Journal articles on the topic 'Bisphosphonate'
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Bergner, R. "Bisphosphonattherapie bei renaler Osteopathie." Osteologie 17, no. 03 (2008): 154–58. http://dx.doi.org/10.1055/s-0037-1619862.
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ZusammenfassungBisphosphonate sind in der Therapie der Osteoporose und maligner Knochenerkrankungen inzwischen Standard. Da Bisphosphonate ausschließlich renal ausgeschieden werden, ist eine schwere Niereninsuffizienz eine Kontraindikation für den Einsatz der meisten Bisphosphonate. Bei Dialysepatienten liegen jedoch in der Regel ausgeprägte Veränderungen des Knochenstoffwechsels vor, die zumindest teilweise den Einsatz von Bisphosphonaten sinnvoll erscheinen lassen. Tierexperimentelle Studien belegen, dass durch die Gabe eines Bisphosphonats die Veränderungen eines hyperparathyreoiden Knochens verhindert werden konnten. Daten zu Clodronat, Pamidronat und Ibandronat zeigen, dass diese Bisphosphonate gut dialysabel sind und ein Einsatz bei Dialysepatienten von dieser Seite her möglich ist. In ersten Pilotstudien an Dialysepatienten konnte dieser positive Effekt aus den tierexperimentellen Studien bestätigt werden. Es fehlen jedoch derzeit größere placebokontrollierte Studien, die den Einsatz von Bisphosphonaten in der Therapie der renalen Osteopathie soweit belegen, dass dieser als allgemeine Therapieempfehlung ausgesprochen werden kann.
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Anghelescu, Doralina L., Varayini Pankayatselvan, Rosa Nguyen, Deborah Ward, Jianrong Wu, Huiyun Wu, Denaya D. Edwards, and Wayne Furman. "Bisphosphonate Use in Pediatric Oncology for Pain Management." American Journal of Hospice and Palliative Medicine® 36, no. 2 (August 16, 2018): 138–42. http://dx.doi.org/10.1177/1049909118793114.
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The use of bisphosphonates for pain control in children with cancer is not extensively studied. We retrospectively evaluated 35 children with cancer treated with intravenous bisphosphonates for pain management at a single institution from 1998 through 2015. We analyzed pain scores and opioid and adjuvant medication consumption before bisphosphonate administration, daily for 2 weeks, and at 3 and 4 weeks after administration. We also determined the time interval between diagnosis and first administration of bisphosphonates and duration of life after bisphosphonate administration. Mean pain scores were 2.45 (±2.96) and 0.75 (±1.69) before and 14 days after bisphosphonate administration, respectively ( P = .25), and morphine equivalent doses of opioids were 5.52 (±13.35) and 5.27 (±9.77), respectively ( P = .07). Opioid consumption was significantly decreased at days 4 to 8, days 11 to 12, and week 3 after first bisphosphonate administration. The median duration of life after first bisphosphonate administration was 80 days, indicating its use late in the course of treatment. Bisphosphonates did not significantly improve pain outcomes at 2 weeks, but opioid consumption was reduced at several time points during the first 3 weeks. The use of bisphosphonates earlier in the course of pediatric oncological disease should be evaluated in prospective investigations.
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Klotz, Christopher, Franz Jakob, Matthias Kohl, Simon von Stengel, Uwe Lange, Friederike Thomasius, Katharina Kerschan-Schindl, Michael Uder, and Wolfgang Kemmler. "Effekt von additivem körperlichem Training zur Bisphosphonat-Therapie auf die Knochendichte: Eine systematische Übersichtsarbeit und Meta-Analyse." Osteologie 31, no. 03 (August 2022): 184–94. http://dx.doi.org/10.1055/a-1904-5706.
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Zusammenfassung Hintergrund Körperliches Training und antiresorptive pharmakologische Therapie wirken über unterschiedliche Mechanismen auf den Knochenstoffwechsel ein. Die vorliegende Arbeit beschäftigt sich mit dem Ansatz, ob eine Bisphosphonat-Behandlung durch zusätzliches körperliches Training additive Effekte auf die Knochendichte (BMD) an Lendenwirbelsäule (LWS) und/oder Schenkelhals (SH) ausübt. Methoden Unsere systematische Literaturrecherche von fünf elektronischen Datenbanken gemäß PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) schloss kontrollierten Studien mit einer Dauer von mehr als 6 Monaten und mindestens zwei Studienarmen: (a) Bisphosphonate (B), (b) Bisphosphonate und körperliches Training (B+E) bis zum 26. August 2021, ein. Studien mit anderen pharmazeutischen Therapien oder Krankheiten mit relevanten Auswirkungen auf den Knochenstoffwechsel wurden ausgeschlossen. Die vorliegende Analyse wurde als random-effects Meta-Analyse durchgeführt. Ergebnismaße waren standardisierte mittlere Differenzen (SMD) für BMD-Änderungen an LWS und Schenkelhals (SH). Ergebnisse Unsere Suche identifizierte vier geeignete Studien mit insgesamt 247 Teilnehmern. Zusammenfassend zeigte die kombinierte Intervention (B+E) verglichen mit der isolierten Bisphosphonat-Therapie keine signifikant höheren Effektstärken an LWS (SMD: 0,66, 95%-CI: − 0,63 bis 1,94) oder SH-BMD (0,49 − 0,42 bis 1,40). Wir beobachteten für beide Studienendpunkte (BMD-LWS, BMD-SH) eine sehr hohe Heterogenität der Ergebnisse der eingeschlossenen Studien (I2: 89 bzw. 92%). Die Wahrscheinlichkeit eines „small study“ bzw. Publikations-Bias liegt in beiden Fällen ebenfalls recht hoch. Schlussfolgerung Wir konnten keinen signifikant überlegenen Effekt einer kombinierten Intervention aus Bisphosphonaten und körperlichem Training im Vergleich zu isolierter Bisphosphonat-Therapie auf die BMD an LWS oder SH erfassen. Allerdings zeigten die vorliegenden Einzelstudien eine hohe Heterogenität, die wir primär auf unterschiedlichen Trainingsprotokolle der Studien zurückführen. Schlüsselworte körperliches Training, Bisphosphonate, Knochendichte, Meta-Analyse
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Stepaniuk, Kevin. "Bisphosphonate Related Osteonecrosis of the Jaws: A Review." Journal of Veterinary Dentistry 28, no. 4 (December 2011): 277–81. http://dx.doi.org/10.1177/089875641102800413.
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Bisphosphonate use has increased in veterinary medicine over the last decade. During this time, bisphosphonate related osteonecrosis of the jaws (BRONJ) in human patients has been identified. Only recently was a dog model for BRONJ developed for human oral surgery and medicine. Veterinary patients treated with bisphosphonates may be at an increased risk for BRONJ. There has been little, to no, investigation of potential long term side-effects of bisphosphonate use in veterinary patients; potential sequelae are unknown. The history of bisphosphonates, their use, and BRONJ in veterinary patients are discussed.
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Thirunavukarasu, Ananthi, Hugo Grancho Pinto, and Kevin Guy Seymour. "Bisphosphonate and Implant Dentistry – is it Safe?" Primary Dental Journal 4, no. 3 (September 2015): 30–33. http://dx.doi.org/10.1308/205016815815944650.
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Bisphosphonates are a group of drugs that are commonly used to alter bone metabolism in order to prevent bone loss in diseases such as osteoporosis and bone cancers. Unfortunately, the use of bisphosphonates has been associated with bisphosphonate-related osteonecrosis of the jaws. The debate as to whether it is wise to consider implant therapy in patients being treated with bisphosphonate therapy remains a grey area. This review will present the latest evidence and guidelines available on bisphosphonates and their possible effects on implant dentistry. The risk factors, co-morbidities, clinical presentation and findings from various imaging modalities for bisphosphonate-related osteonecrosis of the jaws are highlighted. The management of patients being treated with bisphosphonates, in whom dental implants might be considered or have already been placed, will also be discussed. Finally, the areas requiring future research are considered.
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Kawai, Toshiyuki, Kohei Nishitani, Yaichiro Okuzu, Koji Goto, Yutaka Kuroda, Shinichi Kuriyama, Shinichiro Nakamura, and Shuichi Matsuda. "Bisphosphonate use is associated with a decreased joint narrowing rate in the non-arthritic hip." Bone & Joint Research 11, no. 11 (November 1, 2022): 826–34. http://dx.doi.org/10.1302/2046-3758.1111.bjr-2022-0155.r1.
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Aims The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip. Methods We retrospectively reviewed standing whole-leg radiographs from patients who underwent knee arthroplasties from 2012 to 2020 at our institute. Patients with previous hip surgery, Kellgren–Lawrence grade ≥ II hip osteoarthritis, hip dysplasia, or rheumatoid arthritis were excluded. The rate of hip joint space narrowing was measured in 398 patients (796 hips), and the effects of the use of bisphosphonates were examined using the multivariate regression model and the propensity score matching (1:2) model. Results A total of 45 of 398 (11.3%) eligible patients were taking an oral bisphosphonate at the time of knee surgery, with a mean age of 75.8 years (SD 6.2) in bisphosphonate users and 75.7 years (SD 6.8) in non-users. The mean joint space narrowing rate was 0.04 mm/year (SD 0.11) in bisphosphonate users and 0.12 mm/year (SD 0.25) in non-users (p < 0.001). In the multivariate model, age (standardized coefficient = 0.0867, p = 0.016) and the use of a bisphosphonate (standardized coefficient = −0.182, p < 0.001) were associated with the joint space narrowing rate. After successfully matching 43 bisphosphonate users and 86 non-users, the joint narrowing rate was smaller in bisphosphonate users (p < 0.001). Conclusion The use of bisphosphonates is associated with decreased joint degeneration in non-arthritic hips after knee arthroplasty. Bisphosphonates slow joint degeneration, thus maintaining the thickness of joint cartilage in the normal joint or during the early phase of osteoarthritis. Cite this article: Bone Joint Res 2022;11(11):826–834.
