Effect of Calcium and Vitamin D Supplementation (Dairy vs. Pharmacological) on Bone Health of Underprivileged Indian Children and Youth with Type-1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (n = 203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8 ±â€¯307.8, B-983.2 ±â€¯352.9, C-792.8 ±â€¯346.8. TBLHBMD-A-± 0.2, B-0.8 ±â€¯0.2, C-0.6 ±â€¯0.2, p < 0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7 ±â€¯1.1, B-0.6 ±â€¯1.4, C- -0.7 ±â€¯1.1; Girls- A-1.1 ±â€¯1.1, B-0.9 ±â€¯3.4, C- -1.7 ±â€¯1.3, p < 0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9 ±â€¯28.6, B-15.3 ±â€¯16.5, C-7.6 ±â€¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.

Hypomagnesemia with Secondary Hypocalcemia (HSH): a Case Report.

BACKGROUND: Hypomagnesemia with secondary hypocalcemia (HSH) is a genetic disorder arising from the body's impaired capacity to absorb and retain magnesium (Mg2+) consumed through diet. Consequently, Mg2+ levels in blood are significantly reduced, a condition referred to as hypomagnesemia. Insufficient levels of Mg2+ and calci-um (Ca2+) can lead to neurological complications that manifest during infancy, such as painful muscle spasms (tet-any) and seizures. METHODS: We reported a case of HSH involving a 10-year-old male patient from a Han Chinese family. He was admitted due to recurrent convulsions experienced over the past two years. The patient's initial episode occurred two years prior, when he collapsed without apparent cause and exhibited limb numbness, convulsions, and a disordered state of consciousness, accompanied by hypocalcemia. Cranial CT scans revealed multiple symmetrical calcifications in the basal ganglia, corona radiata, and cerebellar dentate nucleus. RESULTS: During the hospital stay, the patient was administered the following treatments: Calcium Carbonate and Vitamin D3 Tablets (1.5 g of calcium carbonate and 125 IU of Vitamin D3 per tablet, 1 tablet/time) once daily, Calcitriol Soft Capsules (0.25 µg of calcitriol per capsule, 1 capsule/time) twice daily, Potassium Chloride Sustained-release Tablets (0.5 g of potassium chloride per tablet, 1 tablet/time) thrice daily, Potassium Aspartate and Mag-nesium Aspartate Tablets (158 mg of potassium aspartate and 140 mg of magnesium aspartate per tablet, 1 tablet/ time) thrice daily, and intravenous infusions of Magnesium Sulfate Injection (2.5 g/time) twice daily. After three days in the hospital, the patient's initial symptoms subsided, resulting in discharge with a prescription of ongoing oral medications including Calcium Carbonate and Vitamin D3 Tablets, Calcitriol Soft Capsules, and Potassium Aspartate and Magnesium Aspartate Tablets, with the same usage and dosage as the above three drugs. A month subsequent, the serum levels of Mg2+, Ca2+, potassium (K+), and phosphorus were 0.96 mmol/L, 2.52 mmol/L, 4.06 mmol/L, and 1.63 mmol/L, respectively. CONCLUSIONS: Primary HSH is an uncommon manifestation of parathyroid hypoplasia, clinically characterized by low levels of Mg2+, Ca2+, and K+ in the blood. Our findings serve to enrich and consolidate the knowledge for future case studies and follow-up investigations.

The in vitro study of interaction between antacids and anti-diabetic drug sitagliptin in the treatment of type II diabetes.

Hyperglycemia is a long-lasting syndrome that occurs either when the pancreas cannot produce enough insulin, or the body cannot effectively utilize that insulin to regulate blood sugar levels. Non-insulin-dependent hyperglycemia, also known as type II diabetes, causes a common consequence of severe damage to many of the body's organs mainly the blood vessels and nerves. The majority of people around the world are suffering from non-insulin-dependent diabetes. The present work showed a great effort to investigate any possible interaction between antacids and sitagliptin (anti-diabetic drug) in the treatment of type II diabetes with gastrointestinal tract problems. The in vitro studies were carried out in simulated gastric juice pH 2.0 and intestinal pH 7.4 at 37oC. MgCO3, NaHCO3, Mg(OH)2, Al(OH)3 and CaCO3 were used as antacids in these studies. It has been observed that % release of sitagliptin was significantly enhanced in the presence of calcium carbonate and magnesium carbonates.

