 0.39-0.77, P < 0.001). Subgroup analysis suggested that there was a positive effect of dairy product consumption on the BMD of the total hip starting from 12 months and the femoral neck starting from 18 months. There was also a positive association with the BMD in the four sites in people living in low-calcium intake countries. CONCLUSION This meta-analysis provides evidence that dairy products can increase BMD in healthy postmenopausal women. Dairy product consumption should be considered an effective public health measure to prevent osteoporosis in postmenopausal women.
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Fermented Milk Products and Bone Health in Postmenopausal Women: A Systematic Review of Randomized Controlled Trials, Prospective Cohorts, and Case-Control Studies.
Ong, AM, Kang, K, Weiler, HA, Morin, SN
Advances in nutrition (Bethesda, Md.). 2020;(2):251-265
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Abstract
Milk and milk product consumption is positively associated with bone mineral density (BMD). Emerging evidence suggests that fermented milk products (FMPs) may have specific beneficial effects on skeletal health. We conducted a systematic review and meta-analysis to assess the effect of FMPs on bone health indicators in postmenopausal women given their increased risk for osteoporosis and fragility fractures. Electronic databases were searched for randomized controlled trials (RCTs) and prospective cohort and case-control studies that examined the relation between FMPs and bone health outcomes (fracture incidence, BMD, BMD T-score, and percentage change in bone turnover markers) in postmenopausal women. Two reviewers independently conducted abstract and full-text screenings and data extractions. Risk of bias was assessed using the RoB 2.0 tool and the Newcastle-Ottawa scale for interventional and observational studies. Pooled RRs were obtained using a random-effects model by the DerSimonian-Laird method. Three RCTs, 3 prospective cohorts, and 3 case-control studies met the inclusion criteria. Results of the meta-analysis of 3 cohort studies (n = 102,819) suggest that higher yogurt consumption was associated with reduced hip fracture risk (pooled RR: 0.76; 95% CI: 0.63, 0.92, I2 = 29%), but no difference in hip fracture risk was found between higher and lower cheese consumption (pooled RR: 0.89; 95% CI: 0.73, 1.10, I2 = 0%). Case-control studies revealed that cheese intake had either a null or a protective effect against osteoporosis (BMD T-score ≤-2.5). Daily yogurt or cheese intervention (<2 mo) decreased bone resorption marker concentrations, but had no effect on bone formation markers. In postmenopausal women, of the FMPs studied, only greater yogurt consumption was associated with a reduced risk of hip fracture compared with low or no intake. Daily cheese intake may be associated with higher BMD T-scores, but evidence was limited. Additional and longer-term trials examining these relations are warranted.
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Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials.
Akhlaghi, M, Ghasemi Nasab, M, Riasatian, M, Sadeghi, F
Critical reviews in food science and nutrition. 2020;(14):2327-2341
Abstract
BACKGROUND Osteoporosis is a common bone disease characterized by reduced bone mass resulting from continuous bone resorption. METHODS PubMed, Scopus, and Embase were searched to find published trials on the effect of soy isoflavones on bone mineral density (BMD) and bone turnover markers (bone-specific alkaline phosphatase, osteocalcin, osteoprotegerin, pyridinoline, deoxypyridinoline, C-telopeptide, and N-telopeptide). Random-effects inverse-variance model was used to calculate the pooled effects. RESULTS A total of 5313 articles were found, screened, and assessed for eligibility, and finally 52 trials were included in the meta-analysis. Consumption of soy isoflavones caused significant improvement in BMD of lumbar spine (mean difference (MD) = 0.76%; 95% CI: 0.09, 1.42%; p = 0.03), hip (MD = 0.22%; 95% CI: 0.02, 0.42%; p = 0.04), and femoral neck (MD = 2.27%; 95% CI: 1.22, 3.31%; p < 0.001). Subgroup analysis showed that in all 3 sites, the improvement was significant in normal weight subjects and interventions longer than a year, although trial location and dosage were also factors influencing isoflavones' impact on BMD. Among markers of bone turnover, osteoprotegerin (MD = 5.79; 95% CI: 3.08, 8.51 pg/ml; p < 0.001), pyridinoline (MD = -5.13; 95% CI: -7.76, -2.50 nmol/mmol; p < 0.001), and C-telopeptides (MD = -0.08; 95% CI: -0.16, -0.00 ng/ml; p = 0.04) were favorably affected by isoflavones while osteocalcin and bone alkaline phosphatase did not change. Subgroup analysis of bone markers showed that in overweight/obese individuals and dosages <90 mg/day, isoflavones are more effective. CONCLUSIONS Soy isoflavones prevent osteoporosis-related bone loss in any weight status or treatment duration. They increase BMD in normal weight subjects and diminish bone resorption in overweight/obese individuals. Although bone resorption may be decelerated over short-term isoflavone consumption, periods longer than a year are probably needed to affect BMD. Isoflavones also appear benefits on bone in any dose or subjects' ethnicity.
