Search

Active surveillance (AS) is an attractive alternative to immediate treatment for men with low-risk prostate cancer. Thus, the identification of environmental factors that promote the progression of indolent disease towards aggressive stages is critical to optimize clinical management. Epidemiological studies suggest that calcium-rich diets contribute to an increased risk of developing prostate cancer and that vitamin D reduces this risk. However, the potential effect of these nutrients on the progression of early-stage prostate tumours is uncertain, as studies in this setting are scarce and have not provided unambiguous conclusions. By contrast, the results of a preclinical study from our own group demonstrate that a diet high in calcium dose-dependently accelerated the progression of early-stage prostate tumours and that dietary vitamin D prevented this effect. The extent to which the conclusions of preclinical and epidemiological studies support a role for calcium and vitamin D and the relevance of monitoring and adjustment of calcium and/or vitamin D intake in patients on AS require further investigation.

Ethanol (EtOH) dosage, frequency, and paired associative learning affect the risk of alcoholism. Recently, Spanagel et al. reported that acamprosate calcium (Acam Ca) prescribed for alcoholism exerts an anti-relapse effect via Ca. Ca is contained in foods, sometimes consumed with alcohol. Therefore, we investigated the association among oral Ca ingestion, EtOH-induced locomotor sensitization, and plasma Ca levels on how to consume Ca for moderate drinking. We used DBA/2 CrSlc mice, and CaCl 2 as water-soluble Ca salts. For pre-administration, elemental Ca (50, 75, 100, or 150 mg/kg, per os (p.o.)) or water for control was administered 1 h before EtOH (2 g/kg, 20 v/v (%) EtOH in saline) administration intraperitoneal (i.p.) for locomotor sensitization or for plasma Ca level changes. For post-administration, elemental Ca (100 mg/kg) was administered 1 h after EtOH. Moreover, we employed bepridil and the dopamine D1 antagonist, SCH-23390 to further examine the mechanism of EtOH-induced sensitization. The locomotor sensitization segmentalized for 300 s had two peaks (0-90 s and 180-300 s). Pre-administration of Ca (50, 75, and 100 mg/kg) significantly reduced the 0-90-s peak, selectively blocked by SCH-23390, but "non-dose dependently" as Ca 150 mg/kg did not have this effect. Bepridil blocked the suppressive effect of pre-administration of Ca (100 mg/kg). The effective pre-doses of Ca (50-100 mg/kg) maintained plasma Ca basal levels against EtOH-induced decrease of Ca. On the contrary, post-administration of Ca inversely led to significant promotion of sensitization of both locomotor peaks. Oral Ca intake had diverse effects on EtOH-induced sensitization depending on Ca dosage and timing.

Objective: To determine the effect of the daily intake of calcium and vitamin D-enriched milk (with or without fructooligosaccharides [FOS]) on vitamin D, bone metabolism, and cardiovascular risk factors., Materials and Methods: Two-year randomized controlled study, including 500 healthy postmenopausal women, assigned to 500 mL/day of skimmed milk to one of three groups: Low-dose (L): (120 mg/100 mL calcium, vitamin D 3 30 UI/100 mL), group A: calcium and vitamin D (180 mg/100 mL and 120 UI/100 mL), and group B: calcium and vitamin D (180 mg/100 mL and 120 UI/100 mL) and FOS (5 g/L). We evaluated serum 25(OH)D, bone mineral density (BMD) by Dual Energy X-ray Absorptiometry, and biochemical data of glucose and lipid metabolism., Results: After 24 months, vitamin D concentrations did not change in the control group, but increased in group A and group B, p < 0.001. We observed an increase in femoral neck BMD and an improvement in fasting plasma glucose, HbA 1c , total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B 100., Conclusions: Daily intake of milk enriched with calcium and vitamin D in postmenopausal healthy women induces a significant improvement in vitamin D status, a significant increase in BMD at femoral neck, and also favorable effects on glucose and lipid profile.

Purpose: Pregnancy is characterised by increased bone turnover, but high bone turnover with resorption exceeding formation may lead to negative maternal bone remodelling. Recent studies are conflicting regarding the effect of calcium on skeletal health in pregnancy. The aim of this study was to examine the seasonal effect of serum 25-hydroxyvitamin D (25OHD) and dietary calcium on a marker of bone resorption., Methods: This was prospective study of 205 pregnant women [two cohorts; early pregnancy at 13 weeks (n = 96), and late pregnancy at 28 weeks (n = 109)]. Serum 25OHD and urine cross-linked N-telopeptides of type I collagen (uNTX) were measured at both time points. Intakes of vitamin D and calcium were recorded using 3-day food diaries at each trimester., Results: Compared to summer pregnancies, winter pregnancies had significantly lower 25OHD and significantly higher uNTX. Higher calcium intakes were negatively correlated with uNTX in winter, but not summer. In late pregnancy, compared to those reporting calcium intakes ≥1000 mg/day, intakes of <1000 mg/day were associated with a greater increase in uNTX in winter pregnancies than in summer (41.8 vs. 0.9%). Increasing calcium intake in winter by 200 mg/day predicted a 13.3% reduction in late pregnancy uNTX., Conclusions: In late pregnancy, during winter months when 25OHD is inadequate, intakes of dietary calcium <1000 mg/day were associated with significantly increased bone resorption (uNTX). Additional dietary calcium is associated with reduced bone resorption in late pregnancy, with greater effect observed in winter. Further research regarding optimal dietary calcium and 25OHD in pregnancy is required, particularly for women gestating through winter.

Objectives: To determine the incidence of hypovitaminosis D and to evaluate a supplementation intervention. We hypothesized that patients would exhibit high adherence with a free sample, and levels would become sufficient., Design: Prospective observational study., Setting: Level 1 trauma center., Patients: One hundred forty-four consecutive, skeletally mature patients treated for acute fractures., Intervention: All were provided 600 mg calcium and 800 IU vitamin D3 capsules twice daily., Main Outcome Measurements: Serum 25(OH) D levels were obtained on presentation and after supplementation. Patient surveys determined adherence, vitamin D intake, and sun exposure., Results: Ninety-one men and 53 women, mean age 45 years, mean body mass index 28.1, were studied. Mean baseline 25(OH) D level was 20.2 ng/mL, including 9 patients taking vitamin D supplements before injury. All others (mean baseline 16.9 ng/mL) were prescribed calcium and vitamin D and were offered free supplements when discharged. Seventy-seven patients completed surveys, and mean 25(OH) D level was 36.7 ng/mL after a mean of 7.0 weeks of supplementation (P < 0.0001). Seventy-nine percent reported adherence to supplement recommendations. All adherent patients achieved normal levels. Sixteen patients were nonadherent, with 10 who forgot to take the supplement, 4 choosing not to use it, 1 choosing to sell the sample, and 1 losing the sample., Conclusion: Hypovitaminosis D was present in 97% of orthopaedic trauma patients who were not already taking supplements. The intervention was effective in reducing hypovitaminosis D within several weeks, with all supplemented patients achieving normal levels. Seventy-nine percent of patients adhered to recommendations. Further study to determine the long-term cost-effectiveness of this strategy seems warranted., Level of Evidence: Therapeutic, Level II. See Instructions for Authors for a complete description of levels of evidence.

The World Health Organization (WHO) recommends calcium supplementation for prevention of pre-eclampsia, but factors affecting adoption and acceptability of the recommendations among pregnant women have not been examined. We explored adoption of the WHO guidelines in Kenya, using the trials of improved practices. We recruited 38 pregnant women and assigned participants to three regimens representing potential trade-offs among daily dose, bioavailability, and acceptability. Participants were provided with supplements, requested to select preferred product type, counselled on how to take them, and interviewed 4 times over 6 weeks to assess their experiences. We tracked bottle opening with electronic monitors, as proxy for supplement consumption. We analysed interview transcripts thematically. All participants were willing to try the supplements. Average daily consumption ranged from 77 to 1,577 mg/d. Most participants (74%) chose the chewable product. Participants preferred its "sweet taste" and liked the ability to consume it without water. Women in the 2-dose regimen were least likely to switch; however, women assigned to the 3-dose regimen, or who switched to the 3-dose regimen, consumed the most calcium per day. Difficulties with the 4-dose regimen included afternoon doses when women were likely to forget and having to wait hours after supper for last dose. Use of an illustrated calendar, keeping supplements in conspicuous locations and requesting support from relatives were strategies that supported adherence. Pregnant women are likely to adopt Ca supplementation, with appropriate programmatic adaptations. Careful attention to product attributes, regimen complexity, and strategies for reassuring and reminding women are needed to adapt the WHO guidelines., (© 2017 John Wiley & Sons Ltd.)