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Bourrion, Bastien, Cécile Souty, Lucie Fournier, Ana-Maria Vilcu, Thierry Blanchon, Pierre-Yves Böelle, Thomas Hanslik, and Mathilde François. "Bisphosphonate Use and Hospitalization for Hip Fractures in Women: An Observational Population-Based Study in France." International Journal of Environmental Research and Public Health 18, no. 16 (August 20, 2021): 8780. http://dx.doi.org/10.3390/ijerph18168780.
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Bisphosphonates are widely used in the treatment of women at risk of osteoporotic hip fracture; however, the overall effectiveness of bisphosphonates in the prevention of osteoporotic fractures has not been studied in real life. To investigate whether the use of bisphosphonates in women aged 50 years and over is associated with a decrease in hospitalization for osteoporotic hip fractures, a historical prospective cohort study was conducted between 2009 and 2016 from a permanent representative sample consisting of 1/97 of the French health insurance beneficiaries. Bisphosphonate use was defined according to medication persistence and adherence regarding bisphosphonate dispensations. The primary outcome was the hospitalization rate for osteoporotic hip fracture. Among the 81,268 women included, 2005 were exposed to bisphosphonates. The median time of bisphosphonate exposure was 12 (IQR, 3–29) and 17 (IQR, 5–42) months for the persistence and adherence definitions, respectively. Exposure to bisphosphonates was not associated with a decrease in hospitalization for hip fracture: weighted HRadherence = 0.66 (95% CI, 0.33 to 1.33); HRpersistance = 0.77 (95% CI, 0.38 to 1.57). In real life, bisphosphonate use does not appear to reduce hospitalization for hip fractures, as to date, it is probably prescribed as primary prevention and for a duration too short to be effective.
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Lloyd, Ashley A., Bernd Gludovatz, Christoph Riedel, Emma A. Luengo, Rehan Saiyed, Eric Marty, Dean G. Lorich, et al. "Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance." Proceedings of the National Academy of Sciences 114, no. 33 (July 31, 2017): 8722–27. http://dx.doi.org/10.1073/pnas.1704460114.
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Bisphosphonates are the most widely prescribed pharmacologic treatment for osteoporosis and reduce fracture risk in postmenopausal women by up to 50%. However, in the past decade these drugs have been associated with atypical femoral fractures (AFFs), rare fractures with a transverse, brittle morphology. The unusual fracture morphology suggests that bisphosphonate treatment may impair toughening mechanisms in cortical bone. The objective of this study was to compare the compositional and mechanical properties of bone biopsies from bisphosphonate-treated patients with AFFs to those from patients with typical osteoporotic fractures with and without bisphosphonate treatment. Biopsies of proximal femoral cortical bone adjacent to the fracture site were obtained from postmenopausal women during fracture repair surgery (fracture groups, n = 33) or total hip arthroplasty (nonfracture groups, n = 17). Patients were allocated to five groups based on fracture morphology and history of bisphosphonate treatment [+BIS Atypical: n = 12, BIS duration: 8.2 (3.0) y; +BIS Typical: n = 10, 7.7 (5.0) y; +BIS Nonfx: n = 5, 6.4 (3.5) y; −BIS Typical: n = 11; −BIS Nonfx: n = 12]. Vibrational spectroscopy and nanoindentation showed that tissue from bisphosphonate-treated women with atypical fractures was harder and more mineralized than that from bisphosphonate-treated women with typical osteoporotic fractures. In addition, fracture mechanics measurements showed that tissue from patients treated with bisphosphonates had deficits in fracture toughness, with lower crack-initiation toughness and less crack deflection at osteonal boundaries than that of bisphosphonate-naïve patients. Together, these results suggest a deficit in intrinsic and extrinsic toughening mechanisms, which contribute to AFFs in patients treated with long-term bisphosphonates.
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Ntep, Ntep David Bienvenue, Ernest Kenna, Siafa Antoine Bola, and Messanga Charles Bengondo. "The Potential Role of Angiogenic Osteoclast Inhibition in the Occurrence of Bisphosphonate-related Osteonecrosis of the Jaw." Case Reports in Dental Science 1, no. 1 (June 30, 2020): 15–21. http://dx.doi.org/10.46619/crds.2020.1-1004.
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Bisphosphonate-related osteonecrosis of the jaw is a serious complication of systemic bisphosphonate administration, the mechanism of which remains unclear. Many hypotheses regarding pathophysiology are discussed, including the most commonly cited: suppression of bone remodeling and suppression of angiogenesis, but none of these would explain all the unique features of bisphosphonaterelated jaw osteonecrosis. Bisphosphonates are potent inhibitors of osteoclasts, and recent studies have shown that osteoclasts are important for bone angiogenesis. Therefore, we hypothesize that bisphosphonates inhibit osteoclastic stimulation of angiogenesis, thereby contributing to the occurrence of osteonecrosis of the jaws. This theory would partially explain the pathophysiology of bisphosphonate-related osteonecrosis of the jaw to the unfathomable.
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Sawatari, Yoh, and Robert E. Marx. "Bisphosphonates and Bisphosphonate Induced Osteonecrosis." Oral and Maxillofacial Surgery Clinics of North America 19, no. 4 (November 2007): 487–98. http://dx.doi.org/10.1016/j.coms.2007.07.003.
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Paskins, Zoe, Fay Crawford-Manning, Elizabeth Cottrell, Nadia Corp, Jenny Wright, Clare Jinks, Simon Bishop, et al. "Acceptability of bisphosphonates among patients, clinicians and managers: a systematic review and framework synthesis." BMJ Open 10, no. 11 (November 2020): e040634. http://dx.doi.org/10.1136/bmjopen-2020-040634.
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ObjectiveTo explore the acceptability of different bisphosphonate regimens for the treatment of osteoporosis among patients, clinicians and managers, payers and academics.DesignA systematic review of primary qualitative studies. Seven databases were searched from inception to July 2019. Screening, data extraction and quality assessment of full-articles selected for inclusion were performed independently by two authors. A framework synthesis was applied to extracted data based on the theoretical framework of acceptability (TFA). The TFA includes seven domains relating to sense-making, emotions, opportunity costs, burden, perceived effectiveness, ethicality and self-efficacy. Confidence in synthesis findings was assessed.SettingAny developed country healthcare setting.ParticipantsPatients, healthcare professionals, managers, payers and academics.InterventionExperiences and views of oral and intravenous bisphosphonates.ResultsTwenty-five studies were included, mostly describing perceptions of oral bisphosphonates. We identified, with high confidence, how patients and healthcare professionals make sense (coherence) of bisphosphonates by balancing perceptions of need against concerns, how uncertainty prevails about bisphosphonate perceived effectiveness and a number of individual and service factors that have potential to increase self-efficacy in recommending and adhering to bisphosphonates. We identified, with moderate confidence, that bisphosphonate taking induces concern, but has the potential to engender reassurance, and that both side effects and special instructions for taking oral bisphosphonates can result in treatment burden. Finally, we identified with low confidence that multimorbidity plays a role in people’s perception of bisphosphonate acceptability.ConclusionBy using the lens of acceptability, our findings demonstrate with high confidence that a theoretically informed, whole-system approach is necessary to both understand and improve adherence. Clinicians and patients need supporting to understand the need for bisphosphonates, and clinicians need to clarify to patients what constitutes bisphosphonate treatment success. Further research is needed to explore perspectives of male patients and those with multimorbidity receiving bisphosphonates, and patients receiving intravenous treatment.PROSPERO registration numberCRD42019143526.
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Neogi, Tuhina, Shanshan Li, Christine Peloquin, Devyani Misra, and Yuqing Zhang. "Effect of bisphosphonates on knee replacement surgery." Annals of the Rheumatic Diseases 77, no. 1 (October 7, 2017): 92–97. http://dx.doi.org/10.1136/annrheumdis-2017-211811.
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PurposeBone remodelling as a therapeutic target in knee osteoarthritis (OA) has gained much interest, but the effects of antiresorptive agents on knee OA have been conflicting, with no studies to date examining the effects of bisphosphonate use on the clinically relevant endpoint of knee replacement (KR) surgery.MethodsWe used data from The Health Improvement Network (THIN), a general practitioner electronic medical records representative of the general UK population. We identified older women who had initiated bisphosphonate use after their incident knee OA diagnosis. Each bisphosphonate initiator was propensity score-matched with a non-initiator within each 1-year cohort accrual block. The effect of bisphosphonates on the risk of KR was assessed using Cox proportional hazard regression. Sensitivity analyses to address residual confounding were also conducted.ResultsWe identified 2006 bisphosphonate initiators, who were matched to 2006 non-initiators(mean age 76, mean body mass index 27), with mean follow-up time of 3 years. The crude incidence rate of KR was 22.0 per 1000 person-years among the initiators, and 29.1 among the non-initiators. Bisphosphonate initiators had 26% lower risk of KR than non-initiators(HR 0.74, 95% CI 0.59 to 0.93); these results were similar when additionally adjusted for potential confounders in the propensity score (HR 0.76, 95% CI 0.60 to 0.95). Results of sensitivity analyses supported this protective effect.ConclusionsIn this population-based cohort of older women with incident knee OA, those with incident bisphosphonate users had lower risk of KR than non-users of bisphosphonates, suggesting a potential beneficial effect of bisphosphonates on knee OA.
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I, Bashir. "Bisphosphonates in Postmenopausal Women with Osteoporosis to Prevent Future Fractures." Journal of Orthopaedics & Bone Disorders 3, no. 2 (2019): 1–8. http://dx.doi.org/10.23880/jobd-16000179.
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Postmenopausal women who have osteoporosis are at increased risk of future fractures. Bisphosphonates are drugs that are used to treat osteoporosis by acting on the osteoclasts to inhibit bone resorption. Several studies have shown that bisphosphonate s can maintain or even increase bone mineral density in osteoporosis patients. This review study analyzed the literature on clinical experiments with bisphosphonate therapy in postmenopausal women to determine if these drugs are efficacious in preventing f uture fractures. Four out of five studies found that women treated with bisphosphonates were at decreased risk of future fractures, and six of six studies found that bisphosphonate therapy increases bone mineral density relative to placebo control. Althoug h further work is warranted to understand the level of bone mineral density increase that is associated with fracture prevention, this study implies that bisphosphonate therapy can be used to help prevent future fractures in postmenopausal osteoporotic wom en. The study is significant in that it helps to underscore the efficacy of bisphosphonate therapy in postmenopausal women, and it may be generalizable to other populations with osteopo s rosis who are at increased risk of fractures.
