The Effect of Disease-specific Treatment on Bone Turnover Markers in Patients With Primary Aldosteronism
Condition: Primary Aldosteronism
MeSH terms: Hyperaldosteronism
Study type: Observational

Summary: 
      Primary aldosteronism (PA) is a disorder of the adrenal gland causing an autonomous
      overproduction of mineralocorticoids, leading to arterial hypertension. Although rare, it is
      the most frequent cause of secondary hypertension. Early detection is important to avoid end
      organ damage, specifically cardiovascular and metabolic morbidity. Recent studies showed a
      positive correlation between patients with PA with lower bone density especially at the
      spine, with significant improvement post treatment, either medically or surgically. There was
      also a positive correlation between high aldosterone renin ratio with higher levels of intact
      parathyroid hormone (iPTH) which is responsible for cortical bone loss especially at the
      distal forearm.

      We hypothesize that our patients with PA have a higher level of iPTH, with lower bone density
      especially at the distal forearm, with improvement post treatment.
    

Detailed description: 
      In 2004, through an animal model study, rats given aldosterone/salt treatment were found to
      have reduction in bone mineral density (BMD) and cortical bone strength. This was believed to
      be due to hypermagnesuria and hypercalciuria leading to bone loss.

      This led to subsequent studies which found the association between PA with low serum ionized
      calcium, increased urine calcium and magnesium, raised intact parathyroid hormone (PTH)
      levels with subsequent low bone mineral density.

      In one small study of 11 patients with confirmed PA taken from a cohort of 188 patients with
      adrenal incidentaloma, BMD of vertebral, total and neck of femur was found to be lower than
      non-PA patients, with a higher prevalence of vertebral osteoporotic fractures (72.7% among PA
      patients vs 20% among non-PA patients). Serum PTH was significantly higher in PA group
      compared to non-PA group. Six months of treatment either medically or surgically led to
      significant decrease of urinary calcium excretion and PTH in PA group. Lumbar spine BMD
      showed significant improvement one year after treatment in 5 patients.

      The cross-sectional and interventional data from the GECOH study, which was conducted in a
      tertiary center in Austria on patients confirmed to have PA, looked at differences in PTH
      levels between patients with PA (n=10) and essential hypertension (EH) (n=182) and found PTH
      levels to be significantly higher in PA patients compared with EH group. Treatment with
      either adrenalectomy or mineralocorticoid receptor antagonists led to a significant decrease
      of PTH concentrations. Both of these studies had no significant differences in serum Vitamin
      D level in both cases and controls, as well as pre and post treatment for PA patients.
      However in the latter study, PTH reduction was found to be more significant in PA patients
      who underwent adrenalectomy compared to patients treated medically with mineralocorticoid
      receptor antagonists.

      A recent large-scale study on more than 3000 German general adult population showed a
      significant but non linear association between aldosterone-renin ratio with plasma PTH
      concentrations, especially in subjects with ARR>90th percentile, despite normal Vitamin D
      levels. This was believed to be due to the presence of parathyroid receptors type 1 in the
      adrenals as well as the parathyroid glands expressing mineralocorticoid receptors. However,
      calcium intake status as well as calcium levels were not assessed in this study.

      This findings were all echoed in a few other studies which showed a positive association
      between PTH levels with PA which was not affected by Vitamin D status.

      It is well known that high PTH level is associated with low bone mass and higher osteoporotic
      fracture risk due to the stimulation effect of PTH on the osteoclastic and osteoblastic
      activity of the bones resulting in the release of calcium and phosphate from the bone.

      Up to date, to our knowledge, there has been no study on the association between PA with bone
      turnover markers. The use of this sensitive marker as a surrogate indicator of improvement in
      bone mass pre and post treatment in patients with PA either medically or surgically is novel.
      The relationship between calcium intake in the patients with the bone metabolism and blood
      parameters were not looked into previously. In addition, the involvement of peripheral
      cortical bone mass (distal radius), which is usually associated with elevated PTH, in this
      group of patients has not been studied.

      In this study, we aim to:

        1. Assess the BMD of vertebrae, total and femoral neck, and distal third radius in PA
           patients compared to non-PA.

        2. Evaluate the effect of specific treatments on bone turnover markers and BMD in patients
           with PA

        3. Assess the relationship between BMD and bone turnover markers with serum iPTH, calcium,
           magnesium and vitamin D levels.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This is a prospective study conducted in out-patient clinics of a tertiary care center. The
        study population consists of patients referred to our centres for endocrine hypertension.
      
Biospecimen description: 
      Blood samples
    
Keywords: bone mineral density; bone turnover markers; primary aldosteronism treatment