Calcium (Carbonate)

OBJECTIVE: This study aims to determine whether preoperative supplementation of vitamin D reduces the incidence of hypocalcemia following total thyroidectomy. METHODS: Conducted in conformity with the PRISMA statement, a systematic review and meta-analysis of randomized clinical trials (RCT) was performed assessing postoperative hypocalcemia and postoperative symptomatic hypocalcemia. RESULTS: The search strategy yielded 3808 potentially relevant publications, with eight RCTs ultimately included. These eight trials included a total of 902 patients (22.73% male, n = 205/902), with a median age of 48.9 years (95% CI, 43.5-53.5). Four trials administered only vitamin D in the interventional arm, three trials administered both calcium and vitamin D in the interventional arm, and one trial administered vitamin D in the interventional arm and calcium in both arms. Pooled results from the eight included trials showed a reduced risk of postoperative hypocalcemia in the intervention arm (RR, 0.77; 95% CI, 0.62-0.96; p = 0.02). When excluding the studies that administered calcium supplements in addition to vitamin D, the pooled results showed a similar reduced risk of postoperative hypocalcemia (RR, 0.74; 95% CI, 0.57-0.96; p = 0.03). Analysis of six trials reporting the incidence of postoperative symptomatic hypocalcemia (n = 564) showed a reduced risk in the vitamin D arm, with or without calcium, compared to the control arm (RR, 0.56; 95% CI, 0.34-0.93; p = 0.023). CONCLUSIONS: Our findings suggest that preoperative vitamin D administration, with or without calcium carbonate, significantly reduces the risk of postoperative hypocalcemia and symptomatic hypocalcemia in patients undergoing total thyroidectomy. © 2025 Wiley Periodicals LLC.

BACKGROUND: Skeletal muscle cramps are common and often occur in association with pregnancy, advanced age, exercise or motor neuron disorders (such as amyotrophic lateral sclerosis). Typically, such cramps have no obvious underlying pathology, and so are termed idiopathic. Magnesium supplements are marketed for the prophylaxis of cramps but the efficacy of magnesium for this purpose remains unclear. This is an update of a Cochrane Review first published in 2012, and performed to identify and incorporate more recent studies. OBJECTIVES: To assess the effects of magnesium supplementation compared to no treatment, placebo control or other cramp therapies in people with skeletal muscle cramps. SEARCH METHODS: On 9 September 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, CINAHL Plus, AMED, and SPORTDiscus. We also searched WHO-ICTRP and ClinicalTrials.gov for registered trials that might be ongoing or unpublished, and ISI Web of Science for studies citing the studies included in this review. SELECTION CRITERIA: Randomized controlled trials (RCTs) of magnesium supplementation (in any form) to prevent skeletal muscle cramps in any patient group (i.e. all clinical presentations of cramp). We considered comparisons of magnesium with no treatment, placebo control, or other therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Two review authors assessed risk of bias. We attempted to contact all study authors when questions arose and obtained participant-level data for four of the included trials, one of which was unpublished. We collected all data on adverse effects from the included RCTs. MAIN RESULTS: We identified 11 trials (nine parallel-group, two cross-over) enrolling a total of 735 individuals, amongst whom 118 cross-over participants additionally served as their own controls. Five trials enrolled women with pregnancy-associated leg cramps (408 participants) and five trials enrolled people with idiopathic cramps (271 participants, with 118 additionally crossed over to control). Another study enrolled 29 people with liver cirrhosis, only some of

OBJECTIVES: A number of studies have hypothesized that vitamin D is a potential factor in the prevention of falls in the elderly; however, the effect of vitamin D is still inconsistent and not quantitative. We conducted this meta-analysis to assess the effect of vitamin D on falls among elderly individuals. METHODS: The PubMed and Cochrane Library databases were searched from the earliest possible year up to December 2016. Two authors working independently reviewed the trials, and odds ratios (ORs) were calculated using a fixed-effect or random-effect model by Review Manager 5.3. We included only double-blind randomized, controlled trials (RCTs) of vitamin D in elderly populations that examined fall results. RESULTS: A total of 26 articles were included in which 16,540 elderly individuals received vitamin D supplementation, while 16,146 were assigned to control groups. The meta-analysis showed that combined vitamin D plus calcium supplementation has a significant effect on the reduction in the risk of falls (OR for the risk of suffering at least one fall, 0.87; 95% CI, 0.80-0.94). However, no significant association between vitamin D2 or D3 and a reduction in the risk of falls was found (OR, 0.77; 95% CI, 0.58-1.03 for vitamin D2, and OR, 1.08; 95% CI, 0.98-1.20 for vitamin D3). CONCLUSIONS: Combined calcium plus vitamin D supplementation is statistically significantly associated with a reduction in fall risks across various populations.

AIMS: Researchers are commonly requested to describe potential benefits of their research for New Zealand in funding applications, but such benefits can be difficult to precisely determine. Recently, we reported that calcium supplements increase cardiovascular risk. We investigated the impact of this research on prescriptions of calcium supplements in New Zealand. METHODS: Data on the number of calcium supplement prescriptions in New Zealand from 2000-2012 were obtained from the Ministry of Health and the total costs of calcium carbonate from PHARMAC. RESULTS: Calcium prescriptions increased rapidly between 2000 and 2007, plateaued after the publication of a randomised controlled trial in 2008, and then rapidly declined after publication of a meta-analysis in 2010. Since 2007, monthly prescriptions have decreased by 66%. From 2000 to 2006, the annual cost of calcium carbonate increased from $1.2 to $2.4 million, but from 2007 to 2012, the annual cost decreased by $1.5 million, with a cumulative reduction in cost of $3.9 million. There were substantial regional variations in declines in prescription numbers, and in 2012 prescribing rates. CONCLUSION: Public-good funding of independent researchers to conduct randomised clinical trials with meaningful clinical outcomes and meta-analyses of such trials can translate into substantial benefits through cost savings.

