Quantitative analysis of efficacy and associated factors of calcium intake on bone mineral density in postmenopausal women.
A model-based meta-analysis method was performed to quantitatively analyze the efficacy characteristics of calcium intake in BMD increase among postmenopausal women. We found that age and calcium intake dose were key factors affecting the efficiency and onset of BMD change, and daily 1200 mg calcium was suggested to be a beneficial dosage.



This paper aims to quantify the efficacy of calcium intake in preventing bone mineral density (BMD) decrease among postmenopausal women and to investigate the factors that may affect the efficacy.



Comprehensive literature search was conducted in PubMed and EMBASE from January 2016. Placebo-controlled or no-treatment controlled randomized trials focused on calcium intake for the management of osteoporosis in postmenopausal women were included. The clinical and demographic characteristics of participants and efficacy data, defined as the mean percentage change of spine BMD (L2-L4) at each observation time point compared with that of baseline, were extracted from the studies. Model-based meta-analysis (MBMA) was used to describe the time course of BMD change by calcium intake and identify the related factors.



This study includes 17 trials involving 2537 subjects. The results showed that a classic pharmacodynamic maximal effect (Emax) model could describe the time course of BMD change by calcium intake. Using this model, we found that age and calcium intake dose were key factors affecting the efficiency and onset of BMD change. A 60-year-old woman administered with 800 mg/day calcium can achieve a maximum BMD increasing rate of 2.38%, and the time to reach 50% of this maximum (known as onset time) was 9.44 months. An increase of 0.0817% per year was noted in the maximal effect value for women aged between 50 and 83 years. For calcium dose interval from 250 to 2000 mg/day, the onset time was expressed as 9.44 × (dose/800)-1.33months. Two-year calcium intake of 700, 1200, and 2000 mg/day resulted in a maximum efficacy of BMD of 68.0, 81.3, and 89.6%, respectively. This indicates that the final efficacy had already reached the plateau (>80% Emax) under the 1200-mg/day dose.



Calcium intake can effectively postpone the tendency of BMD decrease in postmenopausal women. An increased calcium dose contributes to the shortening of the onset time. Considering the drug-acting rate and safety into account, menopausal women can be administered with a rational dose of 1200 mg/day to reduce bone loss.
Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China.
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Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China.
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Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China.
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Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China.
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Dong
Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China. qingshan.zheng@drugchina.net.
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Zheng
Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China. lilujin666@163.com.
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Li
D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002118:Calcium / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D008954:Models, Biological; D015663:Osteoporosis, Postmenopausal / Q000503:physiopathology / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic
D050071:Bone Density Conservation Agents; D002118:Calcium
Bone mineral density; Calcium intake; Postmenopausal women