Objectives. Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs. Methods. We present an evaluation of current literature relating to the pathogenesis and treatment of AFFs in the context of bisphosphonate use. Results. Six broad themes relating to the pathogenesis and management of bisphosphonate-related AFFs are presented. The key themes in fracture pathogenesis are: bone microdamage accumulation; altered bone mineralisation and altered collagen formation. The key themes in fracture management are: medical therapy and surgical therapy. In addition, primary prevention strategies for AFFs are discussed. Conclusions. This article presents current knowledge about the relationship between bisphosphonates and the development of AFFs, and highlights key areas for future research. In particular, studies aimed at identifying at-risk subpopulations and organising surveillance for those on long-term therapy will be crucial in both increasing our understanding of the condition, and improving population outcomes. Cite this article: N. Kharwadkar, B. Mayne, J. E. Lawrence, V. Khanduja. Bisphosphonates and atypical subtrochanteric fractures of the femur. Bone Joint Res 2017;6:144–153. DOI: 10.1302/2046-3758.63.BJR-2016-0125.R1

Introduction

Basicervical fracture of the femur is one type of hip fracture, which is regarded as an extra and intra-capsular fracture. We experienced an atypical type of this fractures, the fracture line exist between subcapital portion at anterior aspect and base of the neck at posterior aspect, running through the neck with a shearing fracture line shown in the coronal plane. We investigate the characteristic and result of this fractures in our cases.

This study was designed to compare atypical hip fractures with a matched cohort of standard hip fractures to evaluate the difference in outcomes. Patients from the American College of Surgeons National Surgical Quality Improvement Program's (NSQIP) targeted hip fracture data file (containing a more comprehensive set of variables collected on 9,390 specially targeted hip fracture patients, including the differentiation of atypical from standard hip fractures) were merged with the standard 2016 NSQIP data file. Atypical hip fracture patients aged 18 years and older in 2016 were identified via the targeted hip fracture data file and matched to two standard hip fracture controls by age, sex, and fracture location. Patient demographics, length of hospital stay, 30-day mortality, major and minor complications, and other hip-specific variables were identified from the database. Binary outcomes were compared using the McNemar's test for paired groups, and continuous outcomes were compared using a paired t-test. Ninety-five atypical hip fractures were identified, and compared to 190 age, sex, and fracture location matched standard hip fracture controls. There was no statistical difference in body mass index (BMI), race, ASA score, smoking status, timing of fixation, or functional status between the two groups (P>0.05). Thirty-day mortality was significantly higher in the atypical hip fracture group (atypical 7.36%, standard 2.11% p. This is the first study, to our knowledge, that demonstrates an increase in the rate of mortality in atypical hip fractures. Comparing atypical hip fractures with a matched cohort of standard hip fractures revealed a significantly greater 30-day mortality rate with an odds ratio of 3.62 in atypical hip fractures (95% CI 1.03–12.68). Prospective, clinical studies are recommended to further investigate these findings

Aims. The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones. Methods. Three groups (seven per group) of 12-week-old mice were: 1) ovariectomized and 20 weeks thereafter treated weekly for 24 weeks with 100 μm/kg subcutaneous ibandronate (OVX+IBN); 2) ovariectomized (OVX); or 3) sham-operated (SHAM). Quantitative fracture analysis generated biomechanical properties for the femoral neck. Tibiae were microCT scanned and trabecular (proximal metaphysis) and cortical parameters along almost its whole length measured. Results. Fracture analyses revealed that OVX+IBN significantly reduced yield displacement (vs SHAM/OVX) and resilience, and increased stiffness (vs SHAM). OVX+IBN elevated tibial trabecular parameters and also increased cortical cross-sectional area and second moment of area around minor axis, and diminished ellipticity proximally. Conclusion. These data indicate that combined ovariectomy and bisphosphonate generates cortical changes linked with greater bone brittleness and modified fracture characteristics, which may provide a basis in mice for interrogating the mechanisms and genetics of atypical fracture aetiology. Cite this article: Bone Joint Open 2020;1-9:512–519

Introduction. Since the concept of severely suppressed bone turnover (SSBT) after long-term bisphosphonate (BPs) use, SSBT have been believed as the major cause of low-energy femoral fractures, which are called atypical femoral fractures. Here we present several cases of stress fractures with bowing femoral shaft deformity, which can be another cause of low-energy femoral fractures in the elderly. Materials and Methods. From 1998 to 2012, we treated thirteen cases of low-energy fractures of femoral shaft. All cases were females with an average age of 77.0 (67–88) years. Retrospectively, we assessed fracture type, X-ray of contralateral side, bowing deformity of femur, and duration of BPs use. Result. All cases were classified as simple fracture; AO/OTA type 32-A. In eleven cases, incomplete fracture of contralateral side was found by X-ray and confirmed by a bone scintigram. In twelve cases, obvious bowing deformity of the femoral shaft was noted. BPs were used only in seven cases, and the medication period was not so long. Just one case had taken Alendronate for ten years, and this case showed no bowing deformity. Discussion. Shane defined atypical femoral fracture, and indicated that the same fractures may develop even without BPs use. According to this definition, our advocating stress fractures by bowing deformity will also be included in atypical fractures. We think stress fractures by bowing deformity should be discriminated from atypical fractures by SSBT