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Chlebowski, Rowan T., Zhao Chen, Jane A. Cauley, Garnet Anderson, Rebecca J. Rodabough, Anne McTiernan, Dorothy S. Lane, et al. "Oral Bisphosphonate Use and Breast Cancer Incidence in Postmenopausal Women." Journal of Clinical Oncology 28, no. 22 (August 1, 2010): 3582–90. http://dx.doi.org/10.1200/jco.2010.28.2095.
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Purpose Emerging clinical evidence suggests intravenous bisphosphonates may inhibit breast cancer while oral bisphosphonates have received limited evaluation regarding breast cancer influence. Patients and Methods The association between oral bisphosphonate use and invasive breast cancer was examined in postmenopausal women enrolled onto the Women's Health Initiative (WHI). We compared a published hip fracture prediction model, which did not incorporate bone mineral density (BMD), with total hip BMD in 10,418 WHI participants who had both determinations. To adjust for potential BMD difference based on bisphosphonate use, the hip fracture prediction score was included in multivariant analyses as a BMD surrogate. Results Of the 154,768 participants, 2,816 were oral bisphosphonate users at entry (90% alendronate, 10% etidronate). As calculated hip fracture risk score was significantly associated with both BMD (regression line = 0.79 to 0.0478 log predicted fracture; P < .001; r = 0.43) and breast cancer incidence (P = .03), this variable was incorporated into regression analyses to adjust for BMD difference between users and nonusers of bisphopshonate. After 7.8 mean years of follow-up (standard deviation, 1.7), invasive breast cancer incidence was lower in bisphosphonate users (hazard ratio [HR], 0.68; 95% CI, 0.52 to 0.88; P < .01) as was incidence of estrogen receptor (ER) –positive invasive cancers (HR, 0.70; 95% CI, 0.52 to 0.94, P = .02). A similar but not significant trend was seen for ER-negative invasive cancers. The incidence of ductal carcinoma in situ was higher in bisphosphonate users (HR, 1.58; 95% CI, 1.08 to 2.31; P = .02). Conclusion Oral bisphosphonate use was associated with significantly lower invasive breast cancer incidence, suggesting bisphosphonates may have inhibiting effects on breast cancer.
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Zhou, Jifang, Karen Sweiss, Edith A. Nutescu, Jin Han, Pritesh R. Patel, Naomi Y. Ko, Todd A. Lee, Brian C. H. Chiu, and Gregory S. Calip. "Racial Disparities in Intravenous Bisphosphonate Use Among Older Patients With Multiple Myeloma Enrolled in Medicare." JCO Oncology Practice 17, no. 3 (March 2021): e294-e312. http://dx.doi.org/10.1200/op.20.00479.
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PURPOSE: Intravenous (IV) bisphosphonates reduce the risk of skeletal-related events in patients with multiple myeloma (MM). However, data describing racial differences in IV bisphosphonate utilization outside of clinical trial settings are limited. We evaluated population-level IV bisphosphonate initiation and discontinuation among patients of age ≥ 65 years with MM. METHODS: We conducted a retrospective cohort study of patients of age ≥ 65 years diagnosed with first primary MM between 2001 and 2011. Patients were identified using the SEER-Medicare linked database and followed through December 2013. Cumulative incidences of IV bisphosphonate initiation and time to discontinuation among users were compared between racial and ethnic groups. In Fine and Gray competing risk models, we estimated subdistribution hazard ratios (SHRs) and 95% CIs for initiation and discontinuation. RESULTS: We included 14,231 eligible patients with MM (median age, 76 years; 52% male). Over a median follow-up of 23.1 months, 54% of patients received at least one IV bisphosphonate dose. Our final analytical sample included 10,456 non-Hispanic (NH) Whites, 2,267 NH Blacks, 548 Asian and Pacific islanders, and 815 Hispanic and Latino patients. A higher proportion of White patients (56.1%) newly received IV bisphosphonates after MM diagnosis compared with NH Blacks (45.4%). Compared with White patients, NH Black patients were less likely to initiate IV bisphosphonates (SHR, 0.74; 95% CI, 0.70 to 0.79) and slightly more likely to discontinue treatment (SHR, 1.10; 95% CI, 1.01 to 1.19). CONCLUSION: Approximately half of the patients with MM of age ≥ 65 years did not receive IV bisphosphonates, with significant delay among racial minority groups. These findings highlight the need for improvement of IV bisphosphonate uptake in patients with MM of age ≥ 65 years.
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Gnant, Michael, Catherine Van Poznak, and Lowell Schnipper. "Therapeutic Bone-Modifying Agents in the Nonmetastatic Breast Cancer Setting: The Controversy and a Value Assessment." American Society of Clinical Oncology Educational Book, no. 37 (May 2017): 116–22. http://dx.doi.org/10.1200/edbk_177357.
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Clinical trials and meta-analyses investigating bisphosphonates as an adjuvant breast cancer therapy have shown a consistent trend, with postmenopausal women and women receiving ovarian suppression with gonadotropin-releasing hormone therapy gaining improved breast cancer outcomes with the use of adjuvant bisphosphonate therapy. The interpretation of these data is controversial, because the primary endpoints of the majority of adjuvant bisphosphonate studies have been negative. Pros and cons as well as the value of adjuvant bisphosphonate therapy are discussed here.
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Beck, V., E. Solomayer, M. Krimmel, C. Reinert, and T. Fehm. "Bisphosphonate-induced osteonecrosis of the jaw: Incidence and risk factors in patients with breast cancer and gynecological malignancies." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 1113. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.1113.
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1113 Background: Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption. They are successfully used in conditions of increased bone turnover such as osteoporosis or bone metastases. Since 2003 multiple cases of bisphosphonate-induced osteonecrosis of the jaw (ONJ) were reported. Our purpose was to describe the incidence and risk factors of ONJ in patients with breast cancer or gynecological malignancies. Patients and Methods: ONJ was assessed retrospectively for all patients with breast cancer or gynecological malignancies treated with bisphosphonates at the Department of Gynecology and Obstetrics, University Hospital Tuebingen during April 1999 until May 2006. Results: 10 of 310 (3%) patients with breast cancer or gynecological malignancies developed ONJ while receiving bisphosphonate therapy. All patients with ONJ were treated for bone metastases. Except one all patients with ONJ had a history of recent dental procedures. All patients had received zoledronic acid as part of their bisphosphonate regimen. In 4 of 10 patients this was the only bisphosphonate given. The remaining 6 patients had received at least one of the other bisphosphonates (alendronate, ibandronate, clodronate or pamidronate) before or after zoledronic acid therapy during their course of disease. Time of exposure to bisphosphonates and the number of treatment cycles were significant risk factors for the development of ONJ (p<0.001). In patients diagnosed with ONJ the mean number of treatment cycles was 27 ±18 cycles (median: 21 cycles, range 6–62 cycles) and the mean duration of bisphosphonate therapy was 29 ±20 months (median: 22 months, range 1–67 months). In contrast, the mean number of treatment cycles in patients without manifestation of ONJ was 11 ±12 cycles (median: 6 cycles, range 1–90 cycles). The mean duration of therapy was 12 months (median: 7 months, range 1–81 months). Conclusion: Osteonecrosis of the jaw is regarded a major side effect of bisphosphonate therapy. Length of exposure to bisphosphonates and the number of treatment cycles seem to be the most important risk factors for the development of ONJ. In addition, recent dental procedures favours the development of an ONJ. No significant financial relationships to disclose.
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Okçu, Mehmet, Fatmanur Aybala Koçak, Samet Sancar Kaya, and Figen Tuncay. "Is there a familial predisposition to bisphosphonate-induced atypical femoral fractures?" Turkish Journal of Physical Medicine and Rehabilitation 67, no. 3 (September 1, 2021): 370–73. http://dx.doi.org/10.5606/tftrd.2021.5248.
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Bisphosphonates are commonly used in the treatment of osteoporosis. Atypical femoral fracture (AFF) is a well-known adverse effect of bisphosphonate use. The importance of genetic factors has been demonstrated in bone quality, bone turnover, and in the response to osteoporosis treatment. Herein, we present two cases of bilateral AFFs after bisphosphonate use for a short period of time in members of the same family (mother and her daughter) and discuss genetic predisposition to bisphosphonate-induced AFFs in the light of literature data.
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Sapkota, S., S. Baig, T. Hess, A. M. O’Connell, J. Menk, M. Shyne, P. Fazeli, K. Ensrud, and A. Shmagel. "Vitamin D and bisphosphonate therapy in systemic lupus erythematosus patients who receive glucocorticoids: are we offering the best care?" Lupus 29, no. 3 (January 29, 2020): 263–72. http://dx.doi.org/10.1177/0961203320903086.
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Objective This study aimed to evaluate management practices for glucocorticoid (GC)-induced osteoporosis (GIOP) in systemic lupus erythematosus (SLE) patients using 2017 American College of Rheumatology guidelines as a gold standard. Methods We conducted a retrospective cohort study using a clinical database from the years 2011 to 2016. SLE cases with >90 days continuous prednisone use at doses of ≥7.51 mg daily were identified. Osteoporosis risk factors were assessed via chart review. The Fracture Risk Assessment (FRAX) score was estimated for patients > 40 years of age. Vitamin D, bisphosphonate prescriptions, and osteoporotic (OP) fractures were ascertained through chart review. A classification tree was used to identify the key patient-related predictors of bisphosphonate prescription. Results A total of 203 SLE patients met the inclusion criteria. The recommended dose of vitamin D supplement was prescribed to 58.9% of patients < 40 years of age and 61.5% of patients ≥ 40 years of age. Among patients aged ≥ 40 years, 25% were prescribed bisphosphonates compared to 36% who met indications for bisphosphonates per the ACR guidelines. Another 10% were prescribed a bisphosphonate, despite not having indication per the ACR guidelines, which was considered as overtreatment. Among patients aged ≥ 40 years, older age and a higher FRAX score for major OP fracture and hip fracture predicted bisphosphonate prescription. In a classification tree analysis, patients with FRAX scores (for major OP fracture) of ≥ 23.5% predicted bisphosphonate prescription in this SLE population. Among patients who had OP fractures in the follow-up period, nine (6.50%) were inpatients receiving appropriate GIOP care versus 12 (13.6%) who were inpatients not receiving ACR-appropriate care ( p = 0.098). Conclusions In clinical practice, fewer SLE patients with or at risk for GIOP are prescribed vitamin D and bisphosphonates than recommended by the 2017 ACR guidelines. Also, in this study, another 10% were prescribed a bisphosphonate, despite not having an indication per the ACR guidelines. Patients were most likely to receive a bisphosphonate prescription if they had a major OP FRAX score of > 23.5%.
