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Calcium supplements: Benefits and risks
Abstract
Calcium is an essential element in the diet, but there is continuing controversy regarding its optimal intake, and its role in the pathogenesis of osteoporosis. Most studies show little evidence of a relationship between calcium intake and bone density, or the rate of bone loss. Re-analysis of data from the placebo group from the Auckland Calcium Study demonstrates no relationship between dietary calcium intake and rate of bone loss over 5 years in healthy older women with intakes varying from <400 to >1500 mg day(-1) . Thus, supplements are not needed within this range of intakes to compensate for a demonstrable dietary deficiency, but might be acting as weak anti-resorptive agents via effects on parathyroid hormone and calcitonin. Consistent with this, supplements do acutely reduce bone resorption and produce small short-term effects on bone density, without evidence of a cumulative density benefit. As a result, anti-fracture efficacy remains unproven, with no evidence to support hip fracture prevention (other than in a cohort with severe vitamin D deficiency) and total fracture numbers are reduced by 0-10%, depending on which meta-analysis is considered. Five recent large studies have failed to demonstrate fracture prevention in their primary analyses. This must be balanced against an increase in gastrointestinal side effects (including a doubling of hospital admissions for these problems), a 17% increase in renal calculi and a 20-40% increase in risk of myocardial infarction. Each of these adverse events alone neutralizes any possible benefit in fracture prevention. Thus, calcium supplements appear to have a negative risk-benefit effect, and so should not be used routinely in the prevention or treatment of osteoporosis.
© 2015 The Association for the Publication of the Journal of Internal Medicine.
... While pharmacological interventions remain the cornerstone of treatment, there is a growing body of evidence suggesting that nutritional supplementation can play a significant role in managing these conditions by addressing specific nutrient deficiencies and modulating disease 3 pathways [1,2]. Among the supplements gaining attention for their therapeutic potential are omega-3 fatty acids, vitamin D, calcium, chromium, and curcumin. ...
... Calcium supplementation, often used in conjunction with vitamin D, plays a crucial role in maintaining bone health and preventing osteoporosis [3]. Chromium, an essential trace element, has demonstrated potential in enhancing glucose metabolism and improving glycemic control in diabetes [4]. ...
... A systematic review of calcium supplementation in postmenopausal women revealed significant improvements in bone mineral density [11]. Calcium supplementation, particularly in combination with vitamin D, has been shown to reduce fracture risk in older adults, with studies recommending daily doses of 1000-1200 mg to maintain bone health [3]. Furthermore, calcium intake plays a role in reducing the incidence of osteoporotic fractures, a common complication of aging. ...
Introduction: Nutritional supplementation has become an integral part of managing chronic medical conditions, offering potential benefits in improving patient outcomes and quality of life. This review explores the evidence supporting the role of dietary supplements in selected chronic conditions, including cardiovascular disease, diabetes, osteoporosis, and inflammatory disorders, while highlighting potential risks and limitations. Materials and Methods: A systematic review of peer-reviewed literature was conducted using databases such as PubMed, Scopus, and Google Scholar. Studies published between 2010 and 2023 were included if they examined the clinical impact of supplements like omega-3 fatty acids, vitamin D, calcium, chromium, and curcumin. Meta-analyses, randomized controlled trials, and observational studies were prioritized. Data extraction focused on efficacy, safety, and recommended dosages. Results: Evidence suggests that omega-3 fatty acids reduce inflammation and improve lipid profiles in cardiovascular patients. Vitamin D and calcium significantly enhance bone mineral density in osteoporosis. Chromium and alpha-lipoic acid demonstrate modest improvements in glycemic control for diabetes. However, concerns about supplement overuse, potential drug interactions, and variability in product quality persist. Conclusions: While supplementation offers therapeutic benefits in managing specific chronic conditions, its efficacy depends on patient-specific factors, including baseline nutrient status and disease severity. Clinicians must adopt an evidence-based approach, ensuring personalized recommendations and emphasizing the importance of quality control in supplementation practices. Further research is needed to clarify long-term effects and optimal dosages.
... Calcium is a key intracellular messenger and co-factor for various enzymes [2,3]. Ionized calcium, the physiologically active moiety, plays an essential role in many vital physiologic processes, including nerve impulse initiation and neurotransmission, cardiac conduction and contractility, blood coagulation, hormonal secretion, bone formation, skeletal and smooth muscle function, and a host of other crucial and diverse physiological functions [4][5][6][7]. ...
... In our study, those who had an early drop in serum calcium levels within 48 hours had a higher incidence of permanent hypocalcemia (odds ratio = 1.75) compared to those with late onset. A study conducted by Reid et al. (2015) demonstrated that calcium supplementation is critical during the early postoperative period. This finding is supported by our study, where nearly half of the patients required calcium supplementation for up to three months, and some continued to need it for over two years [4]. ...
... A study conducted by Reid et al. (2015) demonstrated that calcium supplementation is critical during the early postoperative period. This finding is supported by our study, where nearly half of the patients required calcium supplementation for up to three months, and some continued to need it for over two years [4]. The 14.3% incidence of calcium supplementation-related complications, such as renal stones and gastrointestinal issues, mirrors reports in the literature on the long-term risks of calcium supplementation. ...
Introduction: Total thyroidectomy is a common surgery in otorhinolaryngology, with hypocalcemia being a potential complication, either transient or permanent. Calcium plays a critical role in many physiological processes, including nerve transmission, cardiac function, and muscle activity. Postoperative hypocalcemia can occur within 48 hours or be delayed up to four days. Risk factors include thyroid size, vascularity, retrosternal extension, and surgical extent. Timely treatment is essential, especially in acute cases, to avoid long-term complications. The objective of the study is to evaluate the impact of retrosternal extension and central compartment clearance on postoperative hypocalcemia in patients undergoing total thyroidectomy and the duration and severity of hypocalcemia.
Methods: A retrospective analysis was conducted on patients who underwent total thyroidectomy at a tertiary rural hospital from January 2016 to June 2024. Patients were categorized into two groups: those with retrosternal extension and/or central compartment clearance and those without. Postoperative serum calcium levels were documented over four days post-surgery, and the incidence and duration of hypocalcemia were compared between the groups.
Results: Out of 69 patients, 21 (30.4%) developed hypocalcemia postoperatively. Patients with retrosternal extension had a higher incidence of hypocalcemia (odds ratio = 3.58) compared to those without. Additionally, patients with central compartment clearance showed a higher risk of early postoperative hypocalcemia. The severity of hypocalcemia was greater in patients with malignancy and more extensive surgical procedures. Recovery time varied, with some patients requiring long-term calcium supplementation beyond one year.
Conclusion: Retrosternal extension and central compartment clearance significantly increase the risk of postoperative hypocalcemia. Although not statistically significant, the trends suggest a need for careful surgical techniques and rigorous postoperative calcium management to prevent prolonged hypocalcemia. Further prospective studies are recommended to confirm these findings and improve postoperative care strategies.
... Release rate was quantifed according to Chinese Pharmacopeia 2020, Book 4, Issue 0931, Method 2. Te rotator was set at 50 rpm, and release medium was 700 mL chloride hydrate solution (pH � 1). 5 mL samples were taken at 5,10,15,20,30,45,60,90, and 120 min, the same volume of medium was supplemented after each sampling. Calcium concentration was measured according to Mohammad's reports using a Spec-trAA-240FS fame atomic absorption spectroscopy (FAAS) system (Agilent, USA) [16]. ...
... Samples of standard vitamin D 3 (Shuangjing Pharmacy, China) and CCCG containing 800 IU were radiated under UV light at the distance of 20 cm. Samples were taken at the timing of 0, 5,10,15,20,30,45,60,90, and 120 min. Vitamin D 3 measurement was carried out with high-performance liquid chromatography (HPLC) according to Chinese Pharmacopeia 2020, Book 4, Issue 0512. ...
... limitation of the calcium carbonate supplements currently used includes the adverse efects on gastrointestinal tract and urinary calculus. Tey are manifested by the change of gastric emptying, the increase of calcium ion concentration in urine and urine acidity, which can promote the formation of calculus [20,21]. In addition to calcium supplement, it is worth noting that calcium carbonate exists in various polymorphs, such as calcite, aragonite, and vaterite [22]. ...
Osteoporosis (OP) has been a global health concern, and calcium supplements are still an effective method to relieve the disease. In this study, we investigated the pharmaceutical properties, antiosteoporosis, and adverse effects of a novel calcium supplement named compound calcium carbonate granule (CCCG). The dissolution rate, stability of vitamin D3, and drug permeability of the calcium supplements were explored. And the osteoporosis was constructed in mice with retinoic acid (100 mg/kg/d) for 21 days, and orally treated with CCCG (0.34, 0.68, and 1.36 g/kg/d) for 36 days to evaluate the efficacy against osteoporosis and the occurrence of kidney stones. The results showed that CCCG exhibited higher dissolution rate and better vitamin D3 stability than the standard calcium carbonate granule. CCCG also displayed more absorption in Caco-2 cell model. On the other hand, CCCG alleviated the deterioration in femur microstructure and oxidative stress in the liver and kidney, and increased the expression of bone metabolic markers. CCCG also exhibited lower risk of nephrolithiasis than the commercial calcium carbonate granule. In summary, from the perspectives of both pharmaceutics and efficacy, we illustrated the profiles of an intriguing calcium supplement, which could possibly be an alternative of commonly used ones. Practical Application. Calcium carbonate is widely used to supplement calcium, primarily because of its high calcium load, low cost, and good efficacy. Now, we provided a new calcium supplement named CCCG, which was prepared by inclusion and complexation techniques. Vitamin D3 in CCCG was made into vitamin D-β-cyclodextrin inclusion complex by inclusion technology, which improved the stability of vitamin D3. And calcium carbonate was converted to a water-soluble calcium citrate complex via complexation techniques to accelerate the release of calcium ions and minimize the risk of kidney stone formation. From the perspective of both pharmaceutics and efficacy, we illustrated the profiles of an intriguing calcium supplement, which could possibly be an alternative for the supplemental and preventive treatment of osteoporosis.
... Because balance is the difference between intake and output, there is a mathematical inevitability that a positive relationship will be found between balance and intake even if there is no biological basis for it. Subsequent observational studies and clinical trials of calcium supplementation have not demonstrated that postmenopausal bone loss can be halted with these calcium intakes [14][15][16]. More recent calcium balance studies in adults which avoided the statistical error of the Heaney studies concluded that "calcium balance was highly resistant to a change in calcium intake across a broad range of typical dietary calcium intakes (415-1,740 mg/day…)" [17]. ...
... Calcium intakes ranged from 300 mg/day to 2000 mg/ day. Both studies demonstrated ongoing loss of total body bone mineral which was unrelated to calcium intakes across the study periods [14,15]. A similar 2-year study in older men also showed no effect of calcium intake on bone balance [19]. ...
Purpose of Review
To assess the efficacy of calcium supplements in preventing fractures, and to review their adverse effects, particularly on the cardiovascular system.
Recent Findings
There is now a large body of trial evidence demonstrating that calcium supplements do not prevent fractures in community-dwelling adults. They commonly produce gastrointestinal side-effects, sometimes serious, and increase the risk of renal calculi. Meta-analyses of adverse events from clinical trials suggest that the risk of MI is increased by 10–20% with calcium supplementation, though dietary calcium intake does not appear to be a cardiac risk factor. Ingestion of a calcium bolus increases circulating calcium concentrations for the following 8 h, accompanied by acute increases in blood coagulability and calcification propensity, with blood pressures > 5 mmHg higher than placebo-treated individuals. Mendelian randomization studies demonstrate that circulating calcium levels are a significant risk factor for cardiovascular disease, so the acute calcium-elevating effect of supplements might contribute to increased cardiovascular risk.
Summary
The current balance of evidence suggests that calcium supplements have little role in the prevention or treatment of osteoporosis, since estrogen and bisphosphonates prevent fractures without their co-administration. Specific studies are needed to address whether calcium is benficial with anabolic bone medicines.
... Increased potassium intake lowers the risk of cardiovascular disease as well as the incidence of stroke, demonstrating the strong connection between dietary potassium and cardiovascular health [7]. The impact of supplemental calcium and phosphorus on cardiovascular outcomes, however, is still debatable [8,9]. Therefore, further research is needed to determine how calcium, phosphorus, and potassium intake affect erectile dysfunction. ...
... However, it is important to remember that consuming too much calcium may have detrimental effects on cardiovascular health [37,38]. Therefore, maintaining a calcium intake of 500-1,000 mg per day may be an appropriate choice [9]. ...
Background
Erectile dysfunction is now a common disorder of sexual function, and its relationship to dietary calcium, phosphorus, and potassium has not been well studied. We set out to determine if dietary intakes of calcium, phosphorus, and potassium are related to erectile dysfunction in U.S. men.
Methods
For this cross-sectional investigation, we used data from NHANES 2001–2004. To investigate the connection of dietary calcium, phosphorus, and potassium intake with erectile dysfunction, we employed multivariate logistic regression, smoothed curve fitting, and subgroup analysis.
Results
This cross-sectional study comprised 3,556 eligible male subjects in total, with a weighted mean age of 49.93±18.13 years. After controlling for race and age, the greatest tertile of calcium consumption was found to have a 34% lower risk of erectile dysfunction than the lowest tertile (OR = 0.66; 95% CI = 0.52–0.84; p = 0.0006). The risk of erectile dysfunction was found to be reduced by 33% (OR = 0.67; 95% CI = 0.52–0.87; p = 0.0024) for the highest tertile of phosphorus intake compared to the lowest tertile of phosphorus intake and by 35% (OR = 0.65; 95% CI = 0.50–0.83; p = 0.0006) for the highest tertile of potassium intake compared to the lowest tertile of potassium intake in the fully adjusted model.
Conclusion
Erectile dysfunction and dietary consumption of calcium, phosphorus, and potassium are inversely associated with the U.S. population. To confirm the accuracy of our findings, additional prospective studies are necessary. Furthermore, it is imperative to do further fundamental research at the molecular level to gain a deeper understanding of the underlying mechanisms.
... Vitamin K formulation contains phytonadione (vitamin K1) while calcium gluconate formulation contains mainly calcium. The relatively lower frequency of prescription of Vitamin K and calcium gluconate may be as a result of the specificity of their use and clinical application (Reid et al., 2015;Papich, 2016;Simes et al., 2020), in contrast to Vitamin B-Complex injection, multivitamin injection and tablets & oral V-MF which are generally used to handle several deficiency disorders/diseases and in resuscitating recuperating patients (EFSA, 2006;Rock-Cheryl, 2007;Menon et al., 2008). Earlier reports by Adisa et al. (2015), also showed that calcium gluconate was the second least frequently prescribed vitamin/mineral in selected health facilities in Ibadan Nigeria, as was also found in this present study. ...