Cytotoxicity, Dermal Toxicity, and In Vivo Antifungal Effect of Griseofulvin-Loaded Vaterite Carriers Administered via Sonophoresis.

The search for novel therapeutic strategies to treat fungal diseases is of special importance nowadays given the emerging threat of drug resistance. Various particulate delivery systems are extensively being developing to enhance bioavailability, site-specific penetration, and therapeutic efficacy of antimycotics. Recently, we have designed a novel topical formulation for griseofulvin (Gf) drug, which is currently commercially available in oral dosage forms due to its limited skin permeation. The proposed formulation is based on vaterite carriers that enabled effective incorporation and ultrasonically assisted delivery of Gf to hair follicles improving its dermal bioavailability. Here, we evaluated the effect of ultrasound on the viability of murine fibroblasts co-incubated with either Gf-loaded carriers or a free form of Gf and investigated the influence of both forms on different subpopulations of murine blood cells. The study revealed no sufficient cyto- and hemotoxicity of the carriers, even at the highest investigated concentrations. We also conducted a series of in vivo experiments to assess their multi-dose dermal toxicity and antifungal efficiency. Visual and histological examinations of the skin in healthy rabbits showed no obvious adverse effects after US-assisted application of the Gf-loaded carriers. At the same time, investigation of therapeutic efficiency for the designed formulation in comparison with free Gf and isoconazole drugs in a guinea pig model of trichophytosis revealed that the vaterite-based form of Gf provided the most rapid and effective cure of infected animals together with the reduction in therapeutic procedure number. These findings pave the way to improving antifungal therapy of superficial mycoses and justifying further preclinical studies.

The nanoformula of zoledronic acid and calcium carbonate targets osteoclasts and reverses osteoporosis.

Osteoporosis is known as an imbalance in bone catabolism and anabolism. Overactive bone resorption causes bone mass loss and increased incidence of fragility fractures. Antiresorptive drugs are widely used for osteoporosis treatment, and their inhibitory effects on osteoclasts (OCs) have been well established. However, due to the lack of selectivity, their off-target and side effects often bring suffering to patients. Herein, an OCs' microenvironment-responsive nanoplatform HA-MC/CaCO3/ZOL@PBAE-SA (HMCZP) is developed, consisting of succinic anhydride (SA)-modified poly(ß-amino ester) (PBAE) micelle, calcium carbonate shell, minocycline-modified hyaluronic acid (HA-MC) and zoledronic acid (ZOL). Results indicate that HMCZP, as compared with the first-line therapy, could more effectively inhibit the activity of mature OCs and significantly reverse the systemic bone mass loss in ovariectomized mice. In addition, the OCs-targeted capacity of HMCZP makes it therapeutically efficient at sites of severe bone mass loss and allows it to reduce the adverse effects of ZOL, such as acute phase reaction. High-throughput RNA sequencing (RNA-seq) reveals that HMCZP could down-regulate a critical osteoporotic target, tartrate-resistant acid phosphatase (TRAP), as well as other potential therapeutical targets for osteoporosis. These results suggest that an intelligent nanoplatform targeting OCs is a promising strategy for osteoporosis therapy.

In vitro cytogenetic analysis of two different anti-phosphates (sevelamer hydrochloride and calcium carbonate) agents used by patients with hyperphosphatemia.

Sevelamer hydrochloride (SH) and calcium carbonate (CaCO3) are two agents included in the phosphate-binding group which are frequently prescribed in the treatment of patients with hyperphosphatemia. However, there are no satisfactory studies on the genotoxic effects of SH in vitro. This study was conducted to reveal the genotoxic and/or cytotoxic potential of these two drugs in cultured human peripheral lymphocytes. Human peripheral lymphocytes were treated with SH and CaCO3 at sublethal concentrations for 24 or 48 h for micronucleus assay and 1 h in the comet assay. CaCO3 and SH stimulated a slight increase in micronucleus formation however this increase was not significant compared to the control group. According to the findings of the comet test, only one concentration of the SH caused significant DNA damage (2 mg/ml, 48 h) whereas CaCO3 did not cause important DNA breakage. No significant oxidative damage or anti-radical effect caused by test substances was observed on the pure pBR322 plasmid DNA in a cell-free medium. Also, it was found that the drugs were devoid of mutagenic activity in the Ames test, but had a weak cytotoxic effect. Both test substances, particularly SH, significantly reduced the nuclear division index compared to the control group. In conclusion, the cytotoxic effect of SH was evident on the basis of in vitro tests and slightly higher than CaCO3.

