Calcium + Vitamin D

BACKGROUND: Postmenopausal osteoporosis (PMO) is a major cause of fragility fractures worldwide. While exercise and calcium/vitamin D are standard preventive measures, the synergistic effects of their combined use on bone mineral density (BMD) remain unclear. METHODS: We systematically searched eight databases through October 2025 and synthesized data using Review Manager version 5.4. Subgroup, sensitivity, and meta-regression analyses were conducted to examine heterogeneity and test the robustness of results. Risk of bias was assessed using the Cochrane RoB 2.0 tool, and the certainty of evidence was graded with the GRADE framework. RESULTS: 13 RCTs involving postmenopausal women were included. Compared with calcium and vitamin D supplementation alone, combined interventions significantly increased lumbar spine (SMD = 0.31, 95% CI [0.06, 0.55]) and femoral neck BMD (SMD = 0.47, 95% CI [0.09, 0.84]), with consistent but nonsignificant trends at other skeletal sites. Subgroup analyses showed that whole-body vibration produced the greatest and most consistent benefits at both sites, while mind-body or traditional Chinese exercises (e.g., Baduanjin) significantly improved lumbar spine BMD. Shorter interventions (≤6 months) yielded greater gains in BMD, whereas longer durations provided no additional advantage. CONCLUSIONS: Exercise combined with calcium and vitamin D supplementation effectively improves bone mineral density in postmenopausal women, especially at the lumbar spine and femoral neck. Whole-body vibration and mind-body exercises show the greatest benefits, with short-term interventions proving most effective. This combined approach offers a practical, evidence-based strategy to preserve skeletal health in aging women.

BACKGROUND: The purpose of this investigation was to determine risk factors for osteoporosis (OP) in patients with rheumatoid arthritis (RA) through comprehensive literature review and meta-analysis. METHODS: A comprehensive database exploration covered PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Chinese Biomedical databases from inception to December 31, 2024. Study quality was assessed using the Newcastle-Ottawa Scale for Healthcare Research and Quality (AHRQ). Data analyses involved STATA 18 to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias assessment involved funnel plots in conjunction with Egger's test. RESULTS: Fifty-seven articles were incorporated in the meta-analysis. Significant risk factors for OP in RA patients included female (OR = 2.10), advancing age (OR = 1.11), prior fracture (OR = 2.83), disease duration (OR = 1.16), and postmenopausal status (OR = 3.96). Laboratory and clinical parameters that correlated with increased risk included elevated CTX (OR = 1.01), higher DAS28 scores (OR = 1.60), increased ESR (OR = 1.05), higher Sharp Scores (OR = 1.12), and RF titers (OR = 1.01). Glucocorticoid therapy constituted a significant risk factor (OR = 2.34). Protective factors included higher BMI (OR = 0.86), adequate 25-(OH)-D levels (OR = 0.88), and calcium and/or vitamin D supplementation (OR = 0.49). No significant associations were found between OP in individuals with RA and smoking history, alcohol consumption, PTH levels, or DMARD therapy. This meta-analysis systematically identified risk factors for OP among individuals with RA. Female, advanced age, prior fracture, longer disease duration, postmenopausal status, CRP, ESR, CTX, RF titers, DAS28, Sharp Score, and glucocorticoid therapy increased OP risk. Conversely, higher BMI, adequate 25-(OH)-D status, and calcium/vitamin D supplementation demonstrated protective effects. CONCLUSION: This meta-analysis reveals female, age, postmenopausal status, prior fracture, and glucocorticoid therapy as major risk factors for osteoporosis in rheumatoid arthritis, with higher BMI as protective factors to quantify the impact of each risk factor

3. Osteoporos Int. 2025 Jun;36(6):981-993. doi: 10.1007/s00198-025-07479-0. Epub 2025 Apr 9. Clinical presentation, risk factors and management of pregnancy-associated osteoporosis: a systematic review and meta-analysis. Orhadje E(1), Makaram N(1), Berg K(1), Hauser B(1)(2), Ralston SH(3)(4). A

BACKGROUND & OBJECTIVES: Calcium and vitamin D, separately or in combination are usually prescribed to prevent fragility fractures in elderly population. However, there are conflicting results regarding the ideal dosage and overall efficacy obtained from randomized controlled trials (RCTs) conducted in the past. The objective of this study was to assess the fracture risk with the administration of calcium or vitamin D alone or in combination in elderly population (>60 yr). METHODS: PubMed, Cochrane and Embase databases were searched to identify the studies from inception to February 2021 with keywords, 'vitamin D', 'calcium' and 'fracture' to identify RCTs. The trials with comparing vitamin D, calcium or combination with either no medication or placebo were included for final analyses. The data were extracted and the study quality was assessed by two reviewers. The principal outcome measure was fractures around hip joint and secondary outcomes assessed were vertebral and any other fracture. RESULTS: Eighteen RCTs were considered for the final analysis. Neither calcium nor vitamin D supplementation was associated with risk of fractures around hip joint [risk ratio (RR) 1.56; 95% confidence interval (CI), 0.91 to 2.69, I[2]=28%; P=0.11]. In addition, the combined administration of calcium and vitamin D was also not associated with fractures around the hip joint in comparison to either no treatment or placebo. The incidence of vertebral (RR 0.95; 95% CI, 0.82 to 1.10, I[2]=0%; P=0.49) or any other fracture (RR 0.83; 95% CI 0.65 to 1.06, I[2]=0%; P=0.14) was not significantly associated with the administration of calcium and vitamin D either individually or in combination. Further subgroup analysis of the results did not vary with the dosage of calcium or vitamin D, dietary calcium intake sex, or serum 25-hydroxyvitamin D levels. INTERPRETATION & CONCLUSIONS: The present meta-analysis of RCTs on calcium, vitamin D or a combination of the two in comparison to no treatment or placebo did not support the routine administration protocol of calcium and vitamin D either alone or in combination to lower the risk of fractures in elderly population.