OBJECTIVE: There is increasing evidence to suggest that ossein-hydroxyapatite complex (OHC) is more effective than calcium supplements in maintaining bone mass. The aim of this meta-analysis was to determine whether OHC has a different clinical effect on bone mineral density (BMD) compared with calcium carbonate (CC). METHODS: A meta-analysis of randomized controlled clinical trials was carried out to evaluate the efficacy of OHC versus CC on trabecular BMD. We identified publications on clinical trials by a search of electronic databases, including MEDLINE (1966-November 2008), EMBASE (1974-November 2008), and the Cochrane Controlled Clinical Trials Register.The primary endpoint was percent change in BMD from baseline. Data were pooled in a random-effects model, and the weighted mean difference was calculated. A sensitivity analysis that excluded trials without full data was performed. RESULTS: Of the 18 controlled trials initially identified, 6 were included in the meta-analysis. There was no significant heterogeneity among the included trials. The percent change in BMD significantly favored the OHC group (1.02% [95% CI, 0.63-1.41], P < 0.00001). These results were confirmed in the sensitivity analysis. CONCLUSIONS: OHC is significantly more effective in preventing bone loss than CC.

OBJECTIVE: To perform a meta-analysis of data from available published trials comparing the bioavailability of calcium carbonate with that of calcium citrate. DATA SOURCES: The whole set was comprised of 15 studies involving 184 subjects who underwent measurement of calcium absorption from calcium carbonate and calcium citrate. Category A excluded four studies for lack of physiological relevance, use of a mixed preparation with low content of calcium carbonate, or wide variability in results. Category B was comprised of five studies (from Category A) involving 71 subjects who took calcium supplements on an empty stomach. Category C was comprised of six studies (from Category A) involving 65 subjects who took calcium preparations with meals. METHOD: The meta-analysis of calcium absorption data from calcium carbonate and calcium citrate, with calculation of effect size and 95% confidence intervals. RESULTS: Calcium absorption from calcium citrate was consistently significantly higher than that from calcium carbonate by 20.0% in the whole set, by 24.0% in Category A, by 27.2% on an empty stomach, and by 21.6% with meals. CONCLUSION: Calcium citrate is better absorbed than calcium carbonate by approximately 22% to 27%, either on an empty stomach or co-administered with meals.

OBJECTIVE: To review the effect of supplemental calcium on blood pressure. DATA SOURCE: We searched MEDLINE and EMBASE for 1996 to May 1994. We contacted authors of eligible trials to ensure accuracy and completeness of data and to identify unpublished trials. STUDY SELECTION: We included any study in which investigators randomized people to calcium supplementation or placebo and measured blood pressure for at least 2 weeks. Fifty-six articles met the inclusion criteria, and 33 were eligible for analysis, involving a total of 2412 patients. DATA EXTRACTION: Two pairs of independent reviewers abstracted data and assessed validity according to six quality criteria. DATA SYNTHESIS: We calculated the differences in blood pressure change between the calcium supplementation group and the control group and pooled the estimates, with each trial weighted with the inverse of the variance using a random-effects model. Predictors of blood pressure reduction that we examined included method of supplementation, baseline blood pressure, and the methodological quality of the studies. The pooled analysis showed a reduction in systolic blood pressure of -1.27 mm Hg (95% confidence interval [CI], -2.25 to -0.29 mm Hg; P=.01) and in diastolic blood pressure of -0.24 mm Hg (95% CI, -0.92 to 0.44 mm Hg; P=.49). None of the possible mediators of blood pressure reduction explained differences in treatment effects. CONCLUSIONS: Calcium supplementation may lead to a small reduction in systolic but not diastolic blood pressure. The results do not exclude a larger, important effect of calcium on blood pressure in subpopulations. In particular, further studies should address the hypothesis that inadequate calcium intake is associated with increased blood pressure that can be corrected with calcium supplementation.

BACKGROUND: Transient hypoparathyroidism is a common complication after total thyroidectomy, prolonging hospitalization and necessitating calcium and/or vitamin D replacement. Evidence from prospective randomized trials on preventive supplementation remains limited. This study aimed to evaluate whether prophylactic calcium and vitamin D supplementation reduces transient hypoparathyroidism and shortens hospital stay after total thyroidectomy. METHODS: In this single-center, prospective, randomized, controlled, open-label trial, 600 patients undergoing total thyroidectomy without central neck dissection were randomized to receive prophylactic oral calcium carbonate/gluconate and alfacalcidol (group A, n = 300) or standard postoperative care (group B, n = 300). Primary outcomes were biochemical and symptomatic hypocalcemia and the need for intravenous calcium. Secondary outcomes included postoperative serum calcium levels and length of hospital stay. Statistical analyses used χ2, Student's t test, Mann-Whitney U test, and odds ratio and 95% confidence interval. RESULTS: Laboratory hypocalcemia (serum calcium <8.5 mg/dL) occurred significantly less often in group A (16.9% vs 39.9%; odds ratio 0.305, 95% confidence interval 0.207-0.451, P < .001). Symptomatic hypocalcemia was also reduced (5.6% vs 12.3%; odds ratio 0.427, 95% confidence interval 0.232-0.785, P < .005), as was the need for intravenous calcium (1.8% vs 9.3%; odds ratio 0.175, 95% confidence interval 0.070-0.441, P < .001). Group A demonstrated higher mean serum calcium levels on postoperative days 1 and 2 (P < .001) and a shorter hospital stay (1.25 days vs 1.7 days, P < .001). Supplementation benefits were consistent across subgroups stratified by malignancy status and preoperative vitamin D levels. CONCLUSION: Routine calcium and vitamin D supplementation after total thyroidectomy significantly reduces transient hypoparathyroidism and shortens hospitalization. These findings support its use as a standard postoperative strategy to enhance recovery and reduce health care resource utilization.