Effect of lanthanum carbonate and calcium carbonate on the progression of coronary artery calcification among hemodialysis patients with vascular calcification risk: a randomized controlled trial.

BACKGROUND: Coronary artery calcification (CAC) is predictive of cardiovascular events. We assessed whether a non-calcium-based phosphate binder, lanthanum carbonate (LC), could delay CAC progression compared with a calcium-based phosphate binder, calcium carbonate (CC), in hemodialysis patients. METHODS: This was a subsidiary of the LANDMARK study, which is a multicenter, open-label, randomized control study comparing LC and CC for cardiovascular events among Japanese hemodialysis patients with hyperphosphatemia who were at risk of vascular calcification. Participants were randomly assigned (1:1) to receive LC or CC. The changes in the total Agatston score of CAC 2 years from baseline were the primary outcome. Secondary outcomes included the changes in the total Agatston score at 1 year from baseline and the changes in serum phosphate, corrected calcium, and intact parathyroid hormone concentrations. RESULTS: Of 239 patients, 123 comprised the full analysis set. The median daily drug dose (mg) was 750 [interquartile range (IQR), 750‒1500] in the LC group and 3000 (IQR, 3000‒3000) in the CC group; it remained constant throughout the study period. There was no significant difference in the change in total Agatston score from baseline to 2 years between the LC and CC groups [368 (95% confidence interval, 57-680) in the LC group vs. 611 (105-1118) in the CC group; difference, 243 (- 352-838)]. CONCLUSIONS: LC-based treatment for hyperphosphatemia did not delay CAC for 2 years compared with CC-based treatment in hemodialysis patients with at least one risk factor for vascular calcification.

Meta-Analysis of Effects of Nutritional Intervention Combined with Calcium Carbonate D3 Tablets on Bone Mineral Density, Bone Metabolism, and Curative Effect in Patients with Osteoporosis.

To investigate the changes in bone mineral density, bone metabolism, and efficacy of nutritional intervention combined with calcium carbonate D3 tablets in patients with osteoporosis, a RevMan 5.2 software meta-analysis was conducted in this study. According to the therapeutic direction of nutritional intervention combined with calcium carbonate D3 tablets for osteoporosis patients, relevant literature were searched in Wanfang Medical, CNKI, VIP, and PubMed literature databases at home and abroad. Keywords included bone mineral density, bone metabolism, blood calcium (Ca), blood phosphorus (P), osteocalcin (OC), bone mineral density (BMD), serum alkaline phosphatase (ALP), efficacy, osteoporosis, and nutritional intervention. Literature that met the criteria were deleted, and meta-analysis was performed using RevMan 5.2 software. The results indicate that a total of 10 Chinese literature were included. Compared with the monotherapy group, the clinical efficacy, osteocalcin, BMD, alkaline phosphatase, calcium, and phosphorus were significantly higher in the combination group (P < 0.05). Based on calcium carbonate D3, treatment combined with nutritional intervention can enhance the clinical efficacy, bone metabolism, and bone mineral density of patients with osteoporosis, and nutritional intervention combined with calcium carbonate D3 tablets is a feasible program to promote the recovery of patients with osteoporosis.

Hungry bone syndrome like presentation following single-dose denosumab for hypercalcaemia secondary to sarcoidosis with IgA nephropathy.

