Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

Coronary calcium score in patients with post-surgical hypoparathyroidism.

Objective: This study aimed to evaluate the cardiovascular risk of patients with post-surgical hypoparathyroidism through coronary calcium score (CACS) evaluation andcardiovascular risk calculators. Subjects and methods: Patients with post-surgical hypoparathyroidism (HG = 29) were compared to a control group (CG = 29), matched by sex and age. Demographic and clinical data were captured by a questionnaire or patient files. Both groups performed a thoracic-computed tomography to evaluate the CACS and the cardiovascular risk was calculated by two risk calculators. Results: In the HG, the supplementation of calcium varied between 500 to 2,000 mg/day and the mean calcitriol was 0.5 ± 0.29 mcg/day. The mean serum calcium and phosphorus were 8.32 ± 0.68 and 4.92 ± 0.87 mg/dL, respectively, and in the range recommended for hypoparathyroidism. The Brazilian Society of Cardiology's risk calculator showed a difference among groups, with no patient in the HG with low risk, but the CACS was similar. A positive CACS in the HG was associated with obesity and high BMI but not with calcium and/or vitamin D supplementation. Conclusion: In conclusion, patients with hypoparathyroidism did not show increased CACS, and it was not related to supplementation.

Calcium supplementation for the prevention of pre-eclampsia: Challenging the evidence from meta-analyses.

OBJECTIVE: To investigate the validity of the conclusion from Cochrane reviews and meta-analyses that treatment with calcium supplementation during pregnancy reduces the risk for pre-eclampsia by 55%, which has been influential in international guidelines and future research. DESIGN: Sensitivity analysis of data from Cochrane reviews of trials evaluating high-dose calcium supplementation (of at least 1 g/day) for reduction of pre-eclampsia risk. SETTING: Systematic review and meta-analysis. POPULATION: The Cochrane reviews and meta-analyses included 13 trials enrolling a total of 15 730 women. Random-effects meta-analysis of these studies resulted in a mean risk ratio (RR, calcium/placebo) of 0.45 (95% confidence interval [CI] 0.31-0.65; p < 0.0001). METHODS: We carried out a sensitivity analysis of evidence from the relevant Cochrane review, to examine the impact of study size. MAIN OUTCOME MEASURES: pre-eclampsia. RESULTS: In the three largest studies, accounting for 13 815 (88%) of total recruitment, mean RR was 0.92 (95% CI 0.80-1.06) and there was no evidence of heterogeneity between studies (I2 = 0). With inclusion of the smaller studies, mean RR decreased to 0.45 and I2 increased to 70%. CONCLUSIONS: In assessment of the effect of calcium supplementation on pre-eclampsia risk, the naive focus on the mean of the random-effects meta-analysis in the presence of substantial heterogeneity is highly misleading.

Does preoperative calcium and 1, 25 OH vitamin D supplementation impact postoperative hypocalcemia and length of stay following pediatric thyroidectomy?

OBJECTIVE: To investigate whether perioperative calcium and 1,25 OH vitamin D supplementation (PCDS) influences the rates of postoperative hypocalcemia and length of stay (LOS) following pediatric thyroidectomy. STUDY DESIGN: Retrospective Cohort Review. SETTING: Tertiary children's hospital. METHODS: 94 patients who underwent completion or total thyroidectomy with or without concomitant neck dissection from 2010 to 2020 at a single institution were included. Patients with pre-existing hypocalcemia or preoperative vitamin D insufficiency were excluded. Rates of postoperative hypocalcemia and LOS were compared for patients receiving PCDS to those receiving no supplementation. RESULTS: Thirty percent of patients with PCDS had documented postoperative hypocalcemia compared to 64% of patients without PCDS (p = 0.01). Patients with PCDS had a median LOS of 30 h compared to 36 h (p = 0.002). Multivariable analyses confirmed that patients with PCDS had lower odds of postoperative hypocalcemia (OR: 0.32, CI: 0.11, 0.89) and shorter LOS by 17 h (SE: 8, p = 0.04) after adjustment for confounders. CONCLUSION: PCDS is associated with significantly lower risk of hypocalcemia and shorter LOS. Standardizing preoperative care for pediatric patients undergoing thyroidectomy may decrease variability and improve outcomes following surgery.

