American Society Of Bone And Mineral Research Research Articles

Case series: Osteonecrosis of the jaw related to denosumab preceded by bisphosphonates in cancer and osteoporotic patients

AimsThe purpose of this study was to assess the incidence of medication-related osteonecrosis of the jaw (MRONJ) in cancer and osteoporotic patients taking denosumab (DSB) preceded by bisphosphonates (BP). MethodsThe data collection tool was adapted from the American Society of Bone and Mineral Research (ASBMR) consisting of patient details, comorbidities, clinical history, dose, and duration of DSB and preceding BP, diagnosis and MRONJ stage, management and outcomes. The staging of MRONJ follows recommendations of the American Association of Oral and Maxillofacial Surgeons (AAOMS). This retrospective case series used data from seven patients treated at the Department of Oral Surgery, Edinburgh Dental Institute over a one-year period. ResultsAll patients had a history of bisphosphonate therapy prior to commencement of denosumab therapy. One out of 7 showed no development of osteonecrosis of the jaw yet was categorized as a high-risk case. Of the remaining six cases, osteonecrosis of the jaw was present as stage 2 in four cases and stage 3 in 2 cases. Four cases developed MRONJ 8 weeks after dental extraction. The remaining two cases developed MRONJ at 12 and 20 weeks after extraction. ConclusionsThe main conclusion of this study is the potentially cumulative effect of BP and DSB in the development of MRONJ with dental extraction as a triggering factor. Further research is required before the cumulative effect of these anti-resorptive agents become fully understood.

Review of certain articles of the American society of bone and mineral research (ASMBR) annual congress 2019

The annual congress of the American Society of Bone and Mineral Research (ASBMR) presents the most significant results among the basic and clinical research in the field of osteoporosis and other metabolic bone diseases. Professor of Medicine John Bilezikian, M.D., Columbia University College of Physicians and Surgeons New York, New York and Lynda F. Bonewald Ph.D. Director, Indiana Center for Musculoskeletal Health, Indianapolis, Indiana, every year present the most outstanding abstracts before the ASBMR. However, not all of these researches are relevant for Russia, as some of them relates to the epidemiology and pharmacoeconomics of osteoporosis specifically in the US. This review presents only a very limited selection of congress abstracts, combined on topics that seem relevant today.

Determinants of Oral Bisphosphonate Use Beyond 5 Years.

Few studies have examined factors that determine bisphosphonate (BP) continuation beyond 5 years in clinical practice. To investigate factors associated with BP continuation among women who completed 5 years of BP therapy. Women who received 5 consecutive years of oral BP treatment entered the cohort during 2002-2014 and were followed up to 5 additional years. Multivariable logistic regression was used to evaluate the association of demographic and clinical factors with adherent treatment continuation. The cohort included 19,091 women with a median age of 72 years. Baseline and time-varying factors associated with increased odds of BP continuation after 5 years were (a) most recent bone mineral density (BMD) T-score -2 to -2.4 (OR = 1.31, 95% CI = 1.25-1.38), T-score -2.5 to -2.9 (OR = 1.48, 95% CI = 1.39-1.57), and T-score ≤ -3.0 (OR = 1.57, 95% CI = 1.47-1.68) versus T-scores above -2.0; (b) index date before 2008 (OR =1.35, 95% CI = 1.29-1.41); and (c) diabetes mellitus (OR = 1.08, 95% CI = 1.01-1.16). In contrast, factors associated with decreased odds of BP continuation were (a) recent hip (OR = 0.61, 95% CI = 0.52-0.71) or humerus (OR = 0.79, 95% CI = 0.66-0.94) fracture or fracture other than hip, wrist, spine, or humerus (OR = 0.90, 95% CI = 0.84-0.97); (b) Charlson Comorbidity Index score > 2 (OR = 0.91, 95% CI = 0.84-0.98); (c) history of rheumatoid arthritis (OR = 0.89, 95% CI = 0.80-0.99); (d) Hispanic (OR = 0.89, 95% CI=0.85-0.94) or Asian (OR = 0.90, 95% CI = 0.85-0.94) race/ethnicity; and (e) use of proton pump inhibitors (OR = 0.65, 95% CI = 0.59-0.71). Patient age and fracture before BP initiation were not associated with treatment continuation. Clinical factors predicting continued BP treatment beyond 5 years include low BMD T-score, absence of recent fracture, and earlier era of treatment. Use of proton pump inhibitors was associated with lower likelihood of BP continuation. Other clinical and demographic factors were also noted to have variable effects on BP treatment continuation. This study was supported by a grant from the National Institute on Aging and National Institute of Arthritis, Musculoskeletal and Skin Diseases at the National Institutes of Health (NIH; R01AG047230, S1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Kaiser Permanente. Lo has received previous research funding from Amgen and Sanofi, unrelated to the current study. Adams has received previous research funding from Merck, Amgen, Otsuka, and Radius Health, unrelated to the current study. Ettinger has served as an expert witness for Teva Pharmaceuticals, unrelated to the current study. Ott previously attended a scientific advisory meeting for Amgen but declined the honorarium. The other authors have nothing to disclose. These data were presented at the 2018 Annual Meeting of the American Society of Bone and Mineral Research (ASBMR), September 28-October 1, 2018, Montreal, Quebec, Canada.