A woman in her mid-50s with IgA nephropathy, sarcoidosis and steroid-induced diabetes mellitus presented with generalised paraesthesia and spontaneous tetany. She had received denosumab 60 mg subcutaneously 8 weeks previously for parathyroid hormone independent hypercalcaemia.At admission, she had severe hypocalcaemia (5 mg/dL), hypophosphataemia (1.9 mg/dL), hypomagnesaemia (1.4 mg/dL) and elevated serum creatinine (1.48 mg/dL) with prolonged QTc (corrected QT interval) on electrocardiograph. She initially received intravenous calcium and magnesium followed by oral calcium carbonate and calcitriol. Her prednisolone dose was tapered to 5 mg/day. Evaluation showed secondary hyperparathyroidism (1474 pg/mL) and elevated 1,25-dihydroxy vitamin D (195 pg/mL). After 1 week of oral calcium carbonate (3000 mg/day) and calcitriol (1.5 µg/day), she achieved normocalcaemia (8.1 mg/dL).To conclude, denosumab for hypercalcaemia with renal insufficiency causes prolonged severe symptomatic hypocalcaemia and hypophosphataemia mimicking hungry bone syndrome. It is important to periodically monitor for hypocalcaemia after denosumab.

Chinese Proprietary Medicine Xianling Gubao Capsule for Osteoporosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Objective: To assess the benefit and harm of Chinese medicine Xianling Gubao (XLGB) capsule compared to conventional medication or placebo to inform clinical practice. Methods: We included randomized controlled trials (RCTs) with Jadad score ≥3 of XLGB capsule compared to pharmaceutical medication, placebo, or no treatment for primary osteoporosis. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database (Sino-Med) from their inception till November 13th, 2021. Study selection and data extraction were done by two authors independently. The methodological quality of the RCTs was assessed using Cochrane's risk of bias tool. The effect size was presented as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI). Results: Our searches identified 2292 records and after exclusions, eight trials involving 846 participants were included. There was no statistically significant difference between conventional medications with or without XLGB on new fracture (RR: 0.50, 95% CI: [0.13, 1.87]). Quality of life by SF-36 questionnaire of XLGB plus calcium carbonate, vitamin D3, and calcitriol was improved than that of without XLGB (MD: 6.72 scores, 95% CI: [2.82, 10.62]). XLGB increased bone mineral density similarly as calcium carbonate plus vitamin D3 (MD: 0.21, 95% CI: [-0.16, 0.58]) or as alendronate sodium, calcium carbonate plus vitamin D3 (MD: 0.00, 95% CI: [-0.10, 0.10]), but it had no additional effect as an add-on treatment to conventional medications (MD: 0.13, 95% CI: [-0.12, 0.37]). XLGB relieved pain via visual analog scale more effectively when combined with medications (MD: -1.55 score, 95% CI: [-2.47, -0.63]). XLGB as monotherapy did not increase adverse events (RR: 0.63, 95% CI: [0.28, 1.41]), or as an add-on treatment (RR: 0.25, 95% CI: [0.03, 2.16]). Conclusion: This systematic review shows that XLGB capsule appears to be safe and has a beneficial effect on the quality of life and pain relief when used alone or in combination with conventional medications in osteoporosis patients. Further large, rigorous trials are warranted to test its long-term benefit.

Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial.

In hypoparathyroidism (HypoPT), calcium supplementation is virtually always required, although the disease is likely to be associated with an increased risk of nephrolithiasis. The use of calcium citrate (Ca-Cit) theoretically could have a positive impact on the nephrolithiasis risk because citrate salts are used to reduce this risk. Our objective was to evaluate the potential therapeutic advantage of Ca-Cit in comparison with calcium carbonate (CaCO3 ) in HypoPT, on nephrolithiasis risk factors, as well as to their ability to maintain desirable serum calcium levels. We also evaluated these preparations on quality of life (QOL). This randomized, double-blind, crossover trial recruited 24 adults with postsurgical chronic hypoparathyroidism at Campus Bio-Medico University of Rome. Participants were randomized 1:1 to Ca-Cit or CaCO3 for 1 month and then crossed over to the other treatment for another month. The primary outcomes were changes in albumin-adjusted serum calcium and in ion activity product of calcium oxalate levels (AP[CaOx] index). Secondary efficacy outcomes included changes in SF-36 survey score, fatigue score, constipation, and adverse events. No difference in terms of AP(CaOx) index was observed between the two groups. However, Ca-Cit was associated with a significant reduction in the oxalate/creatinine ratio compared with CaCO3 (-2.46 mmol/mol [SD 11.93] versus 7.42 mmol/mol [SD 17.63], p = 0.029). Serum calcium and phosphorus concentration was not different between the two calcium preparations. Ca-Cit was associated with less constipation (p = 0.047). No difference was found in QOL scores. Although Ca-Cit did not modify the AP(CaOx) index when compared with CaCO3, it was associated with a reduction in urinary oxalate excretion that could have a potential beneficial effect on nephrolithiasis risk. These results are likely to have clinical implications in HypoPT, particularly those who do not tolerate CaCO3 and those affected by nephrolithiasis. A longer-term experience is needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial.

