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Fracture risk increases in primary aldosteronism
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The risk for osteoporotic fracture and bone fracture at any site may be higher among adults with primary aldosteronism and aldosterone-producing adenoma compared with adults with essential hypertension, study data show.
Likwang Chen, PhD, associate investigator at the Institute of Population Health Sciences, National Health Research Institutes in Taiwan, and colleagues evaluated data from the Taiwan National Health Insurance database on 2,533 adults with primary aldosteronism, including 921 adults with aldosterone-producing adenoma diagnosed between 1997 and 2010 to determine the long-term effect of hyperaldosterone on fracture risk and possible risk mitigation by therapies. Participants were matched to adults with essential hypertension for comparison: 10,132 for primary aldosteronism and 3,684 for aldosterone-producing adenoma. Follow-up was a mean 5.3 years.
Compared with the essential hypertension group, the primary aldosteronism group had a greater risk for osteoporotic fracture (P < .001) and higher rate of bone fracture at any site (P < .001). The aldosterone-producing adenoma group also had a higher risk for bone fracture at any site compared with the essential hypertension group (P < .001).
The incident rate of bone fracture at any site was higher among the primary aldosteronism group (14.4 per 1,000 person-years) compared with the essential hypertension group (8.3 per 1,000) and the aldosterone-producing adenoma group (11.2 per 1,000) compared with the essential hypertension group (6.5 per 1,000).
The primary aldosteronism group had a higher excessive risk for fracture at any site compared with the essential hypertension group (P < .001); the same was true for the aldosterone-producing adenoma group vs. essential hypertension group (P < .001).
The risk for osteoporotic fracture may also be higher among women with primary aldosteronism (P = .008) and women with aldosterone-producing adenoma (P = .049) treated with mineralocorticoid receptor antagonists (MRA).
“[Primary aldosteronism] and hyperaldosterone were tightly associated with higher risk of bone fracture, even in the case where the competing risk of death was controlled,” the researchers wrote. “Particularly, MRA treatment might not effectively reduce osteoporotic fracture and fracture at any site among female [primary aldosteronism] patients, regardless of whether they were general [primary aldosteronism] or [aldosterone-producing adenoma] patients. It calls for more research and effort to advance early diagnosis and effective treatment in [primary aldosteronism] patients who suffer significantly higher risks from bone fracture and death.” – by Amber Cox
Disclosure: Chen is employed by Taiwan’s National Health Research Institutes, which financially supported the study.
Perspective
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John W. Funder
Primary aldosteronism is associated with increased urinary calcium excretion and osteoporosis. Wu and colleagues have compared fracture rates in 2,533 patients with primary aldosteronism (921 with aldosterone-producing adenoma) against those with essential hypertension (controls) by 1:4 propensity score matching. Fractures at any site in patients with primary aldosteronism were 14.4 per 1,000 person years (kpy), 11.2 kpy for aldosterone-producing adenoma, and (by subtraction) thus 16.2% kpy in bilateral disease. Controls for primary aldosteronism as a whole have rates of 8.3 kpy, and for aldosterone-producing adenoma 6.5 kpy. At least some of the disparity in both primary aldosteronism and essential hypertension may reflect differences in age, being about 4 years higher in bilateral patients than in those with aldosterone-producing adenoma and 2 years higher in controls for primary aldosteronism than aldosterone-producing adenoma. No data are given for biochemical cure after surgery, but complete clinical cure was found in approximately 40% of aldosterone-producing adenoma cases, and some presumably partially cured aldosterone-producing adenoma patients are recorded as also being on mineralocorticoid receptor antagonists. Intriguingly, use of these drugs in women was associated with a considerably higher risk in primary aldosteronism patients, with no significant effect in men, consistent with a marked anti-androgen effect in women. In conclusion, primary aldosteronism has clearly higher levels of fracture than matched essential hypertension; the role of age has not been accounted for between adenoma and bilateral disease; and mineralocorticoid receptor antagonists appear to accelerate bone loss in women, but not men.
Disclosure: Funder reports financial or business/organizational interests with the Department of Veterans Affairs, Garnett Passe and the Rodney Williams Memorial Foundation and serving as a consultant for Pfizer/Japan.
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