What therapy is recommended for men at increased risk of fracture due to osteoporosis?

Treatment Recommendations for Men with Increased Fracture Risk Due to Osteoporosis

Oral bisphosphonates (alendronate or risedronate) are the first-line treatments for men at high risk of fracture due to osteoporosis. 1

Risk Assessment and Diagnosis

• Use FRAX as the appropriate tool for fracture risk assessment and to establish intervention thresholds in men with osteoporosis 1
• A female reference database should be used for the densitometric diagnosis of osteoporosis in men 1
• Men at high risk include those with:
  • Prior fragility fracture 1
  • BMD T-score ≤ -2.5 at hip or spine 1
  • FRAX (GC-adjusted) 10-year risk for major osteoporotic fracture ≥ 10% 1
  • FRAX (GC-adjusted) 10-year risk for hip fracture > 1% 1

First-Line Treatment

• Oral bisphosphonates (alendronate or risedronate) are strongly recommended as first-line treatment for men at high risk of fracture 1
• Ensure adequate calcium intake (1,000-1,200 mg/day) and vitamin D intake (600-800 IU/day; serum level ≥20 ng/ml) 1
• Recommend lifestyle modifications:
  • Balanced diet
  • Maintaining weight in recommended range
  • Smoking cessation
  • Regular weight-bearing or resistance training exercise
  • Limiting alcohol intake to 1-2 alcoholic beverages/day 1

Second-Line Treatment Options

If oral bisphosphonates are not appropriate (due to comorbidities, patient preference, or concerns about adherence):

1. IV bisphosphonates (zoledronic acid) - administered as annual IV infusion 1, 2
2. Denosumab - 60mg subcutaneously every 6 months 3
   • FDA approved for treatment to increase bone mass in men with osteoporosis at high risk for fracture 3
   • Particularly useful for patients with swallowing difficulties or gastrointestinal conditions 2

Treatment for Very High-Risk Patients

For men at very high risk of fracture (multiple fractures, very low BMD):

• Sequential therapy starting with a bone-forming agent followed by an anti-resorptive agent is strongly recommended 1
• Bone-forming agents to consider:
  • Teriparatide - FDA approved for men with primary or hypogonadal osteoporosis at high risk for fracture 4
  • Abaloparatide - considered appropriate first-line treatment for men with osteoporosis at very high risk of fracture 1

Special Considerations

• Assess serum total testosterone as part of pre-treatment evaluation 1
• Consider appropriate hormone replacement therapy in men with low levels of total or free serum testosterone 1
• For men with glucocorticoid-induced osteoporosis (daily dosage equivalent to 7.5 mg or greater of prednisone expected for at least 6 months), oral bisphosphonates are recommended as first-line therapy 1

Monitoring and Follow-up

• Use biochemical markers of bone turnover to assess adherence to anti-resorptive therapy 1
• Be aware that up to 64% of men may be non-adherent to bisphosphonate therapy by 12 months, highlighting the need for close monitoring 2
• Consider BMD testing after 1-2 years of therapy 2

Pitfalls and Caveats

• Exclude secondary causes of osteoporosis, as 30-60% of men with vertebral fractures have another illness contributing to bone disease 5
• Common secondary causes include hypogonadism, glucocorticoid excess, gastrointestinal disease, and thyrotoxicosis 5
• Although men with osteoporosis have a higher rate of fractures, the majority of fractures occur in men with T-scores > -2.5, suggesting factors beyond BMD are important in determining risk 6
• Discontinuation of treatment without follow-up can lead to rebound bone loss 2
• For denosumab, be aware of risk of severe hypocalcemia in patients with advanced chronic kidney disease 3