BACKGROUND: Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents. METHODS: We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study. RESULTS: Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo. CONCLUSIONS: Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence. REGISTRATION: PROSPERO, No. CRD42022296376.

Milk contains a number of bone-beneficial nutrients. However, milk, due to the D-galactose content, might have unfavorable effects on bone health. A meta-analysis of randomized controlled trials (RCTs) was performed to clarify the effects of milk supplementation on bone mineral density (BMD), bone turnover markers [N-terminal telopeptide of type I collagen (NTx), C-terminal telopeptide of type 1 collagen (CTx), osteocalcin, bone alkaline phosphatase (BALP), and procollagen type 1 N-propeptide (P1NP)], and hormonal indices related to bone metabolism [parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], and insulin-like growth factor 1 (IGF-1)] in adults. The PubMed and Web of Science databases were searched. A random-effects model was used to estimate the pooled effect sizes. A total of 20 RCTs were included. The trial duration ranged from 1 mo to 36 mo. Milk supplementation resulted in a small but significant increase in BMD at the hip (+0.004 g/cm2; n = 9 RCTs) and lumbar spine (+0.025 g/cm2; n = 7), but did not significantly affect whole-body BMD (n = 3) and femoral neck BMD (n = 7). Milk supplementation reduced the concentrations of P1NP (-5.20 ng/mL; n = 9), CTx (-0.16 ng/mL; n = 9), and NTx (-8.66 nmol bone collagen equivalents/mmol creatinine; n = 3). The concentrations of osteocalcin (n = 9) and BALP (n = 3) were not affected by milk supplementation. Reduced parathyroid hormone PTH (-1.01 pg/mL; n = 13) concentrations and increased IGF-1 (+1.79 nmol/l; n = 4) concentrations were observed with milk supplementation. 25(OH)D (+3.73 ng/mL; n = 11) concentrations were increased with vitamin-D fortified milk supplementation. The addition of milk to the diet may potentially increase the likelihood of preventing bone loss by restoring bone homeostasis through the modulation of the calcium-vitamin D-PTH axis, bone remodeling rate, and growth hormone/IGF-1 axis. © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

BACKGROUND: Magnesium plays a key role in bone health and may, therefore, represent an interesting nutrient for the prevention of bone loss and osteoporosis. The aim of this systematic review and meta-analysis was to investigate the impact of magnesium intake from any source on bone mineral density (BMD), bone mineral content (BMC), bone turnover markers, and fracture risk in older adults. METHODS: A systematic search was conducted using Embase, Medline Ovid and Cochrane Central from database inception to October 2020. All studies that related magnesium intake with bone health outcomes among adults aged ≥60 years were included. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias assessments. Authors were contacted for missing data. RESULTS: Once 787 records were screened, six cohort studies, one case-control study and five cross-sectional studies were included. Qualitative evaluation demonstrated a positive trend between higher magnesium intake and higher hip and femoral neck BMD. Meta-analysis of four studies showed a significant positive association between magnesium intake and hip BMD (pooled beta: 0.03, 95% CI: 0.01-0.06, p < 0.05). CONCLUSIONS: This systematic review indicates that a higher magnesium intake may support an increase in hip and femoral neck BMD. Due to limited research no associations with BMD at other sites or fractures were found. There is a need for properly designed cohort studies to determine the association between magnesium intake and bone health in older adults. Next, large and long-term randomized controlled trials in older adults are needed to determine whether an increase in magnesium (supplementation) intake can improve bone health. The combination of several bone nutrients (calcium, vitamin D, protein, magnesium and potentially more) may be needed for the most optimal effect on bone health and to delay or prevent the development of osteoporosis.

The objective of this review was to assess the impact of preventive nutrition interventions on health and nutritional status of adolescents aged 10-19 years in low- and middle-income countries (LMICs). We searched the databases until 5 February 2019 without any restrictions on publication, date, language, or publication status. A total of 10 studies (15 papers) including 10,802 participants assessing the impact of micronutrient supplementation/fortification were included in this review. We did not find any study assessing the impact of nutrition education and counseling or macronutrient supplementation among adolescents. Among primary outcomes, we are uncertain of the effect of iron supplementation with or without folic acid on anemia (daily supplementation; relative risk (RR): 1.04, 95% confidence interval (CI) 0.42, 2.57; one study; 1160 participants; low-quality evidence; weekly supplementation; RR: 1.07, 95% CI: 0.46, 2.52; one study; 1247 participants; low-quality evidence). We are also uncertain of the effect of various micronutrient supplementation/fortification on body mass index (BMI) (calcium/vitamin D supplementation; (MD: -0.01 kg/m2; 95% CI: -1.20, 1.17; two studies; 730 participants; I2 94%; very-low-quality evidence, iron supplementation with or without folic acid; MD: 0.47 kg/m2; 95% CI: -0.17, 1.11; two studies; 652 participants; I2 37%; very-low-quality evidence, zinc supplementation; MD: 0.35 kg/m2; 95% CI: -0.15, 0.85; one study; 382 participants; very-low-quality evidence) and multiple micronutrient (MMN) fortification; MD: 0.23 kg/m2, 95% CI: -0.11, 0.57; two studies; 943 participants; I2 22%; very-low-quality evidence). None of the included studies reported any other primary outcomes including morbidity or adverse effects. Among secondary outcomes, iron supplementation with or without folic acid may improve hemoglobin concentrations, and calcium/vitamin D supplementation may improve serum 25(OH)D levels, while calcium only supplementation and calcium and vitamin D supplementation may marginally improve total body bone mineral density (BMD). We are uncertain of the effect of MMN fortification on hemoglobin concentrations, calcium supplement

