History Of Bisphosphonate Use Research Articles

Atypical femur fracture in a male without history of bisphosphonate use: a case report

BackgroundAtypical femur fractures are a rare occurrence, especially in bisphosphonate-naïve men, and merit reporting owing to their unusual presentation and clinical implications. This case report highlights a unique instance of atypical femur fractures in a 73-year-old male with no prior bisphosphonate exposure.Case presentationThe patient, a 73-year-old Indian male with no history of bisphosphonate use, presented with left thigh pain and swelling following a minor fall. Radiographic assessment unveiled a closed left mid diaphyseal femoral shaft fracture. Subsequent imaging revealed an impending fracture in the contralateral femur. A comprehensive diagnostic evaluation, encompassing radiographic analysis, laboratory tests, and clinical assessment confirmed the diagnosis. Surgical management via intramedullary nailing was pursued for both fractures. Notably, the patient’s medical history was characterized by radiographic manifestations, the infrequent occurrence of atypical femur fractures in men, and associated risk factors. Treatment encompassed anabolic bone therapy employing teriparatide, alongside discontinuation of antiresorptive agents.ConclusionsThis case underscores the significance of considering atypical femur fractures in older individuals with limited trauma history. It accentuates the role of anabolic agents in the therapeutic regimen and contributes to the evolving understanding of atypical femur fractures. The report underscores the need for vigilant monitoring and tailored management strategies in similar cases, thereby enhancing clinical practice and patient care.

Evaluation of core decompression outcome in systemic lupus erythematosus with hip osteonecrosis: a retrospective cohort study

BackgroundOsteonecrosis is a major cause of morbidity for patients with systemic lupus erythematosus (SLE). Although core decompression is an approved and trusted technique to prevent further joint deterioration, this surgical method seems to be less beneficial for SLE patients. We aimed to evaluate the outcomes of core decompression in SLE patients with primary stages of femoral head osteonecrosis.MethodsIn this study, 23 patients (39 affected hip joints) with osteonecrosis of the femoral head with stage II of the disease, based on the Ficat-Arlet classification system, underwent core decompression. Also, patients demographic characteristics, clinical data, medication history, comorbidities, immunological findings, hip plain radiographs, history of total hip arthroplasty after core decompression, and patients satisfaction with joint function according to the Oxford hip score questionnaire were obtained.ResultsIn the study, 53.8% of affected joints showed signs of radiographic deterioration in follow-up imaging. Sixty-one and a half percent (61.5%) of patients had unsatisfactory joint performance. A third (33.3%) of affected hip joints underwent total hip arthroplasty up to 5 years from core decompression. SLE patients with a history of receiving bisphosphonate were 83.2% less dissatisfied with their joint function than patients without a history of bisphosphonate use (P < 0.02). Of the 23 studied cases, the mean cumulative dose of prednisolone before and after core decompression surgery was 46.41 mg and 14.74 mg respectively. Besides, one case (2.6%) that had a high anti-phospholipid antibodies level during follow-up did not have any radiographic deterioration, and 9 cases (23.1%) had some degrees of radiographic deterioration.ConclusionsThe patients group that used bis-phosphonate, had a higher level of satisfaction with joint function after core decompression. Patients with high-level anti-phospholipid antibodies are related to a poor prognosis after core decompression.

Bisphosphonates and atypical femoral fractures: Is the location of the fracture associated with the time of consolidation?

IntroductionBisphosphonates are commonly prescribed to mitigate the effects of osteoporosis, a condition associated with an increased risk of fracture.However, despite their success, there has been growing concern regarding the long-term use of bisphosphonates because of the increased risk of atypical subtrochanteric fractures of the femur (AFFs).The objective of this study was to describe a cohort of patients with AFFs and evaluate the risk of evolving to non-union, the time of consolidation associated with the location of the fracture, the time of use of the drug, and the implant involved in its treatment. MethodsThis retrospective study recruited patients between June 2008 and May 2018. We identified patients with AFFs according to the task force criteria and a history of bisphosphonate use.We included all patients older than 65 years, with long-term use of bisphosphonates, AFF criteria according to the task force, and a follow-up of 12 months or longer.We studied the following variables: the time of use of bisphosphonates, localization of the fracture according to Hyodo et al., implant use, and fracture healing time, considering the presence of bone callus observed in two radiologic projections, which were measured in weeks. ResultsBetween June 2008 and May 2018, 72 patients met the task force criteria for AFFs.A total of 67 patients were included in this study. From this total, 37 were in the proximal region of the femur and 31 corresponded to the diaphyseal region.Univariate and multivariate analyses showed statistical significance in the time of bone healing compared with the different locations of the fracture along the femur. ConclusionAccording to our study, the localization of AFFs in patients with a history of bisphosphonate use influences the duration of bone healing.

