|
1: Clin Cancer Res. 2006 Oct 15;12(20):6309s-14s.
Skeletal complications of breast cancer therapies.
Hirbe A, Morgan EA, Uluckan O, Weilbaecher K.
Authors' Affiliation: Division of Oncology, Departments of Medicine and Cellular Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri.
Nonsurgical treatment options, such as hormonal therapy, chemotherapy, radiation, and bisphosphonate therapy, are undoubtedly improving outcomes for women with breast cancer; however, these therapies also carry significant skeletal side effects. For example, adjuvant hormonal treatments, such as aromatase inhibitors that disrupt the estrogen-skeleton axis, have the potential to cause decreased bone mineral density. Similarly, chemotherapy often induces primary ovarian failure in premenopausal women, resulting in decreased levels of circulating estrogen and subsequent osteopenia. In both cases, women receiving these therapies are at an increased risk for the development of osteoporosis and skeletal fracture. Furthermore, women undergoing radiation therapy to the upper body may have an increased incidence of rib fracture, and those receiving bisphosphonates may be vulnerable to the development of osteonecrosis of the jaw. Therefore, women with breast cancer who are undergoing any of these therapies should be closely monitored for bone mineral loss and advised of skeletal health maintenance strategies.
2: Expert Opin Drug Saf. 2006 Nov;5(6):743-5.
Osteonecrosis of the jaw: what do bisphosphonates do?
Aspenberg P.
Osteonecrosis of the jaw is a new disease, partly caused by bisphosphonates. It is commonly assumed that the bisphosphonates somehow cause cell death (osteocyte necrosis) within the jawbone, which makes it prone to chronic infection. In this article, an alternative pathogenetic theory is suggested, based on the normal effect of bisphosphonates. According to the new theory, the bone is alive until it is injured and infected, and the reduced resorptive ability due to bisphosphonates hinders the formation of a fresh bone surface for re-establishment of bone cell coverage. The theories are compared, based on the recent, very scarce literature. None of them can be completely refuted, but the demonstration of living osteocytes within the lesion and the number of necessary assumptions speak against the theory of a primary, bisphosphonate-induced necrosis.
3: Aust Fam Physician. 2006 Oct;35(10):801-3
Bisphosphonates and osteonecrosis of the jaw.
Sambrook P, Olver I, Goss A.
Australian and New Zealand Bone and Mineral Society, Osteoporosis Australia, Medical Oncology Group of Australia, and the Australian Dental Association, Australia.
Recently an association between bisphosphonate use and a rare dental condition termed 'osteonecrosis of the jaw' (ONJ) has been reported. Patients with osteoporosis and Paget disease who take bisphosphonates have a significantly reduced risk of fracture and other skeletal complications. This represents significant health benefits, against which the small risk of ONJ needs to be considered. In patients with bone malignancy, the risk of ONJ needs to be balanced against the benefit of therapy on the underlying malignancy. There are still many uncertainties about this condition. This position paper seeks to summarise what is currently known about ONJ to provide information to medical practitioners and dental practitioners.
4: Rev Endocr Metab Disord. 2006 Oct 17;
Postmenopausal osteoporosis. What have we learned since the introduction of bisphosphonates?
Chaiamnuay S, Saag KG.
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA.
Over the past 12 years bisphosphonates have become a mainstay of treatment for postmenopausal osteoporosis. As a class, bisphosphonates significantly suppress bone turnover and increase BMD at the lumbar spine and other site through their direct inhibitory effects on osteoclasts. Alendronate and risedronate reduce the incidence of clinical vertebral and non-vertebral fractures. Etidronate and both oral and intravenous ibandronate reduce the incidence of clinical vertebral fractures, but data from primary analyses for reduction in non-vertebral fractures are currently less robust. Intravenous administration of zoledronate is under late-stage investigation for use in postmenopausal osteoporosis. Combinations of alendronate with estrogen or raloxifene provide a greater reduction in bone turnover markers and greater increases in BMD, but fracture risk reduction has not been determined. Overall, bisphosphonates are well tolerated. The most common side effects of oral bisphosphonates are upper gastrointestinal symptoms. Newer safety concerns about the use of bisphosphonates include osteonecrosis of the jaw and oversuppression of bone turnover. The optimal duration of bisphosphonate treatment has not been clearly established.
5: Oncology (Williston Park). 2006 Aug;20(9):1053-62; discussion 1065-6
Osteonecrosis of the jaw in cancer patients receiving IV bisphosphonates.
Van Poznak C, Estilo C.
Department of Internal Medicine, University of Michigan, Comprehensive Cancer Center, Ann Arbor 48109-0848, USA.
Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past few years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate therapy but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. The condition involves exposed bone of the maxilla or mandible. Although it is often associated with a recent dental surgical procedure, spontaneous ONJ can also occur. Patients commonly present with symptoms. Through case reporting and clinical experience, there is a suggestion that the incidence of ONJ in patients with cancer receiving intravenous bisphosphonates ranges between 1% and 10%. Management of ONJ focuses on maximizing oral health, conservative actions with mouth rinses, antibiotics, and avoidance of unnecessary invasive dental procedures. The currently available data on ONJ are reviewed.