Human studies have shown that individuals with colon cancer tend to have lower serum 25-hydroxy-vitamin D 3 [25(OH)D 3 ] levels compared with healthy controls, but whether this link is causative, a result of the disease or an indicator of another factor altogether has yet to be demonstrated. In humans, vitamin D, calcium and UV exposure are inextricably linked; therefore, understanding the individual and combined roles of each of these will require animal models specifically designed to address these questions. To begin to untangle this network, our group has employed the Apc Pirc/+ rat, which contains a truncating mutation in the Apc gene, leading to the development of colonic tumors. Our group previously utilized this model to demonstrate that vitamin D supplementation above normal does not reduce colonic tumor burden and, in fact, increased tumor multiplicity in a dose-dependent manner. In the current study, we tested whether vitamin D deficiency plays a causative role in tumor development using two strains which differ in their susceptibility to intestinal tumorigenesis. In the colon, vitamin D deficiency did not increase the development of tumors in either strain, and was actually protective in one strain. Unexpectedly, low dietary calcium combined with vitamin D deficiency significantly suppressed tumor development in the small intestine and colon of both strains. The vast majority of tumors in the human intestine occur in the colon, and we find no evidence to support a direct role of vitamin D deficiency in increasing colonic tumorigenesis, and low calcium might protect against tumor development.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Purpose: Some research findings suggest that calcium plus vitamin D (VitD) might have a preventive effect on nonalcoholic fatty liver disease development. Moreover, contradictory evidence also exists regarding calcium and VitD deficient diets. This study aimed to evaluate the effect of four different dietary calcium and VitD 3 (cholecalciferol) levels on the development of high-fat, high-fructose (HFHFr) diet-induced nonalcoholic fatty liver disease and AMP-activated protein kinase (AMPK) phosphorylation., Methods: Thirty male Wistar rats were fed with normal or HFHFr diet containing low calcium (0.2%) and VitD 3 (250 IU/kg) (LCD), normal calcium (0.5%) and VtD 3 (1000 IU/kg) (CN), high calcium (1.2%) and VitD 3 (4000 IU/kg) (HCD) or very high amount of calcium (2.4%) and VitD 3 (10,000 IU/kg) (VHCD). After 60 days, anthropometric, metabolic and hepatic parameters were evaluated. The effect of the experimental diets on liver AMPK phosphorylation was also investigated., Results: Rats fed on high calcium plus VitD 3 diets, especially VHCD, demonstrated lower adiposity, serum liver enzymes, hepatic lipid accumulation and steatosis. The LCD diet also decreased hepatic lipid content and fatty changes. No evidence indicating the involvement of AMPK in the observed associations was found (P value = 0.51)., Conclusions: The results showed high calcium plus VitD 3 intakes considerably prevent biochemical and hepatic changes induced by HFHFr diet, probably via an insulin and AMPK-independent pathway. A low intake of these two nutrients was also linked with a significant decrease in HFHFr diet-induced hepatic steatosis.

We investigated the effects of high-Ca fat-free milk phase (MD) (prescription of approximately 1500 mg of Ca/d) v. low-Ca phase (CD) (prescription of approximately 800 mg of Ca/d) in an energy-restricted diet on the metabolic syndrome (MetS) and cardiometabolic measures in individuals with type 2 diabetes mellitus (T2DM) and low habitual Ca consumption (<600 mg/d). In this randomised cross-over design, fourteen adults with T2DM (49·5 (sd 8·6) years, BMI 29·4 (sd 4·5) kg/m2) consumed either MD or CD for 12 weeks, with a washout of 18 weeks between phases. A breakfast shake containing 700 mg (MD) or 6·4 mg (CD) of Ca was consumed in the laboratory. In addition, energy-restricted diets were prescribed (800 mg of dietary Ca/d). Waist circumference (WC), fasting glucose, fasting TAG, systolic (SBP) and diastolic blood pressure (DBP), fasting total cholesterol, fasting LDL-cholesterol, fasting HDL-cholesterol, HDL:LDL ratio, HDL:TAG ratio and lipid accumulation product (LAP) index were assessed at baseline and after each phase. Ca consumption during the study was equivalent to 1200 mg/d during MD and 525 mg/d during CD. There was a greater reduction in WC, SBP, DBP and LAP index after MD compared with CD. HDL:LDL ratio increased and total cholesterol, LDL-cholesterol, SBP, DBP and LAP index decreased only in MD. The consumption of approximately 1200 mg of Ca/d (700 mg from fat-free milk+500mg from other dietary sources) associated with an energy-restricted diet decreased some of the MetS components and cardiometabolic measures in adults with T2DM.

Introduction: Postmenopausal osteoporosis is a highly prevalent disease. Prevention through lifestyle measures includes an adequate calcium intake. Despite the guidance provided by scientific societies and governmental bodies worldwide, many issues remain unresolved., Aims: To provide evidence regarding the impact of calcium intake on the prevention of postmenopausal osteoporosis and critically appraise current guidelines., Materials and Methods: Literature review and consensus of expert opinion., Results and Conclusion: The recommended daily intake of calcium varies between 700 and 1200mg of elemental calcium, depending on the endorsing source. Although calcium can be derived either from the diet or supplements, the former source is preferred. Intake below the recommended amount may increase fragility fracture risk; however, there is no consistent evidence that calcium supplementation at, or above, recommended levels reduces risk. The addition of vitamin D may minimally reduce fractures, mainly among institutionalised people. Excessive intake of calcium, defined as higher than 2000mg/day, can be potentially harmful. Some studies demonstrated harm even at lower dosages. An increased risk for cardiovascular events, urolithiasis and even fractures has been found in association with excessive calcium intake, but this issue remains unresolved. In conclusion, an adequate intake of calcium is recommended for general bone health. Excessive calcium intake seems of no benefit, and could possibly be harmful., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Adequate calcium intake during pregnancy is important in the prevention of pre-eclampsia. A substantial proportion of pregnant women do not meet the recommended daily calcium intake, even in developed countries. Nonetheless, calcium supplementation is not routinely advised to pregnant women in most countries. We aimed to predict the impact of advising pregnant women to use calcium supplements (1,000 mg/day) on the number of cases of pre-eclampsia prevented and related health care costs. By use of a decision-analytic model, we assessed the expected impact of advising calcium supplementation to either (1) all pregnant women, (2) women at high risk of developing pre-eclampsia, or (3) women with a low dietary calcium intake compared with current care. Calculations were performed for a hypothetical cohort of 100,000 pregnant women living in a high-income country, although input parameters of the model can be adjusted so as to fit other settings. The incidence of pre-eclampsia could be reduced by 25%, 8%, or 13% when advising calcium supplementation to all pregnant women, women at high risk of pre-eclampsia, or women with a low dietary calcium intake, respectively. Expected net financial benefits of the three scenarios were of €4,621,465, €2,059,165, or €2,822,115 per 100,000 pregnant women, respectively. Advising pregnant women to use calcium supplements can be expected to cause substantial reductions in the incidence of pre-eclampsia as well as related health care costs. It appears most efficient to advise calcium supplementation to all pregnant women, not subgroups only., (© 2017 John Wiley & Sons Ltd.)

There are care gaps in the evaluation and treatment of osteoporosis after a fragility fracture. The Joint Commission is considering adoption of core measures. We compared compliance between two secondary fracture prevention programs in our institution. Incorporating strengths of both may provide the best outcomes for secondary fracture prevention., Purpose: There are significant care gaps in the evaluation and treatment of osteoporosis after occurrence of fragility fracture. The Joint Commission is considering adoption of a core measure set on osteoporosis-associated fractures, including laboratory assessment, bone density testing, and osteoporosis pharmacologic therapy. We compared compliance to these proposed measures between two secondary fracture prevention programs in patients hospitalized for acute fracture in an open medical system., Methods: We conducted a retrospective, single center medical records review of a nurse practitioner-led Fracture Liaison Service (FLS), a physician-led Fracture Prevention Program (FPP), and a historical time without any secondary fracture prevention program (Usual Care) for baseline care. Primary outcomes were the completion of five laboratory tests (calcium, 25-hydroxy vitamin D, renal function, liver function, and complete blood count), order placement and completion of dual x-ray absorptiometry (DXA) scan within 3 months, prescription of osteoporosis medication within 3 months, and medication adherence at 6 months after hospital discharge., Results: Completion of all five laboratory tests was higher in FPP versus FLS (84.7 vs. 36.9%, p < 0.001). DXA scan completion was higher in FPP than FLS but not statistically significant (66.7 vs. 54.9%, p = 0.11). Medication prescription at 3 months and adherence at 6 months were significantly higher in FPP versus FLS (65.3 vs. 24.0%, p < 0.001 and 70.8 vs. 27.7%, p < 0.001, respectively)., Conclusion: Incorporating strengths of both FLS (care coordination) and FPP (physician direction) may provide the best outcomes for secondary fracture prevention by ensuring laboratory and DXA testing and initiating osteoporosis medication.