... Specifically, the annual frequency of prescriptions for calcium gluconate ranged from 2.1% to 2.7% during the study period, while that of iron dextran ranged from 12.8% to 15.8% and that of vitamin K ranged from 0.9% to 1.2% (Table 2). The lack of significant variations in the frequency of prescriptions for calcium gluconate, iron dextran and Vitamin K across the study period is thought be as a result of the earlier stated strict specificity of their clinical use and application (Reid et al., 2015;Papich, 2016;Simes et al., 2020), in comparison with the others such as Vitamin B-Complex injection, multivitamin injection and tablets & oral V-MF which are routinely used to handle several deficiency diseases/disorders and overall patient recuperation (EFSA, 2006;Rock-Cheryl, 2007;Menon et al., 2008). ...
... Calcium is essential for the development and maintenance of strong bones and teeth. It is also necessary for muscle contraction, including the beating of the heart [81,82]. ...
... Calcium is essential for the development and maintenance of strong bones and teeth while it is also necessary for muscle contraction, including the beating of the heart [111,112]. Chromium helps maintain normal blood sugar levels by enhancing the action of insulin and also contributes to the metabolism of carbohydrates, fats, and proteins [113,114]. ...
... In general, calcium doses ≥ 1000 mg/day were used in supplement studies. Studies have found that, with the exception of people with very low calcium intake, doses of 250-600 mg per day have little or no effect on bone mineral density [20]. Collectively, these findings suggest that calcium supplementation, as a less potent antiresorptive agent, reduces bone turnover regardless of baseline calcium intake. ...
Objective
Despite the well-known benefits of calcitriol and bisphosphonates in managing osteoporosis, limited research has explored the combined therapeutic effects of these agents on bone metabolism, immune function, and clinical outcomes in postmenopausal osteoporosis patients. This study aims to evaluate the clinical efficacy and safety of calcitriol combined with bisphosphonates in the treatment of postmenopausal osteoporosis through a retrospective cohort analysis.
Methods
A total of 152 postmenopausal osteoporosis patients treated at our hospital from March 2019 to June 2021 were enrolled and divided into two groups based on the treatment received. The control group received calcitriol alone, while the study group received calcitriol combined with bisphosphonates. Treatment outcomes were assessed by comparing Visual Analogue Scale (VAS) scores for pain, Barthel Index for daily living ability, and Oswestry Disability Index (ODI) for dysfunction before and after treatment. Bone metabolism markers (BALP, BGP, PINP, TRACP), immune cytokines (IL-6, TGF-β1, TNF-α, IL-10), and bone mineral density (BMD) were measured. The incidence of adverse reactions was also recorded.
Results
The total effective rate in the study group was 96.05%, significantly higher than 84.21% in the control group (P < 0.05). Post-treatment VAS and ODI scores decreased significantly in both groups, with greater improvement in the study group (P < 0.05). Barthel Index scores increased more in the study group (P < 0.05). Bone metabolism markers (BALP, BGP, PINP, TRACP) and inflammatory cytokines (IL-6, TGF-β1, TNF-α) decreased more significantly in the study group, while IL-10 levels and BMD increased more markedly (P < 0.05). The incidence of adverse reactions was lower in the study group (2.63%) than in the control group (5.26%), but the difference was not statistically significant (P > 0.05).
Conclusion
The combination of calcitriol and bisphosphonates demonstrates superior clinical efficacy and safety in treating postmenopausal osteoporosis, effectively reducing pain and disability, enhancing bone metabolism and immune function, and improving bone mineral density and daily living ability.
... To the best of our knowledge, this study presents evidence that the role of Calcium (and probably cathelicidin) in rosacea should be further discussed and researched. Moreover, Calcium supplements appear to have a negative risk-benefit effect, 34 and should be used with caution in rosacea patients. ...
Purpose
Recent advances in epidemiological and genetic studies have provided some insights regarding the pathophysiology of rosacea, but the majority of its underlying mechanisms are still poorly understood. In particular, more data are needed to fully understand the role of micronutrients in rosacea development. This study aimed to explore the causality of associations between Calcium, Copper, Selenium, Zinc, Iron, Potassium and Magnesium with the risk of rosacea.
Patients and Methods
This was a two-sample Mendelian Randomization (MR) study that used data from genome-wide association studies (GWAS) on serum levels of selected micronutrients as exposure and rosacea as the outcome. The analysis primarily employed the Inverse Variance Weighted (IVW) method. Additional methods included weighted median, weighted mode, and MR-Egger regression. Sensitivity analysis included MR-Egger, MR-PRESSO, Cochran’s Q, and leave-one-out methods. A total of 301 Instrumental Variables were selected for analysis.
Results
The genetic prediction indicated a statistically significant association between serum Calcium levels and higher rosacea risk (Odds Ratio (OR) = 2.27, 95% Confidence Interval (CI): 2.02–2.55, P < 0.001), further confirmed by all supplementary MR methods. Significant association was also found between serum Potassium levels and lower rosacea risk (OR = 0.36, 95% CI: 0.14–0.93, P = 0.0354), further confirmed by the weighted-median method. Sensitivity analyses showed that the results were robust and not driven by any single factor, with low probability of horizontal pleiotropy.
Conclusion
This study found an evidence of a causal association between genetically predicted serum levels of Calcium and Potassium with the risk of rosacea. The roles of these micronutrients should be further studied in rosacea, especially as a link to neurovascular dysregulation and oxidative stress.
... They have better bioavailability, solubility and absorption rates compared to calcium carbonate. Additionally, they are not as affected by changes in gastric pH (Reid et al., 2015). Fishbones, cuttlebones, shrimp shells, crab shells and other shells are the most common marine sources of calcium organic acids. ...
Calcium is an important mineral that is essential for human health,
particularly bone health. Marine biological calcium is a plentiful supply
with a complicated active structure that is well accepted. India has a
long coastline, and seafood is an important element of its cuisine,
culture and economy. However, seafood processing generates a
significant amount of waste, which causes environmental issues and
creates waste management challenges. Simultaneously, calcium
deficiency is a serious public health problem in India, impacting people
of all ages. This article presents a solution to both of these issues at
the same time by extracting calcium supplements from seafood trash.
The article investigates and assesses the viability of using discarded
seafood shells as a source of calcium supplements and the provision
of a low-cost and long-term solution.
... Las variables numéricas fueron proporcionadas en formato de promedio junto con su respectiva desviación estándar, la cual se calculó como la suma de la media y la resta de la desviación estándar 11 . Las discrepancias en promedios fueron analizadas mediante la prueba de t de Student de dos colas para conjuntos de datos que no están relacionados entre sí. ...
Introducción: En Ecuador, el 94% de las personas no sigue las pautas recomendadas para ingerir alimentos que contienen calcio, el cual está vinculado con la salud de los huesos y se relaciona de manera opuesta con el índice de masa corporal, contribuyendo al riesgo de sobrepeso y obesidad. La cantidad diaria recomendada (RDA) de calcio para adolescentes se establece en 1.300 miligramos por día. Objetivo: Describir cómo la ingesta de calcio y el estado nutricional influyen en la densidad mineral ósea (DMO) de los estudiantes que están cursando la formación de auxiliar de enfermería. Métodos: Un estudio transversal, retrospectivo con 49 estudiantes de 19 a 21 años, aparentemente sanos. La cantidad de alimentos consumidos fue evaluada a través de un análisis que consistió en que los participantes recordaran y detallaran todo lo que habían comido en un periodo de 24 horas. Resultados: En la muestra de individuos examinados, donde más de la mitad eran mujeres (51%), se descubrió que un porcentaje del 18% tenía obesidad y un 25% mostraba sobrepeso. El 68% de los jóvenes consumió una cantidad menor al 50% de la cantidad de calcio recomendada para la ingesta. En hombres, el consumo medio de calcio se situó en 658 miligramos por día con una desviación estándar de 328 miligramos, mientras que en mujeres fue de 568 miligramos por día con una desviación estándar de 299 miligramos. El puntaje Z estandarizado de la DMO fue dentro del rango considerado normal para hombres y mujeres, con una desviación estándar mayor de -1. Conclusión: No se encontró ninguna correlación entre la cantidad de calcio consumida por los estudiantes y la densidad ósea de sus huesos. Se encontró una asociación entre la mineralización ósea y el estado nutricional, observándose que la densidad mineral ósea era más alta en las personas con obesidad.
... Another study reported that calcium supplementation benefits in pregnancy, is prominent in populations with a low baseline calcium intake compared to those with adequate calcium intake (17). Although excessive intake of calcium has some undesirable effects such as constipation, reduced iron absorption, flatulence, urinary stone, and myocardial infarction (18)(19). However, acceptable calcium intake in pregnancy could prevent fetal growth restriction, preterm birth, and reduce fracture risks (20). ...
... Another study reported that calcium supplementation benefits in pregnancy, is prominent in populations with a low baseline calcium intake compared to those with adequate calcium intake (17). Although excessive intake of calcium has some undesirable effects such as constipation, reduced iron absorption, flatulence, urinary stone, and myocardial infarction (18)(19). However, acceptable calcium intake in pregnancy could prevent fetal growth restriction, preterm birth, and reduce fracture risks (20). ...
... Do vậy, hạ calci máu nếu không được phát hiện sớm để điều trị kịp thời sẽ rất nguy hiểm với bệnh nhân, đặc biệt ở những bệnh nhân có những triệu chứng muộn khi đã xuất viện. Bên cạnh đó, việc sử dụng thường quy các chế phẩm calci và vitamin D với mục đích phòng ngừa hạ calci máu sẽ không có lợi và có thể có các tác dụng phụ như chán ăn, buồn nôn, đầy hơi, táo bón gây khó chịu cho bệnh nhân nếu bệnh nhân thuộc nhóm nguy cơ thấp hoặc không hạ calci, điều này sẽ làm tăng thêm chi phí cho người bệnh trong việc sử dụng thuốc và cần làm thêm xét nghiệm theo dõi điều trị trong một khoảng thời gian dài [7]. Năm 2018, Ủy ban Phẫu thuật thuộc Hiệp hội tuyến giáp Hoa Kỳ (American Thyroid Association -ATA) đã đưa ra khuyến nghị về nồng độ parathyroid hormone (PTH) huyết thanh ở người lớn được đo sau 20 phút kể từ khi phẫu thuật cắt bỏ tuyến giáp có giá trị ≥15 pg/mL sẽ không cần theo dõi và bổ sung calci và ngược lại, nếu PTH huyết thanh <15 pg/mL sẽ cần bổ sung calci và/hoặc định lượng nồng độ calci máu để theo dõi liên tiếp cho đến khi nồng độ calci trở về bình thường [5]. ...
Mục tiêu: Xác định nồng độ PTH và CalciTP huyết tương ở bệnh nhân ung thư tuyến giáp thể biệt hóa trước và sau phẫu thuật triệt căn tại Bệnh viện Trung ương Thái Nguyên giai đoạn 2023-2024. Đối tượng và phương pháp nghiên cứu: Mô tả cắt ngang có theo dõi dọc trên 65 bệnh nhân được chẩn đoán Ung thư tuyến giáp thể biệt hóa được phẫu thuật triệt căn tại Bệnh viện Trung ương Thái Nguyên từ tháng 4/2023 đến tháng 4/2024. Kết quả: Độ tuổi trung bình của bệnh nhân là 45,5 tuổi, trong đó bệnh nhân nữ chiếm đa số (92,3%). Kết quả mô bệnh học sau phẫu thuật chủ yếu là Ung thư biểu mô tuyến giáp thể nhú, chiếm 95,4%. Hầu hết bệnh nhân được phẫu thuật cắt tuyến giáp toàn bộ (90,8%) và nạo vét hạch cổ trung tâm là (66,2%) với thời gian phẫu thuật trung bình là 93,87 phút. Sự dao động của nồng độ PTH tại các thời điểm trước phẫu thuật, sau phẫu thuật 1 ngày và sau phẫu thuật 1 tháng lần lượt là: 40,43pg/mL, 19,84pg/mL và 36,41pg/mL. Nồng độ calci toàn phần tại các thời điểm trước phẫu thuật, sau phẫu thuật 1 ngày và sau phẫu thuật 1 tháng lần lượt là: 2,31mmol/l, 2,12mmol/l và 2,27mmol/l. Tỷ lệ hạ calci máu cao nhất là ở thời điểm sau phẫu thuật 1 ngày, chiếm 35,4%. Kết luận: Nồng độ PTH và CalciTP huyết tương sau phẫu thuật triệt căn có sự biến thiên và đều thấp hơn thời điểm trước phẫu thuật (p<0,05). Trong đó nồng độ PTH và CalciTP huyết tương giảm mạnh nhất ở thời điểm sau phẫu thuật 1 ngày và phục hồi một phần ở thời điểm 1 tháng.
... It helps regulate cellular processes, such as cell division and gene expression, by acting as a secondary messenger in many hormone and neurotransmitter pathways. This regulation is critical for maintaining the health and function of cells and for the body's response to external signals [90]. ...
Metals are integral components of the natural environment, and their presence in the food supply is inevitable and complex. While essential metals such as sodium, potassium, magnesium, calcium, iron, zinc, and copper are crucial for various physiological functions and must be consumed through the diet, others, like lead, mercury, and cadmium, are toxic even at low concentrations and pose serious health risks. This study comprehensively analyzes the presence, importance, and consequences of metals in the food chain. We explore the pathways through which metals enter the food supply, their distribution across different food types, and the associated health implications. By examining current regulatory standards for maximum allowable levels of various metals, we highlight the importance of ensuring food safety and protecting public health. Furthermore, this research underscores the need for continuous monitoring and management of metal content in food, especially as global agricultural and food production practices evolve. Our findings aim to inform dietary recommendations, food fortification strategies, and regulatory policies, ultimately contributing to safer and more nutritionally balanced diets.
... Thus, calcium and phosphate levels are affected, and this may lead to hypocalcemia and hyperphosphatemia [4]. Hypocalcemia is an abnormality of ionized blood calcium, due to increased calcium loss or decreased calcium entry into circulation [5][6][7]. In its acute form, it can cause neuromuscular manifestations (paresthesia, muscle spasms, and epileptic seizures) or cardiac manifestations (ST-segment and QT prolongation without T-wave modification, atrioventricular blocks, and ventricular fibrillation) [8]. ...
Objective: Familial isolated hypoparathyroidism is a rare genetic disorder due to no or low production of the parathyroid hormone, disturbing calcium and phosphate regulation. The resulting hypocalcemia may lead to dental abnormalities, such as enamel hypoplasia. The aim of this paper was to describe the full-mouth rehabilitation of a 15-year-old girl with chronic hypocalcemia due to a rare congenital hypoparathyroidism. Clinical considerations: In this patient, in the young adult dentition, conservative care was preferred. Onlays or stainless-steel crowns were performed on the posterior teeth, and direct or indirect (overlays and veneerlays) were performed on the maxillary premolars, canines, and incisors, using a digital wax-up. The mandibular incisors were bleached. The treatment clearly improved the patient’s oral quality of life, with fewer sensitivities, better chewing, and aesthetic satisfaction. The difficulties were the regular monitoring and the limited compliance of the patient. Conclusion: Despite no clinical feedback in the literature, generalized hypomineralized/hypoplastic teeth due to hypoparathyroidism in a young patient can be treated as amelogenesis imperfecta (generalized enamel defects) with a conservative approach for medium-term satisfactory results. Highlights: This study provides new insights into the management of enamel hypoplasia caused by familial isolated hypoparathyroidism, helping to improve patient outcomes in similar cases.
