Use Of Bisphosphonates In Patients Research Articles

The Healing and therapeutic effects of perioperative bisphosphonate use in patients with fragility fractures: meta-analysis of 19 clinical trials.

Previous evidence suggests that bisphosphonates (BPs) may lower the risk of recurrent fractures and enhance functional recovery in patients with fractures. However, there has been controversy regarding the optimal timing of treatment initiation for patients with fragility fractures. We conducted a meta-analysis to evaluate the available evidence on the use of BPs during the perioperative period and compared it to both non-perioperative periods and non-usage. Electronic searches were performed using PubMed, EMBASE, Web of Science and the Cochrane Library published before February 2023, without any language restrictions. The primary outcomes included fracture healing rate, healing time, and new fractures. We also examined a wide range of secondary outcomes. Random effects meta-analysis was used. A total of 19 clinical trials involving 2543 patients were included in this meta-analysis. When comparing patients with non-perioperative BPs use in 4-6 weeks and approximately 10-12 weeks post-surgically, the overall risk ratios (RRs) of perioperative BPs use for healing rate were 1.06 (95% CI: 0.81, 1.38, p=0.69) and 1.02 (95% CI: 0.94, 1.11, p=0.65), respectively, suggesting no difference in healing rate between perioperative and non-perioperative BP initiation. For healing time, the overall mean difference between perioperative and non-perioperative periods was -0.19 week (95% CI: -1.03, 0.64, p=0.65) at approximately 10-12 weeks, indicating no significant impact of perioperative BP initiation on healing time. In terms of new fractures, the overall RR with BP use was 0.35 (95% CI: 0.17-0.73, p=0.005), when compared to patients without BPs use. This suggests a protective impact of BP use against new fractures compared to patients without BP use. Perioperative BP use was associated with a markedly higher likelihood of having adverse experiences, including fever (RR: 23.78, 95% CI: 8.29, 68.21, p< 0.001), arthralgia (RR: 10.20, 95% CI: 2.41, 43.16, p=0.002), and myalgia (RR: 9.42, 95% CI: 2.54, 34.87, p< 0.001), compared with non-BPs use. Treatment with BP during the perioperative period does not affect the healing process and has positive effects on therapy for patients with fragility fractures. These compelling findings underscore the potential efficacy of BP use during the perioperative period as a viable treatment option for patients with fragility fractures.

Real-life short-term effectiveness of anti-osteoporotic treatments: a longitudinal cohort study

Introduction:Randomized clinical trials have shown that anti-osteoporotic treatments can increase bone mineral density (BMD) and reduce the incidence of fragility fractures. However, data on the real-life effectiveness of anti-osteoporotic medications are still scarce.Methods:We conducted a cohort study on women at high risk of fracture. We retrieved clinical and densitometric data from the DeFRA database, which derives from the DeFRA tool, a web-based fracture risk assessment tool. Multivariable Cox regression survival models were employed to analyze the effectiveness of different anti-osteoporotic drugs on fracture. In sensitivity analyses, we conducted 1:1 propensity score matching analyses.Results:Data on 50,862 women were available. Among these, 3574 individuals had at least two consecutive visits. The crude fracture rate was 91.9/1000 person-year for non-treated patients. The crude fracture rate in bisphosphonate users was 72.1/1000 person-year, in denosumab users was 58.2/1000 person-year, and in teriparatide users was 19.3/1000 person-year. Overall, we found that bisphosphonate use was associated with a 30% lower risk of fracture compared to no treatment [adjusted hazard ratio (aHR): 0.70, 95% confidence interval (CI): 0.50–0.98]. Treatment with denosumab and teriparatide were associated with 60% and 90% lower risk of fracture, respectively (aHR: 0.43, 95% CI: 0.24–0.75 and aHR: 0.09, 95% CI: 0.01–0.70). Bisphosphonate use was associated with a lower risk of fracture only after 1 year of treatment.Conclusion:In conclusion, we found that all anti-osteoporotic medications considered in the study effectively reduced the risk of fracture in the real-life. The effect of bisphosphonate on fracture risk was apparent only after the first year of treatment. Our findings do not support the use of bisphosphonates in patients at imminent risk of fracture.

Adjuvant bisphosphonate use in patients with early stage breast cancer: a physician survey.

