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1.
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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2.
Changes in Bone Metabolism After Sleeve Gastrectomy Versus Gastric Bypass: a Meta-Analysis.
Tian, Z, Fan, XT, Li, SZ, Zhai, T, Dong, J
Obesity surgery. 2020;(1):77-86
Abstract
BACKGROUND Gastric bypass (GB) and sleeve gastrectomy (SG) are two common types of bariatric surgery that carry many potential complications. Among these complications, bone metabolism-related diseases have attracted substantial attention; however, no meta-analysis of them has been performed to date. METHODS We searched PubMed, Web of Science, The Cochrane Library, and Embase to identify relevant studies published before January 2019. The following indicators were evaluated: serum parathyroid hormone (PTH), calcium, phosphorus and 25-hydroxyvitamin D levels, body mass index (BMI), and bone mineral density (BMD). RESULTS Thirteen studies met our inclusion criteria. Overall results showed that patients undergoing GB had lower levels of 25-hydroxyvitamin D (MD = - 1.85, 95% CI (- 3.32, - 0.39) P = 0.01) and calcium (MD = - 0.15, 95% CI (- 0.24, - 0.07) P = 0.0006) as well as higher levels of PTH (MD = 3.58, 95% CI (0.61, 7.09) P = 0.02) and phosphorus (MD = 0.22, 95% CI (0.10, 0.35) P = 0.0005). The results of BMI and BMD were comparable in each group. CONCLUSION Our meta-analysis suggested that obese patients undergoing GB had lower levels of serum calcium and 25-hydroxyvitamin D as well as higher levels of serum phosphorus and PTH. To prevent postoperative bone metabolism-related diseases, appropriate postoperative interventions should be undertaken for particular surgical procedures.
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3.
Vitamin D supplementation for term breastfed infants to prevent vitamin D deficiency and improve bone health.
Tan, ML, Abrams, SA, Osborn, DA
The Cochrane database of systematic reviews. 2020;(12):CD013046
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Abstract
BACKGROUND Vitamin D deficiency is common worldwide, contributing to nutritional rickets and osteomalacia which have a major impact on health, growth, and development of infants, children and adolescents. Vitamin D levels are low in breast milk and exclusively breastfed infants are at risk of vitamin D insufficiency or deficiency. OBJECTIVES To determine the effect of vitamin D supplementation given to infants, or lactating mothers, on vitamin D deficiency, bone density and growth in healthy term breastfed infants. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to 29 May 2020 supplemented by searches of clinical trials databases, conference proceedings, and citations. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs in breastfeeding mother-infant pairs comparing vitamin D supplementation given to infants or lactating mothers compared to placebo or no intervention, or sunlight, or that compare vitamin D supplementation of infants to supplementation of mothers. DATA COLLECTION AND ANALYSIS Two review authors assessed trial eligibility and risk of bias and independently extracted data. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS We included 19 studies with 2837 mother-infant pairs assessing vitamin D given to infants (nine studies), to lactating mothers (eight studies), and to infants versus lactating mothers (six studies). No studies compared vitamin D given to infants versus periods of infant sun exposure. Vitamin D supplementation given to infants: vitamin D at 400 IU/day may increase 25-OH vitamin D levels (MD 22.63 nmol/L, 95% CI 17.05 to 28.21; participants = 334; studies = 6; low-certainty) and may reduce the incidence of vitamin D insufficiency (25-OH vitamin D < 50 nmol/L) (RR 0.57, 95% CI 0.41 to 0.80; participants = 274; studies = 4; low-certainty). However, there was insufficient evidence to