There is strong evidence to support the use of bisphosphonates in the prevention of osteoporotic fractures. There has, however, been growing concern that prolonged use of bisphosphonates can lead to the development of atypical femoral fractures and can protract healing time. We conducted a retrospective study looking at all femoral fractures between 2011–2013. Of 109 patients, 12 were diagnosed with atypical femoral fractures. The mean age of presentation was 69 (52–92). Five patients held no history of falls and presented with hip pain. The remaining seven sustained minor falls. Seven patients were on bisphosphonates on presentation. Bisphosphonates were discontinued in five cases and continued in two. Bisphosphonates commenced in one patient who subsequently developed second fracture. All fractures were managed with intramedullary nailing. Healing time was prolonged in all cases (mean healing time 7.3 months). Three patients needed further surgeries to achieve union. Overall, we observed that patients with prolonged bisphosphonate intake were more susceptible to atypical fractures with a delayed recovery time. Increasing awareness amongst medical professionals may aid timely diagnoses and subsequent referrals to orthopaedics. Recognition of these fractures may also permit early discontinuation of bisphosphonates, which may prevent future fractures and reduced healing times

Osteoporosis is a global health issue with 200 million people suffering worldwide and it is a common condition in the elderly. Bisphosphonates including alendronate and risendronate are considered as the first line treatment for osteoporosis. However, there is increasing evidence that bisphosphonate (BP) therapy is associated with atypical fractures. Animal studies have reported a dose-dependent association between the duration of BP therapy and the accumulation of micro-damage. We tested the hypothesis that hip fracture patients treated with BP exhibited greater micro-damage density than untreated fracture and ‘healthy’ aging non-fracture controls. Trabecular bone cores from patients treated with BP were compared with patients who had not received any treatment for bone metabolic disease (ethics reference: R13004). Non-fractured cadaveric femora from individuals with no history of bone metabolic disease were used as controls. Cores were imaged in high spatial resolution (∼1.3µm) using Synchrotron X-ray tomography (Diamond Light Source Ltd.) A novel classification system was devised to characterise features of micro-damage in the Synchrotron images: micro-cracks, diffuse damage and perforations. Synchrotron micro-CT stacks were visualised and analysed using ImageJ, Avizo and VGStudio MAX. Our findings show that the BP group had the highest micro-damage density across all groups. The BP group (7.7/mm. 3. ) also exhibited greater micro-crack density than the fracture (4.3/mm. 3. ) and non-fracture (4.1/mm. 3. ) controls. Furthermore, the BP group (1.9/mm. 3. ) demonstrated increased diffuse damage when compared to the fracture (0.3/mm. 3. ) and non-fracture (0.8/mm. 3. ) controls. In contrast, the BP group (1.9mm. 3. ) had fewer perforations than fracture (3.0/mm. 3. ) and non-fracture controls (3.9/mm. 3. ). BP inhibits bone remodelling, thereby reducing the number of perforated trabeculae, but over-suppression leads to micro-damage accumulation. Accumulated damage could weaken the trabecular bone in the femoral head and neck, increasing the risk of a fracture during a trip or fall

Summary Statement. Atypical femoral fractures consist of a thin fracture line extending through the lateral cortex. The adjacent bone is undergoing resorption and mechanical abrasion and is often replaced with woven bone. The mechanical environment seems to inhibit healing. Background. The pathophysiology behind bisphosphonate-associated atypical femoral fractures remains unclear. Histological findings at the fracture site itself might provide important clues. So far only one case describing the histological appearance of the fracture has been published. Methods. Between 2008 and 2013, bone biopsies comprising the fracture site were collected from 8 patients with 4 displaced and 4 undisplaced atypical femoral fractures. Seven female patients reported continuous bisphosphonate use for an average of 9.5 years. One patient was a man, not using bisphosphonates. The bone biopsies were evaluated histologically, with Fourier transformed infrared imaging (FTIR) and micro-computed tomography. Results. The 4 undisplaced fractures engaged the whole cortical thickness and comprised a 150 to 200 µm wide, meandering fracture gap filled with amorphous necrotic material. Von Kossa staining showed occasional mineralised elements with bony structure within the amorphic material. Active resorption and remodeling was common in the close vicinity of the fracture, but seldom reached into the fracture gap. In some areas, the bone adjacent to the gap appeared to undergo fragmentation and disintegration, possibly due to abrasion. Woven bone was common adjacent to the fracture gap, and appeared to have been formed in defects caused by abrasion or where resorption cavities had reached into the fracture gap. Periosteal and endosteal callus was found in all cases. Far away from the fracture, large areas of osteonal bone with only empty osteocyte lacunae were found in some samples. In one patient, the remodeling process bridged the fracture gap at some points. The fracture was otherwise similar to the other undisplaced fractures. This patient had suffered from thigh pain since her bisphosphonate treatment was discontinued 18 months earlier, when the atypical fracture was diagnosed. Discussion. Atypical femoral fractures show signs of increased remodeling in the vicinity of the fracture gap. The narrow width of the gap and its necrotic contents suggest that micromotion leads to strains between the fracture fragments that precludes survival of ingrowing cells. Moreover, there seemed to be continuous mechanical fragmentation of the bone at the crack, and replacement of fragmented areas with woven bone. Thus, it appears that the fracture line is not static, but moves in the bone over time, like the changes in the course of a meandering river