OBJECTIVE: Inconsistent findings in regard to association between different concentrations of vitamin D, calcium or their combination and the risk of fracture have been reported during the past decade in community-dwelling older people. This study was designed to compare the fracture risk using different concentrations of vitamin D, calcium or their combination. DESIGN: A systematic review and network meta-analysis. DATA SOURCES: Randomised controlled trials in PubMed, Cochrane library and Embase databases were systematically searched from the inception dates to 31 December 2017. OUTCOMES: Total fracture was defined as the primary outcome. Secondary outcomes were hip fracture and vertebral fracture. Due to the consistency of the original studies, a consistency model was adopted. RESULTS: A total of 25 randomised controlled trials involving 43 510 participants fulfilled the inclusion criteria. There was no evidence that the risk of total fracture was reduced using different concentrations of vitamin D, calcium or their combination compared with placebo or no treatment. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of hip or vertebral fractures. CONCLUSIONS: The use of supplements that included calcium, vitamin D or both was not found to be better than placebo or no treatment in terms of risk of fractures among community-dwelling older adults. It means the routine use of these supplements in community-dwelling older people should be treated more carefully. PROSPERO REGISTRATION NUMBER: CRD42017079624. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of calcium-vitamin D co‑supplementation on insulin, insulin sensitivity, and glycemia. A systematic search was carried out in Web of Science, PubMed, EMBASE, Scopus, and Cochrane library without any language and time restriction up to 12 August 2018, to retrieve the RCTs, which examined the effect of calcium and vitamin D co-supplementation on fasting blood glucose (FBG), insulin, HOMA-B, HOMA-IR, and QUICKI. Meta-analyses were carried out using a random effects model, and I2 indexes were used to evaluate the heterogeneity. Search yielded 2225 publications. Twelve RCTs with 4395 patients were eligible. Results demonstrated that calcium and vitamin D co‑supplementation had significantly reducing effects on FBG, HOMA-IR and circulating levels of insulin. As the subgroup analysis demonstrated, short-term (≤12 weeks) calcium and vitamin D co‑supplementation had a significant reducing effect on FBG. However, beneficial effects of calcium and vitamin D co‑supplementation on circulating level of insulin and HOMA-IR were seen in both short-term and long-term (>12 weeks) supplementations. Furthermore, we found that high doses of vitamin D and calcium co-supplementation (vitamin D≥2000 mg/day and calcium≥1000 mg/day) had significantly reducing effects on FBG, HOMA-IR and insulin. Present meta-analysis indicated the beneficial effects of high-dose and short-term combined vitamin D and calcium supplementation on insulin, insulin resistance and glycemia; however, further large-scale RCTs with adequate and multiple dosing schedules are needed. © Georg Thieme Verlag KG Stuttgart · New York.

Erratum in JAMA Netw Open. 2025 Aug 1;8(8):e2529919. doi: 10.1001/jamanetworkopen.2025.29919. IMPORTANCE: Weight loss (WL) in older adults is associated with bone loss, increasing the risk of fracture. Because skeletal tissue is responsive to mechanical stress, replacing lost weight externally may be an innovative way to minimize WL-associated bone loss in this population. OBJECTIVE: To examine the effect of 12 months of weighted vest use during WL on indicators of bone health compared with WL alone and WL plus resistance training (RT). DESIGN, SETTING, AND PARTICIPANTS: This single-blind, 12-month randomized clinical trial of older adults living with obesity was conducted at an academic medical center from September 1, 2019, to April 30, 2024. INTERVENTIONS: WL (caloric restriction targeting 10% WL with adequate calcium, vitamin D, and protein), WL plus weighted vest (WL+VEST; 8 h/d, weight replacement titrated up to 10% total WL), or WL plus progressive RT (WL+RT; supervised 3 sessions weekly). MAIN OUTCOMES AND MEASURES: Main outcomes included 12-month change in computed tomography-acquired trabecular volumetric bone mineral density (vBMD) and dual-energy X-ray absorptiometry-acquired areal bone mineral density (aBMD) of the total hip. Secondary outcomes included change in additional computed tomography- and dual-energy X-ray absorptiometry-acquired measures of musculoskeletal health and bone turnover biomarkers. RESULTS: A total of 150 older (mean [SD] age, 66.4 [4.6] years) adults (112 [74.7%] women) living with obesity (mean [SD] body mass index, 33.6 [3.3]) were randomized (50 to WL, 50 to WL+VEST, and 50 to WL+RT), with 133 (88.7%) completing the trial. Similar significant WL, ranging from 9.0% to 11.2%, was achieved in all groups. During 12 months, mean (SD) self-reported weighted vest wear time was 7.1 (1.5) h/d, with 78.0% (29.9%) of lost weight replaced in the vest; participants randomized to the WL+RT group attended a mean (SD) of 71.4% (19.1%) of sessions. A significant decrease in total hip trabecular vBMD was observed at 12 months in all treatment groups (ranging from -1.2% to -1.9%), with no difference between the WL+VEST and WL groups (estimat

