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      Fratura espontânea bilateral do fémur e ingestão crónica de bifosfonatos

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          Abstract

          Os bifosfonatos são considerados a terapia de primeira linha no tratamento e prevenção da osteoporose pós-menopáusica, conduzindo a um aumento da densidade mineral óssea e à diminuição do risco de fratura. A sua eficácia tem sido amplamente confirmada por vários estudos, no entanto, têm surgido na literatura relatos que apontam para uma possível associação entre o uso de bifosfonatos e o risco aumentado de fraturas não-osteoporóticas. Relatamos o caso de uma mulher de 66 anos, com antecedentes de osteoporose comprovada após estudo osteodensitométrico, sem fatores major de risco, medicada com bifosfonatos suplementados com cálcio oral ininterruptamente há 13 anos que sofreu uma fratura bilateral do fémur após traumatismo de baixa energia. Ambas as fraturas, espaçadas temporalmente por um ano, foram tratadas cirurgicamente e no estudo complementar efetuado não se detetou nenhuma alteração no metabolismo do cálcio nem critérios sugestivos de metastização óssea ou osteoporose. O caso apresentado cumpre os critérios aceites de fratura atípica do fémur fazendo assim exaltar a possibilidade de se tratar de um efeito adverso após a toma crónica de bifosfonatos. Se por um lado a evidência científica ainda não estabeleceu esta associação de forma inequívoca, por outro a eficácia destes fármacos na prevenção de fraturas osteoporóticas é amplamente suportada por estudos clínicos randomizados. Com este caso procurámos contribuir para a crescente discussão sobre uma possível relação entre a terapêutica crónica com bifosfonatos e o seu impacto na remodelação óssea.

          Translated abstract

          Bisphosphonates are considered a first-line therapy on the treatment and prevention of postmenopausal osteoporosis, increasing bone mineral density and reducing the risk of fracture. Its effectiveness has been widely confirmed by several studies however there have been reports in the literature suggesting a possible association between the use of bisphosphonates and an increased risk of non-osteoporotic fractures. We report a case of a 66-years old woman with history of osteoporosis, confirmed by bone mineral density, without major risk factors, treated continuously for the last 13-years with bisphosphonates supplemented by oral calcium, who suffered a bilateral femur fracture after low-energy trauma. Both fractures, separated temporally for 1-year, were surgically treated and on the complementary study made we weren’t able to detect any alteration on calcium metabolism, osteoporosis or neoplastic disease. This case fulfils the criteria for atypical femur fracture exalting the possibility of the side effects after chronic use of bisphosphonates. If in one hand scientific evidence has not yet been unequivocally established, on the other hand the efficacy of these drugs on the prevention of osteoporotic fractures is widely supported by randomised clinical studies. With this case we expect to contribute for the growing discussion about a possible link between the chronic therapy with bisphosphonates and their impact on bone turnover.

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          Most cited references26

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          Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research.

          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. © 2010 American Society for Bone and Mineral Research.
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            Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group.

            Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmenopausal osteoporosis. To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis. Randomized, double-blind, placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998. Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received calcium, 1000 mg/d. Vitamin D (cholecalciferol, up to 500 IU/d) was provided if baseline levels of 25-hydroxyvitamin D were low. Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessments of radiographs; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry. The 2.5 mg/d of risedronate arm was discontinued after 1 year; in the placebo and 5 mg/d of risedronate arms, 450 and 489 subjects, respectively, completed all 3 years of the trial. Treatment with 5 mg/d of risedronate, compared with placebo, decreased the cumulative incidence of new vertebral fractures by 41 % (95% confidence interval [CI], 18%-58%) over 3 years (11.3 % vs 16.3%; P= .003). A fracture reduction of 65% (95% CI, 38%-81 %) was observed after the first year (2.4% vs 6.4%; P<.001). The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39% (95% CI, 6%-61 %) (5.2 % vs 8.4%; P = .02). Bone mineral density increased significantly compared with placebo at the lumbar spine (5.4% vs 1.1 %), femoral neck (1.6% vs -1.2%), femoral trochanter (3.3% vs -0.7%), and midshaft of the radius (0.2% vs -1.4%). Bone formed during risedronate treatment was histologically normal. The overall safety profile of risedronate, including gastrointestinal safety, was similar to that of placebo. These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis.
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              Bisphosphonate use and atypical fractures of the femoral shaft.

              Studies show conflicting results regarding the possible excess risk of atypical fractures of the femoral shaft associated with bisphosphonate use. In Sweden, 12,777 women 55 years of age or older sustained a fracture of the femur in 2008. We reviewed radiographs of 1234 of the 1271 women who had a subtrochanteric or shaft fracture and identified 59 patients with atypical fractures. Data on medications and coexisting conditions were obtained from national registries. The relative and absolute risk of atypical fractures associated with bisphosphonate use was estimated by means of a nationwide cohort analysis. The 59 case patients were also compared with 263 control patients who had ordinary subtrochanteric or shaft fractures. The age-adjusted relative risk of atypical fracture was 47.3 (95% confidence interval [CI], 25.6 to 87.3) in the cohort analysis. The increase in absolute risk was 5 cases per 10,000 patient-years (95% CI, 4 to 7). A total of 78% of the case patients and 10% of the controls had received bisphosphonates, corresponding to a multivariable-adjusted odds ratio of 33.3 (95% CI, 14.3 to 77.8). The risk was independent of coexisting conditions and of concurrent use of other drugs with known effects on bone. The duration of use influenced the risk (odds ratio per 100 daily doses, 1.3; 95% CI, 1.1 to 1.6). After drug withdrawal, the risk diminished by 70% per year since the last use (odds ratio, 0.28; 95% CI, 0.21 to 0.38). These population-based nationwide analyses may be reassuring for patients who receive bisphosphonates. Although there was a high prevalence of current bisphosphonate use among patients with atypical fractures, the absolute risk was small. (Funded by the Swedish Research Council.).
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                rpot
                Revista Portuguesa de Ortopedia e Traumatologia
                Rev. Port. Ortop. Traum.
                Sociedade Portuguesa de Ortopedia e Traumatologia (Lisboa )
                1646-2122
                December 2013
                : 21
                : 4
                : 535-541
                Affiliations
                [1 ] Centro Hospitalar e Universitário de Coimbra, EPE Portugal
                Article
                S1646-21222013000400010
                51cfe661-f78f-4dcc-b040-491b1fd339dc

                http://creativecommons.org/licenses/by/4.0/

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                Product

                SciELO Portugal

                Self URI (journal page): http://www.scielo.mec.pt/scielo.php?script=sci_serial&pid=1646-2122&lng=en
                Categories
                ORTHOPEDICS

                Orthopedics
                Pathological fracture,bisphosphonates,low energy trauma,osteoporosis,Fratura patológica,bifosfonatos,trauma de baixa energia,osteoporose

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