Assessment of Bone Microarchitecture in Postmenopausal Women on Long-Term Bisphosphonate Therapy With Atypical Fractures of the Femur

Abstract

Reports of atypical femoral fractures (AFFs) in patients receiving long-term bisphosphonate therapy have raised concerns regarding the genesis of this rare event. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), we conducted a study to evaluate bone microarchitecture in patients who had suffered an AFF during long-term bisphosphonate treatment. The aim of our study was to evaluate if bone microarchitecture assessment could help explain the pathophysiology of these fractures. We compared bone volumetric density and microarchitectural parameters measured by HR-pQCT in the radius and tibia in 20 patients with AFFs with 35 postmenopausal women who had also received long-term bisphosphonate treatment but had not experienced AFFs, and with 54 treatment-naive postmenopausal women. Control groups were similar in age, body mass index (BMI), and bone mineral density (BMD). Mean age of the 20 patients with AFFs was 71 years, mean lumbar spine T-score was À2.2, and mean femoral neck T-score was À2. Mean time on bisphosphonate treatment was 10.9 years (range, 5-20 years). None of the patients had other conditions associated with AFFs such as rheumatoid arthritis, diabetes or glucocorticoid use. There were no statistically significant differences in any of the parameters measured by HR-pQCT between postmenopausal women with or without treatment history and with or without history of atypical fractures. We could not find any distinctive microarchitecture features in the peripheral skeleton of women who had suffered an atypical fracture of the femur while receiving bisphosphonate treatment. This suggests that risk of developing an atypical fracture is not related to bone microarchitecture deterioration. Our results indicate that there may be other individual factors predisposing to atypical fractures in patients treated with bisphosphonates, and that those are independent of bone microarchitecture. In the future, identification of those factors could help prevent and understand the complex physiopathology of these rare events.

Incidence of Atypical Femur Fractures in Cancer Patients: The MD Anderson Cancer Center Experience

“…BPs increase mean tissue age and mineralization, resulting in an increased propensity for microcracks and reduced bone resilience that collectively increase the fracture risk . Furthermore, the mineral content (mineral/matrix ratio) of cortical bone but not cancellous bone has been shown to be increased by BP treatment . The aim of this study is to assess the incidence and risk factors for AFF in a large cancer center.…”

“…(27) Furthermore, the mineral content (mineral/matrix ratio) of cortical bone but not cancellous bone has been shown to be increased by BP treatment. (28) The aim of this study is to assess the incidence and risk factors for AFF in a large cancer center.…”

Atypical Femoral Fractures—Ongoing and History of Bone-Specific Therapy, Concomitant Diseases, Medications, and Survival

“…A study in postmenopausal women with a mean age of 71 years evaluated bone microarchitecture in glucocorticoid-na€ ıve patients with rheumatoid arthritis or diabetes who had sustained an AFF during long-term BP treatment. No association with altered microarchitecture features in the peripheral skeleton was observed suggesting other individual predisposing or contributing factors (21).…”

Long‐term follow‐up of bone density, general and reproductive health in female survivors after treatment for haematological malignancies

“…To our knowledge, only one earlier study has analysed the effects of hormonal replacement therapy on BMD and observed a reduction in the rate of BMD decrease after 12 months (15). There are, however, many studies showing the effects of bisphosphonates on BMD in this group of patients with positive results (13,20,22). The increase in mineral density and reduced fracture risk associated with bisphosphonates treatment may be counterbalanced by a decrease in tissue heterogeneity, which could impair tissue mechanical properties and might lead to atypical fractures (23,24).…”