HTN: Calcium (2015)

Varenna M, Manara M, Galli L, Binelli L, Zucchi M, Sinigaglia L. The association betweeen osteoporosis and hypertension: The role of a low dairy intake. Calcif Tissue Int. 2013; 93: 86-92. PubMed ID: 23652773
Study Design:
Cross-Sectional Study
D - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
  • To confirm the association between osteoporosis and hypertension
  • To examine if low calcium intake from dairy sources could be a pathogenic link between osteoporosis and hypertension. 
Inclusion Criteria:
  • Female
  • Post-menopausal
  • Caucasian
  • Consecutive subjects that visited the Gaetano Pini Institue's Bone Metabolic Unit in Milan, Italy from January 2002 to July 2008 for first densitometry screening for osteoporosis
  • Subjects with serum calcium and creatinine within normal reference limits
  • Subjects that completed informed consent.
Exclusion Criteria:
  • Past or current use of anti-resorptive drugs, calcium, vitamin D supplements or hormone replacement therapy
  • Drug treatments known to effect calcium metabolism, including diuretics and beta-blockers
  • Could not recall exactly the drugs they took
  • Had altered their food intake behavior in the past ten years for medical reasons or for weight loss
  • Major chronic disease other than essential hypertension.
Description of Study Protocol:


Subjects were recruited from referrals for a densitometry screening for osteoporosis at the Bone Metabolic Unit in Gaetano Pini Institute. More than 90% of subjects were residents of Milan, Italy, or adjoining towns.


All subjects were clinically evaluated, including a dietary intake assessment, osteoporosis and hypertension assessment, covariates assessment and anthropometric measurement.

Statistical Analysis

  • Shapiro-Wilk test for normality of distribution
  • Parametric tests:
    • Women with or without osteoporosis
    • Women with or without hypertension
    • Students T-test (continuous variables)
    • X2 test (categorical variables).
  • Unconditional logistic regression:
    • Dairy intake and presence of osteoporosis, hypertension or both diseases
    • Included in model variables statistically significant in univariable analysis along with other variables with clinical relevance to outcomes (i.e., age, smoking, caffeine intake, physical activity).
  • Crude and adjusted odds ratios and 95% confidence intervals: By quartiles of dairy intake
  • Two-sided testing at 95% significance level
  • SPSS software.
Data Collection Summary:

Timing of Measurements

One measurement time.

Dependent Variables

  • Osteoporosis assessment:
    • Lumbar bone mineral density value of 0.759g per cm2 (World Health Organization criteria)
    • Bone mineral density at lumbar level by dual-energy X-ray absorptiometry
    • DXA quality assurance measurements; identical scan protocol for all participants.
  • Hypertension assessment:
    • Systolic blood pressure 140mm Hg or more, or diastolic blood pressure 90mm Hg or more, or current use of anti-hypertensive medication
    • Blood pressure measured on left arm, in seated position, taking the mean of two measurements repeated at least five minutes apart.

Independent Variables

  • Dietary intake:
    • Weekly food-frequency questionnaire
    • Intake assessed by the number of standardized 300mg Ca servings
    • Categorized into four groups according to number of weekly servings:
      • Seven or less, eight to 11, 12 to 15, 16 or more
      • Lowest quartile less than 400mg per day; highest quartile higher than 800mg per day.
  • Covariates:
    • Interviewed with a structured questionnaire, covering:
      • Reproductive variables
      • Past medical history related to chronic diseases and medical treatments
      • Lifestyle habits:
        • Smoking (non-smokers; current smokers)
        • Alcohol
        • Coffee (high, low)
        • Physical activity (inactive, active)
      • Incidence of fracture after menopause (none, one or more)
      • Height and body weight with calibrated stadiometers.
Description of Actual Data Sample:
  • Initial N: N=3,301 females
  • Attrition (final N): N=3,301 females
  • Age: Mean age of  57.5 years (±4.4 years)
  • Ethnicity: Caucasian
  • Other relevant demographics: Reside in Milan, Italy or adjoining towns.


  • Mean age at menarche: 13.1 years (±1.6 years)
  • Mean age at menopause: 50.8 years (±3.1 years)
  • Mean BMI: 23.9 (±3.4)
  • Osteoporosis: 25.7% (N=850)
  • Hypertension: 25.0% (N=826).


Bone Diseases Unit, Gaetano Pini Institute, Milan, Italy.