BACKGROUND: Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has a further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. METHODS/DESIGN: We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11-19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM) Z-score at 48 weeks, measured by dual-energy X-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip strength at 48 and 96 weeks and TBLH-BMCLBM Z-scores at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. DISCUSSION: This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual in childhood is critical for optimising adolescent and early adult bone health and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR20200989766029 . Registered on 3 September 2020.

Coordination Polymer-Coated CaCO3 Reinforces Radiotherapy by Reprogramming the Immunosuppressive Metabolic Microenvironment.

Radiotherapy is widely exploited for the treatment of a large range of cancers in clinic, but its therapeutic effectiveness is seriously crippled by the tumor immunosuppression, mainly driven by the altered metabolism of cancer cells. Here, a pH-responsive nanomedicine is prepared by coating calcium carbonate (CaCO3 ) nanoparticles with 4-phenylimidazole (4PI), an inhibitor against indoleamine 2,3-dioxygenase 1 (IDO-1), together with zinc ions via the coordination reaction, aiming at reinforcing the treatment outcome of radiotherapy. The obtained pH-responsive nanomedicine, coined as acidity-IDO1-modulation nanoparticles (AIM NPs), is able to instantly neutralize protons, and release 4PI to suppress the IDO1-mediated production of kynurenine (Kyn) upon tumor accumulation. As a result, treatment with AIM NPs can remarkably enhance the therapeutic efficacy of radiotherapy against both murine CT26 and 4T1 tumors by eliciting potent antitumor immunity. Furthermore, it is shown that such combination treatment can effectively suppress the growth of untreated distant tumors via the abscopal effect, and result in immune memory responses to reject rechallenged tumors. This work highlights a novel strategy of simultaneous tumor acidity neutralization and IDO1 inhibition to potentiate radiotherapy, with great promises to suppress tumor metastasis and recurrence by eliciting robust antitumor immunity.

Effects of lanthanum carbonate and calcium carbonate on cardiovascular calcification in hemodialysis patients: A systematic review and meta-analysis.

OBJECTIVE: This paper was written to systematically review and meta-analyze the evidence on the efficacy of lanthanum carbonate (LC) and calcium carbonate (CC) and the risk of cardiovascular calcification on hemodialysis (HD) patients. MATERIALS AND METHODS: The Cochrane library, PubMed, Web of Science, Chinese journal full-text database (CNKI), WANGFANG DATA, and Sino Med were searched between January 1946 and December 2020. The literature with respect to the randomized controlled clinical trial comparing LC and CC in HD patients was selected. The main outcomes include coronary artery calcification score (CACS), cardiovascular events, and serum phosphorus (mmol/L). The statistical program used for meta-analysis was Stata V14.0. RESULTS: Of 388 original titles screened, data was extracted from 9 studies (625 participants). LC can significantly reduce the progression of coronary artery calcification compared to CC (standardized mean deviation (SMD) = -0.59, 95% CI: -0.94 to -0.25, p < 0.01). The LC group had lower serum phosphorus levels (SMD = -1.35, 95% CI: -2.33 to -0.36, p < 0.01), lower serum calcium levels (SMD = -1.03, 95% CI: -1.83 to -0.23, p = 0.012), and lower fibroblast growth factor 23 (FGF-23) level (SMD = -4.80, 95% CI: -7.96 to -1.64, p = 0.003) than the CC group. The Egger regression test of CACS showed no potential publication bias (p = 0.72). CONCLUSION: Compared with CC, LC can significantly delay the process of coronary artery calcification, and at the same time reduce patients' serum phosphate, serum calcium, and FGF-23. Therefore, we recommend LC as a phosphorus-lowering drug for HD patients.