Osteoporosis: long-term treatment versus drug holiday-what is the evidence?

The occurrence of multiple vertebral fractures after discontinuation of denosumab in the treatment of osteoporosis has reopened the debate on the optimal treatment duration and drug holidays.In principle, there is a difference in this regard between the discontinuation of medications such as bisphosphonates and substances without bone retention such as selective estrogen receptor modulators (SERMs), denosumab or teriparatide. Even after the end of application bisphosphonates have avery long half-life in the bones. After cessation of drug intake there is a slow, slight increase of bone turnover markers. Even after cessation of the SERM raloxifene, a decline in bone density can be observed, as with the termination of teriparatide. In contrast to these osteoporosis medications, after cessation of denosumab, asteep and rapid increase in markers of bone resorption above baseline levels ("rebound") and a reduction in bone mineral density to initial values can be observed.Osteoporosis is a disease that carries an increased risk of fracture, which is reduced for the duration of osteoporosis treatment. In certain situations, the fracture risk is only temporarily raised. In these situations, cessation of the osteoporosis treatment is possible. Beyond these special clinical situations, however, osteoporosis needs to be addressed as achronic disease with a permanently increased fracture risk and the indication for therapy should be evaluated according to the extent of the risk of fracture.What happens after discontinuation of anti-osteoporosis drugs? The various effects on bone turnover markers, bone mineral density and fracture incidence of the individual drug groups are presented in detail, as are the resulting recommendations of the task forces of the American Society of Bone and Mineral Research (ASBMR) and the European Calcified Tissue Society (ECTS).

Atypical subtrochanteric femur fracture following bisphosphonates: A grey area of diagnosis and management

Background and objective: Osteoporosis is a common orthopaedic problem of the geriatric population. Bisphosphonates have been effectively used to control osteoporosis and improve the bone strength. Bisphosphonates has particularly been used in glucocorticoid induced osteoporosis. However, there are emerging concerns over the risk of atypical femoral pathological fractures consequent to prolonged use of BPN therapy. This study was designed to report the diagnosis and treatment of atypical subtrochanteric femur fractures after bisphosphonate treatment. Subject and methods: We report a rare case of atypical femur fracture in a 70-year-old female patient who has been taking bisphosphonates for glucocorticoid-induced osteoporosis for 5 years. She suffered a subtrochanteric fracture after tripping on the doorstep. The fracture was fixed using a titanium proximal femur nail. The patient was followed up by X-ray examination 1 year after operation. This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Jagadguru Sri Shivarathreeshwara Hospital, India. Written informed consent was obtained from the patient. Results: The postoperative period was uneventful, and the patient recovered well. The patient was independently ambulatory with good function of her left hip. Conclusion: Atypical femoral fractures are defined clearly by the American Society of Bone and Mineral Research (ASBMR) criteria. Many reports in the literature have reported atypical femoral fractures after bisphosphonates therapy but do not meet the ASBMR criteria. The risk ratio of atypical femoral fractures after bisphosphonates use is high. Regular monitoring and screening of patients on bisphosphonates therapy by radiographs allow us to diagnose these fractures early and treat them successfully.

Intramedullary Nail Fixation of Atypical Femur Fractures With Bone Marrow Aspirate Concentrate Leads to Faster Union: A Case-Control Study.

