-
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.
-
2.
Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial.
Abildgaard, J, Johansen, MY, Skov-Jeppesen, K, Andersen, LB, Karstoft, K, Hansen, KB, Hartmann, B, Holst, JJ, Pedersen, BK, Ried-Larsen, M
Medicine and science in sports and exercise. 2022;(1):38-46
Abstract
INTRODUCTION/PURPOSE The increased risk of fractures with type 2 diabetes (T2D) is suggested to be caused by decreased bone turnover. Current international guidelines recommend lifestyle modifications, including exercise, as first-line treatment for T2D. The aim of this study was to investigate the effects of an exercise-based lifestyle intervention on bone turnover and bone mineral density (BMD) in persons with T2D. METHODS Persons with T2D were randomized to either a 12-month lifestyle intervention (n = 64) or standard care (n = 34). The lifestyle intervention included five to six weekly aerobic training sessions, half of them combined with resistance training. Serum markers of bone turnover (osteocalcin, N-terminal propeptide of type-I procollagen, reflecting bone formation, and carboxyterminal collagen I crosslinks, reflecting bone resorption) and BMD (by DXA) were measured before the intervention and at follow-up. RESULTS From baseline to follow-up, s-propeptide of type-I procollagen increased by 34% (95% confidence interval [CI], 17%-50%), serum-carboxyterminal collagen I crosslink by 36% (95% CI, 1%-71%), and s-osteocalcin by 31% (95% CI, 11-51%) more in the lifestyle intervention group compared with standard care. Loss of weight and fat mass were the strongest mediators of the increased bone turnover. Bone mineral density was unaffected by the intervention (ΔBMD, 0.1%; 95% CI, -1.1% to 1.2%). CONCLUSIONS A 12-month intensive exercise-based lifestyle intervention led to a substantial but balanced increase in bone turnover in persons with T2D. The increased bone turnover combined with a preserved BMD, despite a considerable weight loss, is likely to reflect improved bone health and warrants further studies addressing the impact of exercise on risk of fractures in persons with T2D.
-
3.
Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis.
Zhang, YS, Zheng, YD, Yuan, Y, Chen, SC, Xie, BC
Frontiers in endocrinology. 2021;:735824
Abstract
PURPOSE Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients. METHODS Embase, Medline, ClinicalTrials.gov, and Cochrane CENTRAL were searched for relevant trials. All data analyses were performed with STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining data for the fracture effects of anti-diabetic drugs, including sodium-glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides, α-glucosidase inhibitors, thiazolidinediones, biguanides, insulin, and sulfonylureas. RESULTS One hundred seventeen eligible randomized controlled trials (RCTs) with 221,364 participants were included in this study. Compared with placebo, trelagliptin (RR 3.51; 1.58-13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 0.04-0.93) and voglibose (RR 0.03; 0-0.11) decreased the risk of fracture. Other medications were comparable in terms of their effects on fracture risk, and no statistical significance was observed. In terms of fractures, voglibose (0.01%) may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity analysis results were consistent with those of the main analysis. No statistically significant differences were observed in the regression coefficients of age (1.03; 0.32-2.1), follow-up duration (0.79; 0.27-1.64), and sex distribution (0.63; 0.15-1.56). CONCLUSIONS We found varied results on the association between the use of anti-diabetic drugs and fracture risk. Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference. Other drugs were comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits. The risk of fracture was independent of age, sex distribution, and the duration of exposure to anti-diabetic drugs. When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients. SYSTEMATIC REVIEW REGISTRATION This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464).
-
4.
Nutritional Supplements and Skeletal Health.
Tabatabai, LS, Sellmeyer, DE
Current osteoporosis reports. 2021;(1):23-33
Abstract
PURPOSE OF REVIEW Nutrition influences skeletal health throughout the lifespan, from the impact of maternal intakes during development, through the development of peak bone mass, to the rate of bone loss during aging. However, there are limited data available on the effects of nutritional supplements on bone density, let alone fracture risk. This review will assess the current literature, focusing on human studies, and emphasizing nutrients where bone density or fracture data are available. RECENT FINDINGS Calcium and vitamin D supplements, in combination, reduce fracture risk, particularly in populations with low intakes. Extensive recent analyses have supported the safety of these interventions at recommended intakes. There is growing evidence that specific isoflavones may improve bone density although fracture data are lacking. Multiple other nutrient supplements may benefit skeletal health, but data are limited. The effect size of nutrient interventions are relatively small, requiring large sample sizes for trials with bone outcomes, may be difficult to blind, and the impact of supplementation may depend on baseline intake. However, nutrition is the only intervention that can be implemented life long and on a population wide basis. Further investigation is needed into the potential benefits of nutritional supplements to determine in which settings supplements may add benefit in addition to dietary intakes.