PurposeDespite the increasing use of adjuvant bone-modifying agents (BMAs) such as zoledronate and clodronate in the treatment of patients with early stage breast cancer (EBC), little is known about real world practice patterns. A physician survey was performed to address this deficit and determine interest in clinical trials of alternative strategies for BMA administration.MethodsCanadian oncologists treating patients with EBC were surveyed via an anonymized online survey. The survey collected information on: physician demographics, knowledge and interpretation of adjuvant bisphosphonate guidelines, and real world prescribing practices. Questions also determined thoughts around the design of future adjuvant BMA trials.ResultsOf 127 surveyed physicians, 53 eligible invitees responded (response rate 42%). The majority of physicians are offering high-risk postmenopausal patients adjuvant BMAs. The most common BMA regimen was adjuvant zoledronate (45/53, 85%) every 6 months for 3 years. Concerns around toxicities and repeated visits to the cancer centre were perceived as the greatest barriers to adjuvant bisphosphonate use. Respondents were interested in future trials of de-escalation of BMAs comparing a single infusion of zoledronate vs. 6-monthly zoledronate for 3 years. The most favoured primary endpoints for such a trial included disease recurrence and fragility fracture rates.ConclusionQuestions around optimal use of adjuvant bisphosphonates in patients with EBC still exist. There is interest among physicians in performing trials of de-escalation of these agents. The results of this survey will assist in designing pragmatic clinical trials to address this question.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10549-021-06147-1.

Adjuvant bisphosphonate use in patients with early stage breast cancer: Patient perspectives on treatment acceptability and potential de-escalation

BackgroundDespite the increasing use of adjuvant bisphosphonates for early stage breast cancer (EBC), little is known about the patient experience with such treatments. A patient survey was performed to identify current prescribing practices, perceptions around the role of treatment, the impact of treatment on patients’ quality of life, and future trial designs. MethodsEBC patients who had either completed or were currently receiving adjuvant bisphosphonates were sent an anonymized survey. The survey collected information on patient and disease characteristics, bisphosphonate scheduling, compliance, and tolerance. Questions also assessed patient interest in trials of de-escalated bisphosphonate therapy. ResultsA total of 255 patients were contacted, with 164 eligible respondents (eligible response rate 164/255, 64.3%). Median patient age was 52 years (range 28 to 82 years). The majority (111/163, 68.1%) were postmenopausal at the time of diagnosis, 23.3% (38/163) were premenopausal, and 7.4% (12/163) were perimenopausal. Most patients (78%) had received chemotherapy. Zoledronate was the most commonly used bisphosphonate (92%), with the majority receiving treatment every 6 months for 3 years (73%). While 66% (107/161) of respondents had experienced side effects with treatment, most had, or expected to, complete treatment (154/163, 94%). Provided there was no detriment in breast cancer outcomes, there was strong interest in future studies of de-escalating adjuvant bisphosphonate therapy. ConclusionWhile most patients tolerate their treatment, there is interest in performing trials of de-escalation of these agents.

RISK FACTORS FOR INFECTIOUS COMPLICATIONS IN ONCOLOGICAL PATIENTS WITH OSTEONECROSIS OF THE JAW FROM BISPHOSPHONATES

Objective: To evaluate the association between clinical factors with the number of infection events due to medication-related necrosis of the jaw (MRONJ) secondary to the use of injectable bisphosphonates in patients with cancer. Study design: Retrospective, observational study that included 21 cases of MRONJ and the following variables: age, underlying disease, necrosis classification, bone involved, triggering factor, frequency of bisphosphonate use, total number of doses of the drug, smoking history, underlying disease activity at the time of MRONJ diagnosis, chronic use of corticosteroids, and previous or current use of chemotherapy, immunosuppressants, and antiangiogenic drugs. The endpoint of interest was the number of exacerbations (new active infections). Results: Only 33% of the patients did not present with any infectious episode after the initial event; 28.6% had 1 episode, 19% had 3 episodes, 9.5% had 2 episodes, 1 patient presented 6 episodes, and 1 patient presented 7 episodes of exacerbation. Among the variables studied, classification of osteonecrosis (Class 2 + 3 vs Class 1, P = .05) and frequency of drug use (Monthly vs Quarterly; P = .002) showed significant association with the number of infectious events. Conclusions: The recurrence of MRONJ-associated infection was frequent in oncological patients and was associated with the monthly use of bisphosphonates and MRONJ classification.

