Abstract
Background Calcium is widely recognized as an effective intervention for the prevention of osteoporosis. However, some recent studies and meta-analyses indicate that calcium supplements may be ineffective to prevent fracture. The association of dietary calcium intake with vertebral fracture and spinal volumetric bone mineral density (vBMD) in low calcium intake population is unknown. Methods China Action on Spine and Hip Status (CASH) study is a multi-center, community-based cohort study of 3,457 participants from 12 centers across China from March 2013 and August 2017. We documented their baseline dietary calcium intake using validated food frequency questionnaires with a median of 10 years before the spine CT screening of CASH study. Vertebral fracture of CT images was defined as the primary outcome and the main measures included volumetric bone mineral density at participants' median of 10 years visit and dietary calcium intake at baseline. Odds ratio (OR) and 95% confidence interval (CI) were obtained for the associations of vertebral fracture with dietary calcium from ordinal logistic regression models (if outcome defined as three categories) or dichotomous logistic regression models (when mild, moderate, or severe fracture were combined and defined as prevalent fracture and no fracture as reference group). Because only 14.5% reached Chinese Dietary Reference Intakes (CDRI) calcium target of ≥800 mg/day, we selected 500, 600, 700, 800 mg/day of calcium intake from food as cutpoints for modeling, respectively. Findings Of the 3457 CASH participants, 3273 (94.7%) were used for analysis including 2052 women (mean [SD] age, 52.1 [9.0] years) and 1221 men (53.3 [9.1] years). Total vertebral fracture prevalence was 16.5% (n=551). The mean daily calcium intake from the FFQ was calculated as 517.0±266.4 mg. 8% reduction of fracture risk was observed per 100 unit increase of calcium intake from food among females (OR, 0.92; 95% CI, 0.87-0.97), but results among males were not significant (OR, 0.98; 95% CI, 0.92-1.04). No interaction was detected between vBMD and calcium intake from food (P>0.05). When high calcium intake groups had enough sample sizes (i.e. calcium ≥500 or ≥600 mg/day), negative assciations of fracture risk with calcium intake were found among females (≥500 vs. <500 mg/day: OR, 0.62; 95% CI, 0.47-0.80; ≥600 vs. <600 mg/day: OR, 0.59; 95% CI, 0.44-0.79), but this trend as not shown when cutpoints of calcium intake were set as 700 or higher. The same regressions were performed for male participants, but no siginificance was found. A positive correlation of calcium intake and vBMD was observed for females (P=0.01), but there was a non-significant negative trend for males (P=0.16). Interpretation Higher dietary calcium intake was associated with lower vertebral fracture among healthy women with low calcium intake. Further, higher calcium intake in women was related to a modestly greater volumetric spine BMD. Among men, more data are required and our results could not provide evidence to support a possible overall benefit of a higher calcium intake in reducing the risk of vertebral fractures. Funding: The foundation from the capital health research and development of special (no. 2014-2-1122), Beijing Bureau of Health 215 Program (No. 2009-2-03), the Ministry of Science and Technology of the China (Grants 2012BAI10B02). This work was also sponsored by the China government grants from CAMS Innovation Fund for Medical 19 Sciences (CIFMS, 2016-I2M-2-004) and Construction of Basic Information Technology Support System and Platform for National Prevention and Treatment of Cardiovascular Diseases. Declaration of Interest: We declare no competing interests. Ethical Approval: The protocol and informed consent for the CASH study were reviewed and approved by the institutional review board of Beijing Jishuitan Hospital (approval number No. 201210-01; No. 201512-02).
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