BACKGROUND: Anabolic resistance accelerates muscle loss in aging and obesity, thus predisposing to sarcopenic obesity. METHODS: In this retrospective analysis of a randomized clinical trial, we examined baseline predictors of the adaptive response to three months of home-based resistance exercise, daily physical activity, and protein-based, multi-ingredient supplementation (MIS) in a cohort of free-living, older males (n = 32). RESULTS: Multiple linear regression analyses revealed that obesity and a Global Risk Index for metabolic syndrome (MetS) were the strongest predictors of Δ% gains in lean mass (TLM and ASM), LM/body fat ratios (TLM/%BF, ASM/FM, and ASM/%BF), and allometric LM (ASMI, TLM/BW, TLM/BMI, ASM/BW), with moderately strong, negative correlations to the adaptive response to polytherapy r = -0.36 to -0.68 (p < 0.05). Kidney function, PA level, and chronological age were only weakly associated with treatment outcomes (p > 0.05). Next, we performed a subgroup analysis in overweight/obese participants with at least one other MetS risk factor and examined their adaptive response to polytherapy with two types of protein-based MIS (PLA; collagen peptides and safflower oil, n = 8, M5; whey/casein, creatine, calcium, vitamin D3, and fish oil, n = 12). The M5 group showed greater improvements in LM (ASM; +2% vs. -0.8%), LM/body fat ratios (ASM/FM; +3.8% vs. -5.1%), allometric LM (ASM/BMI; +1.2% vs. -2.5%), strength (leg press; +17% vs. -1.4%), and performance (4-Step-Stair-Climb time; -10.5% vs. +1.1%) vs. the PLA group (p < 0.05). Bone turnover markers, indicative of bone accretion, were increased pre-to-post intervention in the M5 group only (P1NP; p = 0.036, P1NP/CTX ratio; p = 0.088). The overall anabolic response, as indicated by ranking low-to-high responders for Δ% LM (p = 0.0079), strength (p = 0.097), and performance (p = 0.19), was therefore significantly higher in the M5 vs. PLA group (p = 0.013). CONCLUSIONS: Our findings confirm that obesity/MetS is a key driver of anabolic resistance in old age and that a high-quality, whey/casein-based MIS is more effective than a collagen-based alternative for maintaining musculoskeletal health in individuals

Vitamin D status has long been related to falls risk. In this planned secondary analysis of a vitamin supplementation trial in postmenopausal women, standardized 25-hydroxyvitamin D concentration up to 60 ng/mL was not associated with increased falls. Women with 25(OH)D ≥ 60 ng/mL had higher odds of ≥ 2 falls. PURPOSE: Falls are common and cause fractures. High circulating 25(OH)D may increase falls risk; thus, recent guidance recommends 25(OH)D not exceed 50 ng/mL. Prior falls studies have not reported standardized 25(OH)D (s25D) data. The purpose of this planned secondary analysis of a 4-year calcium/vitamin D supplementation trial was to evaluate the association of s25D with falls. METHODS: This study recruited 2,303 postmenopausal women. The analytic dataset consisted of pooled concatenated data from years 2-4 (NTotal = 5,732). Serum 25(OH)D was measured annually and subsequently retrospectively standardized using Vitamin D Standardization Program methods. Falls were recorded by diary. Incidence for ≥ 1 fall and ≥ 2 falls was assessed by s25D group (≤ 20, 20- < 30, 30- < 40, 40- < 50, 50- < 60 and ≥ 60 ng/mL) using multivariable logistic regression. RESULTS: Mean (SD) baseline s25D was 32.6 ng/mL (8.3) with no difference between supplement and placebo groups. s25D increased to 41.3 ng/mL at year 2 in the supplement group then remained stable. By s25D group, incidence for ≥ 1 fall varied from 22-32% (p = 0.19). For ≥ 2 falls incidence varied (p = 0.03) from 6% (< 20 ng/mL) to 17% (≥ 60 ng/mL.) There was no significant association between s25D and ≥ 1 fall. Those with s25D ≥ 60 ng/mL had a higher adjusted odds of ≥ 2 falls (OR = 1.99 ± 1.2-3.3) compared to women with s25D of 30- < 40 ng/mL. CONCLUSION: s25D up to 60 ng/mL was not associated with greater risk for ≥ 1 or ≥ 2 falls. Women with a s25D ≥ 60 ng/mL were at higher odds for ≥ 2 falls, however this group included only ~ 2% of study observations; therefore, confirmation in other cohorts is necessary. © 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.