Purpose: Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) frequently occur in women being treated for breast cancer. Prior studies suggest high prevalence of vitamin D deficiency in breast cancer patients with musculoskeletal (MS) pain. We conducted a randomized, placebo-controlled trial to determine if 30,000 IU vitamin D3 per week (VitD3) would prevent worsening of AIMSS in women starting adjuvant letrozole for breast cancer., Methods: Women with stage I-III breast cancer starting adjuvant letrozole and 25(OH)D level ≤40 ng/ml were eligible. All subjects received standard daily supplement of 1200 mg calcium and 600 IU vitamin D3 and were randomized to 30,000 IU oral VitD3/week or placebo. Pain, disability, fatigue, quality of life, 25(OH)D levels, and hand grip strength were assessed at baseline, 12, and 24 weeks. The primary endpoint was incidence of an AIMSS event., Results: Median age of the 160 subjects (80/arm) was 61. Median 25OHD (ng/ml) was 25 at baseline, 32 at 12 weeks, and 31 at 24 weeks in the placebo arm and 22, 53, and 57 in the VitD3 arm. There were no serious adverse events. At week 24, 51% of women assigned to placebo had a protocol defined AIMSS event (worsening of joint pain using a categorical pain intensity scale (CPIS), disability from joint pain using HAQ-II, or discontinuation of letrozole due to MS symptoms) vs. 37% of women assigned to VitD3 (p = 0.069). When the brief pain inventory (BPI) was used instead of CPIS, the difference was statistically significant: 56 vs. 39% (p = 0.024)., Conclusions: Although 30,000 IU/week of oral vitamin D3 is safe and effective in achieving adequate vitamin D levels, it was not associated with a decrease in AIMSS events based on the primary endpoint. Post-hoc analysis using a different tool suggests potential benefit of vitamin D3 in reducing AIMSS.

Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated until the albumin-corrected serum calcium concentration decreased to 10.0 mg/dL or less or until dose escalation was considered not necessary or feasible. Serum calcium concentration at the baseline was 12.1 ± 1.3 mg/dL (mean ± standard deviation; range 10.4-14.6 mg/dL) and decreased to 10.1 ± 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At the end of the titration phase, at least a 1 mg/dL reduction in serum calcium concentration from the baseline was observed in five patients (three with carcinoma and two with PHPT), and it decreased to the normocalcemic range in five patients (three with carcinoma and two with PHPT). Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder. Cinacalcet effectively relieved hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and might be effective in those with intractable PHPT. The drug might be tolerable and safe at a dosage of at most 75 mg three times a day.

Purpose: This study aims to evaluate access to anti-osteoporosis medication (AOM) and the factors affecting their prescription for Korean elderly patients with a hip fracture., Methods: A cross-sectional study was conducted on hip fracture patients aged 65 years or more using national-level data from 2013 to 2014. The prescription rates of AOM within 3 months after hip fracture were determined and the factors affecting AOM prescriptions were identified through multivariate logistic regression., Results: A total of 6307 elderly patients were selected from a national medical insurance database, giving an estimated 15,768 patients nationally in a nine-month period. One-third of the patients (33.5%) received an AOM prescription and only 9.4% of the patients were prescribed an AOM with calcium and vitamin D supplements. Being 80 years and older (adjusted OR, 0.78; 95% CI, 0.70-0.88) and having three or more comorbid diseases (adjusted OR, 0.66; 95% CI, 0.55-0.78) were associated with a lower likelihood of an AOM prescription. Female sex (adjusted OR, 2.54; 95% CI, 2.17-2.98), an osteoporosis diagnosis (adjusted OR, 2.50; 95% CI, 2.15-2.91), concurrent thiazolidinedione therapy (adjusted OR, 2.11; 95% CI, 1.29-3.45) and a dual-energy X-ray absorptiometry (DXA) examination after hip fracture (adjusted OR 4.11; 95% CI, 3.67-4.62) were all significant predictive factors for AOM prescription. Bisphosphonates were the most frequently prescribed AOMs (92.2%)., Conclusions: The AOM prescription rate for elderly patients with hip fractures was suboptimal in Korea. Factors affecting an AOM prescription were age, sex, clinical comorbidity, osteoporosis status, concurrent thiazolidinedione therapy, and receiving a DXA examination after hip fracture., (Copyright © 2017. Published by Elsevier B.V.)

Background: Evidence supports the role of lifestyle interventions as a primary intervention strategy among individuals with dyslipidemia. The role of micronutrients, and calcium in particular, on cholesterol metabolism is not clear and warrants further investigation., Objective: The aim of this study is to conduct a meta-analysis of controlled clinical trials that have examined the effects of calcium supplements on blood lipids among adults., Methods: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched up to March 2016 for calcium supplements clinical trials. Other trials were selected from searching bibliography of reviews, meta-analysis, and included trials. Clinical trials with random allocation to calcium supplementation or calcium plus vitamin D supplementation, or control were selected. Data collected included study design, participant characteristics, information of the intervention, and outcomes. Data synthesis was conducted using random effect models., Results: A total of 22 trials, representing 4071 participants, met the eligibility criteria. Compared with control group, calcium supplements significantly reduced low-density lipoprotein cholesterol level by -0.12 mmol/L (95% confidence interval, -0.22 to -0.02) and increased high-density lipoprotein cholesterol level by 0.05 mmol/L (95% confidence interval, 0.00 to 0.10). Subgroup analyses revealed that the associations were consistent across study duration and vitamin D cosupplementation status., Conclusions: Calcium supplementation has beneficial effect on blood lipids. Such supplements may be useful as a nonpharmaceutical strategy in cholesterol control.

Objective: The development of alternative approaches to prevent and/or treat osteoporosis, as a chronic progressive bone disease, is being considered currently. Among dietary supplements, probiotics may have favorable effects on bone metabolism. Therefore, the aim of this study was to evaluate the effects of a multispecies probiotic supplementation on bone biomarkers and bone density in osteopenic postmenopausal women., Methods: This randomized double-blind placebo-controlled clinical trial was performed on 50 patients with osteopenia aged 50-72 years. Participants were randomly assigned to take either a multispecies probiotic supplement (GeriLact; n = 25) or placebo (n = 25) for 6 months. GeriLact contains 7 probiotic bacteria species. Participants received 500 mg Ca plus 200 IU vitamin D daily. Bone mineral density (BMD) of lumbar spine and total hip and blood biomarkers including bone-specific alkaline phosphatase (BALP), osteocalcin (OC), collagen type 1 cross-linked C-telopeptide (CTX), deoxypyridinoline (DPD), parathyroid hormone (PTH), 25-OH vitamin D, and serum pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-1β) were assessed at baseline and at the end of the study., Results: The multispecies probiotic significantly decreased BALP (p = 0.03) and CTX (p = 0.04) levels in comparison with the control group but had no effect on BMD of the spine and total hip. Moreover, there was a statistically significant decrease in serum PTH (p = 0.01) and TNF-α (p = 0.02) in the intervention group compared to the placebo group., Conclusions: These results may suggest the favorable effects of the multispecies probiotic supplementation for 6 months on bone health in postmenopausal women due to slowing down the rate of bone turnover.

Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. l-Arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found that both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in association with colorectal cancer. We conducted a two-phase case-control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma [OR (95% CI):1.36 (1.11-1.68)] and multiple/advanced adenoma [OR (95% CI): 1.68 (1.28, 2.20)] than those who carried the GG genotype. The P values for interactions between calcium:magnesium intake ratio and rs2720574 were .002 for all adenomas and <.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma [OR (95% CI): 1.73 (1.27-2.36)] and advanced/multiple adenomas [1.62 (1.05-2.50)], whereas among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64 (0.42-0.99)] and advanced/multiple adenomas [0.55 (0.31-1.00)]., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Nothing is known about how well stone formers understand physician's explanations of stone formation, and a few data are available on adherence to provided recommendations. In this study, two groups of recurrent calcium stone formers (RCSFs) were compared. Group 1: 153 consecutive RCSF (118 men, 35 women) referred 1/2011-6/2014. At least 3 months after a 60-75 min consultation explaining metabolic evaluation and therapeutic measures, RCSF received a questionnaire by mail, regarding understanding of stone formation and adherence to therapeutic recommendations (diet, lifestyle, drug treatment). Response rate was 62 %. Group 2 (control): 81 consecutive RCSFs referred 7/2014-3/2016 (60 men, 21 women) were asked to answer the same questionnaire in the stone center while waiting for their follow-up consultation 3 months after starting prevention; response rate was 100 %. Alkali citrate was prescribed in 45 %. Answer sheets were analyzed anonymously, and frequencies of answers were compared by Chi-square test., Results: 67 % (group 1) and 62 % (group 2) indicated >80 % understanding of the given information (NS). Over 80 % adherence to recommendations occurred in 26 and 30 % (NS). Most frequent changes in dietary/lifestyle habits were increases in calcium (93 vs. 89 %) and fluid intakes (81 vs. 78 %); lowering psychosocial stress (23 vs. 24 %) was least popular. Adherence to 100 % on 6-7 days/week was significantly more frequent for medication than for dietary/lifestyle interventions, both in group 1 (84 vs. 24 %, p < 0.001) and group 2 (91 vs. 28 %, p < 0.001)., Conclusions: (1) results do not differ whether RCSFs are voluntarily participating by mail or asked to answer questionnaires in the stone clinic; (2) pathophysiologic explanations of stone disease are understood to >80 % by 2/3 of RCSFs; (3) after 3 months, perfect adherence to recommended treatment is more frequent on alkali citrate than on dietary/lifestyle measures; and (4) increasing calcium and fluid intake are the most popular dietary measures.

