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 Table of Contents  
Year : 2019  |  Volume : 4  |  Issue : 3  |  Page : 50-52

Atypical subtrochanteric femur fracture following bisphosphonates: A grey area of diagnosis and management

Department of Orthopaedics, Jagadguru Sri Shivarathreeshwara Hospital, Mysore, India

Date of Submission20-Mar-2019
Date of Acceptance20-Jun-2019
Date of Web Publication9-Sep-2019

Correspondence Address:
Supreeth Nekkanti
Department of Orthopaedics, Jagadguru Sri Shivarathreeshwara Hospital, Mysore
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2542-4157.265975

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Background and objective: Osteoporosis is a common orthopaedic problem of the geriatric population. Bisphosphonates have been effectively used to control osteoporosis and improve the bone strength. Bisphosphonates has particularly been used in glucocorticoid induced osteoporosis. However, there are emerging concerns over the risk of atypical femoral pathological fractures consequent to prolonged use of BPN therapy. This study was designed to report the diagnosis and treatment of atypical subtrochanteric femur fractures after bisphosphonate treatment.
Subject and methods: We report a rare case of atypical femur fracture in a 70-year-old female patient who has been taking bisphosphonates for glucocorticoid-induced osteoporosis for 5 years. She suffered a subtrochanteric fracture after tripping on the doorstep. The fracture was fixed using a titanium proximal femur nail. The patient was followed up by X-ray examination 1 year after operation. This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Jagadguru Sri Shivarathreeshwara Hospital, India. Written informed consent was obtained from the patient.
Results: The postoperative period was uneventful, and the patient recovered well. The patient was independently ambulatory with good function of her left hip.
Conclusion: Atypical femoral fractures are defined clearly by the American Society of Bone and Mineral Research (ASBMR) criteria. Many reports in the literature have reported atypical femoral fractures after bisphosphonates therapy but do not meet the ASBMR criteria. The risk ratio of atypical femoral fractures after bisphosphonates use is high. Regular monitoring and screening of patients on bisphosphonates therapy by radiographs allow us to diagnose these fractures early and treat them successfully.

Keywords: American Society of Bone and Mineral Research criteria; atypical femur fracture; bisphosphonate therapy; femur fracture; glucocorticoid-induced osteoporosis; older adult; subtrochanteric fracture

How to cite this article:
Mahadevappa P, Nekkanti S, Nanjesh P, Moogali A, Patel S. Atypical subtrochanteric femur fracture following bisphosphonates: A grey area of diagnosis and management. Clin Trials Orthop Disord 2019;4:50-2

How to cite this URL:
Mahadevappa P, Nekkanti S, Nanjesh P, Moogali A, Patel S. Atypical subtrochanteric femur fracture following bisphosphonates: A grey area of diagnosis and management. Clin Trials Orthop Disord [serial online] 2019 [cited 2020 Jul 3];4:50-2. Available from: http://www.clinicalto.com/text.asp?2019/4/3/50/265975

  Introduction Top

Alendronate is a potent inhibitor of bone resorption.[1] It was the first drug of its class approved for the treatment of osteoporosis by the United States of America Food and Drugs Administration in 1995.[1] Bisphosphonates (BPNs) have effectively reduced the incidence of vertebral and femoral neck fractures in postmenopausal women.[2],[3] Although BPNs have been used successfully to treat osteoporosis, their negative role on bone remodelling and increased microdamage has raised concerns among the treating surgeons.[4],[5] Unlike typical fractures of the hip seen commonly around the neck of femur, intertrochanteric fractures and femoral shaft regions, atypical femoral fractures (AFFs) occur in the subtrochanteric region which is rare. Subtrochanteric fractures following BPN therapy are reported to be three fractures per 10,000 person-year in some populations.[2],[6] We report a rare case of an atypical subtrochanteric femur fracture in a 70-year-old lady who has treated with ibandronic acid for glucocorticoid-induced osteoporosis for 1 year.

  Subject and methods Top

A 70-year-old female patient presented with a history of diffuse left thigh pain since 1 month for which she was taken to a local hospital. On reviewing the examination notes of the patient, she did not present with any deformity, point tenderness and abnormal mobility. The range of movements of the hip was normal. The patient refused a radiograph of her thigh. One week later, she tripped over the door step, but she did not fall down. After this, she was unable to bear weight on the affected side. She was taken again to the local hospital where plain radiographs were taken and showed a fracture of the left proximal femur. The limb was immobilised using a Thomas splint and skin traction and referred to our hospital for further management. This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Jagadguru Sri Shivarathreeshwara Hospital, India. Written informed consent was obtained from the patient.

On examination, left lower limb was externally rotated; tenderness was present over the left upper thigh; abnormal mobility was present; and hip range of motion was not able to elicit because of pain. A plain radiograph revealed a left-sided transverse subtrochanteric femur fracture [Figure 1]A. Skin traction with 2 kg weight was applied and evaluated.
Figure 1: Pre-and post-operative X-ray images
Note: (A) Pre-operative X-ray shows a left-sided transverse subtrochanteric femur fracture. (B) Post-operative X-ray after closed reduction and internal fixation with proximal femoral nail.

