Protective effect of bisphosphonate on the cortical bone at key locations of the femur in aromatase inhibitor-associated bone loss: A three-dimensional cortical bone mapping study

Aromatase inhibitor treatment in breast cancer is associated with accelerated bone loss and an increased risk of fracture. Bisphosphonates (BPs) are the mainstay treatment of aromatase inhibitor-associated bone loss (AIBL), which might improve femoral bone at key locations prone to fracture. To test this hypothesis, we performed three-dimensional cortical bone mapping based on quantitative computed tomography (QCT) scans in postmenopausal women with early breast cancer who were receiving aromatase inhibitors. Data of subjects who had both baseline and at least one follow-up QCT at Severance Hospital (South Korea) between 2005 and 2015 were analyzed (BP users, n = 93; BP non-users, n = 203). After exclusion of BP users with low medication persistence (proportion of days covered: <50%), BP users and non-users were 1:1 matched (n = 54 for each group) in terms of age, lumbar spine volumetric bone mineral density (LSvBMD), femoral neck areal BMD (FNaBMD), and total hip areal BMD (THaBMD). During a median follow-up of 2.1 years, BP use attenuated bone loss in LSvBMD (+7.2% vs. −3.8%, p < 0.001), FNaBMD (+1.3% vs. −2.7%, p < 0.001), and THaBMD (-0.3% vs. −2.5%, p = 0.024). BP had a protective effect on cortical parameters of femoral bone: estimated cortical thickness (CTh) (+3.3% vs. + 0.1%, p = 0.007) and cortical mass surface density (CMSD, cortical mass per unit surface area was calculated by multiplying cortical BMD with CTh) (+3.4% vs. −0.3%, p < 0.001). CMSD increased by up to 15% at key locations such as the superior part of the femoral neck and greater trochanter. BP prevented the thinning of average CTh of the femoral neck (-1.4% vs. −6.1%, p < 0.001), particularly at the superior anterior quadrant of femoral neck (absolute difference: +12.8% point vs. non-users). Compared to BP non-users, BP users had improved cross-sectional moment of inertia (+4.4% vs. −0.7%, p = 0.001) and less increase in buckling ratio (+1.3% vs. + 7.5%, p < 0.001). In summary, BP use prevented cortical bone deficits observed in AIBL at key locations of the proximal femur.