... Calcium serves as a second messenger and plays a crucial role in numerous physiological processes, such as preserving bone health, facilitating cellular coagulation, transmitting neurotransmitters, sustaining muscle contraction, stimulating enzyme activity, and regulating immune function (Pu et al., 2016). To maintain good health, the World Health Organization (WHO) suggests that adults consume 1000 mg of calcium daily, while those over 65 should aim for 1300 mg daily (Reid et al., 2015). However, a study that examined the calcium intake of 74 countries worldwide revealed that Southeast Asia has a low calcium intake (<400 mg/day), and Africa and South America have a moderate calcium intake (400−700 mg/day), far below the WHO recommendations (Balk et al., 2017). ...
Sucrose emerges as a chelating agent to form a stable sucrose‐metal‐ion chelate that can potentially improve metal‐ion absorption. This study aimed to analyze the structure of sucrose‐calcium chelate and its potential to promote calcium absorption in both Caco‐2 monolayer cells and mice. The characterization results showed that calcium ions mainly chelated with hydroxyl groups in sucrose to produce sucrose‐calcium chelate, altering the crystal structure of sucrose (forming polymer particles) and improving its thermal stability. Sucrose‐calcium chelate dose dependently increased the amount of calcium uptake, retention, and transport in the Caco‐2 monolayer cell model. Compared to CaCl2, there was a significant improvement in the proportion of absorbed calcium utilized for transport but not retention (93.13 ± 1.75% vs. 67.67 ± 7.55%). Further treatment of calcium channel inhibitors demonstrated the active transport of sucrose‐calcium chelate through Cav1.3. Cellular thermal shift assay and quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) assays indicated that the ability of sucrose‐calcium chelate to promote calcium transport was attributed to its superior ability to bind with PMCA1b, a calcium transporter located on the basement membrane, and stimulate its gene expression compared to CaCl2. Pharmacokinetic analysis of mice confirmed the calcium absorption‐promoting effect of sucrose‐calcium chelate, as evident by the higher serum calcium level (44.12 ± 1.90 mg/L vs. 37.42 ± 1.88 mmol/L) and intestinal PMCA1b gene expression than CaCl2. These findings offer a new understanding of how sucrose‐calcium chelate enhances intestinal calcium absorption and could be used as an ingredient in functional foods to treat calcium deficiency.
Practical Application
The development of high‐quality calcium supplements is crucial for addressing the various adverse symptoms associated with calcium deficiency. This study aimed to prepare a sucrose‐calcium chelate and analyze its structure, as well as its potential to enhance calcium absorption in Caco‐2 monolayer cells and mice. The results demonstrated that the sucrose‐calcium chelate effectively promoted calcium absorption. Notably, its ability to enhance calcium transport was linked to its strong binding with PMCA1b, a calcium transporter located on the basement membrane, and its capacity to stimulate PMCA1b gene expression. These findings contribute to a deeper understanding of how the sucrose‐calcium chelate enhances intestinal calcium absorption and suggest its potential use as an ingredient in functional foods for treating calcium deficiency.
... It is important to ask patients on calcium supplements about constipation, bloating, kidney stones, and possible vascular disease, which though not proven, is certainly a consideration in SSc [21]. As such, a dietary source rather than pill supplementation of calcium is preferred [22]. Supplementation with calcium alone does not reduce fracture risk, and vitamin D supplementation, rather than calcium, though controversial, may reduce falls risk in the elderly when combined with other prevention approaches [14,23,24]. ...
Bone health in systemic sclerosis (SSc) is an essential management consideration for rheumatologists caring for these patients. Screening for reduction in bone density includes a detailed health history, which includes SSc disease features such as intestinal malabsorption, patulous esophagus, and calcinosis. The established International Society for Clinical Densitometry (ISCD) guidelines provide an official position statement on important topics in skeletal assessment. Bone health laboratory testing are indicated in all SSc patients, especially if a low serum albumin or vitamin deficiencies are detected. Bone health treatment considerations include adequate weight bearing exercise, calcium, and vitamin D in all SSc patients. The key findings of this chapter is that SSc patients are at increased risk for low bone density and comorbidities may affect choice of treatment such as oral bisphosphonates in SSc patients with significant esophageal disease or renal impairment and osteoanabolic therapies in SSc patients with calcinosis are important.
... N º 2 6 -2 0 2 0 I S S N : 1 6 4 6 -8 8 4 8 Os cálculos renais no trato urinário são, normalmente, compostos por oxalato de cálcio. Uma elevada ingestão de cálcio, proveniente de fontes alimentares ou de suplementos, está associada a um aumento de excreção urinária deste mineral, o que pode permitir um aumento de risco de litíase renal (Houtkooper et al., 2017; National Institutes of Health: Office of Dietary Supplements, 2018; Reid, Bristow & Bolland, 2015). Uma estratégia para prevenir este aumento do risco de formação de cálculos renais, passa por consumir quantidades adequadas de cálcio, de forma a assegurar as doses diárias recomendadas de ingestão, evitando assim o consumo em excesso deste mineral (Houtkooper et al., 2017). ...
O cálcio desempenha um papel fundamental na formação óssea, na regulação da contração muscular, na transmissão de impulsos nervosos e na secreção hormonal. A adequada concentração deste elemento no organismo é fundamental para a homeostasia em todas as fases da vida do ser humano. No metabolismo do cálcio, a vitamina D tem um contributo essencial para a absorção deste mineral e para a sua deposição óssea. De acordo com os valores de Dietary Reference Intakes (DRI), a quantidade de cálcio que deve ser ingerida diariamente consegue ser obtida através de uma dieta equilibrada com fontes alimentares ricas em cálcio, como laticínios, hortofrutícolas, leguminosas, peixe e ovos. Contudo, sempre que tal não se possa verificar, a suplementação é uma alternativa a considerar. Este artigo de revisão bibliográfica tem como objetivo principal indicar os grupos que poderão necessitar de suplementação e os riscos que o excesso da ingestão de cálcio poderá trazer. De facto, atualmente a indústria farmacêutica disponibiliza variadas fórmulas farmacêuticas que têm compostos à base de cálcio como substância ativa, podendo ser usados na prevenção e tratamento de diversas patologias, que geralmente estão relacionadas com a carência do mesmo na alimentação diária. Incluem-se aqui suplementos para grupos de risco de insuficiência em cálcio, assim como fármacos para doenças como osteoporose, raquitismo ou osteomalacia. Os suplementos de cálcio mais usados são o carbonato de cálcio e o citrato de cálcio. É de notar que existem interações entre o cálcio e alguns alimentos ou medicamentos.
... Another study reported that calcium supplementation benefits in pregnancy, is prominent in populations with a low baseline calcium intake compared to those with adequate calcium intake (17). Although excessive intake of calcium has some undesirable effects such as constipation, reduced iron absorption, flatulence, urinary stone, and myocardial infarction (18)(19). However, acceptable calcium intake in pregnancy could prevent fetal growth restriction, preterm birth, and reduce fracture risks (20). ...
Background: Hypertension in pregnancy with or without proteinuria is one of the foremost reasons of maternal death and morbidity in the world. This study investigated the role of a high calcium diet (HCa) in N G -nitro-L-arginine methyl ester (L-NAME) administered to pregnant rats. Methods: Thirty-two female rats of the Sprague-Dawley strain were randomly assigned into 4 groups of control, L-NAME (0.3g/ L of water), L-NAME + HCa (2.5%), and HCa diet (2.5%) group. Following confirmation of mating, HCa was administered from day 3 to day 18 of pregnancy while L-NAME was administered from day 12 to 18. The rats were sacrificed on the 19th day and blood pressure measurements were obtained. Blood and placenta were collected for biochemical and oxidative assays. Results: Blood pressure was reduced in L-NAME + HCa rats compared with L-NAME (p<0.05). Placenta and fetal weight were decreased in rats receiving L-NAME, L-NAME + HCa and HCa compared with control (p<0.05). HCa diet had no effect on L-NAME impaired oxidative status. No significant difference was observed in the liver enzymes and CRP levels across the groups. However, there was a significant reduction in the platelet count of L-NAME + HCa and HCa groups when compared with the control and L-NAME. Calcium and magnesium levels in the serum and placenta homogenate were not different but their excretion was significantly increased in the urine samples of the L-NAME + HCa and HCa groups. Conclusion: This study showed that HCa reduced the blood pressure of pregnant rats administered L-NAME but had no effect on oxidative stress. This implies that HCa alone might not sufficiently ameliorate the negative effects of hypertension in pregnancy.
... This directly inhibits intestinal peristalsis and causes constipation. 40 Psychological and emotional abnormalities, like anxiety or depression, could also induce constipation in patients. 41 It has been reported that abnormal scores on the anxiety and depression scale could increase the risk of constipation; This might be due to psychological factors, like anxiety and depression that affect the sensory, motor, and secretory functions of the gastrointestinal tract. ...
Purpose
Constipation is a common complication of diabetic patients, which has a negative impact on their own health. This study aims to establish and internally validate the risk nomogram of constipation in patients with type 2 diabetes mellitus (T2DM) and to test its predictive ability.
Patients and Methods
This retrospective study included 746 patients with T2DM at two medical centers. Among the 746 patients with T2DM, 382 and 163 patients in the Beilun branch of the First Affiliated Hospital of Zhejiang University were enrolled in the training cohort and the validation cohort, respectively. A total of 201 patients in the First Affiliated Hospital of Nanchang University were enrolled in external validation cohorts. The nomogram was established by optimizing the predictive factors through univariate and multivariable logistic regression analysis. The prediction performance of the nomogram was measured by the area under the receiver operating characteristic curve (AUROC), the calibration curve, and the decision curve analysis (DCA). Furthermore, its applicability was internally and independently validated.
Results
Among the 16 clinicopathological features, five variables were selected to develop the prediction nomogram, including age, glycated hemoglobin (HbA1c), calcium, anxiety, and regular exercise. The nomogram revealed good discrimination with an area under the receiver operating characteristic curve (AUROC) of 0.908 (95% CI = 0.865–0.950) in the training cohort, and 0.867 (95% CI = 0.790–0.944) and 0.816 (95% CI = 0.751–0.881) in the internal and external validation cohorts, respectively. The calibration curve presented a good agreement between the prediction by the nomogram and the actual observation. The DCA revealed that the nomogram had a high clinical application value.
Conclusion
In this study, the nomogram for pretreatment risk management of constipation in patients with T2DM was developed which could help in making timely personalized clinical decisions for different risk populations.
... Based on this pathophysiological background, many authors expressed their concern about prescribing such supplementations to SF patients, particularly for those who are also hypercalciuric [107][108][109]. ...
Patients with urolithiasis, and particularly those with hypercalciuria, frequently have a marked reduction of bone mineral content up to the levels of osteoporosis, with a significant increase in bone fracture risk. For these reasons, the indication to prescribe vitamin D and/or calcium supplementations is very frequent in such patients. On the other hand, both calcium supplementation, and even more vitamin D therapy, can worsen the risk of developing urolithiasis by increasing calcium, phosphate, and oxalate urinary excretion. Despite the clinical and practical relevance of this issue, the evidence on this topic is scarce and contradictory. Therefore, some concerns exist about how and whether to prescribe such supplements to a patient with a history of kidney stones. In this narrative review, we resume some pivotal pathophysiological concepts strictly related to the dealt topic, and we draw some considerations and personal opinions on the pros and cons of such prescriptions. Finally, we share with the reader our pragmatic algorithm for handling the urolithiasis risk in patients who have strong indications to be prescribed vitamin D and calcium supplementations.
... In addition, the absorption rate of calcium is about 20 to 40% in adults, which is extremely low among nutrients [4]. However, if the intake of calcium is drastically increased by supplementation or other method, excretion from the body will be promoted due to the rapid increase in blood calcium concentration [5]. It is also known that a rapid increase in blood calcium level leads to an increased risk of coronary artery disease [6,7]. ...
Dietary calcium supplementation has been shown to be an effective adjunct therapy in an inflammatory bowel disease model. Soluble dietary fiber reduces intestinal pH and is known to enhance calcium absorption. Although many circadian clock regulations of nutrient absorption in the intestinal tract have been reported, the effects of clock regulation on calcium absorption have yet to be understood. In this study, we investigated the timing of efficient calcium intake by measuring urinary calcium excretion in mice. The diurnal variations in channel-forming tight junctions (claudins) were detected in both the jejunum and ileum. Following 2 days of feeding with a Ca²⁺-free diet, Ca²⁺-containing diets with or without soluble fiber (inulin) were fed at specific timings, and urine was subsequently examined every 4 hours. There was an evident increase in urinary calcium concentration when the inulin diet was fed at the beginning of the resting period. The Claudin 2 (Cldn2) expression level also showed a significant day-night change, which seemed to be a mechanism for the increased calcium excretion after inulin intake. This diurnal rhythm and enhanced Cldn2 expression were abolished by disruption of the suprachiasmatic nucleus, the central clock in the hypothalamus. This study suggests that intestinal calcium absorption might be modulated by the circadian clock and that the intake of inulin is more effective at the beginning of the resting period in mice.
... It is also involved in blood clotting 16 . Most of the calcium is found in bones 17 . School feeding programs have been defined by World Bank as "targeted social safety nets that provide both educational and health benefits to the most vulnerable children, thereby increasing enrollment rates, reducing absenteeism, and improving food security at the household level 18 . ...
Background: The school feeding program was introduced in Nigeria in 2004 with the aim of encouraging school enrolment and reducing micro and macronutrient deficiencies in the country. Minerals and vitamins are required in minute quantities for the normal functioning of the body. Objective: The objective of the study was to determine the concentration of vitamins A, D and E and some mineral composition (Copper, Magnesium, Sodium, Calcium, and Potassium) in cooked Pasta samples given to the National Home Grown School Feeding Program in some selected schools in Gombe LGA of Gombe State. Methodology: Cooked Pasta (Jollof spaghetti) was collected from three (3) randomly selected schools (Bubayero primary school, Tudun-Wadan Pantami primary school, Pantami primary school) in Gombe, Nigeria. Moisture content in the food samples was done according to the Standard method described by the AOAC. For the determination of vitamin levels, the food samples collected were dried in an oven (GenLab) for three (3) days at 50oC and grounded using mortar and pestle into a fine powder, stored in airtight containers and analyzed using a UV spectrophotometer. Atomic Absorption Spectrophotometer (Buck Scientific) was used to determine copper, calcium and magnesium, while Flame photometry was used for the analysis of sodium and potassium. Results: Each of the analyzed samples had a very high moisture content ranging from 73.7% in Bubayero Primary School and Tudun-wadan Pantami Primary School been the lowest with 69.2%. Bubayero Primary School Pasta sample had the highest level of Vitamin A (573.23 IU/100g) and the lowest level of Vitamin C (2.00mg/100g). The least Vitamin A content was found in Tudun-Wadan Pantami Primary school Pasta sample (363.40 IU/100g). Sample from Pantami Primary School had the lowest concentrations of three out of the four minerals detected. Copper was not detected in all the samples. Conclusion: Pasta samples analyzed from different schools have low levels of the required minerals and water-soluble vitamin C which may be compensated with the addition of some vegetables such as spinach and may still be cost-effective.
