What are the causes of osteoporosis in men?

Causes of Osteoporosis in Men

The most important causes of osteoporosis in men are advanced age (>70 years), low body weight (BMI <20-25 kg/m²), significant weight loss (>10%), physical inactivity, oral corticosteroid use, previous fragility fracture, and androgen deprivation therapy, with secondary causes identifiable in 30-60% of cases. 1

Primary Risk Factors

Age-Related and Constitutional Factors

• Advanced age (>70 years) is the single strongest risk factor for osteoporosis in men, with trabecular bone loss occurring primarily through decreased trabecular thickness while maintaining connectivity (unlike women who lose trabecular connectivity) 1
• Low body weight (BMI <20-25 kg/m²) represents a major constitutional risk factor that significantly increases fracture probability 1
• Weight loss exceeding 10% (compared with usual young/adult weight or recent weight loss) substantially elevates osteoporosis risk 1
• Physical inactivity (no regular walking, stair climbing, weight carrying, housework, or gardening) is a well-established modifiable risk factor 1

Previous Fracture History

• Prior fragility fracture (fracture from standing height or lower) is among the most important predictors of future osteoporotic fractures 1
• Men with previous vertebral or hip fractures have markedly elevated risk for subsequent fractures 2

Medication-Induced Causes

Corticosteroids

• Oral corticosteroid use is one of the most important and common causes of secondary osteoporosis in men 1
• Glucocorticoid excess (predominantly exogenous) represents a frequent secondary cause in men with vertebral fractures 3

Androgen Deprivation Therapy

• Androgen deprivation therapy (both pharmacologic and orchiectomy) is a strong predictor of both osteoporosis and fracture in men, with dose-dependent effects 1
• Men receiving ≥9 doses of gonadotropin-releasing hormone agonist have a relative risk of 1.45 for osteoporotic fracture 1
• Men who underwent orchiectomy have a relative risk of 1.54 for fracture 1

Secondary Causes (Present in 30-60% of Cases)

Hypogonadism

• Hypogonadism is found in up to 20% of men with vertebral crush fractures, though clinical features of testosterone deficiency may not always be apparent 4
• Both total and free testosterone levels decline with age, though there is no abrupt "andropause" comparable to menopause in women 3
• Hypogonadal osteoporosis is associated with increased bone resorption and decreased mineralization 4

Gastrointestinal and Malabsorption Disorders

• Gastrointestinal disease predisposes to bone disease through intestinal malabsorption of calcium and vitamin D 3
• Gastric surgery is a recognized secondary cause of osteoporosis in men 4
• Celiac disease and other malabsorption syndromes contribute to bone loss 1

Other Endocrine Disorders

• Thyroid disease and thyroid replacement therapy have plausible physiologic rationales but insufficient data in men to confirm as definitive risk factors 1
• Hyperparathyroidism has been associated with osteoporosis though data in men are limited 1

Chronic Diseases

• Spinal cord injury is a moderate predictor of both low BMD and osteoporotic fracture in men 1
• Chronic liver and kidney disease are associated with increased fracture risk 2
• Inflammatory bowel disease and rheumatoid arthritis increase osteoporosis risk 2
• Multiple myeloma and systemic mastocytosis have been associated with osteoporosis in men 3

Lifestyle and Modifiable Factors

Smoking and Alcohol

• Cigarette smoking is a moderate predictor of increased risk for low bone mass and probable fracture risk 1
• Alcohol use results in increased probability of fracture but has not been consistently associated with decreased BMD in available studies 1
• Excess alcohol consumption (beyond moderate intake) is recognized as a risk factor 2

Nutritional Deficiencies

• Low dietary calcium intake is a moderate predictor of increased risk for low bone mass 1
• Vitamin D deficiency is a potentially modifiable risk factor, though data in men specifically are insufficient to determine its role in low BMD-mediated fracture 1, 5

Conditions with Insufficient Evidence in Men

The following conditions have plausible physiologic rationales and supporting data in women, but insufficient evidence specifically in men to confirm as definitive risk factors: 1

• Respiratory disease (independent of steroid use)
• Type 2 diabetes (studies show mixed results, with some showing no association or even increased BMD) 1
• Dietary vitamin D intake as an independent factor
• Anticonvulsant drug use (recognized association but limited male-specific data) 3, 4

Clinical Pitfall

A critical error is failing to search for secondary causes in men with osteoporosis, as 30-60% of men with vertebral fractures have an underlying illness contributing to bone disease—a substantially higher proportion than in women. 1, 3 This necessitates a complete evaluation including hypogonadism screening, assessment for glucocorticoid exposure, gastrointestinal disease evaluation, and screening for other endocrine and systemic disorders. 6