The Effect of Preoperative Bisphosphonate Use on Total Hip Arthroplasty Outcomes

BackgroundPatients undergoing total hip arthroplasty (THA) commonly have osteoporosis for which bisphosphonates (BPs) are Food and Drug Administration (FDA)-approved for treatment. Bisphosphonate use post-THA is associated with decreased periprosthetic bone loss or revisions, and increased longevity of implants. However, evidence is lacking for preoperative bisphosphonate use in THA recipients. This study investigated the association between bisphosphonate use pre-THA and outcomes. MethodsA retrospective review of a national administrative claims database was conducted. Among THA recipients who had a prior diagnosis of hip osteoarthritis and osteoporosis/osteopenia, the treatment group (BP-exposed) consisted of patients who had a history of bisphosphonate use at least 1 year before THA; controls (BP-naive) comprised patients who did not have preoperative bisphosphonate use. The BP-exposed were matched to BP-naive in a 1:4 ratio by age, sex, and comorbidities. Logistic regressions were used to calculate the odds ratio for intraoperative and 1-year postoperative complications. ResultsThe BP-exposed group had significantly higher rates of intraoperative and 1-year postoperative periprosthetic fractures (odds ratio (OR): 1.39, 95% confidence interval (CI): 1.23, 1.57) and revisions (OR: 1.14, 95% CI: 1.04, 1.25) compared with the BP-naive controls. BP-exposed also experienced higher rates of aseptic loosening, dislocation, periprosthetic osteolysis, and stress fracture of the femur or hip/pelvis compared to the BP-naive controls, but these values were not statistically significant. ConclusionThe use of bisphosphonates in THA patients preoperatively is associated with higher rates of intraoperative and 1-year postoperative complications. These findings may impact the management of patients undergoing THA who have a prior diagnosis of osteoporosis/osteopenia and use of bisphosphonates. Level of evidenceRetrospective Cohort Study (Level 3).

Therapeutic strategy for atypical ulnar fracture in long use of bisphosphonate: A systematic review

BackgroundAtypical fractures are caused by the combined effects of severe suppression of bone metabolism (SSBT) due to long-term bisphosphonate therapy and chronic repetitive bone microdamage. Atypical ulnar fractures (AUFs) due to SSBT are rare, and there is no standard treatment strategy for such fractures. The relevant literature was reviewed, and the treatment strategy for AUF is discussed. MethodsA systematic review was conducted. All studies on ulnar fractures in individuals with a history of bisphosphonate use were included, and the data were extracted and analyzed from the perspective of the therapeutic strategy. ResultsForty limbs of 35 patients were included. As for the treatment of AUF, 31 limbs were treated surgically, and conservative treatment with casting was performed for 9 limbs. The bone fusion rate was 22/40 (55.0%), and non-union was seen in all patients treated conservatively. There was a significant difference in the bone fusion rate between patients with surgical treatment and those with conservative treatment. The bone fusion rate of patients with parathyroid hormone (PTH) and surgery was 82.3% (14/17 limbs); the bone fusion rate with PTH and bone graft was 69.2% (9/13 limbs). However, there were no significant differences in the fusion rate in the groups with or without PTH, with or without bone grafting, or the combination of the two treatments. There was also no significant difference in the bone fusion rate in the groups with or without low-intensity pulsed ultrasound (LIPUS) treatment. ConclusionsBased on the literature review, surgery is necessary to achieve bone union, but surgery alone is not adequate to achieve bony union. Bone grafting and the administration of PTH and LIPUS may promote early bone fusion, but the present study did not show significant advantages of these additional treatments for bone union.

Functional and Radiological Outcome in Atypical Subtrochanteric Femur Fracture After Surgical Fixation: A Retrospective Observational Study.