ПРИМЕНЕНИЕ АУТОЛОГИЧНОЙ ПЛАЗМЫ ПРИ ЛЕЧЕНИИ МЕДИКАМЕНТОЗНО АССОЦИИРОВАННОГО ОСТЕОНЕКРОЗА ЧЕЛЮСТЕЙ

Subject. Drug-associated jaw osteonecrosis is a serious complication that can occur in patients receiving bisphosphonate therapy for bone metastases in malignant neoplasms. The studies are due to the widespread use of bisphosphonates in patients with proven bone metastases, with myeloma, and malignant neoplasms of various locations. Due to the toxic effects of bisphosphonates on soft tissues, the healing process is sluggish, often with a relapse. The task of finding optimal methods of stimulating local regenerative processes is urgent, since the use of general-action drugs can provoke continued growth of the primary tumor. The aim of the study was to develop a method for treating patients with a diagnosis of “drug-associated jaw osteonecrosis” using autologous plasma, which will further reduce the number of relapses and increase the effectiveness of treatment. Methodology. Patients with a diagnosis of “medically associated jaw osteonecrosis” underwent sequestrectomy with boundaries determined by perfusion by laser Doppler flowmetry, an APRF clot was placed on the bottom of the bone wound, and autologous plasma was injected into the wound edges in the postoperative period. Results. The result of applying this technique in the early postoperative period was a partial discrepancy of the edges of the wound, but the absence of sections of the exposed bone in the wound. After 6–8 weeks, we observed complete healing of the postoperative wound. The number of relapses was reduced from 16 to 3 (by 57.56 %). Conclusions. The use of autologous plasma in the treatment of drug-associated osteonecrosis is the most optimal way to stimulate local regenerative processes in the absence of the possibility of using general-action drugs.

Effects of systematic bisphosphonate use in patients under orthodontic treatment: a systematic review

Bisphosphonates are a class of drugs prescribed for several osseous related disorders owing to their ability to regulate bone turnover, which could in turn affect orthodontic treatment outcomes. To examine the effect of bisphosphonate (BP) use on orthodontic patients through clinical and radiographic measurements. Systematic and unrestricted search of 17 databases complemented with additional hand-searches were performed up to March 2019. Articles reporting on human patients with a history of BPs administration that received orthodontic treatment were eligible for inclusion. Data regarding the medical profile of the patients, the specific type of malocclusion and the performed treatment plan, as well as the clinical and radiographic outcomes were extracted. Quality assessment was performed by the ROBINS-I tool for the cohort studies and by a slightly modified checklist from the original one proposed by Agbabiaka et al. for the case reports. 7 articles (1 retrospective cohort study and 6 case reports) were eventually included in the present review including 122 subjects (29 patients and 93 controls) reporting on the clinical and radiographic changes following orthodontic treatment of patients during or after BPs use. BPs seem to have a controversial effect on the clinical and patient-reported variables, even though the majority of the included patients presented with compromised treatment results and a rather slow rate of tooth movement. Most radiographic findings revealed mild root resorption, widened periodontal ligament spaces and sclerotic changes on the surrounding alveolar bone. However, these results should be interpreted with caution, due to the limited number of the eligible articles and their limitations. The included studies were of rather low quality due to study design and incomplete reporting. BP administration seems to be associated with compromised clinical outcomes, prolonged treatment time, and moderate changes on the roots and surrounding tissues of orthodontic patients. Non-registered. None.

The pharmacoeconomic analysis of medicines affecting the bone structure and mineralization

Osteoporosis is the most common metabolic disease of bones and is characterized by decrease of bone strength, which leads to a high risk of fractures. The seriousness of this disease is in its prolonged asymptomatic course; moreover, the disease affects a significant part of the population, especially older age groups.Aim. To conduct the pharmacoeconomic analysis of the use of bisphosphonates in patients with postmenopausal osteoporosis by the cost-effectiveness method.Materials and methods. The cost-effectiveness ratio was calculated. The average retail prices of medicines for 2017 obtained according to the data of the PharmXplorer analytical system of “Morion” company were used to calculate the cost of osteoporosis pharmacotherapy.Results. Analysis of the cost of treatment showed that Alendon-70 (Micro Labs) was the cheapest drug in the alendronic acid group; its cost per treatment course for three years was 1092 UAH. Ibandronic acid-Vista, 150 mg, (Mistral Capital Management) was the cheapest drug in the group of ibandronic acid; its cost per course of treatment for three years was 11,405.88 UAH. Medicines on the basis of strontium ranelate were presented at the Ukrainian market only by one manufacturer. The results of the pharmacoeconomic analysis showed that ibandronate was the dominant method compared to strontium ranelate since it was more effective (62.0 % versus 41.0 %) and had a lower value for the cost-effectiveness ratio (18,396.58 UAH versus 150,602.56 UAH).Conclusions. The data obtained suggest that the use of bisphosphonates, including ibandronate, is effective and cost-effective in menopausal osteoporosis.

