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In December 2019, Corona Virus Disease 2019 (COVID-19) was first identified and designated as a pandemic in March 2020 due to rapid spread of the virus globally. At the beginning of the pandemic, only a few treatment options, mainly focused on supportive care and repurposing medications, were available. Due to its effects on immune system, vitamin D was a topic of interest during the pandemic, and researchers investigated its potential impact on COVID-19 outcomes. However, the results of studies about the impact of vitamin D on the disease are inconclusive. In the present narrative review, different roles of vitamin D regarding the COVID-19 have been discussed to show that vitamin D supplementation should be recommended carefully., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Pre-eclampsia and eclampsia are common causes of morbidity and mortality, especially in low-income countries. Reducing adverse outcomes associated with hypertensive disorders of pregnancy has been the ultimate priority in recent years. We aim to evaluate the association between calcium supplementation and preeclampsia and gestational hypertension risk among pregnant women., Methods: A systematic literature search was performed in electronic databases from inception to 15th July 2023, including only randomized controlled trials. Odds ratio (OR) were, and their corresponding 95% confidence interval (95% CI)., Results: A total of 26 studies with 20,038 patients (10,003 patients with calcium supplements and 10,035 patients with placebo group) were included in the analysis. The Pooled analysis of primary outcome shows that calcium supplements reduce the risk of preeclampsia by 49% (OR, 0.51(95%CI: 0.40-0.66), P<0.001), and reduce the risk of gestational hypertension by 30% (OR, 0.70 (95%CI: 0.58-0.85)), P<0.001) compared to placebo. There was a trend of lower incidence of preterm delivery (OR, 0.88 (95%CI: 0.71-1.09), P=0.23), labor induction (OR, 0.90 (95%CI: 0.78-1.03), P=0.13), small for gestational age (OR, 0.70 (95% CI:0.37-1.32), P = 0.27), low birth weight (OR, 0.96 (95%CI: 0.86-1.08), P=0.53), perinatal mortality (OR, 0.88 (95%CI: 0.72-1.09), P=0.24), and maternal mortality (OR, 0.48 (95%CI: 0.12-1.84), P=0.28) among calcium supplementation group compared with the placebo group, however, statistical signifance was not achieved., Conclusion: This study shows that calcium supplements are associated with a significant reduction in the risk of preeclampsia and gestational hypertension and a trend toward better maternal and fetal-related outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Neuroinflammation plays a key role in early brain injury (EBI) of subarachnoid hemorrhage (SAH), and NLRP3 inflammasome plays an important role in the development of neuroinflammation after SAH, but the mechanism of NLRP3 inflammasome activation after SAH is still unclear. TRPV1 is a non-selective calcium channel that is involved in the pathology of neuroinflammation, but its role in SAH has not been revealed. Our study showed that TRPV1 was significantly upregulated after SAH and was predominantly expressed in microglia/macrophages. Antagonism of TRPV1 was effective in ameliorating neurological impairment, brain edema, neuronal damage, and reducing the inflammatory response (evidenced by reducing the number of CD16/32 positive microglia/macrophages, inhibiting the expression of CD16, CD32, CD86, IL-1b, TNF-a and blocking NLRP3 inflammasome activation). However, this effect can be abolished by NLRP3 inflammasome antagonist MCC950. In vitro experiment confirmed that TRPV1 activated NLRP3 inflammasome by increasing intracellular calcium levels. In conclusion, TRPV1 mediates EBI after SAH via calcium/NLRP3, and TRPV1 is a potential therapeutic target after SAH.

Objective: A significant problem that compels clinicians in the conventional treatment of hypoparathyroidism is patients' non-adherence to treatment. This study aimed to evaluate the effects of adequate Ca intake with dietary recommendations among hypoparathyroidism patients who persistently use Ca supplementation irregularly on plasma Ca and phosphate levels., Methods: This prospective, randomized, controlled study was conducted on patients diagnosed with chronic hypoparathyroidism who persistently interrupt Ca supplementation therapy and therefore have a hypocalcemic course. Patients with a total daily Ca intake below 800 mg were randomized. All patients were advised to keep the doses of active vitamin D and Ca supplements they were currently using. The patients in the study group (n=32) were advised to consume 1,000-1,200 mg of Ca daily, and the patients in the control group (n=35) were advised to continue their diet according to their daily habits. After 12 weeks of follow-up, the patients' laboratory values were compared between groups to assess treatment goals., Results: The mean of the total Ca level was 8.56±0.36 mg/dL in the study group and was found to be significantly higher than that in the control group, which was 7.67±0.48 mg/dL (p<0.001). The mean serum phosphate and serum Ca-P product levels were significantly higher in the study group (p<0.001) but did not exceed the safe upper limits in any patient., Conclusion: A suitable increase in dietary Ca intake could effectively control hypocalcemia in patients with hypoparathyroidism who persistently interrupt the recommended calcium supplementation.

This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K 1 supplementation led to a modest effect on parameters of hip geometry., Purpose: Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment., Methods: We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K 1  ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K 1 (1 mg/day) arm, vitamin K 2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K 1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed., Results: Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K 1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K 1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K 1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K 1 arm: -1.02[5.07], p = 0.03)., Conclusion: The addition of vitamin K 1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed., Trial Registration: The study was registered at Clinicaltrial.gov:NCT01232647., (© 2023. The Author(s).)

Background: Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and reduced quality of life. Osteoporosis is considered a major public health concern worldwide. For this reason, preventive measurements need to be addressed throughout the life course. Exercise and a healthy diet are among the lifestyle factors that can help prevent the disease, the latter including intake of key micronutrients for bone, such as calcium and vitamin D. The evidence on whether supplementation with calcium and vitamin D improves bone mineral density (BMD) in premenopausal women is still inconclusive. In this age group, bone accrual is considered to be the goal of supplementation, so BMD is relevant for the future stages of life., Objectives: To evaluate the benefits and harms of calcium and vitamin D supplementation, alone or in combination, to increase the BMD, reduce fractures, and report the potential adverse events in healthy premenopausal women compared to placebo., Search Methods: We used standard, extensive Cochrane search methods. The latest search was 12 April 2022., Selection Criteria: We included randomised controlled trials in healthy premenopausal women (with or without calcium or vitamin D deficiency) comparing supplementation of calcium or vitamin D (or both) at any dose and by any route of administration versus placebo for at least three months. Vitamin D could have been administered as cholecalciferol (vitamin D 3 ) or ergocalciferol (vitamin D 2 )., Data Collection and Analysis: We used standard Cochrane methods. Outcomes included total hip bone mineral density (BMD), lumbar spine BMD, quality of life, new symptomatic vertebral fractures, new symptomatic non-vertebral fractures, withdrawals due to adverse events, serious adverse events, all reported adverse events and additional withdrawals for any reason., Main Results: We included seven RCTs with 941 participants, of whom 138 were randomised to calcium supplementation, 110 to vitamin D supplementation, 271 to vitamin D plus calcium supplementation, and 422 to placebo. Mean age ranged from 18.1 to 42.1 years. Studies reported results for total hip or lumbar spine BMD (or both) and withdrawals for various reasons, but none reported fractures or withdrawals for adverse events or serious adverse events. Results for the reported outcomes are presented for the three comparisons: calcium versus placebo, vitamin D versus placebo, and calcium plus vitamin D versus placebo. In all comparisons, there was no clinical difference in outcomes, and the certainty of the evidence was moderate to low. Most studies were at risk of selection, performance, detection, and reporting biases. Calcium versus placebo Four studies compared calcium versus placebo (138 participants in the calcium group and 123 in the placebo group) with mean ages from 18.0 to 47.3 years. Calcium supplementation may have little to no effect on total hip or lumbar spine BMD after 12 months in three studies and after six months in one study (total hip BMD: mean difference (MD) -0.04 g/cm 2 , 95% confidence interval (CI) -0.11 to 0.03; I 2 = 71%; 3 studies, 174 participants; low-certainty evidence; lumbar spine BMD: MD 0 g/cm 2 , 95% CI -0.06 to 0.06; I 2 = 71%; 4 studies, 202 participants; low-certainty evidence). Calcium alone supplementation does not reduce or increase the withdrawals in the trials (risk ratio (RR) 0.78, 95% CI 0.52 to 1.16; I 2 = 0%; 4 studies, 261 participants: moderate-certainty evidence). Vitamin D versus placebo Two studies compared vitamin D versus placebo (110 participants in the vitamin D group and 79 in the placebo group), with mean ages from 18.0 to 32.7 years. These studies reported lumbar spine BMD as a mixture of MDs and percent of change and we were unable to pool the results. In the original studies, there were no differences in lumbar BMD between groups. Vitamin D alone supplementation does not reduce or increase withdrawals for any reason between groups (RR 0.74, 95% CI 0.46 to 1.19; moderate-certainty evidence). Calcium plus vitamin D versus placebo Two studies compared calcium plus vitamin D versus placebo (271 participants in the calcium plus vitamin D group and 270 in the placebo group; 220 participants from Woo 2007 and 50 participants from Islam 2010). The mean age range was 18.0 to 36 years. These studies measured different anatomic areas, one study reported total hip BMD and the other study reported lumbar spine BMD; therefore, data were not pooled for this outcome. The individual studies found no difference between groups in percent of change on total hip BMD (-0.03, 95% CI -0.06 to 0; moderate-certainty evidence), and lumbar spine BMD (MD 0.01, 95% CI -0.01 to 0.03; moderate-certainty evidence). Calcium plus vitamin D supplementation may not reduce or increase withdrawals for any reason (RR 0.82, 95% CI 0.29 to 2.35; I 2 = 72%; 2 studies, 541 participants; low-certainty evidence)., Authors' Conclusions: Our results do not support the isolated or combined use of calcium and vitamin D supplementation in healthy premenopausal women as a public health intervention to improve BMD in the total hip or lumbar spine, and therefore it is unlikely to have a benefit for the prevention of fractures (vertebral and non-vertebral). The evidence found suggests that there is no need for future studies in the general population of premenopausal women; however, studies focused on populations with a predisposition to diseases related to bone metabolism, or with low bone mass or osteoporosis diagnosed BMD would be useful., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: Symptomatic hypocalcemia has a variety of underlying etiologies,with hypoparathyroidism and vitamin D deficiency being the most common. However,rarer etiologies such as pseudohypoparathyroidism, as is present in the current case, should not be overlooked. Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders characterized by parathyroid hormone (PTH) resistance. The diagnosis of this rare genetic condition is often delayed,due to its myriad presentations,leading to an initially inappropriate approach and therapy., Materials: A 19-year-old male,K/C/O seizure disorder since 18 years,presented to ER in generalized convulsive status epilepticus since 2 hours.Developmentally he had poor growth spurt. No h/o trauma, fever, vomiting, headache. Patient continued to have seizures occasionally despite being compliant to Tab Sodium Valproate 250mg BD.O/E: Patient was drowsy but arousable. He had short stature.Height-35 kg, Weight-136 cm and BMI 18.92 kg/m2.Bilateral cataractous lens+. Examination of limbs revealed brachydactyly of the fingers and fourth toes. Chvostek and Trousseau signs were positive. Knuckle knuckle Dimple Dimple Sign+ Result: ECG showed showed prolonged QT interval. Blood investigations showed Serum calcium-5.8, Serum phosphorus-8.7, iPTH-193, TSH-15.4. MRI brain revealed diffuse bilateral calcifications of basal ganglia. Given the clinical,radiographic and laboratory findings, diagnoses of PHP type Ia with primary hypothyroidism was made.Patient was admitted to wards,hypocalcemia corrected with intravenous and oral calcium and vitamin D.Discharged on 50 ug levothyroxine, oral calcium, vitamin D3 oral solution weekly. The patient is being followed up at half monthly intervals and has remained seizure free since discharge., Conclusion: PHP type Ia (GNAS gene mutation) is the most common form of PHP and associated with Albright's hereditary osteodystrophy (AHO), resistance to multiple hormones. This case stresses the pivotal role of a complete biochemical investigation of the calcium phosphate metabolism in every References Melmed S, Koenig R, Rosen C, Auchus R, Goldfine A. Williams textbook of endocrinology: South Asia edition, 2 vol set-E-book. Elsevier India; 2020 Jun 30. Mantovani G, Bastepe M, Monk D, De Sanctis L, Thiele S, Ahmed SF, Bufo R, Choplin T, De Filippo G, Devernois G, Eggermann T. Recommendations for diagnosis and treatment of pseudohypoparathyroidism and related disorders: an updated practical tool for physicians and patients. Hormone research in paediatrics. 2020;93(3):182-96., (© Journal of the Association of Physicians of India 2011.)

