SAN FRANCISCO, California—Long-standing concern that the bisphosphonate-induced changes in bone metabolism that might result in poor bone quality and impaired microdamage repair received some support from 2 studies reported at the 2008 AAOS meeting. Seo Kiat Goh, MB, and colleagues from Singapore described “an unusual configuration of subtrochanteric fractures in patients on alendronate (Fosamax^®, Merck & Co, Inc) therapy.¹ Andrew Neviaser, MD, and colleagues from New York described a particular type of nontraumatic femoral shaft fracture that appeared to be associated with long-term alendronate use.²

Dr. Goh’s group conducted a retrospective review of low-energy subtrochanteric fractures in postmenopausal patients taking alendronate, following a recent increase in such fractures seen in the department of orthopaedic surgery at Singapore General Hospital. They found 17 cases occurring within a 20-month period in patients with a mean age of 66 years. “These patients were incidentally found to be on alendronate therapy for an average of 4.8 years,” Dr. Goh said. More than half of the patients had bilateral findings of stress reactions or fractures, and 76% had symptoms of prodromal pain.

Review of plain radiographs revealed a characteristic fracture configuration and included

• Cortical thickening in the lateral side of the subtrochanteric region
• Transverse fracture
• Medial cortical spike

“These insufficiency fractures could possibly have developed from the oversuppression of bone turnover from prolonged alendronate therapy, in keeping with recently published evidence. This study further highlights the need for heightened awareness of alendronate’s potential adverse effects,” Dr. Goh explained.

Dr. Neviaser’s group at the Hospital for Special Surgery in New York found a similar characteristic pattern in low-stress fractures of the femoral shaft in patients taking alendronate. The group reported 70 nontraumatic, nonpathologic fractures (59 females, 11 males) in patients of average age 74.7. A total of 36% of these patients were being treated with alendronate, and average duration of use was 6.19 years.

The femoral shaft fracture pattern included

• Simple, transverse pattern
• Occurrence in an area of cortical hypertrophy
• Breaking of the cortex on one side

“These insufficiency fractures could possibly have developed from the oversuppression of bone turnover from prolonged alendronate therapy, in keeping with recently published evidence. This study further highlights the need for heightened awareness of alendronate’s potential adverse effects.”—Seo Kiat Goh, MB.Using this constellation of factors, the investigators were able to correctly predict with a mean 89% accuracy whether patients had been taking bisphosphonates. The presence of femoral shaft fracture was 83% sensitive and 98% specific for alendronate use.

“Nontraumatic, nonpathologic fractures of the femoral shaft with a simple, transverse pattern and hypertrophy of the diaphysial cortex are pathognomonic for alendronate use. This may result from propagation of a stress fracture whose repair is retarded by diminished osteoclast activity and impaired microdamage repair,” Dr. Neviaser concluded.

References

1. Goh SK, Kwek EBK, Koh, JSB, et al. An emerging pattern of subtrochanteric stress fracture: a long-term complication of alendronate? Presented at: AAOS annual meeting; March 7, 2008; San Francisco, Calif. Presentation 390.
2. Neviaser A, Lane JM, Lenart B, et al. Nontraumatic femoral shaft fractures associated with bisphosphonate use. Presented at: AAOS annual meeting; March 7, 2008; San Francisco, Calif. Presentation 431.