What causes osteoporosis in men?

Causes of Osteoporosis in Men

The primary causes of osteoporosis in men are hypogonadism, alcoholism, and glucocorticoid exposure, which together account for 40-60% of cases. 1 These factors, along with age over 70, low body weight, weight loss, physical inactivity, and previous fragility fractures, significantly increase the risk of developing osteoporosis in men.

Major Risk Factors

Primary Risk Factors:

• Hypogonadism:

  • Strong evidence from case-control studies shows significant associations between low testosterone levels and osteoporosis 1
  • Accounts for up to 20% of men with vertebral crush fractures 2
  • Leads to increased bone resorption and decreased mineralization 2

• Androgen Deprivation Therapy:

  • All studies report significant association between androgen deprivation therapy for prostate cancer and risk for low BMD/fracture 1
  • Men receiving 9+ doses of gonadotropin-releasing hormone agonist or orchiectomy had relative risks of 1.45 and 1.54 for osteoporotic fractures 1

• Alcohol Use:

  • Relative risk of approximately 2.0 with alcohol use of 3-4 drinks per day 1
  • Risk increases with higher daily alcohol intake 1
  • Paradoxically, alcohol use was associated with increased hip BMD in some studies 1

• Glucocorticoid Use:

  • Major cause of secondary osteoporosis in men 1
  • Significantly increases risk for low BMD and fractures 1

Additional Significant Risk Factors:

• Age: Men over 70 years have significantly higher risk 1
• Low Body Weight: BMI <20-25 kg/m² 1
• Weight Loss: >10% compared to usual adult weight 1
• Physical Inactivity: No regular physical activity 1
• Previous Fragility Fracture: Strong predictor of future fractures 1
• Cigarette Smoking: Moderate predictor of increased risk for low bone mass 1
• Low Dietary Calcium: Moderate predictor of increased risk 1
• Spinal Cord Injury: Moderate predictor of both low BMD and fracture 1
• Family History: Significant associations with low BMD in large studies 1

Hormonal Factors

• Sex Hormone Binding Globulin (SHBG):

  • Elevated levels found in 53.5% of elderly men with low bone density 3
  • Negatively correlated with bone mineral density at femoral sites 3
  • Independent predictor of bone mass in multiple regression analysis 3

• Parathyroid Hormone (PTH):

  • Independent predictor of bone mass in healthy elderly men 3
  • Mild increases in PTH levels associated with lower BMD 3

Secondary Causes

Secondary causes of osteoporosis may be detected in about 55% of men with vertebral crush fractures 2. Major secondary causes include:

• Steroid therapy
• Hypogonadism
• Skeletal metastases
• Multiple myeloma
• Gastric surgery
• Anticonvulsant treatment

Clinical Implications and Pitfalls

1. Underdiagnosis: Men are not routinely screened for osteoporosis, leading to underdiagnosis 4

2. Higher Mortality: Men have greater mortality after fractures and increased complications including infection and major cardiovascular events 4

3. Hypogonadism Detection: Clinical features of testosterone deficiency may not always be present even when hypogonadism is contributing to osteoporosis 2

4. Thyroid Disease: While thyroid disease has been studied as a risk factor, most studies do not show a statistically significant association with osteoporosis in men 1

5. Type 2 Diabetes: Most studies show no association or even an increase in BMD in men with type 2 diabetes 1

Diagnostic Approach

When evaluating men for osteoporosis, clinicians should:

1. Assess for primary risk factors (age, weight, activity level, alcohol use)
2. Screen for hypogonadism with serum testosterone and luteinizing hormone levels
3. Review medication history, particularly for glucocorticoid use
4. Consider family history of osteoporosis or fractures
5. Evaluate calcium and vitamin D intake
6. Consider DXA screening for men over 70 or those with multiple risk factors

By identifying these risk factors early, appropriate interventions can be implemented to reduce fracture risk and associated morbidity and mortality in men with osteoporosis.