... Calcium ion concentrations in the serum need to be regulated in a very tight range, which is accomplished through the hormonal metabolite of vitamin D (calcitriol) and parathyroid hormone working in tandem. In late life, calcium requirements decline and taking calcium supplements can lead to increased risk of myocardial infarction and stroke with little benefit regarding bone fracture (Reid et al., 2015). This increase in CVD risk has been especially noted in calcium doses over 1400 mg per day (Michaelsson et al., 2013). ...
Vitamins and certain minerals are micronutrients required for life. Vitamins are generally substances that the human body cannot make from other components of the diet. Vitamin D is an exception, but is generally treated as a vitamin. While most can be obtained through dietary sources, the amounts in many diets are not high enough for optimal health. Thus, it is often useful to obtain them through supplements. This article outlines the importance of key vitamins and minerals and mentions good dietary sources.
... As a commonly used drug (Ding et al., 2018;Zweifler, Koh, Daignault-Newton, & McCauley, 2021). However, in recent years, many studies have found that excessive intake of PTH can enhance the activity of osteoclasts, promote bone absorption, and eventually lead to the side effects of bone calcium release into the blood (Esbrit, Herrera, Portal-Núñez, Nogués, & Díez-Pérez, 2016;Reid, Bristow, & Bolland, 2015;Wein & Kronenberg, 2018). As a traditional Chinese medicine component, APT has been widely used in the treatment of a variety of diseases without toxic side effects (Gao, Wang, He, Wang, & Yang, 2020;He et al., 2016;Zhang et al., 2020). ...
Osteoporosis, a systemic bone disease that is characterized by a reduction in bone mass and destruction of bone microstructure, is becoming a serious problem worldwide. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into bone‐forming osteoblasts, and play an important role in maintaining homeostasis of bone metabolism, thus being a potential therapeutic target for osteoporosis. Although the phytochemical alpinetin (APT) has been reported to possess a variety of pharmacological activities, it is still unclear whether APT can influence the osteogenic differentiation of on BMSCs and if it can improve osteoporosis. In this study, we found that APT treatment was able to enhance osteogenic differentiation levels of human BMSCs in vitro and mouse ones in vivo as revealed by multiple osteogenic markers including increased alkaline phosphatase activity and osteocalcin expression. Mechanistically, the protein kinase A (PKA)/mTOR/ULK1 signaling was involved in the action of APT to enhance the osteogenic differentiation of BMSCs. In addition, oral administration of APT significantly mitigated the bone loss in a dexamethasone‐induced mouse model of osteoporosis through strengthening PKA signaling and autophagy. Altogether, these data demonstrate that APT promotes osteogenic differentiation in BMSCs by augmenting the PKA/mTOR/ULK1 autophagy signaling, highlighting its potential therapeutic application for treating osteoporotic diseases.
... Calcium supplementation, one of the most effective approaches to reduce the risk of SOP [7], is difficult in the elderly because of the degenerative decay of intestinal absorption and renal reabsorption [8]. Research has shown that calcium absorption can be promoted by bisphosphonate (BPs), which inhibits osteoclast activity and attenuates bone loss [9]. ...
Antler bone calcium (AB−Ca) and bioactive peptides (ABPs) were extracted from antler bones (Cervus elaphus) to maximize their value. In this study, 0.14 g calcium was obtained from 1 g antler bone. The peptide−calcium chelate rate was 53.68 ± 1.80%, and the Gly, Pro, and Glu in ABPs were identified to donate most to the increased calcium affinity through the mass spectrometry. Fourier transform infrared spectroscopy showed that calcium predominantly interacted with amino nitrogen atoms and carboxyl oxygen atoms, thereby generating a peptide–calcium chelate. The peptide−calcium chelates were characterized using scanning electron microscopy. A Caco-2 cell monolayer model showed that ABPs significantly increased calcium transport. Furthermore, the D-gal-induced aging mouse model indicated that the ABPs + AB−Ca group showed higher Ca and PINP levels, lower P, ALP, and CTX-1content in serum, and considerably higher tibia index and tibia calcium content. Results showed that ABPs + AB-Ca increased bone formation and inhibited bone resorption, thereby providing calcium supplements for ameliorating senile osteoporosis (SOP).
... We and others demonstrated small beneficial effects of calcium supplements on axial bone density, though we also found that loss of total body bone density was not completely prevented (3), casting doubt on the validity of calcium balance studies as measures of bone balance. Since that time, we have repeatedly demonstrated total body bone balance measured with DXA is not related to customary calcium intake ( Fig. 1) (4,5,6). The bone mineral density (BMD) benefit associated with the introduction of calcium supplements occurs in the first year of treatment and is about 1%. ...
Fractures occur in about half of older White women, and almost a third of older White men. However, 80% of the older individuals who have fractures do not meet the bone density definition of osteoporosis, suggesting that this definition is not an appropriate threshold for offering treatment. Fracture risk can be estimated based on clinical risk factors with or without bone density. A combination of calculated risk, fracture history, and bone density is used in treatment decisions. Medications available for reducing fracture risk act either to inhibit bone resorption or to promote bone formation. Romosozumab is unique in that it has both activities. Bisphosphonates are the most widely used interventions because of their efficacy, safety, and low cost. Continuous use of oral bisphosphonates for >5 years increases the risk of atypical femoral fractures, so is usually punctuated with drug holidays of 6–24 months. Denosumab is a further potent anti-resorptive agent given as 6-monthly s.c. injections. It is comparable to the bisphosphonates in efficacy and safety but has a rapid offset of effect after discontinuation so must be followed by an alternative drug, usually a bisphosphonate. Teriparatide stimulates both bone formation and resorption, substantially increases spine density, and reduces vertebral and non-vertebral fracture rates, though data for hip fractures are scant. Treatment is usually limited to 18–24 months, followed by the transition to an anti-resorptive. Romosozumab is given as monthly s.c. injections for 1 year, followed by an anti-resorptive. This sequence prevents more fractures than anti-resorptive therapy alone. Because of cost, anabolic drugs are usually reserved for those at very high fracture risk. 25-hydroxyvitamin D levels should be maintained above 30 nmol/L, using supplements if sunlight exposure is limited. Calcium intake has little effect on bone density and fracture risk but should be maintained above 500 mg/day using dietary sources.
... It is anticipated that organisms without durative pathology catch several times after eating to balance the blood values. Previously, it has been considered that calcium absorption decreases with age, and important independent positive predictors are dietary fat and serum estradiol and 1,25-dihydroxyvitamin D3 [43]. Intestinal calcium absorption increases during a high-protein diet [44] and dietary protein positively influences calcium metabolism that influences bone health and is associated with molecular, cellular, and endocrine bases of the interactions [45]. ...
(1) Background: Although the effects of diets used worldwide, such as the Mediterranean diet, have been repeatedly studied, the effects of diet plans developed by national nutritionists are unknown. Our cross-sectional study aimed to assess the effects of the commercial Fitlap diet plan, widely used among Estonians, on bone mineral density (BMD), while considering other influential factors (physical activity, body composition, and macro- and micro-nutrients). (2) Methods: A total of 68 women participated (followers of Fitlap diet—FDF, n = 34; age-matched controls, n = 34). Body composition, bone mineral density (BMD), including the whole body (WB) and areal BMD from the femoral neck (FN) and lumbar spine (LS), and blood micro-nutrient levels were measured. The menu analysis was based on dietary recalls. (3) Results: The Fitlap diet contains significantly more calcium (p < 0.001) and magnesium (p = 0.007). FDF consume more fiber (coef. 6.49; p < 0.001) and protein (coef. 20.12; p < 0.001), which influences fat-free mass (coef. 3674.8; p = 0.008) and vitamin B12 blood values (coef. 184.98; p < 0.001). The only influencing factor of WB BMD, LS, and FN aBMD was fat-free mass (coef. in all locations 0.000009; and p = 0.015; p = 0.015; p = 0.01, respectively). (4) Conclusions: Fitlap is an example of a commercial diet plan that has no negative effects on bones.
... La supplémentation en calcium influence positivement le CMO et la DMO (Rizzoli et al., 2010). L'apport calcique augmente la concentration calcique sérique et diminue la sécrétion de l'hormone parathyroïdien (PTH) ce qui cause une augmentation de la densité minérale osseuse au niveau de la hanche et de la colonne vertébrale (Reid et al., 2015). Ses effets semblent dépendants du site osseux et de la dose journalière de calcium ingérée (Bonjour et al., 1997). ...
Les buts de cette thèse étaient de définir les déterminants de la santé osseuse chez les jeunes femmes en surpoids et obèses et d'explorer les effets de deux programmes longitudinaux d'entraînement physique (force vs. endurance) sur les paramètres osseux chez les jeunes femmes en surpoids et obèses. Deux études préliminaires et six études principales ont été menées. La première étude préliminaire a montré que la VO2 max (L/mn) est un déterminant positif de la masse osseuse chez les enfants en surpoids. La deuxième étude préliminaire a démontré que l'IMC est un déterminant négatif du CSI, du BSI et de l'ISI chez les jeunes femmes. La première étude principale a montré que l'obésité est associée à de faibles valeurs de CSI, de BSI et d'ISI chez les jeunes femmes. La deuxième étude principale a montré que la VO2 max (ml/mn/kg) est positivement corrélée au CSI et à l'ISI chez les jeunes femmes. La troisième et la quatrième étude ont montré que la surcharge pondérale est associée à une augmentation du CMO et de la DMO mais pas du TBS et que le TBS est corrélé positivement à la VO2 max (L/mn). La cinquième étude principale chez 68 jeunes femmes en surpoids et obèses a montré que la détente verticale, la VO2 max (L/mn), la puissance maximale (watts) et la force maximale en demi-squat sont positivement corrélées aux paramètres osseux chez les jeunes femmes en surpoids et obèses. La sixième étude principale a montré que les deux types d'entrainement physique (force et endurance) sont efficaces pour augmenter le CMO CE et la DMO lombaire et diminuer le poids et la masse grasse. L'entrainement de force était aussi efficace pour l'augmentation du TBS et les indices de résistance osseuse du col fémoral (CSI, BSI et ISI).
... Teeth and bones are rich in calcium [30]. Most of the calcium is found in bones [31].The calcium contents of the samples ranged from (24.03mg/100g -274.26mg/100g).Sample MS 50 (50% malted sorghum and 50% cocoa powder) has the highest value with 274.26mg/100g while sample MS10 (90% malted sorghum and 10% cocoa powder) had the lowest value with 24.03mg/100g. Holistically, the result obtained indicated that cocoa was a good source of calcium. ...
In this study, the fortification of malted sorghum with cocoa powder to produce non–alcoholic beverage was investigated. Cocoa powder was blended with malted sorghum in different proportion to produce fortified sorghum beverage products at ratio MS 10- (90% malted sorghum and 10% cocoa powder), MS 20 - (80 % malted sorghum and 20% cocoa powder), MS30 - (70% malted sorghum and 30% cocoa powder), MS 40 - (60% malted sorghum and 40%cocoa powder), MS 50 - (50% malted sorghum and 50% cocoa powder), MS 60 - (Ovaltine beverage) as control. The vitamins, minerals, alkaloids, glucose, and sensory properties of all the fortified sorghum beverage samples were determined using standard methods. The range of results for vitamin B and C contents of the samples were (1.27mg/100g 1.97mg/100g) and (24.77mg/100g-54.48mg/100g) respectively. The respective values for glucose and alkaloids of the samples were (67.55%-71.02%) and (0.99%-3.13%).The contents of calcium (24.03mg/100g-274.26mg/100g), Magnesium (217.28mg/100g-322.97mg/100g), potassium (269.20mg/100g-699.63mg/100g), phosphorus (20.80mg/100g-81.91mg/100g) and zinc (2.21mg/100g-7.18mg/100g) of the malted sorghum beverage. The fortification of malted sorghum with cocoa powder enhanced the mineral content of the beverage except phosphorus. Also, the addition of cocoa powder had varying effects on the organoleptic perception of the developed food products. This work showed that all the samples were accepted by panelist with sample MS 20 - (80%malted sorghum and 20% cocoa powder) preferred to other samples except the control (ovaltine). Aims: To investigate the effects of malted sorghum with cocoa powder to produce non–alcoholic beverage on vitamins, minerals, alkaloids, glucose contents and sensory properties. Study Design: The vitamin, minerals, alkaloids, glucose, and sensory properties of all the fortified sorghum beverage samples were determined using standard methods. Place and Duration of Study: Department of Food Technology, Federal Polytechnic Offa, Kwara State, between June 2019 and July 2020. Methodology: The method of Owolarafe et al. (2007) was adopted for production of cocoa powder. The method of Hallen et al. (2004) was used to produce malted sorghum flour. The method of Belšcak-Cvitanović et al. (2010) was adopted for the production of cocoa/sorghum beverage. Sample: Alkaloids in the sample were determined using the method of Harbone, 2003. Vitamin B and were determined, total glucose, minerals were analysed/calculated and sensory evaluation was also carried out. Results: There was consistent increase in vitamin B12 of all the samples. The vitamin B content of all the samples ranged from (1.27mg/100g –1.79mg/100g). Sample MS 60 (Ovaltine beverage) which is the control sample had the highest value with (1.79mg/100g). The result of vitamin C content obtained from this study showed an inconsistent increase. The value obtained ranged from 24.77mg/100g to 54.48mg/100g.Fortifying malted sorghum with 50% cocoa powder improved the vitamin C content. The result obtained from this study showed that cocoa was a good source of alkaloids. Alkaloids values in this study were significantly (p<0.05) higher in fortified malted sorghum samples than in the control sample MS 60 (Ovaltine beverage) except sample MS 10 (90% malted sorghum and 10% cocoa powder which showed (0.99%).The glucose content obtained from this study indicated that there was an inconsistent increase among the samples. Glucose value ranged from (67.55% -71.02%). All the sample variations had increase in minerals studied except phosphorus which decreased with increase in percentage of malted sorghum. It can be deduced from the result of this study that sample MS20 was rated best after the control sample (ovaltine) while sample MS50 was rated lowest in terms of sweetness. Conclusion: The fortification of malted sorghum with cocoa powder enhanced the nutritional content of the beverage. The fortified beverage had radical scavenging activity due the increase in antioxidant such as alkaloid and could be used for health promotion and disease prevention as an alternative to beverages with low nutritional / nutraceuticals value.
... of Americans regularly take calcium supplementation [6]. However, calcium supplementation has not delivered the desired effect in preserving bone mass and preventing frailty fractures [7]. A review of 33 clinical studies found that supplementing with calcium, vitamin D, or both, failed to reduce fracture risk among otherwise healthy elderly individuals [8]. ...