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Mustafa, W., R. O'Byrne, B. Okpaje, A. Gabr, B. Ali, A. Mohamed, S. Cameron, et al. "233 BISPHOSPHONATES: ANOTHER COMPLEX DRUG TO PRESCRIBE." Age and Ageing 50, Supplement_3 (November 2021): ii9—ii41. http://dx.doi.org/10.1093/ageing/afab219.233.
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Abstract Background Bisphosphonates provide effective treatment for osteoporosis. They accumulate a bone reservoir lasting for 3 years and beyond. The 2021 NICE guidelines recommend a medication review and a ‘drug holiday’ after 5 years of oral bisphosphonate therapy for low-fracture risk patients. Continuing treatment for high risk individuals is advised: age=/>75, previous hip or vertebral fracture, one or more fractures during treatment, recent DEXA scan with T score =/<−2.5, and/or current treatment with oral glucocorticoids. This retrospective audit aimed to assess compliance with NICE guidelines in a primary care setting. Methods Data were collected using the Health One online medical record system in an urban general practice. Inclusion criteria: all patients =/> 65 years old, prescribed oral bisphosphonate therapy for osteoporosis for >5 years. Exclusion criteria: deceased, did not attend clinic >1 year, patients on bisphosphonate treatment for conditions other than osteoporosis. Results 137 patients with a history of bisphosphonate therapy were identified. 76 patients were on bisphosphonate treatment for greater than 5 years. Of the 76 patients, 33 were classified as low-fracture risk and appropriately commenced a drug holiday, while 22 correctly remained on bisphosphonates due to a high fracture risk. The remaining 21 patients inappropriately continued therapy without receiving a medication review, repeat DEXA or fracture-risk assessment. Conclusion One third of patients on bisphosphonates beyond 5 years were not assessed for a drug holiday. The aim of a bisphosphonate ‘drug holiday’ is to reduce poly-pharmacy and prevent rare but serious long-term adverse events (such as atypical fractures, osteonecrosis of the jaw, gastric cancer and atrial fibrillation). Factors which had an impact on inappropriate prescribing should be assessed. Incorporating computer-based prescribing alerts could support safe prescribing practices.
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Utari, Tita Ratya, Muhammad Fariez Kurniawan, and Shylvia Muchsin Andewa. "<strong>The controlled release profile of risedronate emulgel to inhibit relapse movement in orthodontic treatment</strong>." Padjadjaran Journal of Dentistry 34, no. 1 (April 9, 2022): 66. http://dx.doi.org/10.24198/pjd.vol34no1.32628.
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Introduction: Relapse is one of the undesirable effects of orthodontic treatment. Prevention of relapse has been carried out with the use of retainer devices. Several studies also have been carried out to prevent relapse with pharmacological agents such as bisphosphonates. One of the strongest bisphosphonates is risedronate. Systemic use of bisphosphonates can cause bisphosphonate-related necrosis of the jaw (BRONJ). Systemic effects can be minimised by topical preparations locally, where the virgin coconut oil (VCO) emulgel is one of the topical preparations which controls the release of drugs. This study aims to analyse the release profile of risedronate emulgel as a material to inhibit relapse movement. Methods: This research was conducted in an experimental laboratory. Group 1 was emulgel without bisphosphonate risedronate with virgin coconut oil (VCO), Group 2 was VCO emulgel with bisphosphonates risedronate, and Group 3 was a pure bisphosphonate risedronate solution. Each group weighing 100 mg was placed in 10 ml PBS, and the release test was conducted with UV/VIS Spectrophotometer wavelength λ 262 nm at intervals of 1, 2, 4, 8, 24, 48, and 96 hours with three replications at each group. Results: Grup 2 yielded a controlled drug release of risedronate until 96 hours, while a pure solution of risedronate resulted in an uncontrolled drug release of risedronate, which was released entirely in 4 hours. Conclusion: Risedronate emulgel with VCO had a controlled drug release compared to pure bisphosphonate solution to potentially be applied topically to inhibit relapse movement.
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Ataallah, Basma, Christina Nania, and Neel Shah. "PSAT188 Keeping An Eye On Bisphosphonates: Drug Induced Uveitis." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A205. http://dx.doi.org/10.1210/jendso/bvac150.421.
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Abstract Introduction Bisphosphonates are considered the treatment of choice for osteoporosis. They have strong anti-osteoclastic activity and are potent inhibitors of bone resorption. Ocular inflammation, including conjunctivitis, uveitis, episcleritis and scleritis, is a rare side effect of bisphosphonates. A few cases in the literature have reported ocular inflammation secondary to bisphosphonate use. But largely, it has been an underrecognized cause of uveitis. We report a case of unilateral uveitis secondary to bisphosphonate therapy that was completely resolved after discontinuation of the medication. Case report A 68-year-old female with a history of osteoporosis diagnosed in 2019 on routine bone density scan presented for treatment evaluation. She had a history of multiple fractures after falling from standing height but no history of kidney stones, hypercalcemia, or GERD. She was started on alendronate 70mg once a week in 2019 with stabilization in bone density on repeat scan in 2020. After several weeks of treatment, she developed left eye uveitis and was treated with phenylephrine 2.5% and prednisolone acetate 1% ophthalmic solution. Because of these symptoms, the patient had diagnostic studies done which revealed positive ANA. She then had an extensive rheumatology workup, including serum SM antibody, ANCA screen, RNP antibody, Sjogren's antibodies, DNA (DS) antibody, and HLA-B27 DNA typing, which were all negative. Due to some case reports citing an association of bisphosphonate use with eye inflammation, the bisphosphonate was stopped with gradual improvement in her eye symptoms. An attempt to restart alendronate resulted in worsening eye symptoms, so the therapy was ultimately switched to denosumab. Discussion The incidence of ocular inflammation after bisphosphonate initiation is 0.08%. Symptoms usually develop 24 hours to a few weeks after starting treatment. The potential pathogenesis of bisphosphonate-induced ocular inflammation is thought to be secondary to bloodstream absorption and secretion of the medication into tears from the lacrimal gland causing irritation to the eyes’ mucous membranes. Originally it was thought that ocular inflammation only occurred with nitrogen-containing bisphosphonates, due to the nitrogen group possibly playing a role in activating gamma delta T cells leading to the release of acute phase reactants, such as cytokines. More recently, both nitrogen and non-nitrogen containing bisphosphonates have been associated with reported cases of ocular inflammation. Presentation can be either unilateral or bilateral, but the majority of reported cases were unilateral. All patients receiving bisphosphonates who develop signs and symptoms of ocular inflammation should be referred promptly to an ophthalmologist. The drug should be discontinued once the diagnosis is made to prevent further progression. In conclusion, clinicians should be aware of the potential for ocular inflammation upon bisphosphonate initiation. Patients may benefit from switching to a different class of medication, such as denosumab, if they experience symptoms of ocular inflammation with bisphosphonates. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
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Licata, Angelo A. "Discovery, Clinical Development, and Therapeutic Uses of Bisphosphonates." Annals of Pharmacotherapy 39, no. 4 (April 2005): 668–77. http://dx.doi.org/10.1345/aph.1e357.
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OBJECTIVE: To review the literature concerning the history, development, and therapeutic uses of bisphosphonates. DATA SOURCES: English-language articles were identified through a search of MEDLINE (through December 2004) using the key word bisphosphonate. Reference lists of pivotal studies, reviews, and full prescribing information for the approved agents were also examined. STUDY SELECTION AND DATA EXTRACTION: Selected studies included those that discussed the discovery and initial applications of bisphosphonates, as well as their historical development, pharmacokinetic and pharmacodynamic properties, and current therapeutic uses. DATA SYNTHESIS: Bisphosphonates structurally resemble pyrophosphates (naturally occurring polyphosphates) and have demonstrated similar physicochemical effects to pyrophosphates. In addition, bisphosphonates reduce bone turnover and resist hydrolysis when administered orally. The information gained from initial work with etidronate generated a considerable scientific effort to design new and more effective bisphosphonates. The PCP moiety in the general bisphosphonate structure is essential for binding to hydroxyapatite and allows for a number of chemical variations by changing the 2 lateral side chains (designated R1 and R2). The R1 side chain determines binding affinity to hydroxyapatite, and the R2 side chain determines antiresorptive potency. Accordingly, each bisphosphonate has its own characteristic profile of activity. CONCLUSIONS: The bisphosphonates reduce bone turnover, increase bone mass, and decrease fracture risk and therefore have a significant place in the management of skeletal disorders including osteoporosis, Paget's disease, bone metastases, osteogenesis imperfecta, and heterotopic ossification.
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Guthrie, Ariane, Kathleen Fairman, and Dawn Knudsen Gerber. "Fractured Timelines: Reporting Patterns for Bisphosphonate-Associated Atypical Fractures and Implications for Postmarket Surveillance." Senior Care Pharmacist 37, no. 11 (November 1, 2022): 555–64. http://dx.doi.org/10.4140/tcp.n.2022.555.