determine if vitamin D given to the infant reduces the risk of vitamin D deficiency (25-OH vitamin D < 30 nmol/L) up till six months of age (RR 0.41, 95% CI 0.16 to 1.05; participants = 122; studies = 2), affects bone mineral content (BMC), or the incidence of biochemical or radiological rickets (all very-low certainty). We are uncertain about adverse effects including hypercalcaemia. There were no studies of higher doses of infant vitamin D (> 400 IU/day) compared to placebo. Vitamin D supplementation given to lactating mothers: vitamin D supplementation given to lactating mothers may increase infant 25-OH vitamin D levels (MD 24.60 nmol/L, 95% CI 21.59 to 27.60; participants = 597; studies = 7; low-certainty), may reduce the incidences of vitamin D insufficiency (RR 0.47, 95% CI 0.39 to 0.57; participants = 512; studies = 5; low-certainty), vitamin D deficiency (RR 0.15, 95% CI 0.09 to 0.24; participants = 512; studies = 5; low-certainty) and biochemical rickets (RR 0.06, 95% CI 0.01 to 0.44; participants = 229; studies = 2; low-certainty). The two studies that reported biochemical rickets used maternal dosages of oral D3 60,000 IU/day for 10 days and oral D3 60,000 IU postpartum and at 6, 10, and 14 weeks. However, infant BMC was not reported and there was insufficient evidence to determine if maternal supplementation has an effect on radiological rickets (RR 0.76, 95% CI 0.18 to 3.31; participants = 536; studies = 3; very low-certainty). All studies of maternal supplementation enrolled populations at high risk of vitamin D deficiency. We are uncertain of the effects of maternal supplementation on infant growth and adverse effects including hypercalcaemia. Vitamin D supplementation given to infants compared with supplementation given to lactating mothers: infant vitamin D supplementation compared to lactating mother supplementation may increase infant 25-OH vitamin D levels (MD 14.35 nmol/L, 95% CI 9.64 to 19.06; participants = 269; studies = 4; low-certainty). Infant vitamin D supplementation may reduce the incidence of vitamin D insufficiency (RR 0.61, 95% CI 0.40 to 0.94; participants = 334; studies = 4) and may reduce vitamin D deficiency (RR 0.35, 95% CI 0.17 to 0.72; participants = 334; studies = 4) but the evidence is very uncertain. Infant BMC and radiological rickets were not reported and there was insufficient evidence to determine if maternal supplementation has an effect on infant biochemical rickets. All studies enrolled patient populations at high risk of vitamin D deficiency. Studies compared an infant dose of vitamin D 400 IU/day with varying maternal vitamin D doses from 400 IU/day to > 4000 IU/day. We are uncertain about adverse effects including hypercalcaemia. AUTHORS' CONCLUSIONS For breastfed infants, vitamin D supplementation 400 IU/day for up to six months increases 25-OH vitamin D levels and reduces vitamin D insufficiency, but there was insufficient evidence to assess its effect on vitamin D deficiency and bone health. For higher-risk infants who are breastfeeding, maternal vitamin D supplementation reduces vitamin D insufficiency and vitamin D deficiency, but there was insufficient evidence to determine an effect on bone health. In populations at higher risk of vitamin D deficiency, vitamin D supplementation of infants led to greater increases in infant 25-OH vitamin D levels, reductions in vitamin D insufficiency and vitamin D deficiency compared to supplementation of lactating mothers. However, the evidence is very uncertain for markers of bone health. Maternal higher dose supplementation (≥ 4000 IU/day) produced similar infant 25-OH vitamin D levels as infant supplementation of 400 IU/day. The certainty of evidence was graded as low to very low for all outcomes.
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Effect of carbamazepine on the bone health of people with epilepsy: a systematic review and meta-analysis.