BACKGROUND: HIV has adverse impact on skeletal development in children despite antiretroviral therapy (ART). We investigated the effect of high-dose (20 000 IU) weekly vitamin D3 and daily calcium carbonate (500 mg) supplementation for 48 weeks on bone density and muscle strength and power among peripubertal individuals (11-19 years) with perinatally acquired HIV. METHODS: We conducted an individually randomised, double-blind, placebo-controlled trial. Individuals taking ART for at least 6 months who had a defined caregiver, and knew their HIV status (in those aged >12 years) were recruited from HIV clinics in Harare, Zimbabwe and Lusaka, Zambia. The primary outcome was total body less-head bone mineral density (TBLH-BMD) Z score and secondary outcome was lumbar spine bone mineral apparent density (LS-BMAD) Z score (both measured by dual-energy x-ray absorptiometry). Linear regression was used to compare arms adjusting for country and baseline value of the measure. Pre-specified subgroup analyses by country, age-group, sex, pubertal stage, calcium intake, tenofovir disproxil fumarate use, and baseline vitamin D insufficiency (defined as 25[OH]D <75 nmol/L), and a post-hoc subgroup analysis by viral suppression, were performed. A Participant Advisory Board that included adolescents with HIV, their guardians, and health providers guided study conduct. The trial is registered with the Pan African Clinical Trials Registry, PACTR20200989766029. FINDINGS: Of 842 participants (median age 15 years [IQR 13-17], 448 [53%] female and 394 [47%] male) enrolled between Feb 4 to Nov 23, 2021, 639 (76%) were vitamin D insufficient. At 48 weeks, outcomes were available for 751 (89%) participants. There was no difference by arm in TBLH-BMD Z score (intervention vs control: mean -1·53 [SD 1·18] vs -1·56 [1·12], adjusted mean difference -0·04 [95% CI -0·01 to 0·09]) or in LS-BMAD Z score (intervention vs control: -0·64 [1·17] vs -0·71 [SD 1·16], adjusted mean difference -0·05 [95% CI -0·01 to 0·12]). However, among participants with vitamin D insufficiency at baseline, there was a significantly higher LS-BMAD Z score (adjusted mean difference 0·09 [95% CI 0·02 to 0·16], pinteractio

OBJECTIVE: Postoperative hypocalcemia and hypoparathyroidism are common complications after thyroidectomy, often impairing quality of life (QoL). This study investigates the impact of preoperative calcium and magnesium supplementation on postoperative QoL and hypocalcemia in patients undergoing total thyroidectomy for symptomatic nodular goitre or Graves' disease. METHODS: A total of 62 patients undergoing thyroidectomy for benign thyroid diseases were randomised into two groups. The intervention group (IG, n = 31) received 500 mg calcium carbonate thrice daily and 300 mg magnesium carbonate once daily for 2 weeks preoperatively, while the control group (CG, n = 31) received no supplementation. Laboratory parameters (Ca, Mg, PTH, 25-OH-Vitamin D) were measured at study enrolment (T1), preoperatively (T2), immediately postoperatively (T3) and 6 weeks post-discharge (T4). QoL was assessed using EQ-5D and ThyPro39de questionnaires. RESULTS: QoL significantly improved postoperatively in both groups. Patients with Graves' disease in the IG reported earlier QoL improvements immediately post-surgery (T3). Postoperative hypocalcemia occurred in 19.4% of IG patients and 25% of CG patients, with hypoparathyroidism in 16% and 23%, respectively. The IG demonstrated higher postoperative calcium levels and fewer hypocalcemia symptoms, especially in Graves' disease patients (not significant). Vitamin D deficiency was prevalent (66.7%) but showed no correlation with hypocalcemia. DISCUSSION: Preoperative calcium and magnesium supplementation might have positive effects on postoperative QoL, especially in Graves' disease patients, and may reduce hypocalcemia symptoms. This simple, inexpensive and low-risk intervention may be beneficial in the preoperative setting prior to thyroidectomy. Although the observed effect did not reach statistical significance, it could still be of clinical relevance. The additional benefit of preoperative magnesium supplementation seems to be of minor significance, while the effect of pre-existing vitamin D deficiency remains uncertain. © 2025 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.

Beneficial adaptations to exercise depend on the normal function of the endocrine system. Whether commonly prescribed antihypertensive medication inhibits erythropoietin (EPO) production with exercise, a key response to enhance aerobic capacity, remains unknown. Healthy adults (n = 63, 42.3 ± 16.5 yr, 52% ♀) matched by age, sex, and physical activity were randomized in a blinded and crossover manner to orally ingest valsartan (angiotensin II type 1 receptor-blockade, AT1-blockade) or placebo (calcium carbonate, PBO) 4 h before starting the experimental protocol. Before and after 1 h of moderate cycling exercise, blood samples were taken to measure circulating EPO and EPO-regulating hormones along with blood pressure. Cardiac structure/function and peak pulmonary O2 consumption (VO2peak) were assessed during exercise. AT1-blockade decreased heart volumes (left atrium and ventricle) during exercise compared with PBO, particularly in men (P ≤ 0.036). Whole-body O2 extraction and VO2peak were unaffected by AT1-blockade irrespective of sex (P ≥ 0.325). Before and after exercise, AT1-blockade reduced arterial blood pressures (systolic, diastolic) in both sexes (P < 0.001). A condition × time interaction was detected for circulating EPO (P = 0.002), such that AT1-blockade decreased EPO at 3-h post-exercise compared with PBO (P ≤ 0.025). The effect of exercise on EPO-regulating hormones (angiotensin II, aldosterone, copeptin) was diminished with AT1-blockade. Sex per se did not influence the endocrine response to AT1-blockade. In conclusion, in a randomized, double-blind and placebo-controlled study design, AT1-blockade abolishes the acute EPO response to exercise in women and men. Antihypertensive medications hindering AT1 signaling may restrict key endocrine responses to exercise. © The Author(s) 2025. Published by Oxford University Press on behalf of American Physiological Society.