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Background Case reports of atypical fractures associated with bisphosphonates first appeared in the literature in 2005, with a larger number of reports published in 2007-2009. Objective To describe reporting trends of bisphosphonate-associated atypical fractures relative to increasing awareness across medical and lay communities. Methods Disproportionality analyses were performed to assess odds of reporting atypical fractures associated with oral bisphosphonates using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reporting odds ratios (RORs) were assessed according to prespecified time periods (pre-awareness [1995-2006], growing-awareness [2007-2009], and post-warning [2010-2021]). Results There were 182 atypical fracture reports (n = 18 bisphosphonate-associated) during the pre-awareness period, 177 (n = 69 bisphosphonate-associated) during growing-awareness, and 6,170 (n = 3,150 bisphosphonate-associated) post-warning. Among reports by health care professionals, RORs for bisphosphonate-associated atypical fractures were 1.76, 13.49, and 12.16 across the three time periods. In comparison, RORs among all reporters (including consumers) increased from 1.50 to 7.95 to 18.93 across those three time periods. The highest proportion of reports during the pre-awareness period was for patients 51 to 65 years of age; however, patients 66 years of age and older comprised the largest proportion of reports in the growing-awareness and post-warning periods. Discussion Reporting patterns for atypical fractures associated with bisphosphonate therapy appear to correlate with increasing awareness among the medical and lay community. Conclusion As medication experts, pharmacists play a key role in recognizing risk factors for atypical fractures, utilizing the FDA’s system to support accurate event reporting, and promoting bisphosphonate deprescribing when clinically appropriate.
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Wilkinson, Gregg S., Jacques Baillargeon, Yong-Fang Kuo, Jean L. Freeman, and James S. Goodwin. "Atrial Fibrillation and Stroke Associated With Intravenous Bisphosphonate Therapy in Older Patients With Cancer." Journal of Clinical Oncology 28, no. 33 (November 20, 2010): 4898–905. http://dx.doi.org/10.1200/jco.2010.28.7524.
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Purpose Recent studies have linked the use of intravenous and orally administered bisphosphonates with subsequent development of atrial fibrillation. Patients with cancer who receive intravenous bisphosphonate therapy may be at particular risk for this adverse event because they receive higher doses of these drugs than do patients treated for other indications. We examined the association of intravenous bisphosphonates with atrial fibrillation, all classifications of supraventricular tachycardia (SVT), and stroke among older patients with cancer. Patients and Methods Using Surveillance, Epidemiology, and End Results (SEER) -Medicare–linked data, we identified older (≥ age 65 years) patients with cancer who were treated with intravenous infusions of bisphosphonates between January 1, 1995 and December 31, 2003. We then matched 13,714 bisphosphonate nonusers to 6,857 bisphosphonate users, at a 2:1 ratio, on cancer type, age, sex, presence of bone metastases, and SEER geographic region. Patients were observed until December 31, 2003 or until they lost coverage from Medicare Parts A and B; enrolled in a health maintenance organization; received a diagnosis of atrial fibrillation, any SVT, or stroke; or died. Results Receipt of intravenous bisphosphonates was modestly associated with an increased risk for atrial fibrillation (hazard ratio [HR] = 1.30; 95% CI, 1.18 to 1.43), all SVT (HR = 1.28; 95% CI, 1.19 to 1.38), and stroke (HR = 1.30; 95% CI, 1.09 to 1.54). The risk for all SVT increased 7% for each increase of five bisphosphonate dose equivalents (HR = 1.07; 95% CI, 1.02 to 1.12). Conclusion Clinicians who treat patients with cancer who have received intravenous bisphosphonates should be aware of the possible cardiovascular adverse events associated with this treatment.
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Shalev, Varda, Sarah Sharman Moser, Inbal Goldshtein, Jingbo Yu, Clara Weil, Sophia Ish-Shalom, Vanessa Rouach, and Gabriel Chodick. "Adherence With Bisphosphonates and Long-Term Risk of Hip Fractures: A Nested Case-Control Study Using Real-World Data." Annals of Pharmacotherapy 51, no. 9 (May 23, 2017): 757–67. http://dx.doi.org/10.1177/1060028017710482.
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Background: Hip fracture is a major complication of osteoporosis. Bisphosphonate medication is the mainstay of treatment for osteoporosis. However, concerns have been raised regarding the effectiveness of bisphosphonates in reducing hip fracture risk after long-term use, particularly among patients with suboptimal adherence. Objective: To examine the association between adherence with bisphosphonate therapy and long-term risk of hip fracture. Methods: Included in the present nested case-control study were osteoporotic women (n = 14 357) who initiated bisphosphonate therapy in 2000-2010 and were retrospectively followed for incident hip fracture through November 2014. Within this cohort, each case of primary hip fractures was individually matched to 3 controls without a primary hip fracture. Proportion of follow-up days covered (PDC) with bisphosphonates was calculated from bisphosphonate purchases. Adherence was categorized into the following groups: purchase of 1 or 2 months’ supply (reference group), at least 3 months’ supply to PDC ≤20%, PDC >20% to ≤80%, PDC >80% to ≤100%. Results: Included in the analysis were 426 case-control groups with a mean age (SD) of 73.7 years (7.9). Compared with the reference group, PDC of 80% to 100% with bisphosphonates was associated with a significant reduction in hip fracture risk for patients with 8 to 15 years of follow-up (OR = 0.39; 95% CI = 0.18-0.87). Among patients with a follow-up of up to 3 years, OR was 0.58 (95% CI = 0.31-1.06). Conclusions: Adherence with bisphosphonates among osteoporotic patients is associated with lower risk of hip fracture, with no indication of diminished effectiveness with long-term use.
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Ito, Kouta, Victoria S. Blinder, and Elena B. Elkin. "Cost Effectiveness of Fracture Prevention in Postmenopausal Women Who Receive Aromatase Inhibitors for Early Breast Cancer." Journal of Clinical Oncology 30, no. 13 (May 1, 2012): 1468–75. http://dx.doi.org/10.1200/jco.2011.38.7001.
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Purpose Aromatase inhibitors (AIs) increase the risk of osteoporosis and related fractures in postmenopausal women who receive adjuvant AIs for hormone receptor (HR) –positive early breast cancer (EBC). We compared the cost effectiveness of alternative screening and treatment strategies for fracture prevention. Methods We developed a Markov state transition model to simulate clinical practice and outcomes in a hypothetical cohort of women age 60 years with HR-positive EBC starting a 5-year course of AI therapy after primary surgery for breast cancer. Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER). We compared the following strategies: no intervention; one-time bone mineral density (BMD) screening and selective bisphosphonate therapy in women with osteoporosis or osteopenia; annual BMD screening and selective bisphosphonate therapy in women with osteoporosis or osteopenia; and universal bisphosphonate therapy. Results ICERs for annual BMD screening followed by oral bisphosphonates for those with osteoporosis, annual BMD screening followed by oral bisphosphonates for those with osteopenia, and universal treatment with oral bisphosphonates were $87,300, $129,300, and $283,600 per QALY gained, respectively. One-time BMD screening followed by oral bisphosphonates for those with osteoporosis or osteopenia was dominated. Our results were sensitive to age at the initiation of AI therapy, type of bisphosphonates, post-treatment residual effect of bisphosphonates, and a potential adjuvant benefit of intravenous bisphosphonates. Conclusion In postmenopausal women receiving adjuvant AIs for HR-positive EBC, a policy of baseline and annual BMD screening followed by selective treatment with oral bisphosphonates for those diagnosed with osteoporosis is a cost-effective use of societal resources.
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Hayes, Kaleen N., Elizabeth M. Winter, Suzanne M. Cadarette, and Andrea M. Burden. "Duration of Bisphosphonate Drug Holidays in Osteoporosis Patients: A Narrative Review of the Evidence and Considerations for Decision-Making." Journal of Clinical Medicine 10, no. 5 (March 9, 2021): 1140. http://dx.doi.org/10.3390/jcm10051140.
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Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and the potential for rare adverse events associated with long-term use (atypical femoral fractures and osteonecrosis of the jaw), a drug holiday of two to three years is recommended for most patients after long-term bisphosphonate therapy. The recommendation for a drug holiday up to three years is derived primarily from extensions of pivotal trials with alendronate and zoledronate and select surrogate marker studies. However, certain factors may modify the duration of bisphosphonate effects on a drug holiday and warrant consideration when determining an appropriate time off-therapy. In this narrative review, we recall what is currently known about drug holidays and discuss what we believe to be the primary considerations and areas for future research regarding drug holiday duration: total bisphosphonate exposure, type of bisphosphonate used, bone mineral density and falls risk, and patient sex and body weight.
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Wasserzug, Oshri, Israel Kaffe, Towy Sorel Lazarovici, Tal Weissman, Ran Yahalom, Dan M. Fliss, and Noam Yarom. "Involvement of the Maxillary Sinus in Bisphosphonate-Related Osteonecrosis of the Jaw: Radiologic Aspects." American Journal of Rhinology & Allergy 31, no. 1 (January 2017): 36–39. http://dx.doi.org/10.2500/ajra.2017.31.4395.
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Background The use of bisphosphonates is very common among patients with osteoporosis and multiple myeloma as well as those with bone metastases from various malignancies. The benefits of bisphosphonates are well recognized, but it became evident during the past decade that these medications portend the major adverse effect of osteonecrosis of the jaw, known as bisphosphonate-related osteonecrosis of the jaw. Objective Our aim was to evaluate the specific manifestations of bisphosphonate use on the maxillary sinus in patients with documented bisphosphonate-related osteonecrosis of the jaw. Methods A retrospective review of all the patients diagnosed between October 2003 to August 2014 as having bisphosphonate-related osteonecrosis of the jaw in a large university-affiliated tertiary care medical center. The records of 173 patients diagnosed as having bisphosphonate-related osteonecrosis of the jaw during the study period were retrieved. The available head and neck computed tomographic images were analyzed for cases of involvement of the maxilla. Main Outcome Measures Manifestations of bisphosphonate-related osteonecrosis of the jaw as observed on physical examination and on imaging studies. Results Seventy-one patients (41%) had involvement of the maxilla, 86 patients (49%) had involvement of the mandible, and 16 patients (9%) had involvement of both the maxilla and the mandible. Computerized tomography studies were available for 50 patients with involvement of the maxilla: 36 (72%) had evidence of maxillary sinus opacification (in comparison, the incidence of maxillary sinus opacification as an incidental finding in the general population is reported to be 19%, p < 0.0001). Sixteen patients (32%) had evidence of oroantral fistula, and five patients (10%) had oronasal fistula. Conclusion In addition to its well-established effects on the mandible and maxilla, bisphosphonate-related osteonecrosis of the jaw significantly affected the maxillary sinus. Its radiologic manifestations should be recognized by clinicians and especially by otolaryngologists.