Objective: Secondary hyperparathyroidism commonly occurs in the setting of mid-to low-normal serum calcium levels, often in the setting of chronic kidney disease, phosphate loading, vitamin D deficiency, or insufficient calcium intake or absorption. In this article, we report 9 patients who had adequate kidney function (estimated glomerular filtration rate >60 mL/min/1.73 m 2 ) and normal 25-hydroxy vitamin D level (≥30 ng/dL) and whose secondary hyperparathyroidism resolved after starting adequate oral calcium intake., Methods: Our retrospective case series included 8 women and 1 man; the mean age was 69.0 ± 12.2 years (mean ± standard deviation). The initial intact parathyroid hormone (iPTH) level was 80.6 ± 13.4 pg/mL (reference range [ref], 10-65 pg/mL), corrected serum calcium level was 9.2 ± 0.2 mg/dL (ref, 8.5-10.5 mg/dL), serum phosphate level was 3.6 ± 0.4 mg/dL (ref, 2.5-4.9 mg/dL), 25-hydroxy vitamin D level was 42.2 ± 10.5 mg/dL (ref, 20-50 ng/mL), and estimated glomerular filtration rate was 72.6 ± 14.4 mL/min/1.73 m 2 . Patients were treated clinically with oral calcium 600 mg twice a day., Results: iPTH was retested after a mean duration of 17.6 ± 12.7 days of calcium supplementation; the iPTH level decreased to 51.0 ± 10.6 pg/mL, with all patients achieving iPTH in the normal range with normocalcemia, consistent with hyperparathyroidism being because of insufficient calcium intake or absorption. All patients were normocalcemic after supplementation., Conclusion: Secondary hyperparathyroidism can result from insufficient oral calcium intake. Calcium challenge is an efficacious and cost-effective tool for confirming and treating secondary hyperparathyroidism in the setting of normal vitamin D levels and kidney function., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

The purpose was to assess the effects of three interventions on bone mineral density (BMD) to prevent the onset or progression of osteoporosis in postmenopausal women. Specifically, thirty-nine postmenopausal women, diagnosed with osteopenia or osteoporosis, implemented either high-impact training (G1), the same training + calcium and vitamin D intake (G2), or walked at an intense pace + calcium and vitamin D (G3). Baseline change (BC) in BMD was estimated using the femoral neck and lumbar spine T-scores. Participants were classified as having suffered fractures and/or falls before (24-month) and during the 2-year intervention. The participants-aged 61.8 years-were allocated into G1 ( n = 9), G2 ( n = 16), and G3 ( n = 14). The groups evolved similarly over time; however, participants in G2 exhibited the largest T-score improvements with BC over 20%. G1 and G3 maintained BMD levels (BC = -7 to 13.3%; p > 0.05). Falls occurred similarly across the interventions, while the participants in G2 had the lowest percentage of fracture events ( p = 0.037). Overall, the findings suggest that regular physical exercise may be effective in maintaining or improving BMD in postmenopausal women presenting with osteopenia or osteoporosis. Due to the limited sample size, the results are preliminary and warrant future randomized trials to validate the findings.

Purpose of Review: Low-level evidence and opinion-based clinical practice guidelines highlight the substantial uncertainty in the practice patterns of hyperphosphatemia management in patients with chronic kidney disease (CKD). This manuscript reviews the evidence for the choice of phosphate binders and its impact on clinical outcomes., Recent Findings: Phosphate binders are among the most common medications prescribed for patients on dialysis. Clinical practice guidelines recommend lowering phosphate levels toward normal range and restricting calcium-based binders in all CKD patients. There is substantial gap in the evidence underlying these recommendations with lack of any placebo-controlled, randomized trials showing survival benefits for any class of phosphate-binders. Despite the lack of evidence for specific phosphate target or if lowering phosphate improves survival, use of phosphate binders has remained central strategy in approach to hyperphosphatemia. Use of binders has added to the cost and contributed significant pill burden. Restriction of calcium-based binders to avoid positive calcium balance and consequent vascular calcification risk has a physiological rationale and weight of observational studies., Summary: There is currently no conclusive evidence that definitively guides the choice of any specific binders for management of hyperphosphatemia in patients with CKD. Use of noncalcium-based binders has a theoretical advantage in restricting total calcium intake to decrease the risk of vascular calcification but no proven benefits for mortality., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Most low- and middle-income countries present suboptimal intakes of calcium during pregnancy and high rates of mortality due to maternal hypertensive disorders. Calcium supplementation during pregnancy is known to reduce the risk of these disorders and associated complications, including preeclampsia, maternal morbidity, and preterm birth, and is, therefore, a recommended intervention for pregnant women in populations with low dietary calcium intake (e.g., where ≥25% of individuals in the population have intakes less than 800 mg calcium/day). However, this intervention is not widely implemented in part due to cost and logistical issues related to the large dose and burdensome dosing schedule (three to four 500-mg doses/day). WHO recommends 1.5-2 g/day but limited evidence suggests that less than 1 g/day may be sufficient and ongoing trials with low-dose calcium supplementation (500 mg/day) may point a path toward simplifying supplementation regimens. Calcium carbonate is likely to be the most cost-effective choice, and it is not necessary to counsel women to take calcium supplements separately from iron-containing supplements. In populations at highest risk for preeclampsia, a combination of calcium supplementation and food-based approaches, such as food fortification with calcium, may be required to improve calcium intakes before pregnancy and in early gestation., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Objective: To assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day., Design: Two year cluster randomised controlled trial., Setting: 60 accredited residential aged care facilities in Australia housing predominantly ambulant residents., Participants: 7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years)., Intervention: Facilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight)., Main Outcome Measures: Group differences in incidence of fractures, falls, and all cause mortality., Results: Data from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121 v 203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42 v 93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879 v 2423; 0.89, 0.78 to 0.98; P=0.04). The risk reduction for hip fractures and falls achieved significance at five months (P=0.02) and three months (P=0.004), respectively. Mortality was unchanged (900 v 1074; hazard ratio 1.01, 0.43 to 3.08)., Conclusions: Improving calcium and protein intakes by using dairy foods is a readily accessible intervention that reduces the risk of falls and fractures commonly occurring in aged care residents., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12613000228785., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: funding support from the organisations listed above; SI has received lecture fees from Abbott; TVN has received research support and lecture fees from Amgen, MSD, and Novartis; ES has received research support from Amgen and MSD and lecture fees from Amgen, Eli Lilly, and Allergan; ES is a scientific consultant for StraxCorp and shareholder; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The role of dietary calcium in cardiovascular disease prevention is unclear. We aimed to determine the association between calcium intake and incident cardiovascular disease and mortality. Data were extracted from the European Prospective Investigation of Cancer, Norfolk (EPIC-Norfolk). Multivariable Cox regressions analysed associations between calcium intake (dietary and supplemental) and cardiovascular disease (myocardial infarction, stroke, heart failure, aortic stenosis, peripheral vascular disease) and mortality (cardiovascular and all-cause). The results of this study were pooled with those from published prospective cohort studies in a meta-analsyis, stratifying by average calcium intake using a 700 mg/day threshold. A total of 17,968 participants aged 40-79 years were followed up for a median of 20.36 years (20.32-20.38). Compared to the first quintile of calcium intake (< 770 mg/day), intakes between 771 and 926 mg/day (second quintile) and 1074-1254 mg/day (fourth quintile) were associated with reduced all-cause mortality (HR 0.91 (0.83-0.99) and 0.85 (0.77-0.93), respectively) and cardiovascular mortality [HR 0.95 (0.87-1.04) and 0.93 (0.83-1.04)]. Compared to the first quintile of calcium intake, second, third, fourth, but not fifth quintiles were associated with fewer incident strokes: respective HR 0.84 (0.72-0.97), 0.83 (0.71-0.97), 0.78 (0.66-0.92) and 0.95 (0.78-1.15). The meta-analysis results suggest that high levels of calcium intake were associated with decreased all-cause mortality, but not cardiovascular mortality, regardless of average calcium intake. Calcium supplementation was associated with cardiovascular and all-cause mortality amongst women, but not men. Moderate dietary calcium intake may protect against cardiovascular and all-cause mortality and incident stroke. Calcium supplementation may reduce mortality in women., (© 2020. The Author(s).)