Background: Concerning the chemopreventive potential of calcium against colorectal neoplasms, strong evidence from initial randomized controlled trials (RCTs) of colorectal adenoma has not been confirmed from the most recent large RCT. To explain the conflicting results, a new hypothesis was proposed that the benefit of calcium may be confined to lean individuals., Methods: To test this hypothesis, we examined heterogeneity of the associations of calcium intake with adenoma and CRC, using data from the most recent meta-analyses of observational studies and conducting subgroup analysis by average body mass index (BMI) of study population., Results: An inverse association of calcium intake with adenoma and CRC did not vary by population average BMI. By anatomical subsites of CRC, while there was no significant evidence of heterogeneity by population average BMI (P heterogeneity  > 0.05), the benefit of calcium was confined to studies with population average BMI of ≥25 kg/m 2 for both colon cancer and rectal cancer, contradicting the hypothesis., Conclusions: In our study-level meta-analysis, we found no evidence to support that the chemopreventive potential of calcium, if real, may be stronger in leaner individuals.

Objective: To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP)., Methods: We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users., Results: Because of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made., Conclusion: This guideline provides direction for clinicians and patients making treatment decisions. Clinicians and patients should use a shared decision-making process that accounts for patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies., (© 2017, American College of Rheumatology.)

Purpose of Review: Nutritional rickets and osteomalacia are common in dark-skinned and migrant populations. Their global incidence is rising due to changing population demographics, failing prevention policies and missing implementation strategies. The calcium deprivation spectrum has hypocalcaemic (seizures, tetany and dilated cardiomyopathy) and late hypophosphataemic (rickets, osteomalacia and muscle weakness) complications. This article reviews sustainable prevention strategies and identifies areas for future research., Recent Findings: The global rickets consensus recognises the equal contribution of vitamin D and dietary calcium in the causation of calcium deprivation and provides a three stage categorisation for sufficiency, insufficiency and deficiency. For rickets prevention, 400 IU daily is recommended for all infants from birth and 600 IU in pregnancy, alongside monitoring in antenatal and child health surveillance programmes. High-risk populations require lifelong supplementation and food fortification with vitamin D or calcium. Future research should identify the true prevalence of rickets and osteomalacia, their role in bone fragility and infant mortality, and best screening and public health prevention tools.

Background: Among Chinese immigrants, osteoporosis is undertreated, misdiagnosed, and a leading cause of fragility fractures. In orthopaedic surgery departments, prevention education and health behavior change programs are necessary to improve their bone health., Purpose: The purpose of this study was to examine the effectiveness of an osteoporosis prevention education program on participants' self-efficacy with regard to exercise and nutrition when provided by an orthopaedic surgery team during an annual Chinese Health Fair in Santa Clara County, CA., Methods: This pilot study used a single-group pretest and posttest design. Chinese immigrants at risk of osteoporosis were recruited during a 1-day health fair. The Bone Health Intervention (BHI) included orthopaedic surgeon consultation, visual aids including osteoporosis images and bone models, a video that included a discussion on calcium and vitamin D in the Chinese diet and culturally-acceptable exercise, and osteoporosis educational handouts. The Osteoporosis Self-Efficacy Scale (OSES) was utilized to measure participants' confidence in the ability to participate in self-care behaviors related to physical activity and calcium intake before and after the intervention. Paired t tests were used to compare participants' OSES scores pre- and postintervention., Results: There was a significant increase in mean OSES scores postintervention, indicating that the intervention could be an effective method of increasing participants' self-efficacy regarding calcium intake and time spent in exercising., Conclusion: These results indicate that a culturally meaningful education program can potentially reduce fragility fracture risk. Orthopaedic health providers are ideal candidates to deliver preventive care education to improve outcomes for Chinese immigrants.

Purpose of Review: The scope of this review was to review the newest developments in the context of the existing knowledge on premenopausal bone fragility. Fragility fractures are common in postmenopausal women and men and diagnostic criteria for osteoporosis have been agreed and multiple pharmacological treatments have been developed over the last 25 years. In premenopausal women, fragility fractures and very low bone mass are uncommon and osteoporosis in premenopausal women has therefore attracted much less interest., Recent Findings: Recent studies have highlighted that lifestyle and dietary habits affect premenopausal bone mass. Bone mass may be improved by sufficient intake of calcium and vitamin D together with increased physical activity in premenopausal women with idiopathic osteoporosis. If pharmacological treatment is needed, teriparatide has been demonstrated to efficiently increase bone mass; however, no fracture studies and no comparative studies against antiresorptive therapies have been conducted. Pregnancy affects bone turnover and mass significantly, but pregnancy-associated osteoporosis is a rare and heterogeneous condition., Summary: The diagnosis of osteoporosis should only be considered in premenopausal women with existing fragility fractures, diseases or treatments known to cause bone loss or fractures. Secondary causes of osteoporosis should be corrected or treated if possible. The women should be recommended sufficient intake of calcium and vitamin and physical activity. In women with recurrent fractures or secondary causes that cannot be eliminated, for example glucocorticoid or cancer treatment, pharmacological intervention with bisphosphonates or teriparatide (not in the case of cancer) may be considered.

Background: Risk behaviors and hormone use place transgender individuals (TIs) in jeopardy for osteoporosis., Purpose: The purpose of this study was to expand the science about the knowledge, health beliefs, and osteoporosis (OP) preventing behaviors of TIs., Methods: This was a mixed-methods pilot study of a convenience sample of 31 TIs 30 years and older. Participants completed an online Osteoporosis Bone Health Survey. Fifteen participants were randomly selected for an interview to describe their perceptions of bone health., Results: Transgender individuals performed poorly on the knowledge measure. There were no significant findings for osteoporosis health beliefs. Participants' daily dietary dairy calcium intake was 800 mg and daily walking activity was 17 minutes. Perceptions of bone health revealed two essential elements, knowing and doing., Conclusion: Determining TIs' bone health perception is important because of their unique healthcare issues. Healthcare providers need to be aware of TIs' bone health needs to help enhance TIs' OP knowledge, health beliefs, and preventing behaviors.

Objective: To estimate the association between osteoporosis treatment and severe periodontitis in postmenopausal women., Methods: This cross-sectional study comprised of 492 postmenopausal women, 113 women in osteoporosis treatment, and 379 not treated. Osteoporosis treatment consisted of systemic estrogen alone, or estrogen plus progestin, and calcium and vitamin D supplements, for at least 6 months. Severe periodontitis was defined as at least two interproximal tooth sites with clinical attachment loss of at least 6 mm, and at least one interproximal site with probing depth of at least 5 mm; and dental caries experience was measured using the decayed, missing, and filled teeth (DMFT) index. Analysis included descriptive statistics and Poisson multivariate analysis with robust variance., Results: Women receiving osteoporosis treatment had less periodontal probing depth, less clinical attachment loss, and less gingival bleeding than women not receiving treatment for osteoporosis (P ≤ 0.05). In the osteoporosis treatment group, the estimated mean DMFT index score was approximately 20, the most frequent component being the number of missing teeth, and in the nontreated group, the DMFT index was approximately 19. The prevalence of severe periodontitis was 44% lower in the osteoporosis treatment group than in the nontreatment group. The prevalence ratioadjusted was 0.56, 95% confidence interval was 0.31 to 0.99 (P = 0.05), after adjustments for smoking, age, family income, and visit to the dentist., Conclusions: The results suggest that women treated with estrogen for postmenopausal osteoporosis have a lower prevalence of severe periodontitis than women not receiving treatment.