Background: Treatment for osteoporosis can have catastrophic side effects, including the uncommon fracture known as an atypical femur fracture (AFF), which is related to the long-term usage of antiresorptive agents. Bisphosphonate therapy may lead to significant and chronic suppression of bone turnover, impairing the bone's remodelling property and finally leading to incomplete or complete atypical femur fracture. AFF was defined by the American Society for Bone and Mineral Research (ASBMR) Task Force in 2010 and is far less prevalent than proximal femur (hip) fracture, with an incidence of 2 to 78 per 100,000 patients per year following two to eight years of bisphosphonate therapy, respectively. Due to the rarity of the fracture, it is still not clear what the functional and radiological outcome will be after surgery.Aim: To identify the functional and radiological outcomes of surgical fixation of atypical femur fractures.Methods: The study was conducted in a tertiary healthcare centre after scientific and ethical clearance from the competent authority. Between January 2018 and December 2021, individuals who were diagnosed with an atypical subtrochanteric femoral fracture associated with the use of bisphosphonates and treated surgically were retrospectively evaluated. The study's inclusion and exclusion criteria were used to include 20 patients. The features of an atypical subtrochanteric fracture were congruent with the radiographic findings. Most of the patients were treated with internal fixation with intramedullary osteosynthesis in standard with or without plate osteosynthesis. They were then followed up for a year to look at the functional and radiological outcomes.Results: All of the 20 patients who were included had an atypical subtrochanteric fracture, with 15 of them being female and 5 of them being male. The patients' mean age at surgery was 65.12 (range 49 to 82) years, and their average history of bisphosphonate use was 3 (range 2.5 to 5) years. All patients were treated surgically. We found that five months was the mean period for bone union (p = 0.990). Within six months, bone union was achieved in 11 patients (55 %) (p = 0.884). Five patients (about 25%) had implant failure and non-union, requiring two to three revision surgeries. At three, six, and nine months, the mean visual analogue score (VAS) was 4.14, 3.12, and 1.85, respectively. The modified Hip Harris Score had a mean of 72.66 and 15 patients (about 75% of them) could walk normally again after a fracture. The mean of the modified HHS was 72.66, and the VAS at three, six, and nine months was 4.14, 3.12, and 1.85, respectively.Conclusion: AFFs are rare fractures that must be treated effectively, and most of them require surgery. Successful treatment of AFF is possible by the use of intramedullary fixation, which enhances axial stability, serves as an internal splint, and lessens the likelihood of implant failure. A good functional and radiological prognosis can come from a stable fixation and a fracture that has been reduced anatomically.

Atypical Fracture of Radial Diaphysis After Sauvé-Kapandji Procedure: A Retrospective Radiographic Evaluation of Fracture Progression.

The Sauvé-Kapandji procedure (SK), which combines distal radioulnar joint arthrodesis with creation of an ulnar pseudarthrosis, achieves good outcomes with few complications for patients with distal radioulnar joint instability or arthritis. The authors describe a case of atypical fracture of the radial diaphysis that occurred in a 79-year-old woman with rheumatoid arthritis who had undergone SK 18 years earlier. The patient had taken alendronate for osteoporosis for 13 years but had discontinued treatment 2 years before onset of symptoms. Retrospective review of serial radiographs revealed focal cortical thickening at the fracture site beginning 18 months before the onset of prodromal pain and becoming more evident over time. The patient underwent surgical repair of the fracture, which had occurred at the attachment of the pronator teres. Histopathological examination of bone excised from the fracture site and from the iliac graft used for fracture repair revealed markedly fewer trabecular osteoblasts than normal and no osteoclasts, indicating severe suppression of bone turnover. It is important to evaluate the radial diaphysis on radiographs taken after SK for early signs of atypical fracture, especially in patients with rheumatoid arthritis and a history of bisphosphonate use. Given the patient's history of bisphosphonate use and the similar radiographic appearance to atypical femoral fractures, the authors applied the term atypical radial fracture to this case. [Orthopedics. 2023;46(5):e317-e320.].

The Effects of CNI and Mtori-Based Regimens on Bone Mineral Density After Renal Transplantation.

