1) A study found that long-term use of alendronate (Fosamax) for osteoporosis may paradoxically increase the risk of subtrochanteric femoral fractures. 2) The study examined 22 patients with 34 fractures who had taken alendronate for 4-14 years. The fractures showed features including transverse orientation and lateral cortical thickening. 3) Radiologists need to recognize these fracture patterns and alert clinicians, as incomplete fractures may progress or require treatment changes given the risks of alendronate. Further research is needed to establish correlations and guidelines.

1. Radiologists Should Be Vigilant of Alendronate-associated Femoral Fractures
Patients receiving alendronate—such as the popular drug Fosamax®—for osteoporosis may
paradoxically be at risk for subtrochanteric femoral fractures, a scientific paper session has revealed.
“At our institution we have seen an increasing number of such fractures and we feel it is an extremely
important topic, deserving description in the radiology literature as the clinical implications are
profound,” said session presenter Sarah Shock Chan, M.D., a fellow at New York University Hospital for
Joint Diseases.
Dr. Chan and colleagues examined radiographic, scintigraphic, CT and MR images from 22 patients with
a total of 34 fractures (12 were bilateral). The patients had been on alendronate therapy for a minimum
of 4 years and up to 14 years. Most patients reported minor or no trauma. Twenty of the fractures were
complete, and two of the incomplete fractures later progressed to complete, the researchers observed.
“All fractures were mainly transverse,” Dr. Chan noted, “and the majority were less than 5 centimeters
from the lesser trochanter.” Each demonstrated an appreciated “skirt” of lateral buttressing, suggesting
chronicity and a lateral origin, the researchers found.
Dr. Chan and colleagues found focal cortical thickening at the lateral aspect of the femoral cortex in all
the fractures, as well as medial beaking and superior displacement and varus angulation at the fracture
site.
“Many radiologists as well as clinicians are not familiar with this phenomenon or of the characteristic
fracture pattern,” Dr. Chan said. “The radiologist first needs to recognize the radiographic and MR
imaging features of these fractures, especially of the incomplete fractures, as these can progress to
complete fractures with little or no trauma.”
Dr. Chan explained that while the function of alendronate—destroying the osteoclasts responsible for
removing old bone—results in increased bone density, it also suppresses bone turnover and remodeling,
increasing microdamage and decreasing healing ability. She cited a 2001 study by Mashiba et al which
demonstrated suppressed bone remodeling in a beagle model, and a 2005 study by Odvina et al that
revealed a lack of surface osteoclasts, osteoblasts and osteoid tissue in patients on alendronate.
Dr. Chan acknowledged the need for further study to determine true correlation between long-term
alendronate therapy and these characteristic fractures. “Further investigations are needed to determine
if the fractures are also associated with other available biophosphonates,” she added.
In the case of incomplete fractures, the radiologist must alert the clinician that not only that there is a

2. pending fracture, but that the fracture could be related to Fosamax treatment, Dr. Chan advised. The
clinician must then determine whether the risk of osteoporotic fractures outweighs the risk of
alendronate-related changes and decide whether to stop or change the medication. “At our institution,
patients with these fractures are taken off Fosamax and placed on Forteo® (teriparatide) if they need
continued osteoporisis treatment,” said Dr. Chan. “However, no definite treatment guidelines currently
exist.”
The orthopedist must also decide whether an incomplete fracture should be treated prophylactically
with hardware fixation, Dr. Chan noted. In cases of unilateral fractures, she said, it is advisable to assess
the contralateral femur for changes such as lateral cortical thickening.
Radiologists should be aware of these fractures and their possible association with alendronate therapy,
Dr. Chan advised. “The presence of lateral cortical thickening—or a "skirt" of lateral cortical thickening—
is likely the earliest sign of these fractures,” she said. She recommended that prospective studies be
performed on both symptomatic and asymptomatic patients receiving alendronate and controls to
determine if lateral cortical thickening can be identified in all patients on alendronate. “Also, an
objective definition of lateral cortical thickening needs to be determined,” she added.