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Evaluating adherence, tolerability and safety of oral calcium citrate in elderly osteopenic subjects: a real-life non-interventional, prospective, multicenter study.
Rondanelli, M, Minisola, S, Barale, M, Barbaro, D, Mansueto, F, Battaglia, S, Bonaccorsi, G, Caliri, S, Cavioni, A, Colangelo, L, et al
Aging clinical and experimental research. 2024;36(1):38
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The occurrence of fractures and osteoporosis are significant concerns in elderly adults, as ageing remains one of the primary risk factors for these conditions. While the incidence of fracture and risk may vary, the incidence of fragility fractures significantly increases with advancing age, particularly after the age of 50 years. This study's aim was to evaluate the adherence, tolerability, and safety of calcium citrate administration in an "outpatient" population in routine clinical practice. This study was a non-interventional, prospective, multicentre study. Two-hundred and sixty-eight individuals (comprised 245 females (91.4%) and 23 males (8.6%)) were enrolled. Results showed a high rate of adherence to calcium citrate supplementation over a one-year period in osteopenic elderly subjects. Additionally, the incidence of adverse reactions was low (3.9%), further emphasizing the tolerability of calcium citrate. Authors concluded that future studies designed to assess the long-term impact of calcium citrate supplementation on hard endpoints, such as bone density, fractures/falls, quality of life measures and adherence are needed.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The occurrence of fractures and osteoporosis are significant concerns in older adults, as ageing remains one of the primary risk factors for this condition.
- Calcium supplementation, usually with vitamin D, is a recommended complement to other specific pharmacological treatments of osteoporosis.
- This non-interventional, prospective multicentre study suggests a 91% adherence to calcium citrate supplementation over one year in elderly osteopenic patients with generally good (80%) tolerability and 4% reporting gastrointestinal adverse effects.
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:
Introduction
A non-interventional, prospective multicentre study was conducted to evaluate the adherence, safety, and tolerability of calcium citrate supplementation in elderly osteopenic subjects.
Method:
A total of 231 Caucasian female (91%) and male (8%) participants with a median age of 70 received 500mg of calcium citrate supplementation daily for one year. Adherence was assessed based on tolerability, compliance, and persistence. Safety evaluations included monitoring of adverse reactions (ARs), physical examinations, and clinical laboratory evaluations.
Results
A total of 222 out of 231 participants (96%) completed the study. Nine subjects did not return for assessments or complete their diaries.
The primary and secondary findings of this study were as follows:
- An average adherence of 91% of oral calcium citrate supplementation was observed which was higher than the reported reference rate of 57% (p = 0.0179).
- Subjects with adherence <80% experienced a higher frequency of adverse events compared to those with adherence >80% (32/77; 42% vs 16/145%, (p = 0.0001).
- Gastrointestinal ARs were the most commonly reported, with constipation comprising 50% of all reported ARs.
- Reductions in systolic (130.7 ± 16.9 mmHg to 127.9 ± 14.5 mmHg) (p = 0.0102) and diastolic blood pressure 79.5 ± 8.7 mmHg to 77.4 ± 8.6 mmHg (baseline to V2) (p = 0.0116) were observed from baseline to the second visit.
- Positive changes were also noted in nutritional status (p = 0.0116), circulatory system disorders (p = 0.0001), and muscles/skeleton disorders (p = 0.0067) from baseline to post-baseline visit.
Conclusion:
This study revealed a 91% adherence to calcium citrate supplementation over one year in older adults with osteopenia, Additionally, the 4% incidents of ARs reported were related to gastrointestinal disorders.
Clinical practice applications:
- The prevalence of osteoporosis rises as individuals age, with approximately 10% of women at 60 years, 20% at 70 years, and 40% at 80 years.
- Calcium supplementation, usually with vitamin D, is a recommended complement to other specific pharmacological treatments of osteoporosis.
- The safety of calcium supplements remains controversial regarding an increased risk of cardiovascular events. Therefore, it is essential to investigate the safety profile of calcium in these populations.