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She was a known diabetic on regular oral medication in the past 20 years. She was recently diagnosed with hypertension on treatment. She was evaluated for a chronic cough, morning stiffness and pain in small joints of hand 5 years back, and was diagnosed to have interstitial lung disease with rheumatoid arthritis with hypothyroidism. She was administered intravenous cyclophosphamide 900 mg monthly once for 1 year. She was initially given oral methylprednisolone 10 mg once daily and gradually tapered to a current dose of 5 mg daily over 5 years. She has also been taking oral hydroxychloroquine 200 mg daily once, subcutaneous ibandronic acid 150 mg, monthly once since 5 years. The last dose of ibandronic acid she took was ten days before the injury. She is also taking oral thyroxine 12.5 mcg daily since 5 years for hypothyroidism. Daily calcium and weekly vitamin D3 supplementation and oral aspirin 75 mg weekly twice or thrice were also a part of her medications. Coronary angiography was done 1 year back for chest pain and study was found to be normal.

After 3 days of presentation in our hospital, she underwent surgery-closed reduction and internal fixation with proximal femoral nail [Figure 1]B. Low molecular weight heparin 40 mg was given for 5 days which were followed by oral rivaroxaban for 15 days. Subsequently, rivaroxaban was stopped, and oral ecosprin 75 mg was continued daily. Daily injection of teriparatide (20 mcg subcutaneous) was started postoperatively after 4 weeks. Her calcium and vitamin D3 supplementation, hydroxychloroquine were continued. BPNs and methylprednisolone were discontinued. Hip, knee and ankle mobilisation was started on the 3rd postoperative day. Toe touch weight bearing was allowed only after 8 weeks.

  Results Top

The postoperative period was uneventful, and the patient recovered well. Regular radiographs at 1-year follow-up showed good fracture healing [Figure 2]. The patient was independently ambulatory with good function of her left hip.
Figure 2: X-ray views of the left hip at 1-year follow-up.
Note: (A) Anteroposterior view. (B) Lateral view.

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  Discussion Top

The etiology of AFF is poorly understood. BPN is believed to have a strong affinity for mineralised tissue. They bind to the calcium crystals and induce a cellular effect on the osteoclasts during bone resorption. The BPNs have a long half-life, and their effect lasts long after the BPN therapy has been stopped. Due to decreased bone turnover, the BPN induces microdamage and reduces the bone strength, leading to microcracks and pathological fractures.[7] Mashiba and Komatsubara demonstrated decreased bone turnover and microdamage in animal model bones when administered BPN.[8] BPN has also been hypothesized to be involved in collagen fibre cross-linking, increased mature collagen shaping and greater bone stiffness.[9] Another theory has been published to explain the AFF is the decreased vascularisation during BPN therapy. Wood et al.[10] reported the anti-angiogenic properties of BPN. Fournier et al.[11] observed a 40% reduction in the vascularity of the bone following BPN therapy in mouse models. This was attributed to the anti-osteoclastic activity of BPN.

The risk ratio of AFF after BPN therapy has been overestimated in a few studies due to inadequate selection criteria.[6],[12],[13] American Society of Bone and Mineral Research (ASBMR) criteria for AFF had been useful in identifying genuine cases of AFF. The risk ratio reduced by 1.5 times when the ASBMR criteria were used to screen their studies. The major criteria to define an AFF include (1) proximal fracture line under the lesser trochanter and distal fracture line above the femoral condyle, (2) transverse or only slightly oblique fracture line (angle < 30°), (3) no trauma or low-energy trauma, (4) non-comminuted fracture and (5) complete fracture crossing from one cortex to the other, with or without a medical cortical beak or incomplete fracture (or fissure) involving only the outer cortex.[14] Our patient’s injury pattern met all the major criteria for an AFF.

The minor criteria include (1) periosteal reaction along the lateral cortex, (2) increased cortical thickness, (3) prodrome pain in the groin or thigh (4) bilateral fracture, (5) delayed healing, (6) co-morbidities: rheumatoid arthritis, vitamin D deficiency, hypophosphatasia and (7) concomitant treatments: bisphosphonates, glucocorticoids, proton pump inhibitors. Our patient was under concomitant treatment with BPN and glucocorticoids for rheumatoid arthritis and interstitial lung disease.

Unlike stress fractures which predominantly involve the medial cortex of proximal femur, AFF usually starts from the lateral cortex and proceed medially. AFF is observed commonly in the geriatric population as in our patient whereas stress fractures present in athletes.

When a patient presents with unexplained thigh or groin pain with normal radiographs, it is necessary to perform an MRI or a CT scan to rule out AFF. The bone scan usually shows increased uptake over the lateral cortex of the proximal femur in AFF.

There is lack of evidence of the appropriate surgical management of AFF. Displaced fractures need to be reduced and surgically fixed. A contralateral femur radiograph is strongly recommended to avoid missing bilateral AFF injuries.

Shane et al.[14],[15] recommended a symptom-based treatment approach of AFF. Asymptomatic patients are advised to reduce their activity level. Patients with groin or thigh pain are advised to use crutches and avoid weight bearing. After 3 months of conservative management, if symptoms persist with no radiological improvement, surgical fixation is considered. Patients at risk for AFF with moderate to severe pain are recommended candidates for prophylactic surgery.[14],[15]

Incomplete fractures are easy to treat with intramedullary nails. There is little evidence to suggest the correct treatment for dislocated AFFs. Grady et al.[16] reported two failures of healing of AFFs after intramedullary nails. Weil et al.[17] reported good outcomes with AFF treated by intramedullary nails. Our patient had a good functional outcome of her left hip after 1-year follow-up.

Pharmacological management of patients with AFF usually is centred around supplementing the depleted levels of calcium and vitamin D. Antiresorptive drugs are usually avoided due to the pathogenesis of BPN in AFF. Teriparatide holds good promise in improved fracture healing. Our patient was administered teriparatide 4 weeks after surgery to allow improved bone healing.

In conclusion, AFFs are rare to occur. BPN therapy has a genuine risk of pathological fractures as in our patient. The real risk ratio is overestimated in the literature due to inadequate selection criteria of the fractures. Early diagnosis is possible when a high index of suspicion is borne by the treating surgeon. Intramedullary nailing of these fractures usually has a good functional outcome although cases of delayed healing have been reported.

Author contributions

Patient diagnosis and surgical treatment: PM; patient management, data collection and manuscript writing: SN; surgery, data collection and documentation: PN; documentation and data collection and follow-up: SP. All authors approved the final version of the paper.

Conflicts of interest

The authors have no conflicts of interests to declare.

Financial support


Institutional review board statement

This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Jagadguru Sri Shivarathreeshwara Hospital, India. Written informed consent was obtained from the patient.

Declaration of patient consent

The authors certify that they have obtained the patient consent form. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initial will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Reporting statement

This study followed the Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals developed by the International Committee of Medical Journal Editors.

Biostatistics statement

The biostatisticians of Jagadguru Sri Shivarathreeshwara Hospital reviewed the statistical methods of this study.

Copyright transfer agreement

The Copyright License Agreement has been signed by the authors before publication.

Data sharing statement

Individual participant data that underlie the results reported in this article, after deidentification (text, and tables), will be available upon request. Data will be available immediately following publication, No end date; for anyone who wishes to access the data. In order to gain access, data requestors will need to sign a data access agreement. Proposals should be directed to drsupreethn@gmail.com..

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Peer review

Externally peer reviewed.

Open access statement

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

P-Reviewers: Zeng H, Chen Y; S-Editor: Li CH; L-Editors: Qiu Y, Wang L; T-Editor: Jia Y

  References Top

Goh SK, Yang KY, Koh JSB, et al. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br. 2007;89:349-353.   Back to cited text no. 1
Black DM, Kelly MP, Genant HK, et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med. 2010;362:1761-1771.   Back to cited text no. 2
Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet. 1996;348:1535-1541.   Back to cited text no. 3
Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res. 2000;15:613-620.   Back to cited text no. 4
Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CYC. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005;90:1294-1301.   Back to cited text no. 5
Gedmintas L, Solomon DH, Kim SC. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: a systematic review and meta-analysis. J Bone Miner Res. 2013;28:1729-1737.   Back to cited text no. 6
Papapoulos SE. Bisphosphonates: how do they work? Best Pract Res Clin Endocrinol Metab. 2008;22:831-847.   Back to cited text no. 7
Mashiba T, Turner CH, Hirano T, Forwood MR, Johnston CC, Burr DB. Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sites in beagles. Bone. 2001;28:524-531.   Back to cited text no. 8
Zioupos P, Currey JD, Hamer AJ. The role of collagen in the declining mechanical properties of aging human cortical bone. J Biomed Mater Res. 1999;45:108-116.   Back to cited text no. 9
Wood J, Bonjean K, Ruetz S, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther. 2002;302:1055-1061.   Back to cited text no. 10
Fournier P, Boissier S, Filleur S, et al. Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res. 2002;62:6538-6544.   Back to cited text no. 11
Schilcher J, Aspenberg P. Incidence of stress fractures of the femoral shaft in women treated with bisphosphonate. Acta Orthop. 2009;80:413-415.   Back to cited text no. 12
Feldstein AC, Black D, Perrin N, et al. Incidence and demography of femur fractures with and without atypical features. J Bone Miner Res. 2012;27:977-986.   Back to cited text no. 13
Shane E, Burr D, Ebeling PR, et al. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2010;25:2267-2294.   Back to cited text no. 14
Shane E, Burr D, Abrahamsen B, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2014;29:1-23.   Back to cited text no. 15
Grady MK, Watson JT, Cannada LK. Treatment of femoral fracture nonunion after long-term bisphosphonate use. Orthopedics. 2012;35:e991-995.   Back to cited text no. 16
Weil YA, Rivkin G, Safran O, Liebergall M, Foldes AJ. The outcome of surgically treated femur fractures associated with long-term bisphosphonate use. J Trauma. 2011;71:186-190.  Back to cited text no. 17


  [Figure 1], [Figure 2]


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