Introduction: In our clinical experience, need for doses of active vitamin D and calcium supplements changes during the period following a diagnosis of postsurgical hypoparathyroidism (HypoPT), but only sparse data are available. In the present study, we aimed to investigate the magnitude of changes in need for activated vitamin D (alfacalcidol) and calcium supplements during initiation of therapy as well as time to be expected until a stable phase was achieved. Furthermore, we determined the frequency of (unexpected) episodes of hypo- and hypercalcaemia after reaching a steady state for alfacalcidol and calcium., Methods: Retrospective study of twenty-four patients with chronic postsurgical HypoPT (>6 months) diagnosed from 2016 to 2018. Data were extracted from medical records on doses of alfacalcidol and calcium as well as ionized plasma calcium levels (P-Ca 2+ ) from time of diagnosis and until 86 weeks after surgery., Results: Patients were treated with alfacalcidol and calcium in order to maintain a stable concentration of P-Ca 2+ . Our data demonstrated a great variation in treatment needs until 11 weeks after surgery, where the mean doses of alfacalcidol stabilize, while calcium doses stabilized a bit earlier. After the stable phase had emerged, 21 out of 24 patients continued to have one or more episodes of spontaneous hypo- or hypercalcaemia., Conclusions: Patients with chronic HypoPT attain a steady state for alfacalcidol 11 weeks after the diagnosis. Continuous monitoring of P-Ca 2+ is of continued importance after reaching steady state due to a high frequency of spontaneous hypo- or hypercalcaemia., Competing Interests: The authors declare that they have no conflicts of interest., (© 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Cadmium (Cd) is a toxic non-essential element, while calcium (Ca) is an essential element with high chemical similarity to Cd. Dietary intake is the major Cd exposure pathway for non-smokers. A multi-concentration dietary intervention experiment was designed to explore the optimum concentration of Ca in diet with obvious protective effects against the toxicity of livers and kidneys induced by Cd in mice. The mice were divided into six groups with different concentrations of Cd and Ca in their food: control-group (no Cd or Ca), Ca-group (100 g/kg Ca, without Cd), Cd-group (2 mg/kg Cd, without Ca), CaL+Cd-group (2 mg/kg Cd, 2 g/kg Ca), CaM+Cd-group (2 mg/kg Cd, 20 g/kg Ca) and CaH+Cd-group (2 mg/kg Cd, 100 g/kg Ca). The organ indexes, oxidative stress biomarkers, lesions and Cd concentrations were detected after a 30-day exposure period. Results showed that serum Aspartate Aminotransferase (AST) level in CaH+Cd-group was significantly lower than that in Cd-group, while close to that in control-group. The contents of Serum Blood Urea Nitrogen (BUN) in different groups showed the same trend. Concentrations of all oxidative stress biomarkers (GSH-Px, SOD, CAT, GSH and MDA) in CaH+Cd-group were close to the normal levels of control-group while significantly different from those in Cd-group. The only exception was the Malondialdehyde (MDA) levels in kidneys. This study suggests that Ca plays a protective role in relieving the Cd-induced toxicity of livers and kidneys and a concentration of 100 g/kg for Ca in diet showed the best protective effects. These findings could provide a clue for further studies concerning human diet intervention for Cd control., Competing Interests: The authors have declared that no competing interests exist.

Objective: To prevent osteoporotic fractures in nursing home residents a combination of bisphosphonates, calcium and vitamin D is recommended. This study assessed the prevalence of pharmacological osteoporosis prevention in nursing home residents from eight countries, and assessed its association with patient characteristics., Design: Cross-sectional analyses of the SHELTER study data. We assessed the overall prevalence of osteoporosis medication (OM) use (vitamin D, calcium and bisphosphonates) in residents stratified for falls and fractures over last 30 days, health instability with high mortality risk, cognitive impairment, and dependence in walking., Setting and Participants: Nursing home residents in the Czech Republic, England, Finland, France, Germany, Italy, The Netherlands and Israel., Results: Of 3832 eligible residents, vitamin D, calcium and bisphosphonates were used by 16.2%, 10.4%, and 4.5% respectively. All 3 classes of OM together were used by 1.5% of all residents. Of residents with a recent fracture, 9.5% used a bisphosphonate (2.7% all 3 OMs). In patients with recent falls, 20.8% used vitamin D and 15.3% calcium. In residents with severe cognitive impairment, 15.5% used vitamin D and 9.3% used calcium. Of the bisphosphonate users, 33.7% also used both vitamin D and calcium, 25.8% used only calcium in addition and 17.4% only vitamin D in addition. The use of any OM varied widely across countries, from 66.8% in Finland to 3.0% in Israel., Conclusions and Implications: We found substantial pharmacological under-treatment of prevention of osteoporosis in residents with recent falls, fractures and dependence in walking. Only two-thirds of bisphosphonate users also took a vitamin D-calcium combination, despite guideline recommendations. On the other hand, possible over-treatment was found in residents with high mortality risk in whom preventive pharmacotherapy might not have still been appropriate. The prevalence of pharmacological prevention of osteoporosis differed substantially between countries. Efforts are needed to improve pharmacotherapy in residents., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Poverty may be a barrier to acquiring adequate nutrient levels for the prevention of osteoporosis. Age and nutritional intake are major factors that contribute to osteoporosis prevalence. This study examined the relationship between markers of poverty with calcium / vitamin D intake and osteoporosis. A cross-sectional analysis of the United States population was performed using National Health and Nutrition Examination Survey (NHANES) data from 2007-2010 and 2013-2014 for older US adults (n = 3,901 participants, 50 years old and older). Odds of inadequate calcium / vitamin D intake and dietary supplement use and risk of probable osteoporosis were calculated in order to determine the relative difference and possible associations between household income, the Family Monthly Poverty Level Index, food security, and participation in the Supplemental Nutrition Assistance Program (SNAP). A sub-analysis of ethnic disparities and biological sex was also performed. In general, women age 50 and older consistently have inadequate calcium intake, regardless of economic level including poverty. While inadequate calcium intake has a larger prevalence among women, markers of poverty increased the risk of inadequate calcium intake in all men and risk of osteoporosis among some subgroups, with the exception of SNAP program participation. Over one fourth of Non-Hispanic black men in the US are below the poverty line. Approximately half of this population has inadequate calcium (58.9%) and vitamin D (46.7%) intake. Typically, osteoporosis risk is relatively low for Non-Hispanic Black males, however considering poverty status, risk is significantly increased (Relative Risk Ratio [RR]: 2.057 ± 0.012) for those with low income suggesting that calcium and vitamin D supplementation may be of benefit for this population., Competing Interests: KM, LL and SHM are currently salaried employees of Pharmavite LLC. CS is currently a salaried employee of Frost & Sullivan. LT has received compensation as a research consultant from DSM Nutritional Products and the National Cattlemen's Beef Association. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Gestational hypercalcemia is associated with an increased risk of maternal, fetal and neonatal morbidity and mortality. Hypercalcemia may develop during pregnancy in individuals who were previously asymptomatic. The increased sensitivity during pregnancy may be related to physiological, gestational alterations in vitamin D and calcium metabolism and may be influenced by gene variants. The prevalence is unknown. We investigated the prevalence of hypercalcemia in trimester 3 (T3) in a population representative prospective cohort study (n = 1832) in South-West Sweden. Women with serum albumin (Alb) adjusted calcium (Ca Alb ) ≥ 2.65 mmol/L in T3 (n = 30) were matched to normo-calcemic controls, and markers of calcium and vitamin D metabolism were investigated in trimester 1 (T1) and T3. Serum concentrations of Ca, phosphate (P), Magnesium (Mg), Alb and creatinine (Cr), parathyroid hormone (PTH; T3 only), vitamin D metabolites (total 25(OH)D, 1,25(OH) 2 D, 24,25(OH) 2 D, and free 25(OH)D) were analysed in T1 and T3. Ca Alb (Payne; inter-laboratory difference: UEA = 0.15 + 0.9*UGOT; UEA 2.54 = UGOT 2.65) and estimated glomerular filtration rate (eGFR; modified 4-variable MDRD) and vitamin D metabolites ratios (VMR) were calculated. Normally and non-normally distributed data were presented as mean (SD) or median (95 %CI). Group differences in relationships between vitamin D metabolites and with PTH were investigated with multiple regression analyses. Hypercalcemia in T3 was found in 1.7 % of women. PTH concentrations suggestive of primary hyperparathyroidism was found in 1 woman and none had 25(OH)D or 24,25(OH) 2 D concentrations in the toxicity range or suggestive of mutations in the CYP24A1 gene. Ca Alb was significantly higher in hypercalcemic cases compared to controls in T1 (2.44 (2.30-2.80) vs 2.37 (2.25-2.49) mmol/L) and T3 (2.63 (2.52-2.78) vs 2.46 (2.31-2.58) mmol/L). Serum P was higher among cases than controls in T3 (1.12 (0.16) vs 1.07 (0.18) mmol/L) but not in T1 (1.12 (0.18) and 1.12 (0.16) mmol/L). PTH in T3 was lower in cases (1.6 (1.6-2.8) vs 2.3 (2.1-2.8) pmol/L) but 1,25(OH) 2 D concentrations were similar. There were no significant group differences in serum 25(OH)D, free 25(OH)D, 24,25(OH) 2 D, Mg, Alb, Cr and eGFR. Regression analyses did not show significant differences between cases and controls in relationships between vitamin D metabolites and with PTH, except for the free 25(OH)D-PTH relationship and a higher free:total 25(OH)D ratio in cases at T1. In conclusion, most common causes of hypercalcemia were excluded in the majority of women. Hypercalcemic women had a relatively high serum 1,25(OH) 2 D concentration despite an appropriately suppressed PTH, suggestive of abnormal gestational adaptions., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Vitamin D and calcium have different biological functions, so the need for supplementation, and its safety and efficacy, need to be evaluated for each separately. Vitamin D deficiency is usually the result of low sunlight exposure (e.g., in frail older people, those who are veiled, those with dark-skin living at higher latitudes) and is reversible with calciferol 400-800 IU/day. Calcium supplements produce a 1% increase in bone density in the first year of use, without further increases subsequently. Vitamin D supplements do not improve bone density in clinical trials except in analyses of subgroups with baseline levels of 25-hydroxyvitamin D <30 nmol/L. Supplementation with calcium, vitamin D, or their combination does not prevent fractures in community-dwelling adults, but a large study in vitamin D-deficient nursing home residents did demonstrate fracture prevention. When treating osteoporosis, co-administration of calcium with anti-resorptive drugs has not been shown to impact on treatment efficacy. Correction of severe vitamin D deficiency (<25 nmol/L) is necessary before use of potent anti-resorptive drugs to avoid hypocalcemia. Calcium supplements cause gastrointestinal side effects, particularly constipation, and increase the risk of kidney stones and, probably, heart attacks by about 20%. Low-dose vitamin D is safe, but doses >4000 IU/day have been associated with more falls and fractures. Current evidence does not support use of either calcium or vitamin D supplements in healthy community-dwelling adults.