BACKGROUND: The aim of the study was to provide a gender-based analysis of the results of a large, multi-centre randomized controlled trial (RCT) comparing a novel cell-free aragonite-based scaffold with the standard of care (i.e. debridement/microfractures) for the treatment of chondral/osteochondral defects in knees with or without concurrent osteoarthritis. MATERIALS AND METHODS: A total of 251 patients were included: 167 patients in the scaffold group and 84 in the control. In the scaffold group, there were 105 males and 59 females, whereas the control group consisted of 51 males and 32 females. Patients were evaluated up to 48 months after the treatment. The primary endpoint was the change from baseline to 48 months in the KOOS overall score. Treatment failures were defined as any secondary invasive intervention, including intra-articular injection or any surgery in the treated joint. All patients underwent magnetic resonance imaging (MRI) at 12 and 24 months to assess the percentage of defect fill after surgery. RESULTS: Both males and females in the scaffold group achieved significantly better results than controls in any KOOS subscale, as well as in KOOS overall, up to the final 48 months follow-up. Outcomes reported by females were non-inferior to those of males in the implant group. At 24 months' MRI evaluation, 86.2% of male patients in the scaffold group presented at least 75% defect fill compared with 32.6% in the control group. In the scaffold group, 87.6% of female patients presented at least 75% defect fill, compared with 28% in the control group (p < 0.0001 in both cases). Responders' rate and failure rate were also significantly better in the scaffold group for both males and females. CONCLUSION: The aragonite scaffold outperformed the control group at 48 months' evaluation. The gender-based analysis proved that males and females in the scaffold group presented comparable clinical and radiographical results, both significantly better than their counterparts treated by debridement/microfractures. LEVEL OF EVIDENCE: I-Randomized controlled trial. TRIAL REGISTRATION: Clinicaltrial.gov ID: NCT03299959 (registered on 14 September 2017). © 2025. The

OBJECTIVE: To investigate the effectiveness and safety of combining zoledronic acid with calcium supplements and calcitriol in treating primary osteoporosis in elderly patients. METHODS: Seventy-eight elderly patients with primary osteoporosis were recruited. They were randomly assigned in a 1:1 ratio to either the CC group (calcium carbonate D3 tablets + calcitriol soft capsules) or the CCZ group (calcium carbonate D3 tablets + calcitriol soft capsules + zoledronic acid injection). The treatment duration was 1 year. Bone mineral density (BMD), bone metabolism markers, quality of life (QoL), clinical efficacy, and incidence of adverse reactions (ARs) were assessed. RESULTS: CCZ group showed increased BMD in the lumbar spine (L1~L4 segments), femoral neck, and hip after treatment relative to CC group. Serum levels of bone-specific alkaline phosphatase, cross-linked type 1 collagen C-terminal peptide, and N-terminal propeptide of type 1 procollagen decreased, while osteocalcin levels increased. The QoL Questionnaire of the European Foundation for Osteoporosis scores decreased (P < 0.05 for all comparisons). The clinical effective rates were 76.93% in the CC group and 92.31% in the CCZ group, with AR rates of 23.08% and 12.82%, respectively (P < 0.05 for both). CONCLUSION: Zoledronic acid treatment in elderly patients with primary osteoporosis demonstrates significant efficacy by increasing bone density, improving bone metabolism, enhancing QoL, and exhibiting high safety. © 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

BACKGROUND/OBJECTIVES: Facial bone density, including the jawbone, declines earlier than that of the lumbar spine and calcaneus. Calcium maltobionate is reported to mitigate bone resorption and maintain bone density of the lumbar spine in post-menopausal women, but its effects on facial bone density remain understudied. Therefore, this study compared variations in facial bone mineral density with variations in calcaneal bone mineral density and bone resorption markers among healthy women, examining differences between pre- and post-menopause and the effects of continuous calcium maltobionate intake. METHODS: This randomized, double-blind, placebo-controlled, parallel-group trial involved 48 healthy Japanese women aged 30-69 years, divided into two groups. The test food group received tablets containing calcium maltobionate, while the placebo group received tablets containing a maltose and calcium carbonate mixture for 24 weeks. Calcaneal and facial bone densities were measured pre- and post-intervention in both groups. RESULTS: Post-intervention calcaneal bone mineral density and bone resorption marker deoxypyridinoline (DPD) showed no statistical difference between groups in pre-menopausal women. However, in post-menopausal women, the test food group exhibited significantly higher calcaneal bone density and lower DPD levels compared with the placebo group. Facial bone mineral density increased significantly in the test food group compared with the placebo group in post-menopausal participants, with similar trends observed in pre-menopausal participants. CONCLUSIONS: Facial bone mineral density could serve as a useful indicator for monitoring bone health from middle age onward. Moreover, continuous calcium maltobionate intake appears to mitigate bone density decline in pre- and post-menopausal women, contributing to osteoporosis prevention (UMIN-CTR ID: 000046391).

OBJECTIVE: This study compared the efficacy of calcium (Ca) citrate and Ca carbonate supplementation on Ca absorption following Roux-en-Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG), and one-anastomosis gastric bypass (OAGB) surgeries. SETTING: A single specialized bariatric center. METHODS: A randomized, double-blinded, crossover study between October 2023 and February 2024. One hundred fifty participants 6 months postmetabolic bariatric surgery (MBS) were randomly selected from the electronic patient record system to create a pool of patients to randomize for the study. The intestinal absorption of Ca carbonate and Ca citrate among groups divided by surgical procedure was compared over 8 hours of testing. Measurements included serum and urine Ca concentrations for peak values (Cmax) and area under the curve (AUC0-8h), along with parathyroid hormone (PTH) levels to calculate minimum PTH (PTHmin) and cumulative PTH decline (AUC0-8h). RESULTS: In total, 50 per each surgery group were included with an average age of 40.5 ± 7.6 years, of whom 128 (85.3%) were female. The participants' average BMI was 30.3 ± 2.0 kg/m2. The average time elapsed after MBS was 9.8 ± 1.0 months. Ca citrate intake significantly lowered PTH levels and showed enhanced relative Ca bioavailability compared to Ca carbonate. Specifically, PTH levels were notably reduced from 3 to 6 hours postadministration with Ca citrate, with significant differences (P < .001). Ca citrate also demonstrated superior relative bioavailability, as evidenced by a higher AUC0-8h of 76.1 mg/dL·h versus 74.7 mg/dL·h for carbonate (P = .001) and a Cmax of 9.8 mg/dL compared to 9.5 mg/dL for carbonate (P < .001). Additionally, urinary Ca excretion over 9 hours was significantly greater in the citrate group at 83.7 mg/dL compared to 68.6 mg/dL for carbonate (P < .001). CONCLUSION: The study demonstrates that Ca citrate was significantly better than carbonate in reducing PTH levels, enhancing relative Ca bioavailability, and increasing urinary Ca excretion. Additionally, Ca citrate resulted in higher cumulative urinary Ca excretion, indicating better Ca absorption.