Dilated cardiomyopathy in patients with hypoparathyroidism: A narrative review.

Background: Hypoparathyroidism is a rare endocrine disorder characterized by low blood calcium levels, elevated phosphorus levels, and insufficient parathyroid hormone production. It can lead to dilated cardiomyopathy (DCM), a cardiac condition characterized by enlarged ventricles and reduced heart function. This review aims to explore the relationship between hypoparathyroidism and DCM, the impact of calcium on cardiac function, and the potential for DCM reversal with calcium supplementation. Methods: A comprehensive literature search was conducted using PubMed, Google Scholar, and relevant keywords and Mesh terms. Case reports evaluating dilated cardiomyopathy in patients with Hypoparathyroidism were included in the study. Additionally, references cited in each study were carefully examined to identify relevant reports. The cases included in the review were analyzed, and common cardiac manifestations, diagnostic approaches, and management were identified. Results: DCM in hypoparathyroidism presents with symptoms of heart failure, reduced ejection fraction, and impaired left ventricular function. Laboratory tests show low serum calcium levels and elevated phosphate levels. Prompt diagnosis and treatment with calcium and vitamin D supplementation can lead to improvements in cardiac function. Conclusion: Hypoparathyroidism-induced DCM is reversible with timely calcium and vitamin D supplementation. Patient compliance with prescribed medications and supplements is crucial to prevent and manage cardiac complications. Regular follow-up check-ups and monitoring of calcium levels can aid in early detection and improve patient outcomes. Educating patients about the importance of treatment adherence can significantly reduce the risk of developing DCM and other cardiac symptoms associated with hypoparathyroidism. Routine follow-up of DCM among patients with endocrine disorders is recommended.

Coronary calcium score in patients with post-surgical hypoparathyroidism

ABSTRACT Objective: This study aimed to evaluate the cardiovascular risk of patients with post-surgical hypoparathyroidism through coronary calcium score (CACS) evaluation and cardiovascular risk calculators. Subjects and methods: Patients with post-surgical hypoparathyroidism (HG = 29) were compared to a control group (CG = 29), matched by sex and age. Demographic and clinical data were captured by a questionnaire or patient files. Both groups performed a thoracic-computed tomography to evaluate the CACS and the cardiovascular risk was calculated by two risk calculators. Results: In the HG, the supplementation of calcium varied between 500 to 2,000 mg/day and the mean calcitriol was 0.5 ± 0.29 mcg/day. The mean serum calcium and phosphorus were 8.32 ± 0.68 and 4.92 ± 0.87 mg/dL, respectively, and in the range recommended for hypoparathyroidism. The Brazilian Society of Cardiology's risk calculator showed a difference among groups, with no patient in the HG with low risk, but the CACS was similar. A positive CACS in the HG was associated with obesity and high BMI but not with calcium and/or vitamin D supplementation. Conclusion: In conclusion, patients with hypoparathyroidism did not show increased CACS, and it was not related to supplementation.

The significance of short-term preoperative calcium and activated vitamin D3 supplementation in thyroidectomy: a randomized trial and prospective study.

