Emerging evidence has linked the long-term use of alendronate (fosamax) with subtrochanteric insufficiency fractures. However, findings to date have been anecdotal. The aims of this study were to determine the incidence of subtrochanteric insufficiency fractures and identify whether they were more prevalent following the introduction of alendronate in Australia. All patients that presented between January 2007 and February 2009 with low- energy subtrochanteric fracture were identified. Similar data were collected between January 1995 and February 1997 as this was immediately prior to introduction of alendronate in Australia. The radiographs were examined for failure due to pre- existing insufficiency fracture. Characteristic findings were a transverse fracture line on the tension side of the femur with lateral cortical thickening immediately adjacent to the fracture. Relevant details from the history were recorded. We also separately identified all patients that presented between 2007 and 2009 with a proximal femoral fracture and determined the proportion taking alendronate. One hundred and seventeen patients with low-energy subtrochanteric fracture were included. Seventy-nine patients presented between 2007 and 2009 and 38 presented between 1995 and 1997. Forty-one of the 79 (52%) patients were identified as having radiograph findings suggestive of underlying insufficiency fracture, whilst none were identified prior to the introduction of alendronate. Of the 41 patients with subtrochanteric insufficiency fracture, 40 (98%) had been taking alendronate and one had been taking risedronate. Twenty-nine of the 41 (71%) complained of prodromal pain in the affected femur. Eighteen of the 41 (44%) demonstrated subtrochanteric insufficiency changes on the contralateral side and 9 of 41 (22%) sustained spontaneous non-traumatic fracture during activities of daily living. Of the 38 patients without insufficiency changes, 12 (32%) had been taking alendronate. Alendronate use was therefore strongly suggestive of insufficiency fracture (sensitivity = 98%, specificity = 84%, PPV = 77%, NPV = 99%, LR+ = 6). The mean duration of alendronate use in those with insufficiency fracture was 7.1 years (95% CI, 6.6-7.6 years). The mean duration in those without was 3.2 years (95% CI, 2.6-3.8 years, P<0.0001). Three hundred and ninety eight patients presented with a low-energy proximal femur fracture between 2007 and 2009. Of these, only 52 (13%, P<0.0001) were taking alendronate. This is the largest study in the literature on subtrochanteric insufficiency fractures and alendronate therapy. Confirming recent reports, alendronate use was strongly suggestive of subtrochanteric insufficiency fracture. Our findings provide the most compelling evidence to date of the potential long-term sequelae of alendronate but more research is needed before definitive conclusions can be made

Introduction. Fixation patterns of cementless stem were known as proximal or distal part. Distal fixation was seen in fully porous coated stem and stress shielding of the proximal femur was indicative. These phenomena did not lower the clinical results, but technical difficulties were more and more in revision surgery because of infection or dislocation. There was lot of reports that alendronate was effective for treatment of osteoporosis by induction of apoptosis in osteoclasts. We can expect alendronate to modify the bone quality around the stem after cementless THA. Objectives. We studied prospectively that quantitative computed tomography (QCT) measured bone mineral density around the stem between alendronate group and control. We tried to clarify that stress shielding after cementless THA can be prevented by use of alendronate or not. Materials and methods. From September 2011, 60 patients underwent total hip arthroplasty with cementless stems. Thirty patients took alendronate (35mg/week) after surgery (Group A) and remaining 30 patients were control (Group C). Between two groups, gender, age at surgery, diagnosis and body mass index were similar. Two types of stem were used as Zweimuller type or taperlock type. Just after THA, femoral shaft divided by Gruen zone measured bone mineral density (BMD) with QCT and forearm also measured BMD by DEXA. Following examination was performed at 6 months, 12 months and 24 months after surgery. Results. Gender of two groups was as follow: four males and twenty-six females in Group A and two males and twenty-eight females in Group C. The age at surgery was 67.6+7.9y in group A and 62.5+13.3y in group C. Zweimuller type was used for 18 patients and taperlock type was used for 12 patients in group A. Zweimuller type was used for 14 patients and taperlock type was used for 16 patients in group C. BMD of forearm were not different between two groups and it meant that bone quality and osteoporosis of groups was similar. On the other hands, femoral BMD of group A was higher than that of group C. Especially BMD of group C was relatively low in zone 1 and 7. Conclusion. Weekly use of alendronate (35mg) might be useful for preventing stress shielding after cementless THA