Background: Since glucocorticoids are used in low maintenance doses today, the relationship between calcineurin inhibitors (CNI) and osteoporosis has become clinically significant in osteoporosis after solid organ transplantation. However, there is evidence that the mammalian target of rapamycin inhibitors (mTORi) may be beneficial via osteoclast inhibition. Objective: The bone mineral density (BMD) changes are investigated in renal transplant patients under CNI or mTORi-based maintenance regimens during the first five-year post-transplant course. Methods: This study consists of thirty-three renal allograft recipients with less than one year of dialysis history. The exclusion criteria were: being older than 50 years old, history of bisphosphonate use, parathyroidectomy, CNI-mTORi switch after the post-transplant third month, diuretic use, and history of malignancy. First and fifth-year BMD scores and simultaneous laboratory parameters were evaluated. Results: CNI (n=21) and mTORi group (n=12) had similar demographics, dialysis vintages, first and fifth-year serum parathormone, calcium, phosphate, magnesium, alkaline phosphatase, and 25-OH-vitamin D levels. The femur neck scores of the CNI group decreased from -0.82 (±0.96) to -1.52 (±0.92) (p=0.020). We observed a significant decrease in the CNI group compared to the mTORi group [-0.70 (±0.68) and 0.30 (±0.36), respectively; p<0.01] when the BMD score changes were evaluated among years. The mean femur neck score of the mTORi group increased insignificantly from -1.13 (±0.65) to -0.82 (±0.56) at the fifth-year DXA scan (p=0.230). Similar trends were also observed in L1-4 scores. Conclusion: Our study suggests that CNI-based treatment is associated with decreased femur neck BMD scores, and mTORi-based treatment tends to be beneficial in the post-transplant five-year follow-up.

Relationship between torus mandibularis and mandibular cortical bone width using computed tomography

AbstractPurposeThis study aimed to investigate the relationship between mandibular cortical width (MCW) and torus mandibularis (TM) using computed tomography (CT).Materials and methodsThis retrospective case–control study included 34 patients with TM and 34 age‐ and sex‐matched patients without TM who underwent CT at our hospital between April 2017 and December 2020. TM was identified by a radiologist from CT scans as an exostosis continuous with the lingual cortical bone of the mandible. Patients with a history of bisphosphonate use, malignancy, or mandibular fractures were excluded from this study. The MCW was measured by estimating the thickness of the cortical bone at the lower edge of the bilateral mandible using a CT coronal slice and calculating the average value. Nonparametric Mann–Whitney U tests were used to assess the differences in continuous variables based on the MCW and mandibular cortical index status.ResultsThe MCW was significantly associated with the TM.ConclusionThe results of this study suggested that the MCW may be associated with the development of TM. MCW on CT images may help predict the future development of TM.

Differences in femur geometry and bone markers in atypical femur fractures and the general population

This study aimed to identify differences in femur geometry between patients with subtrochanteric/shaft atypical femur fractures (AFFs) and the general population, and to evaluate the biomechanical factors related to femoral bowing in AFFs. We retrospectively reviewed 46 patients. Data on age, and history and duration of bisphosphonate use were evaluated. Femur computed tomography images were reconstructed into a 3D model, which was analyzed with a geometry analysis program to obtain the femur length, femur width and length, and femoral bowing. Patients were divided into two groups according to fracture location: the subtrochanteric and shaft AFF groups. We compared all parameters between groups, and also between each group and a general population of 300 women ≥ 60 years. Thirty-five patients had a history of bisphosphonate use (average duration, 6.1 years; range, 0.8–20 years). There was no statistical difference in bone turnover markers between the two groups. The shaft AFF group had a lower radius of curvature (ROC) (P = 0.001), lower bone mineral density (BMD, T score) (P = 0.020), and lower calcium (P = 0.016). However, other parameters and rate of bisphosphonate use were not significantly different. There were no significant differences in the parameters of the subtrochanter AFF group and the general population, but the shaft AFF group demonstrated a wider femur width (P < 0.001), longer anteroposterior length (P = 0.001), and lower ROC (P < 0.001) than the general population. Femoral bowing and width increased in shaft AFFs, but similar to subtrochanter AFFs compared to the general population. Our results highlight the biomechanical factors of femur geometry in AFFs.

Health-related quality of life outcomes after surgical treatment of atypical femur fractures: a multicenter retrospective cohort study.

