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Endocrinology of bone mineralization: An update.
Jannin, A, Kerlan, V, Desailloud, R
Annales d'endocrinologie. 2022;(1):46-53
Abstract
Throughout the world, millions of people suffer from fragilizing osteopathies such as osteomalacia and osteoporosis. Osteomalacia is a rare disorder, corresponding to mineralization abnormalities in adult bone, as opposed to rickets in children. Renal phosphate loss and hypophosphatasia are the main causes of vitamin-resistant osteomalacia. Diagnosis is based on clinical history, phosphocalcic metabolism assessment and, if necessary, molecular characterization, and must be rapid in order to initiate the most appropriate treatment and consider new treatments such as burosumab if necessary. Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fracture. Fracture-related burden is expected to increase over the coming decades linked to the aging of population and a treatment gap. In order to reduce this treatment gap, it is important to develop two strategies: improvement of screening and of treatment. Systematic screening using the FRAX® fracture risk assessment tool could be useful to increase anti-osteoporosis medical treatment and reduce fracture rates. The question of treatment sequencing in osteoporosis is another challenge, notably after denosumab cessation, complicated by a decrease in bone mineral density and increased risk of fracture. New treatments are also available, including romosozumab, a humanized monoclonal antibody, which promotes bone formation and inhibits bone resorption by inhibiting sclerostin. Romosozumab is approved in several countries, including France, for treating severe osteoporosis in postmenopausal women at high risk of fracture and free of cardiovascular comorbidity. Endocrinologists need to be aware of these fragilizing osteopathies in order to improve both diagnosis and treatment.
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Association between incident falls and subsequent fractures in patients attending the fracture liaison service after an index fracture: a 3-year prospective observational cohort study.
Vranken, L, Wyers, CE, Van der Velde, RY, Janzing, HMJ, Kaarsemakers, S, Driessen, J, Eisman, J, Center, JR, Nguyen, TV, Tran, T, et al
BMJ open. 2022;(7):e058983
Abstract
OBJECTIVES To evaluate the risk of subsequent fractures in patients who attended the Fracture Liaison Service (FLS), with and without incident falls after the index fracture. DESIGN A 3-year prospective observational cohort study. SETTING An outpatient FLS in the Netherlands. PARTICIPANTS Patients aged 50+ years with a recent clinical fracture. OUTCOME MEASURES Incident falls and subsequent fractures. RESULTS The study included 488 patients (71.9% women, mean age: 64.6±8.6 years). During the 3-year follow-up, 959 falls had been ascertained in 296 patients (60.7%) (ie, fallers), and 60 subsequent fractures were ascertained in 53 patients (10.9%). Of the fractures, 47 (78.3%) were fall related, of which 25 (53.2%) were sustained at the first fall incident at a median of 34 weeks. An incident fall was associated with an approximately 9-fold (HR: 8.6, 95% CI 3.1 to 23.8) increase in the risk of subsequent fractures. CONCLUSION These data suggest that subsequent fractures among patients on treatment prescribed in an FLS setting are common, and that an incident fall is a strong predictor of subsequent fracture risk. Immediate attention for fall risk could be beneficial in an FLS model of care. TRIAL REGISTRATION NUMBER NL45707.072.13.
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Risk factors for vitamin D deficiency in Abu Dhabi Emirati population.
Al Zarooni, AAR, Nagelkerke, N, Al Marzouqi, FI, Al Darmaki, SH
PloS one. 2022;(2):e0264064
Abstract
OBJECTIVE There have been concerns regarding the high prevalence of vitamin D deficiency in the United Arab Emirates and the association between this prevalence and cardiovascular risk. Vitamin D deficiency is a global public health problem, with a high prevalence in the Abu Dhabi national population. This cross-sectional retrospective observational study aimed to elucidate vitamin D deficiency symptoms and contributing factors in this context. METHOD AND SAMPLING Among 12346 participants presenting for their Weqaya population comprehensive cardiovascular risk factor screening, 700 were randomly selected and telephoned, among whom 400 completed a questionnaire that elicited information on dietary intake, sun exposure, clothing, physical activity, and symptoms related to vitamin D deficiency. RESULTS Higher vitamin D levels were noted in participants who consumed extra servings of cod liver oil, tuna, salmon, and eggs; who wore clothes with their arms and legs exposed; and who performed daily physical activity. Symptoms of hypovitaminosis D (bone pain) were more frequently found in females. Fatigue is significantly associated with low vitamin D and younger participants. Strategies focusing on health promotion and lifestyle interventions should be implemented to address vitamin D deficiency.