The study aimed at analyzing the therapeutic effect of salmon calcitonin on patients with lumbar spine fracture after operation. Eighty-eight cases with lumbar spine fracture who underwent percutaneous vertebroplasty (PVP) in The Huichang People's Hospital from February 2020 to February 2023 were separated into two groups. The 44 cases in the control group were treated with calcium carbonate and Vitamin D3 tablets, on the basis, the salmon calcitonin was applied to treat the 44 cases in study group. The pain degree, bone metabolism index and matrix metalloproteinase levels were determined and compared between two groups. Lumbar function and daily living activity ability in two groups were evaluated, and adverse reactions during treatment were observed. The pain degree in study group was alleviated after treatment for 3 mo compared with the control group (p<0.05). The bone specific alkaline phosphatase (BALP) and osteocalcin (OC) levels were increased, while beta C-terminal cross-linked telopeptides of type I collagen (β-CTX) levels were decreased in study group after treatment for 3 mo compared with control group (p<0.05). After treatment for 3 mo, the serum matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) levels in study group were lower than those in control group (p<0.05). Three months after treatment, the Oswestry Disability Index (ODI) score was lower and Barthel Index (BI) score was higher in study group than those of control group (p<0.05). No severe adverse reactions were observed in both groups during treatment (p>0.05). Salmon calcitonin can relieve the pain degree, improve the levels of bone metabolism and matrix metalloproteinase, and improve the lumbar spine function and ability of daily living activity in patients with lumbar spine fracture.

INTRODUCTION: The aim of this study was to analyze the effectiveness of acupuncture as an early intervention in the treatment of osteoporosis and prevention of osteoporosis. METHODS: This multicenter, randomized, controlled clinical trial was conducted in 226 patients with osteoporosis for 6 months. Participants were randomized to the control group (n = 110) and the acupuncture group (n = 116), both groups received basic treatment with daily calcium carbonate and vitamin D3 tablet (containing calcium 600 mg/tablet) supplementation (n = 116), and the acupuncture group received additional acupuncture treatment. Bone mineral density (BMD), Berg Balance Scale (BBS), bone metabolism indexes, and lower limb muscle strength and balance indexes were tested to evaluate the therapy outcomes of the two groups. RESULTS: After 6 months of treatment, BBS11 (p = 0.046), BBS12 (p = 0.042), and total BBS scores (p = 0) in the acupuncture group were significantly higher than those before treatment; comparing between groups, BBS8 in the acupuncture group was higher than that in the control group after 3 and 6 months, with statistically significant differences (p = 0.036 and 0.0270). After 6 months of treatment, the total BBS score of the acupuncture group was significantly higher than that of the control group, and the difference was statistically significant (p = 0.039). After 6 months of treatment, the BMD of total bone of femoral neck (p = 0.031) and hip joint (p = 0.013) in the acupuncture group was significantly higher than that before treatment, but there was no statistical difference with the control group. The time of five sit-to-stand test (FTSST) was shortened in the acupuncture group, and the difference was statistically significant (p = 0.023), but there was no significant change in the control group (p > 0.05). In addition, the specific sequences of blood phosphorus (p = 0.007), β-collagen (p = 0.009), and N-osteocalcin (p = 0.007) were significantly lower than before treatment after 3 months of acupuncture treatment, and the blood phosphorus level continued to decrease after 6 months of treatment (p = 0.007). In addition, the levels of N-osteocalcin in the acupunctur

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, with chemoresistance to 5-fluorouracil (5-FU) and dose-limiting toxicities posing major therapeutic challenges. This study investigates the synergistic potential of 5-FU combined with bioactive compounds from Polygonum minus (PM) extract and thymoquinone (TQ) in free and calcium carbonate (CaCO3)-nanoparticle-encapsulated forms (5-FU-CaCO₃, TQ-CaCO3) against SW480 and SW620 CRC cell lines. Cytotoxicity (MTT assay), combination index (CI), and apoptosis/necrosis (Annexin V/PI flow cytometry) were evaluated at 24 -72 h. Both free-drug (FTP: 5-FU+TQ+PM) and CaCO3-encapsulated (FT-NP/PM: 5-FU-CaCO3+TQ-CaCO3+PM) combinations exhibited dose- and time-dependent cytotoxicity in SW480 and SW620 cells. In SW620 cells, the encapsulated FT-NP/PM showed superior cytotoxicity compared to the free combination, with IC50 values decreasing from 11.75 µg/mL (24 h) to 6.70 µg/mL (72 h), whereas FTP declined from 17.75 µg/mL to 6.54 µg/mL. In SW480 cells, both formulations demonstrated comparable effects, maintaining cytotoxicity over time (FTP: 15.38-7.68 µg/mL; FT-NP/PM: 16.98-8.81 µg/mL). Combination index analysis confirmed strong synergism at lower concentrations (CI < 0.4) in both cell lines, with FT-NP/PM showing slightly greater synergy, particularly in SW620. Higher concentrations tended toward additive or antagonistic effects. Apoptosis and necrosis analyses further supported these results, where FT-NP/PM induced higher necrosis and late apoptosis compared to FTP, especially after 72 h in SW620 cells. In SW480, apoptosis remained the predominant mode of cell death, with nanoencapsulation sustaining the response over time. These findings underscore the therapeutic advantage of combining natural compounds with conventional chemotherapy. Overall, the synergistic interaction between 5-FU, TQ, and PM, enhanced by CaCO3-mediated delivery, improved cytotoxic and apoptotic effects, especially in the chemoresistant SW620 cells, suggesting the potential of FT-NP/PM as an optimized combination strategy for colorectal cancer treatment.