... of Americans regularly take calcium supplementation [6]. However, calcium supplementation has not delivered the desired effect in preserving bone mass and preventing frailty fractures [7]. A review of 33 clinical studies found that supplementing with calcium, vitamin D, or both, failed to reduce fracture risk among otherwise healthy elderly individuals [8]. ...
Context
The 24-hour urinary calcium excretion (UCaE) not only serves as an important indicator of calcium metabolism balance but also correlates with metabolic diseases. However, the distribution of 24-hour UCaE and its relationship with bone metabolism are unknown.
Objective
To investigate the distribution of 24-hour UCaE and its association with bone metabolism.
Methods
In this multicenter cross-sectional study, 1239 participants underwent physical examinations at 9 tertiary hospitals. Multivariate linear regression was used to explore bone metabolism associated with 24-hour UCaE. The relationship of bone metabolism with 24-hour urinary calcium excretion/urinary creatinine (UCaE/Ucr) was analyzed by using restrictive cubic splines fitting multiple linear regression model.
Results
The 24-hour UCaE median range was 2.27 mmol overall, 2.24 mmol in men, and 2.28 mmol in women. For men, the highest 24-hour UCaE/Ucr was observed in those aged between 30 and 44 years (median: 0.70), whereas the lowest was found aged between 18 and 29 years (median: 0.46). For women, the 24-hour UCaE/Ucr showed a gradual increase with advancing age. In the adjusted model, 24-hour UCaE/Ucr was independently positively associated with 25(OH)D in both men (P = .032) and women (P < .001). It was independently associated with parathyroid hormone (PTH) (P = .031), type Ⅰ collagen-containing cross-linked C-telopeptide (β-CTX) (P = .021) and procollagen type I N-propeptide (P1NP) (P = .048) in men, but not in women. The prevalence of hypercalciuria was 11.6% (men 7.5%; women 14.0%) and significantly varied across age groups and regions (P < .05).
Conclusion
This study established reference intervals for 24-hour UCaE in the Chinese population. This study found gender differences in the relationship between 24-hour UCaE and bone metabolism.
The fracture risk assessment tool (FRAX®) is useful in clinical practice for assessing ten-year major osteoporotic and hip fracture risk. This cross-sectional study aimed at assessing possible predictors of the FRAX® score for Jordanian women. Univariate and multivariate linear regression analysis was used to evaluate predictors of the FRAX® score. A total of 400 women were included in the study, hypertension was the most common medical condition, 66.3% ( n = 265) of the participants did not have their vitamin D status checked, 9.0% of the respondents had insufficiency ( n = 36), while 7.5% had deficiency ( n = 30). Higher age at menopause and longer duration since menopause were predictors of higher scores for major osteoporotic fractures and hip fractures, with both p-values < 0.001. Using the FRAX® score for early identification of women with high risk, especially those with longer years of menopause provides an opportunity of early preventive measures.
Calcium là một khoáng chất đóng vai trò rất quan trọng đối với cơ thể, là thành phần chính cấu thành nên xương và răng (99% nằm trong xương và răng), chỉ có 1% ở trong máu, nhưng tham gia vào các phản ứng chuyển hóa và nhiều chức năng quan trọng của cơ thể như hoạt động của các tế bào, làm đông máu, điều hòa sự co bóp cơ trong đó có cơ tim, giúp hấp thụ vitamin B12 trong ruột, hỗ trợ sự phân phát, thu nhận và dẫn truyền các tín hiệu thần kinh…Calcium rất cần cho sự sống của con người, nhưng cơ thể lại không thể tự tổng hợp được mà cần phải đưa từ bên ngoài vào qua đường thực phẩm. Nhiều nghiên cứu đã được công bố cho thấy lượng calcium thấp trong suốt cuộc đời có liên quan đến khối lượng xương thấp, gia tăng tỷ lệ gãy xương và nhiều vấn đề về sức khoẻ liên quan. Các cuộc khảo sát dinh dưỡng ở nhiều quốc gia đã chỉ ra rằng ở nhiều khu vực trên thế giới lượng calcium được cung cấp hàng ngày rất thấp so với nhu cầu, còn rất nhiều người không nhận được lượng calcium cần thiết để phát triển, duy trì sức khỏe của hệ cơ xương và sức khỏe chung
Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants.
Methods: We performed a case-control study nested in a cohort of patients aged 40–99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered.
Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01–1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10–1.66) and 1.03 (95% CI: 0.88–1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1 year = 1.10; 95% CI:0.82–1.49; AOR>1–3 years = 1.41; 95% CI:1.01–1.97; AOR>3 years = 1.81; 95% CI:1.25–2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1 year = 0.59; 0.30–1.16). An interaction between oral bisphosphonates and calcium supplements was suggested.
Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.
Background
Bisphosphonates have been associated with atrial fibrillation, but studies carried out thus far have not shown that they are also associated with an increased risk of ischaemic stroke (IS). None, however, separated by IS subtype (cardioembolic vs non-cardioembolic).
Objectives
The present study aimed to test the hypothesis that use of oral bisphosphonates (oBs) increases specifically the risk of cardioembolic IS.
Methods
A nested case-control study was performed using the Spanish primary healthcare database BIFAP (period: 2002-2015). Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for exact age, sex, and index date (first recording of IS). The association of IS (overall and by subtype) with the use of oBs within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their corresponding 95%CI using conditional logistic regression. Only oBs initiators were considered. (Figure 1).
Results
A total of 4,568 cardioembolic IS cases (matched with 21,697 controls) and 9,213 non-cardioembolic IS cases (matched with 44,212 controls) were included. For cardioembolic IS, the use of oBs was associated with an AOR of 1.35(1.10-1.66), in a duration dependent manner (AOR≤1year=1.10;0.82-1.49; AOR>1-3years=1.41;1.01-1.97; AOR>3years=1.81;1.25-2.62; p for trend=0.001). Such increased risk only appeared when patients used concomitantly calcium supplements and was completely blunted by anticoagulants. No increased risk was observed for non-cardioembolic IS (AOR=1.03;0.88-1.21).
Conclusion
The long-term use of oBs with calcium supplements increases the risk of cardioembolic IS, while leaves materially unaffected the risk of non-cardioembolic IS.
Figure 1.
Acknowledgements
The authors would like to acknowledge the excellent collaboration of the primary care physicians (general practitioners/paediatricians), as well as the support from the regional health administrations providing BIFAP data.
Disclosure of Interests
None Declared.
Adequate intake of fruits has been linked with the reduction in the risk of chronic diseases and maintenance of body weight. Fruits and Their Roles in Nutraceuticals and Functional Foods covers recent research related to the bioactive compounds present in a variety of fruits
Zusammenfassung
Osteoporose und Sarkopenie sind entscheidende Faktoren für den altersabhängigen Anstieg des Frakturrisikos. Eine knochenbewusste Ernährung ist entscheidender Bestandteil sowohl der Prävention als auch der Basistherapie der Osteoporose. Eine ausreichende Zufuhr von Calcium als wichtiger Bestandteil des Knochengewebes ist sowohl zur Erreichung der peak bone mass während der Wachstumsphase als auch bei Osteoporose essentiell. Gerade auch unter einer medikamentösen Osteoporosetherapie sollte auf eine ausreichende Zufuhr geachtet werden. Ein Großteil der europäischen Gesellschaft weist einen Vitamin-D-Mangel auf. Neben einem Effekt auf die Calciumhomöostase und die Knochenmineralisation, beeinflusst Vitamin D auch die Muskulatur und das Sturzrisiko. Gerade eine kombinierte Substitution von Calcium und Vitamin D scheint sich günstig auf das Frakturrisiko auszuwirken. Ebenso ist ein Mangel von Vitamin K weit verbreitet. Vitamin K hat eine relevante Funktion bei der Knochenmineralisation sowie bei der Verhinderung von ektopen Mineralisationen. Welche Wirkung eine Substitution auf das Frakturrisiko hat, wird aktuell noch kontrovers diskutiert. Proteine sind ein wesentlicher Baustein von Muskulatur und Knochen. Darüberhinaus führt eine erhöhte Zufuhr zur Sekretion von IGF-I, welches verschiedene günstige Effekte auf den Knochenstoffwechsel hat. Bezüglich einer Senkung des Frakturrisikos sind auch hier inkonsistente Studienergebnisse zu finden. Der über längere Zeit postulierte negative Effekt von tierischem Eiweiß auf die Knochenhomöostase konnte in neueren Studien nicht verifiziert werden.
Purpose of review:
This article describes an approach to symptom management in people with multiple sclerosis (MS), emphasizing healthy lifestyles and evidence-based treatments.
Recent findings:
Growing evidence supports healthy nutrition, exercise, and emotional well-being (wellness) as foundational for MS symptom management. A stepped approach starts with healthy lifestyle practices and adds nonpharmacologic, pharmacologic, and procedural-based therapies balancing levels of evidence, risks, and potential benefits. The growing availability of cannabis and widespread use of dietary supplements in self-management of MS symptoms raise both therapeutic promises and challenges.
Summary:
Wellness approaches for MS symptom management foster self-reliance and should be reinforced early and often. Recognition of symptom clusters and medical comorbidities helps limit polypharmacy.
Herbal nutraceuticals are playing an important part in the nutraceutical market where global demand for nutraceutical products is increasing at a high rate ever before. Herbal products containing phytochemicals such as carotenoids, lutein, phenolic compounds, plant-based sterols, etc., provide numerous health benefits to human health beyond basic nutrition. Herbs such as garlic, ginger, ginkgo biloba, ginseng, turmeric, onion, ashwagandha, brahmi, etc., have been used by our ancestors for treatment for various health problems. Different countries have developed their regulatory framework for trade and marketing of novel nutraceutical products in their premises. This chapter emphasizes on classification, health benefits, and government regulations with the current global market and future prospective for herbal nutraceuticals.
The health benefits of docosahexaenoic (DHA) and eicosapentaenoic (EPA) in omega-3 containing supplements are compelling. However, their source and pharmaceutical regulation in Ghana presents two potential problems; quality and safety. This study investigated the quality and safety of some omega-3 containing supplements on the Ghanaian market. Twenty-two over-the-counter commercial brands of omega-3 fish oil supplements were analyzed for their pharmaceutical quality, heavy (mercury), and trace (sodium, potassium, magnesium, iron, and calcium) metal contents to check if they pose health risks to consumers. On their quality attributes, which was evaluated by the uniformity of weight, disintegration time, and content of DHA and EPA, all products sampled passed the uniformity of weight except sample H and S. All sampled products passed the disintegration tests except for brand C and E and all samples did not meet the DHA content per the manufacturers’ label and standard requirements. On EPA content, only samples B and S passed. Almost 90% of the supplements sampled were not of the required quality. Sodium and potassium were detected in all samples, even though none was stated on their labels. All samples contained calcium, iron, and magnesium, but only 5 (24%) manufacturers stated it on their labels. The mercury content ranged from 0.4 to 125 µg/l in the analyzed fish oil supplements. Based on the risk assessment with particular reference to the hazard quotient, consumers taking the products over a prolonged period are at risk of adverse health effects.
The nature of continuous bone remodeling can be determined, thanks to the measurement of molecules released by osteoblasts and osteoclasts in the bone formation and resorption processes. These bone turnover markers (BTMs) can be measured in blood or urine. When on a diagnostic imaging test such as an x-ray, it is observed that the cortical bone is thinner and the trabeculae are less numerous and thinner, it is affirmed that the bone is osteoporotic. There is a more objective definition that differentiates between the concepts of osteoporosis and osteopenia based on the bone mineral density (BMD) T-score. This definition, however, is very controversial.BTMs are powerful research tools for epidemiologists who study populations’ fracture risks, but not for their routine use for identifying individual patients who would optimally benefit from pharmaceutical therapies for osteoporosis. Nevertheless, unlike the limitations of the use of BTMs to identify patients at risk for rapid bone loss, their use in guiding osteoporosis therapy has a clearer potential utility. The pattern of change in BTMs in response to treatment is well-described. BTMs may be useful also for patients with “secondary” bone loss due to hyperparathyroidism, hyperthyroidism, vitamin D deficiency, and paraproteinemia.KeywordsBone cellsBone metabolismBone turnover markersMineralizationOsteoporosis
Osteoporosis in men is a common but often overlooked disorder by clinicians. The criterion for osteoporosis diagnosis in men is similar to that in women-namely, a bone mineral density (BMD) that is 2·5 standard deviations or more below the mean for the young adult population (aged 20-29 years; T-score -2·5 or lower), measured at the hip or lumbar spine. Sex steroids are important for bone health in men and, as in women, oestrogens have a key role. Most men generally have bigger and stronger bones than women and typically have less bone loss during their lifetime. Men typically fracture less often than women, although they have a higher mortality rate after a fracture. Secondary osteoporosis is more common in men than in women. Lifestyle changes, adequate calcium, vitamin D intake, and exercise programmes are recommended for the management of osteoporosis in men. Bisphosphonates, denosumab, and teriparatide have been shown to increase BMD and are used for pharmacological treatment. In this Review, we report an updated overview of osteoporosis in men, describe new treatments and concepts, and discuss persistent controversies in the area.
The nutrition societies of Germany, Austria and Switzerland are the joint editors of the ‘reference values for nutrient intake'. They have revised the reference values for the intake of calcium and published them in June 2013. The reference values for the calcium intake for infants are derived from the calcium content of breast milk. For infants from 4 to <12 months of age, the calcium intake from solid foods is included in addition to the calcium intake from breast milk. Thus, the reference values for infants are estimated values; they are 220 mg/day for infants to <4 months and 330 mg/day for infants from 4 to <12 months of age. As a parameter for determining the calcium requirement in children and adolescents, calcium retention is taken into account. The average requirement is calculated by the factorial method. A balanced calcium metabolism is calculated based upon calcium balance studies and used as a parameter for the determination of the calcium requirement in adults. On the basis of the average requirement, recommended calcium intake levels for children, adolescents and adults are derived. Depending on age, the recommended calcium intake ranges between 600 mg/day for children aged 1 to <4 years and 1,200 mg/day for adolescents aged 13 to <19 years; for adults, it is 1,000 mg/day.
The menopausal transition is characterized by rapid bone loss. Few data exist on the role of nutrition.
The objective of the study was to ascertain which dietary factors influence perimenopausal skeletal loss.
A longitudinal study was conducted of 891 women aged 45-55 y at baseline and 50-59 y at follow-up 5-7 y later. Bone mineral density (BMD) was measured by using dual-energy X-ray absorptiometry at the lumbar spine and femoral neck (FN). Nutrient intakes were assessed after the baseline visit and 5 y later, by using the same food-frequency questionnaire.
After adjustment for energy intake and other confounders, higher intakes of calcium were correlated with change in FN BMD (ie, reduced loss) (r = 0.073, P < 0.05), and the intake of modest amounts of alcohol was associated with less lumbar spine bone loss (P < 0.01 for quartile of alcohol intake). Greater FN BMD loss was associated with increased intake of polyunsaturated fatty acids (r = -0.110, P < 0.01), monounsaturated fatty acids (r = -0.069, P < 0.05), retinol (r = -0.067; P < 0.05), and vitamin E (r = -0.110; P < 0.01). The latter 2 nutrients were highly correlated with polyunsaturated fatty acids. For premenopausal women, calcium and nutrients found in fruit and vegetables (vitamin C, magnesium, and potassium) were associated with FN BMD, and calcium, vitamin C, and magnesium were associated with change in FN BMD.