Effect of lanthanum carbonate on the progression of coronary artery calcification in hemodialysis patients: A meta-analysis of randomized controlled trials.

INTRODUCTION: Coronary artery calcification and cardiac abnormalities are common in hemodialysis patients. The value of lanthanum carbonate over calcium-based phosphate binders in managing the progression of coronary artery calcification is debated. We reviewed all randomized controlled trials (RCTs) comparing the two strategies in these patients. METHODS: RCTs comparing lanthanum carbonate with calcium-based phosphate binders used in adult hemodialysis patients were identified in the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal, and Wanfang databases. FINDINGS: Ten RCTs involving 687 patients were suitable for inclusion. Compared with calcium-based phosphate binders, lanthanum carbonate yielded lower coronary artery calcium scores (weighted mean difference, WMD: -74.28, 95% CI: -149.89, 1.33), change in coronary artery calcium scores (WMD: -105.18, 95% CI: -113.83, -96.53), and left ventricular mass index (WMD: -29.95, 95% CI: -54.25, -7.45). Lanthanum carbonate was significantly associated with lower levels of serum phosphate (WMD: -0.18, 95% CI: -0.26, -0.10), calcium (WMD: -0.22, 95% CI: -0.25, -0.20), and fibroblast growth factor 23 (FGF23) (standard mean difference: -3.78, 95% CI: -5.60, -1.96) but not intact parathyroid hormone (WMD: -4.23, 95% CI: -64.12, 55.65). Moreover, a reduced risk of nonfatal cardiovascular events (OR: 0.31, 95% CI: 0.10-0.97) but not all-cause mortality (OR: 1.08, 95% CI: 0.39-3.01) in lanthanum carbonate therapy was observed. DISCUSSION: In hemodialysis patients, lanthanum carbonate therapy may impede the progression of coronary artery calcification and left ventricular mass index and lead to reduced serum phosphate, calcium, FGF23, and nonfatal cardiovascular events compared with calcium-based phosphate binders. However, more well-designed RCTs are required for confirmation.

Calcium carbonate-enriched cheese to improve nutrition, compliance and phosphorus control in patients on kidney replacement therapy.

BACKGROUND: Patients on renal replacement therapy face many dietary limitations, and cheese is often limited because of its high phosphate content; we have developed cheese with added calcium carbonate (CaCO3) to provide patients with a nutritional opportunity while improving their phosphate control. METHODS: The present double-blind crossover study was aimed to compare the new modified cheese with an equivalent standard product in 16 patients. The increase in inter-dialysis phosphorus (ΔP) and pre-dialysis calcium were used as the primary endpoints for efficacy and safety. RESULTS: The median ΔP (and IQR) was significantly lower with the modified cheese compared with the standard product: 2.5 (1.9-2.9) mg/dL vs. 2.7 (2.2-3.4) mg/dL, respectively (p < 0.02). No difference was observed in pre-dialysis serum calcium levels. CONCLUSIONS: The described modified cheese may represent an interesting means of overcoming some of the dietary limitations in patients on dialysis to help them achieve better nutrition and quality of life.

Colchicine-Containing Nanoparticles Attenuates Acute Myocardial Infarction Injury by Inhibiting Inflammation.

