Case Reports: Subtrochanteric Femoral Stress Fractures after Prolonged Alendronate Therapy

Cermak, Katerina; Shumelinsky, Felix; Alexiou, J.; Gebhart, Michaël

doi:10.1007/s11999-009-1192-0

Cited by 54 publications

(39 citation statements)

References 27 publications

(58 reference statements)

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“…The ellipsoid thickening was a local response to the microfracture; our laboratory investigations and bone mineral density readings were all within the reference ranges and corresponded with those reported previously [4,18,19]. Given that reiterative tensile stress is one of the factors associated with a subtrochanteric insufficiency fracture [7], we determined that plate fixation on the femoral tension side was a more valid procedure than intramedullary nailing. Some reports have advised discontinuance of alendronate therapy after the identification of atypical radiographic patterns on the proximal femur, thigh pain, or after an Fig.…”

Section: Discussionsupporting

confidence: 82%

“…Thereafter, an increasing number of subtrochanteric or femoral shaft fractures associated with long-term alendronate treatment have been reported [4,[7][8][9][10][11][12][13]. Goh et al [8] described patients who sustained fractures in the subtrochateric region, and five of nine patients (56%) had prodromal pain in the affected hip.…”

Section: Discussionmentioning

confidence: 99%

“…This external cortical reaction in the lateral femoral tension side is thought to be caused by microfractures at these high stress points on the skeleton [9,13,18,20,21]. The subtrochanteric region of the femur is subject to large bending forces with compression stress on the medial cortex and tensile stress on the external cortex [4,7,22]. The microdamage to the bone is repaired through normal physiological remodeling processes by the action of both osteoblasts and osteoclasts [17,23].…”

Section: Discussionmentioning

confidence: 99%

“…Clinical trials have shown its effectiveness in the treatment of fractures related to postmenopausal osteoporosis [6]. However, some recent reports have described unusual subtrochanteric or femoral shaft fractures following longterm alendronate therapy [4,[7][8][9][10][11][12][13]. Although no causal relationship between long-term alendronate treatment and these atypical stress fractures has been established, some reports suggest that the severe suppression of bone turnover by alendronate may lead to accumulated microdamage to the bone that subsequently results in complete fracture [4,12].…”

Section: Introductionmentioning

confidence: 99%

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Histological finding of atypical subtrochanteric fracture after long-term alendronate therapy

Kajino

Kabata

Watanabe

et al. 2012

Journal of Orthopaedic Science

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Histological finding of atypical subtrochanteric fracture after long-term alendronate therapy

Kajino

Kabata

Watanabe

et al. 2012

Journal of Orthopaedic Science

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“…Most of the hip fracture patients in the present Finnish nationwide database study used bisphosphonates, mainly alendronate. In a recent nationwide register study from The side effects of bisphosphonates include osteonecrosis of the jaw, (35) esophageal irritation, musculoskeletal pain, subtrochanteric femoral stress fractures (alendronate), (36) and atrial fibrillation. (37) According to a recent published secondary analysis using the results of three randomized bisphosphonate trials (n ¼ 14,195), the occurrence of fractures of the subtrochanteric or diaphyseal femur was rare, even in women with osteoporosis who received bisphosphonates for up to 10 years.…”

Section: Post-hip Fracture Use Of Osteoporotic Drugs Lower Mortalitymentioning

confidence: 99%

Post–hip fracture use of prescribed calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs is associated with lower mortality: A nationwide study in Finland

Nurmi-Lüthje

Sund

Juntunen

et al. 2011

Journal of Bone and Mineral Research

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We previously found a positive association between calcium plus vitamin D and antiosteoporotic drugs and survival among hip fracture patients. Our aim was to verify this observation using a nationwide database. A retrospective cohort of home-discharged hip fracture patients aged 50 years or older (n ¼ 23,615) was enrolled from the national database. Primary exposure was medical treatment for osteoporosis, and the outcome was all-cause mortality. Cumulative mortalities were calculated using the Kaplan-Meier estimator. The relationship between mortality and medication purchases was modeled using Cox's proportional hazards regression with timedependent covariates for medication use. One in 4 women and 1 in 10 men with a hip fracture were treated for osteoporosis in Finland. Unadjusted 1-year mortality was lower among patients who purchased calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs than among those who did not purchase these medications [hazard ratio (HR) ¼ 0.74, 95% confidence interval (CI) 0.67-0.81]. The difference in unadjusted cumulative mortality remained in favor of the drug users for at least 5 years. Among men, the use of calcium plus vitamin D or vitamin D supplements was associated with lower 1-year mortality even after adjustments for observed confounders (HR ¼ 0.74, 95% CI 0.56-0.97). Among women, the use of antiosteoporotic drugs was associated with lower mortality (HR ¼ 0.79, 95% CI 0.67-0.93). There was a tendency to even better survival in both genders if calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs were used simultaneously, the HR being 0.72 (95% CI 0.50-1.03) in men and 0.62 (95% CI 0.50-0.76) in women. ß

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Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Second Report of a Task Force of the American Society for Bone and Mineral Research

Shane

Burr

Abrahamsen

et al. 2013

Journal of Bone and Mineral Research

1,499

1,417

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Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may be associated with higher risk ($100 per 100,000 personyears). BPs localize in areas that are developing stress fractures; suppression of targeted intracortical remodeling at the site of an AFF could impair the processes by which stress fractures normally heal. When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs.

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Case Reports: Subtrochanteric Femoral Stress Fractures after Prolonged Alendronate Therapy

Abstract: Although bisphosphonates play an important role in preventing pathologic fractures in patients with cancer, these subtrochanteric stress fractures associated with prolonged use of alendronate should not be ignored.

Cited by 54 publications

References 27 publications

Histological finding of atypical subtrochanteric fracture after long-term alendronate therapy

Histological finding of atypical subtrochanteric fracture after long-term alendronate therapy

Post–hip fracture use of prescribed calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs is associated with lower mortality: A nationwide study in Finland

Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Second Report of a Task Force of the American Society for Bone and Mineral Research

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