Titanium (Ti) is well known in orthopedic implant materials such as total hip replacement arthroplasty. Osseointegration of orthopedic implants is defined as the formation of a direct interface between the implant and the bone without intervening soft tissue. Unmodified Ti is not sufficient to complete adhesion between Ti surface and host bone with subsequent implant loosening over time and ultimately implant failure. An effective approach to enhance the biological activity of orthopedic implants and improve post-implantation healing is to modify the implant surface. The aim of this study was to investigate the effect of functionalized titanium (Ti) with alendronate (Aln) and bone morphogenic protein-2 (BMP-2) for enhancement of osteoblast activity in vitro. Aln and/or BMP-2 were sequentially immobilized to the heparinized-Ti (Hep-Ti) surface. The compositions of pristine Ti and Hep-Ti with or without Aln and/or BMP-2 were characterized by scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). Osteoblast activities on all Ti substrates were investigated by cell proliferation assays, alkaline phosphate (ALP) activity, calcium deposition, gene expressions of osteocalcin and osteopontin. The modified Ti surface with heparin, Aln, BMP-2 and Aln/BMP-2 showed similar morphologies compared to that of pristine Ti on scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). Aln or BMP-2 from Aln/Hep-Ti, BMP-2/Hep-Ti or Aln/BMP-2/ Hep-Ti substrates exhibited sustained release profiles up to 4 weeks. No significant cytotoxic effects were observed for incubation periods for up to 48 h. the ALP activity of MG-63 cells cultured on Hep-Ti was not significantly different compared to those cultured on pristine Ti for 7, 14, and 21 days. Alkaline phosphatase(ALP) activities of osteoblasts cultured on Ti groups immobilized with Aln, BMP-2, or Aln/BMP-2 were significantly increased when compared to pristine Ti(p < 0.05). Calcium deposition was markedly increased in Aln/BMP-2/Hep-Ti compared to Aln/Hep-Ti or BMP-2/Hep-Ti, respectively (p < 0.05). mRNA expressions of osteocalcin(OCN) and osteopontin(OPN) of osteoblasts grown on Aln/Hep-Ti, BMP-2/Hep-Ti, and Aln/BMP-2/Hep-Ti were significantly higher than of those grown on pristine Ti (p < 0.05). Based on the results of the in vitro studies, we showed that co-delivery of alendronate and BMP-2 had an additive effect on osteoblast activity and mineralization when compared with pristine Ti as well as alendronate or BMP-2 alone. Functionalized Ti systems with alendronate and BMP-2 can give a good solution to solve the most common problems associated with orthopedic and dental implants. Furthermore, in vivo studies required to determine the optimal doses of alendronate and BMP-2 for clinical application

Introduction. Achieving durable implant–host bone fixation is the major challenge in uncemented revision hip arthroplasty when significant bone stock deficiencies are encountered. The purpose of this study was to develop an experimental model which would simulate the clinical revision hip scenario and to determine the effects of alendronate coating on porous tantalum on gap filling and bone ingrowth in the experimental model. Methods. Thirty-six porous tantalum plugs were implanted into the distal femur, bilaterally of 18 rabbits for four weeks. There were 3 groups of plugs inserted; control groups of porous tantalum plugs (Ta) with no coating, a 2nd control group of porous tantalum plugs with micro-porous calcium phosphate coating, (Ta-CaP) and porous tantalum plugs coated with alendronate (Ta-CaP-ALN). Subcutaneous fluorochrome labelling was used to track new bone formation. Bone formation was analysed by backscattered electron microscopy and fluorescence microscopy on undecalcified histological sections. Results. The relative increase in mean volume of gap filling, bone ingrowth and total bone formation was 124%, 232% and 170% respectively in Ta-CaP-ALN compared with the uncoated porous tantalum (Ta) controls, which was statistically significant. The contact length of new bone formation on porous tantalum implants in Ta-CaP-ALN was increased by 700% (8-fold) on average compared with the uncoated porous tantalum (Ta) controls. Discussion. Alendronate coated porous tantalum significantly modulated implant bioactivity compared with controls. This study has demonstrated the significant enhancement of bone-implant gap filling and bone ingrowth, which can be achieved by coating porous tantalum with alendronate. It is proposed that, when faced with the clinical problem of revision joint replacement in the face of bone loss, the addition of alendronate as a surface coating would enhance biological fixation of the implant and promote the healing of bone defects

