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.

New Frontiers in Osteoporosis Therapy

2020 ◽  
Vol 71 (1) ◽  
pp. 277-288 ◽  
Author(s):  
Cheng Cheng ◽  
Kelly Wentworth ◽  
Dolores M. Shoback
Keyword(s):  
Genetic Disorders ◽  
Femoral Fractures ◽  
Clinical Trial Data ◽  
Osteonecrosis Of The Jaw ◽  
Bone Biology ◽  
Mineral Density ◽  
Osteoporosis Therapy ◽  
Peptide Analog ◽  
Sequential Treatments

Current osteoporosis medications reduce fractures significantly but have rare and serious adverse effects (osteonecrosis of the jaw, atypical femoral fractures) that may limit their safety for long-term use. Insights from basic bone biology and genetic disorders have led to recent advances in therapeutics for osteoporosis. New approaches now in clinical use include the antisclerostin monoclonal antibody romosozumab, as well as the parathyroid hormone–related peptide analog abaloparatide. Clinical trial data show significant antifracture benefits with recently approved romosozumab. Studies using abaloparatide build on our longstanding experience with teriparatide and the importance of consolidating the bone mineral density gains achieved from an anabolic agent by following it with an antiresorptive. Combination and sequential treatments using osteoporosis medications with different mechanisms of action have also been tested with promising results. On the horizon is the potential for cell-based therapies (e.g., mesenchymal stem cells) and drugs that target the elimination of senescent cells in the bone microenvironment.

scholarly journals THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis

2018 ◽  
Vol 179 (1) ◽  
pp. R31-R45 ◽  
Author(s):  
Athanasios D Anastasilakis ◽  
Stergios A Polyzos ◽  
Polyzois Makras
Keyword(s):  
Fracture Risk ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Mineral Density ◽  
Atypical Femoral Fractures ◽  
Term Administration ◽  
Treatment Naïve ◽  
Fracture Risk Reduction ◽  
Pretreated Patients

The most widely used medications for the treatment of osteoporosis are currently bisphosphonates (BPs) and denosumab (Dmab). Both are antiresorptives, thus targeting the osteoclast and inhibiting bone resorption. Dmab achieves greater suppression of bone turnover and greater increases of bone mineral density (BMD) at all skeletal sites, both in naïve and pretreated patients. No superiority on fracture risk reduction has been documented so far. In long-term administration, BPs reach a plateau in BMD response after 2–3 years, especially at the hip, while BMD increases progressively for as long as Dmab is administered. Both BPs and Dmab are generally considered safe, although they have been correlated to rare adverse events, such as osteonecrosis of the jaw and atypical femoral fractures. Dmab should be preferred in patients with impaired renal function. BPs are embedded in the bone, from which they are slowly released during bone remodeling, therefore continuing to act for years after their discontinuation. In contrast, Dmab discontinuation fully and rapidly reverses its effects on bone markers and BMD and increases the risk for fractures; therefore, Dmab discontinuation should be discouraged, especially in previously treatment-naïve patients, regardless of the conventional fracture risk. In case of discontinuation, other treatment, mainly BPs, should immediately follow, although the optimal sequential treatment strategy is yet to be defined. Combination of teriparatide with Dmab or zoledronic acid, but not alendronate, provides increased BMD gains at all sites. In conclusion, both BPs and Dmab are safe and efficient therapeutic options although their particularities should be carefully considered in an individual basis.

Risk factors for development of atypical femoral fractures in patients on long-term oral bisphosphonate therapy

Bone ◽  
2013 ◽  
Vol 56 (2) ◽  
pp. 426-431 ◽  
Author(s):  
Paola Franceschetti ◽  
Marta Bondanelli ◽  
Gaetano Caruso ◽  
Maria Rosaria Ambrosio ◽  
Vincenzo Lorusso ◽  
...  
Keyword(s):  
Risk Factors ◽  
Femoral Fractures ◽  
Bisphosphonate Therapy ◽  
Atypical Femoral Fractures ◽  
Oral Bisphosphonate

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 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.

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