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Experimental and molecular docking studies of estrogen-like and anti-osteoporosis activity of compounds in Fructus Psoraleae.
Cai, XY, Zhang, ZJ, Xiong, JL, Yang, M, Wang, ZT
Journal of ethnopharmacology. 2021;:114044
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Fructus Psoraleae (FP), dry mature fruits of Cullen corylifolium (L.) Medik., has been used clinically to treat kidney yang deficiency-induced impotence, asthma and cold pain in waist and knee caused by kidney deficiency. A study of the source of the significant kidney-enhancing effect of FP revealed that it may be due to its strong estrogen-like activity. AIM OF THE STUDY This study aimed to investigate the estrogen-like activity of the FP extract and 13 bioactive compounds in it, as well as the mechanisms underlying their estrogen-like and anti-osteoporosis activities. MATERIALS AND METHODS The estrogen-like activities of the 75% ethanol-only FP extract, and 75% ethanol plus petroleum ether, ethyl acetate, n-butanol or water FP extracts were each measured using Cell Counting Kit-8 (CCK-8) and luciferase reporter gene assays. The compounds were identified by high-performance liquid chromatography analysis. The activation of estrogen receptor signaling by the compounds was compared with that by estradiol (E2) using the molecular docking software MOE-Dock 2008.10. The activation of the ER-Wnt-β-catenin signaling pathway was investigated using an alkaline phosphatase (ALP) assay, qPCR analysis and Western blot analysis. RESULTS The results revealed that the 75% ethanol plus ethyl acetate extract showed the highest estrogen-like activity among the four 75% ethanol extract fractions (further extracted with petroleum ether, ethyl acetate, n-butanol or water). Some compounds in FP showed strong estrogenic effect and anti-osteoporosis activity, and activated the Wnt-β-catenin pathway. The isoflavone compound was the most active. CONCLUSIONS This study demonstrated that FP has a strong estrogen-like activity and some of its component compounds have anti-osteoporosis activity by activating the ER-Wnt-β-catenin signaling pathway. Our detections provide a new insight into the mechanisms underlying the estrogen-like and anti-osteoporosis activities of FP, as well as a better understanding of structure effects.
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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.
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The effect of magnetic therapy and moderate aerobic exercise on osteoporotic patients: A randomized clinical study.
Eid, MM, El-Gendy, AM, Abdelbasset, WK, Elkholi, SM, Abdel-Fattah, MS
Medicine. 2021;(39):e27379
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Abstract
BACKGROUND Osteoporosis is a frequent musculoskeletal condition with significant complications that would be a global health problem and one of the major causes of mortality and morbidity. OBJECTIVES The current study aimed to ascertain the impact of pulsed magnetic therapy, aerobic exercise, and a combination of both modalities on osteoporotic female patients postthyroidectomy. METHODS Between May 2018 and September 2019, 45 female patients with osteoporosis were included in the randomized clinical study, their age ranged from 40 to 50 years, had thyroidectomy for at least 6 months ago, and had an inactive lifestyle for at least the previous 6 months. Patients were assigned randomly into 3 equal groups. Group A (magnetic therapy group): received routine medical treatment (bisphosphonates, calcium, and vitamin D) in addition to pulsed magnetic therapy on the hip region for 12 weeks (3 sessions/week). Group B (exercise group): received routine medical treatment plus moderate-intensity aerobic exercise for 12 weeks (3 sessions/week). Group C (combined magnetic therapy and exercise therapy group): received routine medical treatment plus pulsed magnetic therapy and moderate-intensity aerobic exercise for 12 weeks (3 sessions/week). The 3 groups were assessed for bone mineral density (BMD) at baseline by dual-energy x-ray absorptiometry and after 12 weeks of treatment. RESULTS The results showed that within-group analysis a statistically significant increase was reveled (P < .05) for BMD in the 3 studied groups. Comparing the results among the 3 tested groups revealed a significant increase (P < .05) in posttesting mean values of BMD in group (C) compared to group (A) and group (B). No significant statistical difference in BMD means values between the 2 groups (A) and (B) after testing was detected. CONCLUSION Combination of both pulsed magnetic therapy and moderate-intensity aerobic exercise showed significant improvement in BMD at the hip region than using any of the 2 modalities alone.