AIM: This study evaluated two novel combination therapies using 5-Fluorouracil (5-FU), Thymoquinone (TQ), and cockle shell - derived calcium carbonate nanoparticles (CaCO3 NPs) against HT-29 colorectal cancer (CRC) cells under hyperglycemic conditions. METHODS: 5-FU and TQ were successfully encapsulated into CaCO3 NPs through encapsulation at various drug-to-nanoparticle ratios. Physicochemical characterization was performed to confirm the morphology, and particle stability. Drug release studies assessed pH-responsive behavior, while biocompatibility was evaluated on NIH/3T3 cells. Cytotoxicity and cell cycle analyses were conducted on HT-29 cells under glycemic and hyperglycemic conditions. RESULTS: High encapsulation efficiency was achieved at a 1:5 drug-to-nanoparticle ratio while maintaining the aragonite structure and stable physicochemical properties. The nanoformulations exhibited pH-sensitive drug release with enhanced release at acidic pH (4.8), simulating the tumor microenvironment. Improved biocompatibility and reduced toxicity were observed in normal NIH/3T3 cells compared to free drugs. Both 5-FU:TQ-CaCO3 NPs and 5-FU-CaCO3 NPs:TQ combinations significantly inhibited HT-29 proliferation and induced G1 cell cycle arrest, especially under hyperglycemic conditions. Combination index analysis confirmed synergistic effects of both treatments. CONCLUSION: The findings suggest the potential therapeutic efficacy of 5-FU:TQ-CaCO3 NPs and 5-FU-CaCO3 NPs:TQ in treating CRC associated with hyperglycemia and demonstrate the capability of biogenic CaCO3 NPs to effectively deliver chemotherapeutic agents of different polarity with minimal toxicity.

The mechanism of action of integrase strand transfer inhibitors involves binding to magnesium ions in the active site of the HIV integrase enzyme, making them susceptible to chelation-type drug-drug interactions with metal cation-containing medications. This study evaluated the potential of metal cation-containing antacids and mineral supplements to impact bictegravir (BIC) exposure and assessed alternative approaches for combined use. This was an open-label, single-dose, Phase 1 study in adult participants without HIV. The pharmacokinetics and safety of BIC (administered as part of a single-tablet combination with emtricitabine [F] and tenofovir alafenamide [TAF; B/F/TAF]) were assessed when co-administered with maximum-strength aluminum/magnesium-containing antacid (referred to as "aluminum/magnesium-containing antacid"), calcium carbonate, or ferrous fumarate under fasted and fed conditions, and administered 2 hours before or after the antacid. Pharmacokinetic parameters were compared using analysis of variance to calculate geometric least-squares mean ratios and 90% confidence intervals. Forty-two participants were enrolled. BIC exposure (area under the plasma concentration-time curve extrapolated to infinity) was reduced by 79%, 33%, and 63%, respectively, when co-administered with aluminum/magnesium-containing antacid, calcium carbonate, and ferrous fumarate under fasted conditions. Co-administration of B/F/TAF with calcium carbonate or ferrous fumarate with a meal and administration of B/F/TAF 2 hours before the antacid reduced the impact of the interactions. B/F/TAF was well tolerated alone or in combination with metal cation-containing medications. Co-administration of BIC and calcium/iron-containing supplements with a meal and administration of BIC 2 hours or more before aluminum/magnesium-containing antacids are some of the effective strategies to mitigate chelation effects on BIC exposure.This study was registered at NCT05502341/NCT06333808.

The study was conducted to evaluate the prevalence of Drug-Drug Interactions (DDIs) of Azithromycin and its impact on patient mortality and microbial resistance during the first wave of COVID-19. The study was performed in tertiary care hospitals located in various areas of Karachi, Pakistan. A cross sectional retrospective study on a sample size of 300 patients was conducted (Jan - Dec 2020) on in-patients receiving Azithromycin as part of their therapeutic regimen. Data was collected using a structured and validated tool. The Medscape Drug Reference database was applied to assess the DDIs. The presence of DDIs was observed in 224 patients (75 %) involving 28 drugs with a total of 346 interactions. Among them, majority (60 %) were severe followed by moderate (33 %) and mild interactions (7 %). Among 300 patients, a total of 41 mortalities was observed with highest percentage (90%) in patients with drugs causing severe interactions i.e. enoxaparin and hydroxychloroquine. The moderate interaction group exhibited 10% mortality involving piperacillin. Additionally, out of 346 interactions, only one due to calcium carbonate was found to affect the bioavailability of azithromycin. Our data reveals the high prevalence of DDIs with Azithromycin during the first wave of COVID-19, which has most likely contributed towards the mortality.