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Isoflavone combined with exercise on bone mineral density in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.
Qiu, S, Ma, Y, Jiang, C
Journal of the Chinese Medical Association : JCMA. 2020;(7):678-685
Abstract
BACKGROUND This meta-analysis of randomized control trials (RCTs) aimed to evaluate the effects of isoflavones supplementation combined with exercise training on bone mineral density (BMD) in postmenopausal women. METHODS Two reviewers did a complete search of two electronic database (Medline, PubMed) records up to January 31, 2019. Risk of bias was classified based on the Cochrane Collaboration tool. The pooled standard mean difference (SMD) combined with 95% confidence interval (CI) was used as the effect size of BMD values. RESULTS A total of four RCTs with 609 participants were included for meta-analysis. The BMD did not differ significantly between isoflavone supplementation combined with exercise training group and placebo group (sub-whole body: SMD = 0.00, 95% CI, -0.23 to 0.24; lumbar spine: SMD = 0.15, 95% CI, -0.30 to 0.60; total hip: SMD = 0.05, 95% CI, -0.18 to 0.298; femoral neck: SMD = 0.10, 95% CI, -0.23 to 0.43; trochanter: SMD = 0.09, 95% CI, -0.14 to 0.33; ward's triangle: SMD = -0.03, 95% CI, -0.24 to 0.30). In addition, combined intervention did not provide additive effects on BMD improvements compared with exercise or isoflavone supplementation alone. The trials included in this meta-analysis were small and some had methodological limitations. CONCLUSION The present meta-analysis reveals that isoflavone supplements combined with exercise training do not significantly increase BMD in postmenopausal women. In addition, combined intervention does not provide additive effects on BMD improvements compared with exercise or isoflavone supplementation alone.
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Calcium supplementation for improving bone density in lactating women: a systematic review and meta-analysis of randomized controlled trials.
Cai, G, Tian, J, Winzenberg, T, Wu, F
The American journal of clinical nutrition. 2020;(1):48-56
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Abstract
BACKGROUND Clinical trials evaluating the effect of calcium supplementation on bone loss in lactating women have been small, with inconsistent results. OBJECTIVES We aimed to determine the effect of calcium supplementation on bone mineral density (BMD) in lactating women. METHODS An electronic search of databases was conducted from inception to January 2020. Two authors screened studies, extracted data, and assessed the risk of bias of eligible studies. Percentage change in BMD was pooled using random-effects models and reported as weighted mean differences (WMDs) with 95% CIs. Risk of bias was assessed using the Cochrane risk of bias tool. RESULTS Five randomized controlled trials including 567 lactating women were included. All had a high risk of bias. Mean baseline calcium intake ranged from 562 to 1333 mg/d. Compared with control groups (placebo/no intervention), calcium supplementation (600/1000 mg/d) had no significant effect on BMD at the lumbar spine (WMD: 0.74%; 95% CI: -0.10%, 1.59%; I2 = 47%; 95% CI: 0%, 81%; n = 527 from 5 trials) or the forearm (WMD: 0.53%; 95% CI: -0.35%, 1.42%; I2 = 55%; 95% CI: 0%, 85%; n = 415 from 4 trials). BMD at other sites was assessed in single trials: calcium supplementation had a small to moderate effect on total-hip BMD (WMD: 3.3%; 95% CI: 1.5%, 5.1%) but no effect on total body or femoral neck BMD. CONCLUSIONS Overall, the meta-analysis indicates that calcium supplementation does not provide clinically important benefits for BMD in lactating women. However, there was adequate dietary intake before supplementation in some studies, and others did not measure baseline calcium intake. Advising lactating women to meet the current recommended calcium intakes (with supplementation if dietary intake is low) is warranted unless new high-certainty evidence to the contrary from robust clinical trials becomes available. More research needs to be done in larger samples of women from diverse ethnic and racial groups.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42015022092.