A Randomized Trial of Zoledronic Acid to Prevent Bone Loss in the First Year after Kidney Transplantation.

Bone and mineral disorders commonly affect kidney transplant (KTx) recipients and have been associated with a high risk of fracture. Bisphosphonates may prevent or treat bone loss in such patients, but there is concern that these drugs might induce adynamic bone disease (ABD). In an open label, randomized trial to assess the safety and efficacy of zoledronate for preventing bone loss in the first year after kidney transplant, we randomized 34 patients before transplant to receive zoledronate or no treatment. We used dual-energy x-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone biopsies to evaluate changes in bone in the 32 evaluable participants between the time of KTx and 12 months post-transplant. Both groups of patients experienced decreased bone turnover after KTx, but zoledronate itself did not affect this outcome. Unlike previous studies, DXA showed no post-transplant bone loss in either group; we instead observed an increase of bone mineral density in both lumbar spine and total hip sites, with a significant positive effect of zoledronate. However, bone biopsies showed post-transplant impairment of trabecular connectivity (and no benefit from zoledronate); HR-pQCT detected trabecular bone loss at the peripheral skeleton, which zoledronate partially attenuated. Current immunosuppressive regimens do not contribute to post-transplant central skeleton trabecular bone loss, and zoledronate does not induce ABD. Because fractures in transplant recipients are most commonly peripheral fractures, clinicians should consider bisphosphonate use in patients at high fracture risk who have evidence of significantly low bone mass at these sites at the time of KTx.

Лазерная доплеровская флоуметрия - метод определения границ секвестрэктомии при бисфосфонатном остеонекрозе челюсти

osteonecrosis of the is a severe complication that can occur in patients receiving bisphosphonate therapy due to bone metastases. The relevance of research is conditioned by spread use of bisphosphonates in patients with proved bone metastases in myeloma. Despite the active study of the problem, a high percentage of relapses of the disease remains, the direct criteria of sequestrectomy determination lines during surgical treatment. The study was conducted on the basis of the Department of maxillofacial surgery MAI CCCH №23”, where patients with the diagnosis of Bisphosphonate osteonecrosis of the jaw in the period from December 2017 to December 2018 were treated.

An audit into the use of bisphosphonates for patients with non-small cell lung cancer and bone metastases at a tertiary cancer centre

An audit into the use of bisphosphonates for patients with non-small cell lung cancer and bone metastases at a tertiary cancer centre

Медикаментозноассоциированные остеонекрозы челюсти - теории патогенеза, особенности клинической, рентгенологической картины: обзор литературы и собственные наблюдения

Medication-associated osteonecrosis of the jaw - severe complication that can happen in patients received therapy with bisphosphonates and in persons that are taking narcotic surrogates (desomorphine, pervitin). The relevance of the research is conditioned by wide use of bisphosphonates in patients with proven bone metastases, during myeloma, Paget disease. The remaining number of people that used narcotic surrogates, the use of red phosphor during self-crafted production of desomorphine and pervitin by patients with drug addiction is considerable. In hese two categories atypical forms of osteomyelitis are developing. The article is based on retrospective study of clinical record and data of radiological examinations of patients that are staying on the treatment in the department of maxillofacial surgery of MAI «Central city clinical hospital №23» in 2003 - 2017.

Impact of the U.S. Food and Drug Administration's Safety-Related Announcements on the Use of Bisphosphonates After Hip Fracture.