Objective: The aim was to explore the effects of preoperative calcium and activated vitamin D3 supplementation on post-thyroidectomy hypocalcemia and hypo-parathyroid hormone-emia (hypo-PTHemia). Methods: A total of 209 patients were randomly divided into control group (CG) and experimental group (EG). Oral calcium and activated vitamin D3 supplementation were preoperatively administered to EG, whereas a placebo was administered to CG. Data on serum calcium, phosphorus, and PTH concentrations before operation, on postoperative day 1 (POPD1), at postoperative week 3 (POPW3), and on the length of postoperative hospitalization were collected. Results: The serum calcium, phosphorus, and PTH concentrations, as well as the incidence of postoperative hypocalcemia and hypo-PTHemia, did not significantly differ between EG and CG. Subgroup analysis revealed that the serum calcium concentrations of the experimental bilateral thyroidectomy subgroup (eBTS) on POPD1 and POPW3 were higher than that of the control bilateral thyroidectomy subgroup (cBTS) (P < 0.05); the reduction of serum calcium in eBTS on POPD1 and POPW3 was less than those in cBTS (P < 0.05). However, significant differences were not observed between the unilateral thyroidectomy subgroups (UTS) (P > 0.05). Moreover, the incidence of postoperative hypocalcemia in cBTS on POPD1 was significantly higher than that in eBTS (65.9% vs 41.7%) (P < 0.05). The length of hospitalization in cBTS (3.55 ± 1.89 days) was significantly longer than that (2.79 ± 1.15 days) in eBTS (P < 0.05). Conclusion: Short-term preoperative prophylactic oral calcium and activated vitamin D3 supplementation could effectively reduce the incidence of postoperative hypocalcemia and decrease the length of postoperative hospitalization in patients who have undergone bilateral thyroidectomy.

A randomized field trial assessing the timing of postpartum calcium bolus administration on milk yield of multiparous Holstein cows.

Recent studies have shown that cows with subclinical hypocalcemia (SCH) at 4 d in milk (DIM), regardless of their blood Ca concentration before that time point, suffer from an increased early-lactation disease risk and reduced milk yield, whereas cows experiencing a transient reduction in blood Ca that regain normocalcemia by 4 DIM are at a reduced risk of disease and have greater milk yields. With a goal of improving outcomes for dyscalcemic cows with SCH at 4 DIM, our primary objective was to assess the effect of a herd-level oral Ca bolus strategy that delayed supplementation to 24 and 48 h postpartum on productive performance of multiparous Holstein cows. Our secondary objectives were to assess the effects of delayed Ca bolus supplementation on blood Ca concentration, disease incidence within 30 DIM, and pregnancy risk to first service. At calving, multiparous cows on a single commercial dairy farm in Iran were randomly assigned to 1 of 3 treatment groups: (1) control, no Ca bolus administration (CON; n = 95); (2) traditional bolus, one Ca bolus administered immediately following calving and a second Ca bolus administered 24 h after calving (TRD, n = 102); or (3) experimental bolus, one Ca bolus administered 24 h after calving with a second Ca bolus administered 48 h after calving (EXP, n = 99). Blood samples were collected at 0, 24, 48, 72, and 96 h, and 7 d after parturition, with sampling occurring before bolus administration for the TRD (0 and 24 h) and EXP (24 and 48 h) groups. A general linear mixed model was created to analyze the change milk yield over the first 4 monthly tests and serum Ca concentrations over 7 DIM. Given the lack of disease events diagnosed within 30 DIM, no statistical analysis was conducted for this outcome. The effect of treatment group on risk of pregnancy to first service was assessed using Poisson regression. The incidence of dyscalcemia within CON cows was 72%. We found no difference in mean monthly milk yield among treatment groups across the first 4 tests, with an average monthly production of 51.8 ± 8.8 kg/d for CON cows, 52.5 ± 8.7 kg/d for TRD cows, and 51.8 ± 8.7 kg/d for EXP cows. Mean blood Ca concentration also did not differ across 7 DIM among treatment groups and was 2.04 mmol/L [95% confidence interval (CI) = 2.00 to 2.07 mmol/L] for CON cows, 2.06 mmol/L (95% CI = 2.03 to 2.09 mmol/L) for TRD cows, and 2.09 mmol/L (95% CI = 2.05 to 2.12 mmol/L) for EXP cows. The risk of pregnancy to first service was numerically greater for CON than TRD and EXP cows but not statistically different; however, our study was underpowered for this outcome. Under the conditions of our study, our findings suggest that delaying oral Ca bolus supplementation to 24 and 48 h postpartum has no effect on milk production across the first 4 monthly tests.