When denosumab is discontinued, antiresorptive therapy is critical to reduce high-turnover bone loss. The ideal duration of antiresorptive therapy after denosumab is uncertain. This study demonstrates that both 1 and 2 years of alendronate maintained bone density gains achieved with 1 year of denosumab. BACKGROUND: When denosumab is discontinued, antiresorptive therapy is critical to attenuate high-turnover bone loss. The ideal choice and duration of antiresorptive therapy are not yet defined, however. In the Comparison of Alendronate or Raloxifene following Denosumab (CARD) study, we demonstrated that 12 months of alendronate was better able to maintain the bone mineral density (BMD) gains achieved with 12 months of denosumab versus 12 months of raloxifene. In this extension, we wished to determine if 12 months of alendronate would be sufficient in maintaining these denosumab-induced BMD gains. METHODS: In the CARD study, postmenopausal osteoporotic women aged 60-79 at high fracture risk received 12 months of denosumab 60-mg SC every 6 months followed by 12 months of either alendronate 70 mg weekly (N = 26) or raloxifene (N = 25). All subjects in the alendronate arm were then offered participation in a 1-year extension in which they were randomized to continue alendronate for an additional 12 months (N = 10) or to receive calcium and vitamin D alone (N = 8). The primary outcome was change in spine BMD between months 24 and 36. Exploratory endpoints included changes in areal BMD (aBMD) at other anatomic sites as well as changes in serum bone turnover markers. RESULTS: The CARD study demonstrated the effectiveness of 12 months alendronate in preserving denosumab-induced BMD gains. In the extension, aBMD was maintained at the spine, total hip, and femoral neck in both those randomized to an additional year of alendronate and those randomized to calcium/vitamin D alone. We did, however, observe a transient comparative decrease between months 24-30 in the calcium/vitamin D group at the total hip (P = 0.008) and femoral neck (P = 0.040). At the end of 24 months of the CARD study, bone turnover markers serum c-telopeptide (CTX) and procollagen N-propeptide of type I c

BACKGROUND: Due to increasing older populations worldwide, injuries, disabilities and deaths caused by falls among the elderly represent a growing human and societal problem. We aimed to improve health among men of at least 70 years of age with low-normal to low testosterone and mobility problems by using testosterone undecanoate (TU) injections, progressive strength training, and oral supplements of vitamin D, calcium and protein. METHODS: This was a single-centre, randomized, placebo-controlled, double-blind trial with 148 older men with a median age of 77 (73-81) years, testosterone levels at median 8 (5-9) nmol/L (full range from 1.1 to 12.9 nmol/L) and mobility problems, recruited at University Hospital of Copenhagen, Herlev Hospital, Denmark. Participants were randomized into four arms for 20 weeks: (1) TU therapy (n = 37); (2) progressive resistance training with supplements of calcium, vitamin D and protein (n = 36); (3) both interventions combined (n = 36); or (4) no intervention (n = 39). The main outcome measure was the 30-s chair stand test, due to test performance correlating with the risk of serious fall injuries and lower extremity muscle strength. Outcome measurements were performed at baseline and after 20 weeks. RESULTS: After the intervention, the combination group receiving progressive resistance training, TU and supplements achieved a median score of 13 (11-15) compared to the control group at 10 (0-14) in the 30-s chair stand test (P = 0.003). This median improvement of 3.0 was clinically important. Compared to the control group, participants in the combination group also increased quality of life (P < 0.05) and reduced both tiredness (P < 0.05) and leg fat (P < 0.05) and had higher variability in the RR interval (P < 0.01). The group receiving TU reduced gynoid and leg fat compared to the control group (both P < 0.05). Blood tests improved for several variables, especially in the combination group. There was no statistically significant increase in adverse effects from either the supplements or training. CONCLUSIONS: In men ≥70 years old with low-normal to low testosterone and mobility problems, supplements of testosterone, calcium, vitami

Background: In vitro studies have shown that genistein inhibits the CYP240 enzyme, which is involved in the degradation of 1,25-dihydroxycholecalciferol and its precursor 25-hydroxycholecalciferol, and increases their plasma levels. However, no clinical studies have primarily assessed the synergistic effect of isoflavones on vitamin D levels. The aim of this study was to evaluate the possible additive effect of genistein supplementation on vitamin D levels, calcium metabolism and bone remodeling markers in healthy postmenopausal women during the spring-summer months. Patients and methods: We made a prospective, double-blind study with 150 healthy postmenopausal women that were randomized to three groups. One received placebo, another received calcium (1000 mg/day) and vitamin D (cholecalciferol, 800 U/day) and the third received calcium (1000 mg/day), vitamin D (cholecalciferol, 800 U/day) and genistein (90 mg/day). The study period was from May to September (spring-summer). Vitamin D, PTH, CTX and P1NP were determined by electrochemiluminescence at baseline and after 12 weeks. Results: Vitamin D levels increased in all groups: placebo (23±9 ng/ml vs. 29±10 ng/ml, p<0.05), calcium+vitamin D (26±10 ng/ml vs. 33±8 ng/ml, p<0.05) and calcium+vitamin D+genistein (24±9 ng/ml vs. 31±8 ng/l, p<0.05) without between-group differences. At study end, the percentage of women with vitamin D <20 ng/ml (11%) and <30 ng/ml (39%) had fallen without between-group differences. The effects on calcium metabolism and bone remodeling markers were similar between groups: rises in vitamin D were significantly linked to reductions in PTH, CTX and P1NP. Conclusion: Adding genistein to supplementation with calcium and vitamin D provided not additional changes in vitamin D levels, calcium metabolism or bone remodeling markers in healthy Spanish postmenopausal women during the spring-summer months.