Purpose: Osteoporosis is associated with both lower health-related quality of life and depression in older people. We examined the independent and combined effects of a multi-component exercise program and calcium-vitamin D 3 fortified milk on health-related quality of life (HR-QoL) and depression in older men., Methods: In this 12-month, factorial design randomized controlled trial, 180 healthy community-dwelling men aged 50-79 years with normal to below average bone mineral density were allocated into one of four groups: exercise + fortified milk; exercise; fortified milk; or controls. Exercise consisted of high-intensity resistance training with weight-bearing exercise (3 days per week; 60-75 min per session). Men assigned to fortified milk consumed 400 ml/day of low-fat milk containing 1000 mg/day calcium and 800IU/day vitamin D 3 . Questionnaires were used to assess HR-QoL (SF-36) and depressive symptoms (Center for Epidemiologic Studies Depression Scale) at baseline, and 6 and 12 months. A linear mixed model analysis was used to test whether there was a synergistic interaction between exercise and calcium-vitamin D 3. If no significant interactions were detected, the main effects of exercise and fortified milk were examined., Results: Mean adherence to the exercise program and fortified milk was 67% (95% CI 61, 73%) and 90% (95% CI 86, 93%), respectively. There were no exercise-by-fortified milk interactions nor main effects of exercise or calcium-vitamin D for any of the HR-QoL measures or depressive symptoms., Conclusion: In healthy community-dwelling older men, exercise training and/or calcium-vitamin D fortified milk did not improve HR-QoL or depressive symptoms.

The effect of calcium on prevention of osteoporosis and related fracture which are aging issues is unclear. The aim of this study is to explore the association of calcium intake with vertebral fracture. This study enrolled 3,457 participants from China Action on Spine and Hip Status (CASH) study from 2013 and 2017. Dietary calcium intake was collected using validated food frequency questionnaires (FFQ). Vertebral fracture of CT images was defined as the primary outcome. The mean calcium intake of men and women were 522.75mg/day and 507.21mg/day, respectively. 6% reduction in the odds of fracture risk was observed per 100 unit increase of calcium intake from food among females (OR, 0.94; 95% CI, 0.89-0.99), but results among males were not significant. We divided calcium intake into quintiles when modelling its associations with fracture risk, negative associations of fracture risk with calcium intake were found among females. In a population with low usual calcium intake, higher dietary calcium intake was associated with fewer vertebral fracture in women and that no such association was seen in men.

There is vigorous interest among patients, caregivers, clinicians, and scientists to identify useful dietary interventions for inflammatory bowel diseases (IBD). Through the Cochrane Collaboration, we recently performed a systematic review and meta-analysis of dietary interventions for the induction or maintenance of remission in Crohn's disease (CD) and ulcerative colitis (UC) to assess the latest state of research. The current quality of evidence was formally graded to be low or very low for various methodological reasons, such as small sample sizes, heterogeneity among studies, and incomplete reporting. There are nonetheless emerging observational studies that progressively advance our knowledge and provide hope for a role of diet among traditional therapies to improve inflammation and symptoms. Further investments and concerted efforts in research are needed to significantly move the needle in identifying effective dietary therapies for IBD., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This is the second update of this Cochrane Review. Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer., Objectives: To determine whether vitamins and minerals and other potential agents, alone or in combination, reduce lung cancer incidence and lung cancer mortality in healthy populations., Search Methods: We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews., Selection Criteria: We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer., Data Collection and Analysis: Four review authors independently selected the trials to be included in the review, assessed their methodological quality and extracted data. For dichotomous outcomes we calculated risk ratios (RRs) and 95% confidence intervals (CIs) and pooled results using the random-effects model. We assessed the risk of bias using Cochrane's 'Risk of bias' assessment tool and certainty of evidence using the GRADE approach., Main Results: In this update, we identified three new trials for a total of 12 studies. Six analysed vitamin A, three vitamin C, three combined vitamin D3 + calcium, four vitamin E combined with other products, one selenium supplements and nine studied combinations of two or more products. Four studies included only men and five only women. Vitamin A results in little to no difference in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19; 5 RCTs, 212314 participants; high-certainty evidence) and lung cancer mortality (RR 1.06, 95% CI 0.81 to 1.38; 3 RCTs, 190118 participants; high-certainty evidence). But in smokers or asbestos workers vitamin A increases the risk of lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 RCTs, 43995 participants; high-certainty evidence), lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38; 2 RCTs, 29426 participants; high-certainty evidence) and all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 RCTs, 32883 participants; high-certainty evidence). Vitamin A increases the risk of minor side effects, such as yellowing of the skin and minor gastrointestinal symptoms (high-certainty evidence). Vitamin C likely results in little to no difference in lung cancer incidence (RR 1.29, 95% CI 0.67 to 2.49; 2 RCTs, 14953 participants; moderate-certainty evidence). In women, vitamin C increases the risk of lung cancer incidence (RR 1.84, 95% CI 1.14 to 2.95; 1 RCT, 7627 participants; high-certainty evidence). In men, vitamin C results in little to no difference in mortality for lung cancer (RR 0.81, 95% CI 0.53 to 1.23; 1 RCT, 7326 participants; high-certainty evidence). Vitamin D + calcium may result in little to no difference in lung cancer incidence in postmenopausal women (RR 0.90, 95% CI 0.39 to 2.08; 3 RCTs, 37601 women; low-certainty evidence). Vitamin E results in little to no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 RCTs, 36841 participants; high-certainty evidence) or to lung cancer mortality (RR 0.96, 95% CI 0.77 to 1.18; 2 RCTs, 29214 participants; high-certainty evidence), but increases the risk of haemorrhagic strokes (hazard ratio (HR), 1.74, 95% CI 1.04 to 2.91; 1 RCT, 14641 participants; high-certainty evidence). Calcium results in little to no difference in lung cancer incidence in postmenopausal women (RR 0.65, 95% CI 0.13 to 3.18; 1 RCT, 733 participants) or in risk of renal calculi (RR 1.94, 95% CI 0.20 to 18.57; 1 RCT, 733 participants; low-certainty evidence). Selenium in men results in little to no difference in lung cancer incidence (RR 1.11, 95% CI 0.80 to 1.54; 1 RCT, 17448 participants; high-certainty evidence) and lung cancer mortality (RR 1.09, 95% CI 0.72 to 1.66; 1 RCT, 17448 participants; high-certainty evidence) and increases the risk for grade 1 to 2 dermatitis (RR 1.16, 95% CI 1.04 to 1.31; 1 RCT, 17448 participants; high-certainty evidence) and for alopecia (RR 1.28, 95% CI 1.07 to 1.53; 1 RCT, 17448 participants; high-certainty evidence). The combination of vitamins A, C, E + selenium + zinc results in little to no difference in lung cancer incidence (RR 0.64, 95% CI 0.28 to 1.48; 1 RCT, 12741 participants; high-certainty evidence)., Authors' Conclusions: Well-designed RCTs have shown no beneficial effect of supplements for the prevention of lung cancer and lung cancer mortality in healthy people. Vitamin A supplements increase lung cancer incidence and mortality in smokers or persons exposed to asbestos. Vitamin C increases lung cancer incidence in women. Vitamin E increases the risk of haemorrhagic strokes., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

We compared the cumulative network meta-analyses with the recommendations in postmenopausal osteoporosis practice guidelines and actual prescribing practices in the USA. There was no apparent discrepancy between guideline recommendations and drug prescribing rankings, with the exception of vitamin D and calcium, when we used cumulative NMAs as references., Purpose: To compare the results of cumulative network meta-analyses (NMAs) with the recommendations in postmenopausal osteoporosis practice guidelines and actual prescribing practices in the USA., Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus were searched to retrieve randomized controlled trials (RCTs) in July 2017. The Agency for Healthcare Research and Quality's National Guideline Clearinghouse and associated society websites were searched to retrieve guidelines in June 2018. We used the Medical Expenditure Panel Survey (MEPS) to analyze prescription data from 1996 to 2015. Two independent investigators selected eligible RCTs. One investigator selected potential eligible guidelines, which were confirmed by another investigator. Two independent investigators extracted data from included RCTs. One investigator extracted recommendations from guidelines, which were confirmed by another investigator. (Registration: UMIN000031894) RESULTS: We analyzed data from 1995, 2000, 2005, 2010, and 2015. We chose hip fracture as the primary outcome of cumulative NMAs. We included 51 trials, 17 guidelines, and 5099 postmenopausal osteoporosis patients from the MEPS. Bisphosphonate, including alendronate, and combination of vitamin D and calcium (vDCa) were consistently recommendable from an efficacy viewpoint in NMAs and recommended in guidelines. Alendronate was the most prescribed drug (more than 30% over the observation period); however, vDCa was seldom prescribed. The maximum proportion was 5.3% from 2011 to 2015., Conclusions: In postmenopausal osteoporosis, there was no apparent discrepancy between guideline recommendations and drug prescribing rankings, with the exception of vDCa, when we used cumulative NMAs as references.