To evaluate bone marrow aspirate concentrate (BMAC) use in the treatment of AFF. Retrospective case control. Level 1 trauma center. Complete AFF, defined according to American Society of Bone and Mineral Research (ASBMR) criteria, from September 2009 to April 2015 with minimum 1-year follow-up. Operative treatment with antegrade intramedullary nails. Beginning June 2014, BMAC from the ipsilateral iliac crest was added to all AFFs. Time to union as determined by a blinded panel of 3 attending orthopaedic surgeons, union rates, complications. Thirty-five patients with 36 AFFs were reviewed, of which 33 AFFs were included and 11 received BMAC. Alendronate was the most commonly prescribed bisphosphonate, with a similar mean duration of use in controls and BMAC cases (5.6 versus 6 years, P = 0.79). BMAC use significantly decreased time to union (3.5 versus 6.8 months, P = 0.004). Varus malreduction was associated with a significant delay in union (9.7 versus 4.7 months, P = 0.04). Overall, 1 year union rate was 86.2% and nonsignificantly higher in BMAC compared with controls (100.0% versus 77.3%, P = 0.11). Multivariate analysis revealed BMAC and varus malreduction as independent predictors of time to union. There were no complications related to BMAC use. Our findings support intramedullary nailing of AFFs as an effective treatment option with a low surgical complication rate and highlight the importance of avoiding varus malreduction. BMAC use significantly reduced time to fracture union without an increase in surgical complication rates. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Compliance with established guidelines for the radiological reporting of atypical femoral fractures.

Atypical femoral fractures (AFFs) are important to diagnose early to avoid progression to complete fracture. We set out to determine the reporting accuracy of AFFs. We conducted a retrospective analysis of imaging performed between November 2010 and June 2013 to analyse the X-ray reporting of AFFs and to describe the key clinical considerations. Radiological reports were reviewed from the 3805 separate femoral images for search terms thought likely to identify AFFs. This identified 1558 patients. The identified radiographs were reviewed by radiologists with reference to the 2010 American Society of Bone and Mineral Research (ASBMR) criteria. Within these 1558 patients, 16 patients met the radiological criteria for AFF according to the 2010 ASBMR task force statement of which, although all were identified as fractures, 15 were not reported as "atypical" by the original reporting author and none was formally classified as AFF by the original reporting author. Within the 1558 patients, there were an additional 17 patients labelled as having "atypical" fracture features originally, although only 1 patient met the 2010 ASBMR task force criteria for AFF. Only 13 of 16 patients had imaging of the contralateral femur, and there was a significant delay for those who were imaged (111 ± 44 days). Furthermore, two of the patients with an AFF had previous radiographs demonstrating cortical changes indicative of AFFs prior to formal diagnosis. Whilst AFFs are rare diagnoses, the compliance with published guidelines for their radiological classification is low. We have raised awareness of the importance of recognizing AFFs to guide management.

Trends in Media Reports, Oral Bisphosphonate Prescriptions, and Hip Fractures 1996-2012: An Ecological Analysis.

Bisphosphonates are effective for the treatment of osteoporosis despite recent reports of safety concerns such as atypical femur fracture. We conducted an ecological analysis of relevant media reports, oral bisphosphonate use, and fracture outcomes in the United States. Trends in media reports and public interest of bisphosphonates were quantified using data from Google Trends. Data from the Medical Expenditure Panel Survey (MEPS) and the National Inpatient Sample (NIS) were used to estimate the trends in oral bisphosphonate use among patients aged 55 years and older and hospitalizations for intertrochanteric and subtrochanteric fractures, respectively. These trends in the prevalence of oral bisphosphonate use and the age-adjusted incidence rate of intertrochanteric and subtrochanteric fractures were examined from 1996 to 2012. A series of spikes in Internet search activity for alendronate (Fosamax) occurred between 2006 and 2010 immediately following media reports of safety concerns. Oral bisphosphonate use declined by greater than 50% between 2008 and 2012 (p < 0.001) after increasing use for more than a decade. The decline was more common in patients with lower education levels. Intertrochanteric hip fractures declined from 1996 through 2006 (p < 0.001) and continued to decline from 2008 to 2012 (p < 0.05). Subtrochanteric and diaphyseal fractures showed a steady and significant increase from 2002 to 2011 (p < 0.05). However, the incidence decreased from a peak of 30.5 per 100,000 in 2011 to 26.7 per 100,000 in 2012. The plateauing and subsequent decline in oral bisphosphonate use since 2006 coincided with reports of safety concerns of bisphosphonates, despite the fact that U.S. Food and Drug Administration (FDA) and American Society of Bone and Mineral Research (ASBMR) reports did not recommend any safety restrictions on their use. This decline in oral bisphosphonate use was followed by the decline in the incidence of subtrochanteric and diaphyseal fractures.