Although menopausal status and hormone replacement therapy use dominate women's bone health, diet may influence early postmenopausal bone loss. Fruit and vegetable intake may protect against premenopausal bone loss.
Supplementation with elemental calcium 500 mg/day alone for 2 years is able to decrease bone turnover and is effective in retarding bone loss at lumbar spine and slowing bone loss at femoral neck in elderly Thai women who had low dietary calcium intake.
Introduction
Most elderly Thais have a total dietary calcium intake of less than the recommended amount. The aim of the study was to investigate the effect of calcium supplementation on bone mineral density and biochemical indices of bone remodeling in Thai postmenopausal women.
Methods
Four hundred and four healthy postmenopausal women 60 years old or older without osteoporosis were recruited and conducted in a randomized, double-blinded, placebo-controlled trial. They were randomly given elementary calcium 500 mg/day or placebo for 2 years. Dietary calcium intake was calculated from the nutrient compositional analysis of the 3-day food records. Serum 25 hydroxyvitamin D was measured by radioimmunoassay and bone turnover markers were determined by electrochemiluminescence immunoassay.
Results
The age of the subjects was 65.8 ± 4.4 years. All baseline characteristics of the subjects in the calcium-supplemented group and the placebo group were not statistically different. At the end of the study, significant decreases in serum C-terminal telopeptide of type I collagen and serum total procollagen type I amino terminal propeptide in the calcium-supplemented group were observed, while there was no change in the placebo group. In addition, plasma parathyroid hormone decreased, although not significantly, only in the calcium-supplemented group. Percent changes from baseline of lumbar spine (L2–L4) bone mineral density increased 2.76 % in the calcium-supplemented group and 0.87 % in the placebo group, whereas the percent changes from baseline of femoral neck decreased 0.21 % in the calcium-supplemented group and 0.90 % in the placebo group.
Conclusions
Calcium supplementation is necessary for the decrease of bone turnover and prevention of bone loss in Thai elderly women.
Calcium supplements have been reported to increase the risk of myocardial infarction (MI). We wished to determine whether the effects of calcium supplements on cardiovascular risk vary across different population groups. We modeled the effect of calcium (with or without vitamin D) on the time to incident cardiovascular events in prespecified subgroups based on age, dietary calcium intake, body mass index, smoking history, history of hypertension,
diabetes and prevalent cardiovascular disease, using interaction terms in Cox proportional hazards models in two randomized controlled trial data sets—our re-analysis of the Women’s Health Initiative Calcium and Vitamin D study (WHI CaD), and our pooled patient-level meta-analysis of trials of calcium supplements with or without vitamin D. For women in WHI CaD not taking calcium supplements at randomization (n ¼16 718), we found no significant interactions between treatment allocation, the risk of MI, stroke or coronary revascularization, or any of the baseline variables. In the pooled patient-level data set of six trials of calcium with or without vitamin D (n ¼24 869), there were also no significant interactions between treatment allocation, risk of MI or stroke, and any of the baseline variables. We found no evidence that the increased cardiovascular risk from calcium supplements differs across varying patient subpopulations. These findings suggest that targeted prescription of calcium supplements to specific population subgroups, such as younger people and those with low dietary calcium intake, should not be endorsed.
Objectives:
This analysis was aimed at assessing the benefits of total calcium intake from diet and supplements on both femoral neck and lumbar vertebral bone mineral density (BMD) in a representative sample of older U.S. women and men.
Design:
For 1384 women and men aged 50-70 and 71+ yr, quintiles of total calcium intake were tested for their association with hip and spine BMD after adjusting for body mass index. All data in this observational study were cross-sectional.
Data source:
Subjects included elderly residents statistically representative of the United States, women and men aged 50 yr and older in the National Health and Nutrition Examination Survey 2005-2006 cohort.
Main outcome measures:
Calcium intakes and femoral and lumbar BMD were evaluated.
Results:
Total calcium intakes ranged from means of 400+ mg/d in quintile 1 to 2100+ in quintile 5. Little difference in hip or lumbar BMD was found in relation to total calcium consumption in women and men across five quintiles, especially for those aged 50-70, in models adjusted for body mass index only. Femoral hip BMD in men 71 and older increased slightly with high calcium intake (3.6% higher density, P = 0.0391), whereas femoral BMD in women 71 and older decreased slightly with high calcium intake (-3.2%, P = 0.0132). Lumbar BMD remained fairly consistent across all quintiles, but greater variation within each quintile was found compared with the hip.
Conclusions:
A usual high calcium intake beyond the recommended dietary allowance of elderly women and men, most commonly achieved by calcium supplements, did not provide any benefit for hip or lumbar BMD. A dietary intake of calcium approaching or meeting the current recommendations was not related to higher BMD of the hip or lumbar spine in late life compared with lower intakes of calcium in older adults.
Dietary phosphorous overload and excessive calcium intake from calcium-containing phosphate binders promote coronary artery calcification (CAC) that may contribute to high mortality of dialysis patients. CAC has been found in patients in early stages of nondialysis-dependent CKD. In this population, no study has evaluated the potential role of phosphorus binders on mortality. This study aimed to evaluate all-cause mortality as the primary end point in nondialysis-dependent CKD patients randomized to different phosphate binders; secondary end points were dialysis inception and the composite end point of all-cause mortality and dialysis inception.
This is a randomized, multicenter, nonblinded pilot study. Consecutive outpatients (n=212; stage 3-4 CKD) were randomized to either sevelamer (n=107) or calcium carbonate (n=105). Phosphorus concentration was maintained between 2.7 and 4.6 mg/dl for patients with stage 3-4 CKD and between 3.5 and 5.5 mg/dl for patients with stage 5 CKD. The CAC score was assessed by computed tomography at study entry and after 6, 12, 18, and 24 months. All-cause mortality, dialysis inception, and the composite end point were recorded for up to 36 months.
In patients randomized to sevelamer, all-cause mortality and the composite end point were lower; a nonsignificant trend was noted for dialysis inception.
Sevelamer provided benefits in all-cause mortality and in the composite end point of death or dialysis inception but not advantages in dialysis inception. Larger studies are needed to confirm these results.
In this population-based cohort of 1,254 older Scottish women we found significant interactions between the mechanical component of self-reported habitual physical activity (PA) and dietary calcium (Ca) in BMD, independent of other risk factors. At low and/or medium Ca intakes BMD was higher amongst the most active people.
Although there is general agreement that increased activity (PA) and dietary calcium (Ca) consumption may help maintain bone mass in later life and prevent fractures, the amount required remains uncertain.
In 2001-2003, 1,847 postmenopausal women (mean +/- SD age: 69.3 +/- 5.5 years) underwent bone mineral density (BMD) measurement and, in 2004, 68.7% (n = 1,254) completed a bone-specific Physical Activity Questionnaire (bsPAQ) and a food frequency questionnaire. The bsPAQ measures the metabolic and mechanical components of PA. Interactions of PA and Ca in BMD were examined using ANCOVA.
Significant interactions were identified in the BMD of the lumbar spine (LS), right hip (RH) and left hip (LH), after adjustment for confounders, between tertiles of PA classified according to the mechanical component and tertiles of energy-adjusted Ca intake (ANCOVA p = 0.006, p = 0.004 and p = 0.013 respectively). For example, at medium Ca intakes LH BMD was higher by 7.8% in the highest tertile of PA compared with the lowest tertile of PA.
These data suggest that health promotion campaigns to increase PA would be most effective in populations with a low/medium calcium intake.
Objectives:
To investigate the effects of personal calcium supplement use on cardiovascular risk in the Women's Health Initiative Calcium/Vitamin D Supplementation Study (WHI CaD Study), using the WHI dataset, and to update the recent meta-analysis of calcium supplements and cardiovascular risk.
Design:
Reanalysis of WHI CaD Study limited access dataset and incorporation in meta-analysis with eight other studies. Data source WHI CaD Study, a seven year, randomised, placebo controlled trial of calcium and vitamin D (1g calcium and 400 IU vitamin D daily) in 36,282 community dwelling postmenopausal women. Main outcome measures Incidence of four cardiovascular events and their combinations (myocardial infarction, coronary revascularisation, death from coronary heart disease, and stroke) assessed with patient-level data and trial-level data.
Results:
In the WHI CaD Study there was an interaction between personal use of calcium supplements and allocated calcium and vitamin D for cardiovascular events. In the 16,718 women (46%) who were not taking personal calcium supplements at randomisation the hazard ratios for cardiovascular events with calcium and vitamin D ranged from 1.13 to 1.22 (P = 0.05 for clinical myocardial infarction or stroke, P = 0.04 for clinical myocardial infarction or revascularisation), whereas in the women taking personal calcium supplements cardiovascular risk did not alter with allocation to calcium and vitamin D. In meta-analyses of three placebo controlled trials, calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.21 (95% confidence interval 1.01 to 1.44), P = 0.04), stroke (1.20 (1.00 to 1.43), P = 0.05), and the composite of myocardial infarction or stroke (1.16 (1.02 to 1.32), P = 0.02). In meta-analyses of placebo controlled trials of calcium or calcium and vitamin D, complete trial-level data were available for 28,072 participants from eight trials of calcium supplements and the WHI CaD participants not taking personal calcium supplements. In total 1384 individuals had an incident myocardial infarction or stroke. Calcium or calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.24 (1.07 to 1.45), P = 0.004) and the composite of myocardial infarction or stroke (1.15 (1.03 to 1.27), P = 0.009).
Conclusions:
Calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially myocardial infarction, a finding obscured in the WHI CaD Study by the widespread use of personal calcium supplements. A reassessment of the role of calcium supplements in osteoporosis management is warranted.
To investigate whether calcium supplements increase the risk of cardiovascular events.
Patient level and trial level meta-analyses.
Medline, Embase, and Cochrane Central Register of Controlled Trials (1966-March 2010), reference lists of meta-analyses of calcium supplements, and two clinical trial registries. Initial searches were carried out in November 2007, with electronic database searches repeated in March 2010.
Eligible studies were randomised, placebo controlled trials of calcium supplements (>or=500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than one year. The lead authors of eligible trials supplied data. Cardiovascular outcomes were obtained from self reports, hospital admissions, and death certificates.
15 trials were eligible for inclusion, five with patient level data (8151 participants, median follow-up 3.6 years, interquartile range 2.7-4.3 years) and 11 with trial level data (11 921 participants, mean duration 4.0 years). In the five studies contributing patient level data, 143 people allocated to calcium had a myocardial infarction compared with 111 allocated to placebo (hazard ratio 1.31, 95% confidence interval 1.02 to 1.67, P=0.035). Non-significant increases occurred in the incidence of stroke (1.20, 0.96 to 1.50, P=0.11), the composite end point of myocardial infarction, stroke, or sudden death (1.18, 1.00 to 1.39, P=0.057), and death (1.09, 0.96 to 1.23, P=0.18). The meta-analysis of trial level data showed similar results: 296 people had a myocardial infarction (166 allocated to calcium, 130 to placebo), with an increased incidence of myocardial infarction in those allocated to calcium (pooled relative risk 1.27, 95% confidence interval 1.01 to 1.59, P=0.038).
Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.
Antifracture efficacy of high-dose vitamin D (800 IU) and calcium (1000 mg) remains controversial. To determine whether daily 800 IU of vitamin D and 1000 mg of calcium supplementation prevents fractures, we randomized 3432 women of the population-based Osteoporosis Risk Factor and Prevention (OSTPRE) Study cohort (ages 65 to 71 years) living in the region of northern Savonia, Finland (latitude 62 degrees to 64 degrees N) for 3 years to receive 800 IU of cholecalciferol and 1000 mg of calcium as calcium carbonate or to a control group that did not receive placebo. The main outcome measure was incident fractures. Fracture data were collected in telephone interviews and validated. Data on 3195 women, 1586 in the intervention group and 1609 in the control group, were available for analysis. In adjusted Cox proportional hazards models, the risk of any fracture decreased in the vitamin D and calcium group by 17% [adjusted hazard ratio (aHR) = 0.83; 95% confidence interval (CI) 0.61-1.12], and the risk of any nonvertebral fracture decreased by 13% (aHR = 0.87; 95% CI 0.63-1.19). The risk of distal forearm fractures decreased by 30% (aHR = 0.70; 95% CI 0.41-1.20), and the risk of any upper extremity fractures decreased by 25% (aHR = 0.75; 95% CI 0.49-1.16), whereas the risk of lower extremity fractures remained essentially equal (aHR = 1.02; 95% CI 0.58-1.80). None of these effects reached statistical significance. In conclusion, this study did not produce statistically significant evidence that vitamin D and calcium supplementation prevents fractures in a 65- to 71-year-old general population of postmenopausal women.
Objective
To investigate whether calcium supplements increase the risk of cardiovascular events.
Design
Patient level and trial level meta-analyses.
Data Sources
Medline, Embase, and Cochrane Central Register of Controlled Trials (1966-March 2010), reference lists of meta-analyses of calcium supplements, and two clinical trial registries. Initial searches were carried out in November 2007, with electronic database searches repeated in March 2010.
Study Selection
Eligible studies were randomized, placebo controlled trials of calcium supplements (. 500 mg/day), with 100 or more participants of mean age more than 40 years and study duration more than 1 year. The lead authors of eligible trials supplied data. Cardiovascular outcomes were obtained from self-reports, hospital admissions and death certificates.
Results
Fifteen trials were eligible for inclusion, five with patient level data (8,151 participants, median follow-up 3.6 years, interquartile range 2.7-4.3 years) and 11 with trial level data (11,921 participants, mean duration 4.0 years). In the five studies contributing patient level data, 143 people allocated to calcium had a myocardial infarction compared with 111 allocated to placebo (hazard ratio 1.31, 95% confidence interval 1.02-1.67, p = 0.035). Nonsignificant increases occurred in the incidence of stroke (1.20, 0.96-1.50, p = 0.11), the composite end point of myocardial infarction, stroke, or sudden death (1.18, 1.00 to 1.39, p = 0.057), and death (1.09, 0.96-1.23, p = 0.18). The meta-analysis of trial level data showed similar results: 296 people had a myocardial infarction (166 allocated to calcium, 130 to placebo), with an increased incidence of myocardial infarction in those allocated to calcium (pooled relative risk 1.27, 95% confidence interval 1.01-1.59, p = 0.038).
Conclusion
Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.
Background: The role of total calcium intake in the prevention of hip fracture risk has not been well established.
Objective: The objective of the study was to assess the relation of calcium intake to the risk of hip fracture on the basis of meta-analyses of cohort studies and clinical trials.