Background: Osteoporosis is the most common condition contributing to 95% of fractures in older patients hospitalized for fracture treatment. Despite the significant impact of fragility fractures on patient morbidity and mortality, efforts in optimizing osteoporotic treatment and prevention remain inadequate. In contrast, in patients with limited life expectancy, withholding specific osteoporosis drug treatment appears reasonable. The threshold between under- and overtreatment is still unclear., Methods: In 2016, we implemented a fracture liaison service (FLS) for 18 months to improve the quality of osteoporosis care. We collected prospectively the patient's history, current treatment for osteoporosis, and risk factors for fragility fractures using a standardized protocol. Recommendations for drug therapy are discussed during the interdisciplinary ward round. The primary outcome parameter was a recommendation for specific osteoporosis drug treatment. We included 681 patients (mean age 82.5 years, 502 (73.7%) females). The inclusion criteria were the following: age of 70 years or older, admission to geriatric fracture center between April 2016 and December 2018., Results: Based on our data, specific osteoporosis drug therapy was recommended in 467 (68.6%) patients. Six hundred fifty-one (95.6%) patients received vitamin D3, and 546 (80.2%) calcium. After adjustment, only age (every 5 years, OR 0.57; 95% CI 0.45-0.72; p < 0.0001), cognitive impairment (OR 0.41; 95% CI 0.23-0.74; p = 0.003), pre-fracture mobility (OR 1.54; 95% CI 1.34-1.75; p < 0.0001), and living in a nursing home (OR 0.52; 95% CI 0.27-0.99; p = 0.049) remained as independent predictors for an indication of specific osteoporosis drug therapy., Conclusion: We found a higher rate of recommendations for specific osteoporosis drug therapy compared with usual treatment rates in literature. Though in some cases withholding of specific osteoporosis drug therapy seems reasonable, the main proportion of fragility fracture patients is undertreated. Our results could be a benchmark for the quality of osteoporosis care in older fragility fracture patients treated in a geriatric fracture center.

Secondary analyses of data from the Age-Related Eye Disease Study (AREDS) revealed that higher calcium intakes were associated with slower progression to age-related macular degeneration (AMD). Earlier, primary analyses had revealed that a supplement containing copper reduced the odds of developing AMD while lengthening life. Because ocular lesions are being reported increasingly in neuropathy from copper deficiency and because higher dietary calcium can have beneficial effects on copper metabolism, it is hypothesized that the association of calcium intakes with better vision was mediated by improved copper utilization of study participants who were eating too little copper. Nutrition surveys reveal that amounts of copper proved insufficient for men and women in controlled studies are readily available to the general population. Observations on eye anatomy of animals deficient in copper and on decreased retinal superoxide dismutase, an enzyme dependent on copper for activity, in people with AMD support this hypothesis. Eradication of AMD will require new approaches based on hypotheses that fail falsification., Competing Interests: Declaration of Competing Interest The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Context: Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency., Objective: To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)]., Design: Open-label extension study; 5-year interim analysis., Setting: 12 US centers., Patients: Adults (N = 49) with chronic hypoparathyroidism., Intervention(s): rhPTH(1-84) 25 or 50 µg/d initially, with 25-µg adjustments permitted to a 100 µg/d maximum., Main Outcome Measure(s): Safety parameters; composite efficacy outcome was the proportion of patients with ≥50% reduction in oral calcium (or ≤500 mg/d) and calcitriol (or ≤0.25 µg/d) doses, and albumin-corrected serum calcium normalized or maintained compared with baseline, not exceeding upper limit of normal., Results: Forty patients completed 60 months of treatment. Mean albumin-corrected serum calcium levels remained between 8.2 and 8.7 mg/dL. Between baseline and month 60, levels ± SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 ± 236.24 mg/24 hours, 1.0 ± 0.78 mg/dL, and 8.5 ± 8.29 mg2/dL2, respectively. Serum creatinine level and estimated glomerular filtration rate were unchanged. Treatment-emergent adverse events (AEs) were reported in 48 patients (98.0%; hypocalcemia, 36.7%; muscle spasms, 32.7%; paresthesia, 30.6%; sinusitis, 30.6%; nausea, 30.6%) and serious AEs in 13 (26.5%). At month 60, 28 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ∼12 months, and then declined to values that remained above baseline., Conclusion: Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters., (Copyright © 2019 Endocrine Society.)

Physiologic changes during pregnancy include calcium, phosphate, and calciotropic hormone status. Calcium metabolic disorders are rare in pregnancy and management with close calcium and vitamin D control and supplementation. Primary hyperparathyroidism is mostly asymptomatic and does not affect conception or pregnancy. It requires control of plasma calcium levels. Surgical intervention may be indicated. Data on severe cases are missing. Osteoporosis in or before pregnancy is rare but usually diagnosed from fractures. Medical treatment other than supplementation is contraindicated. Vitamin D deficiency is common and may affect conception and increase complications. Current evidence does not prove vitamin D supplements effective in improving outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The physical gut barrier, comprised of a thick mucus layer and the epithelium, plays an important role in defense against microbes and foreign antigens. Calcium and vitamin D may be involved in maintaining the integrity of the intestinal mucosal barrier, the dysfunction of which may lead to endotoxemia and inflammation, and contribute to colorectal carcinogenesis. We investigated supplemental calcium (1200 mg, daily) and/or vitamin D 3 (1000 IU daily) effects on intestinal barrier function-related biomarkers in a subset of 105 participants from a large colorectal adenoma recurrence chemoprevention clinical trial. We assessed expression of the tight junction proteins claudin-1 (CLDN1), occludin (OCLD), and mucin-12 (MUC12) in the normal-appearing colorectal mucosa using standardized, automated immunohistochemistry and quantitative image analysis. Following 1 year of treatment, in the calcium relative to the no calcium group, the CLDN1, OCLD, and MUC12 expression increased by 14% (P = 0.17), 23% (P = 0.11), and 22% (P = 0.07), respectively. In secondary analyses, the estimated calcium treatment effects were greater among participants with baseline serum 25-OH-vitamin D concentrations below the median value of 22.69 ng/mL (CLDN1: 29%, P = 0.04; OCLD: 36%, P = 0.06; MUC12: 35%, P = 0.05). There were no biomarker expression changes in the vitamin D 3 alone group; however, modest increases were found in the combined calcium/vitamin D 3 group. At baseline, obesity, history of a sessile-serrated adenoma, colorectal MIB-1/Ki-67 expression, and a family history of colorectal cancer were associated with CLDN1, OCLD, and MUC12 expression. Our study supports continued investigation of factors that could affect intestinal mucosal barrier integrity relevant to colorectal carcinogenesis., (© 2019 Wiley Periodicals, Inc.)

With recent advances in the treatment of Spinal Muscular Atrophy (SMA), there is a strong need to increase knowledge on the involvement of organs and systems outside the central nervous system. We investigated bone metabolism, bone mineral density (BMD) and fractures, and their possible correlation with age and motor capacities. Thirty-two children with SMA (27 type 2, 5 type 3), mean age 40 ± 32.3 months, underwent two evaluations at an 18-month interval (V1 and V2). Twelve of these children also underwent a third evaluation at month 36 (V3). Diet, bone metabolism, BMD, X-rays, and motor function (by the Hammersmith Functional Motor Scale Expanded - HFMSE - and the Upper Limb Module - ULM) were assessed. At V1, 25-OH vitamin D 3 (25OH D) therapy was started, and dietary calcium intake adjusted according to the recommended dietary allowance. Low 25OH D levels and asymptomatic vertebral fractures were mainly observed at V1. At all visits, bone resorption markers were higher than normal. At V2 and V3, decreased BMD was observed. Higher spine BMD values at follow-up were associated with HFMSE score >12 at baseline (p<0.03). This study suggests that even young children with SMA are at risk of severe bone fragility. Further investigations of the molecular mechanisms leading to altered bone metabolism in SMA could help identify novel therapeutic targets and establish better guidelines for bone fragility management., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Oral calcium salts are recommended for the treatment of chronic hypoparathyroidism (HypoPT), although dosimetry is variable between individual patients and clinicians. However, patient feedback on calcium salts can be negative, particularly due to gastrointestinal side effects and hypercalciuria-related complications. We begin with a clinical case of a HypoPT patient taking oral calcium salts following thyroid surgery, who requested support in reducing her dose of these with a view to stopping entirely. To evaluate her request, we first describe the usual treatment of HypoPT according to current guidance and then present data from (a) a case note review of a cohort of 24 HypoPT patients managed with a "no calcium" treatment regimen by single physician (b) a comprehensive online survey of HypoPT patients' treatment and experiences (n = 330). The case note review found that target range serum calcium levels were successfully achieved in all 24 patients since transitioning to a "no calcium" regimen, without any breakthrough hypocalcaemia-related symptoms, the development of new renal stones, the occurrence of calcium-related hospital admissions or the finding of significant hypercalciuria. The online survey identified 36% of HypoPT patients who continued to take activated vitamin D, but had discontinued calcium supplements. HypoPT patients not currently taking calcium reported a significantly lower prevalence of adverse effects and outcomes, both compared with their previous experiences whilst taking calcium and also compared with the 64% of patients who continued to take oral calcium. We conclude that, subject to methodological limitations, there are significant issues of tolerability arising from conventional calcium-based treatment regimens for patients with chronic HypoPT. For selected patients, it may be reasonable to facilitate a managed therapeutic transition to "no calcium" regimen, and we also propose that calcium-based regimes be prospectively evaluated against calcium-free (or calcium-low) alternatives., (© 2019 John Wiley & Sons Ltd.)