The U.S. Food and Drug Administration (FDA) issued several announcements related to potential risk of bisphosphonates including osteonecrosis of the jaw (2005), atrial fibrillation (2007), and atypical femur fracture (2010). We aimed to evaluate the impact of three FDA drug safety announcements on the use of bisphosphonates in patients with hip fracture using claims data from a U.S. commercial health plan (2004-2013). We calculated the proportion of patients in each quarter who received a bisphosphonate or other osteoporosis medication in the 6 months following hospitalization for hip fracture. Segmented logistic regression models examined the time trends. Among 22,598 patients with hip fracture, use of bisphosphonate decreased from 15% in 2004 to 3% in the last quarter of 2013. Prior to the 2007 announcement, there was a 4% increase in the odds of bisphosphonate use every quarter (OR 1.04; 95% CI, 1.02 to 1.07). After the 2007 announcement, there was a 4% decrease in the odds of bisphosphonate use (OR 0.96; 95% CI, 0.93 to 0.99) every quarter. The announcement in 2007 was associated with a significant decline in the rate of change of bisphosphonate uses over time (p < 0.001), but no impact on other osteoporosis medication use (p = 0.2). After the 2010 announcement, the odds of bisphosphonate use continued to decrease by 4% (OR 0.96; 95% CI, 0.94 to 0.98) each quarter and the odds of other osteoporosis medication use remained stable over time (OR 0.99; 95% CI, 0.96 to 1.02). The FDA safety announcement related to atrial fibrillation in 2007 was significantly associated with a decrease in bisphosphonate use among patients with hip fracture. © 2016 American Society for Bone and Mineral Research.

Bisphosphonates for Osteoporosis in Patients with Renal Insufficiency: Pharmacists' Practices and Beliefs.

Clinicians often face challenges in deciding how to treat osteoporosis in patients with chronic kidney disease. As background to offering guidance to health care providers, it is important to understand their practices and beliefs. To describe the practices and beliefs of pharmacists regarding use of bisphosphonates for patients with osteoporosis and chronic kidney disease. A cross-sectional survey of pharmacists working in hospitals and related health care settings was conducted. A 34-item online questionnaire was developed consisting of 4 sections: demographic characteristics, practices, beliefs, and comfort level with making decisions about osteoporosis treatment. An e-mail invitation was sent to members of the Canadian Society of Hospital Pharmacists (n = 2499) in November 2012. A total of 367 pharmacists completed the survey. Most of the respondents were women (258 [70%]), had more than 10 years in practice (213 [58%]), and were providing care to 1 or more osteoporosis patients per week (212 [58%]). Over one-third (150 [41%]) stated that they would use a bisphosphonate for patients with creatinine clearance (CrCl) of 15-30 mL/min, but more than half (207 [56%]) stated that they would avoid a bisphosphonate (and recommend another medication) for patients with CrCl below 15 mL/min. Forty-eight percent (176/363) agreed that oral bisphosphonates could be used for patients with renal failure (defined as CrCl < 30 mL/min), so long as dosage adjustments are made. More than half (206/363 [57%]) believed that the adverse effects of oral bisphosphonates increase for patients with renal failure. Respondents expressed a low level of comfort in assessing and initiating osteoporosis treatment for patients with renal failure. Pharmacists had varying beliefs about managing osteoporosis in patients with chronic kidney disease. This study highlights the need for practice tools and targeted education addressing the use of bisphosphonates for these patients.

The Changing Landscape of Smoldering Multiple Myeloma: A European Perspective.

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and bridges monoclonal gammopathy of undetermined significance to multiple myeloma (MM), based on higher levels of circulating monoclonal immunoglobulin and bone marrow plasmocytosis without end-organ damage. Until a Spanish study reported fewer MM-related events and better overall survival among patients with high-risk SMM treated with lenalidomide and dexamethasone, prior studies had failed to show improved survival with earlier intervention, although a reduction in skeletal-related events (without any impact on disease progression) has been described with bisphosphonate use. Risk factors have now been defined, and a subset of ultra-high-risk patients have been reclassified by the International Myeloma Working Group as MM, and thus will require optimal MM treatment, based on biomarkers that identify patients with a >80% risk of progression. The number of these redefined patients is small (∼10%), but important to unravel, because their risk of progression to overt MM is substantial (≥80% within 2 years). Patients with a high-risk cytogenetic profile are not yet considered for early treatment, because groups are heterogeneous and risk factors other than cytogenetics are deemed to weight higher. Because patients with ultra-high-risk SMM are now considered as MM and may be treated as such, concerns exist that earlier therapy may increase the risk of selecting resistant clones and induce side effects and costs. Therefore, an even more accurate identification of patients who would benefit from interventions needs to be performed, and clinical judgment and careful discussion of pros and cons of treatment initiation need to be undertaken. For the majority of SMM patients, the standard of care remains observation until development of symptomatic MM occurs, encouraging participation in ongoing and upcoming SMM/early MM clinical trials, as well as consideration of bisphosphonate use in patients with early bone loss.