Results: In women (7 prospective cohort studies, 170 991 women, 2954 hip fractures), there was no association between total calcium intake and hip fracture risk [pooled risk ratio (RR) per 300 mg total Ca/d = 1.01; 95% CI: 0.97, 1.05]. In men (5 prospective cohort studies, 68 606 men, 214 hip fractures), the pooled RR per 300 mg total Ca/d was 0.92 (95% CI: 0.82, 1.03). On the basis of 5 clinical trials (n = 5666 women, primarily postmenopausal, plus 1074 men) with 814 nonvertebral fractures, the pooled RR for nonvertebral fractures between calcium supplementation (800–1600 mg/d) and placebo was 0.92 (95% CI: 0.81, 1.05). On the basis of 4 clinical trials with separate results for hip fracture (6504 subjects with 139 hip fractures), the pooled RR between calcium and placebo was 1.64 (95% CI:1.02, 2.64). Sensitivity analyses including 2 additional small trials with <100 participants or per-protocol results did not substantially alter results.
Conclusions: Pooled results from prospective cohort studies suggest that calcium intake is not significantly associated with hip fracture risk in women or men. Pooled results from randomized controlled trials show no reduction in hip fracture risk with calcium supplementation, and an increased risk is possible. For any nonvertebral fractures, there was a neutral effect in the randomized trials.
Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 8th Edition is the comprehensive revision of the field-leading reference on bone and mineral health. The eighth edition has been fully revised by the leading researchers and clinicians in the field to provide concise coverage of the widest possible spectrum of metabolic bone diseases and disorders of mineral metabolism. Chapters look to explain basic biological factors of healthy development and disease states and make it easily translatable to clinical interventions. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism is the definitive, one-stop reference for anyone working in the field of bone health and disease. © 2013 by American Society for Bone and Mineral Research. All rights reserved.
There is longstanding concern that calcium supplements might increase cardiovascular risk in patients with renal impairment. The Auckland Calcium Study suggested that the same problem occurs in older people taking these supplements for prevention of osteoporosis. Our subsequent meta-analyses, (which followed protocols finalized before the data was available) confirmed that calcium supplements, with or without vitamin D, adversely affected risk of myocardial infarction and, possibly, stroke. Several groups have re-visited these data, consistently finding an adverse effect of calcium on myocardial infarction, not always statistically significant because some meta-analyses have been under-powered. Whether or not an adverse effect of calcium plus vitamin D on myocardial infarction is found depends on whether two specific groups of subjects are included - those in the Women's Health Initiative who were already taking calcium at the time of randomization, and subjects from an open, cluster-randomized study in which baseline cardiovascular risk was different between groups. Vitamin D alone does not affect vascular risk, so it is unlikely that differences between calcium alone and calcium plus vitamin D are real, and they are more likely to result from the inclusion of studies at high risk of bias. The mechanisms of the adverse cardiovascular effects are uncertain but may be mediated by the increase in serum calcium following supplement ingestion, and the effects of this on vascular function and coagulation. Available evidence suggests the risks of calcium supplements outweigh any small benefits on fracture incidence, so the case for their use is weak. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.
Background:
Low 25-hydroxyvitamin D status has been associated with increased cardiovascular events in epidemiologic studies.
Objective:
We assessed whether vitamin D supplementation reduces cardiac failure, myocardial infarction (MI), and stroke through an analysis of the Randomised Evaluation of Calcium Or vitamin D (RECORD) randomized controlled trial (RCT), a systematic review, and a meta-analysis.
Design:
Two analyses were undertaken. The first analysis was a trial analysis. The RECORD was a factorial RCT that compared vitamin D₃ (800 IU/d), calcium (1000 mg/d), vitamin D plus calcium, and a placebo. Cardiovascular events were collected throughout the trial and 3-y posttrial follow-up. Data were analyzed by using Cox regression. The second analysis was a systematic review. MEDLINE, EMBASE, CENTRAL, conference abstracts, and ongoing trials were searched for RCTs that evaluated vitamin D from 1980 to 2013. RCTs with ≥1 y of follow-up and participants mean or median age ≥60 y were included. Meta-analyses were based on a Bayesian fixed-effects model by using a complementary log-log link function to account for varying lengths of follow-up.
Results:
In the trial analysis, we showed that, for the 5292 participants in the RECORD trial, HRs (95% CIs) for vitamin D compared with no vitamin D for cardiac failure, MI, and stroke were 0.75 (0.58, 0.97), 0.97 (0.75,1.26), and 1.06 (0.8, 1.32), respectively. Twenty-one studies met the inclusion criteria for the systematic review (n = 13,033). Estimated HRs (credible intervals) for vitamin D compared with the placebo or control for on-study events for cardiac failure, MI, and stroke were 0.82 (0.58, 1.15), 0.96 ( 0.83, 1.10), and 1.07 (0.91, 1.29), respectively.
Conclusion:
Vitamin D supplementation might protect against cardiac failure in older people but does not appear to protect against MI or stroke.
Calcium supplementation, particularly with vitamin D has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta-analyses suggesting calcium supplementation with or without vitamin D increase myocardial infarction (MI) risk; however concern has been raised over the design of these meta-analyses. We therefore undertook a meta-analysis of randomized controlled trials with placebo or no-treatment control groups to determine if these supplements increase all-cause mortality and coronary heart disease (CHD) risk including: MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966 to May 24, 2013 for potentially eligible studies, reference lists were checked, and trial investigators contacted where additional unpublished data was required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3,390 CHD events and 4,157 deaths. Two authors extracted the data independently with trial data combined using random-effects meta-analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% CI, 0.96-1.09; P = 0.51). Seventeen trials contributed all-cause mortality data with pooled RR of 0.96 (95%CI, 0.91-1.02; P = 0.18). Heterogeneity among the trials was low for both primary outcomes (I2 = 0%). For secondary outcomes the RR for MI was 1.08; 95% CI, 0.92-1.26; P = 0.32, angina pectoris and acute coronary syndrome 1.09; 95% CI, 0.95-1.24; P = 0.22 and chronic CHD 0.92; 95% CI, 0.73-1.15; P = 0.46. In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increase coronary heart disease or all-cause mortality risk in elderly women. © 2014 American Society for Bone and Mineral Research
Vitamin D insufficiency is associated with many disorders, leading to calls for widespread supplementation. Some investigators suggest that more clinical trials to test the effect of vitamin D on disorders are needed.
We did a trial sequential meta-analysis of existing randomised controlled trials of vitamin D supplements, with or without calcium, to investigate the possible effect of future trials on current knowledge. We estimated the effects of vitamin D supplementation on myocardial infarction or ischaemic heart disease, stroke or cerebrovascular disease, cancer, total fracture, hip fracture, and mortality in trial sequential analyses using a risk reduction threshold of 5% for mortality and 15% for other endpoints.
The effect estimate for vitamin D supplementation with or without calcium for myocardial infarction or ischaemic heart disease (nine trials, 48 647 patients), stroke or cerebrovascular disease (eight trials 46 431 patients), cancer (seven trials, 48 167 patients), and total fracture (22 trials, 76 497 patients) lay within the futility boundary, indicating that vitamin D supplementation does not alter the relative risk of any of these endpoints by 15% or more. Vitamin D supplementation alone did not reduce hip fracture by 15% or more (12 trials, 27 834 patients). Vitamin D co-administered with calcium reduced hip fracture in institutionalised individuals (two trials, 3853 patients) but did not alter the relative risk of hip fracture by 15% or more in community-dwelling individuals (seven trials, 46 237 patients). There is uncertainty as to whether vitamin D with or without calcium reduces the risk of death (38 trials, 81 173).
Our findings suggest that vitamin D supplementation with or without calcium does not reduce skeletal or non-skeletal outcomes in unselected community-dwelling individuals by more than 15%. Future trials with similar designs are unlikely to alter these conclusions.
Health Research Council of New Zealand.
Bisphosphonates are the first-line treatment for osteoporotic (OP) women; however, therapy is not recommended in severe renal impairment (RI). This study examined RI prevalence among OP women. Nearly a quarter of women had moderate RI, and 3.59 % would not be recommended for bisphosphonates, demonstrating a need for better therapeutic alternatives.
Bisphosphonates are the recommended first-line treatment for postmenopausal women with OP. However, bisphosphonates are cleared through the kidney, and therapy is not recommended in severe RI due to adverse treatment effects observed with intravenous formulations. The objective of this study was to examine the prevalence of RI among women with OP aged ≥50 years in the USA.
Women with OP aged ≥50 years were identified using the 2005-2008 National Health and Nutrition Examination Survey (NHANES) data. OP was defined as prior OP diagnosis, previous hip or spine fracture, or measured lumbar spine/femoral neck bone mineral density (BMD) T-score <-2.5. The 2005 Modification of Diet in Renal Disease (MDRD) formula was used to calculate the glomerular filtration rate (GFR). Moderate and severe RI was defined as GFR 30-59 and 15-29 mL/min, respectively. Bisphosphonate therapy was considered not recommended among women with OP if GFR was <35 mL/min.
The prevalence of OP among women in USA aged ≥50 years was 27 % (12.7 million). Nearly a quarter of women with OP (23.54 ± 2.02 %; 2.9 million) had moderate RI and 1.88 ± 0.28 % (230,000) had severe RI. Correspondingly, bisphosphonate therapy would not be recommended for an estimated 439,000 women with OP (3.59 ± 0.73 %).
Nearly a quarter of postmenopausal women with OP have moderate RI, and over 3 % would not be recommended for bisphosphonate treatment. These data reveal a need for better therapeutic alternatives that can be used in this patient population.
A 62-year-old healthy woman presents for routine care. She has no history of fracture, but she is worried about osteoporosis because her mother had a hip fracture at 72 years of age. She exercises regularly and has taken over-the-counter calcium carbonate at a dose of 1000 mg three times a day since her menopause at 54 years of age. This regimen provides 1200 mg of elemental calcium per day. She eats a healthy diet with multiple servings of fruits and vegetables and consumes one 8-oz serving of low-fat yogurt and one glass of low-fat milk almost every day. She recently heard that calcium supplements could increase her risk of cardiovascular disease and wants your opinion about whether or not she should receive them. What would you advise?
Whether calcium or vitamin D supplementation reduces serious vascular outcomes in older people remains unclear. We conducted a meta-analysis based on randomized controlled trials to evaluate the effect of calcium or vitamin D supplementation on the risk of major cardiovascular outcomes.
We performed electronic searches in PubMed, Embase, and the Cochrane Library to identify relevant randomized controlled trials. Odds ratios (ORs) were used to measure the effect of calcium or vitamin D supplementation on the risk of major vascular outcomes with a random-effect model.
Of the 1643 identified studies, we included 11 trials reporting data on 50,252 individuals. These studies reported 2685 major cardiovascular events, 1097 events of myocardial infarction, and 1350 events of stroke. Calcium or vitamin D supplementation did not have an effect on major cardiovascular events (OR, 1.03; 95% confidence interval [CI]: 0.94-1.12; P=0.54), myocardial infarction (OR, 1.08; 95% CI: 0.96-1.22; P=0.21), or stroke (OR, 1.01; 95% CI: 0.91-1.13; P=0.80) when compared to the effect with a placebo. Subgroup analysis indicated that calcium supplementation alone might play an important role in increasing the risk of major cardiovascular events, myocardial infarction, and stroke, but this difference could not be identified as statistically significant. Furthermore, males seem to experience more harmful effects with supplements of calcium or vitamin D than the effects experienced by females.
Calcium supplementation might increase the risk of major cardiovascular events, myocardial infarction, and stroke compared to the risk with a placebo.
Current recommendations for calcium intake call for 1,000 mg per day for women ages 19-50 and 1,200 mg per day for women over age 50 to ensure bone health. Given recent concerns that calcium supplements may raise risk for cardiovascular disease and kidney stones, women should aim to meet this recommendation primarily by eating a calcium-rich diet and taking calcium supplements only if needed to reach the RDA goal (often only ∼500 mg per day in supplements is required).
Phosphate binders (calcium-based and calcium-free) are recommended to lower serum phosphate and prevent hyperphosphataemia in patients with chronic kidney disease, but their effects on mortality and cardiovascular outcomes are unknown. We aimed to update our meta-analysis on the effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease.
We did a systematic review of articles published in any language after Aug 1, 2008, up until Oct 22, 2012, by searching Medline, Embase, International Pharmaceutical Abstracts, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature. We included all randomised and non-randomised trials that compared outcomes between patients with chronic kidney disease taking calcium-based phosphate binders with those taking non-calcium-based binders. Eligible studies, determined by consensus with predefined criteria, were reviewed, and data were extracted onto a standard form. We combined data from randomised trials to assess the primary outcome of all-cause mortality using the DerSimonian and Laird random effects model.
Our search identified 847 reports, of which eight new studies (five randomised trials) met our inclusion criteria and were added to the ten (nine randomised trials) included in our previous meta-analysis. Analysis of the 11 randomised trials (4622 patients) that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders (risk ratio 0·78, 95% CI 0·61-0·98).
Non-calcium-based phosphate binders are associated with a decreased risk of all-cause mortality compared with calcium-based phosphate binders in patients with chronic kidney disease. Further studies are needed to identify causes of mortality and to assess whether mortality differs by type of non-calcium-based phosphate binder.
None.
This study aims to test the added value of calcium and vitamin D (CaD) in fracture prevention among women taking postmenopausal hormone therapy (HT).
This is a prospective, partial-factorial, randomized, controlled, double-blind trial among Women's Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years. A total of 27,347 women were randomized to HT (0.625 mg of conjugated estrogens alone, or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily), and 36,282 women were randomized to 1,000 mg of elemental calcium (carbonate) plus 400 IU of vitamin D3 daily, each compared with placebo. A total of 16,089 women participated in both arms. The predefined outcomes were adjudicated hip fractures and measured bone mineral density.
Interaction between HT and CaD on hip fracture (P interaction = 0.01) was shown. The effect of CaD was stronger among women assigned to HT (hazard ratio [HR], 0.59; 95% CI, 0.38-0.93) than among women assigned to placebo (HR, 1.20; 95% CI, 0.85-1.69). The effect of HT on hip fracture was stronger among women assigned to active CaD (HR, 0.43; 95% CI, 0.28-0.66) than among women assigned to placebo (HR, 0.87; 95% CI, 0.60-1.26). CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake. There was no interaction between HT and CaD on change in hip or spine bone mineral density.
Postmenopausal women at normal risk for hip fracture who are on CaD supplementation experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake.
Muchhas been written concerning the calcium requirements of children and adults. Most of the work which throws light upon this matter has been done in Europe and America, and the conclusions which have been drawn are such that they do not appear to be applicable to the conditions in many tropical countries. Sherman ('37) sets the standard allowance for maintenance of the adult at 0.68 gm. and 1 gm. for the grow ing child. He also states, "It is doubtless better for family food supplies to furnish at least 1 gm. per capita per day. ' ' Leitch ('37) considered the calcium requirements for chil dren and adolescents to range from 0.9 gm. between the ages of 5 and 9, to 1.9 gm. between the ages of 15 and 16 years, and thereafter to decrease gradually to 0.55 gm. at the age of 24 years. The diets of many tropical races consist of cereals, pulses, roots, vegetables and vegetable oils; milk and eggs seldom appear. Our studies are concerned with Ceylon, where the majority of the poorer classes augment such diets with a little fish. A typical diet of the laboring classes with a value of about 3000 calories, which does not include sprats, contains 0.3 gm. calcium daily. But many of the laboring class Ceylon ese take sprats two or three times a week, and this increases the amount of calcium to 0.6 gm. (Nicholls, '37).
