Femoral Insufficiency Fractures Associated with Prolonged Bisphosphonate Therapy

Isaacs, Joseph D.; Shidiak, L.; Harris, Ian A.; Szomor, Zoltan L.

doi:10.1007/s11999-010-1535-x

Cited by 90 publications

(77 citation statements)

References 55 publications

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“…Only nine fractures were in men, but gender was not identified in three large case series. (100,107,108) The majority (160 of 189) occurred after oral alendronate monotherapy: 12 patients were treated with oral risedronate (of these, 1 was followed by oral alendronate, whereas 2 were treated previously with alendronate and another was treated previously with pamidronate), 4 with a combination of intravenous pamidronate followed by intravenous zoledronic acid (myeloma), 4 with either oral or intravenous pamidronate (osteoporosis), 2 with intravenous zoledronic acid (renal cell carcinoma and osteoporosis), 2 with oral alendronate followed by oral ibandronate, and 102 with an unspecified oral BP.…”

Section: Atypical Subtrochanteric and Femoral Shaft Fractures: Clinicmentioning

confidence: 99%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

988

679

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Reports linking long-term use of bisphosphonates (BPs) with atypical fractures of the femur led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address key questions related to this problem. A multidisciplinary expert group reviewed pertinent published reports concerning atypical femur fractures, as well as preclinical studies that could provide insight into their pathogenesis. A case definition was developed so that subsequent studies report on the same condition. The task force defined major and minor features of complete and incomplete atypical femoral fractures and recommends that all major features, including their location in the subtrochanteric region and femoral shaft, transverse or short oblique orientation, minimal or no associated trauma, a medial spike when the fracture is complete, and absence of comminution, be present to designate a femoral fracture as atypical. Minor features include their association with cortical thickening, a periosteal reaction of the lateral cortex, prodromal pain, bilaterality, delayed healing, comorbid conditions, and concomitant drug exposures, including BPs, other antiresorptive agents, glucocorticoids, and proton pump inhibitors. Preclinical data evaluating the effects of BPs on collagen cross-linking and maturation, accumulation of microdamage and advanced glycation end products, mineralization, remodeling, vascularity, and angiogenesis lend biologic plausibility to a potential association with long-term BP use. Based on published and unpublished data and the widespread use of BPs, the incidence of atypical femoral fractures associated with BP therapy for osteoporosis appears to be very low, particularly compared with the number of vertebral, hip, and other fractures that are prevented by BPs. Moreover, a causal association between BPs and atypical fractures has not been established. However, recent observations suggest that the risk rises with increasing duration of exposure, and there is concern that lack of awareness and underreporting may mask the true incidence of the problem. Given the relative rarity of atypical femoral fractures, the task force recommends that specific diagnostic and procedural codes be created and that an international registry be established to facilitate studies of the clinical and genetic risk factors and optimal surgical and medical management of these fractures. Physicians and patients should be made aware of the possibility of atypical femoral fractures and of the potential for bilaterality through a change in labeling of BPs. Research directions should include development of animal models, increased surveillance, and additional epidemiologic and clinical data to establish the true incidence of and risk factors for this condition and to inform orthopedic and medical management. ß

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Section: Atypical Subtrochanteric and Femoral Shaft Fractures: Clinicmentioning

confidence: 99%

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Shane

Burr

Ebeling

et al. 2010

Journal of Bone and Mineral Research

988

679

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“…Early case reports found that atypical fractures occurred in younger people than ordinary fractures, often occurred bilaterally, with prodromal pain, and were not preceded by obvious trauma. (7,8) The atypical fracture appearance was rarely observed prior to the introduction of bisphosphonates. (9) A task force of the American Society for Bone and Mineral Research called for additional epidemiological data to establish the true incidence of these fractures.…”