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Non-Pharmacological Interventions in Osteosarcopenia: A Systematic Review.
Atlihan, R, Kirk, B, Duque, G
The journal of nutrition, health & aging. 2021;(1):25-32
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BACKGROUND Osteosarcopenia is a geriatric syndrome defined by the concomitant presence of osteopenia/osteoporosis (loss of bone mineral density (BMD)) and sarcopenia (loss of muscle mass and/or function), which increases the risk of falls, fractures, and premature mortality. OBJECTIVE To examine the efficacy of non-pharmacological (exercise and/or nutritional) interventions on musculoskeletal measures and outcomes in osteosarcopenic adults by reviewing findings from randomized controlled trials (RCTs). METHODS This review was registered at PROSPERO (registration number: CRD42020179292) and conducted in accordance with the PRISMA guidelines. Electronic databases were searched for RCTs assessing the effect of at least one non-pharmacological intervention (any form of exercise and/or supplementation with protein, vitamin D, calcium or creatine) on any musculoskeletal measure/outcome of interest (BMD, bone strength/turnover, muscle mass and strength, physical performance, falls/fractures) in adults with osteosarcopenia as defined by any proposed criteria. RESULTS Two RCTs (of n=106 older osteosarcopenic adults (≥65 years)) assessing the effects of progressive resistance training (RT) (via resistance bands or machines; 2-3 times/week; ~60 minutes in duration) were eligible for inclusion. The two RCTs demonstrated moderate quality evidence that RT increases muscle mass, strength, and quality, with changes in strength and quality occurring before muscle mass (12 vs 28 weeks). There was low quality evidence that RT increases lumbar spine BMD and maintains total hip BMD when performed for 12 and 18 months, respectively, and moderate quality evidence that RT has no effect on markers of bone turnover or physical performance. No major adverse effects were recorded in either of the RCTs. There were no eligible RCTs examining the impact of nutritional interventions. CONCLUSION Chronic RT is safe and effective at potentiating gains in muscle mass, strength, and quality, and increasing or maintaining BMD in older osteosarcopenic adults. No RCT has examined the effects of protein, vitamin D, calcium, or creatine against a control/placebo in this high-risk population.
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Microscopic Colitis Is Not an Independent Risk Factor for Low Bone Density.
Graziano, EJ, Vaughn, BP, Wang, Q, Chow, LS, Campbell, JP
Digestive diseases and sciences. 2021;(10):3542-3547
Abstract
BACKGROUND Microscopic colitis (MC) is a subtype of inflammatory bowel disease (IBD) with overlapping risk factors for low bone density (LBD). While LBD is a known complication of IBD, its association with MC is not well-established. AIMS Assess the prevalence of LBD in MC compared to control populations, and evaluate if MC predicts LBD when controlling for confounders. METHODS Retrospective, observational case control study of adult patients with pathologically confirmed MC from 2005 to 2015. Bone density measurements were abstracted from dual-energy X-ray absorptiometry (DEXA) reports, and bone density was classified using T-score: normal (T ≥ - 1.0), osteopenia (- 1.0 > T > -2.5) or osteoporosis (T ≤ - 2.5). Demographics, disease, medication history and LBD risk factors were obtained from chart review. Prevalence of LBD was compared to national and local controls. A matched control cohort to MC patients without prior diagnosis of LBD was analyzed with logistic regression to assess the relationship of MC to LBD. RESULTS One hundred and eighteen patients with MC were identified. Osteopenia in women with MC was more prevalent compared to national controls (67% vs. 49%, p = 0.0004), and LBD was more prevalent in MC patients compared to local controls (82% vs. 55%, p < 0.0001). In MC patients without prior diagnosis of LBD matched to controls, there was a higher prevalence of osteopenia (53.2% vs. 36.7%, p = 0.04). However, after controlling for confounders, MC was not associated with LBD (OR 0.83, 95% CI 0.22, 3.16, p = 0.8). CONCLUSIONS While LBD was more prevalent in MC patients compared to control populations, with adjustment for key confounders (including BMI, steroids, smoking, vitamin D and calcium use), MC was not an independent predictor of LBD.
