What effect does spironolactone have on bone density?

Effect of Spironolactone on Bone Density

Spironolactone reduces bone turnover markers in postmenopausal women, suggesting a potentially beneficial effect on bone density by decreasing both bone formation and bone resorption. 1

Mechanism of Action on Bone

Spironolactone is a potassium-sparing diuretic that functions as a mineralocorticoid receptor (MR) antagonist, primarily used for:

• Heart failure
• Hypertension
• Primary hyperaldosteronism
• Edema associated with liver cirrhosis
• Acne in women 2

While not primarily prescribed for bone health, spironolactone appears to influence bone metabolism through its anti-aldosteronergic effects. Aldosterone excess may contribute to bone turnover, and blocking this pathway seems to affect bone metabolism.

Evidence on Bone Effects

The most direct evidence comes from a 2020 study examining bone turnover in postmenopausal women with primary aldosteronism 1. Key findings include:

• Patients treated with spironolactone showed significant decreases in bone turnover markers after one year
• Both bone formation and bone resorption markers decreased with spironolactone treatment
• This effect was not observed in patients treated with adrenalectomy for unilateral primary aldosteronism
• At baseline, patients with primary aldosteronism had only mildly elevated osteocalcin compared to controls

This suggests that spironolactone's mineralocorticoid receptor antagonism may have a stabilizing effect on bone metabolism by reducing excessive turnover.

Potential Mechanisms

The bone effects of spironolactone may be related to several pathways:

1. Aldosterone inhibition: By blocking aldosterone's effects, spironolactone may reduce any negative impacts of excess aldosterone on bone metabolism
2. Anti-fibrotic effects: Spironolactone reduces myocardial fibrosis in heart failure 3, and similar mechanisms might affect bone remodeling
3. Hormonal effects: Spironolactone has anti-androgenic properties that could influence bone metabolism indirectly

Clinical Implications

For patients at risk of osteoporosis who require spironolactone for other indications (heart failure, resistant hypertension, etc.), the potential bone benefits represent a positive secondary effect.

However, it's important to note that:

• The evidence is primarily from studies in patients with primary aldosteronism
• The magnitude of effect on actual bone mineral density (rather than just turnover markers) is not well established
• The long-term impact on fracture risk remains unknown

Monitoring Considerations

When using spironolactone, clinicians should be aware of:

• Potential for hyperkalemia, especially in patients with renal impairment or those taking other potassium-sparing medications 3, 2
• Common side effects including gynecomastia (10%), menstrual irregularities, decreased libido, and fatigue 2
• Need for regular monitoring of serum potassium and renal function

Comparison with Other Medications

Eplerenone, another mineralocorticoid receptor antagonist, has fewer hormonal side effects than spironolactone but is less potent 2. Whether eplerenone has similar effects on bone metabolism is not well established.

Conclusion

The available evidence suggests that spironolactone has a potentially beneficial effect on bone metabolism by reducing bone turnover markers in postmenopausal women. This effect appears to be related to its anti-aldosteronergic properties and may represent an additional benefit for patients requiring this medication for other indications.