title: Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families.
abstract: Hypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (both P<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension.
authors.affiliation: From the Departments of Epidemiology (A.L.K., C.H.B., J.M.Z.) and Human Genetics (C.M.K., J.M.Z.), University of Pittsburgh, PA; Department of Medicine, Indiana University School of Medicine, Indianapolis (J.H.P.); and Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago (V.W.W., A.L.P.). kuipers@pitt.edu.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Kuipers
authors.affiliation: From the Departments of Epidemiology (A.L.K., C.H.B., J.M.Z.) and Human Genetics (C.M.K., J.M.Z.), University of Pittsburgh, PA; Department of Medicine, Indiana University School of Medicine, Indianapolis (J.H.P.); and Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago (V.W.W., A.L.P.).
authors.forename: Candace M
authors.initials: CM
authors.lastname: Kammerer
authors.affiliation: From the Departments of Epidemiology (A.L.K., C.H.B., J.M.Z.) and Human Genetics (C.M.K., J.M.Z.), University of Pittsburgh, PA; Department of Medicine, Indiana University School of Medicine, Indianapolis (J.H.P.); and Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago (V.W.W., A.L.P.).
authors.forename: J Howard
authors.initials: JH
authors.lastname: Pratt
authors.affiliation: From the Departments of Epidemiology (A.L.K., C.H.B., J.M.Z.) and Human Genetics (C.M.K., J.M.Z.), University of Pittsburgh, PA; Department of Medicine, Indiana University School of Medicine, Indianapolis (J.H.P.); and Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago (V.W.W., A.L.P.).
authors.forename: Clareann H
authors.initials: CH
authors.lastname: Bunker
authors.affiliation: From the Departments of Epidemiology (A.L.K., C.H.B., J.M.Z.) and Human Genetics (C.M.K., J.M.Z.), University of Pittsburgh, PA; Department of Medicine, Indiana University School of Medicine, Indianapolis (J.H.P.); and Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago (V.W.W., A.L.P.).
authors.forename: Victor W
authors.initials: VW
authors.lastname: Wheeler
authors.affiliation: From the Departments of Epidemiology (A.L.K., C.H.B., J.M.Z.) and Human Genetics (C.M.K., J.M.Z.), University of Pittsburgh, PA; Department of Medicine, Indiana University School of Medicine, Indianapolis (J.H.P.); and Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago (V.W.W., A.L.P.).
authors.forename: Alan L
authors.initials: AL
authors.lastname: Patrick
authors.affiliation: From the Departments of Epidemiology (A.L.K., C.H.B., J.M.Z.) and Human Genetics (C.M.K., J.M.Z.), University of Pittsburgh, PA; Department of Medicine, Indiana University School of Medicine, Indianapolis (J.H.P.); and Tobago Health Studies Office, Scarborough, Tobago, Trinidad and Tobago (V.W.W., A.L.P.).
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zmuda
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000450:Aldosterone / Q000097:blood*; D000886:Anthropometry; D015415:Biomarkers / Q000097:blood; D044383:Black People / Q000235:genetics*; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000208:ethnology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood*; D010375:Pedigree; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000502:physiology; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D015675:Osteocalcin; D000450:Aldosterone; D012083:Renin
keywords: aldosterone; bone density; hypertension; osteocalcin; renin