Considerations in the Diagnosis and Treatment of Early Lactation Calcium Disturbances.

This article reviews the history of clinical hypocalcemia and the evolving definition of subclinical hypocalcemia, targeting a concept for consideration that not all hypocalcemia is negative. With a goal of presenting bovine practitioners information to assist with individual animal hypocalcemia diagnosis and treatment as well as herd-level monitoring and prevention, we present current methods of direct calcium measurement, therapeutic interventions for clinical hypocalcemia, and postpartum calcium supplementation options and their efficacy. We encourage veterinarians to understand calcium dynamics in the immediate postpartum period and evaluate how individual cow therapy and herd prevention protocols can assist with supporting calcium regulation.

All-cause and cause-specific mortality risks associated with calcium supplementation with or without vitamin D: A nationwide population-based study.

BACKGROUND: Current evidence regarding the mortality outcomes associated with calcium supplementation with or without low-dose vitamin D is conflicting. OBJECTIVES: To investigate the effects of calcium supplementation with or without vitamin D on all-cause and cause-specific mortalities in a large-scale cohort. METHODS: This study used data from the Korean National Health Insurance System database and National Death Registry. A total of 27,846 participants aged >55 years who had taken calcium supplements with or without vitamin D for at least 90 days (calcium supplementation only [CaO], n = 6256; calcium supplementation in combination with vitamin D [CaD], n = 21,590) were matched in a 1:1 ratio to those who did not take calcium or vitamin D supplements (control group) using propensity scores. RESULTS: No difference in all-cause mortality risk was found between the CaO and control groups: (adjusted hazard ratio [HR] = 1.00; 95% confidence interval [CI]: 0.92-1.10). However, all-cause mortality was lower in the CaD group (HR = 0.85; 95% CI: 0.80-0.89) compared with that in the control group. Mortality risk associated with cardiovascular disease (CVD) was decreased in the CaD group when the daily vitamin D dose received was less than 1000 IU (HR = 0.72; 95% CI: 0.64-0.81). Subgroup analysis showed significant effect of vitamin D with calcium in individuals who were female, aged ≥65 years or had previous history of cancer or CVD. CONCLUSION: In combination with calcium, vitamin D supplementation provides better outcomes for all-cause mortality, particularly CVD-associated mortality, in a duration-dependent manner.

High-efficiency production of the antimicrobial peptide pediocin PA-1 in metabolically engineered Corynebacterium glutamicum using a microaerobic process at acidic pH and elevated levels of bivalent calcium ions.

BACKGROUND: Pediocin PA-1 is a bacteriocin of recognized value with applications in food bio-preservation and the medical sector for the prevention of infection. To date, industrial manufacturing of pediocin PA-1 is limited by high cost and low-performance. The recent establishment of the biotechnological workhorse Corynebacterium glutamicum as recombinant host for pediocin PA-1 synthesis displays a promising starting point towards more efficient production. RESULTS: Here, we optimized the fermentative production process. Following successful simplification of the production medium, we carefully investigated the impact of dissolved oxygen, pH value, and the presence of bivalent calcium ions on pediocin production. It turned out that the formation of the peptide was strongly supported by an acidic pH of 5.7 and microaerobic conditions at a dissolved oxygen level of 2.5%. Furthermore, elevated levels of CaCl2 boosted production. The IPTG-inducible producer C. glutamicum CR099 pXMJ19 Ptac pedACDCg provided 66 mg L-1 of pediocin PA-1 in a two-phase batch process using the optimized set-up. In addition, the novel constitutive strain Ptuf pedACDCg allowed successful production without the need for IPTG. CONCLUSIONS: The achieved pediocin titer surpasses previous efforts in various microbes up to almost seven-fold, providing a valuable step to further explore and develop this important bacteriocin. In addition to its high biosynthetic performance C. glutamicum proved to be highly robust under the demanding producing conditions, suggesting its further use as host for bacteriocin production.

