What is the recommended treatment for patients with a high risk of osteoporotic fracture?

From the Guidelines

For patients with a high risk of osteoporotic fracture, oral bisphosphonates, such as alendronate or risedronate, are the first-line treatment recommendation, as they have been shown to reduce the risk of vertebral, non-vertebral, and hip fractures. According to the most recent and highest quality study 1, these medications work by inhibiting bone resorption, helping to maintain or increase bone mineral density and reduce fracture risk. Treatment should be accompanied by calcium supplementation (1000-1200mg daily) and vitamin D (800-1000 IU daily) to support bone health. Weight-bearing exercise and fall prevention strategies are essential complementary measures.

Key Considerations

• The decision to start treatment should be based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications, as recommended by the American College of Physicians 1.
• For patients who cannot tolerate bisphosphonates or have very high fracture risk, alternatives include denosumab (60mg subcutaneously every 6 months), teriparatide or abaloparatide (daily subcutaneous injections for up to 2 years), or romosozumab (monthly injections for 1 year) 1.
• Treatment duration typically ranges from 3-5 years for bisphosphonates, after which a risk reassessment should determine whether to continue, take a drug holiday, or switch therapies, as suggested by the EULAR/EFORT recommendations 1.
• Medication selection should consider the patient's specific fracture risk, comorbidities, and potential side effects, and should be regularly monitored for tolerance and adherence 1.

Additional Recommendations

• Vitamin D and calcium repletion should be ensured in all men above the age of 65 years, as recommended by the evidence-based guideline for the management of osteoporosis in men 1.
• Physical exercise and a balanced diet should be recommended to all men with osteoporosis, as part of a comprehensive treatment plan 1.

From the FDA Drug Label

For the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined herein as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy

The recommended treatment for patients with a high risk of osteoporotic fracture is denosumab (Prolia) or teriparatide, as indicated in the drug labels 2 and 3.

• High risk of fracture is defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.
• Treatment with these medications can help reduce the incidence of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis.

From the Research

Frax Probability and Starting Treatment

The Fracture Risk Assessment Tool (FRAX) is a widely used algorithm to determine the 10-year probability of major osteoporotic fracture and hip fracture in patients 4. The following are key points to consider when using FRAX to guide treatment decisions:

• FRAX calculates the 10-year probability of major osteoporotic fracture (clinical vertebral, hip, forearm, or humerus) and the 10-year probability of hip fracture in men and women based on clinical risk factors and bone mineral density (BMD) of the femoral neck (optional) 4.
• The National Osteoporosis Foundation recommends treating patients with a FRAX 10-year risk score of ≥3% for hip fracture or ≥20% for major osteoporotic fracture to reduce their fracture risk 4, 5.
• Bisphosphonates are widely used in the treatment of osteoporosis and have been shown to reduce fractures in women with osteoporosis and osteopenia 6, 7.
• Zoledronate has been found to be the most effective treatment in preventing vertebral fractures and nonvertebral fractures, and could be considered a first-line option for people at increased risk of fragility fractures 7.

Treatment Options

Treatment options for patients with a high risk of osteoporotic fracture include:

• Bisphosphonates, such as alendronate, ibandronate, risedronate, and zoledronate 6, 7.
• Anabolic drugs, which may be used as initial therapy in individuals at increased risk of fracture, followed by bisphosphonates as sequential therapy 6.
• Other treatments, such as hormone replacement therapy and selective estrogen receptor modulators, may also be considered, although their use is not discussed in the provided evidence.

FRAX Limitations

While FRAX is a useful tool for assessing fracture risk, it has limitations, including:

• FRAX should not be used in all situations, and acceptance and clinical use of FRAX may be a challenge for busy physicians 4.
• FRAX has limited ability to predict hip and wrist fractures 7.
• Additional risk factors, such as frequent falls, are not represented in FRAX and warrant individual clinical judgment 5.