Erratum in Eur J Pharmacol. 2025 Apr 15;993:177383. doi: 10.1016/j.ejphar.2025.177383. Pancreatic cancer (PCa) is one of the most devastating cancers with few clinical signs and no truly effective therapy. In recent years, our team has demonstrated that nucleolin antagonists such as N6L could be a therapeutic alternative for this disease. In order to study a possible clinic development of N6L (multivalent pseudopeptide), we undertook to study the effect of combination of N6L with chemotherapies classically used for PCa on the survival of pancreatic cancer cells. Thus, the combined effect of N6L with either gemcitabine, FOLFOX and paclitaxel (PTX) on the survival of PANC-1, Mia-PaCa-2 and BxPC3 was studied and shown additive effect. In addition, analysis of the data by Combenefit software indicates that there are synergistic effects between N6L and the 3 chemotherapy molecules tested with more sensitive effects with the N6L-PTX combination. This result was confirmed by associating N6L and paclitaxel on porous calcium carbonate particles loaded with cyclodextrin (CD) encapsulating PTX and carrying N6L at their surface. Porous calcium carbonate particles present highly benefits for biological purposes because of their large surface area and their high stability in neutral media. As for CD, it presents the advantage of owing hydrophilic exterior and a less polar cavity in the center. We have then combined the advantageous features of both porous and negatively charged surfaces of calcium carbonate (CaCO3) particles and host molecules CD for developing carrier enabling all at once the loading of PTX (hydrophobic drug) and N6L (cationic drug). This association generates water-soluble particles capable of targeting via N6L and delivering paclitaxel to tumor cells.

Fortimicins (FTMs) are fortamine-containing aminoglycoside antibiotics (AGAs) produced by M. olivasterospora DSM 43868 with excellent bactericidal activities against a wide range of Enterobacteriaceae and synergistic activity against multidrug-resistant (MDR) pathogens. Fortimicin-A (FTM-A), the most active member of FTMs, has the lowest susceptibility to inactivation by the aminoglycoside modifying enzymes (AMEs). Therefore, this study aimed to evaluate the antibacterial activity of FTM-A alone or in combination with other antibiotics against 18 non-clonal clinically relevant MDR Gram-positive and Gram-negative pathogens. This study also aimed to statistically optimize various environmental factors affecting its production using the response surface D-optimal design. Results showed that FTM-A/meropenem combination showed the highest synergistic bactericidal activity (61.1%) followed by its combination with cefotaxime and cefepime (38.8% each). However, FTM-A/gentamicin and FTM-A/doxycycline combinations showed mostly additive effects in 66.6% and 50% of the tested isolates, respectively. For FTM-A production optimization, maximum specific activity (µg/mg) to cell growth was achieved using aminoglycoside production medium followed by yeast extract-malt extract and M65 production medium. A D-optimal quadratic model consisting of 27 different media composition variations was used to predict an optimal composition for FTM-A production and verified experimentally. Lab verification of the model was carried out using HPLC analysis, resulting in a 10.5-fold increase in their production compared to the un-optimized conditions. The model revealed that the initial pH, incubation temperature, and incubation time significantly affected FTMs production (P-value < 0.05), however, the tested range of calcium carbonate 2-7 gL-1 and agitation rate (100-300 rpm) showed no significant effect (P-value > 0.05). In conclusion, the D-optimal design resulted in an effective model and optimized FTMs production on the shake flask level. FTM-A combinations with meropenem, cefotaxime, cefepime, and gentamicin showed mostly synergistic/additive effects and are advised for clinical evaluatio

As an emerging cancer therapeutic modality, ion-interference therapy (IIT), mediated by the elevated levels of intracellular calcium ions (Ca2+), hasgarneredsignificant research attention in the field of cancer theranostics. However, most reported IIT strategies have heavily relied on Ca-based inorganic compounds, such as calcium peroxide and calcium carbonate,whose biosafety remains under investigation due to their high density and uncertainbiodegradability.This study describes a novel strategy for efficiently encapsulating doxorubicin (DOX) andCa2+ using the CaSO4 gradient method fordrugremote loading. In breast cancer cell models, we demonstrated a synergistic anticancer effect between Ca2+ and DOX, and elucidated the reactive oxygen species(ROS)-based antitumor mechanisms. This research represents the first instance of nanomedicine inducing combined chemotherapy/ion-interference therapy for cancer treatment without the use of insoluble inorganic compounds, thus offering enhanced biosafety.

Highly active antiretroviral therapy (HAART) has dramatically lowered rates of mother-to-child HIV transmission among patients with access to treatment. Barriers to complete viral suppression increase rates of transmission, even with only low levels of viral replication. Here, we present the case of a pregnant patient who developed a detectable viral load in pregnancy, thought to be related to calcium supplement consumption or emesis while using a dolutegravir-based HAART regimen. Ultimately, with adjustments, the patient again reached an undetectable viral load and had an uncomplicated perinatal and neonatal outcome. We discuss new data on the use of dolutegravir in pregnancy and precautions for maintaining viral suppression while on antiretroviral therapy in pregnancy. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Background: The calcium supplement is a clinically approved approach for osteoporosis therapy but usually requires a large dosage without targetability and with poor outcome. This modality is not fully explored in current osteoporosis therapy due to the lack of proper calcium supplement carrier. Methods: In this study, we constructed a tetracycline (Tc) modified and simvastatin (Sim) loaded phospholipid-amorphous calcium carbonate (ACC) hybrid nanoparticle (Tc/ACC/Sim). Results: The resulted Tc/ACC/Sim was able to enhance its accumulation at the osteoporosis site. Most importantly, the combination of calcium supplement and Sim offered synergetic osteoblast promotion therapy of osteoporosis with advanced performance than non-targeted system or mono therapy. Conclusion: This platform provides an alternative approach to stimulate bone formation by synergetic promotion of osteoblast differentiation using calcium supplement and Sim. © The author(s).

Ca2+ , a ubiquitous but nuanced modulator of cellular physiology, is meticulously controlled intracellularly. However, intracellular Ca2+ regulation, such as mitochondrial Ca2+ buffering capacity, can be disrupted by 1 O2 . Thus, the intracellular Ca2+ overload, which is recognized as one of the important cell pro-death factors, can be logically achieved by the synergism of 1 O2 with exogenous Ca2+ delivery. Reported herein is a nanoscale covalent organic framework (NCOF)-based nanoagent, namely CaCO3 @COF-BODIPY-2I@GAG (4), which is embedded with CaCO3 nanoparticle (NP) and surface-decorated with BODIPY-2I as photosensitizer (PS) and glycosaminoglycan (GAG) targeting agent for CD44 receptors on digestive tract tumor cells. Under illumination, the light-triggered 1 O2 not only kills the tumor cells directly, but also leads to their mitochondrial dysfunction and Ca2+ overload. An enhanced antitumor efficiency is achieved via photodynamic therapy (PDT) and Ca2+ overload synergistic therapy. © 2020 Wiley-VCH GmbH.