ABSTRACTThe objective of this study was to examine the health‐related quality of life (HRQOL) outcomes for surgically‐treated atypical femur fractures (AFFs) compared to typical femoral diaphyseal fractures. Two large trauma center databases were retrospectively queried for surgically‐treated femur fractures. Fractures were grouped into AFFs and compared to a control cohort. Controls for the AFF group included women with diaphyseal fractures without additional AFF characteristics. Patients were contacted for administration of the Short Form‐36v2 Health Survey. Surveys were completed an average of 30.3 months (range, 6–138 months) and 25.5 months (range, 5–77 months) postoperatively for the AFF and non‐AFF groups, respectively. All patients were female, with 46 patients in the AFF and 26 patients in the non‐AFF group. The average age of the AFF group was 70.1 years compared with an average age of 67.4 years in the non‐AFF group (p = 0.287). Over 90% (91.3%) of patients in the AFF group had a history of bisphosphonate use while 26.9% of patients in the non‐AFF group had used bisphosphonates (p < 0.0001). Patients with AFF reported their postoperative physical and mental health to be no different than similarly aged patients with femoral diaphyseal fractures, as measured by the Short Form 36, version 2 (SF‐36v2) Health Survey. These data suggest that mid‐term patient‐reported quality of life outcomes are similar among women who sustain an AFF compared to a cohort of more typical femoral diaphyseal fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Combination Therapy of PTH and Antiresorptive Drugs on Osteoporosis: A Review of Treatment Alternatives.

Antiresorptive drugs have been widely used for osteoporosis. Intermittent parathyroid hormone (PTH), an anabolic agent, increases osteoblast production rate and inhibits apoptosis of osteoblasts, thus increasing skeletal mass besides improving bone microarchitecture and strength. Combination therapy for osteoporosis produced great interests and controversies. Therefore, we performed a systematic literature search from PubMed, EMBASE, Scopus, Web of Science, CINDHL, and the Cochrane Database of Systematic Reviews using the search terms PTH or teriparatide combined with bisphosphonate, alendronate, ibandronate, risedronate, raloxifene, denosumab, and zoledronic acid with the limit osteoporosis. At last, 36 related articles were included for further analysis. Findings from previous studies revealed that combination therapy in different conditions of naive or previous bisphosphonate treatment might have different outcomes. The use of combination therapy, however, may be an alternative option among osteoporotic patients with a history of bisphosphonate use. Combined teriparatide with denosumab appear to show the most substantial and clinically relevant skeletal benefits to osteoporotic patients. Additional research is necessary to define optimal methods of developing sequential and/or cyclical combinations of PTH and antiresorptive agents.

High bisphosphonate treatment rates and the prevalence of atypical femoral fractures in patients with systematic lupus erythematosus: a single-center retrospective study performed in Japan

Treatment of systemic lupus erythematosus (SLE) often continues with moderate-to-low doses of glucocorticoids for the long term. Bisphosphonates aid in the prevention and management of glucocorticoid-induced osteoporosis (GIOP). However, long-term use of bisphosphonates increases the relative risk of atypical femoral fracture (AFF) and the incidence is typically 16 or 113 per 100,000 person-years in patients treated with bisphosphonates for 5 or 10years, respectively. Here, we explored bisphosphonate prescription rate and prevalence of AFF in patients with SLE. In total, 270 patients with SLE were enrolled. The Japanese Society for Bone and Mineral Research Guideline 2014 for GIOP management and treatment was used. We also explored AFF history through medical records. Most (n = 251) patients were recommended to treat by the GIOP guideline (scores ≥ 3); bisphosphonates, denosumab, teriparatide, or active vitamin D was prescribed for 85.7%. Bisphosphonates were currently used by 66.1% of the patients, and 65% had used them for ≥ 5years. Of all patients, 76.7% had a history of bisphosphonate use, 5 of 270 (1.9%) had histories of AFF. Four of five patients with AFF had taken bisphosphonates for ≥ 3.5years, in addition to moderate doses (≥ 10mg/day) of glucocorticoids. For the SLE patients with a history of bisphosphonate use, the incidence of AFF was calculated to be 278 per 100,000 person-years. Our single-center study found that bisphosphonates were commonly used long term by Japanese patients with SLE. As AFF is not rare, AFF should be cared in patients with SLE.