Zhang, X, Zhong, R, Chen, Q, Li, M, Lin, W, Cui, L
The Journal of international medical research. 2020;(3):300060520902608
Abstract
IMPORTANCE Increasing evidence indicates that carbamazepine (CBZ) treatment in people with epilepsy (PWE) has adverse effects on bone health. OBJECTIVE We conducted a meta-analysis to investigate the effect of CBZ on the bone health of PWE. METHODS Two independent reviewers systematically searched PubMed and EMBASE for eligible studies. Standard mean deviations (SMDs) with 95% confidence intervals were used as a measure to investigate the effect of CBZ on bone-related outcomes in PWE. RESULTS Levels of vitamin D (standardized mean difference [SMD]: −0.62, 95% CI: −0.89 to −0.35) and calcium (SMD: −0.38, 95% CI: −0.67 to −0.09) were significantly lower in the CBZ group than controls. Additionally, significantly higher alkaline phosphatase (SMD: 0.67, 95% CI: 0.52–0.82) was observed in patients using CBZ than controls. However, no significant difference in BMD was found between the two groups (SMD: −0.06, 95% CI: −0.55 to 0.43). Conclusion and significance: This study provided evidence that CBZ treatment has a negative effect on bone health in PWE. Clinical implications are that long-term CBZ treatment may not be a good choice for PWE with skeletal diseases or osteoporosis.
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5.
Primary Aldosteronism and Bone Metabolism: A Systematic Review and Meta-Analysis.
Shi, S, Lu, C, Tian, H, Ren, Y, Chen, T
Frontiers in endocrinology. 2020;:574151
Abstract
BACKGROUND Currently, increasing evidence shows that excess aldosterone may have an impact on bone health, and primary aldosteronism (PA) may be a secondary cause of osteoporosis. This problem is worthy of attention because secondary osteoporosis is always potentially reversible, which affects the selection of treatment for PA to some extent. The present systematic review will assess and summarize the available data regarding the relationship between PA and osteoporosis. METHODS Pubmed and Embase were searched for clinical trials related to the association between PA and bone metabolism. The results were limited to full-text articles published in English, without restrictions for the publication time. The quality of clinical trials was appraised, and the data were extracted. Biochemical parameters of bone turnover in PA patients were assessed using random-effect meta-analysis. Descriptive analysis was performed for other parameters, for data is insufficient. RESULTS A final total of 15 articles were included in this review. The meta-analysis of six studies showed that subjects with PA had higher serum PTH levels (MD=21.50 pg/ml, 95% CI (15.63, 27.37), P<0.00001) and slightly increased urinary calcium levels (MD = 1.65 mmol/24 h, 95% CI (1.24, 2.06), P < 0.00001) than the EH controls. PA is associated with an increased risk of bone fracture. Bone loss in patients with PA may be reversed by MR antagonists or adrenal surgery. CONCLUSIONS PA may be a secondary cause of osteoporosis and is associated with an increased risk of bone fracture. The clarification of the relationships between PA and bone metabolism requires additional prospective randomized controlled studies in a large sample.
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The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials.
Kuang, X, Liu, C, Guo, X, Li, K, Deng, Q, Li, D
Food & function. 2020;(4):3280-3297
Abstract
BACKGROUND Previous studies did not draw a consistent conclusion about the effects of vitamin K combined with vitamin D on human skeletal quality. METHOD AND FINDINGS A comprehensive search on Web of Science, PubMed, Embase and the Cochrane Library (from 1950 to February 2020) and bibliographies of relevant articles was undertaken, with the meta-analysis of eight randomized controlled trials (RCTs) including a total of 971 subjects. Vitamin K combined with vitamin D significantly increased the total bone mineral density (BMD): the pooled effect size was 0.316 [95% CI (confidence interval), 0.031 to 0.601]. A significant decrease in undercarboxylated osteocalcin (-0.945, -1.113 to -0.778) can be observed with the combination of vitamin K and D. Simultaneously, subgroup analysis showed that K2 or vitamin K (not specified) supplement was less than 500 μg d-1, which when combined with vitamin D can significantly increase the total BMD compared with the control group fed a normal diet or the group with no treatment (0.479, 0.101 to 0.858 and 0.570, 0.196 to 0.945). CONCLUSIONS The combination of vitamin K and D can significantly increase the total BMD and significantly decrease undercarboxylated osteocalcin, and a more favorable effect is expected when vitamin K2 is used.
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Effects of Dietary Protein Quantity on Bone Quantity following Weight Loss: A Systematic Review and Meta-analysis.
