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      ATYPICAL FEMORAL FRACTURES DUE TO THE USE OF BISPHOSPHONATES: EPIDEMIOLOGIC STUDY IN A TERTIARY HOSPITAL Translated title: FRATURAS ATÍPICAS DE FÊMUR POR USO DE BIFOSFONATOS: ESTUDO EPIDEMIOLÓGICO EM UM HOSPITAL TERCIÁRIO

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          ABSTRACT

          Objective:

          Show the relationship between atypical femoral fractures and prolonged use of bisphosphonates and analyze the limit of its beneficial use.

          Methods:

          Retrospective cohort study (level of evidence 2B). From Atypical fracture cases, patients who used bisphosphonates were selected and the time period of their use was analyzed. Additionally, the variables sex, age, and the side most affected were studied.

          Results:

          Nine atypical femur fractures were found, all associated with the use of bisphosphonates. The average period of use of this medication was nine years (minimum of three years; maximum of 14 years). The patients’ mean age was of 78 years (69-88 years) and all were women, with the right member being the most affected.

          Conclusion:

          The use of bisphosphonates to prevent osteoporotic fractures has been increasingly frequent and, when used for a prolonged period, it has been related to atypical fractures. Further scientific studies on doses, maximum periods of treatment, and risk-benefit in the indication of these medications are needed to assist in therapeutic management for each case. Level of Evidence II, Retrospective Study.

          RESUMO

          Objetivo:

          Demonstrar relação entre as fraturas atípicas de fêmur e o uso prolongado de bifosfonatos, descrever sua incidência e analisar até qual momento o seu uso é benéfico.

          Métodos:

          Estudo de coorte retrospectivo (nível de evidência 2B). Análise de 151 prontuários de pacientes com diagnóstico de fratura de fêmur em um hospital terciário, no período de janeiro de 2013 a dezembro de 2018. Foram selecionados os casos de fraturas atípicas e, dentre esses, os que faziam uso de bifosfonatos e o tempo de utilização. Ademais, foram estudadas as variáveis sexo, idade e lado mais acometido.

          Resultados:

          Constatadas 9 fraturas atípicas de fêmur, todas associadas ao uso de bifosfonatos. O período médio de uso dessa medicação foi de 9 anos (mínimo - 3 anos; máximo - 14 anos). A idade média dos pacientes foi de 78 anos (69-88 anos) e ocorrência unicamente em mulheres, tendo como membro mais acometido o direito.

          Conclusão:

          O uso dos bifosfonatos na prevenção de fraturas osteoporóticas tem sido cada vez mais frequente e relacionado às fraturas atípicas, quando empregado por tempo prolongado. A coleta de mais informações científicas que estudem doses, períodos máximos de tratamento e risco-benefício na indicação dessas medicações é essencial para auxiliar no manejo terapêutico apropriado para cada caso. Nível de Evidência II, Estudo Retrospectivo .

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          Low-energy femoral shaft fractures associated with alendronate use.

          Andrew Neviaser, Joseph Lane, Brett Lenart … (2015)
          Increasing evidence suggests long-term alendronate use may overly suppress bone metabolism, limiting repair of microdamage and creating risk for insufficiency fractures. The purpose of this study is to demonstrate an association between alendronate use and a specific pattern of low-energy femoral shaft fracture. A retrospective review was performed of patients with femoral shaft fractures admitted to a Level 1 trauma center between January 2002 and March 2007. Seventy low-energy fractures were identified. The medical records were reviewed, and the incidence and duration of alendronate use were recorded. The incidence of a specific femoral shaft fracture in those patients taking alendronate compared with those not being treated was determined. There were 59 females and 11 males. The average age was 74.7 years. Twenty-five (36%) were being treated with alendronate. None of the patients had used or were using other bisphosphonates. Nineteen (76%) of these 25 patients demonstrated a simple, transverse fracture with a unicortical beak in an area of cortical hypertrophy. This fracture pattern was seen in only 1 patient (2%) not being treated with alendronate. Alendronate use was a significant risk factor for the fracture pattern (odds ratio [OR]) 139.33, 95% CI [19.0-939.4], P < 0.0001). This pattern was 98% specific to alendronate users. The average duration of alendronate use in those with the pattern was significantly longer than those who did not exhibit the pattern but were taking alendronate, 6.9 years versus 2.5 years of use, respectively (P = 0.002). Only 1 patient with the fracture pattern had been taking alendronate for less than 4 years. Low-energy fractures of the femoral shaft with a simple, transverse pattern and hypertrophy of the diaphyseal cortex are associated with alendronate use. This may result from propagation of a stress fracture whose repair is retarded by diminished osteoclast activity and impaired microdamage repair resulting from its prolonged use.
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            Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control study.

