What are the effects of osteoporosis after 5 years of treatment with Alendronate (bisphosphonate)?

From the Guidelines

After 5 years of alendronate treatment for osteoporosis, patients should be reassessed for their ongoing fracture risk to determine whether to continue therapy, take a drug holiday, or switch medications. This recommendation is based on the most recent and highest quality study available, which suggests that bisphosphonates, such as alendronate, have a residual effect that persists after discontinuation, and long-term use carries small risks of rare but serious side effects like atypical femur fractures and osteonecrosis of the jaw 1.

Key Considerations

• For patients at high fracture risk (T-score below -2.5, previous fragility fractures, or other significant risk factors), continuing alendronate for up to 10 years is generally recommended 1.
• For those at moderate risk, a drug holiday of 2-3 years may be appropriate while monitoring bone mineral density (BMD).
• During this assessment, a DXA scan should be performed to evaluate current BMD, and fracture risk calculators like FRAX may be used 1.
• Blood tests to check vitamin D, calcium, and bone turnover markers can provide additional information.

Lifestyle Modifications

• Throughout treatment and any drug holiday, patients should maintain adequate calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) intake.
• Patients should also engage in weight-bearing exercise, avoid smoking, and limit alcohol consumption.

The rationale for these recommendations is supported by the latest evidence, which highlights the benefits of bisphosphonates in reducing the risk of hip and vertebral fractures, as well as the potential risks associated with long-term use 1. By reassessing fracture risk and considering individual patient factors, clinicians can make informed decisions about ongoing treatment and minimize the risk of adverse effects.

From the FDA Drug Label

In the two year extension of these studies, treatment of 147 patients with alendronate sodium 10 mg/day resulted in continued increases in BMD at the lumbar spine and trochanter (absolute additional increases between years 3 and 5: lumbar spine, 0.94%; trochanter, 0.88%). BMD at the femoral neck, forearm and total body were maintained.

The use of alendronate for 5 years may help to maintain or increase bone mineral density (BMD) in patients with osteoporosis, which can help to reduce the risk of fractures. However, the exact effect of alendronate on osteoporosis after 5 years of treatment may vary depending on individual factors, such as the patient's initial BMD and the presence of other health conditions. 2

From the Research

Osteoporosis after 5 years of Alendronate

• The effects of discontinuing alendronate after 5 years on osteoporosis have been studied, with results indicating a potential loss of bone mineral density (BMD) 3.
• A narrative review found that the percentage change in BMD after 1 year of discontinuation of alendronate is -0.4% or less at the hip and femoral neck 3.
• However, discontinuing alendronate may increase the risk of vertebral fractures, with one study suggesting a significant increase in risk after discontinuation 3.
• Another study found that alendronate may lead to a clinically important reduction in clinical vertebral fractures in postmenopausal women with osteoporosis, but the evidence is less clear for other types of fractures 4.
• The selection of osteoporosis treatment, including alendronate, should be individualized and based on factors such as underlying fracture risk, medical comorbidities, and medication burden 5.

Treatment Options after Alendronate

• For patients who do not respond adequately to alendronate, transitioning to other therapies such as zoledronic acid, strontium ranelate, denosumab, or teriparatide may be considered 6.
• These alternative therapies may cause further increases in BMD, but the optimal treatment strategy after alendronate is not well established and requires further study 6.
• The use of alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women has been evaluated in several studies, with evidence suggesting that it may reduce the risk of clinical vertebral and non-vertebral fractures 4.

Bone Mineral Density and Fracture Risk

• The loss of BMD after discontinuation of alendronate is a concern, with one study finding a percentage change in BMD of -0.4% or less at the hip and femoral neck after 1 year 3.
• The risk of fractures after discontinuation of alendronate is also a concern, with evidence suggesting that discontinuing alendronate may increase the risk of vertebral fractures 3.
• The relationship between BMD and fracture risk is complex, and further study is needed to fully understand the effects of alendronate on osteoporosis and fracture risk 4.