Background: The role of dietary calcium intake in cardiovascular disease (CVD), stroke, and fracture is controversial. Most previous reports have evaluated populations with high calcium intake. Objective: We aimed to evaluate whether high dietary calcium intake was associated with the risk of CVD, stroke, and fracture in a population with low calcium intake. Design: In a prospective cohort study beginning in 2001 in Ansung-Ansan, Korea, 2158 men and 2153 women aged >50 y were evaluated for all-cause mortality, CVD, stroke, and fractures over a median 9-y follow-up. Results: During follow-up, 242 and 100 deaths, 149 and 150 CVD events, 58 and 82 stroke events, and 211 and 292 incident fractures occurred in men and women, respectively. The first quartiles of energy-adjusted dietary calcium intake were 249 mg/d (IQR: 169 mg/d) in men and 209 mg/d (IQR: 161 mg/d) in women. Both men and women with higher dietary calcium intake tended to have higher fat, protein, sodium, phosphorus, fruit, and vegetable intakes. In men, outcomes were not significantly associated with dietary calcium intake with or without adjustments, and CVD risk tended to increase with increasing energy-adjusted dietary calcium intake, but this was not statistically significant ( P = 0.078 and P = 0.093 with and without adjustment, respectively). In women, CVD risk and dietary calcium intake showed a U-shaped association; the HRs (95% CIs) without adjustment relative to the first quartile were 0.71 (0.47, 1.07), 0.57 (0.36, 0.88), and 0.52 (0.33, 0.83) for quartiles 2, 3, and 4, respectively, and the values after adjustment were 0.70 (0.45, 1.07), 0.51 (0.31, 0.81), and 0.49 (0.29, 0.83) for quartiles 2, 3, and 4, respectively. Conclusion: In Korean women, increased dietary calcium intake was associated with a decreased CVD risk, but it did not influence the risk of stroke or fracture., (© 2017 American Society for Nutrition.)

Vitamin D-dependent rickets type 2A (VDDR2A) is a rare inherited disorder with decreased tissue responsiveness to 1,25-dihydroxyvitamin D [1,25(OH) 2 D], caused by loss of function mutations in the vitamin D receptor (VDR) gene. Approximately 50 types of mutations have been identified so far that change amino acids in either the N-terminal DNA binding domain (DBD) or the C-terminal ligand binding domain (LBD) of the VDR protein. The degree of responsiveness to 1,25(OH) 2 D varies between patients with VDDR2A, which may depend on their residual VDR function. In this report, we describe a female patient with VDDR2A caused by an early stop codon (R30X) in the VDR gene that resulted in a severely truncated VDR protein. She developed alopecia and bowed legs within a year after birth and was diagnosed with rickets at the age of 2. She had been treated with active vitamin D and oral calcium supplementation until 22 years of age, when she developed secondary hyperparathyroidism and high bone turnover. The genetic diagnosis of VDDR2A promoted the discontinuation of active vitamin D treatment in favor of monotherapy with oral calcium supplementation. We observed amelioration of the secondary hyperparathyroidism and normalization of bone metabolic parameters within 6 years.

Description: This guideline updates the 2008 American College of Physicians (ACP) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women. This guideline is endorsed by the American Academy of Family Physicians., Methods: The ACP Clinical Guidelines Committee based these recommendations on a systematic review of randomized controlled trials; systematic reviews; large observational studies (for adverse events); and case reports (for rare events) that were published between 2 January 2005 and 3 June 2011. The review was updated to July 2016 by using a machine-learning method, and a limited update to October 2016 was done. Clinical outcomes evaluated were fractures and adverse events. This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density, including pharmaceutical prescriptions, calcium, vitamin D, and estrogen. Evidence was graded according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system., Target Audience and Patient Population: The target audience for this guideline includes all clinicians. The target patient population includes men and women with low bone density and osteoporosis., Recommendation 1: ACP recommends that clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis. (Grade: strong recommendation; high-quality evidence)., Recommendation 2: ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. (Grade: weak recommendation; low-quality evidence)., Recommendation 3: ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinically recognized osteoporosis. (Grade: weak recommendation; low-quality evidence)., Recommendation 4: ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women. (Grade: weak recommendation; low-quality evidence)., Recommendation 5: ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women. (Grade: strong recommendation; moderate-quality evidence)., Recommendation 6: ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. (Grade: weak recommendation; low-quality evidence).

Background: Early menopause, defined as the cessation of ovarian function before the age of 45 y, affects ∼10% of women and is associated with higher risk of cardiovascular disease, osteoporosis, and other conditions. Few modifiable risk factors for early menopause have been identified, but emerging data suggest that high vitamin D intake may reduce risk. Objective: We evaluated how intakes of vitamin D and calcium are associated with the incidence of early menopause in the prospective Nurses' Health Study II (NHS2). Design: Intakes of vitamin D and calcium from foods and supplements were measured every 4 y with the use of a food-frequency questionnaire. Cases of incident early menopause were identified from all participants who were premenopausal at baseline in 1991; over 1.13 million person-years, 2041 women reported having natural menopause before the age of 45 y. We used Cox proportional hazards regression to evaluate relations between intakes of vitamin D and calcium and incident early menopause while accounting for potential confounding factors. Results: After adjustment for age, smoking, and other factors, women with the highest intake of dietary vitamin D (quintile median: 528 IU/d) had a significant 17% lower risk of early menopause than women with the lowest intake [quintile median: 148 IU/d; HR: 0.83 (95% CI: 0.72, 0.95); P -trend = 0.03]. Dietary calcium intake in the highest quintile (median: 1246 mg/d) compared with the lowest (median: 556 mg/d) was associated with a borderline significantly lower risk of early menopause (HR: 0.87; 95% CI: 0.76, 1.00; P -trend = 0.03). Associations were stronger for vitamin D and calcium from dairy sources than from nondairy dietary sources, whereas high supplement use was not associated with lower risk. Conclusions: Findings suggest that high intakes of dietary vitamin D and calcium may be modestly associated with a lower risk of early menopause. Further studies evaluating 25-hydroxyvitamin D concentrations, other dairy constituents, and early menopause are warranted., (© 2017 American Society for Nutrition.)

Stress fractures are part of a continuum of changes in healthy bones in response to repeated mechanical deformation from physical activity. If the activity produces excessive repetitive stress, osteoclastic processes in the bone may proceed at a faster pace than osteoblastic processes, thus weakening the bone and augmenting susceptibility to stress fractures. Overall stress fracture incidence is about three cases per 1,000 in active duty Servicemembers, but it is much higher among Army basic trainees: 19 per 1,000 for men and 80 per 1,000 for women. Well-documented risk factors include female sex, white ethnicity, older age, taller stature, lower aerobic fitness, prior physical inactivity, greater amounts of current physical training, thinner bones, cigarette smoking, and inadequate intake of vitamin D and/or calcium. Individuals with stress fractures present with focal tenderness and local pain that is aggravated by physical activity and reduced by rest. A sudden increase in the volume of physical activity along with other risk factors is often reported. Simple clinical tests can assist in diagnosis, but more definitive imaging tests will eventually need to be conducted if a stress fracture is suspected. Plain radiographs are recommended as the initial imaging test, but magnetic resonance imaging has higher sensitivity and is more likely to detect the injury sooner. Treatment involves first determining if the stress fracture is of higher or lower risk; these are distinguished by anatomical location and whether the bone is loaded in tension (high risk) or compression (lower risk). Lowerrisk stress fractures can be initially treated by reducing loading on the injured bone through a reduction in activity or by substituting other activities. Higher-risk stress fractures should be referred to an orthopedist. Investigated prevention strategies include modifications to physical training programs, use of shock absorbing insoles, vitamin D and calcium supplementation, modifications of military equipment, and leadership education with injury surveillance., (2017.)

Background : Considerable attention has recently focused on dietary protein's role in the mature skeleton, prompted partly by an interest in nonpharmacologic approaches to maintain skeletal health in adult life. Objective: The aim was to conduct a systematic review and meta-analysis evaluating the effects of dietary protein intake alone and with calcium with or without vitamin D (Ca±D) on bone health measures in adults. Design: Searches across 5 databases were conducted through October 2016 including randomized controlled trials (RCTs) and prospective cohort studies examining 1 ) the effects of "high versus low" protein intake or 2 ) dietary protein's synergistic effect with Ca±D intake on bone health outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments. Strength of evidence was rated by group consensus. Random-effects meta-analyses for outcomes with ≥4 RCTs were performed. Results: Sixteen RCTs and 20 prospective cohort studies were included in the systematic review. Overall ROB was medium. Moderate evidence suggested that higher protein intake may have a protective effect on lumbar spine (LS) bone mineral density (BMD) compared with lower protein intake (net percentage change: 0.52%; 95% CI: 0.06%, 0.97%, I 2 : 0%; n = 5) but no effect on total hip (TH), femoral neck (FN), or total body BMD or bone biomarkers. Limited evidence did not support an effect of protein with Ca±D on LS BMD, TH BMD, or forearm fractures; there was insufficient evidence for FN BMD and overall fractures. Conclusions: Current evidence shows no adverse effects of higher protein intakes. Although there were positive trends on BMD at most bone sites, only the LS showed moderate evidence to support benefits of higher protein intake. Studies were heterogeneous, and confounding could not be excluded. High-quality, long-term studies are needed to clarify dietary protein's role in bone health. This trial was registered at www.crd.york.ac.uk as CRD42015017751., (© 2017 American Society for Nutrition.)