Wright, CS, Li, J, Campbell, WW
Advances in nutrition (Bethesda, Md.). 2019;(6):1089-1107
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Abstract
Research supports the hypothesis that higher total protein intake during weight loss promotes retention of lean soft tissue, but the effect of dietary protein quantity on bone mass, a lean hard tissue, is inconsistent. The purpose of this systematic review and meta-analysis was to assess the effect of dietary protein quantity [higher protein (HP): ≥25% of energy from protein or ≥1.0 g · kg body wt-1 · d-1; normal protein (NP): <25% of energy from protein or <1.0 g · kg body wt-1 · d-1] on changes in bone mineral density (BMD) and content (BMC; total body, lumbar spine, total hip, femoral neck) following a prescribed energy restriction. We hypothesized that an HP diet would attenuate the loss of BMD/BMC following weight loss in comparison to an NP diet. Two researchers systematically and independently screened 2366 publications from PubMed, Cochrane, Scopus, CINAHL, and Web of Science Core Collection and extracted data from 34 qualified publications. Inclusion criteria included the following: 1) healthy subjects ≥19 y; 2) a prescribed energy restriction; 3) measurements of total protein intake, BMD, and BMC; and 4) an intervention duration of ≥3 mo. Data from 10 of the 34 publications with 2 groups of different total protein intakes were extracted and used to conduct a random-effects model meta-analysis. A majority of publications (59%) showed a decrease in bone quantity following active weight loss, regardless of total protein intake. Statistically, the loss of total BMD (P = 0.016; weighted mean difference: +0.006 g/cm2; 95% CI: 0, 0.011 g/cm2) and lumbar spine BMD (P = 0.019; weighted mean difference: +0.017 g/cm2; 95% CI: 0.001, 0.033 g/cm2) was attenuated with an HP versus an NP weight-loss diet. However, the clinical significance is questionable given the modest weighted mean difference and study duration. Higher total protein intake does not exacerbate but may attenuate the loss of bone quantity following weight loss.
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Should vitamin D administration for fracture prevention be continued? : A discussion of recent meta-analysis findings.
Bischoff-Ferrari, HA
Zeitschrift fur Gerontologie und Geriatrie. 2019;(5):428-432
Abstract
In consideration and critical review of four recent meta-analyses on vitamin D and fracture prevention, vitamin D supplementation with or without calcium is supported among older adults age 65 years and older at risk of vitamin D deficiency and fractures if given in daily or equivalent weekly or monthly doses of 800 to 1000 IU and with good adherence. Vitamin D supplementation might not be effective in primary prevention among adults age 50 years and older without vitamin D deficiency and osteoporosis; however, clinical trials on primary prevention are limited. Notably, large annual bolus administration of vitamin D is detrimental with regard to falls and fractures among older adults at risk of fractures and should not be continued in clinical care. Larger monthly doses of 100,000 IU need further evaluation with respect to efficacy and safety.
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Comment on: "Effects of interventions with a physical activity component on bone health in obese children and adolescents: a systematic review and meta-analysis".
Alwardat, M, Alwardat, N
Journal of bone and mineral metabolism. 2019;(2):376-377
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10.
Crystalline arthropathy and bone health.
Chang, I, Gazeley, D
Current opinion in rheumatology. 2018;(2):173-176
Abstract
PURPOSE OF REVIEW The purpose of this review is to provide insight on the proposed association between crystal arthritis and bone health. Crystal arthritis is the most common type of inflammatory arthritis, and fractures contribute to significant morbidity and mortality, therefore, the relationship between the two is of clinical importance. RECENT FINDINGS There have been variable findings regarding hyperuricemia, low bone density and risk of fracture. A recent systematic review and meta-analysis of available literature showed a correlation between increased serum uric acid and lower risk of fracture. Less is known about calcium pyrophosphate deposition disease and bone health, although two large studies have suggested an association with osteopenia. SUMMARY A systematic review and meta-analysis of available data suggest a correlation between increased serum uric acid and lower risk of fracture. Findings support an association between bone health and crystal arthritis which warrants further study and may have implications for how we treat gout.