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The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 3 | Pages 349 - 353
1 Mar 2007
Goh S Yang KY Koh JSB Wong MK Chua SY Chua DTC Howe TS

We carried out a retrospective review over ten months of patients who had presented with a low-energy subtrochanteric fracture. We identified 13 women of whom nine were on long-term alendronate therapy and four were not. The patients treated with alendronate were younger, with a mean age of 66.9 years (55 to 82) vs 80.3 years (64 to 92) and were more socially active. The fractures sustained by the patients in the alendronate group were mainly at the femoral metaphyseal-diaphyseal junction and many had occurred after minimal trauma. Five of these patients had prodromal pain in the affected hip in the months preceding the fall, and three demonstrated a stress reaction in the cortex in the contralateral femur. Our study suggests that prolonged suppression of bone remodelling with alendronate may be associated with a new form of insufficiency fracture of the femur. We believe that this finding is important and indicates the need for caution in the long-term use of alendronate in the treatment of osteoporosis


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 510 - 516
1 Apr 2011
Sugata Y Sotome S Yuasa M Hirano M Shinomiya K Okawa A

Several bisphosphonates are now available for the treatment of osteoporosis. Porous hydroxyapatite/collagen (HA/Col) composite is an osteoconductive bone substitute which is resorbed by osteoclasts. The effects of the bisphosphonate alendronate on the formation of bone in porous HA/Col and its resorption by osteoclasts were evaluated using a rabbit model. Porous HA/Col cylinders measuring 6 mm in diameter and 8 mm in length, with a pore size of 100 μm to 500 μm and 95% porosity, were inserted into a defect produced in the lateral femoral condyles of 72 rabbits. The rabbits were divided into four groups based on the protocol of alendronate administration: the control group did not receive any alendronate, the pre group had alendronate treatment for three weeks prior to the implantation of the HA/Col, the post group had alendronate treatment following implantation until euthanasia, and the pre+post group had continuous alendronate treatment from three weeks prior to surgery until euthanasia. All rabbits were injected intravenously with either saline or alendronate (7.5 μg/kg) once a week. Each group had 18 rabbits, six in each group being killed at three, six and 12 weeks post-operatively. Alendronate administration suppressed the resorption of the implants. Additionally, the mineral densities of newly formed bone in the alendronate-treated groups were lower than those in the control group at 12 weeks post-operatively. Interestingly, the number of osteoclasts attached to the implant correlated with the extent of bone formation at three weeks. In conclusion, the systemic administration of alendronate in our rabbit model at a dose-for-weight equivalent to the clinical dose used in the treatment of osteoporosis in Japan affected the mineral density and remodelling of bone tissue in implanted porous HA/Col composites


The Bone & Joint Journal
Vol. 95-B, Issue 11 | Pages 1544 - 1550
1 Nov 2013
Uchiyama S Itsubo T Nakamura K Fujinaga Y Sato N Imaeda T Kadoya M Kato H

This multicentre prospective clinical trial aimed to determine whether early administration of alendronate (ALN) delays fracture healing after surgical treatment of fractures of the distal radius. The study population comprised 80 patients (four men and 76 women) with a mean age of 70 years (52 to 86) with acute fragility fractures of the distal radius requiring open reduction and internal fixation with a volar locking plate and screws. Two groups of 40 patients each were randomly allocated either to receive once weekly oral ALN administration (35 mg) within a few days after surgery and continued for six months, or oral ALN administration delayed until four months after surgery. Postero-anterior and lateral radiographs of the affected wrist were taken monthly for six months after surgery. No differences between groups was observed with regard to gender (p = 1.0), age (p = 0.916), fracture classification (p = 0.274) or bone mineral density measured at the spine (p = 0.714). The radiographs were assessed by three independent assessors. There were no significant differences in the mean time to complete cortical bridging observed between the ALN group (3.5 months (. se. 0.16)) and the no-ALN group (3.1 months (. se. 0.15)) (p = 0.068). All the fractures healed in the both groups by the last follow-up. Improvement of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, grip strength, wrist range of movement, and tenderness over the fracture site did not differ between the groups over the six-month period. Based on our results, early administration of ALN after surgery for distal radius fracture did not appear to delay fracture healing times either radiologically or clinically. Cite this article: Bone Joint J 2013;95-B:1544–50