Long term use of bisphosphonates (BPs) in osteoporotic patients may be associated with stress fractures of the sub-trochanteric and shaft area of the femur, so called "atypical" femoral fractures (AFF). Specific diagnosis criteria have been defined with 5 major features; the presence of four of them characterizes the AFF. Once a complete fracture occurred, the best surgical treatment is closed reduction and intra medullary nailing. The BPs treatment should be stopped immediately after an AFF occurred. Dietary calcium and vitamin D status should be assessed, and adequate supplementation prescribed. Principle of combination of a systematic bone anabolic treatment is strongly debated. The recombinant parathyroid hormone 1-34 or Teriparatide ® (TPTD) has an anabolic effect on bone and prevent osteoporotic fractures. Available preclinical and clinical data have also demonstrated the role played by TPTD to enhance bone fracture healing and the potential beneficial effect in impaired fracture healing or specific clinical condition like AFFs. Some authors have proposed in incomplete BP use stress fractures different medical management according the MRI findings. Bone anabolic agents may be promising both to prevent healing complications in AFFs and to promote healing in conservative treatment of incomplete AFFs. More clinical studies are needed to confirm this hypothesis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Overweight is epidemic in adolescents and is a major concern because it tracks into adulthood. Evidence supports the efficacy of high-calcium, high-dairy diets in achieving healthy weight in adults. However, no randomized controlled trials of the effect of dairy food on weight and body fat in adolescents have been reported to our knowledge. Objective: The aim was to determine whether increasing calcium intake to recommended amounts with dairy foods in adolescent girls with habitually low calcium intakes would decrease body fat gain compared with girls who continued their low calcium intake. Participants had above-the-median body mass index (BMI; in kg/m 2 ). Design: We enrolled 274 healthy postmenarcheal 13- to 14-y-old overweight girls who had calcium intakes of ≤600 mg/d in a 12-mo randomized controlled trial. Girls were randomly assigned in a 1:1 ratio to 1 of 2 groups within each of 3 BMI percentiles: 50th to <70th, 70th to <85th, and 85th to <98th. The assignments were 1 ) dairy, which included low-fat milk or yogurt servings providing ≥1200 mg Ca/d or 2 ) control, which included the usual diet of ≤600 mg Ca/d. Results: We failed to detect a statistically significant difference between groups in percentage of body fat gain over 12 mo (mean ± SEM: dairy 0.40% ± 0.53% > control; P < 0.45). The effect of the intervention did not differ by BMI percentile stratum. There was no difference in weight change between the 2 groups. Conclusion: Our findings that the dairy group gained body fat similar to the control group provide no support for dairy food as a stratagem to decrease body fat or weight gain in overweight adolescent girls. This trial was registered at clinicaltrials.gov as NCT01066806., (© 2017 American Society for Nutrition.)

Context: We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity., Design and Setting: We performed a nested case-control study within the prospective Women's Health Initiative Observational Study. Incident nonspine fractures were identified in 381 black, 192 Hispanic, 112 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who experienced an incident fracture was chosen. One control was selected per case and matched on age, race/ethnicity, and blood draw date. Bioavailable estradiol (BioE2), bioavailable testosterone (BioT), and sex hormone-binding globulin (SHBG) were measured using baseline fasting serum. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence interval (CI) of fracture across tertiles of hormone., Results: In multivariable and race/ethnicity-adjusted models, higher BioE2 (>8.25 pg/mL) and higher BioT (>13.3 ng/dL) were associated with decreased risk of fracture (OR, 0.65; 95% CI, 0.50 to 0.85; P trend = 0.001 and OR, 0.76; 95% CI, 0.60 to 0.96; P trend = 0.02, respectively). The interaction term between race/ethnicity and either BioE2 or BioT was not significant. There was no association between SHBG and fracture risk. In models stratifying by race/ethnicity, higher BioE2 was associated with a lower risk of fracture in both white women (OR, 0.56; 95% CI, 0.36 to 0.87) and black women (OR, 0.61; 95% CI, 0.39 to 0.96). Higher BioT was associated with a significantly lower fracture risk in only black women (OR, 0.65; 95% CI, 0.43 to 1.00), P trend = 0.03., Conclusions: Serum BioE2 and BioT are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture., (Copyright © 2017 by the Endocrine Society)

Osteoporosis (low bone strength) and sarcopenia (low muscle mass, strength and/or impaired function) often co-exist (hence the term 'sarco-osteoporosis') and have similar health consequences with regard to disability, falls, frailty and fractures. Exercise and adequate nutrition, particularly with regard to vitamin D, calcium and protein, are key lifestyle approaches that can simultaneously optimize bone, muscle and functional outcomes in older people, if they are individually tailored and appropriately prescribed in terms of the type and dose. Not all forms of exercise are equally effective for optimizing musculoskeletal health. Regular walking alone has little or no effect on bone or muscle. Traditional progressive resistance training (PRT) is effective for improving muscle mass, size and strength, but it has mixed effects on muscle function and falls which may be due to the common prescription of slow and controlled movement patterns. At present, targeted multi-modal programs incorporating traditional and high-velocity PRT, weight-bearing impact exercises and challenging balance/mobility activities appear to be most effective for optimizing musculoskeletal health and function. Reducing and breaking up sitting time may also help attenuate muscle loss. There is also evidence to support an interaction between exercise and various nutritional factors, particularly protein and some multi-nutrient supplements, on muscle and bone health in the elderly. This review summary provides an overview of the latest evidence with regard to the optimal type and dose of exercise and the role of various nutritional factors for preventing bone and muscle loss and improving functional capacity in older people.

Background: Fracture is a complex trait, affected by both genetic and environmental factors. A meta-analysis of genome-wide association studies (GWASs) identified multiple bone mineral density (BMD) and fracture-associated loci. Objective: We conducted a study to evaluate whether fracture genetic risk score (Fx-GRS) and bone mineral density genetic risk score (BMD-GRS) modify the association between the intake of calcium with vitamin D (CaD) and fracture risk. Design: Data from 5823 white postmenopausal women from the Women's Health Initiative CaD randomized trial were included. Participants received 1000 mg elemental Ca with 400 IU vitamin D 3 /d or placebo (median follow-up: 6.5 y). Total fracture was defined as first fracture of any type. We computed the Fx-GRS with 16 fracture- and BMD-associated variants, and the BMD-GRS with 50 BMD-associated variants. We used Cox regression and a case-only approach to test for multiplicative interaction. Additive interaction was assessed with the relative excess risk due to interaction (RERI). We analyzed genetic risk score as a continuous variable and a categorical variable based on quartile (quartile 1, quartiles 2-3, and quartile 4). Results: We observed no interaction between the Fx-GRS and CaD on fracture risk; however, we observed a significant multiplicative interaction between the BMD-GRS and CaD assignment ( P -interaction = 0.01). In addition, there was a significant negative additive interaction between placebo assignment and higher BMD-GRS: quartiles 2-3, P RERI = 0.03; quartile 4, P RERI = 0.03. In a stratified analysis, the protective effect of CaD on fracture risk was observed in women in the lowest BMD-GRS quartile (HR: 0.60, 95% CI: 0.44, 0.81) but not in women with a higher BMD-GRS. Conclusions: We observed significant effects of CaD intake on fracture risk only in women with the lowest genetic predisposition to low BMD. Future large-scale studies with functional characterization of GWAS findings are warranted to assess the utility of genetic risk score in analysis of risks and benefits of CaD for bone., (© 2017 American Society for Nutrition.)

Purpose: DNA methylation is one of the most extensively studied mechanisms within epigenetics, and it is suggested that diet-induced changes in methylation status could be involved in energy metabolism regulation. Conjugated linoleic acid (CLA) and calcium supplementation counteract body weight gain, particularly under a high-fat (HF) diet, in adult mice. The aim was to determine whether the modulation of DNA methylation pattern in target genes and tissues could be an underlying mechanism of action., Methods: Mice (C57BL/6J) were divided into five groups according to diet and treatment: normal fat as the control group (12 % kJ content as fat), HF group (43 % kJ content as fat), HF + CLA (6 mg CLA/day), HF + calcium (12 g/kg of calcium) and HF with both compounds. Gene expression and methylation degree of CpG sites in promoter sequences of genes involved in fatty acid metabolism, including adiponectin (Adipoq), stearoyl-CoA desaturase (Scd1) and fatty acid synthase (Fasn), were determined by bisulphite sequencing in liver and epididymal white adipose tissue., Results: Results showed that the methylation profile of promoters was significantly altered by dietary supplementation in a gene- and tissue-specific manner, whereas only slight changes were observed in the HF group. Furthermore, changes in specific CpG sites were also associated with an overall healthier metabolic profile, in particular for calcium-receiving groups., Conclusions: Both CLA and calcium were able to modify the methylation pattern of genes involved in energy balance in adulthood, which opens a novel area for increasing efficiency in body weight management strategies.

