Bisphosphonate Fracture Biopsy Study

Mentor

Joseph Lane, MD

Scope

Recent animal evidence has suggested that bisphosphonates are associated with suppression of bone turnover, potentially leading to accumulation of microdamage, compromising bone strength. We recently performed a radiographic study that identifies a unique x-ray pattern common to osteoporotic patients with subtrochanteric low energy fractures on prolonged alendronate.

Our pattern is characterized as a simple transverse or oblique fracture in a subtrochanteric or diaphyseal region of thickened cortices, with beaking of the cortex at the fracture site. Furthermore, we performed a matched case-control study that provides the first evidence of an association between prolonged alendronate use and these atypical diaphyseal fractures. Based on our data and current evidence in the literature, we hypothesize that bone specimens from patients that present with subtrochanteric or proximal femoral shaft fractures on long-term bisphosphonates will be different in bone remodeling parameters and assessment of bone quality and mineralization from those patients not on bisphosphonates. Specifically, in patients on long term alendronate histomorphometry will show evidence of severe suppression of turnover, TRAP staining will reveal a reduced number of osteoclasts and FTIR will describe altered mineral content and quality that is suggestive of compromised bone strength.

To test this hypothesis we plan to compare bone taken from 15 patients on a bisphosphonate to 15 patients not on a bisphosphonate. The patients will be recruited through the Orthopaedic Fracture Service at New York-Presbyterian Hospital (Cornell). Specimens will be collected during trochanteric nail fixation of the fractures, and the tissue will be taken to Hospital for Special Surgery for analysis. There, it will undergo multiple analyses, including histomorphometric analysis to asses bone formation, resorption and remodeling parameters, Fourier transform infrared microscopy (FTIR) analysis to examine bone quality and mineralization, and TRAP staining to assess osteoclasts.

This research has very important implications for the future of osteoporosis and bisphosphonate therapy. The indications for bisphosphonate therapy are expanding, and more patients are taking the drugs for longer periods of time. We hope to provide evidence that long-term bisphosphonate use severely suppresses bone turnover and abnormally alters bone quality, which may lead to a predisposition for subtrochanteric and proximal femoral shaft fractures. This study would more tightly link prolonged bisphosphonate use with these atypical fractures of the femoral shaft in postmenopausal women, provide caution in the use of bisphosphonates for long periods of time and may help identify a subgroup of patients who are more susceptible to ill-effects of long term use. This study has NYPH IRB approval and is currently under way.

Contact

Rose Mary Fisher
email: fisherr@hss.edu