title: Risk of hypercalcemia in blacks taking hydrochlorothiazide and vitamin D.
abstract: BACKGROUND
  Hydrochlorothiazide, an effective antihypertensive medication commonly prescribed to blacks, decreases urinary calcium excretion. Blacks have significantly higher rates of hypertension and lower levels of 25-hydroxyvitamin D. Thus, they are more likely to be exposed to vitamin D supplementation and thiazide diuretics. The risk for hypercalcemia among blacks using vitamin D and hydrochlorothiazide is undefined.
  
  
  METHODS
  We assessed the frequency of hypercalcemia in hydrochlorothiazide users in a post hoc analysis of a randomized, double-blind, dose-finding trial of 328 blacks (median age 51 years) assigned to either placebo, or 1000, 2000, or 4000 international units of cholecalciferol (vitamin D3) daily for 3 months during the winter (2007-2010).
  
  
  RESULTS
  Of the 328 participants, 84 reported hydrochlorothiazide use and had serum calcium levels assessed. Additionally, a comparison convenience group of 44 enrolled participants who were not taking hydrochlorothiazide had serum calcium measurements at 3 months, but not at baseline. At 3 months, hydrochlorothiazide participants had higher calcium levels (0.2 mg/dL, P <.001) than nonhydrochlorothiazide participants, but only one participant in the hydrochlorothiazide group had hypercalcemia. In contrast, none of the nonhydrochlorothiazide participants had hypercalcemia. In a linear regression model adjusted for age, sex, 25-hydroxyvitamin D at 3 months, and other covariates, only hydrochlorothiazide use (Estimate [SE]: 0.05 [0.01], P = .01) predicted serum calcium at 3 months.
  
  
  CONCLUSIONS
  In summary, vitamin D3 supplementation up to 4000 IU in hydrochlorothiazide users is associated with an increase in serum calcium but a low frequency of hypercalcemia. These findings suggest that participants of this population can use hydrochlorothiazide with up to 4000 IU of vitamin D3 daily and experience a low frequency of hypercalcemia.
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address: pchandler@partners.org.
authors.forename: Paulette D
authors.initials: PD
authors.lastname: Chandler
authors.affiliation: Department of Epidemiology and Biostatistics, Michigan State University, East Lansing.
authors.forename: Jamil B
authors.initials: JB
authors.lastname: Scott
authors.affiliation: Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, Mo.
authors.forename: Bettina F
authors.initials: BF
authors.lastname: Drake
authors.affiliation: Harvard Medical School, Boston, Mass; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Mass.
authors.forename: Kimmie
authors.initials: K
authors.lastname: Ng
authors.affiliation: Harvard Medical School, Boston, Mass; Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
authors.forename: John P
authors.initials: JP
authors.lastname: Forman
authors.affiliation: Harvard Medical School, Boston, Mass; Department of Gastroenterology, Massachusetts General Hospital, Boston, Mass; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Gary G
authors.initials: GG
authors.lastname: Bennett
authors.affiliation: Department of Psychology and Neuroscience, Duke University, Durham, NC.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Hollis
authors.affiliation: Harvard Medical School, Boston, Mass; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass; Division of Pediatrics, Medical University of South Carolina, Charleston.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Harvard Medical School, Boston, Mass; Department of Nutrition, Harvard School of Public Health, Boston, Mass; Center for Community-Based Research, Dana-Farber Cancer Institute, Boston, Mass.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Emmons
authors.affiliation: Harvard Medical School, Boston, Mass; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Mass; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
mesh_terms: D000328:Adult; D000368:Aged; D044383:Black People; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002118:Calcium / Q000097:blood; D004232:Diuretics / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006934:Hypercalcemia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D014807:Vitamin D / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D050071:Bone Density Conservation Agents; D004232:Diuretics; D006852:Hydrochlorothiazide; D014807:Vitamin D; D002118:Calcium
keywords: Black; Hypercalcemia; Hypertension; Thiazide diuretics; Vitamin D