Objective: Few bone mineral density (BMD) data are available in men with anorexia nervosa (AN), and none in those with atypical AN (ATYP) (AN psychological symptoms without low weight) or avoidant/restrictive food intake disorder (ARFID) (restrictive eating without AN psychological symptoms). We investigated the prevalence and determinants of low BMD and estimated hip strength in men with these disorders., Design: Cross-sectional: two centres., Patients: A total of 103 men, 18-63 years: AN (n = 26), ARFID (n = 11), ATYP (n = 18), healthy controls (HC) (n = 48)., Measurements: Body composition, BMD and estimated hip strength (section modulus and buckling ratio) by DXA (Hologic). Serum 25OH vitamin D was quantified, as was daily calcium intake in a subset of subjects., Results: Mean BMI was lowest in AN and ARFID, higher in ATYP and highest in HC (AN 14.7 ± 1.8, ARFID 15.3 ± 1.5, ATYP 20.6 ± 2.0, HC 23.7 ± 3.3 kg/m 2 ) (P < 0.0005). Mean BMD Z-scores at spine and hip were lower in AN and ARFID, but not ATYP, than HC (postero-anterior (PA) spine AN -2.05 ± 1.58, ARFID -1.33 ± 1.21, ATYP -0.59 ± 1.77, HC -0.12 ± 1.17) (P < 0.05). 65% AN, 18% ARFID, 33% ATYP and 6% HC had BMD Z-scores <-2 at ≥1 site (AN and ATYP vs HC, P < 0.01). Mean section modulus Z-scores were lower in AN than HC (P < 0.01). Lower BMI, muscle mass and vitamin D levels (R = 0.33-0.64), as well as longer disease duration (R = -0.51 to -0.58), were associated with lower BMD (P < 0.05)., Conclusions: Men with AN, ARFID and ATYP are at risk for low BMD. Men with these eating disorders who are low weight, or who have low muscle mass, long illness duration and/or vitamin D deficiency, may be at particularly high risk., (© 2019 John Wiley & Sons Ltd.)

Background: Post-surgical hypoparathyroidism is a common complication after thyroid surgery. The incidence is likely to increase given the rising trend in the annual number of thyroid operations being performed. Measures to prevent post-thyroidectomy hypoparathyroidism including different surgical techniques and prophylactic calcium and vitamin D supplements have been extensively studied. The management of post-thyroidectomy hypoparathyroidism however has not been extensively evaluated. Routine use of calcium and vitamin D supplements in the postoperative period may reduce the risk of symptoms, temporary hypocalcaemia and hospital stay. However, this may lead to overtreatment and has no effect on long-term hypoparathyroidism. Current recommendations on the management of post-thyroidectomy hypoparathyroidism is based on low-quality evidence. Existing guidelines do not often distinguish between surgical and non-surgical hypoparathyroidism, and transient and long-term disease.The aim of this systematic review was to summarise evidence on the use of calcium, vitamin D and recombinant parathyroid hormone in the management of post-thyroidectomy hypoparathyroidism. In addition, we aimed to highlight deficiencies in the current literature and stimulate further work in this field., Objectives: The objective of this systematic review was to assess the effects of calcium, vitamin D and recombinant parathyroid hormone in managing post-thyroidectomy hypoparathyroidism., Search Methods: We searched CENTRAL, MEDLINE, PubMed, Embase as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search for all databases was 17 December 2018 (except Embase, which was last searched on 21 December 2017). No language restrictions were applied., Selection Criteria: We planned to include randomised control trials (RCTs) or controlled clinical trials (CCTs) examining the effects of calcium, vitamin D or recombinant parathyroid hormone in people with temporary and long-term post-thyroidectomy hypoparathyroidism., Data Collection and Analysis: Two review authors independently screened titles, abstracts and full texts for relevance., Main Results: Database searches yielded a total of 1751 records. We retrieved potentially relevant full texts and excluded articles on the following basis: not a RCT or CCT; intervention, comparator or both did not match prespecified criteria; non-surgical causes of hypoparathyroidism, and studies on prevention. None of the articles was eligible for inclusion in the systematic review., Authors' Conclusions: This systematic review highlights a gap in the current literature and the lack of high-quality evidence in the management of post-thyroidectomy temporary and long-term hypoparathyroidism. Further research focusing on clinically relevant outcomes is needed to examine the effects of current treatments in the management of temporary and long-term post-thyroidectomy hypocalcaemia.

If all adults with osteoporosis in the European Union (EU) and United States (US) used calcium and vitamin D supplements, it could prevent more than 500,000 fractures/year in the EU and more than 300,000/year in the US and save approximately €5.7 billion and US $3.3 billion annually., Purpose: Evaluate the cost-effectiveness of calcium/vitamin D supplementation for preventing osteoporotic fractures., Methods: A cost-benefit analysis tool was used to estimate the net cost savings from reduced fracture-related hospital expenses if adults with osteoporosis in the EU and US used calcium/vitamin D supplements. A 14% relative risk reduction of fracture with calcium/vitamin D supplementation from a recent systematic review and meta-analysis of randomized, controlled trials was used as the basis for the benefit estimate. Other model inputs were informed by epidemiologic, clinical, and cost data (2016-2017) obtained via the medical literature or public databases. Analyses estimated the total number of avoided fractures and associated cost savings with supplement use. Net cost benefit was calculated by subtracting the supplements' market costs from those savings., Results: The > 30 million persons in the EU and nearly 11 million in US with osteoporosis experience about 3.9 million and 2.3 million fractures/year and have annual hospital costs exceeding €50 billion and $28 billion. If all persons with osteoporosis used calcium and vitamin D supplements, there would be an estimated 544,687 fewer fractures/year in the EU and 323,566 fewer in the US, saving over €6.9 billion and $3.9 billion; the net cost benefit would be €5,710,277,330 and $3,312,236,252, respectively., Conclusions: Calcium and vitamin D supplements are highly cost-effective, and expanded use could considerably reduce fractures and related costs. Although these analyses included individuals aged ≥ 50 years, the observed effects are likely driven by benefits observed in those aged ≥ 65 years.

Purpose of Review: Calcium and vitamin D supplementation is widely recommended for prevention of falls and fracture, particularly in the elderly where calcium intakes and vitamin D levels are often inadequate. A number of meta-analyses have questioned the benefits of untargeted or 'holistic' supplementation for falls and fracture, and raised the possibility of adverse cardiovascular effects. This review provides an update on these controversies., Recent Findings: Recent advances have largely centred around new trials of vitamin D and meta-analyses of published trials and observational studies. These articles have identified holistic vitamin D supplementation with or without calcium is unlikely to be an effective primary prevention strategy for falls or fracture. There has also been high-quality evidence that vitamin D, daily or as a bolus, does not reduce the risk of cardiovascular events., Summary: The benefits of vitamin D and calcium supplements for holistic fall and fracture prevention remain uncertain. Recent evidence supports the concept that high-dose vitamin D has adverse musculoskeletal effects. Future studies should focus on moderate daily doses. Finally, there remain inconsistent findings for adverse cardiovascular effects of calcium supplements with or without vitamin D. This uncertainty should be taken into account when evaluating the risk/benefits of supplementation.