Genistein has a preventive role against bone mass loss during menopause. However, experimental data in animal models of osteoporosis suggest an anti-osteoporotic potential for this isoflavone. We performed a post-hoc analysis of a previously published trial investigating the effects of genistein in postmenopausal women with low bone mineral density. The parent study was a randomized, double-blind, placebo-controlled trial involving postmenopausal women with a femoral neck (FN) density <0.795 g/cm². A cohort of the enrolled women was, in fact, identified at the baseline as osteoporotic ( n = 121) on the basis of their T-score and analyzed thereafter for the 24 months' treatment with either 1000 mg of calcium and 800 IU vitamin D3 (placebo; n = 59); or calcium, vitamin D3, and Genistein aglycone (54 mg/day; genistein; n = 62). According to the femoral neck T-scores, 31.3% of the genistein and 30.9% of the placebo recipients were osteoporotic at baseline. In the placebo and genistein groups, the 10-year hip fracture probability risk assessed by Fracture Risk Assessment tool (FRAX) was 4.1 ± 1.9 (SD) and 4.2 ± 2.1 (SD), respectively. Mean bone mineral density (BMD) at the femoral neck increased from 0.62 g/cm² at baseline to 0.68 g/cm² at 1 year and 0.70 g/cm² at 2 years in genistein recipients, and decreased from 0.61 g/cm² at baseline to 0.60 g/cm² at 1 year and 0.57 g/cm² at 2 years in placebo recipients. At the end of the study only 18 postmenopausal women had osteoporosis in the genistein group with a prevalence of 12%, whereas in the placebo group the number of postmenopausal women with osteoporosis was unchanged, after 24 months. This post-hoc analysis is a proof-of concept study suggesting that genistein may be useful not only in postmenopausal osteopenia but also in osteoporosis. However, this proof-of concept study needs to be confirmed by a large, well designed, and appropriately focused randomized clinical trial in a population at high risk of fractures.

APC/β-catenin pathway malfunction is a common and early event in colorectal carcinogenesis. To assess calcium and vitamin D effects on the APC/β-catenin pathway in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, nested within a larger randomized, double-blind, placebo-controlled, partial 2 × 2 factorial chemoprevention clinical trial of supplemental calcium (1200 mg daily) and vitamin D (1000 IU daily), alone and in combination versus placebo, we assessed APC, β-catenin, and E-cadherin expression in colon crypts in normal-appearing rectal mucosa biopsies from 104 participants at baseline and 1-yr follow up using standardized, automated immunohistochemistry and quantitative image analysis. For vitamin D versus no vitamin D, the ratio of APC expression to β-catenin expression in the upper 40% (differentiation zone) of crypts (APC/β-catenin score) increased by 28% (P = 0.02), for calcium versus no calcium it increased by 1% (P = 0.88), and for vitamin D + calcium versus calcium by 35% (P = 0.01). Total E-cadherin expression increased by 7% (P = 0.35) for vitamin D versus no vitamin D, 8% (P = 0.31) for calcium versus no calcium, and 12% (P = 0.21) for vitamin D + calcium versus calcium. These results support (i) that vitamin D, alone or in combination with calcium, may modify APC, β-catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms; (ii) vitamin D as a potential chemopreventive agent against colorectal neoplasms; and (iii) the potential of APC, β-catenin, and E-cadherin expression as treatable, pre-neoplastic risk biomarkers for colorectal neoplasms. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: To investigate whether osteoporosis or use of calcium supplementations predict all-cause mortality, or death from CVD, in a longitudinal cohort of patients with rheumatoid arthritis (RA)., Methods: Patients in the Oslo RA register (ORAR) were examined, and bone mineral density was measured in 1996. The cohort was linked to the Norwegian Cause of Death registry on December 31, 2010. Death from CVD was defined in 3 following different outcomes: (1) primary atherosclerotic death, (2) atherosclerotic death as one of the 5 listed causes of death, and (3) CVD according to World Health Organization (WHO) definition as primary cause of death. Baseline predictors of all-cause mortality and death from CVD were identified in separate Cox regression models, using backwards selection. Sensitivity analyses were performed including analyses of interactions and competing risk., Results: A total of 609 patients were examined in 1996/1997. By December 31, 2010, 162 patients (27%) had died, resulting in 7439 observed patient-years. Of the deceased, 40 (24.7%) had primary atherosclerotic death. In the final model of all-cause mortality increased baseline ESR [hazard ratio (HR) 1.02 per mm/h, 95% CI: 1.01-1.03], calcium supplementation (1.74, 1.07-2.84), and osteoporosis, defined as a T score ≤2.5 SD at any location, (1.58, 1.07-2.32) predicted higher mortality rates, in models adjusted for age, gender, and a propensity score. In the final model of primary atherosclerotic death, increased ESR (1.03 per mm/h, 1.01-1.05) and calcium supplementation (3.39, 1.41-8.08), predicted higher mortality., Conclusions: Increased baseline ESR and use of calcium supplementation were predictors of increased all-cause mortality and risk of death from CVD in this longitudinal study of patients with RA., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Hungry bone syndrome (HBS) is an important postoperative complication after parathyroidectomy for severe secondary hyperparathyroidism (SHPT). There is, however, little data in the literature on its detailed clinical course, and the associated risk factors remain controversial., Methods: We did a single-center retrospective study on 62 consecutive dialysis patients who underwent total parathyroidectomy for SHPT to examine the risk factors, clinical course and outcome. Data on demographic characteristics, perioperative laboratory parameters including serum calcium, phosphate, alkaline phosphatase (ALP) and parathyroid hormone (PTH), drug treatment for SHPT and operative details of parathyroidectomy were collected., Results: Seventeen (27.4%) patients developed severe postoperative hypocalcemia with HBS. The serum calcium dropped progressively while serum ALP rose after operation until 2 weeks later when serum calcium reached the trough and serum ALP peaked. Serum phosphate also fell but stabilized between 4 and 14 days. The total postoperative calcium and vitamin D supplementation was significantly larger, and hospital stay was significantly longer in the group with HBS as compared with those without HBS. Young age, high body weight, high preoperative ALP level, and low preoperative calcium level independently predicted the development of HBS while preoperative PTH and use of cinacalcet or paricalcitol did not., Conclusion: HBS was common after total parathyroidectomy in patients with SHPT, and it is important to closely monitor the postoperative serum calcium, phosphate and ALP levels in the following 2 weeks, especially for those at risk. The implications of our findings on perioperative management are discussed.

Purpose of Review: The clinical benefits of vitamin D therapy have received substantial attention over the past decade. Recently, several trials looked to clarify the optimal vitamin D dose or serum level needed to promote human health. The purpose of this review is to highlight selected studies published since January 2015., Recent Findings: Several recent trials challenge whether serum vitamin D levels at least 30 ng/ml promote human health. In postmenopausal women with 25-hydroxyvitamin D [25(OH)D] levels 21 ± 3 ng/ml, high-dose vitamin D for 1 year increased calcium absorption by 1%, without changes in bone mineral density, physical function, or falls when compared with low-dose vitamin D and placebo. High-dose vitamin D increased risk of falling in 200 adults 78 ± 5 years old with baseline 25(OH)D levels of ∼19 ± 9 ng/ml. High-dose vitamin D in adults increased the number and duration of upper respiratory tract infections compared with placebo. Asthma patients achieving 25(OH)D levels more than 30 ng/ml during a trial experienced more respiratory infections than those not achieving such levels., Summary: Recent studies are congruent with the Institute of Medicine's conclusion that humans are vitamin D replete when their serum 25(OH)D levels are at least 20 ng/ml. Higher levels seem to promote falls and respiratory infections.

