FDA Drug Safety Podcast for Healthcare Professionals: Safety update for osteoporosis drugs, bisphosphonates, and atypical fractures
Welcome, my name is Jennifer Shepherd, a pharmacist in the Division of Drug
Information. On October 13, 2010, the Food and Drug Administration (FDA) issued a Drug Safety
Communication 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, or 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).
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.
FDA has reviewed all available data,
including data summarized in the American Society for Bone and Mineral Research Task Force report
regarding bisphosphonates and atypical subtrochanteric and diaphyseal femur fractures, released on
September 14, 2010. These atypical femur fractures can occur anywhere in the femoral shaft, from
just below the lesser trochanter to above the supracondylar flare, and are transverse or short
oblique in orientation without evidence of comminution. The fractures can be complete (involving
both cortices) or incomplete (involving the lateral cortex only), and may be bilateral. Many
patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain,
weeks to months before a complete fracture occurs. The exact incidence of atypical femoral fractures
is unknown but appears to account for less than one percent of hip and femoral fractures overall.
Therefore, atypical fractures are very uncommon. Although atypical femoral fractures have been
predominantly reported in patients taking bisphosphonates, they have also been reported in patients
who have not taken bisphosphonates.
The optimal duration of bisphosphonate treatment
for osteoporosis is unknown. Bisphosphonate medications approved for the prevention and/or
treatment of osteoporosis have clinical trial data supporting fracture reduction efficacy through
at least 3 years of treatment and, in some cases, through 5 years. The FDA is continuing its
evaluation of data supporting the safety and effectiveness of long term use (greater than 3 to 5
years) of bisphosphonates for the treatment and prevention of osteoporosis and will provide
additional guidance at the completion of our review.
In summary, FDA is continuing its
ongoing safety review of bisphosphonate use and the occurrence of atypical femur fractures. As of
this notice, the FDA is notifying patients and healthcare professionals of new Warnings and
Precautions information that is being added regarding this risk to the labels of all bisphosphonate
products approved for the prevention or treatment of osteoporosis. A new Limitations of Use
statement will describe the uncertainty of the optimal duration of use of bisphosphonates for the
treatment and/or prevention of osteoporosis. In addition, the FDA will require that a Medication
Guide be included with all bisphosphonate medications approved for osteoporosis indications to
better inform patients of the risk for atypical femur fracture.
At this time, 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
- 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 at www.fda.gov/medwatch.
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.
Thank you for
listening. The FDA is committed to keeping healthcare professionals informed of the latest safety
information. If you have questions about this safety communication, you can reach us at: firstname.lastname@example.org.