radiologists should be vigilant of alendronate

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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

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Page 1: Radiologists Should Be Vigilant Of Alendronate

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

Page 2: Radiologists Should Be Vigilant Of Alendronate

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.