Background: Muscular weakness and severe vitamin D deficiency is prevalent in Somali (veiled) pregnant women, Sweden. The study aims here were to explore adherence to prescribed supplemental vitamin D in new mothers with vitamin D deficiency and its effects on grip strength and upper leg performance in Somali (target group TG) and Swedish women (reference group RG) from spring through winter., Methods: A before- and after study was designed. A cross-sectional sample of women in antenatal care with serum 25-OHD ≤50 nmol/L were prescribed one or two tablets daily (800 or 1600 IU vitamin D3 with calcium) for 10 months. Reminders were made by Somali nurses (TG) or Swedish doctors (RG). Baseline and 10 month measurements of plasma nmol/L 25-OHD, maximal grip strength held for 10 s (Newton, N) and ability to squat (yes;no) were done. Total tablet intake (n) was calculated. Outcome variables were changes from baseline in grip strength and ability to squat. Predicting variables for change in grip strength and ability to squat were calculated using linear and binary regression in final models. Undetectable 25-OHD values (<10 nmol/L) were replaced with '9' in statistic calculations., Results: Seventy-one women (46 TG, 1/3 with undetectable baseline 25-OHD; 25 RG) participated. At the 10-month follow up, 17% TG and 8% RG women reported having refrained from supplement. Mean 25-OHD increased 16 to 49 nmol/L (TG) and 39 nmol/L to 67 nmol/L (RG), (both p < 0.001). Grip strength had improved from 153 to 188 N (TG) (p < 0.001) and from 257 to 297 N (RG) (p = 0.003) and inability to squat had decreased in TG (35 to 9, p < 0.001). Intake of number of tablets predicted increased grip strength (B 0.067, 95%CI 0.008-0.127, p = 0.027). One tablet daily (>300 in total) predicted improved ability to squat (OR 16; 95% CI 1.8-144.6)., Conclusions: Adherence to supplemental vitamin D and calcium should be encouraged as an even moderate intake was associated to improved grip strength and upper leg performance, which was particularly useful for the women with severe 25-OHD deficiency and poor physical performance at baseline., Trial Registration: ClinicalTrials.gov Identifier: NCT02922803 . Date of registration: September 28, 2016.

Context: There are no studies evaluating teriparatide for prevention of post-thyroidectomy hypocalcemia., Objective: Our objective was to evaluate whether teriparatide can prevent postsurgical hypocalcemia and shorten the hospitalization in subjects at high risk of hypocalcemia following thyroid surgery., Design: This was a prospective phase II randomized open-label trial., Setting: This trial was set on a surgical ward., Patients: Twenty-six subjects (six males, 20 females) with intact PTH lower than10 pg/ml 4 hours after thyroidectomy were included., Intervention: Subjects were randomized (1:1) to receive SC administration of 20 mcg of teriparatide every 12 hours until the discharge (treatment group) or to follow standard clinical care (control group)., Main Outcome Measure: Adjusted serum calcium, duration of hospitalization, and calcium/calcitriol supplementation were measured., Results: Overall, the incidence of hypocalcemia was 3/13 in treatment group and 11/13 in the control group (P = .006). Treated patients had a lower risk of hypocalcemia than controls (relative risk, 0.26 [95% confidence interval, 0.09-0.723)]). The median duration of hospitalization was 3 days (interquartile range, 1) in control subjects and 2 days (interquartile range, 0) in treated subjects (P = .012). One month after discharge, 10/13 subjects in the treatment group had stopped calcium carbonate supplements, while only 5/13 in the control group had discontinued calcium. The ANOVA for repeated measures showed a significant difference in calcium supplements between groups at 1-month visit (P = .04) as well as a significant difference between discharge and 1-month visit in the treatment group (P for interaction time group = .04) Conclusions: Teriparatide may prevent postsurgical hypocalcemia, shorten the duration of hospitalization, and reduce the need for calcium and vitamin D supplementation after discharge in high risk subjects after thyroid surgery.

Nutritional rickets continues to be a significant health problem for children worldwide with recent evidence of increasing incidence in many developed countries. It is due to vitamin D deficiency and/or inadequate dietary calcium intake with variation in the relative contributions of each of these dependant on environmental factors such a dietary intake and sunlight exposure. Key to the prevention of rickets is ensuring that pregnant women and their infants receive vitamin D supplementation with good evidence from randomised controlled trials that infants who receive 400iu daily can achieve levels of 25 hydroxyvitamin D of >50nmol/l. However, public health implementation of daily supplementation is more challenging with a need to revisit food fortification strategies to ensure optimal vitamin D status of the population. Treatment of nutritional rickets has traditionally been with vitamin D2 or D3, often given as a daily oral dose for several weeks until biochemical and radiological evidence of healing. However, other treatment regimes with single or intermittent high doses have also proved to be effective. It is now recognised that oral calcium either as dietary intake or supplements should be routinely used in conjunction with vitamin D for treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Vitamin D deficiency is highly prevalent during pregnancy. It has been suggested that vitamin D supplementation during pregnancy may reduce the risk of adverse gestational outcomes., Objectives: To update a previous meta-analysis on the effects of oral vitamin D supplementation (alone or in combination with other vitamins and minerals) during pregnancy on maternal 25(OH)D levels and risk of developing pre-eclampsia, gestational diabetes, preterm birth, impaired glucose tolerance, caesarean section, gestational hypertension and other adverse conditions., Methods: We searched for randomized and quasi-randomized trials through the Cochrane Pregnancy and Childbirth Group's Trials Register, the International Clinical Trials Registry Platform, the Networked Digital Library of Theses and Dissertations, and direct communications with relevant organizations. Assessments of inclusion criteria, extraction of data from included studies, and risk of bias' assessments of the included studies were done independently by two review authors., Results: We included 15 trials, excluded 27 trials and 23 trials are still ongoing/unpublished. Data from seven trials with 868 women suggest that pregnant women supplemented with vitamin D had significantly higher 25(OH)D levels compared to controls (mean difference: 54.7nmol/L; 95% CI 36.6, 72.9). Two trials found a lower risk of preeclampsia (8.9% versus 15.5%; average risk ratio 0.52; 95% CI 0.25, 1.05) and two other trials found no difference in the risk of gestational diabetes with vitamin D supplementation. Also, three trials found that supplementation with vitamin D plus calcium reduced the risk of pre-eclampsia (5% versus 9%; average risk ratio 0.51; 95% CI 0.32, 0.80)., Conclusion: Supplementing pregnant women with vitamin D led to significantly higher levels of 25(OH)D at term compared to placebo/control but results were inconsistent. Vitamin D supplementation, with or without calcium, may be related to lower risk of preeclampsia but more studies are needed to confirm this., (Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.)

Recent studies suggest that supplemental Ca (SC) increases the risk of cardiovascular events, whereas dietary Ca (DC) decreases the risk of cardiovascular events. Although frequently consumed with meals, it remains unclear whether Ca can mitigate or aggravate the deleterious effects of a high-fat meal on cardiovascular risk factors. This study aimed to evaluate the effects of SC or DC on blood pressure (BP) and microvascular function (MVF) in the postprandial period in obese women challenged with a high-fat meal. In this cross-over controlled trial, sixteen obese women aged 20-50 years were randomly assigned to receive three test meals (2908 kJ (695 kcal); 48 % fat): high DC (HDCM; 547 mg DC), high SC (HSCM; 500 mg SC-calcium carbonate) and low Ca (LCM; 42 mg DC). BP was continuously evaluated from 15 min before to 120 min after meals by digital photoplethysmography. Before and 120 min after meals, participants underwent evaluation of serum Ca and microvascular flow after postocclusive reactive hyperaemia (PORH) by laser speckle contrast imaging. Ionised serum Ca rose significantly only after HSCM. Systolic BP increased after the three meals, whereas diastolic BP increased after LCM and HDCM. Hyperaemia peak, hyperaemia amplitude and AUC evaluated after PORH decreased with LCM. After HDCM, there was a reduction in hyperaemia peak and hyperaemia amplitude, whereas HSCM decreased only hyperaemia peak. However, comparative analyses of the effects of three test meals on serum Ca, BP and MVF revealed no significant meal×time interaction. This study suggests that in obese women SC and DC do not interfere with the effects of a high-fat meal on BP and MVF.

Background: Recent randomized data suggest that calcium supplements may be associated with increased risk of cardiovascular disease (CVD) events. Using a longitudinal cohort study, we assessed the association between calcium intake, from both foods and supplements, and atherosclerosis, as measured by coronary artery calcification (CAC)., Methods and Results: We studied 5448 adults free of clinically diagnosed CVD (52% female; aged 45-84 years) from the Multi-Ethnic Study of Atherosclerosis. Baseline total calcium intake was assessed from diet (using a food frequency questionnaire) and calcium supplements (by a medication inventory) and categorized into quintiles. Baseline CAC was measured by computed tomography, and CAC measurements were repeated in 2742 participants ≈10 years later. At baseline, mean calcium intakes across quintiles were 313.3, 540.3, 783.0, 1168.9, and 2157.4 mg/day. Women had higher calcium intakes than men. After adjustment for potential confounders, among 1567 participants without baseline CAC, the relative risk (RR) of developing incident CAC over 10 years, by quintile 1 to 5 of calcium intake, were 1 (reference), 0.95 (0.79-1.14), 1.02 (0.85-1.23), 0.86 (0.69-1.05), and 0.73 (0.57-0.93). After accounting for total calcium intake, calcium supplement use was associated with increased risk for incident CAC (RR=1.22 [1.07-1.39]). No relation was found between baseline calcium intake and 10-year changes in log-transformed CAC among those participants with baseline CAC >0., Conclusions: High total calcium intake was associated with a decreased risk of incident atherosclerosis over long-term follow-up, particularly if achieved without supplement use. However, calcium supplement use may increase the risk for incident CAC., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)