- This study reported adherence, tolerability, and safety of calcium citrate supplementation in osteopenic elderly patients with 4% of patients reporting gastrointestinal adverse effects.
Considerations for future research:
- This study was conducted on 91% Caucasian females and 8% males with a mean age of 70 years therefore, there is a need to include more male and Asian participants from various age groups in further research.
- Future studies are needed to assess the long-term impact of calcium citrate supplementation on bone density, fractures, and quality of life.
Abstract
BACKGROUND Osteoporosis is a common concern in the elderly that leads to fragile bones. Calcium supplementation plays a crucial role in improving bone health, reducing fracture risk, and supporting overall skeletal strength in this vulnerable population. However, there is conflicting evidence on the safety of calcium supplements in elderly individuals. AIM: The aim of this study was to evaluate the adherence, safety and tolerability of calcium citrate supplementation in elderly osteopenic subjects. METHODS In this non-interventional, prospective, multicenter study, subjects received daily 500 mg calcium citrate supplementation for up to one year. Adherence was calculated based on compliance and persistence. Safety was assessed through adverse reactions (ARs), deaths, and clinical laboratory evaluations. RESULTS A total of 268 Caucasian subjects (91.4% female, mean age 70 ± 4.5 years) participated in the study. Mean adherence to treatment was 76.6 ± 29.5% and half of subjects had an adherence of 91% and ~ 33% of participants achieved complete (100%) adherence. ARs were reported by nine (3.9%) subjects, primarily gastrointestinal disorders, with no serious ARs. The frequency of all adverse events (including ARs) was significantly higher in subjects with adherence of < 80% (41.6%; 32/77) vs. those with adherence ≥ 80% (11%; 16/145, p < 0.0001). Both systolic and diastolic blood pressure decreased from baseline to follow-up visit (change of -2.8 ± 13.9 mmHg, p = 0.0102 and -2.1 ± 10.4 mmHg, p = 0.0116, respectively). CONCLUSION This study demonstrated favorable adherence to calcium citrate supplementation in elderly osteopenic subjects. The occurrence of ARs, though generally mild, were associated with lower adherence to calcium supplementation.
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Effects of an 18-month community-based, multifaceted, exercise program on patient-reported outcomes in older adults at risk of fracture: secondary analysis of a randomised controlled trial.
Talevski, J, Gianoudis, J, Bailey, CA, Ebeling, PR, Nowson, CA, Hill, KD, Sanders, KM, Daly, RM
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(5):891-900
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Fragility fractures are associated with both personal and healthcare system burdens. It is well established that bone loss leading to osteopenia or osteoporosis results in increased risk of fractures. Prescription of pharmacological agents is commonly used as first-line treatment. The aim of this study was to evaluate the effect of the Osteo-cise: Strong Bones for Life program on the patient-reported outcomes including health related quality of life (HRQoL), osteoporosis knowledge and osteoporosis attitudes and beliefs. This study is a secondary analysis of an 18-month randomised controlled trial in which participants were randomly allocated to either the community-based Osteo-cise: Strong Bones for Life program (‘Osteo-cise’) or a standard care control group. Results showed that there were no significant effects on HRQoL, osteoporosis knowledge or osteoporosis attitudes and beliefs compared with usual care. However, per protocol analyses revealed that those most adherent to exercise training did experience significant improvements in both HRQoL and osteoporosis knowledge compared with usual care. Authors concluded that their findings highlight the need to identify strategies that promote long-term adherence to multifaceted exercise programs in community-dwelling older adults.
