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Is bone fragility increased alongside adverse cardiovascular effects in a genetic model of primary aldosteronism?

Robert Little, Aarhus University



Primary aldosteronism (PA) is the most common endocrine cause of hypertension. Compared to essential hypertension, PA is associated with increased morbidity and mortality, principally due to enhanced cardiovascular risk. However, it is becoming apparent that elevated aldosterone may also have direct effects on bone metabolism. Clinical reports have shown that PA is associated with increased risk of bone fracture(1); however, there is conflicting data on whether bone mineral density (BMD) is significantly altered in PA patients(2). Hence, the effect of aldosterone may be greatest on bone trabecular structure.

The most common inherited form of PA (Familial hperaldosteronism type ii, FH-II) has been recently traced to mutation of the adrenal chloride channel ClC-2 (gene: ClCN2). A mouse model with the equivalent human mutation (ClCN2 R180Q) has been shown to recapitulate the basic features of FH-II(3). However, an understanding of bone metabolism in these animals remains to be determined.

In ClCN2 R180Q mutant mice I seek to:

  1. Determine BMD and microarchitecture parameters
  2. Assess potential sex difference in bone phenotype of mutants
  3. Assess if ageing has differential effects in the model


  1. Wu VC, Chang CH, Wang CY, et al. Risk of Fracture in Primary Aldosteronism: A Population-Based Cohort Study. J Bone Miner Res. 2017;32(4):743-52.
  2. Notsu M, Yamauchi M, Yamamoto M, et al. Primary Aldosteronism as a Risk Factor for Vertebral Fracture. J Clin Endocrinol Metab. 2017;102(4):1237-43.
  3. Schewe J, Seidel E, Forslund S, et al. Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation. Nat Commun. 2019;10(1):5155.


Grant awarded: £3,800.00


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