Patients With Atypical Femur Fractures Have the Same Mortality as the Background Population—Drug-Channeling Bias, Bisphosphonate Effects, and Public Health Implications

Objectives To determine the skeletal safety and efficacy of long term (≥10 years) alendronate use in patients with osteoporosis.Design Open register based cohort study containing two nested case control studies.Setting Nationwide study of population of Denmark.Participants 61 990 men and women aged 50-94 at the start of treatment, who had not previously taken alendronate, 1996-2007.Interventions Treatment with alendronate.Main outcome measures Incident fracture of the subtrochanteric femur or femoral shaft (ST/FS) or the hip. Non-fracture controls from the cohort were matched to fracture cases by sex, year of birth, and year of initiation of alendronate treatment. Conditional logistic regression models were fitted to calculate odds ratios with and without adjustment for comorbidity and comedications. Sensitivity analyses investigated subsequent treatment with other drugs for osteoporosis.Results 1428 participants sustained a ST/FS (incidence rate 3.4/1000 person years, 95% confidence interval 3.2 to 3.6), and 6784 sustained a hip fracture (16.2/1000 person years, 15.8 to 16.6). The risk of ST/FS was lower with high adherence to treatment with alendronate (medication possession ratio (MPR, a proxy for compliance) >80%) compared with poor adherence (MPR <50%; odds ratio 0.88, 0.77 to 0.99; P=0.05). Multivariable adjustment attenuated this association (adjusted odds ratio 0.88, 0.77 to 1.01; P=0.08). The risk was no higher in long term users (≥10 dose years; 0.70, 0.44 to 1.11; P=0.13) or in current compared with past users (0.91, 0.79 to 1.06; P=0.22). Similarly, MPR >80% was associated with a decreased risk of hip fracture (0.73, 0.68 to 0.78; P<0.001) as was longer term cumulative use for 5-10 dose years (0.74, 0.67 to 0.83; P<0.001) or ≥10 dose years (0.74, 0.56 to 0.97; P=0.03).Conclusions These findings support an acceptable balance between benefit and risk with treatment with alendronate in terms of fracture outcomes, even for over 10 years of continuous use.

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“…More data are therefore needed for an accurate evaluation of the impact of such fractures on patients’ morbidity and mortality. 30 …”

Section: Discussionmentioning

confidence: 99%

Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study

Abrahamsen

Eiken

Prieto-Alhambra

et al. 2016

BMJ

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“…19 Other studies suggest that atypical femoral fracture may be associated with a less favorable prognosis in older patients, 20 but this could be due to differences in demographics, treatment adherence, or postfracture care. 21 In addition, functional outcomes as measured by independent mobility at discharge and at 3 months were comparable between patients with atypical fracture and those with typical fracture. 22…”

Section: Mortality Ratesmentioning

confidence: 78%

Bisphosphonate-related atypical femoral fracture: Managing a rare but serious complication

Silverman

Kupperman

Bukata

2018

CCJM

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“…Patients with atypical fractures might expose the implant to greater stress during the period of fracture healing because of their younger age and more active lifestyle [7,40]. This selection might be an effect of drug channeling bias as a consequence of treating younger and healthier patients with bisphosphonates [41]. On the contrary, elderly patients with common fractures might not seek health care for a non-union or might be deemed unfit to undergo surgery.…”

Section: Discussionmentioning

confidence: 99%

Increased rate of reoperation in atypical femoral fractures is related to patient characteristics and not fracture type. A nationwide cohort study

et al. 2020

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Atypical femoral fractures are burdened with a high rate of reoperation. In our nationwide analysis, the increased rate of reoperation was related to patient background characteristics, such as age and health status, rather than fracture type. Introduction Patients with atypical fractures are complex to treat and burdened with a high risk of reoperation. We hypothesized that patients with surgically treated, complete atypical fractures have a higher risk of any reoperation and reoperation related to healing complications than patients with common femoral shaft fractures but that this increase would become insignificant when adjusted for predefined characteristics. Methods A cohort of 163 patients with atypical fractures and 862 patients with common femoral shaft or subtrochanteric fractures treated from 2008 to 2010 and who had follow-up radiographs and register data available until 31 December 2014 was included. Reoperations were identified by a complementary review of radiographs and register data and were used to calculate risks for any reoperation and reoperations related to healing complications. Results Patients with atypical fractures were more likely to be reoperated for any reason, age-adjusted OR 1.76 (95% CI, 1.08 to 2.86). However, patients with common fractures had a shorter follow-up due to a threefold higher death rate. Accordingly, in a multivariable-adjusted time-to-event model, the increased risk lost statistical significance for any reoperations, cause-specific HR 1.34 (95% CI, 0.85 to 2.13), and for reoperations related to healing complications, HR 1.32 (95% CI, 0.58 to 3.0). Continued use of bisphosphonate in the first year after the fracture did not affect the reoperation rate. Conclusions Our findings suggest that the increased risk of reoperation after an atypical femur fracture is largely explained by patient characteristics and not fracture type.

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Patients With Atypical Femur Fractures Have the Same Mortality as the Background Population—Drug-Channeling Bias, Bisphosphonate Effects, and Public Health Implications

Cited by 6 publications

References 10 publications

Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study

Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study

Bisphosphonate-related atypical femoral fracture: Managing a rare but serious complication

Increased rate of reoperation in atypical femoral fractures is related to patient characteristics and not fracture type. A nationwide cohort study

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