Abstract
UNLABELLED This study identified that an 18-month community-based, multifaceted, exercise program consisting of resistance, weight-bearing impact, and balance/mobility training combined with osteoporosis education and behavioural support can improve health-related quality of life (HRQoL) and osteoporosis knowledge in older adults at risk of fracture, but only for those adherent to the exercise regime. PURPOSE To evaluate the effects of an 18-month community-based exercise, osteoporosis education and behaviour change program (Osteo-cise: Strong Bones for Life) on HRQoL, osteoporosis knowledge and osteoporosis health beliefs. METHODS This was a secondary analysis of an 18-month randomised controlled trial in which 162 older adults aged ≥ 60 years with osteopenia or increased falls/fracture risk were randomized to the Osteo-cise program (n = 81) or control group (n = 81). The program consisted of progressive resistance, weight-bearing impact and balance training (3 days/week); osteoporosis education to facilitate self-management of musculoskeletal health and behavioural support to enhance adherence to exercise. HRQoL, osteoporosis knowledge and osteoporosis health beliefs were assessed using the EuroQoL questionnaire (EQ-5D-3L), Osteoporosis Knowledge Assessment Tool and Osteoporosis Health Belief Scale, respectively. RESULTS Overall, 148 participants (91%) completed the trial. Mean exercise adherence was 55% and mean attendance for the three osteoporosis educational sessions ranged from 63-82%. After 12 and 18 months, there were no significant effects of the Osteo-cise program on HRQoL, osteoporosis knowledge or health beliefs relative to controls. Per protocol analyses (≥ 66% exercise adherence; n = 41) revealed a significant net benefit in EQ-5D-3L utility for the Osteo-cise group relative to controls after 12 months (P = 0.024) and 18 months (P = 0.029) and a significant net improvement in osteoporosis knowledge scores at 18 months (P = 0.014). CONCLUSION This study supports the importance of adherence to exercise regimes, as adherence to the Osteo-cise: Strong Bones for Life program was associated with improvements in HRQoL and osteoporosis knowledge in older adults at increased risk for falls and fractures. TRIAL REGISTRATION NUMBER ACTRN12609000100291.
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Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis.
Akinsuyi, OS, Roesch, LFW
Microbiology spectrum. 2023;11(3):e0032223
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Osteoporosis (OP) is the most common metabolic bone disease associated with aging. Microbiome dysbiosis leading to impaired intestinal immune responses and subsequent production of osteoclastogenic cytokines has been proposed as the mechanism by which gut microbes are associated with osteoporosis. The aim of this study was to identify gut bacteria consistently associated with osteoporosis across different cohorts. This study was a meta-analysis of five studies. Results showed that gut microbial dysbiosis in osteoporosis patients is associated with functional changes, which result in significant changes in metabolites that play a key role in bone metabolism. Authors concluded that their findings set the stage for future studies to provide more comprehensive knowledge on how dysbiosis in the gut microbiome contributes to osteoporosis.
Abstract
Over the past decade, the role of the gut microbiota in many disease states has gained a great deal of attention. Mounting evidence from case-control and observational studies has linked changes in the gut microbiota to the pathophysiology of osteoporosis (OP). Nonetheless, the results of these studies contain discrepancies, leaving the literature without a consensus on osteoporosis-associated microbial signatures. Here, we conducted a comprehensive meta-analysis combining and reexamining five publicly available 16S rRNA partial sequence data sets to identify gut bacteria consistently associated with osteoporosis across different cohorts. After adjusting for the batch effect associated with technical variation and heterogeneity of studies, we observed a significant shift in the microbiota composition in the osteoporosis group. An increase in the relative abundance of opportunistic pathogens Clostridium sensu stricto, Bacteroides, and Intestinibacter was observed in the OP group. Moreover, short-chain-fatty-acid (SCFA) producers, including members of the genera Collinsella, Megasphaera, Agathobaculum, Mediterraneibacter, Clostridium XIV, and Dorea, were depleted in the OP group relative to the healthy control (HC) group. Lactic acid-producing bacteria, including Limosilactobacillus, were significantly increased in the OP group. The random forest algorithm further confirmed that these bacteria differentiate the two groups. Furthermore, functional prediction revealed depletion of the SCFA biosynthesis pathway (glycolysis, tricarboxylic acid [TCA] cycle, and Wood-Ljungdahl pathway) and amino acid biosynthesis pathway (methionine, histidine, and arginine) in the OP group relative to the HC group. This study uncovered OP-associated compositional and functional microbial alterations, providing robust insight into OP pathogenesis and aiding the possible development of a therapeutic intervention to manage the disease. IMPORTANCE Osteoporosis is the most common metabolic bone disease associated with aging. Mounting evidence has linked changes in the gut microbiota to the pathophysiology of osteoporosis. However, which microbes are associated with dysbiosis and their impact on bone density and inflammation remain largely unknown due to inconsistent results in the literature. Here, we present a meta-analysis with a standard workflow, robust statistical approaches, and machine learning algorithms to identify notable microbial compositional changes influencing osteoporosis.