Evaluation of the clinical practice guidelines and consensuses on calcium and vitamin D supplementation in healthy children using the Appraisal of Guidelines for Research and Evaluation II instrument and Reporting Items for Practice Guidelines in Healthcare statement.

Background: This study aimed to assess the methodological and reporting quality of the guidelines and consensus on calcium and vitamin D supplementation in healthy children, and the consistency of these recommendations. Methods: A systematic search of relevant guideline websites and databases, including PubMed, Embase, CNKI, WangFang, and SinoMed, was undertaken from inception to April 7, 2021, by two independent reviewers who assessed the eligible guidelines using the validated Appraisal of Guidelines for Research and Evaluation Instrument II (AGREE II) and the Reporting Items for Practice Guidelines in Healthcare (RIGHT) tools. Overall, the between-reviewer agreement was evaluated using an intra-class correlation coefficient. Results: A total of 24 guidelines and consensuses from 2002 to 2022 were identified from China, the United States, Canada, France, Australia, New Zealand, Europe, and other countries and regions. These were of mixed quality, and scored poorly in the rigor of development, editorial independence, and applicability of the domains of AGREE II. Among the seven domains of the RIGHT checklist, domain one (basic information) had the highest reporting rate (69.3%), whereas domain five (review and quality assurance) had the lowest reporting rate (11.5%). The overall quality of the included guidelines and consensuses was low. Only 12 guidelines were recommended, with modifications. The recommended calcium intake for children of different ages varies greatly (400-1,150 mg/day). Among the included guidelines and consensuses, a vitamin D (VD) prevention dose of 400 IU/day in infants was generally considered safe, and 25-hydroxyvitamin-D [25(OH)D] levels of <20 ng/mL (50 nmol/L) or 20-30 ng/mL (50-75 nmol/L) indicated VD deficiency or insufficiency. However, the recommended amount of VD for children of different age groups and risk strata differed considerably (400-4,000 IU/day or 10-100 µg/day). The choice of VD2 or VD3 supplements and sunlight exposure also differed across the guidelines and consensuses. Conclusion: There is considerable variability in calcium and VD guidelines and consensus development methods in calcium and VD supplementation for healthy children. Therefore, efforts are necessary to strengthen the methodological rigor of guideline development and utilize the best available evidence to underpin recommendations.

Should all pregnant women take calcium supplements in Nepal? GRADE evidence to policy assessment.

BACKGROUND: The WHO recommends oral calcium supplementation (1.5-2.0 g) in pregnant women to reduce the risk of pre-eclampsia living in areas with low dietary calcium intake. Although maternal mortality is high in Nepal and eclampsia causes at least 20% of maternal deaths, implementing WHO recommendations would be a major undertaking. OBJECTIVE: This review aimed to assess whether the current evidence supports the blanket supplementation of calcium to prevent pre-eclampsia among pregnant women in Nepal. METHODS: We used a structured approach to appraise the evidence for calcium supplementation in Nepal. We identified what may influence the impact of calcium supplementation in Nepal and conducted a situation analysis in the country covering maternal mortality, pre-eclampsia occurrence, and existing government policy provisions for supplementation. We also consulted with experts and government officials to explore their perspectives and experience on supplementation. We then used AMSTAR (A MeaSurement Tool to Assess Systematic Reviews) to appraise the Cochrane Systematic Review of calcium supplementation. Finally, we used these data in a GRADE (Grading of Recommendations Assessment, Development and Evaluation)-Evidence to Decision framework to reach a policy recommendation. RESULTS: Our assessment of the Cochrane Review showed that the recommendation made by the WHO is based on weak evidence and trial findings that are not consistent between studies. The Cochrane Review found low certainty of the evidence for benefit (reduction in pre-eclampsia and maternal mortality). Conversely, there is a high certainty of the evidence of undesirable effects (HELLP [haemolysis, elevated liver enzymes and low platelets] syndrome) although this is uncommon. The likely absolute reduction in maternal deaths projected to Nepal was estimated to be low, while the implementation costs were high. Stakeholders also raised several concerns regarding feasibility, acceptability, appropriate dosing, and risk communication. CONCLUSIONS: This review concludes that the blanket supplementation of calcium cannot be recommended in Nepal. A better approach may be to identify high-risk pregnant women and manage their antenatal visits and delivery to prevent mortality from pre-eclampsia.