Our object in this paper is to point out the existence of postmenopausal osteoporosis and to describe its clinical features. Some metabolic data showing the effects of therapy with estrogens and other agents are incorporated in other papers.1It will probably be well to start by explaining and defining the term "osteoporosis." Adult bone is normally subject to two continuous processes—formation and resorption. The mass of bone may be deficient either because resorption is too great (hyperparathyroidism with osteitis fibrosa generalisata) or because formation is too little (osteoporosis or osteomalacia). Formation of bone may be too little, furthermore, either because the osteoblasts do not lay down sufficient osseous matrix or because the matrix, once laid down, is not calcified. The former condition is osteoporosis; the latter, osteomalacia or rickets (fig. 1).It is thought that stresses and strains are an important stimulus to osteoblastic activity and that the atrophy
Description:
New U.S. Preventive Services Task Force (USPSTF) recommendation statement on vitamin D and calcium supplementation to prevent fractures in adults.
Methods:
The USPSTF commissioned 2 systematic evidence reviews and a meta-analysis on vitamin D supplementation with or without calcium to assess the effects of supplementation on bone health outcomes in community-dwelling adults, the association of vitamin D and calcium levels with bone health outcomes, and the adverse effects of supplementation.
Population:
These recommendations apply to noninstitutionalized or community-dwelling asymptomatic adults without a history of fractures. This recommendation does not apply to the treatment of persons with osteoporosis or vitamin D deficiency.
Recommendation:
The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation for the primary prevention of fractures in premenopausal women or in men. (I statement)The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with greater than 400 IU of vitamin D3 and greater than 1000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. (I statement)The USPSTF recommends against daily supplementation with 400 IU or less of vitamin D3 and 1000 mg or less of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women. (D recommendation).
Description:
Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for family and intimate partner violence (IPV).
Methods:
The USPSTF commissioned a systematic evidence review on screening women for IPV and elderly and vulnerable adults for abuse and neglect. This review examined the accuracy of screening tools for identifying IPV and the benefits and harms of screening women of childbearing age and elderly and vulnerable adults.
Population:
These recommendations apply to asymptomatic women (women who do not have signs or symptoms of abuse) of reproductive age and elderly and vulnerable adults.
Recommendation:
The USPSTF recommends that clinicians screen women of childbearing age for IPV, such as domestic violence, and provide or refer women who screen positive to intervention services (B recommendation).The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening all elderly or vulnerable adults (physically or mentally dysfunctional) for abuse and neglect (I statement).
Current standard-dose calcium supplements (eg, 1000 mg/d) may increase the risk for cardiovascular events. Effectiveness of lower-dose supplements in preventing bone loss should thus be considered. This study aimed to assess whether calcium supplements of 500 or 250 mg/d effectively prevent bone loss in perimenopausal and postmenopausal Japanese women. We recruited 450 Japanese women between 50 and 75 years of age. They were randomly assigned to receive 500 mg of calcium (as calcium carbonate), 250 mg of calcium, or placebo daily. Medical examinations conducted three times over a 2-year follow-up period assessed bone mineral density (BMD) of the lumbar spine and femoral neck. One-factor repeated measures ANOVA was used for statistical tests. Subgroup analyses were also conducted. Average total daily calcium intake at baseline for the 418 subjects who underwent follow-up examinations was 493 mg/d. Intention-to-treat analysis showed less dramatic decreases in spinal BMD for the 500-mg/d calcium supplement group compared to the placebo group (1.2% difference over 2 years, p = 0.027). Per-protocol analysis (≥80% compliance) revealed that spinal BMD for the 500-mg/d and 250-mg/d calcium supplement groups decreased less than the placebo group (1.6%, p = 0.010 and 1.0%, p = 0.078, respectively), and that femoral neck BMD for the 500-mg/d calcium supplement group decreased less relative to the placebo group (1.0%, p = 0.077). A low-dose calcium supplement of 500 mg/d can effectively slow lumbar spine bone loss in perimenopausal and postmenopausal women with habitually low calcium intake, but its effect on the femoral neck is less certain. Calcium supplementation dosage should thus be reassessed. (Clinical Trials Registry number: UMIN000001176). © 2012 American Society for Bone and Mineral Research.
Osteoporosis and osteopenia are associated with increased fracture incidence.
The aim of this study was to determine the comparative effectiveness of different pharmacological agents in reducing the risk of fragility fractures.
We searched multiple databases through 12/9/2011.
Eligible studies were randomized controlled trials enrolling individuals at risk of developing fragility fractures and evaluating the efficacy of bisphosphonates, teriparatide, selective estrogen receptor modulators, denosumab, or calcium and vitamin D.
Reviewers working independently and in duplicate determined study eligibility and collected descriptive, methodological quality, and outcome data.
This network meta-analysis included 116 trials (139,647 patients; median age, 64 yr; 86% females and 88% Caucasians; median follow-up, 24 months). Trials were at low to moderate risk of bias. Teriparatide had the highest risk reduction of fractures (odds ratios, 0.42, 0.30, and 0.50 for hip, vertebral, and nonvertebral fractures, respectively) and the highest probability of being ranked first for efficacy (probabilities of 42, 49, and 79% for hip, vertebral, and nonvertebral fractures, respectively). However, differences to denosumab, zoledronate, risedronate, ibandronate, and alendronate were not statistically significant. Raloxifene and bazedoxifene were likely less effective, although these data were limited. Calcium and vitamin D were ineffective given separately but reduced the risk of hip fractures if given in combination (odds ratio, 0.81; 95% confidence interval, 0.68–0.96).
Teriparatide, bisphosphonates, and denosumab are most effective in reducing the risk of fragility fractures. Differences in efficacy across drugs are small; therefore, patients and clinicians need to consider their associated harms and costs.
Calcium's ability to prevent bone loss in early postmenopausal women is controversial. We used data on 394 women from the placebo group of the Early Postmenopausal Interventional Cohort study, a clinical trial of alendronate, to investigate the relation of calcium intake to bone loss. Calcium intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm, and hip) and biochemical markers of bone turnover (serum total alkaline phosphatase, serum osteocalcin, and urinary n-telopeptide crosslink levels) were measured at baseline and annually thereafter. Women whose baseline calcium intake was <500 mg/d were advised to increase their calcium intake. Mean (±SE) BMD decreased by 1.9% ± 0.16% at the lumbar spine and 1.6% ± 0.14% at the hip over the 24-month period. Despite wide variations in baseline calcium intake and changes in calcium intake, these measures were not significantly associated with changes in BMD or bone turnover. Even women whose total calcium intake was > 1333 mg/d (the highest tertile of total calcium intake) showed a decline in BMD of almost 2%, similar to declines in the lower two tertiles of total calcium intake (<869 and 869–1333 mg/d, respectively). Increased calcium intake resulted in modest mean increases of approximately 200 mg/d. We were unable to demonstrate that increases of this magnitude or much greater (1 g/d) were protective against declines in BMD at any site, even in women who had the lowest calcium intake at baseline. In addition to adequate calcium intake, more effective therapy appears to be required when the therapeutic goal is to increase or maintain BMD.
Calcium balance in chronic kidney disease is poorly understood as calcium deficiency is a stimulus for secondary hyperparathyroidism and consequent bone loss while calcium excess promotes extraosseous calcifications. To help resolve this, we evaluated calcium balance in normal individuals and in patients with chronic kidney disease (CKD) on daily diets containing 800 and 2000 mg elemental calcium. Both normal individuals and patients with late stage 3 and stage 4 CKD were in slightly negative to neutral calcium balance on the 800-mg calcium diet. Normal individuals were in modest positive calcium balance on the 2000-mg diet, while patients with CKD on the same diet were in marked positive calcium balance at least over the 9 days of study; and significantly greater than the normal individuals. Increased calcium intake significantly decreased 1,25-dihydroxy-vitamin D and intact parathyroid hormone levels but did not alter the serum calcium concentration. Thus, our findings have important implications for both preventing calcium deficiency and loading in individuals with late stage 3 and stage 4 CKD.
The clinical effects of calcium supplements on adverse events reporting have not been well described. This study reviews randomized controlled trial (RCT) evidence of adverse events to clarify the epidemiology of these events. The hypothesis that patient self-report of myocardial infarction (MI) is increased in individuals receiving calcium supplementation is because of an increase in non-MI events incorrectly perceived by the patient as being because of MI, is examined. In seven RCTs summary self-reported gastrointestinal (GI) adverse event rates were more common in participants receiving calcium. These were described as constipation, excessive abdominal cramping, bloating, upper GI events, GI disease, GI symptoms, and severe diarrhoea or abdominal pain (calcium 14.1%, placebo 10.0%), relative risk (RR) 1.43 95% confidence interval (CI) 1.28 to 1.59, p < 0.001. Adjudicated functional GI hospitalizations in one study were calcium 6.8%, placebo 3.6% (RR 1.92, 95% CI 1.21-3.05, p = 0.006). Direct comparison of self-reported and adjudicated MI events in the two trials of dietary calcium supplementation showed self-reported MI rates of 3.6% in the calcium group and 2.1% in the placebo group. After adjudication the MI rates were 2.4% in the calcium group and 1.6% in the placebo group (RR 1.45, 95% CI 0.88-2.45, p = 0.145). These data support the hypothesis that calcium tablets increase the incidence of adverse GI events, which may account for an increase in self-reported MI in calcium treated patients but not controls.
Predictors of bone loss in elderly Asian women have been unclear. This cohort study aimed to assess lifestyle, nutritional, and biochemical predictors of bone loss in elderly Japanese women.
Subjects included 389 community-dwelling women aged 69 y and older from the Muramatsu cohort initiated in 2003; follow-up ended in 2009. We obtained data on physical characteristics, osteoporosis treatment (with bisphosphonates or selective estrogen receptor modulators), physical activity, calcium intake, serum 25-hydroxyvitamin D, undercarboxylated osteocalcin, serum albumin, and bone turnover markers as predictors. The outcome was a 6-y change in forearm BMD (ΔBMD). Osteoporosis treatment was coded as 0 for none, 1 for sometimes, and 2 for always during the follow-up period. Stepwise multiple linear regression analysis was used to identify independent predictors of ΔBMD.
Mean age of the subjects was 73.3 y. Mean values of ΔBMD and Δweight were -0.019 g/cm(2) (-5.8%) and -2.2 kg, respectively. Stepwise multiple linear regression analysis revealed baseline BMD (β = -0.137, P < 0.0001), osteoporosis treatment (β = 0.0068, P = 0.0105), serum albumin levels (β = 0.0122, P = 0.0319), and Δweight (β = 0.0015, P = 0.0009) as significant independent predictors of ΔBMD. However, none of the other nutritional or biochemical indices were found to be significant predictors of ΔBMD.
Our findings indicate that adequate general nutrition and appropriate osteoporosis medication, rather than specific nutritional regimens, may be effective in preventing bone loss in elderly women.
Evidence on the role of diet during adulthood and beyond on fracture occurrence is limited. We investigated diet and hip fracture incidence in a population of elderly Europeans, participants in the European Prospective Investigation into Cancer and nutrition study.
29, 122 volunteers (10,538 men, 18,584 women) aged 60 years and above (mean age: 64.3) from five countries were followed up for a median of 8 years and 275 incident hip fractures (222 women and 53 men) were recorded. Diet was assessed at baseline through validated dietary questionnaires. Data were analyzed through Cox proportional-hazards regression with adjustment for potential confounders.
No food group or nutrient was significantly associated with hip fracture occurrence. There were suggestive inverse associations, however, with vegetable consumption (hazard ratio (HR) per increasing sex-specific quintile: 0.93, 95% confidence interval (CI): 0.85-1.01), fish consumption (HR per increasing sex-specific quintile: 0.93, 95% CI: 0.85-1.02) and polyunsaturated lipid intake (HR per increasing sex-specific quintile: 0.92, 95% CI: 0.82-1.02), whereas saturated lipid intake was positively associated with hip fracture risk (HR per increasing sex-specific quintile: 1.13, 95% CI: 0.99-1.29). Consumption of dairy products did not appear to influence the risk (HR per increasing sex-specific quintile: 1.02, 95% CI: 0.93-1.12).
In a prospective study of the elderly, diet, including consumption of dairy products, alcohol and vitamin D, did not appear to play a major role in hip fracture incidence. There is however, weak and statistically non-significant evidence that vegetable and fish consumption and intake of polyunsaturated lipids may have a beneficial, whereas saturated lipid intake a detrimental effect.
Background Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures.
Methods In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures.
Findings 698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12.6%] of 2617 vs 367 [13.7%] of 2675; hazard ratio (HR) 0.94 [95% Cl 0.81-1.09]); between participants allocated vitamin D3 and those who were not (353 [13.3%] of 2649 vs 345 [13.1%] of 2643; 1.02 [0.88-1.19]); or between those allocated combination treatment and those assigned placebo (165 [12.6%] of 1306 vs 179 [13.4%] of 1332; HR for interaction term 1.01 [0.75-1.36]). The groups did not differ in the incidence of all new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54.5%) of 5292 were still taking tablets, 451 (8.5%) had died, 58 (1.1%) had withdrawn, and 1897 (35.8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9.4% [95% CI 6.6-12.2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups.
Interpretation The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.
There is no consistent evidence, to our knowledge, that calcium supplementation affects bone mineral density (BMD) in men, despite male osteoporosis being a common clinical problem.
To determine the effects of calcium supplementation (600 mg/d, 1200 mg/d, or placebo) on BMD in men, we conducted a double-blind, randomized controlled trial for a 2-year period at an academic clinical research center. A total of 323 healthy men at least 40 years old (mean age, 57 years) were recruited by newspaper advertisement. Complete follow-up was achieved in 96% of subjects.
The BMD increased at all sites in the group receiving calcium, 1200 mg/d, by 1% to 1.5% more than those receiving placebo. The results for the group receiving calcium, 600 mg/d, were not different from the placebo group at any BMD site. There was no interaction between the BMD treatment effect and either age or dietary calcium intake. There were dosage-related, sustained decreases in serum parathyroid hormone (P < .001), total alkaline phosphatase activity (P = .01), and procollagen type 1 N-terminal propeptide (P < .001) amounting to 25%, 8%, and 20%, respectively, in the group receiving calcium, 1200 mg/d, at 2 years. Tooth loss, constipation, and cramps were unaffected by calcium supplementation, falls tended to be less frequent in the group receiving calcium, 1200 mg/d, but vascular events tended to be more common in the groups receiving calcium vs the group receiving placebo.
Calcium, 1200 mg/d, has effects on BMD in men comparable with those found in postmenopausal women but a dosage of 600 mg/d is ineffective for treating BMD.
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