What is the best treatment for a patient with decreasing bone mineral density (BMD) and a rising Fracture Risk Assessment Tool (FRAX) hip score?

From the Guidelines

The best treatment for a patient with decreasing bone mineral density and rising FRAX hip score is typically bisphosphonate therapy, particularly alendronate (70mg weekly) or risedronate (35mg weekly), as recommended by the 2022 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis 1.

Key Considerations

• Bisphosphonates effectively reduce fracture risk by inhibiting bone resorption, and are strongly recommended over no treatment in high or very high fracture risk adults 1.
• Supplementation with calcium (1000-1200mg daily) and vitamin D (800-1000 IU daily) should accompany bisphosphonate therapy to optimize bone health 1.
• For patients who cannot tolerate bisphosphonates, alternatives include denosumab (60mg subcutaneously every 6 months), raloxifene, or teriparatide depending on fracture risk severity 1.
• Treatment duration typically ranges from 3-5 years initially, with reassessment afterward to determine the need for continued or modified therapy 1.
• Lifestyle modifications are also essential, including weight-bearing exercise, smoking cessation, limiting alcohol consumption, and fall prevention strategies to reduce fracture risk 1.
• Regular monitoring with follow-up DEXA scans every 1-2 years helps assess treatment effectiveness and adjust the treatment plan as needed 1.

Additional Recommendations

• The 2022 American College of Rheumatology guideline recommends risk stratification using FRAX and DXA to determine the need for osteoporosis therapy 1.
• Patients with very high fracture risk may benefit from anabolic agents, such as teriparatide, as initial therapy 1.
• Sequential therapy with anti-resorptive agents, such as bisphosphonates, may be necessary after discontinuation of denosumab or other anabolic agents to prevent rebound bone loss and vertebral fractures 1.

From the FDA Drug Label

Effect on Bone Mineral Density (BMD) EVENITY significantly increased BMD at the lumbar spine, total hip, and femoral neck compared with alendronate at month 12. The treatment differences in BMD were 8.7% at the lumbar spine, 3.3% at the total hip, and 3. 2% at the femoral neck. Twelve months of treatment with EVENITY followed by 12 months of treatment with alendronate significantly increased BMD compared with alendronate alone. The BMD increase with EVENITY over alendronate observed at month 12 was maintained at month 24. The treatment differences in BMD at month 24 were 8.1% at the lumbar spine, 3.8% at the total hip, and 3. 8% at the femoral neck.

For a patient with decreasing bone mineral density (BMD) and a rising Fracture Risk Assessment Tool (FRAX) hip score, the best treatment option appears to be romosozumab (EVENITY), as it has been shown to significantly increase BMD at the lumbar spine, total hip, and femoral neck compared to alendronate.

• The treatment differences in BMD were 8.7% at the lumbar spine, 3.3% at the total hip, and 3.2% at the femoral neck at month 12.
• The BMD increase with EVENITY over alendronate was maintained at month 24.
• Additionally, EVENITY has been shown to reduce the risk of clinical fractures through the end of the primary analysis period, with a hazard ratio of 0.73 (95% CI: 0.61,0.88; p < 0.001) compared to alendronate alone 2.
• Another option could be denosumab (Prolia), which has also been shown to increase BMD at all anatomic sites measured at 3 years, with treatment differences in BMD of 8.8% at the lumbar spine, 6.4% at the total hip, and 5.2% at the femoral neck 3.

From the Research

Treatment Options for Decreasing Bone Mineral Density (BMD) and Rising Fracture Risk

• The patient's condition of decreasing spine BMD by 0.4% and hip BMD by 2.3% indicates a need for effective treatment to prevent fractures.
• According to 4, antiresorptive drugs such as bisphosphonates and the RANKL inhibitor denosumab are currently the most widely used osteoporosis medications, which increase BMD and reduce the risk of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis.

Fracture Risk Assessment Tool (FRAX) and Treatment

• The FRAX hip score is a useful tool in assessing fracture risk, and treatment should be considered for patients with high fracture risk.
• 4 suggests that case finding strategies, such as fracture risk-based screening in primary care using the FRAX, and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates.

Treatment Comparison and Efficacy

• A study 5 compared the efficacy of teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis, and found that combined teriparatide and denosumab increased BMD more than either agent alone.
• Another study 6 found that alendronate reduces the risk of hip fractures by 55% in postmenopausal women with osteoporosis, and that a once-weekly regimen of alendronate administration provides better patient compliance and persistence with the treatment.
• 7 reported that a second course of romosozumab following a period off treatment or on denosumab increased or maintained BMD, respectively, and was well tolerated, providing insight into treatment sequence options.
• A head-to-head trial 8 compared once-weekly alendronate 70 mg with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis, and found that alendronate produced greater gains in BMD and greater reductions in markers of bone turnover than risedronate.