What is the most effective approach for preventing and treating osteoporosis, weight-bearing exercise or medication intervention such as bisphosphonates (e.g. alendronate) or denosumab?

From the Guidelines

The most effective approach for preventing and treating osteoporosis typically involves a combination of weight-bearing exercise and medication, tailored to individual risk factors and disease severity, with bisphosphonates being the first-line medication choice, as recommended by the American College of Physicians in their 2023 guideline update 1. For prevention in those at moderate risk, regular weight-bearing exercise (like walking, jogging, or resistance training for 30 minutes most days) combined with adequate calcium (1000-1200mg daily) and vitamin D (800-1000 IU daily) is often sufficient. However, for those with established osteoporosis or high fracture risk, medication becomes essential alongside lifestyle measures. First-line medications include bisphosphonates such as alendronate (70mg once weekly) or risedronate (35mg once weekly), which work by inhibiting bone resorption. For those who cannot tolerate bisphosphonates or have severe disease, denosumab (60mg subcutaneous injection every 6 months) offers an effective alternative, as suggested by the 2023 American College of Physicians guideline update 1. These medications can reduce fracture risk by 40-70% when used appropriately, as noted in the 2017 American College of Physicians guideline update 1. The decision between prevention-focused approaches versus medication intervention should be based on bone mineral density measurements, fracture risk assessment (FRAX score), and individual factors such as age, gender, and comorbidities, as recommended by the EULAR/EFORT guidelines for management of patients older than 50 years with a fragility fracture and prevention of subsequent fractures 1. Regardless of treatment choice, all osteoporosis management plans should include fall prevention strategies, smoking cessation, and limiting alcohol consumption to optimize bone health, as emphasized in the British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines 1. Key considerations in the management of osteoporosis also include patient education on the importance of adherence to treatment and regular monitoring for tolerance and adherence to prescribed medications, as highlighted in the EULAR/EFORT guidelines 1. In cases where patients have specific conditions, such as prostate cancer, additional considerations may apply, including the use of denosumab or zoledronic acid for preventing skeletal-related events, as noted in the ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of prostate cancer 1. Ultimately, the goal of osteoporosis management is to reduce the risk of fractures and improve quality of life, which can be achieved through a comprehensive approach that incorporates lifestyle modifications, medication, and regular monitoring, as supported by the highest quality evidence available, including the 2023 American College of Physicians guideline update 1.

Some key points to consider in osteoporosis management include:

• The importance of weight-bearing exercise and adequate calcium and vitamin D intake for maintaining bone health
• The use of bisphosphonates as first-line medication for preventing and treating osteoporosis
• The role of denosumab as an alternative for patients who cannot tolerate bisphosphonates or have severe disease
• The need for regular monitoring and assessment of fracture risk to guide treatment decisions
• The importance of patient education and adherence to prescribed medications and lifestyle modifications.

In terms of specific medications and their dosages, the following are commonly used:

• Alendronate: 70mg once weekly
• Risedronate: 35mg once weekly
• Denosumab: 60mg subcutaneous injection every 6 months
• Zoledronic acid: intravenous infusion once yearly.

It is essential to note that the choice of medication and dosage should be individualized based on patient-specific factors, including comorbidities, renal function, and potential side effects, as emphasized in the 2017 American College of Physicians guideline update 1. Additionally, lifestyle modifications, such as smoking cessation, limiting alcohol consumption, and fall prevention strategies, are crucial components of osteoporosis management, as highlighted in the British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines 1. By taking a comprehensive approach to osteoporosis management, healthcare providers can help reduce the risk of fractures and improve quality of life for patients with osteoporosis, as supported by the highest quality evidence available, including the 2023 American College of Physicians guideline update 1.

From the FDA Drug Label

1.1 Treatment of Osteoporosis in Postmenopausal Women Alendronate sodium tablets, USP are indicated for the treatment of osteoporosis in postmenopausal women. In postmenopausal women, alendronate sodium tablets, USP increase bone mass and reduce the incidence of fractures, including those of the hip and spine (vertebral compression fractures).

1. 2 Prevention of Osteoporosis in Postmenopausal Women Alendronate sodium tablets, USP are indicated for the prevention of postmenopausal osteoporosis

The most effective approach for preventing and treating osteoporosis is not explicitly compared between weight-bearing exercise and medication intervention in the provided drug labels.

• Medication intervention: The labels provide information on the use of alendronate for the treatment and prevention of osteoporosis in postmenopausal women, as well as its effects on bone mass and fracture incidence 2.
• Weight-bearing exercise: There is no direct information in the provided drug labels regarding the use of weight-bearing exercise for the prevention and treatment of osteoporosis. Given the lack of direct comparison, no conclusion can be drawn regarding the most effective approach between weight-bearing exercise and medication intervention such as bisphosphonates (e.g., alendronate) or denosumab for preventing and treating osteoporosis 2, 2.

From the Research

Comparison of Weight-Bearing Exercise and Medication Intervention

• Weight-bearing exercise and medication intervention, such as bisphosphonates (e.g., alendronate) or denosumab, are two approaches to preventing and treating osteoporosis 3, 4, 5.
• Medication intervention, including bisphosphonates, has been shown to reduce the risk of osteoporotic fractures in postmenopausal women and older men 6, 7.
• Weight-bearing exercise, along with adequate intake of calcium and vitamin D, avoidance of smoking and excessive alcohol intake, and fall prevention, is also an essential component of osteoporosis prevention and treatment 3, 4, 5.

Effectiveness of Medication Intervention

• Bisphosphonates, such as alendronate, risedronate, ibandronate, and zoledronic acid, have been shown to reduce the risk of new vertebral fractures in women with postmenopausal osteoporosis 7.
• Alendronate, risedronate, and zoledronic acid have also been shown to reduce the relative risk of new nonvertebral and hip fractures 7.
• The efficacy of bisphosphonates is maintained during long-term treatment, with clinical trial extensions of up to 10 years with alendronate and 7 years with risedronate 7.

Role of Weight-Bearing Exercise

• Weight-bearing exercise is recommended for all patients with osteoporosis, as it can help improve bone density and reduce the risk of fractures 3, 4, 5.
• Weight-bearing exercise, along with resistance-training exercise, can help improve muscle strength and balance, reducing the risk of falls and fractures 3, 4, 5.
• While weight-bearing exercise is an essential component of osteoporosis prevention and treatment, medication intervention may be necessary for patients at high risk of fracture or with severe disease 3, 4, 5.

Combination Therapy

• A combination of weight-bearing exercise and medication intervention may be the most effective approach for preventing and treating osteoporosis 3, 4, 5.
• Patients at high risk of fracture should consider treatment with antiresorptive therapy, including bisphosphonates and denosumab, along with weight-bearing exercise and other lifestyle modifications 5.
• Anabolic agents, such as teriparatide, abaloparatide, and romosozumab, may be considered for patients at very high risk or with previous vertebral fractures, in combination with weight-bearing exercise and other lifestyle modifications 5.