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Oral bisphosphonates are associated with increased risk of subtrochanteric and diaphyseal fractures in elderly women: a nested case-control study.

ABSTRACT: To evaluate the association between bisphosphonate use and the risk of atypical femoral fractures among women aged 65 or older.Nested case-control study.General practice research database in Spain.Use of oral bisphosphonates before the occurrence of atypical fractures among cases or the corresponding index date among controls. Bisphosphonate use was categorised as ever versus never users. Ever users were divided according to the total time since first prescription.Cases were defined as women aged 65 years or older with a first diagnosis of subtrochanteric or diaphyseal fracture, recorded in the BIFAP database between 1 January 2005 and 31 December 2008, and with at least 1 year of follow-up before the index date. For each case, five age-matched and calendar-year-matched controls without a history of hip or atypical fracture were randomly selected from the database.OR of atypical femoral fracture by bisphosphonate use was determined using conditional logistic regression. Models were adjusted for comorbidities and use of other medications.The analysis included 44 cases and 220 matched controls (mean age, 82 years). Ever use of bisphosphonates was more frequent in cases than controls (29.6% vs 10.5%). In multivariate analyses, OR (95% CI) of atypical femoral fracture was 4.30 (1.55 to 11.9) in ever versus never users of bisphosphonates. The risk increased with long-term use, with an OR of 9.46 (2.17 to 41.3) comparing those using bisphosphonates over 3 years versus no users (p for trend=0.01).Bisphosphonate use was associated with an increased risk of subtrochanteric or diaphyseal fractures in elderly women in a low fracture risk population, with a higher risk among long-term bisphosphonate users.

SUBMITTER: Erviti J

PROVIDER: S-EPMC3563115 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Oral bisphosphonates are associated with increased risk of subtrochanteric and diaphyseal fractures in elderly women: a nested case-control study.

Erviti Juan J Alonso Alvaro A Oliva Belén B Gorricho Javier J López Antonio A Timoner Julia J Huerta Consuelo C Gil Miguel M De Abajo Francisco F

BMJ open 20130130 1

<h4>Objectives</h4>To evaluate the association between bisphosphonate use and the risk of atypical femoral fractures among women aged 65 or older.<h4>Design</h4>Nested case-control study.<h4>Setting</h4>General practice research database in Spain.<h4>Exposures</h4>Use of oral bisphosphonates before the occurrence of atypical fractures among cases or the corresponding index date among controls. Bisphosphonate use was categorised as ever versus never users. Ever users were divided according to the ...[more]

PMID: 23370011

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Project description:ContextFemoral shaft cortical thickening has been mentioned in reports of atypical subtrochanteric and diaphyseal (S/D) femur fractures, but it is unclear whether thickening precedes fracture or results from a preceding stress fracture and what role bisphosphonates might play in cortical thickening.ObjectiveOur objective was to examine the relationship of cortical thickness to S/D fracture risk as well as establish normal reference values for femoral cortical thickness in a large population-based cohort of older women.DesignUsing pelvic radiographs obtained in 1986-1988, we measured femoral shaft cortical thickness 3 cm below the lesser trochanter in women in the Study of Osteoporotic Fractures. We measured this in a random sample and in those with S/D fractures and femoral neck and intertrochanteric fractures. Low-energy S/D fractures were identified from review of radiographic reports obtained between 1986 and 2010. Radiographs to evaluate atypia were not available. Analysis used case-cohort, proportional hazards models.OutcomesCortical thickness as a risk factor for low-energy S/D femur fractures as well as femoral neck and intertrochanteric fractures in the Study of Osteoporotic Fractures, adjusting for age and bone mineral density in proportional hazards models.ResultsAfter age adjustment, women with thinner medial cortices were at a higher risk of S/D femur fracture, with a relative hazard of 3.94 (95% confidence interval = 1.23-12.6) in the lowest vs. highest quartile. Similar hazard ratios were seen for femoral neck and intertrochanteric fractures. Medial or total cortical thickness was more strongly related to fracture risk than lateral cortical thickness.ConclusionsIn primarily bisphosphonate-naive women, we found no evidence that thick femoral cortices placed women at higher risk for low-energy S/D femur fractures; in fact, the opposite was true. Women with thin cortices were also at a higher risk for femoral neck and intertrochanteric fractures. Whether cortical thickness among bisphosphonate users plays a role in atypical S/D fractures remains to be determined.

Project description:Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants. Methods: We performed a case-control study nested in a cohort of patients aged 40-99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered. Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01-1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10-1.66) and 1.03 (95% CI: 0.88-1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1 year = 1.10; 95% CI:0.82-1.49; AOR>1-3 years = 1.41; 95% CI:1.01-1.97; AOR>3 years = 1.81; 95% CI:1.25-2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1 year = 0.59; 0.30-1.16). An interaction between oral bisphosphonates and calcium supplements was suggested. Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.

Project description:BackgroundHip fractures usually occur in old aged patients with osteoporotic bone. Management of hip fractures in old aged patient is aimed to ambulate patient immediately and to restore the pre-operative ambulation. Proximal femur replacement is an effective treatment option in elderly patient with osteoporotic bones. It allow immediate weight bearing and early return to preoperative ambulatory status and minimizes the chances of systemic complication associated with prolong bed rest associated with internal fixation. This study is aimed to review the outcome of the patients whom underwent proximal femur replacement as primary treatment for the patient with comminuted intertrochanteric and sub trochanteric fracture.Patients and methodThis is a study conducted in our university hospital which is a tertiary-care level-1 trauma center. A retrospective analysis of 21 patients who underwent proximal femur replacement for comminuted intertrochanteric and sub trochanteric fracture, age more than 60 years during the period from April 2011 to March 2018 was conducted. Data collected included: age, gender, comorbidities, mechanism of injury, type of fracture, functional outcome (calculated via Harris Hip Score) and one year mortality.ResultsThe mean age of the patients was 74.05(range 64-91) years, out of which 13 (61.8%) were female and 8 (38.0%) were male. The mean follow up was 32.6(8-91 months).Immediate post-operative ambulation status was full weight bearing (FWB) in 17 patients (80.9%) of the patients while three patients (19.0%) had non-weight bearing (NWB) due to associated co-morbidities. The mean preoperative Harris Hip score was 68.0, while the mean postoperative Harris Hip score was 66.5 at last follow up. Post operatively one patient (4.7%) developed pulmonary embolism, one patient developed dislocation. One patent (4.7%) died of sepsis from implant infection at 8 months after surgery.ConclusionPrimary Proximal femoral replacement in a viable option in old aged patients with poor bone quality who developed intertrochanteric and subtrochanteric fracture. According to our study, with mortality rate comparable to that of primary fixation, yet with the added advantage of immediate post op ambulation and reduced incidences of decubitus ulcers, atelectasis and DVT.

Dataset Information

Oral bisphosphonates are associated with increased risk of subtrochanteric and diaphyseal fractures in elderly women: a nested case-control study.

Publications

Oral bisphosphonates are associated with increased risk of subtrochanteric and diaphyseal fractures in elderly women: a nested case-control study.

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