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Association of Coffee and Tea Intake with Bone Mineral Density and Hip Fracture: A Meta-Analysis.
Chen, CC, Shen, YM, Li, SB, Huang, SW, Kuo, YJ, Chen, YP
Medicina (Kaunas, Lithuania). 2023;59(6)
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Osteoporosis is associated with severe complications, such as osteoporotic fracture and fracture-related functional disability. Risk factors for osteoporosis must be identified and validated at the earliest. The aim of this study was to investigate the association of coffee and tea intake with bone mass density (BMD) and hip fracture risk. This study was a systematic review and meta-analysis of 106 studies. In total, 416,847 individuals (BMD related studies, 99,750 individuals; hip fracture–related studies, 408,562 individuals) were included in the final analysis. Results showed that the daily intake of caffeinated beverages, such as coffee and tea, is not associated with BMD or hip fracture risk, particularly in postmenopausal women. Authors concluded that their findings help reduce the inconsistency in the current literature. Furthermore, it may serve as a reference for future studies aimed at identifying the risk factor for osteoporosis.
Abstract
Background and Objectives: Osteoporosis is characterized by low bone mass and high bone fragility. Findings regarding the association of coffee and tea intake with osteoporosis have been inconsistent. We conducted this meta-analysis to investigate whether coffee and tea intake is associated with low bone mineral density (BMD) and high hip fracture risk. Materials and Methods: PubMed, MEDLINE, and Embase were searched for relevant studies published before 2022. Studies on the effects of coffee/tea intake on hip fracture/BMD were included in our meta-analysis, whereas those focusing on specific disease groups and those with no relevant coffee/tea intake data were excluded. We assessed mean difference (MD; for BMD) and pooled hazard ratio (HR; for hip fracture) values with 95% confidence interval (CI) values. The cohort was divided into high- and low-intake groups considering the thresholds of 1 and 2 cups/day for tea and coffee, respectively. Results: Our meta-analysis included 20 studies comprising 508,312 individuals. The pooled MD was 0.020 for coffee (95% CI, -0.003 to 0.044) and 0.039 for tea (95% CI, -0.012 to 0.09), whereas the pooled HR was 1.008 for coffee (95% CI, 0.760 to 1.337) and 0.93 for tea (95% CI, 0.84 to 1.03). Conclusions: Our meta-analysis results suggest that daily coffee or tea consumption is not associated with BMD or hip fracture risk.
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Effect of a Hop Extract Standardized in 8-Prenylnaringenin on Bone Health and Gut Microbiome in Postmenopausal Women with Osteopenia: A One-Year Randomized, Double-Blind, Placebo-Controlled Trial.