-
5.
Fracture Patterns in Type 1 and Type 2 Diabetes Mellitus: A Narrative Review of Recent Literature.
Van Hulten, V, Rasmussen, N, Driessen, JHM, Burden, AM, Kvist, A, van den Bergh, JP
Current osteoporosis reports. 2021;(6):644-655
-
-
Free full text
-
Abstract
PURPOSE OF REVIEW In this narrative review, we have summarized the literature on fracture risk in T1DM and T2DM with a special focus on fracture site, time patterns, glucose-lowering drugs, and micro- and macrovascular complications. RECENT FINDINGS T1DM and T2DM were associated with an overall increased fracture risk, with preferent locations at the hip, vertebrae, humerus, and ankle in T1DM and at the hip, vertebrae, and likely humerus, distal forearm, and foot in T2DM. Fracture risk was higher with longer diabetes duration and the presence of micro- and macrovascular complications. In T2DM, fracture risk was higher with use of insulin, sulfonylurea, and thiazolidinediones and lower with metformin use. The increased fracture risk in T1DM and T2DM concerns specific fracture sites, and is higher in subjects with longer diabetes duration, vascular complications, and in T2DM with the use of specific glucose-lowering medication.
-
6.
Modifiable lifestyle and environmental factors associated with onset of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational studies.
Xie, W, Huang, H, Deng, X, Gao, D, Zhang, Z
Journal of the American Academy of Dermatology. 2021;(3):701-711
Abstract
BACKGROUND Psoriatic arthritis (PsA) is a progressive joint disease associated with psoriasis. OBJECTIVES To investigate the association of modifiable lifestyle and environmental factors with PsA risk among people with psoriasis. METHODS We conducted a systematic search of PubMed, Embase, and Cochrane Library through May 2, 2020, for observational studies reporting lifestyle or environmental factors for PsA onset in patients with psoriasis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were combined using a random-effects model. RESULTS We included 16 studies comprising 322,967 individuals. Obesity and being overweight were associated with an increased PsA risk in patients with psoriasis (OR, 1.75 [95% CI, 1.42-2.16] and OR, 1.50 [95% CI, 1.08-2.09], respectively), with an increase of approximately 6% for each kg/m2 rise in body mass index (OR, 1.06; 95% CI, 1.03-1.10). The presence of PsA was associated with a history of physical trauma (OR, 1.33; 95% CI, 1.16-1.54) or fracture (OR, 1.46; 95% CI, 1.22-1.74). No significant associations were observed regarding alcohol consumption (OR, 0.99; 95% CI, 0.88-1.13), smoking (OR, 0.89; 95% CI, 0.75-1.06), female hormonal exposure (OR, 1.45; 95% CI, 0.95-2.20), and psychologically traumatic events. LIMITATIONS Inherent limitations in the included observational studies. CONCLUSIONS Several lifestyle and environmental factors are associated with PsA onset among patients with psoriasis. These findings indicate that such risk may be modified with lifestyle changes or avoidance of physical trauma in people with psoriasis.
-
7.
Therapies for Preventing Bone Loss with Glucocorticoid Treatment.
Agarwal, A, Adachi, JD
Current osteoporosis reports. 2021;(1):34-39
Abstract
PURPOSE OF REVIEW We aim to critically review recent recommendations regarding preventative strategies for glucocorticoid-induced osteoporosis and provide a summary of key evidence regarding available interventions. RECENT FINDINGS Lifestyle optimization remains the hallmark of bone health preservation. Early initiation of anti-osteoporotic agents in the setting of glucocorticoid exposure is essential, guided by appropriate risk stratification. Recommendations for calcium and vitamin D intake optimization are well-supported across all risk strata. Bisphosphonates are the mainstay of pharmacological therapy. Newer agents such as denosumab and teriparatide have demonstrated comparative benefit in terms of incident fracture risk reduction and bone mineral density preservation, with comparable adverse events. With due consideration to cost, resource availability, and patient values and preferences, these agents may warrant use as the first-line agents in this setting. Glucocorticoid-induced osteoporosis remains preventable and warrants early and targeted evidence-based therapy.