Impact of the fortification of a rice beverage with different calcium and iron sources on calcium and iron bioaccessibility.

Rice beverages are commonly fortified with minerals to improve their nutritional value. However, the effect of fortification on mineral bioaccessibility is poorly understood. Thus, the effects of fortification of a rice beverage on mineral concentration and bioaccessibility using calcium carbonate (CaCO3), tricalcium phosphate (Ca3(PO4)2), sodium iron EDTA (NaFeEDTA) and ferric pyrophosphate (Fe4(P2O7)3) individually and in combination were studied. Recovery of the added minerals in the rice beverage ranged from 71.4 % to 92.0 % and 61.0 % to 93.3 % for Ca and Fe, respectively. Mineral bioacessibility was shown to be higher for CaCO3(≤39.0 %) compared to Ca3(PO4)2 (≤14.4 %) and for NaFeEDTA (≤50.7 %) compared to Fe4(P2O7)3 (≤3.9 %). No interaction of the different Ca sources was identified; the addition of iron sources did not have a significant effect on Ca bioaccessibility. The addition of NaFeEDTA to the rice beverage was found to be better than the addition of iron pyrophosphate and the simultaneous addition of this iron sources did not result in an additive effect on Fe bioaccessibility. These results may be used to develop plant-based beverages with an improved mineral bioaccessibility.

The effect of calcium supplementation in people under 35 years old: A systematic review and meta-analysis of randomized controlled trials.

Background: The effect of calcium supplementation on bone mineral accretion in people under 35 years old is inconclusive. To comprehensively summarize the evidence for the effect of calcium supplementation on bone mineral accretion in young populations (≤35 years). Methods: This is a systematic review and meta-analysis. The Pubmed, Embase, ProQuest, CENTRAL, WHO Global Index Medicus, Clinical Trials.gov, WHO ICTRP, China National Knowledge Infrastructure (CNKI), and Wanfang Data databases were systematically searched from database inception to April 25, 2021. Randomized clinical trials assessing the effects of calcium supplementation on bone mineral density (BMD) or bone mineral content (BMC) in people under 35 years old. Results: This systematic review and meta-analysis identified 43 studies involving 7,382 subjects. Moderate certainty of evidence showed that calcium supplementation was associated with the accretion of BMD and BMC, especially on femoral neck (standardized mean difference [SMD] 0.627, 95% confidence interval [CI] 0.338-0.915; SMD 0.364, 95% CI 0.134-0.595; respectively) and total body (SMD 0.330, 95% CI 0.163-0.496; SMD 0.149, 95% CI 0.006-0.291), also with a slight improvement effect on lumbar spine BMC (SMD 0.163, 95% CI 0.008-0.317), no effects on total hip BMD and BMC and lumbar spine BMD were observed. Very interestingly, subgroup analyses suggested that the improvement of bone at femoral neck was more pronounced in the peripeak bone mass (PBM) population (20-35 years) than the pre-PBM population (<20 years). Conclusions: Our findings provided novel insights and evidence in calcium supplementation, which showed that calcium supplementation significantly improves bone mass, implying that preventive calcium supplementation before or around achieving PBM may be a shift in the window of intervention for osteoporosis. Funding: This work was supported by Wenzhou Medical University grant [89219029].