Zoledronic acid in children with osteogenesis imperfecta and Bruck syndrome: a 2-year prospective observational study.

Treatment with zoledronic acid (ZA) over 2 years, among 33 children with osteogenesis imperfecta (OI) and five Bruck syndrome cases, showed reduction in fracture rates, pain, and improvement in bone mineral density (BMD) and motor milestones of development. This is the first study reporting the use of bisphosphonates in patients with Bruck syndrome (BS). OI and BS are genetic disorders that result in bone fragility and reduced BMD. There is little literature describing the efficacy and safety of ZA in this population. In this study, we assess the response to treatment with ZA at six monthly intervals in Egyptian children with OI and BS for a period of 2 years. Thirty-three patients with OI and five patients with BS were treated with 0.1 mg/kg ZA intravenously every 6 months for 2 years during which they were followed up using different parameters. A clinical severity score (CSS) was applied to the patients before and 2 years after the start of therapy. Comparison of disease severity and response to ZA treatment between autosomal-dominant (AD) and autosomal-recessive (AR) OI patients was also done. After 6 months of treatment, OI and BS patients showed a significant increase in BMD Z-scores (P < 0.003 in the spine and P < 0.004 in the hip), together with a significant drop in fracture rate (P < 0.001), relief of pain (P < 0.001), and improvement in ambulation (P < 0.001). CSS was significantly reduced after 2 years of treatment in both OI and BS patients. AR-OI patients were more severely affected than AD-OI patients and showed more significant improvement. Zoledronic acid proved to be safe and effective in the treatment of OI and BS. The biannual infusion protocol was convenient to patients. There was a positive correlation between disease severity and benefits of the treatment. The use of the CSS proved to be of value in the assessment of the degree of severity in OI, and with some modifications, it was a valuable tool for the assessment of response to treatment.

Association of Bisphosphonate Use and Risk of Revision After THA: Outcomes From a US Total Joint Replacement Registry.

Total hip arthroplasty (THA) is often performed in patients who are older and may take bisphosphonates to treat a variety of conditions, most commonly osteoporosis. However, the clinical effects of bisphosphonate use on patients who have undergone THA are not well described. (1) Is bisphosphonate use in patients with osteoarthritis undergoing primary THA associated with a change in the risk of all-cause revision, aseptic revision, or periprosthetic fracture compared with patients not treated with bisphosphonates? (2) Does the risk of bisphosphonate use and revision and periprosthetic fracture vary by patient bone mineral density and age? A retrospective cohort study of 12,878 THA recipients for the diagnosis of osteoarthritis was conducted; 17.8% of patients were bisphosphonate users. Data sources for this study included a joint replacement registry (93% voluntary participation) and electronic health records and an osteoporosis screening database with complete capture of cases as part of the Kaiser Permanente integrated healthcare system. The endpoints for this study were revision surgery for any cause, aseptic revision, and periprosthetic fracture. The exposure of interest was bisphosphonate use; patients were considered users if prescriptions were continuously refilled for a period equal to or longer than 6 months. Bone quality (based on dual-energy x-ray absorptiometery ordered based on the National Osteoporosis Foundation's clinical guidelines taken within 5 years of the THA) and patient age (< 65 versus ≥ 65 years) were evaluated as effect modifiers. Patient, surgeon, and hospital factors were evaluated as confounders. Cox proportional hazards models were used. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined. Age- and sex-adjusted risks of all-cause (HR, 0.50; 95% CI, 0.33-0.74; p < 0.001) and aseptic revision (HR, 0.53; 95% CI, 0.34-0.81; p = 0.004) was lower in bisphosphonate users than in nonusers. The adjusted risk of periprosthetic fractures in patients on bisphosphonates was higher than in patients not on bisphosphonates (HR, 1.92; 95% CI, 1.13-3.27; p = 0.016). Lower risks of all-cause revision and aseptic revision were observed in patients with osteopenia (HR, 0.49; 95% CI, 0.29-0.84; and HR, 0.53; 95% CI, 0.29-0.99, respectively) and osteoporosis (HR, 0.22; 95% CI, 0.08-0.62; and HR, 0.33; 95% CI, 0.11-0.99, respectively). Patients considered bisphosphonate users who underwent THA had a lower risk for revision surgery. Bisphosphonate use was associated with a higher risk of periprosthetic fractures in younger patients with normal bone quantity. Evaluation of bone quality and bisphosphonate use for the diagnosis of osteoporosis is encouraged in patients with osteoarthritis who are candidates for primary THA. Further research is required to determine the optimal duration of therapy because long-term bisphosphonate use has been associated with atypical femur fractures. Level III, therapeutic study.