BACKGROUND: Nonnutritive sweeteners (NNSs) are widely used as sugar substitutes to help individuals with diabetes manage glycemic control. However, emerging evidence suggests that even low doses of NNSs, such as saccharin and sucralose, may adversely affect metabolic health by impairing glycemic regulation, potentially through alterations in the gut microbiota. In Malaysia, where gut microbiome research is still limited, particularly among individuals with type 2 diabetes mellitus (T2DM), further investigation is warranted to inform safe and evidence-based use of NNSs. OBJECTIVE: This study aims to evaluate the short-term effects of saccharin and sucralose consumption on glycemic control and gut microbiota composition in adults with T2DM. METHODS: This is a double-blind, randomized, placebo-controlled, crossover trial. A total of 33 adults with T2DM will consume sucralose (5 mg/kg body weight), saccharin (2 mg/kg body weight), or a placebo (calcium carbonate) in capsule form daily for 7 days per intervention arm, with a 4-week washout period. Data collection will include anthropometric measurements, biochemical assessments for glycemic control, dietary records, physical activity levels, and stool samples. The homeostatic model assessment for insulin resistance will be used to assess insulin sensitivity, while 16S rRNA V3-V4 region sequencing will be conducted to profile gut microbiota composition. RESULTS: Recruitment is planned to begin in January 2026 and is expected to conclude by September 2026, with study completion anticipated by March 2027. As of December 2025, no participants have been enrolled. CONCLUSIONS: This trial will contribute novel insights into the effects of short-term NNS consumption on glycemic control and gut microbiota composition in individuals with T2DM. These findings may support evidence-based recommendations for NNS use in diabetes management and enhance understanding of microbiome-diet interactions in an ethnically diverse Asian population. TRIAL REGISTRATION: ClinicalTrials.gov NCT07124585; https://clinicaltrials.gov/study/NCT07124585. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/82695. ©Huey Shin Tan, Harvinder

INTRODUCTION: Upacicalcet is a novel injectable calcimimetic. This phase 3 multicenter open-label study aimed to assess the long-term efficacy and safety of upacicalcet in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). METHODS: Japanese HD patients with serum intact parathyroid hormone (iPTH) levels >240 pg/mL and corrected calcium (cCa) levels ≥8.4 mg/dL were enrolled. Upacicalcet with a dose range of 25-300 µg was administered after each dialysis for 52 weeks. The main efficacy endpoint was the percentage of patients achieving the target iPTH level (60-240 pg/mL). RESULTS: A total of 157 patients were enrolled, of whom 138 completed the study. Overall, 94.2% of patients achieved the target serum iPTH level at week 52. Neither symptomatic hypocalcemia nor cCa level <7.5 mg/dL occurred despite the negligible increase of concomitant vitamin D receptor activators and calcium carbonate. Upacicalcet improved the control of serum phosphate (P) and calcium levels regardless of baseline PTH levels and decreased intact fibroblast growth factor-23 levels. The largest parathyroid glands shrank, irrespective of their baseline volume or prior calcimimetic usage. Upacicalcet was well tolerated, with no adverse events requiring dose reduction. CONCLUSION: This is the first study to show that a calcimimetic improves serum P and cCa control without inducing severe hypocalcemia in patients with iPTH levels ≤300 pg/mL. Upacicalcet is efficacious in HD patients with mild-to-severe SHPT, with few safety concerns. INTRODUCTION: Upacicalcet is a novel injectable calcimimetic. This phase 3 multicenter open-label study aimed to assess the long-term efficacy and safety of upacicalcet in hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). METHODS: Japanese HD patients with serum intact parathyroid hormone (iPTH) levels >240 pg/mL and corrected calcium (cCa) levels ≥8.4 mg/dL were enrolled. Upacicalcet with a dose range of 25-300 µg was administered after each dialysis for 52 weeks. The main efficacy endpoint was the percentage of patients achieving the target iPTH level (60-240 pg/mL). RESULTS: A total of 157 patients were enrolled, of whom 138 co

Adequate calcium intake is important for the prevention of bone loss and osteoporosis. For some populations such as those of Southeast Asia where calcium intake is very low, supplements represent a suitable dietary source of calcium. The objective of this study was to compare the relative oral bioavailability of calcium from calcium glucoheptonate, a highly soluble calcium salt containing 8.2% of elemental calcium, to that of calcium carbonate. A single-dose, randomized-sequence, open-label, two-period crossover study, with a 7-day washout period, was conducted in 24 Indonesian healthy adult volunteers. After a 12-hour (overnight) fast, subjects received either two oral ampoules of 250 mg/10 mL of calcium glucoheptonate each or one effervescent tablet of calcium carbonate containing 500 mg of elemental calcium. The relative oral bioavailability of calcium from calcium glucoheptonate as compared to calcium carbonate was 92% within 6 hours and 89% within 12 hours after study drug administration. The 90% confidence intervals for the mean test/reference ratios of the maximum plasma concentration and the area under the concentration-time curve at 12 hours post-administration were 77.09%-120.31% and 60.58%-122.30%, respectively. Five subjects experienced a total of eight adverse events which were all mild and transient; no serious adverse events or deaths were reported. These results indicate that calcium glucoheptonate is associated with a high relative bioavailability of calcium compared to calcium carbonate, and is well-tolerated. Calcium glucoheptonate might thus be a potential choice for calcium supplementation in Southeast Asian populations. © 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.