PURPOSE: Anti-inflammatory therapy is important for reducing myocardial injury after acute myocardial infarction (MI). New anti-inflammatory drugs and their mechanism are necessary to be explored to improve clinical efficacy. We aimed to improve the efficacy of colchicine on attenuating MI injury by nano-drug delivery systems and to investigate the mechanism of anti-inflammatory. METHODS: A colchicine-containing delivery system based on calcium carbonate nanoparticles (ColCaNPs) was synthesized. The protection against MI by ColCaNPs was evaluated using an in vivo rat model established by ligating the left anterior descending coronary artery. Macrophage polarization and the levels of inflammatory cytokines were determined using immunohistochemistry, Western blot, and ELISA analysis. RESULTS: ColCaNP treatment showed about a 45% reduction in myocardial infarct size and attenuating myocardial fibrosis compared with groups without drug intervention after MI. Furthermore, ColCaNPs significantly decreased the levels of CRP, TNF-α, and IL-1ß in serum and the expression of proinflammatory cytokine in myocardial tissues after MI (p < 0.05). We also found that ColCaNPs notably restrained pyroptosis and inhibited inflammatory response by modulating on M1/M2 macrophage polarization and suppressing TLR4/NFκB/NLRP3 signal pathway. CONCLUSION: Colchicine-containing nanoparticles can protect against MI injury in a clinically relevant rat model by reducing inflammation. In addition, calcium carbonate nanoparticles can increase the cardioprotective effects of colchicine.

Investigating the Preventive Effects of 99Tc-Methylenediphosphonate on a Glucocorticoid-Induced Osteoporosis Rabbit Model.

BACKGROUND AND OBJECTIVE: Osteoporosis is a worldwide healthcare challenge. Conventional medications for osteoporosis prevention are not clinically effective or associated with gastrointestinal tract adverse effects. The present study aimed to comparatively investigate the effects of technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) and calcium carbonate and alendronate on the prevention and treatment of osteoporosis in glucocorticoid-induced osteoporosis rabbit model through evaluating bone alkaline phosphatase (B-ALP), TRAP-5b levels and histopathological parameters. METHODS: Forty healthy female New Zealand rabbits were randomly divided into five groups (each n=8), including control group (Control Group), osteoporosis model group (GIO Group), osteoporosis model + 99Tc-MDP group (99Tc-MDP Group), osteoporosis model + alendronate group (Alendronate Group), and osteoporosis model + calcium carbonate group (calcium carbonate Group). Animals in each group were treated with corresponding interventions for 14 weeks. The blood samples were collected at the first and 14th week, and B-ALP and TRAP-5b levels were detected by enzyme- linked immunosorbent assay (ELISA). The rabbits were anesthetized at the 14th week, and pathological cytological observation was performed on both femurs. RESULTS: The age and weights of rabbits in different groups had no statistically significant differences (P>0.05). B-ALP levels in serum of all groups except for the Control Group decreased after treatment, but the differences were not statistically significant (P>0.05). TRAP-5b levels in serum of all groups increased after treatment. Specifically, differences in the GIO Group and calcium carbonate group were statistically significant (P<0.05), while differences in 99Tc-MDP Group and alendronate Group were not statistically significant (P<0.05). Pathological sections revealed that the control group presented normal bone tissue morphology. The bone tissue morphology of the 99Tc- MDP group and alendronate group was similar to control group and GIO group. Moreover, the calcium carbonate group and GIO group exhibited similar bone tissue morphology. CONCLUSION: 99Tc-MDP has a preventive effect on the glucocorticoid-induced osteoporotic rabbit model. This osteoporosis preventive effect might be attributed to the capacities of 99Tc-MDP in promoting the osteoblasts generation and inhibiting the generation and reducing the activity of osteoclasts.

Tumor-killing nanoreactors fueled by tumor debris can enhance radiofrequency ablation therapy and boost antitumor immune responses.

Radiofrequency ablation (RFA) is clinically adopted to destruct solid tumors, but is often incapable of completely ablating large tumors and those with multiple metastatic sites. Here we develop a CaCO3-assisted double emulsion method to encapsulate lipoxidase and hemin with poly(lactic-co-glycolic acid) (PLGA) to enhance RFA. We show the HLCaP nanoreactors (NRs) with pH-dependent catalytic capacity can continuously produce cytotoxic lipid radicals via the lipid peroxidation chain reaction using cancer cell debris as the fuel. Upon being fixed inside the residual tumors post RFA, HLCaP NRs exhibit a suppression effect on residual tumors in mice and rabbits by triggering ferroptosis. Moreover, treatment with HLCaP NRs post RFA can prime antitumor immunity to effectively suppress the growth of both residual and metastatic tumors, also in combination with immune checkpoint blockade. This work highlights that tumor-debris-fueled nanoreactors can benefit RFA by inhibiting tumor recurrence and preventing tumor metastasis.