Section: Introductionmentioning

confidence: 99%

Incidence of atypical nontraumatic diaphyseal fractures of the femur

Dell

Adams

Greene

et al. 2012

Journal of Bone and Mineral Research

395

278

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Bisphosphonates reduce the rate of osteoporotic fractures in clinical trials and community practice. ''Atypical'' nontraumatic fractures of the diaphyseal (subtrochanteric or shaft) part of the femur have been observed in patients taking bisphosphonates. We calculated the incidence of these fractures within a defined population and examined the incidence rates according to duration of bisphosphonate use. We identified all femur fractures from January 1, 2007 until December 31, 2011 in 1,835,116 patients older than 45 years who were enrolled in the Healthy Bones Program at Kaiser Southern California, an integrated health care provider. Potential atypical fractures were identified by diagnostic or procedure codes and adjudicated by examination of radiographs. Bisphosphonate exposure was derived from internal pharmacy records. The results showed that 142 patients had atypical fractures; of these, 128 had bisphosphonate exposure. There was no significant correlation between duration of use (5.5 AE 3.4 years) and age (69.3 AE 8.6 years) or bone density (T-score À2.1 AE 1.0). There were 188,814 patients who had used bisphosphonates. The age-adjusted incidence rates for an atypical fracture were 1.78/100,000/year (95% confidence interval [CI], 1.5-2.0) with exposure from 0.1 to 1.9 years, and increased to 113.1/100,000/year (95% CI, 69.3-156.8) with exposure from 8 to 9.9 years. We conclude that the incidence of atypical fractures of the femur increases with longer duration of bisphosphonate use. The rate is much lower than the expected rate of devastating hip fractures in elderly osteoporotic patients. Patients at risk for osteoporotic fractures should not be discouraged from initiating bisphosphonates, because clinical trials have documented that these medicines can substantially reduce the incidence of typical hip fractures. The increased risk of atypical fractures should be taken into consideration when continuing bisphosphonates beyond 5 years. ß

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“…Nesta vertente, os nossos resultados são apoiados pela literatura com resultados de odds ratio de 9,46 em doentes com tratamento superior a três anos (Erviti et al) 15 ; 66,9 em doentes com uma mediana de duração de tratamento no grupo entre os 5-9 anos (Meier et al) 5 ; e 1000 em doentes com tratamento médio de 7,1 anos (Isaacs et al), 6 resultados estes também estatisticamente significativos e com intervalos de confiança de 95%.…”

Section: Discussionunclassified

“…6 O mesmo autor defende, se não a suspensão dos bifosfonatos ao fim de cinco anos, pelo menos a pesquisa activa de sintomas prodrómicos e monitorização radiográfica. No caso da nossa população em estudo estavam apenas descritos sintomas prodrómicos com uma duração de seis meses no caso da doente com fractura atípica bilateral simultânea.…”

Section: Discussionunclassified

“…[1][2][3] Contudo, têm vindo a ser descritos casos de fracturas femorais atípicas (com localização subtrocantérica ou diafisária) e publicados estudos que as associam à toma prolongada de bifosfonatos, [4][5][6] nomeadamente acima dos cinco anos, 7 por eventual insuficiência de capacidade regenerativa do osso. 8,9 Existem mesmo estudos que relacionam as fracturas femorais atípicas a tomas menos prolongadas (< 2 anos).…”

Section: Introductionunclassified

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Fracturas Femorais Atípicas e o Tratamento com Bifosfonatos: É um Factor de Risco?

Geada

Mafra²,

Barroso³

et al. 2014

Acta Med Port

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Introduction:Bisphosphonates are effective in preventing osteoporotic fracture, however atypical femoral fractures with a well-defined radiological pattern have been described in association with prolonged treatment with bisphosphonates. Our objectives in this study were to characterize patients ≥ 65 years old with femoral fractures (subtrochanteric/diaphyseal) considered typical and atypical and the relationship between the occurrence of atypical fractures and bisphosphonate use. Material and Methods:We conducted a case-control study with patients admitted in our hospital with subtrochanteric or diaphyseal femur fracture in a period of five and a half years. After applying the exclusion criteria, the 92 fractures (91 patients) were classified as typical or atypical. The determination of prior bisphosphonate treatment was obtained through consultation of the individual medical history. Results: We found 11 atypical fractures (10 patients) and 81 typical fractures (81 patients). The median age of both groups was statistically different (72 years -atypical vs. 80 years -typical, p < 0.01). The reason for the use of bisphosphonates was 0.60 in atypical fractures and 0.01 in typical, and an odds ratio of 101.1 was obtained (p < 0.01). Discussion: Our results are supported and are in agreement with published studies relating to the occurrence of atypical femoral fractures associated with treatment with bisphosphonates. Conclusion:Despite the small number of cases it was possible to demonstrate a statistically significant relation between atypical femoral fractures and treatment with bisphosphonates. One should note that these atypical fractures occurred in patients significantly younger than patients with typical fractures.

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Femoral Insufficiency Fractures Associated with Prolonged Bisphosphonate Therapy

Abstract: Background Emerging evidence has linked the long-term use of bisphosphonates with femoral insufficiency fractures. It has been suggested that the prolonged effect on bone remodeling leads to the accumulation of microfractures and weakening of bone.

Cited by 90 publications

References 55 publications

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

Incidence of atypical nontraumatic diaphyseal fractures of the femur

Fracturas Femorais Atípicas e o Tratamento com Bifosfonatos: É um Factor de Risco?

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