-
8.
Dual-energy CT in musculoskeletal trauma.
Wong, AJN, Wong, M, Kutschera, P, Lau, KK
Clinical radiology. 2021;(1):38-49
Abstract
Dual-energy computed tomography (DECT) combines the advantages of conventional CT with the ability to detect bone marrow oedema (BMO), which was previously limited to magnetic resonance imaging (MRI). By analysing DECT virtual non-calcium (VNCa) maps, radiologists can improve the detection of subtle and occult fractures and approximate the acuity/healing of fractures of indeterminate age. This review highlights the role of DECT in the assessment of musculoskeletal trauma, particularly among elderly, post-menopausal women and those at risk for osteoporosis. DECT is especially useful in investigating trabecular bone predominant regions (e.g., vertebral bodies, pelvis, hip, and long bone metaphyses) for stress (i.e., fatigue or insufficiency) and fragility fractures. CT is often performed first due to its increased availability, especially in the emergency setting, shorter imaging duration, and possible patient contraindications to magnetic resonance imaging (MRI). By enabling BMO detection, DECT may have a role in triaging patients for definitive MRI assessment. Understanding the role of anatomical, pathological, and patient factors in image interpretation can improve radiologist adoption of DECT, increase diagnostic confidence, and improve patient management.
-
9.
Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease: Extended follow-up of the B-PROOF trial.
Oliai Araghi, S, Kiefte-de Jong, JC, van Dijk, SC, Swart, KMA, Ploegmakers, KJ, Zillikens, MC, van Schoor, NM, de Groot, LCPGM, Lips, P, Stricker, BH, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(3):1199-1206
Abstract
BACKGROUND & AIMS In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5-7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk. METHODS Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2-3 years daily supplementation with folic acid (400 μg) and vitamin-B12 (500 μg) versus placebo (n = 2,919). Primary outcome was verified self-reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease. RESULTS A total of 1,298 individuals (44.5%) participated in the second follow-up round with median of 54 months [51-58], (n = 662 and n = 636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0-76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62-1.59 and HR: 0.77; 95% CI: 0.50-1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80-1.44 and OR: 0.85; 95%CI: 0.50-1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic- and any fracture (p = 0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1 μmol/l). No age-dependent effects were present. CONCLUSIONS This study supports and extends previous null-findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated.
-
10.
Vitamin D supplement on prevention of fall and fracture: A Meta-analysis of Randomized Controlled Trials.
Thanapluetiwong, S, Chewcharat, A, Takkavatakarn, K, Praditpornsilpa, K, Eiam-Ong, S, Susantitaphong, P
Medicine. 2020;(34):e21506
-
-
Free full text
-
Abstract
BACKGROUND Vitamin D supplement is one of the current possible interventions to reduce fall and fracture. Despite having several studies on vitamin D supplement and fall and fracture reductions, the results are still inconclusive. We conducted a meta-analysis to examine the effect of vitamin D supplement in different forms and patient settings on fall and fracture. METHODS A systematic literature research was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) to compare the effects of vitamin D supplements on fall and fracture outcomes. Random-effect models were used to compute the weighted mean difference for continuous variables and the risk ratio for binary variables. RESULTS Forty-seven RCTs with 58,424 participants were identified reporting on fall outcome. Twenty-four of 47 studies with 40,102 subjects also reported fracture outcome. Major populations were elderly women with age less than 80 years. Overall, vitamin D supplement demonstrated a significant effect on fall reduction, RR = 0.948 (95% CI 0.914-0.984; P = .004, I = 41.52). By subgroup analyses, only vitamin D with calcium supplement significantly reduce fall incidence, RR = 0.881 (95% CI 0.821-0.945; P < .001, I = 49.19). Vitamin D3 supplement decreased incidence of fall but this occurred only when vitamin D3 was supplemented with calcium. Regarding fracture outcome, vitamin D supplement failed to show fracture lowering benefit, RR = 0.949 (95% CI 0.846-1.064; P = .37, I = 37.92). Vitamin D along with calcium supplement could significantly lower fracture rates, RR = 0.859 (95% CI 0.741-0.996; P = .045, I = 25.48). CONCLUSIONS The use of vitamin D supplement, especially vitamin D3 could reduce incidence of fall. Only vitamin D with calcium supplement showed benefit in fracture reduction.