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Efficacy of vitamin D fortified foods on bone mineral density and serum bone biomarkers: A systematic review and meta-analysis of interventional studies.
Tangestani, H, Djafarian, K, Emamat, H, Arabzadegan, N, Shab-Bidar, S
Critical reviews in food science and nutrition. 2020;(7):1094-1103
Abstract
Vitamin D fortified foods (VDFs) were taken into consideration due to the high prevalence of osteoporosis worldwide. However, the efficacy of VDFs on bone health has not been fully examined. The current meta-analysis was conducted in order to summarize the impacts of VDFs on serum 25-hydroxyvitamin D (25(OH)D), bone mineral density (BMD), and bone turnover markers (BTM). A systematic search up to October 2017 was done via PubMed and Scopus search engines. To pool mean differences, random-effects model (the DerSimonian-Laird estimator) was used. Heterogeneity among studies was examined by Cochrane Q test. 20 trials involving 1786 subjects were included in this meta-analysis. Based on random effect model, there were significant effects of VDFs on serum 25(OH)D (MD:16.94 nmol/L 95% CI: 13.38, 20.50; p < 0.001, I2 = 99.0%), BMD (MD: 0.03 gr/cm2; 95% CI: (0.02, 0.05); p < 0.001, I2 = 58.8%) and paratormone hormone (PTH; MD:-9.22; 95% CI: (-14.97, -3.46); p = 0.002, I2 = 98.8%). VDFs may increase serum 25(OH)D and BMD while decrease serum PTH levels. We did not find any beneficial effect of VDFs on BTM.
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The effects of testosterone on bone health in males with testosterone deficiency: a systematic review and meta-analysis.
Zhang, Z, Kang, D, Li, H
BMC endocrine disorders. 2020;(1):33
Abstract
BACKGROUND Testosterone deficiency (TD) may induce a series of clinical symptoms. Studies have shown that testosterone supplementation may prevent these unfavourable symptoms and improve patients' quality of life. Given the conflicting findings across studies, this systematic review aims to evaluate the effects and risks associated with testosterone supplementation in middle-aged or aging males with TD. METHODS Electronic databases (MEDLINE, EMBASE, PubMed, and Cochrane. Library were searched to December 2019. The risk of bias of individual included studies and the quality of the aggregate evidence were assessed using the GRADE approach. Our primary outcome was bone mineral density (BMD). Meta-analyses were performed. This systematic review was reported according to the PRISMA statement. RESULTS A total of 52 randomized controlled trials (RCTs) were included. When compared with placebo, testosterone supplementation did not increase total BMD (short-term: 1081 participants, MD - 0.01 g/cm2, 95% CI - 0.02 g/cm2 to 0.01 g/cm2; long-term: 156 participants, MD 0.04 g/cm2, 95% CI - 0.07 g/cm2 to 0.14 g/cm2), lumbar spine, hip, or femur neck BMD. Furthermore, testosterone supplementation did not decrease the risk of falling or fracture. Lastly, it was found that testosterone supplementation did not increase the risk of cardiovascular events (1374 participants, RR 1.28, 95% CI 0.62 to 2.64), all-cause mortality (729 participants, RR 0.55, 95% CI 0.29 to 1.04), or prostatic events. However, testosterone supplementation may improve sexual function and quality of life (1328 participants, MD -1.32, 95% CI - 2.11 to - 0.52). CONCLUSIONS The effect of testosterone supplementation on BMD and the risk of falls or fracture remains inconclusive. However, supplementation may benefit patients in the areas of sexual function and quality of life without increasing the risk of cardiovascular events, all-cause mortality, or prostatic events. RCTs with a longer follow-up period are still required. TRIAL REGISTRATION We registered our protocol in PROSPERO (CRD42018109738).