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 5 | Pages 679 - 686
1 May 2010
Das De S Setiobudi T Shen L Das De S

There have been recent reports linking alendronate and a specific pattern of subtrochanteric insufficiency fracture. We performed a retrospective review of all subtrochanteric fractures admitted to our institution between 2001 and 2007. There were 20 patients who met the inclusion criteria, 12 of whom were on long-term alendronate. Alendronate-associated fractures tend to be bilateral (Fisher’s exact test, p = 0.018), have unique radiological features (p < 0.0005), be associated radiologically with a pre-existing ellipsoid thickening of the lateral femoral cortex and are likely to be preceded by prodromal pain. Biomechanical investigations did not suggest overt metabolic bone disease. Only one patient on alendronate had osteoporosis prior to the start of therapy. We used these findings to develop a management protocol to optimise fracture healing. We also advocate careful surveillance in individuals at-risk, and present our experience with screening and prophylactic fixation in selected patients


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1285 - 1291
1 Oct 2019
MacKenzie SA Ng RT Snowden G Powell-Bowns MFR Duckworth AD Scott CEH

Aims. Currently, periprosthetic fractures are excluded from the American Society for Bone and Mineral Research (ASBMR) definition of atypical femoral fracture (AFFs). This study aims to report on a series of periprosthetic femoral fractures (PFFs) that otherwise meet the criteria for AFFs. Secondary aims were to identify predictors of periprosthetic atypical femoral fractures (PAFFs) and quantify the complications of treatment. Patients and Methods. This was a retrospective case control study of consecutive patients with periprosthetic femoral fractures between 2007 and 2017. Two observers identified 16 PAFF cases (mean age 73.9 years (44 to 88), 14 female patients) and 17 typical periprosthetic fractures in patients on bisphosphonate therapy as controls (mean age 80.7 years (60 to 86, 13 female patients). Univariate and multivariate analysis was performed to identify predictors of PAFF. Management and complications were recorded. Results. Interobserver agreement for the PAFF classification was excellent (kappa = 0.944; p < 0.001). On univariate analysis compared with controls, patients with PAFFs had higher mean body mass indices (28.6 kg/m. 2. (. sd. 8.9) vs 21.5 kg/m. 2. (. sd. 3.3); p = 0.009), longer durations of bisphosphonate therapy (median 5.5 years (IQR 3.2 to 10.6) vs 2.4 years (IQR 1.0 to 6.4); p = 0.04), and were less likely to be on alendronate (50% vs 94%; p = 0.02) with an indication of secondary osteoporosis (19% vs 0%; p = 0.049). Duration of bisphosphonate therapy was an independent predictor of PAFF on multivariate analysis (R. 2. = 0.733; p = 0.05). Following primary fracture management, complication rates were higher in PAFFs (9/16, 56%) than controls (5/17, 29%; p = 0.178) with a relative risk of any complication following PAFF of 1.71 (95% confidence interval (CI) 0.77 to 3.8) and of reoperation 2.56 (95% CI 1.3 to 5.2). Conclusion. AFFs do occur in association with prostheses. Longer duration of bisphosphonate therapy is an independent predictor of PAFF. Complication rates are higher following PAFFs compared with typical PFFs, particularly of reoperation and infection. Cite this article: Bone Joint J 2019;101-B:1285–1291


The Bone & Joint Journal
Vol. 103-B, Issue 11 | Pages 1648 - 1655
1 Nov 2021
Jeong S Hwang K Oh C Kim J Sohn OJ Kim JW Cho Y Park KC

Aims

The incidence of atypical femoral fractures (AFFs) continues to increase. However, there are currently few long-term studies on the complications of AFFs and factors affecting them. Therefore, we attempted to investigate the outcomes, complications, and risk factors for complication through mid-term follow-up of more than three years.

Methods

From January 2003 to January 2016, 305 patients who underwent surgery for AFFs at six hospitals were enrolled. After exclusion, a total of 147 patients were included with a mean age of 71.6 years (48 to 89) and 146 of whom were female. We retrospectively evaluated medical records, and reviewed radiographs to investigate the fracture site, femur bowing angle, presence of delayed union or nonunion, contralateral AFFs, and peri-implant fracture. A statistical analysis was performed to identify the significance of associated factors.