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An evaluation of the effects and safety of Zuogui pill for treating osteoporosis: Current evidence for an ancient Chinese herbal formula.
Li, J, Sun, K, Qi, B, Feng, G, Wang, W, Sun, Q, Zheng, C, Wei, X, Jia, Y
Phytotherapy research : PTR. 2021;(4):1754-1767
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Abstract
The aim of this study is to systematically evaluate existing evidence of the Chinese herbal formula, Zuogui pill (ZGP), for the treatment of osteoporosis. A systematic literature search was performed in six electronic databases. The authors independently extracted data in pairs and evaluated the risk of bias. A total of 221 articles were identified initially, of which 12 relevant studies were enrolled. The primary outcome was fracture incidence and bone mineral density (BMD) at different sites. Bone metabolism markers, clinical symptoms, quality of life, and adverse events or adverse drug reactions (ADRs) were secondary outcomes. The results showed that ZGP, combined with anti-osteoporosis drugs, significantly increased BMD at the lumbar spine, Ward's area, and total hip. In terms of markers for improved bone metabolism, ZGP plus conventional drugs dramatically improved the levels of alkaline phosphatase, bone Gla protein, bone alkaline phosphatase, and tartrate-resistant acid phosphatase. Gastrointestinal discomfort, dizziness, and fatigue were found in the combined therapy group. Although the results indicate that ZGP is a potential candidate for osteoporosis, evidence remains insufficient. Further rigorously designed and high-quality trials with a larger sample size are warranted to verify the current conclusions.
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Blood lipid levels in patients with osteopenia and osteoporosis:a systematic review and meta-analysis.
Zhao, H, Li, Y, Zhang, M, Qi, L, Tang, Y
Journal of bone and mineral metabolism. 2021;(3):510-520
Abstract
INTRODUCTION Considering the controversial relationship between blood lipid levels and osteopenia and osteoporosis (OP), we performed this meta-analysis. MATERIALS AND METHODS Using specific keywords and related words, we searched PubMed, Embase, and Cochrane Library databases. The Newcastle-Ottawa Scale form was used to evaluate the quality of the literature. According to the inclusion and exclusion criteria, we systematically screened the literature to extract relevant information and data. ReVman 5.3 and Stata 13.0 software were used for statistical analysis. Results were expressed as the mean difference (MD) and 95% confidence interval (95% CI). The heterogeneity test was conducted according to I2 and Q tests. Egger's test was used to quantitatively evaluate publication bias. RESULTS This analysis involved 12 studies (12,395 subjects). The quality of the literature was acceptable. Among subjects who were not taking lipid-lowering drugs, total cholesterol (TC) (MD = 0.11 mmol/L, 95%CI: - 0.03, 0.25; I2 = 21%; P = 0.36), triglycerides (TG) (MD = - 0.01 mmol/L, 95%CI: - 0.09, 0.07; I2 = 6%; P = 0.34), and low-density lipoprotein cholesterol (LDL-C) (MD = 0.10 mmol/L, 95%CI: 0.00, 0.19; I2 = 0%; P = 0.74) in the osteopenia were not significantly increased/decreased. There were no significant differences in LDL-C (MD = 0.02 mmol/L, 95%CI: - 0.09, 0.13; I2 = 0%; P = 0.74) in postmenopausal women in osteopenia. TG (MD = - 0.04 mmol/L, 95%CI: - 0.14,0.07; I2 = 49%; P = 0.07) was unchanged in the osteoporosis (OP) group in subjects without taking lipid-lowering drugs. HDL-C was elevated in OP group (MD = 0.05 mmol/L, 95%CI: 0.03, 0.07; I2 = 31%; P = 0.15) but not in osteopenia group (MD = 0.01 mmol/L, 95%CI: - 0.01, 0.02; I2 = 38%; P = 0.14) in all subjects. CONCLUSION HDL-C was elevated in patients with OP.