Literature review: Calcium trials

RCT: randomised controlled trial; n=: number of subjects; y: years; Ca: calcium; mg: milligrams; supp: supplement; VitD: vitamin D; IU: international units; μg: micrograms; BMD: bone mineral density; HT/OT: oestrogen therapy (HRT)/osteoporosis treatment; NHANES: National Health and Nutrition Examination Survey; Not sig.: not statistically significant.
  
            Authors
            Subjects
            Design
            Results
            
            Randomised controlled trials
            
            Slemenda et al (1997)
            RCT Identical twin pairs 6-14y
            Ca supplementation for 3y
            BMD increased 3% during supp compared to placebo twin. Difference disaapeared after supp ceased.
        
            Winzenberg et al (2006)
            19 RCTs (n=2859) in children
            Cochrane review. Effect of Ca supplementation on BMD in children.
            No effect on hip or spine BMD. A small effect on total body mineral (volume x density) and upper limb BMD. Only the effect in the upper limb persisted after supp ceased. No effect modification by baseline calcium intake, sex, ethnicity, physical activity or pubertal stage.
            
            Reid et al (2008)
            323 healthy men, ave 57y 
            2y RCT; NZ. Ca supp 1200mg/d or 600mg/d or placebo
            After 2y the 1200mg group's BMD was 1-1.5% > placebo but there was no difference between 600mg/d and placebo.  There ws no age affect. Compliance was ~85% in all groups. The effect was apparent within 1y.

            Reid et al (2015)
            59 RCTs (dietary Ca: n=1,533, Ca supp: n=12,257)
            Systemic review.
            Both diet and supplements -> ↑ BMD compared to placebo by 0.7-1.8%. Difference did not increase after 1y. None of dose, baseline Ca nor concurrent vitamin D changed the results. 
         
            Di Daniele (2004)
            120 women aged >45y
            RCT. Daily Ca+VitD for 30 mth
            BMD was preserved in the Ca+VitD group compared with placebo. The placebo group ↓ BMD ~0.4%/y.
            
            Cong and Zhang (2025)
            11 RCTs (n=43,869 post-menopausal women)
            Systemic review.
            Combined Ca+VitD modestly improved pelvic BMD but not elsewhere. No difference in fracture risk. No duration-response effect. 
            
            Migliorini et al (2025)
            37 RCTs (n=43,397 post-menopausal women on anti-resorptive therapy, mean age 66y)
            Subjects received mean of 833.6mg/d Ca + 92.8mg/d vitD supp over mean 2y.
            Vit D --> ↓ gastrointestinal adverse events and ↓ mortality. Neither Ca not VitD were associated with BMD change.
            
            Aloia et al (1994)
            118 Caucasian women 3-6 years post-menopause
            RCT 1700mg/d Ca; placebo; or HRT. Each participant received 400IU/d VitD.
            Placebo BMD: lumbar -2.1%/y, femoral neck -2.0%, total body Ca -2.0%/y. Ca supp BMD: lumbar: not.sig., femoral neck -0.8%/y, total body calcium -0.5%/y.
          
            Ruml et al (1999)
            63 post-menopausal women (57 <5y postmenopause, six women 5-10y postmenopause.
            800mg/d Ca supp
            Lumbar BMD: Ca supp +1.03%, placebo -2.4%. Femoral neck: did not change in either group. Forearm: Ca supp -0.0%, placebo -3.0%.
            
            Méndez-Sánchez et al (2023)
            7 RCTs (n=941 women 18-42y)
            Cochrane review.
            No difference between Ca supp and placebo. Certainty was moderate to low and most studies at risk of biases.
            
            Larson et al (2005)
            9,605 community-dwelling women >66y; Denmark.
            RCT; 1000mg/d Ca + 400IU/d (10μg) vitD, or nutrition advice.
            Supp saw a 12% ↓ in severe falls.
            
            Pfeifer et al (2009)
            242 community-dwelling women mean 77y; Austria.
            RCT; 1000mg/d Ca or 100mg Ca + 800IU/d (10μg) vitD.
            Compared to Ca, Ca + vitD saw first falls -27% after 1y and -39% after 20m. 
            
            Iuliano et al (2021)
            7,195 aged care residents (68% women), average age 86y; Australia.
            An additional 166mg/d dairy and 12g/d protein --> total Ca and protein 1142mg/d and 69 mg/d or control (700mg/d and 58g/d)
            Added Ca and protein --> - 33% for all fractures, -46% for hip fractures, and -11% for falls. Mortality was unchanged.
            
            Longitudinal cohort studies
            
            Bailey et al (2020)
            Longitudinal cohort study over 10y (n=1,490; 42-52y at baseline).
            Study of Women's Health Across the Nation (SWAN); US.
            Baseline dietary Ca ~750mg/d in both groups. Ca supp associated with relative preservation of hip and spine BMD but in pre-menopausal women only. Non sig. differences in fractures.
            
            Bischoff‐Ferrariet et al (2009)
            Cohort study 4,958 women, 5,003 men ≥20y, not taking supplements.
            NHANES III population‐study; US.
            Higher Ca intake associated with higher BMD in women with low vit D <50 nM and when intake was above the lowest quartile >566mg/d. There was no association in men regardless of vitamin D status of Ca intake.
        
            Warensjö et al (2011)
            Longitudinal cohort study over 19y (n=61,433 women average 54y at baseline)
            Swedish Mammography Cohort. Long term and large number Ca intake and fracture risk.
            Adjusted hip fracture 51% higher in the lowest quintile (<751mg/d) compared to the median quintile (882-996mg/d) of calcium intake. No difference between other quintiles.
            
            Bristow et al (2022)
            Longitudinal cohort studies in women (n=23) and men (n=7) >50y. 
            Systemic review
            71% of studies found no effect of Ca in women or men. A positive association in women was most often associated with HT/OT and age 50-60y. HT/OT likely confounded the results.