Comment in Int J Cancer. 2023 Jul 15;153(2):450-451. doi: 10.1002/ijc.34502. Int J Cancer. 2023 Jul 15;153(2):452-453. doi: 10.1002/ijc.34501. Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow-up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause-specific mortality endpoints among Black women. Intent-to-treat analysis was performed. Among 3325 Black women in the CaD trial who were randomized into either daily calcium (1000 mg of calcium carbonate) plus vitamin D (400 IU D3) or placebos for an average of 7 years, there were 813 deaths, 588 incident cancers, and 837 CVD events during an average of 15.7 years of follow up (52 230 total person-years). Using Cox's proportional hazards models, we calculated hazard ratios and their confidence intervals for outcomes ascertained during the trial period, posttrial follow-up period and overall periods combined. We found that total mortality, cause-specific mortality, and total cancer incidence were almost identical between CaD and placebo groups. These results suggest that calcium plus vitamin D supplementation does not reduce risks of cancer, CVD, or other major causes of death in Black women overall and, thus, other medical, behavioral or social interventions should be considered to narrow health disparities related to these outcomes. However, other finer endpoints, such as colorectal cancer, warrants further investigation. © 2023 UICC.

OBJECTIVE: This trial evaluated a smartphone application's effectiveness in improving adherence to vitamin and mineral supplementation postoperatively. METHODS: This study was a randomized controlled trial comprising 140 patients undergoing bariatric surgery (gastric bypass or sleeve gastrectomy). Participants were randomized 1:1 to the 12-week intervention, using the smartphone application PromMera, or to standard care. The primary end point was adherence to vitamin and mineral supplementation. RESULTS: Initiation rate and overall adherence to supplementation were high in both groups. Change in objectively measured adherence rate from before the intervention to 1 year post surgery, measured with pharmacy refill data, did not differ between groups for vitamin B12 (-9.6% [SD = 27%] vs. -9.3% [SD = 30%]; p = 0.48) or calcium/vitamin D (-12.3% [SD = 29%] vs. -11.5% [SD = 32%]; p = 0.44). A modest effect on the secondary end point (subjectively measured adherence, using the Medication Adherence Report Scale-5) was seen immediately after the intervention (intervention group 0.00 [SD = 1.3] vs. control group -1.2 [SD = 3.5]; p = 0.021), but this effect did not persist 1 year post surgery. No differences were detected in the prevalence of biochemical deficiencies. CONCLUSIONS: The use of the smartphone application PromMera did not obtain a lasting improvement in adherence to vitamin and mineral supplementation 1 year post bariatric surgery. © 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).

INTRODUCTION: Patients receiving radiotherapy are at risk of developing radiotherapy-related insufficiency fractures, which are associated with increased morbidity and pose a significant burden to patients' quality of life and to the health system. Therefore, effective preventive techniques are urgently required. The RadBone randomised controlled trial (RCT) aims to determine the feasibility and acceptability of a musculoskeletal health package (MHP) intervention in women undergoing pelvic radiotherapy for gynaecological malignancies and to preliminary explore clinical effectiveness of the intervention. METHODS AND ANALYSIS: The RadBone RCT will evaluate the addition to standard care of an MHP consisting of a physical assessment of the musculoskeletal health, a 3-month prehabilitation personalised exercise package, as well as an evaluation of the fracture risk and if required the prescription of appropriate bone treatment including calcium, vitamin D and-for high-risk individuals-bisphosphonates. Forty participants will be randomised in each group (MHP or observation) and will be followed for 18 months. The primary outcome of this RCT will be feasibility, including the eligibility, screening and recruitment rate, intervention fidelity and attrition rates; acceptability and health economics. Clinical effectiveness and bone turnover markers will be evaluated as secondary outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Greater Manchester East Research Ethics Committee (Reference: 20/NW/0410, November 2020). The results will be published in peer-reviewed journals, will be presented in national and international conferences and will be communicated to relevant stakeholders. Moreover, a plain English report will be shared with the study participants, patients' organisations and media. TRIAL REGISTRATION NUMBER: NCT04555317. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.

Hypertension is a highly prevalent disease with serious cardiovascular and renal complications. Many studies have demonstrated a weak correlation between the consumption of calcium (or calcium plus vitamin D) and blood pressure, suggesting that calcium supplements might reduce blood pressure. However, the results to date remain controversial. In this study, we assessed the effect of calcium and vitamin D supplementation on the blood pressure of postmenopausal women with hypertension as a population group in which the use of calcium supplements is prevalent. This triple-blind randomized clinical trial enrolled 98 women of postmenopausal age with hypertension in 2019. The study period was 8 weeks with close follow-up. We used 24-h ambulatory blood pressure monitoring to record the initial and final blood pressure in all participants. The changes in both the mean systolic (p = 0.047) and diastolic blood pressure (p = 0.015) were suggestive of an increase in blood pressure after consuming calcium and vitamin D supplements. Among patients who had been using calcium channel blockers, calcium and vitamin D supplementation caused a notable increase compared to baseline systolic (p = 0.019) and diastolic blood pressures (p = 0.001). The present results differ from those of previous studies. This suggests that calcium supplementation for postmenopausal women with hypertension requires the close observation of blood pressure to prevent any further increase, especially in women who are being treated with calcium channel blockers (clinicaltrial.gov registration: NCT04618952). © 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.