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Arponen, Heidi, Ilkka Vuorimies, Jari Haukka, Helena Valta, Janna Waltimo-Sirén, and Outi Mäkitie. "Cranial base pathology in pediatric osteogenesis imperfecta patients treated with bisphosphonates." Journal of Neurosurgery: Pediatrics 15, no. 3 (March 2015): 313–20. http://dx.doi.org/10.3171/2014.11.peds14113.
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OBJECT Cranial base pathology is a serious complication of osteogenesis imperfecta (OI). Our aim was to analyze whether bisphosphonate treatment, used to improve bone strength, could also prevent the development of craniocervical junction pathology (basilar impression, basilar invagination, or platybasia) in children with OI. METHODS In this single-center retrospective study the authors analyzed the skull base morphology from lateral skull radiographs and midsagittal MR images (total of 94 images), obtained between the ages of 0 and 25 years in 39 bisphosphonate-treated OI patients. The results were compared with age-matched normative values and with findings in 70 OI patients who were not treated with bisphosphonates. In addition to cross-sectional data, longitudinal data were available from 22 patients with an average follow-up period of 7.6 years. The patients, who had OI types I, III, IV, VI, and VII, had been treated with zoledronic acid, pamidronate, or risedronate for 3.2 years on average. RESULTS Altogether 33% of the 39 bisphosphonate-treated patients had at least 1 cranial base anomaly, platybasia being the most prevalent diagnosis (28%). Logistic regression analysis suggested a higher risk of basilar impression or invagination in patients with severe OI (OR 22.04) and/or older age at initiation of bisphosphonate treatment (OR 1.45), whereas a decreased risk was associated with longer duration of treatment (OR 0.28). No significant associations between age, height, or cumulative bisphosphonate dose and the risk for cranial base anomaly were detected. In longitudinal evaluation, Kaplan-Meier curves suggested delayed development of cranial base pathology in patients treated with bisphosphonates but the differences from the untreated group were not statistically significant. CONCLUSIONS These findings indicate that cranial base pathology may develop despite bisphosphonate treatment. Early initiation of bisphosphonate treatment may delay development of craniocervical junction pathology. Careful followup of cranial base morphology is warranted, particularly in patients with severe OI.
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Vassaki, Maria, Konstantinos E. Papathanasiou, Chrystalleni Hadjicharalambous, Daphne Chandrinou, Petri Turhanen, Duane Choquesillo-Lazarte, and Konstantinos D. Demadis. "Self-sacrificial MOFs for ultra-long controlled release of bisphosphonate anti-osteoporotic drugs." Chemical Communications 56, no. 38 (2020): 5166–69. http://dx.doi.org/10.1039/d0cc00439a.
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Porta-Sales, Josep, Cristina Garzón-Rodríguez, Silvia Llorens-Torromé, Cinzia Brunelli, Alessandra Pigni, and Augusto Caraceni. "Evidence on the analgesic role of bisphosphonates and denosumab in the treatment of pain due to bone metastases: A systematic review within the European Association for Palliative Care guidelines project." Palliative Medicine 31, no. 1 (July 10, 2016): 5–25. http://dx.doi.org/10.1177/0269216316639793.
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Background: Bisphosphonates and denosumab are well-established therapies to reduce the frequency and severity of skeletal-related events in patients with bone metastasis. However, the analgesic effect of these medications on bone pain is uncertain. Aim: To identify, critically appraise and synthesize existing evidence to answer the following questions: ‘In adult patients with metastatic bone pain, what is the evidence that bisphosphonates and denosumab are effective and safe in controlling pain?’ and ‘What is the most appropriate schedule of bisphosphonate/denosumab administration to control bone pain?’. This review also updates the 2002 Cochrane review ‘Bisphosphonates for the relief of pain secondary to bone metastases’. Design: Standard systematic review and narrative synthesis. Data sources: MEDLINE, EMBASE and Cochrane CENTRAL databases were searched for relevant articles published through 31 January 2014. A manual search was also performed. Study inclusion criteria were: a) conducted in adult patients; b) randomized controlled trial or meta-analisys; c) reported efficacy of bisphosphonates or denosumab on pain and/or decribed side effects versus placebo or other bisphosphonate; and d) English language. Results: The database search yielded 1585 studies, of which 43 (enrolling 8595 and 7590 patients, respectively, in bisphosphonate and denosumab trials) met the inclusion criteria. Twenty-two (79%) of the 28 placebo-controlled trials found no analgesic benefit for bisphosphonates. None of the denosumab studies assessed direct pain relief. Conclusion: Evidence to support an analgesic role for bisphosphonates and denosumab is weak. Bisphosphonates and denosumab appear to be beneficial in preventing pain by delaying the onset of bone pain rather than by producing an analgesic effect per se.
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Govindarajan, Vaidya, Anthony Diaz, Roberto J. Perez-Roman, S. Shelby Burks, Michael Y. Wang, and Allan D. Levi. "Osteoporosis treatment in patients undergoing spinal fusion: a systematic review and meta-analysis." Neurosurgical Focus 50, no. 6 (June 2021): E9. http://dx.doi.org/10.3171/2021.3.focus2175.
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OBJECTIVE Bisphosphonates and teriparatide are the most common therapies used in the treatment of osteoporosis. Their impact on fusion rates in osteoporotic patients following spinal fusion has yet to be concretely defined, with previous systematic reviews focusing heavily on bisphosphonates and lacking clinical insight on the utility of teriparatide. Herein the authors present an updated meta-analysis of the utility of both bisphosphonates and teriparatide in improving spinal fusion outcomes in osteoporotic patients. METHODS After a comprehensive search of the English-language literature in the PubMed and Embase databases, 11 clinical studies were included in the final qualitative and quantitative analyses. Of these studies, 9 investigated bisphosphonates, 7 investigated teriparatide, and 1 investigated a combination of teriparatide and denosumab. Odds ratios and 95% confidence intervals were calculated where appropriate. RESULTS A meta-analysis of the postoperative use of bisphosphonate demonstrated better odds of successful fusion as compared to that in controls during short-term monitoring (OR 3.33, 95% CI 1.72–6.42, p = 0.0003) but not long-term monitoring (p > 0.05). Bisphosphonate use was also shown to significantly reduce the likelihood of postoperative vertebral compression fracture (VCF; OR 0.07, 95% CI 0.01–0.59, p = 0.01) and significantly reduce Oswestry Disability Index scores (mean difference [MD] = −2.19, 95% CI −2.94 to −1.44, p < 0.00001) and visual analog scale pain scores (MD = −0.58, 95% CI −0.79 to −0.38, p < 0.00001). Teriparatide was found to significantly increase fusion rates at long-term postoperative periods as compared to rates after bisphosphonate therapy, with patients who received postoperative teriparatide therapy 2.05 times more likely to experience successful fusion (OR 2.05, 95% CI 1.17–3.59, p = 0.01). CONCLUSIONS The authors demonstrate the benefits of bisphosphonate and teriparatide therapy independently in accelerating fusion during the first 6 months after spinal fusion surgery in osteoporotic patients. In addition, they show that teriparatide may have superior benefits in spinal fusion during long-term monitoring as compared to those with bisphosphonates. Bisphosphonates may be better suited in preventing VCFs postoperatively in addition to minimizing postoperative disability and pain.
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Coskun Benlidayi, Ilke, and Rengin Guzel. "Oral Bisphosphonate Related Osteonecrosis of the Jaw: A Challenging Adverse Effect." ISRN Rheumatology 2013 (May 16, 2013): 1–6. http://dx.doi.org/10.1155/2013/215034.
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Oral bisphosphonates are the most commonly prescribed antiresorptive drugs for the treatment of osteoporosis. However, there are several adverse effects associated with oral bisphosphonates including the bisphosphonate related osteonecrosis of the jaw (BRONJ). With a better understanding of this side effect, reported incidences for BRONJ in oral bisphosphonate users have increased in time. The pathogenesis of BRONJ has not been well determined. Several risk factors such as dentoalveolar surgery, therapy duration, and concomitant steroid usage have been linked to BRONJ. Conservative and surgical methods can be preferred in the treatment. Preventative measures are of great importance for the patients at high risk. In this paper, osteonecrosis of the jaw secondary to oral bisphosphonates was reviewed in order to increase awareness as well as to renew the current knowledge.
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Kim, Hyung Joon, Ha Jin Kim, YunJeong Choi, Moon-Kyoung Bae, Dae Seok Hwang, Sang-Hun Shin, and Jae-Yeol Lee. "Zoledronate Enhances Osteocyte-Mediated Osteoclast Differentiation by IL-6/RANKL Axis." International Journal of Molecular Sciences 20, no. 6 (March 22, 2019): 1467. http://dx.doi.org/10.3390/ijms20061467.
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Bisphosphonates are one of the most widely used synthetic pyrophosphate analogues for the treatment of bone resorbing diseases such as osteoporosis, multiple myeloma, and bone metastases. Although the therapeutic usefulness of bisphosphonates mainly depends on their anti-osteoclastogenic effect, a severe side-effect of bisphosphonates called bisphosphonate-related osteonecrosis of the jaw (BRONJ) could not be explained by the anti-osteoclastogenic effect of bisphosphonates. In the present study, we have evaluated the changes in osteoclastogenesis- or osteoblastogenesis-supporting activities of osteocytes induced by bisphosphonates. Zoledronate, a nitrogen-containing bisphosphonate, markedly increased both the receptor activator of nuclear factor kB ligand (RANKL) as well as sclerostin in osteocyte-like MLO-Y4 cells, which were functionally revalidated by osteoclast/osteoblast generating activities of the conditioned medium obtained from zoledronate-treated MLO-Y4 cells. Of note, the zoledronate treatment-induced upregulation of the RANKL expression was mediated by autocrine interleukin-6 (IL-6) and subsequent activation of the signal transducer and activator of transcription 3 (STAT3) pathway. These results were evidenced by the blunted RANKL expression in the presence of a Janus activated kinase (JAK2)/STAT3 inhibitor, AG490. Also, the osteoclastogenesis-supporting activity was significantly decreased in zoledronate-treated MLO-Y4 cells in the presence of IL-6 neutralizing IgG compared to that of the control IgG. Thus, our results show previously unanticipated effects of anti-bone resorptive bisphosphonate and suggest a potential clinical importance of osteocytes in BRONJ development.
