What is the controversy surrounding the use of bisphosphonates (Bone Protective Agents)?

From the Guidelines

Bisphosphonates, such as alendronate and zoledronic acid, are associated with controversy due to potential risks of atypical femoral fractures and osteonecrosis of the jaw (ONJ), as reported in studies 1.

Key Risks and Considerations

• ONJ is a major complication, especially with more potent bisphosphonates like pamidronate and zoledronic acid, with an incidence of 1% to 10% in patients receiving intravenous bisphosphonates for metastatic bone disease 1.
• Atypical femoral fractures have been reported in patients on long-term bisphosphonate therapy, although a causal relationship has not been established with certainty 1.
• Acute phase reactions can occur with intravenous bisphosphonates, and gastrointestinal side-effects can occur with oral bisphosphonates 1.
• Renal insufficiency is a concern with intravenous bisphosphonates, especially in patients with creatinine clearance less than 30 mL/min 1.

Precautionary Measures

• Use the lowest effective dose for the shortest duration necessary to achieve treatment goals, such as alendronate 70mg weekly or zoledronic acid 5mg annually for 3-5 years, after which a drug holiday can be considered 1.
• Dental examination and prophylactic measures should be considered before starting bisphosphonate therapy, and patients should be advised against unnecessary invasive oral surgery while on bisphosphonate therapy 1.
• Alternative treatments, such as denosumab or teriparatide, may be considered for those at high risk of bisphosphonate-related complications 1.

Individualized Approach

• Weigh the benefits and risks of bisphosphonate therapy on an individual basis, taking into account the patient's bone density, fracture history, and overall health status 1.
• Regular review and reassessment of treatment are crucial to minimize potential harm and optimize therapeutic outcomes 1.

From the FDA Drug Label

Atypical subtrochanteric and diaphyseal femoral fractures have been reported in patients receiving bisphosphonate therapy, including zoledronic acid injection and alendronate sodium. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to just above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients taking bisphosphonates, including alendronate sodium and zoledronic acid injection. Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions, occasionally with bleeding and rarely followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates including alendronate sodium. In post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates that are approved for the prevention and treatment of osteoporosis.

The controversy surrounding the use of bisphosphonates includes the risk of:

• Atypical femoral fractures: which can occur with minimal or no trauma
• Osteonecrosis of the jaw (ONJ): associated with tooth extraction, local infection, and delayed healing
• Esophageal adverse experiences: such as esophagitis, esophageal ulcers, and esophageal erosions
• Severe musculoskeletal pain: which can be incapacitating and may require discontinuation of therapy These risks should be carefully considered and weighed against the benefits of bisphosphonate therapy, and patients should be closely monitored for any signs or symptoms of these adverse events 2, 3, 3.

From the Research

Controversy Surrounding Bisphosphonates

The use of bisphosphonates, also known as bone protective agents, has been a topic of controversy in the medical field. While they have been shown to be effective in preventing and treating osteoporosis, there are concerns about their long-term use and potential side effects. Some of the key points surrounding this controversy include:

• Benefits of long-term use: Studies have shown that bisphosphonates can increase bone mineral density and reduce the risk of fractures, resulting in improved quality of life and reduced morbidity and mortality 4, 5, 6.
• Risks of long-term use: However, long-term use of bisphosphonates has also been associated with rare but severe side effects, such as atypical femoral fractures and medication-related osteonecrosis of the jaw 4, 5, 7.
• Duration of treatment: There is debate about how long patients should be treated with bisphosphonates, with some studies suggesting that treatment should be stopped after 5-10 years to minimize the risk of side effects 5.
• Patient selection: The decision to use bisphosphonates should be based on individual patient risk factors, including the risk of fracture and the presence of other health conditions 8.
• Monitoring and duration of treatment: Regular monitoring of patients taking bisphosphonates is necessary to minimize the risk of side effects and to determine the optimal duration of treatment 8.

Key Considerations

Some key considerations when using bisphosphonates include:

• The balance between the benefits and risks of treatment: While bisphosphonates can be effective in preventing and treating osteoporosis, they can also have serious side effects, and the decision to use them should be based on individual patient risk factors 7.
• The importance of regular monitoring: Regular monitoring of patients taking bisphosphonates is necessary to minimize the risk of side effects and to determine the optimal duration of treatment 8.
• The need for individualized treatment plans: Treatment plans should be tailored to individual patient needs and risk factors, taking into account the potential benefits and risks of bisphosphonate therapy 8.