Cancer patients use health foods (HFs) as complementary and alternative medicine, although the details of their adverse events (AEs) are unclear. We searched three databases [PubMed, "Igaku Chuo Zasshi", and Information System on Safety and Effectiveness for Health Foods website (https://hfnet.nibiohn.go.jp/)] for case reports on AEs related to HF intake in cancer patients published before October 2018. Of the matched reports, 76 studies and 92 patients (31 in Japan, 61 overseas) that met the selection criteria were included in this review. Thus, the severity of AEs and outcomes were not related to either the concomitant use of HF with cancer chemotherapy or cancer stages of patients. AEs caused by HF intake itself accounted for 87%, while drug-HF interaction accounted for 11%. According to the Common Terminology Criteria for Adverse Events (CTCAE) classification, 70% of patients whose grades were identified had severe cases (grades 3 to 5). In Japanese patients, hepatic and respiratory disorders accounted for 52% of the severe cases. Cases were predominantly developed as a result of an allergic mechanism, and mushroom products were mostly used. Overseas, serious cases were induced by products that were already indicated for safety problems. Moreover, notable AEs were recognized, such as hypercalcemia, which were caused by intake of HF containing calcium, vitamin D, and shark cartilage, and bacterial infection caused by probiotic products. Analyzing the details of AEs related to HF intake can help health professionals and cancer patients prevent health hazards.

OBJECTIVE: To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial among Women's Health Initiative (WHI) participants. The predefined primary outcome was low-density lipoprotein cholesterol (LDL-C). RESULTS: Between September 1993 and October 1998, a total of 68,132 women aged 50-79 years were recruited and randomized to the WHI-Dietary Modification (n=48,835) and WHI-Hormone Therapy trials (n=27,347). Subsequently, 36,282 women from WHI-Hormone Therapy (16,089) and WHI-Dietary Modification (n=25,210) trials were randomized in the WHI-Calcium+Vitamin D trial to 1,000 mg elemental calcium carbonate plus 400 international units vitamin D3 daily or placebo. Our study group included 1,521 women who participated in both the hormone therapy and calcium+vitamin D trials and were in the 6% subsample of trial participants with blood sample collections at baseline and years 1, 3, and 6. The average treatment effect with 95% confidence interval, for LDL-C, compared with placebo, was -1.6, (95% confidence interval [CI] -5.5 to 2.2) mg/dL for calcium+vitamin D alone, -9.0 (95% CI -13.0 to -5.1) mg/dL for hormone therapy alone, and -13.8 (95% CI -17.8 to -9.8) mg/dL for the combination. There was no evidence of a synergistic effect of calcium+vitamin D+hormone therapy on LDL-C (P value for interaction=.26) except in those with low total intakes of vitamin D, for whom there was a significant synergistic effect on LDL (P value for interaction=.03). CONCLUSION: Reductions in LDL-C were greater among women randomized to both calcium+vitamin D and hormone therapy than for those randomized to either intervention alone or to placebo. The treatment effect observed in the calcium+vitamin D+hormone therapy combination group may be additive rather than synergistic. For clinicians and patients deciding to begin calcium+vitamin D supplementation, current use of hormone therapy should not influence that decision. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611.

BACKGROUND: Patients admitted to general internal medicine wards might receive a large number of drugs and be at risk for drug-related problems (DRPs) associated with increased morbidity and mortality. This study aimed to detect suboptimal drug use in internal medicine by a pharmacotherapy evaluation, to suggest treatment optimizations and to assess the acceptance and satisfaction of the prescribers. METHODS: This was a 6-month prospective study conducted in two internal medicine wards. Physician rounds were attended by a pharmacist and a pharmacologist. An assessment grid was used to detect the DRPs in electronic prescriptions 24h in advance. One of the following interventions was selected, depending on the relevance and complexity of the DRPs: no intervention, verbal advice of treatment optimization, or written consultation. The acceptance rate and satisfaction of prescribers were measured. RESULTS: In total, 145 patients were included, and 383 DRPs were identified (mean: 2.6 DRPs per patient). The most frequent DRPs were drug interactions (21%), untreated indications (18%), overdosages (16%) and drugs used without a valid indication (10%). The drugs or drug classes most frequently involved were tramadol, antidepressants, acenocoumarol, calcium-vitamin D, statins, aspirin, proton pump inhibitors and paracetamol. The following interventions were selected: no intervention (51%), verbal advice of treatment optimization (42%), and written consultation (7%). The acceptance rate of prescribers was 84% and their satisfaction was high. CONCLUSION: Pharmacotherapy expertise during medical rounds was useful and well accepted by prescribers. Because of the modest allocation of pharmacists and pharmacologists in Swiss hospitals, complementary strategies would be required.

Fourier transform infrared spectroscopy is utilized to examine the effects of increased calcium, vitamin D, and combined calcium-vitamin D supplementation on osteoporotic rabbit bones with induced inflammation. The study includes different bone sites (femur, tibia, humerus, vertebral rib) in an effort to explore possible differences among the sites. We evaluate the following parameters: mineral-to-matrix ratio, carbonate content, and non-apatitic species (labile acid phosphate and labile carbonate) contribution to bone mineral. Results show that a relatively high dose of calcium or calcium with vitamin D supplementation increases the bone mineralization index significantly. On the other hand, vitamin D alone is not as effective in promoting mineralization even with high intake. Mature B-type apatite was detected for the group with calcium supplementation similar to that of aged bone. High vitamin D intake led to increased labile species concentration revealing bone formation. This is directly associated with the suppression of pro-inflammatory cytokines linked to induced inflammation. The latter is known to adversely alter bone metabolism, contributing to the aetiopathogenesis of osteoporosis. Thus, a high intake of vitamin D under inflammation-induced osteoporosis does not promote mineralization but suppresses bone resorption and restores metabolic balance.