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Pramanik, Chandrani, Tianda Wang, Sushanta Ghoshal, Lina Niu, Bradley A. Newcomb, Yaodong Liu, Carolyn M. Primus, et al. "Microfibrous borate bioactive glass dressing sequesters bone-bound bisphosphonate in the presence of simulated body fluid." Journal of Materials Chemistry B 3, no. 6 (2015): 959–63. http://dx.doi.org/10.1039/c4tb02035a.
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Nanki, Toshihiro, Mai Kawazoe, Kiyoko Uno, Wataru Hirose, Hiroaki Dobashi, Hiroshi Kataoka, Toshihide Mimura, Hiroshi Hagino, and Hajime Kono. "Improvement in Glucocorticoid-Induced Osteoporosis on Switching from Bisphosphonates to Once-Weekly Teriparatide: A Randomized Open-Label Trial." Journal of Clinical Medicine 12, no. 1 (December 30, 2022): 292. http://dx.doi.org/10.3390/jcm12010292.
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This randomized, open-label, multicenter, parallel study imitating real-world clinical practice assessed the effect of switching to weekly teriparatide in patients with glucocorticoid-induced osteoporosis (GIO) with a lumbar spine/proximal femur bone mineral density (BMD) T-score ≤ −2.0 or ≤−1.0 and a fragility fracture. Forty-four patients were randomized. The mean durations of the corticosteroid and bisphosphonate administrations were 90.0 and 51.3 months. The baseline BMD at L1–L4 was 0.828 and 0.826 g/cm2 in Groups B (bisphosphonate) and T (teriparatide); at the femur (total), these values were 0.689 and 0.661 g/cm2. The mean change in BMD was numerically higher with teriparatide vs. bisphosphonate but not statistically significant. The mean percentage changes from baseline in BMD at L1–L4 after a 72-week treatment were 0.5% and 4.1% in Groups B and T. The incidence of new fractures was higher in the patients taking bisphosphonates vs. those receiving once-weekly teriparatide at 72 weeks (18.2% vs. 11.8%) and 144 weeks (22.7% vs. 17.6%). The mean percentage change in femur (trochanter) BMD (0.035 [0.007–0.063]; p = 0.02) was significantly greater with teriparatide vs. bisphosphonates. Adverse events (AEs) were more frequent with teriparatide vs. bisphosphonates. Switching to once-weekly teriparatide tended to increase lumbar spine BMD and reduce the occurrence of new fractures vs. bisphosphonates.
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Ruggiero, Salvatore, Julie Gralow, Robert E. Marx, Ana O. Hoff, Mark M. Schubert, Joseph M. Huryn, Bela Toth, Kathryn Damato, and Vicente Valero. "Practical Guidelines for the Prevention, Diagnosis, and Treatment of Osteonecrosis of the Jaw in Patients With Cancer." Journal of Oncology Practice 2, no. 1 (January 2006): 7–14. http://dx.doi.org/10.1200/jop.2006.2.1.7.
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PurposeThis article discusses osteonecrosis of the jaw (ONJ) and offers health care professionals practical guidelines and recommendations for the prevention, diagnosis, and management of ONJ in cancer patients receiving bisphosphonate treatment.MethodsA panel of experts representing oral and maxillofacial surgery, oral medicine, endocrinology, and medical oncology was convened to review the literature and clinical evidence, identify risk factors for ONJ, and develop clinical guidelines for the prevention, early diagnosis, and multidisciplinary treatment of ONJ in patients with cancer. The guidelines are based on experience and have not been evaluated within the context of controlled clinical trials.ResultsONJ is a clinical entity with many possible etiologies; historically identified risk factors include corticosteroids, chemotherapy, radiotherapy, trauma, infection, and cancer. With emerging concern for potential development of ONJ in patients receiving bisphosphonates, the panel recommends a dental examination before patients begin therapy with intravenous bisphosphonates. Dental treatments and procedures that require bone healing should be completed before initiating intravenous bisphosphonate therapy. Patients should be instructed on the importance of maintaining good oral hygiene and having regular dental assessments. For patients currently receiving bisphosphonates who require dental procedures, there is no evidence to suggest that interrupting bisphosphonate therapy will prevent or lower the risk of ONJ. Frequent clinical assessments and conservative dental management are suggested for these patients. For treatment of patients who develop ONJ, a conservative, nonsurgical approach is strongly recommended.ConclusionAn increased awareness of the potential risk of ONJ in patients receiving bisphosphonate therapy is needed. Close coordination between the treating physician and oral surgeon and/or a dental specialist is strongly recommended in making treatment decisions.
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Schöffel, D. "Wirkung von Bisphophonaten auf Osteoporoseschmerzen." Osteologie 17, no. 04 (2008): 219–21. http://dx.doi.org/10.1055/s-0037-1619870.
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ZusammenfassungDie analgetische Wirkung der Bisphosphonate in der Onkologie wurde vielfach nachgewiesen. Bei Nichttumorschmerzen ist deren schmerzstillende Wirkung weniger gut dokumentiert. Zwar gibt es eine Vielzahl tierexperimenteller Daten zur analgetischen Wirkung von Bisphosphonaten, aber nur in einer einzigen placebokontrollierten Studie konnte eine mäßige analgetische Wirkung von Pamidronat nachgewiesen werden. Auf der anderen Seite können Bisphosphonate bei der Erstgabe von Langzeitpräparaten Schmerzen und grippeähnliche Symptome auslösen; dieser Effekt kann durch eine adäquate Vorbehandlung der Patienten verhindert werden.
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Walia, Manpreet S., Saryu Arora, and Bhawana Singal. "Jaw Osteonecrosis a Risk Factor in Bisphosphonate Therapy - A Dental Concern." Journal of Oral Health and Community Dentistry 4, no. 3 (2010): 72–77. http://dx.doi.org/10.5005/johcd-4-3-72.
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ABSTRACT Bisphosphonates are compound used in the treatment of many skeletal disorders such as bone metastases, osteoporosis, Paget's disease, hypercalcaemia of malignancy and bone pain. A new complication of bisphosphonate therapy administration i.e. osteonecrosis of jaw also known as bisphosphonate related osteonecrosis of the jaws seems to be developing. Over suppression of bone turn over is probably the primary mechanism for the development of this condition, although there may be contributing comorbid factors. Complete prevention of this complication is not currently possible. However, preventive dental care reduces this incidence. Conservative debridement of necrotic bone, pain control, infection management, use of antimicrobial oral rinses and withdrawal of bisphosphonates are preferable to aggressive surgical measures for treating this condition.
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Erdem, Yusuf, Zafer Atbasi, Tuluhan Yunus Emre, Gülis Kavadar, and Bahtiyar Demiralp. "Effect of Long-Term Use of Bisphosphonates on Forearm Bone: Atypical Ulna Fractures in Elderly Woman with Osteoporosis." Case Reports in Orthopedics 2016 (2016): 1–4. http://dx.doi.org/10.1155/2016/4185202.
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Osteoporosis is a common musculoskeletal disease of the elderly population characterized by decreased bone mineral density and subsequent fractures. Bisphosphonates are a widely accepted drug therapy which act through inhibition of bone resorption and prevent fractures. However, in long-term use, atypical bisphosphonate induced fractures may occur, particularly involving the lower weight bearing extremity. Atypical ulna fracture associated with long-term bisphosphonate use is rarely reported in current literature. We present a 62-year-old woman with atypical ulna due to long-term alendronate therapy without a history of trauma or fall. Clinicians should be aware of stress fracture in a patient who has complaints of upper extremity pain and history of long-term bisphosphonate therapy.
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Oteri, Giacomo, Ennio Bramanti, Valentina Nigrone, and Marco Cicciù. "Decayed, Missing, and Filled Teeth Index and Periodontal Health in Osteoporotic Patients Affected by BRONJ: An Observational Study." Journal of Osteoporosis 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/231289.
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The aim of this paper is to describe the incidence of decayed, missing, and filled teeth (DMFT) and periodontal disease in 32 osteoporotic patients affected by bisphosphonate-related osteonecrosis of the jaw (BRONJ). Moreover, an investigation between the obtained data and 20 patients treated with bisphosphonate drugs and with no evidence of ONJ has been performed. Osteonecrosis of the jaws is a rare complication in a subset of patients receiving bisphosphonate drugs. Based on a growing number of case reports and institutional reviews, this kind of therapy can cause exposed and necrotic bone specifically in the jawbones. From April 2009 to June 2012, 32 osteoporotic patients treated with oral or intravenous (I.V.) bisphosphonates have been recorded. The patients’ oral health has been compared with 20 bisphosphonates patients with no ONJ. The incidence of decayed, missing, and filled teeth (DMFT) and periodontal disease was recorded in all patients and student’st-test was applied for comparing the two investigated groups data. Data demonstrated how the poor dental hygiene and periodontal disease of the BRONJ patients’ are connected with the occurrence of jawbone necrosis.
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Newcomb, Polly A., Michael N. Passarelli, Amanda I. Phipps, Garnet L. Anderson, Jean Wactawski-Wende, Gloria Y. F. Ho, Mary Jo O'Sullivan, and Rowan T. Chlebowski. "Oral Bisphosphonate Use and Risk of Postmenopausal Endometrial Cancer." Journal of Clinical Oncology 33, no. 10 (April 1, 2015): 1186–90. http://dx.doi.org/10.1200/jco.2014.58.6842.
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Purpose Bisphosphonates are common medications used for the treatment of osteoporosis and are also used to reduce metastases to bone in patients with cancer. Several studies, including the Women's Health Initiative (WHI), have found that use of bisphosphonates is associated with reduced risk of developing breast cancer, but less is known about associations with other common malignancies. This study was aimed at examining the effects of bisphosphonates on the risk of endometrial cancer. Methods We evaluated the relationship between use of oral bisphosphonates and endometrial cancer risk in a cohort of 89,918 postmenopausal women participating in the WHI. A detailed health interview was conducted at baseline, and bisphosphonate use was ascertained from an inventory of regularly used medications at baseline and over follow-up. All women had an intact uterus at the time of study entry. Results During a median follow-up of 12.5 years, 1,123 women were diagnosed with incident invasive endometrial cancer. Ever use of bisphosphonates was associated with reduced endometrial cancer risk (adjusted hazard ratio, 0.80; 95% CI, 0.64 to 1.00; P = .05), with no interactions observed with age, body mass index, or indication for use. Conclusion In this large prospective cohort of postmenopausal women, bisphosphonate use was associated with a statistically significant reduction in endometrial cancer risk.