Osteomyelitis of the mandible exhibiting features of medication-related osteonecrosis in a patient with history of tocilizumab treatment

Osteomyelitis of the jaw of microbial origin manifests in bone with specific radiographic features that are key to the diagnosis. On occasion, other types of bone diseases like medication-related osteonecrosis of the jaw (MRONJ) need to be differentiated from either acute or chronic osteomyelitis. This is especially important if the medical history and physical examination are inconsistent. Apart from a thorough clinical examination, radiographic features hold an important role in the disease process which could ultimately lead to appropriate intervention. Clinician needs to be well-versed with the differential diagnosis of the bone lesions that might mimic osteomyelitis radiographically. Different medications can be attributed to osteonecrosis of the jaw (ONJ). Some monoclonal antibody medications have been attributed in the development of ONJ. Tocilizumab is a monoclonal antibody therapy used for rheumatoid arthritis. Tocilizumab-related osteonecrosis without history of bisphosphonate use has not been reported in the literature. We present a case of osteomyelitis that demonstrated similar radiographic and histological features of MRONJ in a patient treated with tocilizumab for rheumatoid arthritis without history of bisphosphonate use. Further studies are needed to assess relation between tocilizumab and ONJ.

Factors affecting fracture location in atypical femoral fractures: A cross-sectional study with 147 patients

IntroductionMany studies have tried to determine the characteristics of atypical femoral fractures (AFFs) through age-, sex-, and ethnicity-matched comparison with non-AFFs. However, we hypothesized that diaphyseal AFFs would have characteristics different from those of subtrochanteric AFFs. The aim of this study was to evaluate the clinical features of diaphyseal/subtrochanteric AFFs and determine the factors related to fracture location. Patients and methodsOne hundred forty-seven patients with AFF were enrolled, 114 patients (78%) had a history of bisphosphonate use. Forty-nine patients (33%) had bilateral lesion, and 35% of patients had thigh pain. Patients were divided into two groups according to fracture location: 52 patients (35.4%) with subtrochanteric AFF and 95 patients (64.6%) with diaphyseal AFF. The patient demographics and fracture characteristics of the two groups were compared. Multivariate logistic regression analysis was used to adjust for variables related to fracture location. ResultsThe patients in the diaphyseal AFFs group were older and had lower BMI, lower BMD, and larger lateral and anterior bowing. Multivariate analysis revealed that age greater than 65 years and low BMD were related with diaphyseal location. With greater lateral bowing angle, the AFF location was moved from the subtrochanteric area to the diaphyseal area. ConclusionThis study demonstrated that patients with diaphyseal AFFs had different characteristics compared with those with subtrochanteric AFFs.

The effect of chronic dental inflammation on development of Stage 0 medication-related osteonecrosis of the jaw

ObjectiveThe pathogenesis of medication-related osteonecrosis of jaw (MRONJ) is poorly understood. The aim of this prospective study was to determine the effect of chronic dental inflammation on the development of Stage 0 MRONJ based on histopathological findings. MethodsThe study involved patients with a history of bisphosphonate use and an indication for tooth extraction. Before surgery, C-terminal telopeptide test (CTX) values were collected from all patients. All tooth extractions were performed according to a determined protocol. To detect whether any medication-related osteonecrotic changes were present in the non-exposed bone, biopsy samples were taken from the alveolar bone. ResultsA total of 50 patients were included in the study (39 women and 11 men). The patients were mean age of 57.4 ± 12.1 years. In total, 74 teeth were extracted (29 maxillary and 45 mandibular). Histologic examination of three patients (6%) revealed Stage 0 MRONJ. Postoperatively, the complete mucosal healing success rate was 96%. MRONJ risk was not significantly correlated with low CTX value (p = 0.285). ConclusionsChronic inflammation may contribute to Stage 0 MRONJ; however, its role may not be sufficient alone for its development. Application of a predetermined protocol for dentoalveolar processes will help to prevent MRONJ development.

