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  • Of additional interest have been rare cases


    Of additional interest have been rare cases of atypical purchase Dihydromyricetin fracture reported in women with breast cancer [16,17], described as transverse fractures with focal cortical hypertrophy occurring in the femoral diaphysis with minimal trauma [18]. While atypical fractures were initially reported in women receiving oral bisphosphonate therapy for osteoporosis [19], several reports have been published describing atypical femur fractures in patients with cancer receiving high dose intravenous bisphosphonate therapy [17,20–22]. Within Kaiser Permanente Northern California (KPNC), we found that up to 1 in 10 femur fractures occurring in breast cancer patients who received high dose intravenous bisphosphonate therapy (e.g. for bone metastases) demonstrated an atypical fracture pattern [16].
    Methods Kaiser Permanente Northern California (KPNC) is an integrated healthcare delivery system that serves more than 3 million members annually, of whom approximately one-fifth are women aged 50 years and older. Since 1995, electronic databases have been utilized for hospitalization and ambulatory care diagnoses, pharmacy records, and operative and radiology reports, with digital radiologic images since 2005. An extensive KPNC Cancer Registry has also been maintained, with high-quality information on tumor histology and stage of disease at initial presentation [23].
    Results From the source cohort of KPNC women age ≥50 years old experiencing a femur (including pathologic femur) fracture during 2005–2012 (N=12,891), we identified a final femur fracture cohort of 802 women with a prior history of invasive breast cancer, meeting inclusion/exclusion criteria. The mean age at fracture was 80.5±9.6 years, with the majority of women age ≥80 years and older (61.6%) and predominantly of white race (82.2%). More than two-thirds of the study cohort (70.3%) had localized cancer at initial breast cancer diagnosis with a median time between breast cancer diagnosis and fracture of 9.0 years (interquartile range 4.6–14.2 years). The median time to fracture was 7.3 years (interquartile range 3.2–12.3 years) for those who initially presented with regional disease (lymph node or local extension) and only 3.1 years (interquartile range 0.9–6.5) for those with metastatic disease at initial diagnosis (p<0.05 for all comparisons). Table 1 shows the demographic and clinical characteristics of the women with prior breast cancer at the time of fracture by age group. Half of all femur fractures occurred in the femoral neck, with an increasing proportion of pertrochanteric fractures among older patients. Diaphyseal fractures accounted for only 6.2% of fractures, but contributed to 23.6% of fractures in the youngest age group (50–64 years old). Fig. 1 shows the stratification of the cohort by age, fracture site and fracture subtype, with women classified as having a fragility fracture in the absence of adjudicated pathologic or atypical fracture. Overall, 77 (9.6%) fractures were found to be pathologic, with a much greater proportion of fractures that were pathologic in the diaphyseal femur (56.0%) and among younger women (50.0% for age 50–64 years old). Among the 77 women with pathologic fractures, 88.3% were initially identified by a primary or secondary ICD-9 diagnosis for pathologic fracture of the femur (733.14 or 733.15) and an additional 7.8% were identified by ICD-9 198.5 (metastases to bone). However, one fourth (26.9%) of the 93 women with a principal or secondary ICD-9 diagnosis of 733.14 or 733.15 did not have evidence of metastatic disease at the fracture site, where the designation of pathologic fracture reflected osteoporosis, atypical fracture or other non-malignant processes. We identified a total of eight atypical femur fracture cases among women with a history of invasive breast cancer, accounting for 16.0% of those presenting with diaphyseal femur fracture. Three of the eight cases with atypical fracture had received high dose intravenous bisphosphonate therapy and were previously reported [16]. The remaining five cases with atypical fracture received oral bisphosphonate therapy for a total duration of 4–12 years prior to fracture. Of note, there were three additional women classified as having a pathologic fracture (based on positive bone pathology) whose fracture pattern also appeared atypical; these women had also previously received intravenous bisphosphonate therapy [16].