Editorial introductions

Editorial introductions

Reviews of Current Literature

Malden N, Lopes V. An epidemiological study of alendronate-related osteonecrosis of the jaws. A case series from the south-east of Scotland with attention given to case definition and prevalence. J Bone Miner Metab. 2011. [Epub ahead of print[This article presents a close case study series of alendronate-associated osteonecrosis of the jaws (AONJ). From their study the authors draw epidemiologic conclusion regarding AONJ as well as comment on clinical considerations and treatment protocol. Alendronate is the most common bisphosphonate prescribed in the world. Since the first cases of ONJ started to emerge a task force of the American Society of Bone and Mineral Research (ASBMR) proposed recommendations to address key issues with ONJ and bisphosphonates. These include case definition and clinical management as well as epidemiology. In this study, to confirm and stage AONJ, the authors used the definition proposed by American Association of Oral and Maxillofacial Surgeons 2009 position papers on BONJ. The specific details for case definition, as described by ASBMR, fall in to 7 categories of information (A–G): A, patient details—for this article all were white Caucasian except for one, and 82% were female; B, diagnosis/staging of disease—mild to moderate pain, presence of nonvital bone; C, local site and clinical history—64% included a history of dental extraction preceding the condition; D, alendronate dose and duration of presentation—70 mg daily dose; the duration of administration to first ONJ recognition had a mean of 3 years; E, indication for bisphosphonate use—64% were receiving alendronate to counteract the osteoporotic affects of glucocorticosteroids; 36% were receiving the drug for age-related or hormone/menopause-related osteoporosis; an estimate mean of 4.7 years of “disease onset” prior to ONJ onset; F, co-morbidity and duration of ONJ—55% were ASA III; duration of comorbidity to diagnosis of ONJ was difficult to assess, but in 64% it was considered between 5 and 10 years; G, co-medications and duration of ONJ—prednisolone was prescribed in 55% of the cases. Three patients were taking immunosuppressant leflunomide or methotrexate. A known complication of immunosuppressive drugs is oral ulcerations and 27% of patients had concomitant administration of those with alendronate. Four patients with cardiovascular disease were taking statins and two were taking nicorandil. Nicorandil is a drug used in the management of persistent angina pectoris. It has been associated with oral ulcerations, occasionally affecting the alveolar ridges. Thus the authors suggest that drug associated ulcerations, if occurring over bone in the presence of alendronate could initiate the development of ONJ. Thus these drugs should be considered risk factors. 55% of patients who developed ONJ were taking prednisolon and alendronate.Management of ONJ included mild analgesics (64%), antimicrobials in various combinations (73%) that ranged from 1 to 11 weeks, one surgical debridement (64%), chlorhexidine was prescribed to all patients, and 45% of patients discontinued alendronate use at the diagnosis of ONJ. It was decided that the risk associated with discontinuation of alendronate are less then the risks associated with continuation of alendronate. However a case-by-case review with multispecialist discussion is suggested when discontinuation of bisphosphonate therapy is considered as a treatment adjunct to management of AONJ. In this study the duration from diagnosis to resolution ranged from 2 weeks to 20 months (mean of 6.5 months). By tracking alendronate prescriptions the drug patient year (DPY) was calculated. Thus epidemiology could be approximated. In the population studied, the incidence of AONJ as a spontaneous event or in response to a traumatic oral insult is between 0.03% and 0.017% respectively. Where alendronate is prescribed alone or for age-related or hormone-related osteoporosis the prevalence is 0.004%. The presence of comorbidity where comedications are being prescribed with alendronate significantly increases the risk of developing AONJ. It is suggested that rheumatoid arthritis patients receiving alendronate, glucocorticosteroids, and often an immunosuppressant are at an increased risk of ONJ with an incidence of 0.1% of AONJ. This study of 11 patients and an extrapolation to a population of 900 000 with DPY calculations brings our attention to AONJ from another clinical perspective that should benefit our patients and our considerations in their care.

Bisphosphonates' Use Could Be Limited by Fractures

Bisphosphonates' Use Could Be Limited by Fractures