scholarly journals Long-term risks of bisphosphonate therapy

2014 ◽  
Vol 58 (5) ◽  
pp. 523-529 ◽  
Author(s):  
Nelson B. Watts
Keyword(s):  
Lower Risk ◽  
Observational Studies ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Safety Issues ◽  
Femur Fractures ◽  
Atypical Femur Fractures ◽  
Post Marketing ◽  
Risk Patients

The objective this study was to summarize long-term risks associated with bisphosphonate therapy. Search of relevant medical publications for data from clinical trials, trial extensions, observational studies and post-marketing reports. Trial extensions and modifications did not reveal significant long-term safety issues. Observational data suggest at least as many benefits as risks. Post-marketing reports of musculoskeletal pain, osteonecrosis of the jaw and atypical femur fractures have been widely circulated in the lay press. Most focus on long-terms risks has been on osteonecrosis of the jaw and atypical femur fractures which occur in patients who have not received bisphosphonate therapy but may be more frequent (though still uncommon) in patients who have been on treatment for 5 years or longer. Lower-risk patients may be able to stop treatment after 3-5 years for a “drug holiday,” which mitigates these long-term risks; for higher risk patients, therapy through 6-10 years appears to be advisable and offers more benefits than risks.

scholarly journals Duration of Bisphosphonate Drug Holidays in Osteoporosis Patients: A Narrative Review of the Evidence and Considerations for Decision-Making

2021 ◽  
Vol 10 (5) ◽  
pp. 1140
Author(s):  
Kaleen N. Hayes ◽  
Elizabeth M. Winter ◽  
Suzanne M. Cadarette ◽  
Andrea M. Burden
Keyword(s):  
Surrogate Marker ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Narrative Review ◽  
Drug Holiday ◽  
Future Research ◽  
Mineral Density ◽  
First Line Therapy

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.

Medication-Induced Musculoskeletal Changes

2019 ◽  
pp. 322-326
Author(s):  
Winnie A. Mar
Keyword(s):  
Musculoskeletal System ◽  
Gold Standard ◽  
Imaging Modality ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Atypical Femoral Fractures ◽  
Osteoblastic Activity ◽  
Induced Changes

Chapter 117 discusses common medication-induced changes of the musculoskeletal system. The effect of corticosteroids on the musculoskeletal system, including osteoporosis and osteonecrosis, is discussed. Corticosteroids decrease osteoblastic activity, stimulate bone resorption, and decrease intestinal absorption of calcium. Complications of bisphosphonate therapy such as atypical femoral fractures and osteonecrosis of the jaw are reviewed. Myopathies and tendon pathologies are briefly discussed, as well as bony changes potentially seen with long-term voriconazole treatment. For osteoporosis, DXA scan is the gold standard, whereas radiography is usually the first imaging modality performed in patients on voriconazole therapy who present with pain.

scholarly journals Osteonecrosis of the Jaw After Osteoporosis Therapy With Denosumab Following Long-term Bisphosphonate Therapy

2013 ◽  
Vol 88 (4) ◽  
pp. 418-419 ◽  
Author(s):  
Tilman D. Rachner ◽  
Uwe Platzbecker ◽  
Dieter Felsenberg ◽  
Lorenz C. Hofbauer
Keyword(s):  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Osteoporosis Therapy

Osteonecrosis of the Jaw in Multiple Myeloma Patients: Clinical Features and Risk Factors

2006 ◽  
Vol 24 (6) ◽  
pp. 945-952 ◽  
Author(s):  
Ashraf Badros ◽  
Dianna Weikel ◽  
Andrew Salama ◽  
Olga Goloubeva ◽  
Abraham Schneider ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Bone Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Dental Extraction ◽  
Long Bone ◽  
Pathologic Features ◽  
Mixed Bacteria

Purpose To describe the clinical, radiologic, and pathologic features and risk factors for osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients. Patients and Methods A retrospective review of 90 MM patients who had dental assessments, including 22 patients with ONJ. There were 62 men; the median age was 61 years in ONJ patients and 58 years among the rest. Prior MM therapy included thalidomide (n = 67) and stem-cell transplantation (n = 72). Bisphosphonate therapy included zoledronate (n = 34) or pamidronate (n = 17) and pamidronate followed by zoledronate (n = 33). Twenty-seven patients had recent dental extraction, including 12 patients in the ONJ group. Median time from MM diagnosis to ONJ was 8.4 years for the whole group. Results Patients usually presented with pain. ONJ occurred posterior to the cuspids (n = 20) mostly in the mandible. Debridement and sequestrectomy with primary closure were performed in 14 patients; of these, four patients had major infections and four patients had recurrent ONJ. Bone histology revealed necrosis and osteomyelitis. Microbiology showed actinomycetes (n = 7) and mixed bacteria (n = 9). More than a third of ONJ patients also suffered from long bone fractures (n = 4) and/or avascular necrosis of the hip (n = 4). The variables predictive of developing ONJ were dental extraction (P = .009), treatment with pamidronate/zoledronate (P = .009), longer follow-up time (P = .03), and older age at diagnosis of MM (P = .006). Conclusion ONJ appears to be time-dependent with higher risk after long-term use of bisphosphonates in older MM patients often after dental extractions. No satisfactory therapy is currently available. Trials addressing the benefits/risks of continuing bisphosphonate therapy are needed.