Lecomte, M, Tomassi, D, Rizzoli, R, Tenon, M, Berton, T, Harney, S, Fança-Berthon, P
Nutrients. 2023;15(12)
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Osteoporosis is a bone condition characterized by weakened and brittle bones, leading to an increased risk of fractures. Oestrogens play a vital role in maintaining bone health, whereby oestrogen deficiency elevates the risk of osteoporosis and fractures, particularly in menopausal women due to the decline in oestrogen levels. Phytoestrogens, plant-derived compounds capable of interacting with human oestrogen receptors, have presented an intriguing non-pharmaceutical avenue for preventing bone loss. Other phytoestrogens have received some attention in the field, however, limited human research exists on prenylflavonoids, a phytoestrogens found in hops (Humulus lupulus). This randomized, double-blinded, placebo-controlled trial aimed to investigate the effects of a year-long supplementation of standardised hop extract (8-PN) Lifenol® on bone mineral density in postmenopausal women. Additionally, the study explored potential mechanisms, particularly focusing on changes in gut bacteria. Notably, gut bacteria play a role in bone metabolism and the pathogenesis of osteoporosis. They are also, along with the liver, responsible for converting hops phenols into active phytoestrogenic compounds. The trial was completed by 95 postmenopausal, women with Osteopenia aged 50 to 85. They all received calcium and vitamin D3 tablets in addition either a hop extract (100mcg) or a placebo for 48 weeks. Changes were monitored using DXA scans for bone mineral density (BMD) and bone metabolism, blood samples for markers for bone health, a quality of life questionnaire, gut microbiome testing, and tests for short-chain fatty acid (SCFA) levels. In conclusion, the intake of hop extract confirmed a previously observed trend of a slight increase in total bone mineral density (BMD), in addition to the benefits linked to calcium and vitamin D supplementation. Although there were no significant changes in the composition of gut bacteria and SCFA levels, the hop extract candidates had a higher abundance of specific genera associated with total body BMD, suggesting a potential positive impact. Larger studies are required to validate these findings.
Abstract
Estrogen deficiency increases the risk of osteoporosis and fracture. The aim of this study was to investigate whether a hop extract standardized in 8-prenylnaringenin (8-PN), a potent phytoestrogen, could improve bone status of osteopenic women and to explore the gut microbiome roles in this effect. In this double-blind, placebo-controlled, randomized trial, 100 postmenopausal, osteopenic women were supplemented with calcium and vitamin D3 (CaD) tablets and either a hop extract (HE) standardized in 8-PN (n = 50) or a placebo (n = 50) for 48 weeks. Bone mineral density (BMD) and bone metabolism were assessed by DXA measurements and plasma bone biomarkers, respectively. Participant's quality of life (SF-36), gut microbiome composition, and short-chain fatty acid (SCFA) levels were also investigated. In addition to the CaD supplements, 48 weeks of HE supplementation increased total body BMD (1.8 ± 0.4% vs. baseline, p < 0.0001; 1.0 ± 0.6% vs. placebo, p = 0.08), with a higher proportion of women experiencing an increase ≥1% compared to placebo (odds ratio: 2.41 ± 1.07, p < 0.05). An increase in the SF-36 physical functioning score was observed with HE versus placebo (p = 0.05). Gut microbiome α-diversity and SCFA levels did not differ between groups. However, a higher abundance of genera Turicibacter and Shigella was observed in the HE group; both genera have been previously identified as associated with total body BMD. These results suggest that an 8-PN standardized hop extract could beneficially impact bone health of postmenopausal women with osteopenia.
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Dietary Acid Load Was Positively Associated with the Risk of Hip Fracture in Elderly Adults.
Li, CF, Liu, YP, Liu, CY, Zhu, HL, Wu, BH, Li, BL, Chen, YM
Nutrients. 2022;14(18)
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Osteoporosis causes huge disease and economic burdens worldwide. Hip fracture is deemed the most devastating result of osteoporosis owing to its high disability and mortality rate. Dietary acid load (DAL) is often used to evaluate the acid–base equilibrium state of the body. The aim of this study was to examine the association between DAL and the risk of hip fracture among middle-aged and older people (Chinese). This study is a large 1:1 matched case–control study with a total of 1070 (women, 795; men, 275) pairs of cases and controls. Results show that DAL had significant positive associations with the risk of hip fracture among middle-aged and older Chinese people especially in those with a lower body mass index - less than 23 kg/m2. Authors conclude that future prospective studies with objective DAL measures are required in order to further confirm the findings of this study.
