title: Parathyroid Hormone and the Use of Diuretics and Calcium-Channel Blockers: The Multi-Ethnic Study of Atherosclerosis.
abstract: Thiazide diuretic (TZ) use is associated with higher bone mineral density, whereas loop diuretic (LD) use is associated with lower bone density and incident fracture. Dihydropyridine-sensitive calcium channels are expressed on parathyroid cells and may play a role in parathyroid hormone (PTH) regulation. The potential for diuretics and calcium-channel blockers (CCBs) to modulate PTH and calcium homeostasis may represent a mechanism by which they influence skeletal outcomes. We hypothesized that the use of LD and dihydropyridine CCBs is associated with higher PTH, and TZ use is associated with lower PTH. We conducted cross-sectional analyses of participants treated for hypertension in the Multi-Ethnic Study of Atherosclerosis who did not have primary hyperparathyroidism or chronic kidney disease (n = 1888). We used adjusted regression models to evaluate the independent association between TZ, LD, and CCB medication classes and PTH. TZ use was associated with lower PTH when compared with non-TZ use (44.4 versus 46.9 pg/mL, p = 0.02), whereas the use of LD and CCBs was associated with higher PTH when compared with non-users of each medication class (LD: 60.7 versus 45.5 pg/mL, p < 0.0001; CCB: 49.5 versus. 44.4 pg/mL, p < 0.0001). Adjusted regression models confirmed independent associations between TZ use and lower PTH (β = -3.2 pg/mL, p = 0.0007), and LD or CCB use and higher PTH (LD: β = +12.0 pg/mL, p < 0.0001; CCB: +3.7 pg/mL, p < 0.0001). Among CCB users, the use of dihydropyridines was independently associated with higher PTH (β = +5.0 pg/mL, p < 0.0001), whereas non-dihydropyridine use was not (β = +0.58 pg/mL, p = 0.68). We conclude that in a large community-based cohort with normal kidney function, TZ use is associated with lower PTH, whereas LD and dihydropyridine CCB use is associated with higher PTH. These associations may provide a mechanistic explanation linking use of these medications to the development of skeletal outcomes. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Zaheer
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: de Boer
authors.affiliation: Division of Preventive Medicine, University of California, San Diego, CA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Allison
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jenifer M
authors.initials: JM
authors.lastname: Brown
authors.affiliation: Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA.|Kidney Research Institute, University of Washington, Seattle, WA, USA.
authors.forename: Cassianne
authors.initials: C
authors.lastname: Robinson-Cohen
authors.affiliation: Division of Nephrology-Hypertension, University of California, San Diego, CA, USA.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA.|Kidney Research Institute, University of Washington, Seattle, WA, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kestenbaum
authors.affiliation: The New York Academy of Medicine, New York, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Siscovick
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Vaidya
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy / Q000208:ethnology; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000097:blood*; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood*; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage*
chemical_list: D002121:Calcium Channel Blockers; D010281:Parathyroid Hormone; D049993:Sodium Chloride Symporter Inhibitors; D002118:Calcium
keywords: CALCIUM-CHANNEL BLOCKERS; DIURETICS; EPIDEMIOLOGY; HYPERTENSION; PARATHYROID; PARATHYROID HORMONE