The Bone & Joint Journal
Vol. 101-B, Issue 11 | Pages 1402 - 1407
1 Nov 2019
Cehic M Lerner RG Achten J Griffin XL Prieto-Alhambra D Costa ML

Aims

Bone health assessment and the prescription of medication for secondary fracture prevention have become an integral part of the acute management of patients with hip fracture. However, there is little evidence regarding compliance with prescription guidelines and subsequent adherence to medication in this patient group.

Patients and Methods

The World Hip Trauma Evaluation (WHiTE) is a multicentre, prospective cohort of hip fracture patients in NHS hospitals in England and Wales. Patients aged 60 years and older who received operative treatment for a hip fracture were eligible for inclusion in WHiTE. The prescription of bone protection medications was recorded from participants’ discharge summaries, and participant-reported use of bone protection medications was recorded at 120 days following surgery.


Bone & Joint Research
Vol. 6, Issue 3 | Pages 144 - 153
1 Mar 2017
Kharwadkar N Mayne B Lawrence JE Khanduja V

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.


Aims

The aim of this study was to evaluate the outcomes of a salvage procedure using a 95° angled blade plate for failed osteosynthesis of atypical subtrochanteric femoral fractures associated with the long-term use of bisphosphonates. These were compared with those for failed osteosynthesis of subtrochanteric fractures not associated with bisphosphonate treatment.

Patients and Methods

Between October 2008 and July 2016, 14 patients with failed osteosynthesis of an atypical subtrochanteric femoral fracture were treated with a blade plate (atypical group). Their mean age was 67.8 years (60 to 74); all were female. During the same period, 21 patients with failed osteosynthesis of a typical subtrochanteric fracture underwent restabilization using a blade plate (typical group). Outcome variables included the time of union, postoperative complications, Harris Hip Score, and Sanders functional rating scale.


The Bone & Joint Journal
Vol. 95-B, Issue 9 | Pages 1263 - 1268
1 Sep 2013
Savaridas T Wallace RJ Salter DM Simpson AHRW

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing.

A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague–Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology.

The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm-2 (sd 7.63) vs 24.65 Nmm-2 (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007).

Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

Cite this article: Bone Joint J 2013;95-B:1263–8.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 3 | Pages 385 - 390
1 Mar 2012
Thompson RN Phillips JRA McCauley SHJ Elliott JRM Moran CG

We performed a retrospective review of all patients admitted to two large University Hospitals in the United Kingdom over a 24-month period from January 2008 to January 2010 to identify the incidence of atypical subtrochanteric and femoral shaft fractures and their relationship to bisphosphonate treatment. Of the 3515 patients with a fracture of the proximal femur, 156 fractures were in the subtrochanteric region. There were 251 femoral shaft fractures. The atypical fracture pattern was seen in 27 patients (7%) with 29 femoral shaft or subtrochanteric fractures. A total of 22 patients with 24 atypical fractures were receiving bisphosphonate treatment at the time of fracture. Prodromal pain was present in nine patients (11 fractures); 11 (50%) of the patients on bisphosphonates suffered 12 spontaneous fractures, and healing of these fractures was delayed in a number of patients. This large dual-centre review has established the incidence of atypical femoral fractures at 7% of the study population, 81% of whom had been on bisphosphonate treatment for a mean of 4.6 years (0.04 to 12.1).

This study does not advocate any change in the use of bisphosphonates to prevent fragility fractures but attempts to raise awareness of this possible problem so symptomatic patients will be appropriately investigated. However, more work is required to identify the true extent of this new and possibly increasing problem.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 7 | Pages 906 - 914
1 Jul 2008
Ayoub MA