Background: Evidence shows that adequate calcium intake during pregnancy reduces the risk of hypertensive disorders of pregnancy. In most low- and middle-income countries (LMICs) the daily calcium intake is well below recommendations. Mapping calcium intake during pregnancy worldwide and identifying populations with low calcium intake will provide the evidence base for more targeted actions to improve calcium intake., Objective: To assess dietary calcium intake during pregnancy worldwide., Search Strategy: MEDLINE and EMBASE (from July 2004 to November 2017)., Selection Criteria: Cross-sectional, cohort, and intervention studies reporting calcium intake during pregnancy., Data Collection and Analysis: Five reviewers working in pairs independently performed screening, extraction, and quality assessment. We reported summary measures of calcium intake and calculated the weighted arithmetic mean for high-income countries (HICs) and LMICs independently, and for geographic regions, among studies reporting country of recruitment, mean intake, and total number of participants. When available, inadequate intakes were reported., Main Results: From 1880 citations 105 works met the inclusion criteria, providing data for 73 958 women in 37 countries. The mean calcium intake was 948.3 mg/day (95% CI 872.1-1024.4 mg/day) for HICs and 647.6 mg/day (95% CI 568.7-726.5 mg/day) for LMICs. Calcium intakes below 800 mg/day were reported in five (29%) countries from HICs and in 14 (82%) countries from LMICs., Conclusion: These results are consistent with a lack of improvement in calcium dietary intake during pregnancy and confirm the gap between HICs and LMICs, with alarmingly low intakes recorded for pregnant women in LMICs. From the public health perspective, in the absence of specific local data, calcium supplementation of pregnant women in these countries should be universal., Tweetable Abstract: Despite dietary recommendations, women in LMICs face pregnancy with diets low in calcium., (© 2018 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Background: Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic mucosal inflammation, frequent hospitalizations, adverse health economics, and compromised quality of life. Diet has been hypothesised to influence IBD activity., Objectives: To evaluate the efficacy and safety of dietary interventions on IBD outcomes., Search Methods: We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, Embase, Web of Science, Clinicaltrials.gov and the WHO ICTRP from inception to 31 January 2019. We also scanned reference lists of included studies, relevant reviews and guidelines., Selection Criteria: We included randomized controlled trials (RCTs) that compared the effects of dietary manipulations to other diets in participants with IBD. Studies that exclusively focused on enteral nutrition, oral nutrient supplementation, medical foods, probiotics, and parenteral nutrition were excluded., Data Collection and Analysis: Two review authors independently performed study selection, extracted data and assessed bias using the risk of bias tool. We conducted meta-analyses where possible using a random-effects model and calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. We assessed the certainty of evidence using GRADE., Main Results: The review included 18 RCTs with 1878 participants. The studies assessed different dietary interventions for active CD (six studies), inactive CD (seven studies), active UC (one study) and inactive UC (four studies). Dietary interventions involved either the consumption of low amounts or complete exclusion of one or more food groups known to trigger IBD symptoms. There was limited scope for data pooling as the interventions and control diets were diverse. The studies were mostly inadequately powered. Fourteen studies were rated as high risk of bias. The other studies were rated as unclear risk of bias.The effect of high fiber, low refined carbohydrates, low microparticle diet, low calcium diet, symptoms-guided diet and highly restricted organic diet on clinical remission in active CD is uncertain. At 4 weeks, remission was induced in: 100% (4/4) of participants in the low refined carbohydrates diet group compared to 0% (0/3) of participants in the control group (RR 7.20, 95% CI 0.53 to 97.83; 7 participants; 1 study; very low certainty evidence). At 16 weeks, 44% (23/52) of participants in the low microparticle diet achieved clinical remission compared to 25% (13/51) of control-group participants (RR 3.13, 95% CI 0.22 to 43.84; 103 participants; 2 studies; I² = 73%; very low certainty evidence). Fifty per cent (16/32) of participants in the symptoms-guided diet group achieved clinical remission compared to 0% (0/19) of control group participants (RR 20.00, 95% CI 1.27 to 315.40; 51 participants ; 1 study; very low certainty evidence) (follow-up unclear). At 24 weeks, 50% (4/8) of participants in the highly restricted organic diet achieved clinical remission compared to 50% (5/10) of participants in the control group (RR 1.00, 95% CI 0.39 to 2.53; 18 participants; 1 study; very low certainty evidence). At 16 weeks, 37% (16/43) participants following a low calcium diet achieved clinical remission compared to 30% (12/40) in the control group (RR 1.24, 95% CI 0.67 to 2.29; 83 participants; 1 study; very low certainty evidence).The effect of low refined carbohydrate diets, symptoms-guided diets and low red processed meat diets on relapse in inactive CD is uncertain. At 12 to 24 months, 67% (176/264) of participants in low refined carbohydrate diet relapsed compared to 64% (193/303) in the control group (RR 1.04, 95% CI 0.87 to 1.25; 567 participants; 3 studies; I² = 35%; low certainty evidence). At 6 to 24 months, 48% (24/50) of participants in the symptoms-guided diet group relapsed compared to 83% (40/48) participants in the control diet (RR 0.53, 95% CI 0.28 to 1.01; 98 participants ; 2 studies; I² = 54%; low certainty evidence). At 48 weeks, 66% (63/96) of participants in the low red and processed meat diet group relapsed compared to 63% (75/118) of the control group (RR 1.03, 95% CI 0.85 to 1.26; 214 participants; 1 study; low certainty evidence). At 12 months, 0% (0/16) of participants on an exclusion diet comprised of low disaccharides / grains / saturated fats / red and processed meat experienced clinical relapse compared to 26% (10/38) of participants on a control group (RR 0.11, 95% CI 0.01 to 1.76; 54 participants; 1 study; very low certainty evidence).The effect of a symptoms-guided diet on clinical remission in active UC is uncertain. At six weeks, 36% (4/11) of symptoms-guided diet participants achieved remission compared to 0% (0/10) of usual diet participants (RR 8.25, 95% CI 0.50 to 136.33; 21 participants; 1 study; very low certainty evidence).The effect of the Alberta-based anti-inflammatory diet, the Carrageenan-free diet or milk-free diet on relapse rates in inactive UC is uncertain. At 6 months, 36% (5/14) of participants in the Alberta-based anti-inflammatory diet group relapsed compared to 29% (4/14) of participants in the control group (RR 1.25, 95% CI 0.42 to 3.70; 28 participants; 1 study; very low certainty evidence). Thirty per cent (3/10) of participants following the carrageenan-free diet for 12 months relapsed compared to 60% (3/5) of the participants in the control group (RR 0.50, 95% CI 0.15 to 1.64; 15 participants; 1 study; very low certainty evidence). At 12 months, 59% (23/39) of milk free diet participants relapsed compared to 68% (26/38) of control diet participants (RR 0.83, 95% CI 0.60 to 1.15; 77 participants; 2 studies; I² = 0%; low certainty evidence).None of the included studies reported on diet-related adverse events., Authors' Conclusions: The effects of dietary interventions on CD and UC are uncertain. Thus no firm conclusions regarding the benefits and harms of dietary interventions in CD and UC can be drawn. There is need for consensus on the composition of dietary interventions in IBD and more RCTs are required to evaluate these interventions. Currently, there are at least five ongoing studies (estimated enrollment of 498 participants). This review will be updated when the results of these studies are available.

Glucocorticoid-induced osteoporosis (GIOP) is common in patients prescribed with long-term glucocorticoids. Guidelines suggest patients receiving moderate-dose glucocorticoid therapy receive GIOP preventive care. Previous studies have shown preventive care rates are not optimal. We look at GIOP preventive care rates in rheumatology patients and predictors of various components of care., Purpose: Glucocorticoid-induced osteoporosis (GIOP) is a common concern in patients prescribed with long-term glucocorticoids. Studies have shown GIOP preventive care is not provided optimally in the general population; however, little is published on GIOP preventive care among patients with rheumatic disease. The objective of this study is to determine the proportion of rheumatology patients who received GIOP preventive care., Methods: A population-based retrospective quality assurance study of adults seen at the University of Alberta Rheumatology Clinic was performed using the electronic outpatient medical record. Records of adult patients prescribed with prednisone from January 1st to December 31st, 2016 by a rheumatologist were initially included for review. Those who had been prescribed ≥ 7.5 mg/day for ≥ 3 months were assessed for concurrent GIOP preventive care., Results: A total of 745 discreet courses of prednisone were prescribed in 433 patients with 113 meeting the above inclusion criteria. Following the prednisone prescription, 79% were taking vitamin D, 86% were taking calcium, and 50% were prescribed with osteoporosis pharmacotherapy. Twenty-five percent of patients had DXA imaging ordered by the rheumatologist within the first 6 months; of these, 86% of patients completed the DXA., Conclusions: Overall, our study shows that patients under the care of rheumatologists receive better GIOP preventative care than previously reported care in the general population. However, there is still room for improvement. In particular, men, younger patients, and rural patients seem to be at the most at risk of not receiving optimal GIOP prevention.

Osteoporosis is characterized by the loss of bone mass, deterioration of the bone microarchitecture, and an increased risk of fractures; these later complications are associated with significant morbidity and mortality. The asymptomatic and progressive nature of osteoporosis underscores the importance of identifying this entity in early stages. Despite the various treatments available, the prevention of the disease represents the most important aspect of management. An adequate intake of calcium and vitamin D as well as a healthy lifestyle is the basis for maintaining bone health. When osteoporosis is diagnosed, the choice of medications must be individualized considering characteristics of the patient and the risk of fractures. In this article, we review the main causes of osteoporosis, when and how to start treatment, and appropriate therapy and monitoring.

We present a case of Dent disease caused by a novel intronic mutation, 1348-1G>A, of the chloride voltage-gated channel 5 (CLCN5) gene. Cultured proximal tubule cells obtained from the patient showed impaired acidification of the endosome and/or lysosome, indicating that the 1348-1G>A mutation was indeed the cause of Dent disease. Although the prevalence of osteomalacia in Dent disease is low in Japan, several factors-including poor medication adherence-caused severe osteomalacia in the current case. Oral supplementation with calcium and native/active vitamin D therapy, with careful attention to medication adherence, led to the improvement of the patient's bone status.

Introduction: This study provides a benchmark for the nationwide use of osteoporosis screening, prevention and management strategies among Canadians aged 40 years and older (40+) using data collected one year prior to the release of Osteoporosis Canada's latest (2010) clinical practice guidelines., Methods: Data are from the 2009 Canadian Community Health Survey-Osteoporosis Rapid Response Component. The study sample (n = 5704) was divided into four risk subgroups: (1) osteoporosis diagnosis and major fracture; (2) osteoporosis diagnosis only; (3) major fracture only; or (4) neither osteoporosis diagnosis nor major fracture. We calculated descriptive statistics and performed multinomial multivariate logistic regression analyses to examine factors independently associated with osteoporosis screening, prevention and management strategies. Estimates were weighted to represent the Canadian household population (40+) living in the 10 provinces., Results: Approximately 10.1% of the population or 1.5 million Canadians 40+ reported having been diagnosed with osteoporosis. The majority related taking vitamin D or calcium supplements and having been prescribed osteoporosis medication(s), while less than 40% reported regular physical activity. Among those without a reported osteoporosis diagnosis, an estimated 6.7% or 1 million reported having had a major fracture, of which one-third reported having had a bone density test and less than half reported taking vitamin D supplements, calcium supplements or engaging in regular physical activity. Major fracture history was not associated with bone density testing or osteoporosis medication use., Conclusion: A large proportion of Canadians at risk for osteoporosis-those with a major fracture history-are not undergoing bone density testing nor are they engaging in lifestyle approaches known to help maintain healthy bones. This study provides the historical information required to evaluate whether the latest clinical practice guidelines have had an impact on osteoporosis care in Canada., Competing Interests: None.

This study aimed to explore the therapeutic efficacy and safety of alfacalcidol among Chinese postmenopausal women (age >65 years) with osteoporosis or osteopenia.A total of 62 postmenopausal women with osteoporosis or osteopenia (>65 years) were recruited from urban residential community of Beijing. The patients daily took oral calcium and alfacalcidol (Alpha D3, 1 μg) for 9 months. Safety and efficacy assessments were performed at baseline and regular intervals. Alfacalcidol was adjusted to a daily dose of 0.5 μg in case of hypercalcemia or hypercalciuria.A significant improvement in "timed up and go test" and "chair rising test" was achieved 3 months after treatment. Significant decreases in bone turnover markers were observed 3 months after the treatment and lasted throughout the study. Nineteen patients discontinued due to adverse events (17 hypercalciuria, 1 hydronephrosis, and 1 stomach ache), while alfacalcidol was adjusted to a daily dose of 0.5 μg in 18 patients (29.0%). Increased serum creatinine was observed when compared to baseline (P <.001), but all the values were in normal range.The treatment with 1 μg alfacalcidol can significantly improve muscle function and bone metabolism. Regular monitoring of urine calcium and timely dosage-adjustments are very important to guarantee the safety of alfacalcidol treatment in Chinese menopausal women.