Osteoporosis and bone fractures are common problems among older people, particularly older women. These conditions cause disability and reduce quality of life. Progressive loss of bone mineral density is usually the culprit. So far, strategies to prevent bone weakening with age have produced disappointing results. For example, taking calcium supplements in later life only slightly reduces the risk of osteoporosis or fracture. New approaches are needed. Bone mass increases gradually early in life and peaks and plateaus around 20-35 years of age. After that period, bone mass slowly declines. Some scientists suspect that increasing calcium intake during this period of peak bone mass may reduce osteoporosis or fracture risk later in life. A meta-analysis by Liu, Le et al. shows that boosting calcium intake in young adulthood strengthens bones. The researchers analyzed data from 43 randomized controlled trials that enrolled 7,382 participants. About half the studies looked at the effects of taking calcium supplements and the other half analyzed the effects of a high calcium diet. Boosting calcium intake in people younger than age 35 improved bone mineral density throughout the body. It also increased bone mineral density at the femoral neck, where most hip fractures occur. Calcium supplementation produced larger effects in individuals between the ages of 20 and 35 than in people younger than 20. Both high calcium diets and calcium supplements with doses less than 1000 mg/d boosted bone strength. Higher dose calcium supplements did not provide any extra benefits. The analysis suggests people should pay more attention to bone health during early adulthood. Large randomized clinical trials are needed to confirm the long-term benefits of boosting calcium intake during early adulthood. But if the results are validated, taking calcium supplements, or eating more calcium-rich foods between the ages of 20 and 35 may help individuals build healthier bones and prevent fractures and osteoporosis later in life.

Trauma-induced hypocalcemia.

BACKGROUND: Trauma-induced hypocalcemia is an underappreciated complication of severe injury but is well known to result in the derangement of an array of physiological regulatory mechanisms. Existing literature provides a compelling link between hypocalcemia and worse trauma-induced coagulopathy and increased mortality after injury. STUDY DESIGN AND METHODS: This narrative review evaluates available data related to the risk factors, mechanisms, and treatment of hypocalcemia after severe injury. The authors did not perform a systemic review or meta-analysis. RESULTS AND DISCUSSION: The interplay of acidosis, hypothermia, and coagulopathy with hypocalcemia potentiates the bloody vicious cycle of hemorrhagic shock which has been the paradigm of trauma resuscitation for over half a century. However, current screening and treatment of postinjury hypocalcemia are relegated to a secondary consideration in trauma resuscitation. We conclude calcium supplementation should be a primary tier intervention for life-threatening injury.

Effect of calcium supplementation on severe hypocalcemia in patients with secondary hyperparathyroidism after total parathyroidectomy.

BACKGROUND: Severe hypocalcemia (SH) is a dreaded complication of total parathyroidectomy (TPTX) without auto-transplantation. AIM: To compare conventional and preventive calcium supplementation (CS) regimens in terms of SH occurrence after TPTX. METHODS: This retrospective study included patients who underwent TPTX between January 2015 and May 2018 at the China-Japan Friendship Hospital. From January 2015 to May 2016, conventional CS was performed in patients who underwent TPTX, with calcium amounts adjusted according to postoperative serum calcium levels. From October 2016 to May 2018, preventive CS was performed according to preoperative alkaline phosphatase (ALP) levels. The patients were defined as low-risk (ALP < 500 U/L) and high-risk (ALP > 500 U/L) for SH. All preoperative blood samples were collected in the fasting state on the day before surgery. Postoperative blood samples were obtained at 6-7 AM from the first postoperative day. RESULTS: A total of 271 patients were included. These patients were 47.7 ± 11.1 years old, and 57.6% were male. Their mean body mass index (BMI) was 22.9 ± 3.8 kg/m2. There were no significant differences in sex, age, BMI, preoperative ALP, serum calcium, serum phosphorus, calcium-phosphorus ratio, and intact parathyroid hormone (iPTH) between the two CS groups. Compared with conventional CS, preventive CS led to lower occurrence rates of hypocalcemia within 48 h (46.0% vs 74.5%, P < 0.001) and SH (31.7% vs 64.1%, P < 0.001). Multivariable analysis showed that preoperative iPTH levels [odds ratio (OR) = 1.001, 95% confidence interval (CI): 1.000-1.001, P = 0.009), preoperative ALP amounts (OR = 1.002, 95%CI: 1.001-1.003, P = 0.002), preoperative serum phosphorus levels (OR = 8.729, 95%CI: 1.518-50.216, P = 0.015) and preventive CS (OR = 0.132, 95%CI: 0.067-0.261, P < 0.001) were independently associated with SH. In patients with preoperative ALP ≥ 500 U/L, only preventive CS (OR = 0.147, 95%CI: 0.038-0.562. P = 0.005) was independently associated with SH. CONCLUSION: This study suggests that preventive CS could reduce the occurrence of SH, indicating its critical value for hypocalcemia after TPTX.