A natural history of bisphosphonate use in Paget’s disease of bone

A natural history of bisphosphonate use in Paget’s disease of bone

“Bisphosphonates: Possible Modes of Action and Implications for Dental Implant Treatment. A Review of the Literature”

Bisphosphonates (BP) have been commonly used over the past 40 years to treat osteoporosis, Pagets’ disease, hypercalcemia of malignancy, osteolytic lesions of multiple myeloma and bone metastases associated with breast, prostate, lung and other soft tissue tumours. The main aims of this review are to: 1. Highlight the fundamental pharmacophysiological modes of action of both nitrogen and non-nitrogen bisphosphonates on bone 2. Explore their potential effects on oral hard and soft tissues 3. Discuss the implications of bisphosphonate therapy on dental implants, in particular their contribution to implant failure 4. Discuss the current recommendations and guidelines for dental implant therapy in patients receiving bisphosphonate therapy based on the available evidence. Two distinct types of bisphosphonates have been classified and differentiated according to their mode of action, chemical structure, potency, delivery, bioavailability, dosage and half-life. Bisphosphonates are classified as: 1) Nonnitrogen containing bisphosphonates (BP) and 2) Nitrogen containing bisphosphonates (N-BP). 27 studies met the study inclusion and exclusion criteria, with 8 retrospective studies and 2 case series studies evaluating the success rate of dental implants in patients with a history of bisphosphonate use, while the remaining 17 articles consisted of case series and case reports. While there are shortcomings associated with many of the reported studies, there does appear to be a certain risk associated with the both implant placement and the maintanence of osseointegrated implants in patients receiving oral bisphosphonates. A Southern Austrailian study estimated the risk of implant failure in patients receiving oral bisphosphonates to be 0.88%. Late implant failures appear to occur in patients treated with oral bisphosphonate exposure for a period >3 years especially in patients who have existing integrated implants,while early failures appear to occur in patients treated with bisphosphonates before or at the time of implant placement. Although the results from these retrospective studies and case series are conflicting to some extent, they have heightened awareness of the possible complication of BRONJ and bisphosphonate related implant failure from long term bisphosphonate use, be it oral or iv-bisphosphonates.

Atypical Subtrochanteric Femoral Fracture Below an Arthritic Hip: A Case Report.

We present a case of a sixty-nine-year-old woman with an atypical subtrochanteric femoral fracture below an arthritic hip; the patient had a history of long-term bisphosphonate treatment. We performed a one-stage total hip arthroplasty with a plate and cables because the healing of atypical femoral fractures in patients with a history of bisphosphonate use can be prolonged. The combined use of a plate and total hip arthroplasty is a potential intervention for atypical proximal femoral fractures associated with hip arthritis.

Ulnar fractures with bisphosphonate therapy: a systematic review of published case reports.

A systematic review of eight ulnar fractures in seven patients with bisphosphonate therapy was performed to describe the characteristics and predisposing factors. The proximal ulna is likely to be fractured, especially in the dominant limb of elderly female patients using walking aids after 7 to 15 years of bisphosphonate use. Long-term bisphosphonate use has been suggested to result in decreased bone remodelling and increased risk of atypical fractures. While the relationship between bisphosphonate use and atypical femoral fractures has been extensively studied, there is relative rarity and unawareness of these fractures in the forearm. We conducted a systematic review of existing case reports to better describe the characteristics and predisposing factors for fractures occurring in patients with bisphosphonate therapy. The systematic review was conducted according to PRISMA guidelines. All studies with ulnar fractures in individuals with history of bisphosphonate use were included, with data extracted and analysed in totality. Seven patients with eight fractures are included. Predisposing factors include elderly females requiring walking aids. There is a propensity for the proximal ulna to be fractured, especially in the dominant limb used for ambulation or transfer. All patients were on bisphosphonate for 7 to 15 years. All fractures were atraumatic, non-comminuted, transverse in configuration, had localised periosteal or endosteal thickening at the fracture site and generalised cortical thickening of the diaphysis. Ulnar fractures in patients with bisphosphonate therapy demonstrate features similar to those described for atypical femoral fractures, suggesting that these fractures could also possibly be due to bisphosphonate use. However, the ulna appears to be able to tolerate longer periods of alendronate use prior to fracture development. The mechanism and characteristics of these fractures additionally suggest the presence of repetitive stress that accumulates over time due to suppressed bone remodelling in patients on bisphosphonates, eventually resulting in these fractures.