Obesity, a chronic condition associated with several life-threatening diseases, affects a significant proportion of the global population and has long been associated with vitamin D deficiency. The prevalence of both obesity and vitamin D deficiency has increased dramatically in Jordan in recent decades, especially among women. Few studies in Jordan and the surrounding area address this issue. In this study, we hypothesize that calcium and vitamin D have beneficial effects on weight reduction and metabolic profile in obese women. The objective of this study is to examine the effect of vitamin D 3 and calcium supplementation on anthropometric measurements and some blood metabolites. Forty-five obese female subjects with vitamin D deficiency were recruited by a dietitian and randomly assigned to the same weight loss diet in addition to the following treatments (4 groups): control (CON), no prescribed supplements; vitamin D 3 (Diet/D), given a high weekly dose of cholecalciferol (50 000 IU/subject/week); calcium (Diet/Ca), given 1200 mg/dL calcium/subject/day; vitamin D 3 plus Ca (Diet/Ca/D), given cholecalciferol (50 000 IU/subject/week) and calcium (1200 mg/dL calcium/subject/day). Results revealed that after 3 months of supplementation, the Diet/Ca/D group subjects experienced a significant reduction (P ≤ .05) in weight (10.49 kg), BMI (4.61 ± 2 kg/m 2 ), waist circumference (11.41 ± 8.9 cm), body fat percentage (2.43 ± 1.7%), FBG (25.81 ± 11.4 mg/dL), PTH (27.58 ± 8.9 pg/mL), cholesterol (0.56 ± 0.2 mmol/L), and triglycerides (0.53 ± 0.21 mmol/L) when compared to the Diet/Ca and the CON groups. Interestingly, however, the CON group showed a significant increase in serum PTH concentration (9.51 ± 3.8 pg/mL, P ≤ .05). Based on these results, a combined Ca and vitamin D 3 supplement appears to enhance weight loss and improve some of the blood metabolic profiles in obese women subjected to a weight loss diet, thus supporting our study hypothesis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In Mexico, osteoporosis is a public health problem. In this document, the Mexican Association for Bone and Mineral Metabolism defines its position on calcium, vitamin D supplement use, and physical activity as an effective, safe, and cost-effective initiatives to prevent low bone mass., Introduction: In Mexico, osteoporosis is a public health problem that is expected to increase in the decades ahead. Generally, modifiable risk factors for bone health are related with lifestyles, especially nutrition and physical activity., Methods: In this position paper, the Mexican Association for Bone and Mineral Metabolism (AMMOM, by its acronym in Spanish), which is a multidisciplinary group of researchers, dietitians, epidemiologists, nurses, and physicians who study bone and related tissues and communicate the best strategies for diagnosis, treatment, and prevention of bone problems, aims to analyze the association between nutrition and bone health, risk behaviors for low bone mass, and the economic impact that prevention of low bone mass represents for the health care system., Results: Addressing therapeutic management with pharmacological and non-pharmacological approaches, we emphasize the important role the patient plays in the doctor-patient relationship, both in the consulting room and in daily life. Furthermore, the AMMOM defines its position on calcium and vitamin D supplement use as an effective, safe, and cost-effective initiative to prevent low bone mass., Conclusions: In summary, most research and clinical practice related to osteoporosis have focused on diagnosis and treatment, but general measures for primary prevention based on addressing modifiable risk factors as a public health priority to delay the onset of loss of bone mass have not been considered by Mexican authorities. Consequently, the AMMOM task force also seeks to provide information on concrete actions to prevent low bone mass.

Introduction: osteoporosis is a metabolic bone disease that leads to increased bone fragility and increased risk of fracture., Objectives: the aim of the present research was to determine the effectiveness of a diary intake of three different dairy products (250 ml) enriched with vitamins and calcium on decreasing bone mass. METHOS: the present study is a comparative trial of three dairy products fortified with calcium and vitamin D, parallel, randomized, double-blind andsingle-center. Bone mass content (BMC), bone mass density (BMD), T-score and Z-score were measured in different locations, besides biochemical markers along 18 months in premenopausal women. Two hundred and ten volunteers from all the three groups were submitted to the same monitoring procedures, consisting on blood extraction, urine collection and energy X-ray absorptiometry (DEXA) done in the laboratory. The monitoring was carried on three times, first at month 0 (baseline), the second at month 9 (in the middle of the treatment) and, finally, at month 18 (the end of the treatment)., Results: the majority of anatomical locations showed both BMC and BMD decrease ranging between 0.5% and 1.5%. The T-score and the Z-scoreincreased in lumbar spine after the treatment with the dairy products. Moreover, the most noteworthy change on the biomarkers of bone resorption was showed by plasmatic tartrate-resistant acid phosphatase (TRAP), with and increase between 20.7% and 29.5% after the intake of the different products., Conclusions: therefore, the intake of the three dairy products improves the bone mass in lumbar spine, leading to important changes in the concentration of biomarkers of bone resorption. Especially, tartrate-resistant acid phosphatase seems to be strongly influenced by the intake of every dairy product. However, no significant differences were found between the different dairy products used in the present study. Therefore, the intake of dairy product seems to be more determinant than micronutrients supplementation.

Introduction: In this paper we investigated whether cholecalciferol supplementation, prescribed to treat vitamin D deficiency in patients with nephrolithiasis, increased the risk of stone recurrence., Methods: Calcium excretion and urine supersaturation with calcium oxalate (βCaOx) and brushite (βbsh) were evaluated in 33 kidney stone formers (aged 56±17; 12 males), both before and after therapy with cholecalciferol, prescribed as oral bolus of 100.000-200.000 UI, followed by maintenance doses, repeated every week (5.000-10.000 UI) or month (25.000-50.000 UI). During the study, patients followed a dietary regimen which included a daily calcium intake of about 800-1000 mg., Results: Urinary nitrogen, sodium and ash-acid excretion did not significantly change during the study. After cholecalciferol supplementation, the main results were as follows: both serum calcium and phosphate did not vary significantly; 25(OH)VitD₃ increased from 11,8±5,5 to 40,2±12,2 ng/mL (p<0,01); 1,25(OH) ₂ VitD₃ increased from 41,6±17,6 to 54,0±16,0 pg/mL (p<0,01); PTH decreased from 75,0±27,2 to 56,7±21,1 pg/mL (p<0,01); daily urinary calcium increased from 2,7±1,5 to 3,6±1,6 mg/Kg b.w. (p<0,01), whereas fasting urinary calcium did not change significantly. After therapy, βbsh increased from 0,9±0,7 to 1,3±1,3 (p=0,02) and βCaOx did not vary significantly. Before cholecalciferol supplementation, 6/33 patients (18.2%) were hypercalciuric, whereas 13/33 patients (39,4%) showed hypercalciuria after supplementation (pX²=0,03)., Conclusions: Cholecalciferol supplementation for vitamin D deficiency may increase both urinary calcium and urine supersaturation in stone formers. If vitamin D supplements are needed in these patients, a careful monitoring of urine metabolic profile is warranted, in order to customize the metaphylaxis accordingly (hydration, potassium citrate, thiazides)., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Objective: Osteoporotic hip fractures are associated with increased morbidity, mortality, and secondary fractures. Although osteoporosis treatment can reduce future fracture risk, patients often do not receive it. We report results of a coordinator-less fracture liaison service in Israel addressing hip fracture patients. The primary endpoint was attending the Metabolic Clinic. Secondary endpoints included vitamin D measurement, calcium and vitamin D recommendations, initiation of osteoporosis treatment, and mortality 1-year post-fracture., Methods: This prospective study included 219 hip fracture patients who were compared with historical controls. Data on hospitalized patients were collected before and after implementation of a structured protocol for hip fracture patients, led by a multidisciplinary team, without a coordinator., Results: The study included 219 and 218 patients ≥60 years old who were operated on in 2013 and 2012, respectively. Metabolic Clinic visits increased from 6.4 to 40.2% after the intervention ( P<.001). Among 14 patients who attended the Clinic in 2012, 85.7% began osteoporosis therapy; among 88 who attended in 2013, 45.5% were treated at the first visit. Vitamin D measurements and calcium and vitamin D supplementation increased postintervention (0.5-80.1%, P<.001; 30.8-84.7%, P<.001, respectively). Patients receiving osteoporosis medications had lower mortality rates than untreated patients (4.3% vs. 21.8%)., Conclusion: An Orthopedic-Metabolic team implemented by existing staff without a coordinator can improve osteoporosis care for hip fracture patients. Yet, gaps remain as only 40% had Metabolic Clinic follow-up postintervention, and of these, only half received specific treatment recommendations. Hospitals are encouraged to adopt secondary fracture prevention protocols and continuously improve them to close the gaps between current management and appropriate metabolic assessment and treatment., Abbreviations: CHS = Clalit Health Services; CI = confidence interval; FLS = fracture liaison service; HMO = health maintenance organization; OR = odds ratio.

Adverse effects of low vitamin D status and calcium intakes in pregnancy may be mediated through functional effects on the calcium metabolic system. Little explored in pregnancy, we aimed to examine the relative importance of serum 25-hydroxyvitamin D (25(OH)D) and calcium intake on parathyroid hormone (PTH) concentrations in healthy white-skinned pregnant women. This cross-sectional analysis included 142 participants (14 ± 2 weeks' gestation) at baseline of a vitamin D intervention trial at 51.9 °N. Serum 25(OH)D, PTH, and albumin-corrected calcium were quantified biochemically. Total vitamin D and calcium intakes (diet and supplements) were estimated using a validated food frequency questionnaire. The mean ± SD vitamin D intake was 10.7 ± 5.2 μg/day. With a mean ± SD serum 25(OH)D of 54.9 ± 22.6 nmol/L, 44% of women were <50 nmol/L and 13% <30 nmol/L. Calcium intakes (mean ± SD) were 1182 ± 488 mg/day and 23% of participants consumed <800 mg/day. The mean ± SD serum albumin-adjusted calcium was 2.2 ± 0.1 mmol/L and geometric mean (95% CI) PTH was 9.2 (8.4, 10.2) pg/mL. PTH was inversely correlated with serum 25(OH)D ( r = -0.311, p < 0.001), but not with calcium intake or serum calcium ( r = -0.087 and 0.057, respectively, both p > 0.05). Analysis of variance showed that while serum 25(OH)D (dichotomised at 50 nmol/L) had a significant effect on PTH ( p = 0.025), calcium intake (<800, 800⁻1000, ≥1000 mg/day) had no effect ( p = 0.822). There was no 25(OH)D-calcium intake interaction effect on PTH ( p = 0.941). In this group of white-skinned women with largely sufficient calcium intakes, serum 25(OH)D was important for maintaining normal PTH concentration.