Calcium Supplementation, Risk of Cardiovascular Diseases, and Mortality: A Real-World Study of the Korean National Health Insurance Service Data.

Few studies have investigated the effects of calcium supplementation on cardiovascular outcomes in individuals with low calcium intake in real-world settings. This study examined the association between calcium supplementation and cardiovascular outcomes in the Korean population in a real-world setting. This large retrospective cohort study included patients aged ≥45 years first prescribed calcium supplements in 2010. Age- and sex-matched controls were recruited among those who had no prescription for calcium supplements. Longitudinal data were collected on 31 December 2018. Kaplan−Meier estimation and Cox proportional hazard regression analysis were performed. The cumulative incidence of acute myocardial infarction, ischemic stroke, and death was significantly higher in the calcium supplementation group than in the control group (p < 0.05 by log-rank test). The calcium supplementation group had a significantly higher risk of myocardial infarction, ischemic stroke, and death than the control group. Compared to the control group, the hazard ratios (95% confidence intervals) of the incidence of myocardial infarction, stroke, and death in the supplementation group were 1.14 (1.03−1.27), 1.12 (1.05−1.20), and 1.40 (1.32−1.50), respectively, after adjusting for confounding variables. Considering the associated cardiovascular risk, calcium supplementation for osteoporosis treatment should be administered cautiously.

Metformin-induced vitamin B12 deficiency can cause or worsen distal symmetrical, autonomic and cardiac neuropathy in the patient with diabetes.

Metformin blocks the absorption of vitamin B12 through a mechanism that has not been established but could be because of interference with the calcium-dependent binding of the intrinsic factor vitamin B12 complex to the cubam receptor in the terminal ileum. The subsequent deficiency of vitamin B12 may cause or accelerate distal symmetrical and autonomic neuropathy in the patient with diabetes. Several observational studies and meta-analyses have reported a significant association between metformin utilization and vitamin B12 deficiency. Prospective studies have shown that not only do metformin utilizers have lower vitamin B12 levels but they also have higher frequencies of distal symmetrical polyneuropathy and autonomic neuropathy (including cardiac denervation, which is associated with increased incidences of cardiac arrhythmias, cardiac events and mortality). Therefore, periodic monitoring of vitamin B12 is recommended in all patients who utilize metformin, particularly if metformin has been used for over 5 years at which stage hepatic stores of vitamin B12 would probably be depleted. Factors that accelerate the loss of hepatic vitamin B12 stores are proton pump inhibitors, bariatric surgery, being elderly and having an increased turnover of red blood cells. If serum vitamin B12 levels are borderline, measurement of methylmalonic acid and homocysteine levels can detect vitamin B12 deficiency at its earliest stage. Therapies include prophylactic calcium and vitamin B12 supplements, metformin withdrawal, replenishing vitamin B12 stores with intramuscular or oral vitamin B12 therapy and regular monitoring of vitamin B12 levels and vitamin B12 supplements if metformin continues to be utilized. With adequate vitamin B12 replacement, while symptoms of neuropathy may or may not improve, objective findings of neuropathy stabilize but do not improve.