Abstract
Previous studies have shown that dietary acid load (DAL) harms bone health, but the evidence is inconsistent and insufficient. This study examined the relationships between DAL and the risk of hip fracture. This case-control study contained 1070 pairs of 1:1 age-, city-, and gender-matched incident cases and controls (mean age, 71 years) recruited in Guangdong, China. Dietary information was collected using a validated 79-item food frequency questionnaire through face-to-face interviews. DAL was estimated based on established algorithms for the potential renal acid load (PRAL) and net endogenous acid production (NEAP). Higher PRAL and NEAP were dose-dependently associated with a higher risk of hip fracture in both the conditional logistic regression model and restricted cubic spline analysis after adjusting for potential covariates. The multivariate-adjusted odds ratios and 95% CI of hip fracture for tertiles 2 and 3 (vs. 1) of DAL were 1.63 (1.18, 2.25) and 1.92 (1.36, 2.71) for PRAL and 1.81 (1.30, 2.53) and 2.55 (1.76, 3.71) for NEAP in all participants (all p-trends < 0.001), respectively. Subgroup analyses showed more pronounced associations in participants with a lower body mass index. Our findings suggested positive associations between the estimated DAL and the risk of hip fractures in the elderly Chinese population.
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Meta-Analysis of Effects of Nutritional Intervention Combined with Calcium Carbonate D3 Tablets on Bone Mineral Density, Bone Metabolism, and Curative Effect in Patients with Osteoporosis.
Ni, H, Zhang, S, Niu, X, Dai, S
Contrast media & molecular imaging. 2022;2022:3670007
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Osteoporosis is characterised by reduced bone mineral density and changes in bone metabolism, which may increase the risk of bone fractures. Elderly people are more at risk of developing osteoporosis. A calcium carbonate D3 tablet combined with nutritional intervention is commonly recommended by health professionals for the treatment of osteoporosis in the elderly. In this meta-analysis, 10 Chinese literature, 7 high-quality literature and 3 low-quality research were examined to determine the effect of nutritional intervention with calcium carbonate D3 tablets on changes in bone mineral density and bone metabolism in osteoporosis patients. Nutritional intervention in combination with calcium carbonate tablet supplementation showed significant efficacy compared to the use of a single drug. In the combined intervention group, osteocalcin levels, serum alkaline phosphatase levels, serum calcium levels, blood phosphorus levels, and bone mineral density were significantly higher than those in the monotherapy group. This study provides healthcare professionals with an opportunity to gain a better understanding of the efficacy of nutritional intervention coupled with calcium carbonate D3 supplementation on osteocalcin levels, serum alkaline phosphatase levels, serum calcium levels, blood phosphorus levels, and bone mineral density in osteoporosis patients. The validity of the data and the clinical utility of different combinations of therapeutic strategies require further robust research.
Abstract
To investigate the changes in bone mineral density, bone metabolism, and efficacy of nutritional intervention combined with calcium carbonate D3 tablets in patients with osteoporosis, a RevMan 5.2 software meta-analysis was conducted in this study. According to the therapeutic direction of nutritional intervention combined with calcium carbonate D3 tablets for osteoporosis patients, relevant literature were searched in Wanfang Medical, CNKI, VIP, and PubMed literature databases at home and abroad. Keywords included bone mineral density, bone metabolism, blood calcium (Ca), blood phosphorus (P), osteocalcin (OC), bone mineral density (BMD), serum alkaline phosphatase (ALP), efficacy, osteoporosis, and nutritional intervention. Literature that met the criteria were deleted, and meta-analysis was performed using RevMan 5.2 software. The results indicate that a total of 10 Chinese literature were included. Compared with the monotherapy group, the clinical efficacy, osteocalcin, BMD, alkaline phosphatase, calcium, and phosphorus were significantly higher in the combination group (P < 0.05). Based on calcium carbonate D3, treatment combined with nutritional intervention can enhance the clinical efficacy, bone metabolism, and bone mineral density of patients with osteoporosis, and nutritional intervention combined with calcium carbonate D3 tablets is a feasible program to promote the recovery of patients with osteoporosis.