Introduction. Bisphosphonates are among the most commonly prescribed drugs in Osteoporotic Patients. Their mode of action is anti-resorptive. Since remodeling is a key step in fracture healing, there has been concern regarding the effect of bisphosphonates on fracture healing. Objectives. To assess the effect of alendronate on fracture healing in the rabbit ulna osteotomy model. Materials and methods. 16 New Zealand white rabbits were divided into 2 equal groups. Bilateral ulnar osteotomies were performed in the first week. Group 1 was the control group and group 2 was gavaged with alendronate solution (human equivalent dose). 2 rabbits were euthanised at 3 and 6 weeks and the remaining 4 rabbits were euthanised at 8 weeks. Fracture healing was assessed radiologically, with mechanical testing using the Instron 4302 materials testing machine and histologically, in that order. Results. The fractures healed satisfactorily in all the control group animals. However, in the alendronate treated group, there was an abundance of woven bone and little lamellar bone in the callus. However there was no significant difference in mechanical testing. In addition we did not find any evidence of Osteonecrosis in the Bisphosphonate treated group. Conclusion. Bone remodelling in the alendronate treated group is slower but a larger amount of bone callus is formed around the fracture, thus giving the fracture callus a higher ultimate load to failure at an earlier stage

Diphosphonates remain among the most common drug treatments for osteoporosis. Recent evidence has implicated diphosphonate therapy, specifically, alendronate, with low-energy fractures of the subtrochanteric region of the femur. The general conclusion is that prolonged suppression of bone remodelling with alendronate may be associated with a new form of insufficiency fracture of the femur. Three case reports of patients with alendronate related insufficiency are discussed here with their treatment modalities and lessons learnt. One of the three patients had bilateral subtrochanteric stress fracture. A comprehensive review of the literature is presented with the best evidence for investigating, treating and preventing these fractures. Our experience in Launceston has increased awareness amongst the local medical community regarding the long term use of Diphosphnates and the fractures they may cause. Changes to our practice have included: Increased suspicion of patients with hip pain on diphosphonate therapy, imaging the contralateral femur to rule out stress fractures, reassuring GP's and Patients that benefits of Diphosphonate therapy far outweigh the potential risks. There are many unresolved questions about the prolonged use of diphosphonates, but there is sufficient evidence to show subtrochanteric stress fractures do occur. We, as Orthopaedic Surgeons, must be able to recognize this new entity and educate our medical colleagues appropriately

Orthopaedic surgeons frequently assess fragility fractures (FF), however osteoporosis (OP) is often managed by primary care physicians (PCP). Up to 48% of FF patients have had a previous fracture (Kanis et al., 2004). Discontinuity between fracture care and OP management is a missed opportunity to reduce repeat fractures. This studied aimed to evaluate current OP management in FF patients presenting to cast clinic. A single centre, prospective observational study where seven traumatologists screened for FF in cast clinic. FF was defined as a hip, distal radius (DR), proximal humerus (PH), or ankle fracture due to a ground level fall. Patients completed a self-administered questionnaire for demographics, fracture type and treatment, medical and fracture history, and previous OP care. The primary outcome was number of FF patients who received OP investigation and/or treatment. Secondary outcomes included Fracture Risk Assessment Tool (FRAX), repeat fracture rate, and anti-resorptive related fractures. Descriptive statistics were used for analysis. Between November 17, 2014 and October 13, 2015, a total of 1,677 patients attended cast clinic for an initial assessment. FF were identified in 120 patients (7.2%). The FF cohort had a mean age of 65.3 (± 14.3) years, mean BMI of 26.1 (± 5.3), and was comprised of 83.3% females. Fracture distribution was 69 (57.5%) DR, 23 (19%) ankle, 20 (16.5%) PH, and seven (5.8%) hip fractures, with 24 of the FF (19.8%) treated operatively. Thirteen (10.8%) were current smokers and 40 (33.3%) formerly smoked. A history of steroid use was present in 13 patients (10.8%). Ninety (n = 117; 76.9%) of patients ambulated independently. Twenty-two patients (18.3%) reported prior diagnosis of OP, most often by a PCP (n = 19; 73.7%) over 5 years previously. Calcium (n = 59; 49.2%) and Vitamin D (n = 70; 58.3%) were common and 26 patients (21.5%) had a prior anti-resorptive therapy, with Alendronate (n = 9) being most common. One patient had an anti-resorptive-related fracture. Raloxifene was used in ten patients. Forty-seven patients (39.2%) had a prior fracture at a mean age of 61.3 (± 11.9) years, with DR and PH fractures being most common. Eleven patients had two or more prior fractures. A family history of OP was found in 34 patients (28.1%). Mean FRAX score was 20.8% (± 10.8%) 10-year major fracture risk and 5.9% (± 6.6%) 10-year hip fracture risk (n = 30 bone densiometry within one-year). Of the 26 patients with a Moderate (10–20%) or High (> 20%) 10-year major fracture risk, only eight (30.8%) reported a diagnosis of OP and only three (11.5%) had seen an OP specialist. Cast clinics provide an opportunity for OP screening, initiation of treatment, and patient education. This cohort demonstrated a high rate of repeat fractures and poor patient reporting of prior OP diagnosis. This study likely underestimated FF and calls for resource allocation for quantifying true burden of disease and outpatient fracture liaison service