Aims: The optimal treatment of Type II odontoid fractures remains controversial. Our retrospective multicentric study of 114 odontoid process fractures documents experience with management of these fractures and discuss a new classification subtype II T and its surgical treatment. Methods: Fractures were defined using plain radiographs and CT reconstructions as per the Anderson- D’Alonzo classification. We have surgically treated 114 consecutive patients suffering from C2 odontoid fracture. 104 fractures were classified as Type II and 10 as Type III. Two cases of atypical, horizontal, mid-shaft odontoid process fractures were reported. In 55% an anterior two-screw fixation technique was chosen, remaining 45% underwent single-screw fixation. Results: One year follow-up data were available in 86.8% of cases and no major complications were found. Fusion rate calculated 6 months following surgery was 93%. We encountered cases, where the fracture line passes transversally through the middle of the shaft of odontoid process, below the level of transverse atlantal ligament, and we suggest to classify these cases as Type II T fractures. Also we analysed series of 75 surgically treated C1-2 instabilities and out of 11 pseudoarthrosis of the odontoid process 7 unrecognised Type II T fractures were found. Conclusions: Reported atypical fractures, newly classified as Type II T, are highly unstable (especially in rotations). In the authors’ opinion, two- screw technique should be the treatment of choice when internal fixation indicated

Aims

The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone.

Aims

This observational study examines the effect of the COVID-19 pandemic upon the paediatric trauma burden of a district general hospital. We aim to compare the nature and volume of the paediatric trauma during the first 2020 UK lockdown period with the same period in 2019.

Purpose: We report the prevalence of vitamin D deficiency and other causes of secondary osteoporosis in a group of typical and atypical fragility fracture patients. Method: A chart audit of 399 patients (117 males, mean age 64.6, SD 12.8; 282 females, mean age 63.5, SD 14.6) referred from an inner city orthopaedic unit to the Metabolic Bone Disease Clinic (MBDC) over a three-year period was conducted. Fracture locations and etiology: 90 hip (76 fragility), 161 wrist (135 fragility), 8 vertebral (6 fragility), 77 shoulder (62 fragility), 62 other sites (45 fragility), 1 both hip and shoulder (fragility). Results: Thirty percent of patients (42 males, 78 females) had a total of 149 secondary causes of OP recorded. Secondary causes included medication use (oral steroids, anti-convulsants); rheumatic, gastrointestinal and endocrine conditions (RA, IBD, Graves disease, Type I DM, hyperparathyroidism); hypogonadal states (premature ovarian failure, hypogonadism); genetic conditions (hypophosphatasia); hematological conditions (thalassemia); miscellaneous causes (smoking, renal impairment). A total of 308 patients completed blood work, including 269 patients who had a 25-OH vitamin D measurement: 7 patients were deficient at ≤ 25 nmol/l, 137 were insufficient at 26 to 74 nmol/l, and 125 were sufficient at ≥ 75nmol/l. There were no differences between males and females (p = 0.457), or among fracture locations (p 0.246). Over 75% of blood/urine analyses were within the normal range for: 1,25 vitamin D, ALP, ALT, AST, bilirubin, creatinine, T3, T4, homocysteine, magnesium, phosphorus, platelets, serum calcium, protein, albumin, globulin, TSH, tissue transglutaminase, Vit B12, WBC, 24 hour urine calcium and phosphorus. Between 50 and 74% of the blood/urine analyses were within the normal range for: CRP (n = 30; 30% elevated), ESR (n = 173; 43% elevated), testosterone (n = 53; 25% of men below normal), bioavailable testosterone (n = 52; 40% of men below normal), N- telopeptide (n = 5; 30% of women elevated), RBC folate (n = 12; 33% elevated), 24 hour urine creatinine (n = 51; 27% below normal). Conclusion: Half of the fracture patients were vitamin D insufficient. A standardized blood test protocol for all fragility fracture patients is in use

Objectives

Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration.

The December 2012 Shoulder & Elbow Roundup³⁶⁰ looks at: whether allograft is biomechanically superior in large Hill-Sachs defects; glenoid bone loss in shoulder dislocators; repairing irreparable cuff tears; acromioclavicular joint injuries; whether more radiographs equals more surgery; whether reverse TSR is cheaper than hemiarthroplasty; autologous chondrocyte implantation in the shoulder; and fracture of the clavicle.