FDA: Safety update for osteoporosis drugs, bisphosphonates, and atypical fractures

The U.S. Food and Drug Administration (FDA) is updating the public regarding information previously communicated describing the risk of atypical fractures of the thigh, known as subtrochanteric and diaphyseal femur fractures, in patients who take bisphosphonates for osteoporosis.  This information will be added to the Warnings and Precautions section of the labels of all bisphosphonate drugs approved for the prevention or treatment of osteoporosis.

Bisphosphonates are a class of medicines that can be effective at preventing or slowing the loss of bone mass (osteoporosis) in postmenopausal women, thus reducing the risk of common osteoporotic bone fracture. Osteoporotic fractures can result in pain, hospitalization, and surgery.

Atypical subtrochanteric femur fractures are fractures in the bone just below the hip joint. Diaphyseal femur fractures occur in the long part of the thigh bone. These fractures are very uncommon and appear to account for less than 1% of all hip and femur fractures overall. Although it is not clear if bisphosphonates are the cause, these unusual femur fractures have been predominantly reported in patients taking bisphosphonates.

The bisphosphonates affected by this notice are only those approved to treat osteoporosis, including Fosamax, Fosamax Plus D, Actonel, Actonel with Calcium, Boniva, Atelvia, and Reclast (and their generic products).

This notice does not affect bisphosphonate drugs that only are used to treat Paget’s disease or high blood calcium levels due to cancer (i.e., Didronel, Zometa, Skelid, and their generic products).

Although the optimal duration of bisphosphonate use for osteoporosis is unknown, these atypical fractures may be related to long-term term bisphosphonate use.  FDA will require a new Limitations of Use statement in the Indications and Usage section of the labels for these drugs. This statement will describe the uncertainty of the optimal duration of use of bisphosphonates for the treatment and/or prevention of osteoporosis.

A Medication Guide will also be required to be given to patients when they pick up their bisphosphonate prescription.  This Medication Guide will describe the symptoms of atypical femur fracture and recommend that patients notify their healthcare professional if they develop symptoms.

These actions are part of an ongoing safety review of bisphosphonate use and the occurrence of atypical subtrochanteric and diaphyseal femur fractures, as previously announced in a Drug Safety Communication on March 10, 2010.

Additional Information for Patients

If you currently take a bisphosphonate, you should:

• Continue to take your medication unless you are told to stop by your healthcare professional.
• Talk to your healthcare professional if you develop new hip or thigh pain (commonly described as dull or aching pain), or have any concerns with your medications.
• Report any side effects with your bisphosphonate medication to FDA’s MedWatch program using the information at the bottom of the page in the “Contact Us” box.

Additional Information for Healthcare Professionals

FDA recommends that healthcare professionals should:

• Be aware of the possible risk of atypical subtrochanteric and diaphyseal femur fractures in patients taking bisphosphonates.
• Continue to follow the recommendations in the drug label when prescribing bisphosphonates.
• Discuss the known benefits and potential risks of using bisphosphonates with patients.
• Evaluate any patient who presents with new thigh or groin pain to rule out a femoral fracture.
• Discontinue potent antiresorptive medications (including bisphosphonates) in patients who have evidence of a femoral shaft fracture.
• Consider periodic reevaluation of the need for continued bisphosphonate therapy, particularly in patients who have been treated for over 5 years.
• Report any adverse events with the use of bisphosphonates to FDA’s MedWatch program using the information at the bottom of the page in the “Contact Us” box.

Any information provided to MedWatch should be as detailed as possible and include information concerning fracture location/configuration, magnitude of trauma, fracture details (complete or incomplete, bilateral, or comminuted), presence and duration of prodromal thigh or groin pain, duration of bisphosphonate use, relevant medical history, and concomitant use of other medications.

More at FDA.gov.