Summary of Results:

Key Findings

  Comparison of Osteoporosis Comparison of Hypertension
Without (N=2,451) p With
Without (N=2,475) p
Age (years) (mean SD)  59.3 (4.2) 56.9 (4.2) 0.000 57.5 (4.9) 57.5 (4.9) 0.837
Age at menarche (years) (mean SD)  13.3 (1.6) 13.0 (1.6) 0.000 12.9 (1.6) 13.1 (1.6) 0.006
Age at menopause (years) (mean SD) 50 (3.7) 51.1 (2.8) 0.000 49.3 (4.4) 51.3 (2.2) 0.000
BMI (kg/m2) (mean SD) 22.9 (3.7) 24.2 (3.4) 0.000 24.9 (3.8) 23.5 (3.2) 0.000
Overweight (BMI higher than 25) (percent) 172 (20.2) 854 (34.8) 0.000 349 (42.3) 677 (27.4) 0.000
Obesity (BMI higher than 30) (percent) 24 (2.8) 136 (5.5) 0.001 76 (9.2) 84 (3.4) 0.000
Physical inactivity (two or more  sessions per week) (percent) 676 (79.5) 1,805 (73.6) 0.001 637 (77.1) 1,844 (74.5) 0.137
Prior fractures (percent) 90 (10.6) 58 (2.4) 0.000 42 (5.1) 106 (4.3) 0.709
Low dairy (400mg per day or more) (percent) 272 (32.0) 590 (24.1) 0.000 260 (31.5) 602 (24.3) 0.000
Hypertension/ Osteoporosis (percent) 274 (32.2) 552 (22.5) 0.000 274 (33.2) 576 (23.3) 0.000
  • Coffee intake and smoking habits were not different among either hypertensive or osteoporotic groups
  • There was a significantly higher prevalence of hypertensives among osteoporotics as well as a higher prevalence of osteoporotics among hypertensives
  • Proportion of subjects with the lowest quartile of dairy intake was higher in both the "with osteoporosis" and "with hypertension" groups, respectively.
Prevalence of Osteoporosis and Hypertension by Lowest Quartile of Calcium Intake by Dairy Sources
  1° Quartile
(Seven or More Servings)
 Women with osteoporosis (percent) 272 (31.6)
 Crude OR (95% CI) 1.58 (1.27, 1.97)
 Adjusted OR (95% CI) 1.43 (1.12, 1.82)
 Women with hypertension (percent) 260 (30.2)
 Crude OR (95% CI) 1.44 (1.16, 1.80)
 Adjusted OR (95% CI) 1.46 (1.15, 1.85)
Osteoporosis and hypertension
 Women with both (percent) 97 (11.3)
 Crude OR (95% CI) 1.75 (1.23, 2.48)
 Adjusted OR (95% CI) 1.60 (1.10, 2.34)
  *Adjusted for age, BMI, age at menopause, age at menarche, physical activity, high caffeine intake, smoking.
  • Women in the lowest quartile of calcium intake by dairy had a significantly higher risk of:
    • Osteoporosis compared with those in the highest quartile of intake
    • Hypertension compared with those in the highest quartile of intake
    • Having both osteoporosis and hypertension compared to those in the highest quartile of intake
    • Results remain statistically significant after the adjustment for covariates.
  • P for trend:
    • The proportion of women with osteoporosis decreased across increasing quartiles of calcium intake by dairy (P=0.000)
    • The proportion of women with hypertension decreased across increasing quartiles of calcium intake by dairy (P=0.000)
    • The proportion of women with osteoporosis and hypertension decreased across increasing quartiles of calcium intake by dairy (P=0.001).

Other Findings

For osteoporosis, adjusted for the same variables, dairy intake was also directly associated with bone mineral density values (linear regression beta-coefficient=0.007; P=0.000).


Author Conclusion:
This study confirms earlier findings that osteoporosis and hypertension are associated in post-menopausal women. Low calcium intake from dairy sources may increase the risk of both diseases for which there may be a pathogenic link; further longitudinal studies are recommended to confirm results.
Funding Source:
University/Hospital: Gaetano Pini Institute, Milan, Italy
Reviewer Comments:
  • Length of dietary intake monitoring to assess dairy/calcium intake via weekly food frequency questionnaire is unclear in this cross-sectional study
  • No information is given for attrition; in this case the total number of participants screened, but deemed ineligible, for the study
  • Study was limited in ability to generalize results to populations that are non-Caucasian.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) N/A
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? Yes
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? No
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  4.4. Were reasons for withdrawals similar across groups? ???
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes