Clinical management and pathogenesis of atypical fractures of the femur.

Abstract

The Bone & Joint JournalVol. 99-B, No. 3 EditorialFree AccessClinical management and pathogenesis of atypical fractures of the femurCrossMarkM. K. Javaid, R. Handley, M. L. CostaM. K. JavaidAssociate Professor, Metabolic Bone Disease, Botnar Research Centre, NDORMSCorrespondence should be sent to M. K. Javaid; email: E-mail Address: [email protected]University of Oxford, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford, OX3 7LD, UK.Search for more papers by this author, R. HandleyConsultant, Trauma and Orthopaedic Surgery,John Radcliffe Hospital, Oxford University Hospitals Trust, Headley Way, Headington, Oxford, OX3 9DU, UK.Search for more papers by this author, M. L. CostaProfessor of Orthopaedic Trauma Surgery, NDORMSUniversity of Oxford, Kadoorie Centre, Level 3 John Radcliffe Hospital, Oxford, OX3 9DU, UK.Search for more papers by this authorPublished Online:1 Mar 2017https://doi.org/10.1302/0301-620X.99B3.BJJ-2016-1144.R1AboutSectionsView articleSupplemental MaterialPDF/EPUB ToolsDownload CitationsTrack CitationsPermissionsAdd to Favourites ShareShare onFacebookTwitterLinked InRedditEmail View articleAtypical fractures of the femur (AFF) are defined as atraumatic or low-trauma fractures located in the subtrochanteric region or femoral shaft, and have characteristic clinical and radiological features.1 The use of bisphosphonates and denosumab, both anti-resorptives, is associated with a higher risk of AFF; this is unexpected as these therapies significantly reduce the risk of other fragility fractures. The exact pathogenesis of AFFs is not known, and a number of mechanisms are likely to be involved. AFFs can occur without bisphosphonate exposure, e.g. in patients with hypophosphatasia, pycnodysostosis, osteopetrosis, osteoporosis pseudoglioma syndrome and osteogenesis imperfecta. Hence, some patients with AFF may have underlying bone disorders which have not yet been characterised. Micro-indentation studies demonstrate that even though patients with AFF have had typically long durations of bisphosphonate use, their indentation characteristics are more similar to patients with an untreated fracture.2 More studies are now highlighting geometric differences in the lower limb3-5 in those who go on to have an AFF, suggesting mechanisms involving bone growth/adaptation to loading. The absolute risk of AFF is low and the benefits of therapy for osteoporosis considerably outweigh the risks, preventing 137 hip fractures for every AFF with which they are associated.6 However, the risk of AFF is mainly drawn from observational data and it is not known how low adherence to oral bisphosphonates in the wider community has reduced the potential incidence of AFF. The clinical management is divided into three broad areas: - recovery of the fractured side; - reduction of AFF risk on the contralateral side;- reduction of fragility fracture at other sites. The key to this pathway is identification that the patient has had an AFF by the treating clinical team. The 2013 American Society for Bone and Mineral Research (ASBMR) guidelines on the epidemiology, pathogenesis and medical management of atypical fractures7 updated the 2010 guidance. They require at least four ‘major features’ of AFF to make this diagnosis:- fracture as a result of a trauma equivalent to a fall from standing height or less;- the fracture line originates at the lateral cortex and is substantially transverse in its orientation, although it may become oblique as it progresses medially across the femur;- complete fractures extend through both cortices and may be associated with a medial spike – incomplete fractures involve only the lateral cortex;- the fractures are non-communited or minimally comminuted;- localised periosteal or endosteal thickening of the lateral cortex is present at the fracture site (“beaking” or “flaring”); - periprosthetic fractures, or fractures involving primary or secondary bone tumours, are excluded. The successful recognition of an AFF requires increased awareness in all members of the trauma team including orthopaedics, care of the elderly, radiology and specialist nurses. Awareness of this issue needs to be incorporated into the national training learning objectives of each of these specialties. A practical step towards increased awareness would be for the referring team to record the use of anti-resorptive medication in radiology requests for subtrochanteric femoral fragility fractures to alert the reporting radiology team. Another important consideration is a consistent message to the patient and their family. The patient and family are likely to be unaware how a medication they took pains to take properly in order to reduce the risk of fracture can increase the risk of AFF. In addition, clinical teams in both primary and secondary care may have missed the importance of prodromal symptoms. This has to be handled sensitively with timely and clear communication from all involved to ensure the patient receives a consistent transparent message. While there have been Department of Health drug safety updates in 2011 for bisphosphonates8 and 2013 for denosumab,9 these were designed for physicians. Although there is an excellent guide of 12 questions for patients with a fracture of the hip,10 there is no guide for the patient who has had an AFF.There is also little trial evidence to inform clinical management and decision-making for the patient with an AFF. However, pathways based upon basic principles have been developed to harmonise care, and have been implemented in some areas of the country.11Management of the fractured sideThe femur of patients with an AFF is typically brittle with a thick cortex. Intramedullary nailing is the mainstay of treatment. The key orthopaedic principles include: careful reaming in often narrow femoral canals, optimal length of nail to reduce the risk of peri-implant fracture and careful selection of entry point to avoid further varus at the fracture site – choosing a more medial entry point for the nail creates a valgus force at the site of the fracture. While the normal objective in fracture surgery is to restore the pre-injury morphology, in AFF it was from that pre-existing position the bone had failed. Therefore, it would be logical to seek and correct pre-existing varus. The fixation should generally incorporate the femoral neck.12 The aim of surgery is to enable the patient to bear weight as soon as possible after surgery.This is particularly important in an AFF in order to reduce the load on the contralateral side which is also at risk. A characteristic feature of an AFF is delayed healing with fractures sometimes taking over six months to unite, leading to ongoing pain and concern for patients and their clinicians.13,14 It is important to optimise other potential contributors to poor healing, ensuring: 25OH vitamin D > 50 nmol/L, intake of calcium of 700 mg to 1000 mg per day, smoking cessation, consuming less than three units of alcohol per day, improved control of comorbidities (inflammatory diseases, diabetes) and an adequate body mass index. While there was initial enthusiasm for using teriparatide for treating an AFF with improving bone healing15 and also reducing the contralateral risk of AFF, recent observational studies have questioned its efficacy16 and a number of clinical trials are now underway. Management of the contralateral side or incomplete AFFA key aim is to reduce the risk of AFF on the contralateral side. In the emergency setting of an AFF, the assessment of the contralateral side can be neglected. Patients with an AFF should always be asked specifically about symptoms in the groin or leg on the other side, and a baseline radiograph of the contralateral femur should be taken to include the region from the lesser trochanter to the distal supracondylar flare. Clinicians should be aware that pain is not always present, even in patients with an incomplete fracture.Imaging of the contralateral leg should not delay treatment of the fracture. However, all patients with symptoms or suspicion on plain radiographs should have a coronal T1 and short tau inversion recovery MRI of the unfractured side at the earliest appropriate time. If bone marrow oedema is present, patients should have protected weight-bearing, as described below, for three months in the first instance and preferably until the MRI shows no bone oedema. If MRI is not possible, CT should be used to detect a cortical lucency, and new bone formation or nuclear bone scanning, looking for local areas of high uptake. In order to reduce the risk of AFF the key is to stop the anti-resorptive agent. This highlights the importance of making the diagnosis of AFF, as the usual clinical response for patients suffering a fracture while on treatment is to increase the potency of bone therapy.17 From epidemiological studies, the risk of AFF is reduced by 70% within 12 months of stopping oral bisphosphonates.18 It is important to discuss the risk of contralateral fracture with the patient during the acute admission as they remain at higher risk of AFF for at least 12 months. As discussed above, the evidence for using teriparatide or other agents to reduce contralateral AFF is unclear and we await the results of the current randomised controlled trials. There is a significant mechanical component to the aetiology of AFF19 and one objective is to reduce the load of the contralateral side. Hence, patients with symptoms or MRI changes should be encouraged to use a walking aid on the side of the index fracture to reduce the load on the contralateral femur. This contrasts with the usual rehabilitation recommendations after limb surgery where the fractured limb is the one that is protected. Given that most AFFs occur whilst the patient is being managed for osteoporosis in the community, GPs also need to be aware of the key aspects of care. Hence, referrals and consultations from primary care may include those patients with potential incomplete AFFs. Key aspects to consider include:- AFF is very unlikely to affect many patients in your practice. Salient features include: - taking any type of bisphosphonate for at least a year and active treatment within the last 12 months;- the pain is felt typically in the anterior thigh or groin and is dull or aching in nature;- other causes excluded are osteoarthritis from the spine, hip or knee;- if there is a suspicion of an AFF, consider stopping the bisphosphonate and request urgent anteroposterior and lateral radiographs of the whole femur;- if radiograph reports an insufficiency fracture