What are the recommendations for managing osteoporosis in patients taking exemestane (Aromasin)?

Managing Osteoporosis in Patients Taking Exemestane

All postmenopausal women taking exemestane require baseline bone mineral density assessment, periodic monitoring, mandatory calcium (1,000-1,200 mg/day) and vitamin D (800-1,000 IU/day) supplementation, and consideration of bisphosphonates or denosumab if osteoporosis develops or fracture risk is elevated. 1, 2

Bone Loss Risk with Exemestane

Exemestane causes significant, clinically meaningful bone loss that exceeds normal age-related decline:

• Lumbar spine BMD decreases by 2.4-3.5% at 2 years compared to 0.5-2.4% with placebo 1, 2, 3
• Total hip BMD decreases by 1.8-4.6% at 2 years compared to 0.6-2.6% with placebo 1, 2, 3
• Femoral neck BMD decreases by 2.4-4.2% at 2 years 1, 2, 3
• Cortical thickness at distal radius and tibia decreases by approximately 7-8% at 2 years 1, 3
• Bone loss occurs despite calcium and vitamin D supplementation 1, 3

Mandatory Baseline Assessment

Before initiating exemestane, clinicians must:

• Evaluate baseline fracture risk using clinical assessment 1
• Measure bone mineral density with central/axial DXA at lumbar spine, total hip, and femoral neck 1
• Assess 25-hydroxy vitamin D levels due to high prevalence of deficiency in breast cancer patients 2
• Exclude severe osteoporosis (T-score < -4 or >2 vertebral fractures), which is a relative contraindication to exemestane 1

Monitoring During Treatment

• Repeat DXA every 2 years or more frequently if BMD is near treatment threshold 1
• Do not perform DXA more frequently than annually 1
• Continue monitoring throughout the treatment duration 1

Non-Pharmacologic Interventions (Required for All Patients)

• Calcium supplementation: 1,000-1,200 mg/day 1
• Vitamin D supplementation: 800-1,000 IU/day (higher doses if deficient) 1, 2
• Exercise program including balance training, flexibility exercises, endurance exercise, and resistance/progressive strengthening 1
• Smoking cessation and alcohol limitation 1

Pharmacologic Bone Protection

Initiate bisphosphonates or denosumab if:

• T-score ≤ -2.5 at any site (lumbar spine, total hip, or femoral neck) 1
• 10-year fracture probability ≥20% for major osteoporotic fracture using FRAX 1
• 10-year fracture probability ≥3% for hip fracture using FRAX 1

Options for bone-modifying agents:

• Oral bisphosphonates (e.g., alendronate, risedronate) 1, 4
• Intravenous bisphosphonates (e.g., zoledronic acid) 1, 4
• Subcutaneous denosumab at osteoporosis-indicated dosing 1

Use exemestane with caution in postmenopausal women with moderate bone mineral density loss; if used, consider concurrent bone-protective agents 1

Fracture Risk Data

• Fracture incidence with exemestane is 7.1% versus 5.4% with tamoxifen (odds ratio 1.45,95% CI 1.13-1.87) 5
• However, in the MAP.3 prevention trial, no statistically significant difference in skeletal fractures was observed between exemestane and placebo (149 vs 143 events, p=0.72) 1, 6
• The discrepancy likely reflects different patient populations and treatment contexts 1, 5

Alternative Considerations

If severe osteoporosis or very high fracture risk exists:

• Consider alternative endocrine therapies that do not reduce bone density, such as tamoxifen or raloxifene (if appropriate for the clinical indication) 1
• Tamoxifen actually preserves bone mineral density in postmenopausal women 5, 7

Key Clinical Pitfalls to Avoid

• Do not start exemestane without baseline BMD assessment 1, 2
• Do not assume calcium and vitamin D alone are sufficient to prevent bone loss 1, 3
• Do not wait for fractures to occur before initiating bone-protective therapy 1
• Do not use exemestane in patients with severe baseline osteoporosis without concurrent aggressive bone protection 1