Between 2000 and 2006 we performed salvage tibiotalar arthrodesis in 17 diabetic patients (17 ankles) with grossly unstable ankles caused by bimalleolar fractures complicated by Charcot neuro-arthropathy. There were ten women and seven men with a mean age of 61.6 years (57 to 69). A crossed-screw technique was used. Two screws were used in eight patients and three screws in nine. Additional graft from the malleoli was used in all patients. The mean follow-up was 26 months (12 to 48) and the mean time to union was 5.8 months (4 to 8). A stable ankle was achieved in 14 patients (82.4%), nine of whom had bony fusion and five had a stiff fibrous union. The results were significantly better in underweight patients, in those in whom surgery had been performed three to six months after the onset of acute Charcot arthropathy, in those who had received anti-resorptive medication during the acute stage, in those without extensive peripheral neuropathy, and in those with adequate peripheral oxygen saturation (> 95%). The arthrodesis failed because of avascular necrosis of the talus in only three patients (17.6%), who developed grossly unstable, ulcerated hindfeet, and required below-knee amputation.


The Bone & Joint Journal
Vol. 96-B, Issue 5 | Pages 658 - 664
1 May 2014
Teo BJX Koh JSB Goh SK Png MA Chua DTC Howe TS

Management of bisphosphonate-associated subtrochanteric fractures remains opinion- or consensus-based. There are limited data regarding the outcomes of this fracture.

We retrospectively reviewed 33 consecutive female patients with a mean age of 67.5 years (47 to 91) who were treated surgically between May 2004 and October 2009. The mean follow-up was 21.7 months (0 to 53). Medical records and radiographs were reviewed to determine the post-operative ambulatory status, time to clinical and radiological union and post-fixation complications such as implant failure and need for second surgery.

The predominant fixation method was with an extramedullary device in 23 patients. 25 (75%) patients were placed on wheelchair mobilisation or no weight-bearing initially. The mean time to full weight-bearing was 7.1 months (2.2 to 29.7). The mean time for fracture site pain to cease was 6.2 months (1.2 to 17.1). The mean time to radiological union was 10.0 months (2.2 to 27.5). Implant failure was seen in seven patients (23%, 95 confidence interval (CI) 11.8 to 40.9). Revision surgery was required in ten patients (33%, 95 CI 19.2 to 51.2).

A large proportion of the patients required revision surgery and suffered implant failure. This fracture is associated with slow healing and prolonged post-operative immobility.

Cite this article: Bone Joint J 2014;96-B:658–64.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 72 - 77
1 Jan 2008
Sharma S Fraser M Lovell F Reece A McLellan AR

Osteoporosis and fragility fractures in men constitute a considerable burden in healthcare. We have reviewed 2035 men aged over 50 years with 2142 fractures to clarify the epidemiology of these injuries and their underlying risk factors. The prevalence of osteoporosis ranged between 17.5% in fractures of the ankle and 57.8% in those of the hip. The main risk factors associated with osteoporosis were smoking (47.4%), alcohol excess (36.2%), body mass index < 21 (12.8%) and a family history of osteoporosis (8.4%). Immobility, smoking, self-reported alcohol excess, a low body mass index, age ≥72 and loss in height were significantly more common among men with fractures of the hip than in those with fractures elsewhere.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 7 | Pages 956 - 960
1 Jul 2012
Kim T Ha Y Kang B Lee Y Koo K

This prospective multicentre study was undertaken to determine whether the timing of the post-operative administration of bisphosphonate affects fracture healing and the rate of complication following an intertrochanteric fracture. Between August 2008 and December 2009, 90 patients with an intertrochanteric fracture who underwent internal fixation were randomised to three groups according to the timing of the commencement of risedronate treatment after surgery: Group A (from one week after surgery), Group B (from one month after surgery), and Group C (from three months after surgery). The radiological time to fracture healing was assessed as the primary endpoint, and the incidence of complications, including excessive displacement or any complication requiring revision surgery, as the secondary endpoint. The mean time to fracture healing post-operatively in groups A, B and C was 10.7 weeks (sd 4.4), 12.9 weeks (sd 6.2) and 12.3 weeks (sd 7.1), respectively (p = 0.420). At 24 weeks after surgery, all fractures had united, except six that had a loss of fixation. Functional outcomes at one year after surgery according to the Koval classification (p = 0.948) and the incidence of complications (p = 0.386) were similar in the three groups.

This study demonstrates that the timing of the post-operative administration of bisphosphonates does not appear to affect the rate of healing of an intertrochanteric fracture or the incidence of complications.