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FAVIA, GIANFRANCO, GIOVANNI PIETRO PILOLLI, and EUGENIO MAIORANO. "Osteonecrosis of the Jaw Correlated to Bisphosphonate Therapy in Non-oncologic Patients: Clinicopathological Features of 24 Patients." Journal of Rheumatology 36, no. 12 (November 2, 2009): 2780–87. http://dx.doi.org/10.3899/jrheum.090455.
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Objective.Osteonecrosis of the jaws (ONJ) is a well known side effect of bisphosphonate therapies in patients with multiple myeloma or other malignancies. Its real incidence is still undetermined, and only few cases of ONJ in patients taking bisphosphonates for non-oncologic diseases have been reported. It was postulated that the clinical features, predisposing factors, and treatment outcome of this subset of patients might be different from those of oncologic patients.Methods.Over a 4 year period, a total of 102 bisphosphonate-treated patients affected by ONJ were identified. Among these, 24 patients underwent bisphosphonate therapy for non-neoplastic disease and their profile was analyzed.Results.In this study cohort, bisphosphonates had been administered mainly for postmenopausal osteoporosis (20/24 patients, 83.3%), the duration of therapy until presentation of ONJ ranging from 11 to 40 months and the most common triggering event being dentoalveolar surgery. All patients were nonsmokers; 6 manifested multiple ONJ lesions and only 3 of them had possible comorbidities. Surgical debridement was performed in 19 patients for a total of 22 lesions, which were individually considered in the followup. The latter showed complete remission of ONJ in 21/22 lesions.Conclusion.Although it might be considered a rare condition in non-oncologic patients, ONJ is a harmful side effect of bisphosphonate therapies. Clinicians must be aware of this entity, inform patients of the risks related to dental surgery, and possibly undertake adequate preventive measures.
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Kirpichnikov, M. V., V. V. Podolsky, E. N. Yarygina, A. S. Serbin, and K. A. Aleshanov. "Care and management of bisphosphonate-associated osteonecrosis of jaw in patient with pathological fracture of mandible: case study." Medical alphabet 3, no. 23 (November 21, 2019): 34–36. http://dx.doi.org/10.33667/2078-5631-2019-3-23(398)-34-36.
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This is a case study of patient with bisphosphonate associated osteonecrosis of the mandible after an extraction of teeth 4.6 and 4.7 complicated with pathological fracture while receiving intravenous bisphosphonates is discussed. The patients presenting signs and symptoms are reviewed. Bisphosphonates induced osteonecrosis definition and are reviewed management.
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Ebzeev, A. K. "Bisphosphonate-related osteonecrosis of the jaw (BRONJ) in cancer patients." Kazan medical journal 101, no. 2 (April 13, 2020): 226–31. http://dx.doi.org/10.17816/kmj2020-226.
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This literature review focuses on the latest advances in the study of osteonecrosis of the jaw in cancer patients taking bisphosphonates. Prescribing bisphosphonates for the treatment of metastatic bone disease is justifiable and unavoidable measure. The action of bisphosphonates leads to increase in bone tissue strength, but significantly suppressing normal bone remodelling, essential for repair, and becomes vulnerable to mechanical trauma and bacterial invasion. The unique anatomical and physiological features of the jaw bones determine their selective damage. The disease is characterized by progressive jaw necrosis, chronic inflammation of the surrounding tissues complicated by a pathological fracture and persistent oroantral fistula, which aggravates chronic pain and leads to a deterioration in the quality of life of patients. The occurrence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a multifactorial process. Most often, it occurs in patients with long term treatment with zoledronic acid preparations against after tooth extraction. The fact of an increase in the incidence of osteonecrosis is undeniable for objective reasons, the main of which are an increase in cancer, an increase in the life expectancy of cancer patients and their need for bisphosphonate therapy. In the article, it was analyzed the latest scientific reports on the causes of the disease, risk factors and the pathogenesis of the disease. Data on the frequency of jaw osteonecrosis in different countries are presented. It was shown promising developments and summarizes information on existing methods for diagnosing jaw bisphosphonate osteonecrosis. Questions about the key approaches in the treatment of the disease, as well as about new experimental techniques, are examined. The main problems of the prevention of bisphosphonate-related osteonecrosis of the jaws are formulated.
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Wellman, Samuel S., David E. Attarian, and Jordan F. Schaeffer. "Periprosthetic Femoral Insufficiency Fracture in a Patient on Long-term Bisphosphonate Therapy." Duke Orthopaedic Journal 2, no. 1 (2012): 66–69. http://dx.doi.org/10.5005/jp-journals-10017-1021.
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ABSTRACT Recent literature shows an association between long-term bisphosphonate therapy and low-energy fractures of the subtrochanteric femur. It is thought that the pharmacology of bisphosphonates and stress characteristics of the sub-trochanteric femur predispose patients on long-term therapy to fracture. There are few reports in the literature of bisphos-phonate-associated periprosthetic fractures with the characteristic fracture pattern. We report a case in a patient with a 10- year history of sustained bisphosphonate use. The patient is a 79-year-old female that developed new thigh pain 9 years following a cemented total hip arthroplasty. Radiographs revealed lateral cortical thickening and a transverse periprosthetic stress fracture of the lateral femoral cortex at the level of the distal stem. This fracture appears consistent with a bisphosphonate-associated insufficiency fracture, demonstrating that this pattern is not isolated to nonarthroplasty patients. Schaeffer JF, Attarian DE, Wellman SS. Periprosthetic Femoral Insufficiency Fracture in a Patient on Long-term Bisphosphonate Therapy. The Duke Orthop J 2012;2(1):66-69.
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AlQarooni, Sayed Hashim, Ugo Ruggiero, and Sri Priya Suresh. "Atypical fractures secondary to bisphosphonate therapy: A case series and pictorial review." Indian Journal of Musculoskeletal Radiology 3 (June 30, 2021): 45–53. http://dx.doi.org/10.25259/ijmsr_2_2021.
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Osteoporosis is a ubiquitous and chronic process that affects an increasing number of people each year. Various forms of treatment are currently used including bisphosphonates which have been linked to atypical fractures of the femur. We present a case series of eight osteoporosis patients who developed atypical femoral fractures, while on bisphosphonate therapy. This pictorial review aims to increase awareness of bisphosphonate-related atypical fractures, discuss the current literature recommendations, and provide clear learning points from each case-based discussion.
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Yang, Yan-Li, Zi-Jian Xiang, Jing-Hua Yang, Wen-Jie Wang, and Ruo-Lan Xiang. "The incidence and relative risk of adverse events in patients treated with bisphosphonate therapy for breast cancer: a systematic review and meta-analysis." Therapeutic Advances in Medical Oncology 11 (January 2019): 175883591985523. http://dx.doi.org/10.1177/1758835919855235.
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Background: Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival. However, the risk of adverse events associated with bisphosphonate therapy for breast cancer remains poorly defined. Methods: A literature search was conducted using the PubMed, EMBASE, Cochrane and Web of Science libraries. Risk ratio (RR) was calculated to evaluate the adverse events of the meta-analytic results. Osteonecrosis of the jaw (ONJ) incidence was calculated using the random effect model (D+L pooled) for meta-analysis. Results: A total of 47 studies comprising 20,607 patients were included; 23 randomized controlled studies (RCTs) provided data of adverse events for bisphosphonate therapy versus without bisphosphonates. Bisphosphonates were significantly associated with influenza-like illness (RR = 4.52), fatigue (RR = 1.08), fever (RR = 1.82), dyspepsia (RR = 1.25), anorexia (RR = 1.29), and urinary tract infection (RR = 1.32). No differences were observed in other adverse events. We combined the incidence of ONJ in 24 retrospective studies to analyze the incidence of ONJ using bisphosphonates. The pooled probability of ONJ toxicity in the bisphosphonates group was 2%. Conclusions: Bisphosphonates were significantly associated with influenza-like illness, fatigue, fever, dyspepsia, anorexia, and urinary tract infection. Furthermore, bisphosphonates increase the risk of ONJ toxicity.
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Stevenson, Matt D., Jeremy E. Oakley, Myfawny Lloyd Jones, Alan Brennan, Juliet E. Compston, Eugene V. McCloskey, and Peter L. Selby. "The Cost-Effectiveness of an RCT to Establish Whether 5 or 10 Years of Bisphosphonate Treatment Is the Better Duration for Women With a Prior Fracture." Medical Decision Making 29, no. 6 (June 9, 2009): 678–89. http://dx.doi.org/10.1177/0272989x09336077.
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Purpose. Five years of bisphosphonate treatment have proven efficacy in reducing fractures. Concerns exist that long-term bisphosphonate treatment may actually result in an increased number of fractures. This study evaluates, in the context of England and Wales, whether it is cost-effective to conduct a randomized controlled trial (RCT) and what sample size may be optimal to estimate the efficacy of bisphosphonates in fracture prevention beyond 5 years. Method. An osteoporosis model was constructed to evaluate the cost-effectiveness of extending bisphosphonate treatment from 5 years to 10 years. Two scenarios were run. The 1st uses long-term efficacy data from published literature, and the 2nd uses distributions elicited from clinical experts. Results of a proposed RCT were simulated. The expected value of sample information technique was applied to calculate the expected net benefit of sampling from conducting such an RCT at varying levels of participants per arm and to compare this with proposed trial costs. Results. Without further information, the better duration of bisphosphonate treatment was estimated to be 5 years using the published data but 10 years using the elicited expert opinions, although in both cases uncertainty was substantial. The net benefit of sampling was consistently high when between 2000 and 5000 participants per arm were recruited. Conclusions. An RCT to evaluate the long-term efficacy of bisphosphonates in fracture prevention appears to be cost-effective for informing decision making in England and Wales.