scholarly journals Acute Nontraumatic Clavicle Fracture Associated with Long-Term Bisphosphonate Therapy

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Shen Hwa Vun ◽  
Yahya Husami ◽  
Sajan Shareef ◽  
Diane Bramley
Keyword(s):  
Clavicle Fracture ◽  
Critical Evaluation ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Low Energy ◽  
Insufficiency Fractures ◽  
Atypical Fractures

Cases of osteonecrosis of the jaw, insufficiency fractures and atypical low energy or atraumatic fractures of pelvis, femur (subtrochanteric/mid-shaft/distal-third), tibia, fibula, metatarsal, humerus, and ulna related to long-term bisphosphonate therapy have been reported in the literature. We present the case of an acute nontraumatic clavicle fracture, associated with long-term bisphosphonate therapy, which to our knowledge has not been reported previously. This case highlights the need of critical evaluation of patients with atypical fractures during long-term bisphosphonate therapy.

scholarly journals Atypical femur fractures: current understanding and approach to management

2020 ◽  
Vol 12 ◽  
pp. 1759720X2091698
Author(s):  
Lianne Tile ◽  
Angela M. Cheung
Keyword(s):  
Medical Therapy ◽  
Clinical Decision Making ◽  
Osteoporotic Fractures ◽  
Osteoporosis Treatment ◽  
Clinical Decision ◽  
Current Understanding ◽  
Rare Type ◽  
Femur Fractures ◽  
Atypical Femur Fractures

Osteoporosis and resulting osteoporotic fractures are responsible for significant morbidity, excess mortality, and health care costs in the developed world. Medical therapy for osteoporosis has been shown in multiple randomized controlled trials to reduce the risk of vertebral and non-vertebral fractures and hip fractures, and in some studies bisphosphonate medications have been associated with improved survival. Although the overall benefit to risk ratio of osteoporosis medications remains favorable, there have been concerns raised about the long-term safety of these treatments. Atypical femur fracture, which is a rare type of fracture that has been associated with the long-term use of potent antiresorptive bone medications, is a potentially devastating consequence of osteoporosis treatment. This paper reviews our current understanding of atypical femur fractures, their relationship to antiresorptive osteoporosis medications, and proposed strategies for management, in order to inform clinical decision making about the optimal use and duration of medical therapy for the treatment of patients with osteoporosis or at high risk for osteoporotic fractures.

scholarly journals Incidence of venous thromboembolism following initiation of non-steroidal anti-inflammatory drugs in U.S. women

Rheumatology ◽  
2020 ◽  
Vol 59 (9) ◽  
pp. 2502-2511
Author(s):  
Tracy L Kinsey ◽  
Til Stürmer ◽  
Michele Jonsson Funk ◽  
Charles Poole ◽  
Ross J Simpson ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Observational Studies ◽  
Health Study ◽  
Calendar Time ◽  
Vein Thrombosis ◽  
Hazard Ratios ◽  
Risk Patients ◽  
Inflammatory Drugs ◽  
Deep Vein

Abstract Objective To evaluate the risk of venous thromboembolism (VTE, i.e. deep vein thrombosis or pulmonary embolism, or both) following new use of NSAIDs in a long-term cohort of U.S. women. Methods We investigated initiation of coxibs and traditional NSAIDs (excluding aspirin) and incident VTE in 39 876 women enrolled in the Women’s Health Study from 1993–95 and followed with yearly questionnaires until 2012. We defined initiation as the first reported use of NSAIDs for ≥4 days per month. Incident VTE was confirmed by an end point committee. We estimated hazard ratios (HRs) and risk differences (RDs, expressed as percentages) comparing NSAID initiation with non-initiation and acetaminophen initiation (active comparator) via standardization using a propensity score that incorporated age, BMI, calendar time, and relevant medical, behavioural, and socioeconomic variables updated over time. Results The HR (95% CI) for risk of VTE in the as treated analyses comparing initiation with non-initiation, was 1.5 (1.2, 1.8) for any NSAID, 1.3 (1.1, 1.7) for traditional NSAIDs, and 2.0 (1.3, 3.1) for coxibs, with 2-year RDs 0.11, 0.08 and 0.32, respectively. When comparing the risk of VTE after initiation of any NSAID with that after acetaminophen initiation, the HRs were 0.9 (0.6, 1.5), 0.9 (0.5, 1.5) and 1.4 (0.6, 3.4), with 2-year RDs 0.03, –0.01, and 0.13, respectively. Conclusion New use of NSAIDs was associated with increased VTE risk compared with non-use, but the association was null or diminished when compared with acetaminophen initiation. Elevated VTE risks associated with NSAID use in observational studies may in part reflect different baseline risks among individuals who need analgesics and may overstate the risk patients incur compared with pharmacologic alternatives.

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