Bisphosphonate use may affect mechanical properties of bone

BALTIMORE — A study of bone biopsies taken from like-aged postmenopausal women undergoing internal fixation for femoral fractures has found that the women who had taken bisphosphonate treatments for osteoporosis had narrower pattern of aged bone matrix, perhaps indicating a loss of mechanical integrity.

“Osteoporosis is the most common cause of fragility fractures and bisphosphonates have emerged as a cornerstone of osteoporosis treatment,” Brian J. Rebolledo, said at the 2010 Annual Meeting of the Orthopaedic Trauma Association. “The reason for this being, they prevent bone loss and reduce fracture risk. However, recent concerns have been raised about long-term bisphosphonate treatment in the development of atypical femoral fractures.”

Rebolledo presented research conducted at Hospital for Special Surgery and Weill Cornell Medical College that assessed and compared the parameters of bone quality in women who took bisphosphonate therapy and those who did not.

Core biopsies

Brian J. Rebolledo

The researchers enrolled postmenopausal women with proximal femoral fractures treated with internal fixation using intertrochanteric nails. During the surgical procedure, a 1-cm diameter core reamer was used to remove a cylindrical piece of corticocancellous bone prior to the insertion of the helical blade, from the lateral cortex of the femur.

These biopsies were than categorized into bisphosphonate treatment or nontreatment groups. Overall, there were 17 patients in the bisphosphonate group and 15 in the group who never took bisphosphonate therapy.

Race, age and body mass index were recorded and no differences were seen between the groups.

Analysis

The specimens were analyzed by micro-CT to assess bone volume fraction, trabecular number, trabecular thickness, trabecular separation and trabecular connectivity. Histomorphometry was then used to measure the ratio of unmineralized to mineralized bone surface of the trabecular and cortical bone.

Lastly, they were analyzed with Fourier transform infrared imaging (FTIRI) to assess the properties of cortical and trabecular bone in terms of mineral-matrix ratio; carbonate-phosphate ratio; collagen crosslinking maturity and mineral crystallinity.

“The width of these values is representative of the heterogeneity of the samples,” Rebolledo said. “Heterogeneity is important to consider because bone is normally a heterogeneous material due to the constant remodeling and the differing mineralization at time points. And it has also been shown that a high mineral content can lead to brittle bones.

“Therefore a narrower distribution of these parameters can lead to reduced bone toughness,” he said.

The researchers found that the cortical tissue mineral properties “indicated a narrower distribution in the bisphosphonate-treated group.” The mean cortical and trabecular values of all the FTIRI analyses were similar.

“Although bisphosphonates may be the cornerstone treatment, we really don’t know what the long-term effects are on bone quality,” Rebolledo said. “Our data show that the proximal femoral fracture patients treated with bisphosphonates had a narrower distribution of bone compositional parameters, but no change in the tissue microarchitecture. Therefore this raises concerns that long-term bisphosphonate therapy could affect bone quality and may affect some mechanical properties by the loss of heterogeneity.”

Reference:
Rebolledo BJ, Donnelly E, Lorich DG, et al. Altered bone quality in bisphosphonate-related femoral fractures of postmenopausal women. Paper #38. Presented at the 2010 Annual Meeting of the Orthopaedic Trauma Association. Oct. 13-16, 2010. Baltimore.

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