Management of bisphosphonate-related osteonecrosis of the jaw: a literature review.

Osteonecrosis of the jaw (ONJ) is a serious side effect of bisphosphonate use in patients with osteoporosis, Paget's disease, hypercalcemia of malignancy, metastatic bone disease and multiple myeloma, although recently this complication has also been reported in patients under non-bisphosphonate medication, such as denosumab and bevacizumab. The occurrence of ONJ is higher in oncology patients treated with high-dose iv bisphosphonates than in osteoporosis patients treated with oral bisphosphonates. Although multiple hypotheses have been proposed, the exact pathogenic mechanism of ONJ still remains unclear. As treatment protocols based on randomized controlled trials (RCTs) do not exist, we critically reviewed the existing data concerning the management of bisphosphonate-related osteonecrosis of the jaw, including the most recent data for the use of teriparatide and hyperbaric oxygen.

CORR Insights ®: Intramedullary nailing of femoral diaphyseal metastases: is it necessary to protect the femoral neck?

M ore than 1.5 million patients are diagnosed with cancer annually in the US, and more than half a million die each year from metastases [2]. Bone metastases to the femur are common; in fact, the femur is the most common site of osseous metastatic disease resulting in orthopaedic intervention. As such, most general orthopaedic surgeons are likely to encounter this problem. The goal in stabilizing these lesions is to allow the patient to regain mobility and maintain a high quality of life. Experience has shown fixation with intramedullary devices is superior to using plates and screws [3], although this may not apply for periprosthetic femoral bone metastases, where plate fixation may be the treatment of choice. When choosing an intramedullary implant, the conventional wisdom has been to use locked cephalomedullary nails. Locking the nails makes sense because of the inherent instability of the femur when a metastatic lesion is present. The rationale for cephalomedullary nails instead of conventional nails is to prevent femoral neck fractures if a lesion were to develop in this region during the remaining lifespan of the patient, but this theory is supported only by anecdotal evidence. The use of a cephalomedullary nail adds a degree of difficulty to the surgical procedure due to technical aspects of implanting screws in the femoral neck. The additional steps take more surgical time, and entail the use of more fluoroscopy with resultant radiation exposure to the patient, surgeon and staff. Additionally, current high-quality imaging has greatly improved the detection of occult bone lesions, and occult femoral neck lesions seem unlikely to be missed with careful imaging. The use of bisphosphonates for patients with skeletal metastases also has substantially reduced the number of skeletal events requiring surgical intervention [4]. In addition, there is no evidence available to suggest that even if a metastatic bone lesion developed in the femoral neck, that a cephalomedullary nail would be sufficient to prevent a pathologic fracture or the need for surgical revision. Finally, patients with metastatic disease in general have a limited lifespan, with the majority dying in the This CORR Insights is a commentary on the article ‘‘Intramedullary Nailing of Femoral Diaphyseal Metastases: Is it Necessary to Protect the Femoral Neck?’’ by Moon and colleagues available at: DOI: 10.1007/ s11999-014-4064-1. The author certifies that he, or any member of his immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/ licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request. The opinions expressed are those of the writers, and do not reflect the opinion or policy of CORR or the Association of Bone and Joint Surgeons. This CORR Insights comment refers to the article available at DOI: 10.1007/s11999014-4064-1. M. T. Scarborough MD (&) Department of Orthopaedics and Rehabilitation, University of Florida, PO Box 112727, Gainesville, FL 32611, USA e-mail: scarbmt@ortho.ufl.edu CORR Insights Published online: 24 December 2014 The Association of Bone and Joint Surgeons1 2014

Current perspectives on bisphosphonate treatment in Paget's disease of bone.

Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic hypocalcemia may develop. For those intolerant of bisphosphonates, subcutaneous calcitonin can be used for a limited period due to its associated risk of malignancy.