CONTEXT: Exercise and calcium-vitamin D are independently recognized as important strategies to prevent osteoporosis, but their combined effects on bone strength and its determinants remain uncertain. OBJECTIVE: To assess whether calcium-vitamin D(3) fortified milk could enhance the effects of exercise on bone strength, structure, and mineral density in middle-aged and older men. DESIGN, SETTING, PARTICIPANTS: An 18-month factorial design randomized controlled trial in which 180 men aged 50-79 years were randomized to the following: exercise + fortified milk; exercise; fortified milk; or controls. Exercise consisted of progressive resistance training with weight-bearing impact activities performed 3 d/week. Men assigned to fortified milk consumed 400 ml/d of 1% fat milk containing 1000 mg/d calcium and 800 IU/d vitamin D(3). MAIN OUTCOME MEASURES: Changes in bone mineral density (BMD), bone structure, and strength at the lumbar spine (LS), proximal femur, mid-femur, and mid-tibia measured by dual energy x-ray absorptiometry and/or quantitative computed tomography. RESULTS: There were no exercise-by-fortified milk interactions at any skeletal site. Main effect analysis showed that exercise led to a 2.1% (95% confidence interval, 0.5-3.6) net gain in femoral neck section modulus, which was associated with an approximately 1.9% gain in areal BMD and cross-sectional area. Exercise also improved LS trabecular BMD [net gain 2.2% (95% confidence interval, 0.2-4.1)], but had no effect on mid-femur or mid-tibia BMD, structure, or strength. There were no main effects of the fortified milk at any skeletal site. CONCLUSION: A community-based multi-component exercise program successfully improved LS and femoral neck BMD and strength in healthy older men, but providing additional calcium-vitamin D(3) to these replete men did not enhance the osteogenic response.

143. Harv Heart Lett. 2009 Jun;19(10):8. Ask the doctor. Since having a heart attack, I have been taking lisinopril, Zocor, Plavix, aspirin, a multivitamin, fish oil, calcium, vitamin D, coenzyme Q(10), chia oil, B-50 complex, grape seed extract, Nu-Zymes, Natural Energy supplement, Super C22 and astragalus. I am thinking of taking a brain booster called Procera AVH. Will it interfere with my heart medications? Lee T.

BACKGROUND: Adequate calcium intake can have a favorable effect on some metabolic variables. OBJECTIVE: The objective of the study was to determine the effects of daily calcium intake and of supplementation with calcium and vitamin D (calcium+D) during a weight-loss intervention on blood pressures, plasma lipid and lipoprotein concentrations, and glucose and insulin concentrations in low calcium consumers. DESIGN: Healthy, overweight or obese women (n = 63) with a daily calcium intake of < 800 mg/d were randomly assigned in a double-blind manner to 1 of 2 groups: the group consuming 2 tablets/d of a calcium + vitamin D supplement (600 mg elemental calcium and 200 IU vitamin D/tablet) or the group consuming placebo; both groups observed a 700 kcal/d energy restriction. These 63 women then completed a 15-wk weight-loss intervention. RESULTS: Initial daily calcium intake was significantly correlated with plasma HDL cholesterol (r = 0.41, P < 0.001) and with 2-h postload glycemia (r = -0.29, P < 0.05) during an oral-glucose-tolerance test, independent of fat mass and waist circumference. After the 15-wk intervention, significantly greater decreases in total:LDL and LDL:HDL (P < 0.01 for both) and of LDL cholesterol (P < 0.05) were observed in the calcium+D group than in the placebo group. The differences in total:HDL and LDL:HDL were independent of changes in fat mass and in waist circumference. A tendency for more beneficial changes in HDL cholesterol, triacylglycerol, and total cholesterol was also observed in the calcium+D group (P = 0.08). CONCLUSION: Consumption of calcium+D during a weight-loss intervention enhanced the beneficial effect of body weight loss on the lipid and lipoprotein profile in overweight or obese women with usual low daily calcium intake.

145. Z Orthop Ihre Grenzgeb. 2005 May-Jun;143(3):278. doi: 10.1055/s-2005-871821. [Osteoporosis--treatment with Calcium/Vitamin D]. [Article in German] [No authors listed]

146. J Am Geriatr Soc. 1984 May;32(5):405-7. doi: 10.1111/j.1532-5415.1984.tb02050.x. Hazards of treating osteoporosis and hypertension concurrently with calcium, vitamin D, and distal diuretics. Drinka PJ, Nolten WE.

147. Med Klin. 1976 Sep 3;71(36):1439-43. [Studies on calcium absorption out of a calcium-vitamin-D-preparation using calcium-47 (author's transl)]. [Article in German] Seim KE, Sattler EL. Calcium absorption in man was studied by means of labelling an ampoule of Frubiase Calcium forte with calcium-47. For comparative purpose a solution containing the same amount of calcium salts as the ampoule was labelled as well. Already 10 minutes after oral administration of Ca-47 in 10 ml of Frubiase Calcium forte radioactivity was statistically significant measurable in blood. At the same time there was no significant radioactivity demonstrable out of the calcium salt solution. Between 45 and 120 minutes following oral application of the isotope both groups showed a statistically significant difference concerning the measurable blood activity. The Frubiase Calcium forte values were always higher, especially one and two hours after administration of the radiocalcium (up to 40%). The levels at these times correlate well with the total calcium absorption. Measurements over the compact bone region of the ankle demonstrated significantly higher values of calcium-47 in case of Frubiase Calcium forte compared with the calcium salt solution. These findings indicate in the case of Frubiase Calcium forte a higher bone mineral accretion. There is a good direct proportionality between the amount of these values and the total calcium absorption.