            F Edobor-Osula, Dean Lorich, S Lyman … (2009)
            Recent evidence has linked long-term bisphosphonate use with insufficiency fractures of the femur in postmenopausal women. In this case-control study, we have identified a significant association between a unique fracture of the femoral shaft, a transverse fracture in an area of thickened cortices, and long-term bisphosphonate use. Further studies are warranted. Although clinical trials confirm the anti-fracture efficacy of bisphosphonates over 3-5 years, the long-term effects of bisphosphonate use on bone metabolism are unknown. Femoral insufficiency fractures in patients on prolonged treatment have been reported. We performed a retrospective case-control study of postmenopausal women who presented with low-energy femoral fractures from 2000 to 2007. Forty-one subtrochanteric and femoral shaft fracture cases were identified and matched by age, race, and body mass index to one intertrochanteric and femoral neck fracture each. Bisphosphonate use was observed in 15 of the 41 subtrochanteric/shaft cases, compared to nine of the 82 intertrochanteric/femoral neck controls (Mantel-Haenszel odds ratio (OR), 4.44 [95% confidence interval (CI) 1.77-11.35]; P = 0.002). A common X-ray pattern was identified in ten of the 15 subtrochanteric/shaft cases on a bisphosphonate. This X-ray pattern was highly associated with bisphosphonate use (OR, 15.33 [95% CI 3.06-76.90]; P < 0.001). Duration of bisphosphonate use was longer in subtrochanteric/shaft cases compared to both hip fracture controls groups (P = 0.001). We found a significantly greater proportion of patients with subtrochanteric/shaft fractures to be on long-term bisphosphonates than intertrochanteric/femoral neck fractures. Bisphosphonate use was highly associated with a unique X-ray pattern. Further studies are warranted.
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              Bilateral low-energy simultaneous or sequential femoral fractures in patients on long-term alendronate therapy.

              Nirmal Tejwani, Craig M Capeci (2009)
              While alendronate therapy has been shown to decrease the risk of vertebral and femoral neck fractures in postmenopausal osteoporotic patients, recent reports have associated long-term alendronate therapy with unilateral low-energy subtrochanteric and diaphyseal femoral fractures in a small number of patients. To our knowledge, there has been only one report of sequential bilateral femoral fractures in patients on long-term bisphosphonate therapy. We retrospectively reviewed the case log of the senior author over the last four years to identify patients who presented with a subtrochanteric or diaphyseal femoral fracture after a low-energy mechanism of injury (a fall from standing height or less) and who had been taking alendronate for more than five years. Radiographs were reviewed, and the fracture patterns were recorded. Serum calcium levels were recorded when available. Seven patients who sustained low-energy bilateral subtrochanteric or diaphyseal femoral fractures while on long-term alendronate therapy were identified. One patient presented with simultaneous bilateral diaphyseal fractures, two patients had sequential subtrochanteric fractures, and four patients had impending contralateral subtrochanteric stress fractures noted at the time of the initial fracture. Of the latter four, one patient had a fracture through the stress site and the other three patients had prophylactic stabilization of the site with internal fixation. No patient had discontinued alendronate therapy prior to the second fracture. All patients were women with an average age of sixty-one years, and they had been on alendronate therapy for an average of 8.6 years. All fractures were treated with reamed intramedullary nailing and went on to union at an average of four months. In patients on long-term alendronate therapy who present with a subtrochanteric or diaphyseal femoral fracture, we recommend radiographs of the contralateral femur and consideration of discontinuing alendronate in consultation with an endocrinologist. If a contralateral stress fracture is found, prophylactic fixation should be considered.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Acta Ortop Bras
                Journal ID (iso-abbrev): Acta Ortop Bras
                Journal ID (publisher-id): aob
                Title: Acta Ortopedica Brasileira
                Publisher: ATHA EDITORA
                ISSN (Print): 1413-7852
                ISSN (Electronic): 1809-4406
                Publication date (Electronic, pub): 15 April 2022
                Publication date (Electronic, collection): Mar-Apr 2022
                Volume: 30
                Issue: 2
                Electronic Location Identifier: e238821
                Affiliations
                [1 ]Fundação Hospitalar São Lucas, Centro Especializado em Ortopedia e Traumatologia, Cascavel, PR, Brazil
                [2 ]Centro Universitário Assis Gurgacz, Cascavel, PR, Brazil
                Author notes
                Correspondence: Fernanda da Costa Golfieri. Rua Pernambuco, 1561, apt. 22, Cascavel, PR, Brazil, 85810021. fer.golfieri@ 123456hotmail.com

                AUTHORS’ CONTRIBUTIONS: Each author contributed individually and significantly to the development of this article. FCG: acquisition, analysis and interpretation of the data, writing of the article, final approval of the manuscript, responsibility for all aspects of the study; MZ: acquisition, analysis and interpretation of the data, writing of the article; PPVP: conception and design of the study, critical review, final approval of the manuscript.

                All authors declare no potential conflict of interest related to this article.

                Author information
                http://orcid.org/0000-0002-3521-4557
                http://orcid.org/0000-0002-2109-8874
                http://orcid.org/0000-0003-0200-0357
                Article
                Other ID: 00501
                DOI: 10.1590/1413-785220223002238821
                PMC ID: 9177062
                SO-VID: 74739a11-395a-4110-8b7a-98fea33cdece
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License

                History
                Date received : 29 May 2020
                Date accepted : 19 November 2021
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 17
                Categories
                Subject: Update Article
                Subject: Hip and Osteometabolic Diseases

                Keywords: bisphosphonates,adverse effects,insufficiency fractures,subtrochanteric fractures,femoral fractures,osteoporosis,bifosfonatos,efeitos adversos,fraturas por insuficiência,fraturas subtrocantericas,fraturas do fêmur,osteoporose
                Data availability:
                Keywords: bisphosphonates, adverse effects, insufficiency fractures, subtrochanteric fractures, femoral fractures, osteoporosis, bifosfonatos, efeitos adversos, fraturas por insuficiência, fraturas subtrocantericas, fraturas do fêmur, osteoporose

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