or localised periosteal reaction, consider urgent assessment and make the patient non-weight-bearing with a crutch on the opposing side to the painful thigh. The role of prophylactic nailing The 2013 ASBMR guidelines recommend prophylactic nailing in patients with cortical lucency or those with ongoing pain despite two months of conservative therapy. However, this procedure is not without risk of significant morbidity and potential mortality and therefore requires careful case-by-case discussion between orthopaedic surgeon, physician and patient. Often a ‘watch and wait’ policy is used, alerting the patient of the importance of reporting symptoms of pain or discomfort on the contralateral side. This often increases anxiety in many patients and, while unavoidable, should be explicitly discussed with the patient and their family as part of their management. A watch and wait policy can only work if the patient is given easy and timely access to expert assessment and repeat MR imaging. The Fracture Liaison Service may facilitate this. Management of generalised fragility fracture riskThe management of a patient with an AFF requires re-assessment of the risk of fragility fracture. This includes a history of bone and falls risk factors, physical examination for secondary causes of osteoporosis and spine fractures, and selected investigations including blood, urine and dual-energy X-ray absorptiometry techniques to rule out secondary causes and to guide treatment. Recently, there has been a shift in the aims of the treatment of osteoporosis, away from the prevention of low bone density towards the specific prevention of fracture. It is likely that there is a subset of patients who were appropriately commenced on lifelong therapy decades ago but, in light of current knowledge, would no longer be considered of sufficient risk to warrant pharmacological treatment.In those patients thought to be at high enough risk to warrant pharmacological therapy for bone health, the options are limited. Use of strontium ranelate or teriparatide are not thought to increase the risk of AFF. However, recent warnings from the Medicines and Healthcare products Regulatory Agency have limited the range of patients who can have strontium20 and, in the United Kingdom, National Institute for Health and Care Excellence technology appraisal 161 thresholds21 often lead to the need for ‘individual funding requests’ for teriparatide via the Clinical Commissioning Group, with mixed results. Even if teriparatide is approved, it is not clear what to do after 24 months of treatment, as most centres usually switch to a potent anti-resorptive therapy with the aim of maintaining the skeletal benefits in patients without an AFF. Another option is to use raloxifene or hormone therapies, but both have their own restrictions and risks.There are three options: - prophylactic nailing of the contralateral side accepting the associated surgical morbidity and mortality and then starting anti-resorptive therapy; - the introduction of anti-resorptive therapy, with close monitoring for features of an AFF. The choice of therapy is influenced by the ease of stopping the biological action, should features develop;- keep the patient off anti-osteoporosis treatment with the aim of review if or when re-fractures occur, or repeating the DXA scan every two to three years, hence balancing the impact of fragility fracture versus AFF. However, while the risk of fragility fracture can be estimated, the risk of AFF is unknown, but is considered high if the patient is re-exposed to an anti-resorptive therapy. This is a significant limitation of the shared decision-making process.Overall, therapy with anti-osteoporosis medication is generally safe and AFFs are rare. The management of a patient with an AFF is complex and involves several disciplines with experience with AFF. There is little strong evidence to inform clinical decisions at an individual patient level, but this article highlights key principles for the management of both the AFF and, importantly, the contralateral limb. National and international guidelines would help to standardise care and act as a model against which new interventions and pathways can be tested.Take home message:- Atypical subtrochanteric fractures have been associated with the use of both bisphosphonates and denosumab.- The balance of benefit versus risk still favours anti-osteoporosis medication to reduce fragility fracture risk. An estimated 137 hip fractures are prevented for each observed AFF in patients treated with bisphosphonates for osteoporosis. - Surgical fixation should be designed to facilitate weight-bearing on the fractured femur. - The contralateral side should always be assessed for pain and radiological signs of involvement. - Further work is required to understand when to recommend prophylactic nailing, and whether to start osteoporosis therapies to prevention fragility fracture at other sites. References 1 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. Crossref, Medline, ISI, Google Scholar2 Güerri-Fernández RC, Nogués X, Quesada Gómez JM, et al. Microindentation for in vivo measurement of bone tissue material properties in atypical femoral fracture patients and controls. J Bone Miner Res 2013;28:162–168. 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