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One-year supplementation with Lactobacillus reuteri ATCC PTA 6475 counteracts a degradation of gut microbiota in older women with low bone mineral density.
Li, P, Ji, B, Luo, H, Sundh, D, Lorentzon, M, Nielsen, J
NPJ biofilms and microbiomes. 2022;8(1):84
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Osteoporosis is a highly prevalent bone disease in the elderly population and is characterised by decreased bone mineral density, deteriorated bone microarchitecture, reduced bone strength and increased susceptibility to fragility fractures. Due to the lack of awareness about osteoporosis, there is the need to develop a novel and effective intervention for its prevention and treatment. The aim of this study was to gain mechanistic insight into the effect of Lactobacillus reuteri ATCC PTA 6475 on bone metabolism and identify factors important for a good response to the probiotic. This study was based on a placebo-controlled cohort trial where 68 elderly women had been randomised to supplementation with the probiotic strain L. reuteri ATCC PTA 6475 or placebo. For this secondary analysis, 20 out of the 68 elderly women with bone loss who supplemented with probiotic L. reuteri ATCC PTA 6475 were selected. Results showed that after one-year probiotic supplementation, there was decreased inflammation and significantly increased gene richness of the gut microbiota in the good responders, whereas there was altered microbial composition and function, including enrichment of E. coli and its biofilm formation in the poor responders. Authors conclude that L. reuteri ATCC PTA 6475 supplementation might promote bone formation by modulating the gut microbiota composition and function, which could be crucial for the development of novel osteoporosis treatments.
Abstract
Recent studies have shown that probiotic supplementation has beneficial effects on bone metabolism. In a randomized controlled trial (RCT) we demonstrated that supplementation of Lactobacillus reuteri ATCC PTA 6475 reduced bone loss in older women with low bone mineral density. To investigate the mechanisms underlying the effect of L. reuteri ATCC PTA 6475 on bone metabolism, 20 women with the highest changes (good responders) and the lowest changes (poor responders) in tibia total volumetric BMD after one-year supplementation were selected from our previous RCT. In the current study we characterized the gut microbiome composition and function as well as serum metabolome in good responders and poor responders to the probiotic treatment as a secondary analysis. Although there were no significant differences in the microbial composition at high taxonomic levels, gene richness of the gut microbiota was significantly higher (P < 0.01 by the Wilcoxon rank-sum test) and inflammatory state was improved (P < 0.05 by the Wilcoxon signed-rank test) in the good responders at the end of the 12-month daily supplementation. Moreover, detrimental changes including the enrichment of E. coli (adjusted P < 0.05 by DESeq2) and its biofilm formation (P < 0.05 by GSA) observed in the poor responders were alleviated in the good responders by the treatment. Our results indicate that L. reuteri ATCC PTA 6475 supplementation has the potential to prevent a deterioration of the gut microbiota and inflammatory status in elderly women with low bone mineral density, which might have beneficial effects on bone metabolism.
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Nutrition in Menopausal Women: A Narrative Review.
Silva, TR, Oppermann, K, Reis, FM, Spritzer, PM
Nutrients. 2021;13(7)
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Menopause is the permanent cessation of menstrual cycles following the loss of ovarian follicular activity. It is associated with increased prevalence of obesity, metabolic syndrome, cardiovascular disease, and osteoporosis. The aim of this narrative review was to discuss the current evidence on the association between dietary patterns and clinical endpoints in postmenopausal women (body composition, bone mass, and risk markers for cardiovascular disease), and thereby providing novel insight into the establishment of optimal dietary guidelines for healthy postmenopausal period. Research shows that: - the changes in weight and fat distribution in women are associated with aging and mainly with the decrease in oestradiol levels during peri- and post-menopause. - calcium, vitamin D, vitamin K, selenium, magnesium, and beta-carotene adequate intake could be linked with better BMD in postmenopausal women. - diet is a major modifiable risk factor for cardiovascular disease and could be a powerful intervention to reduce cardiovascular risks in postmenopausal women. - the Mediterranean diet is composed of healthy foods that have anti-inflammatory and antioxidant properties. Authors indicate that future studies evaluating the effects of low-fat, plant-based diets on fat mass in post-menopausal women are needed.