The senior author has treated a series of patients with subtrochanteric and diaphyseal femoral stress fractures associated with long-term alendronate or other bisphosphonate usage. Several patients completely fractured their femurs prior to referral. Most patients had consulted other physicians and were referred for presumed neoplasms. All patients had been diagnosed with osteoporosis and had been treated with bisphosphonates. Their plane radiographs revealed abnormalities that are pathognomonic of bisphosphonate-associated stress fractures. However, due to the subtle nature of these new unfamiliar abnormalities, most were unrecognized as such by clinicians (including experienced ISTA member hip surgeons) and radiologists. This series is presented to illustrate this pattern of impending fracture. The authors have reviewed and will present a series (n=17) of femoral stress fractures in bisphosphonate-treated patients to illustrate the clinical and radiographic pattern of these stress fractures, and review their treatment. The most common lesion is a subtrochanteric lateral cortical thickening that in actuality is a horizontal plane “dreaded black line” of a stress fracture with surrounding proximal and distal cortical thickening of the endosteal and periosteal bone. The stress fracture line is obscured unless a near-perfect radiographic projection is obtained. The lesion is best seen with CT scans. MRI scans reveal the stress fracture lines with surrounding edema (Fig 1), which may be misinterpreted as a tumor. Without treatment, a low-impact completed fracture will likely occur. Many bisphosphonate-associated impending subtrochanteric femoral stress fractures are misdiagnosed as trochanteric bursitis, leading to subsequent displaced subtrochanteric fractures [Fig. 2 - Note subtle impending fracture lesion on right, completed fracture on left]. The clinical and subtle radiographic findings must be recognized by orthopaedic surgeons, particularly hip surgeons, to prevent these complete fractures. These fractures are preventable with internal fixation. Long-term administration of bisphosphonates can have adverse effects, and alternatives to long-term continuous dosing must be investigated to determine optimal administration regimens

Objectives

There remains conflicting evidence regarding cortical bone strength following bisphosphonate therapy. As part of a study to assess the effects of bisphosphonate treatment on the healing of rat tibial fractures, the mechanical properties and radiological density of the uninjured contralateral tibia was assessed.

Osteoporosis is common and the health and financial cost of fragility fractures is considerable. The burden of cardiovascular disease has been reduced dramatically by identifying and targeting those most at risk. A similar approach is potentially possible in the context of fragility fractures. The World Health Organization created and endorsed the use of FRAX, a fracture risk assessment tool, which uses selected risk factors to calculate a quantitative, patient-specific, ten-year risk of sustaining a fragility fracture. Treatment can thus be based on this as well as on measured bone mineral density. It may also be used to determine at-risk individuals, who should undergo bone densitometry. FRAX has been incorporated into the national osteoporosis guidelines of countries in the Americas, Europe, the Far East and Australasia. The United Kingdom National Institute for Health and Clinical Excellence also advocates its use in their guidance on the assessment of the risk of fragility fracture, and it may become an important tool to combat the health challenges posed by fragility fractures.