Abstract
Among the various aspects of health promotion and lifestyle adaptation to the postmenopausal period, nutritional habits are essential because they concern all women, can be modified, and impact both longevity and quality of life. In this narrative review, we discuss the current evidence on the association between dietary patterns and clinical endpoints in postmenopausal women, such as body composition, bone mass, and risk markers for cardiovascular disease. Current evidence suggests that low-fat, plant-based diets are associated with beneficial effects on body composition, but further studies are needed to confirm these results in postmenopausal women. The Mediterranean diet pattern along with other healthy habits may help the primary prevention of bone, metabolic, and cardiovascular diseases in the postmenopausal period. It consists on the use of healthy foods that have anti-inflammatory and antioxidant properties, and is associated with a small but significant decrease in blood pressure, reduction of fat mass, and improvement in cholesterol levels. These effects remain to be evaluated over a longer period of time, with the assessment of hard outcomes such as bone fractures, diabetes, and coronary ischemia.
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Probiotic supplements and bone health in postmenopausal women: a meta-analysis of randomised controlled trials.
Yu, J, Cao, G, Yuan, S, Luo, C, Yu, J, Cai, M
BMJ open. 2021;11(3):e041393
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Osteoporosis is a disease where bone density is decreased and is often seen in postmenopausal women. Current prescribed treatments are costly and can often have serious side effects and as a result natural treatments are often requested. Probiotics have been shown in previous studies to be of benefit to bones, however no large review of all the available studies has been performed. This systematic review and meta-analysis of current randomised control trials (RCT’s) aimed to summarise the effect of probiotics on bone density in postmenopausal women. The results showed that only five RCT’s were available on the effect of probiotics on bone density of which there were 497 postmenopausal women. Bone density at the base of the spine was increased in women taking probiotics, however there was no difference seen in bone density of the hip. Bone markers for bone degradation were decreased, however other markers associated with bone density changes were unaffected. It was concluded that probiotics may increase bone density at the base of the spine, however more high-quality studies are needed. This study could be used by healthcare professionals to understand how probiotics may be of benefit to postmenopausal women, however definitive recommendations based on this study may need to be made with caution.
Abstract
OBJECTIVE Osteoporosis is a common disease in postmenopausal women. Several studies have analysed the associations between dietary supplementation with probiotics and bone health in postmenopausal women, but the results are still controversial. We conducted this meta-analysis to assess the effects of probiotics supplement on bone mineral density (BMD) and bone turnover markers for postmenopausal women. DESIGN Systematic review and meta-analysis. METHODS We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to November 2020 for randomised controlled trials (RCTs) assessing probiotic supplements and osteoporosis in postmenopausal women. Study-specific risk estimates were combined using random-effect models. RESULTS Five RCTs (n=497) were included. Probiotic supplements were associated with a significantly higher BMD in the lumbar spine (standardised mean difference, SMD=0.27, 95% CI 0.09 to 0.44) than in control. There was no difference between probiotic supplements and BMD in hips (SMD=0.22, 95% CI -0.07 to 0.52). Collagen type 1 cross-linked C-telopeptide levels in the treatment groups were significantly lower than those of the placebo group (SMD=-0.34, 95% CI -0.60 to -0.09). In subgroup meta-analysis, levels of bone-specific alkaline phosphatase, osteoprotegerin, osteocalcin and tumour necrosis factor did not differ between the probiotic and placebo groups. CONCLUSIONS We conclude cautiously that supplementation with probiotics could increase lumbar BMD. More RCTs are recommended to validate or update these results.