6: Wien Klin Wochenschr. 2006 Aug;118(15-16):473-8.
Osteonecrosis of the jaws and bisphosphonate treatment in cancer patients.
Wutzl A, Eisenmenger G, Hoffmann M, Czerny C, Moser D, Pietschmann P, Ewers R, Baumann A.
Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Austria. arno.wutzl@meduniwien.ac.at
PURPOSE: Osteonecrosis of the jaws is described as an intraoral complication after administration of intravenous nitrogen-containing bisphosphonates. In a retrospective study, patients with osteonecrosis of the jaws after bisphosphonate treatment were evaluated with regard to diagnostic investigations and therapeutic management. PATIENTS AND METHODS: Seventeen patients with osteonecrosis of the jaws after bisphosphonate treatment who were referred to our department between July 2004 and June 2005 were included in this study. Computer tomography, magnetic resonance imaging, scintigraphy, bacteriology and biopsy were used in diagnostic evaluation. All patients were treated surgically. RESULTS: The reasons for bisphosphonate treatment were multiple myeloma in 12 patients, breast cancer with bone metastasis in four patients and histiocytosis X in one patient. Five patients had received intravenous pamidronate and 12 patients zoledronic acid. The median number of treatment cycles for pamidronate was 36 times (range 4-100) in 38 months (range 4-100). Zolendric acid was given 23.5 times (range 5-39) in 26 months (range 5-39). Nine patients had a lesion in the mandible, eight in the maxilla. Clinical symptoms were exposed bone, pain and local inflammation of the mucosa. Computer tomography showed sclerotic areas in the osteonecrosis zone. The biopsy did not show a metastatic lesion. Sequestrectomy and decortication was adequate in the follow-up. CONCLUSION: Nitrogen-containing bisphosphonates appear to be associated with the risk of developing osteonecrosis of the jaws. To reduce this risk, patients should be evaluated by a dentist before beginning treatment with intravenous bisphosphonates.
7: J Dent Hyg. 2006 Summer;80(3):10. Epub 2006 Jul 1.
Bisphosphonate-associated osteonecrosis of the jaw: a literature review and clinical practice guidelines.
Pickett FA; American Academy of Oral Medicine.
East Tennessee State University, Dental Hygiene Program, USA. fpickett@preferred.com
BACKGROUND: Osteonecrosis of the jaw has recently been reported as a possible adverse drug effect from bisphosphonate therapy. Reports are coming from all over the world. Norvartis, a pharmaceutical manufacturer of two implicated drug products, has notified dentists in the United States and made recommendations for dental management of cases. MECHANISM OF ACTION: The exact mechanism of bisphosphonate effects leading to osteonecrosis of the jaw is unknown. The condition can affect both the maxilla and the mandible. Most cases developed following oral infection or dental treatment. PREVENTION AND MANAGEMENT: Clinical guidelines for prevention and management have recently been published. Dental hygienists have a major role in patient education related to awareness of the potential drug effect and to preventive oral health education.
8: Dent Today. 2006 Aug;25(8):52, 54-7.
Bisphosphonate-associated osteonecrosis of the jaw: conclusions based on an analysis of case series.
Landesberg R, Wilson T, Grbic JT.
Division of Oral and Maxillofacial Surgery, Columbia University College of
Dental Medicine, USA. RL1351@columbia.edu
ONJ appears to be associated with BPs; however, the pathophysiology, incidence, and co-morbidities require further investigation. The major risk factors identified to date appear to be cancer (or chemotherapy for cancer) and dental procedures or oral trauma. A clear definition of ONJ is critical to understanding this disease entity. Although recommendations regarding the prevention and management of ONJ exist, clinical studies are needed to establish more definitive guidelines for the management of ONJ. The use of intensive hyperbaric oxygen therapy may be beneficial to patients with ONJ.
9: Mayo Clin Proc. 2006 Aug;81(8):1100-3.
Primary surgical therapy for osteonecrosis of the jaw secondary to bisphosphonate therapy.
Kademani D, Koka S, Lacy MQ, Rajkumar SV.
Division of Oral Diagnosis and Oral and Maxillofacial Surgery, Mayo Clinic
College of Medicine, Rochester, MN 55905, USA. kademani.deepak@mayo.edu
Bisphosphonate chemotherapy is commonly used in the treatment of bone diseases such as osteoporosis, Paget disease, and multiple myeloma and to limit bone pain and hypercalcemia associated with malignant metastatic bone lesions. The introduction of bisphosphonate therapy has improved the quality of life in a vast majority of patients, showing clear medical efficacy. However, since 2003 a growing number of reports have described necrotic bone lesions (osteonecrosis of the jaw [ONJ]) affecting maxillofacial bones in patients who have received chemotherapy with intravenous bisphosphonate therapy. Unfortunately, the development of ONJ has been refractory to conventional treatment modalities. Several treatment options have been proposed for ONJ, most of which focus
primarily on conservative management with local irrigation and empirical
long-term antibiotic therapy. However, results of treatment have been associated with high failure rates, progression of disease, and continued decline in patients' quality of life. We describe 2 patients in whom primary surgical salvage was performed successfully for ONJ. Our experience indicates that with appropriate technique, primary surgical treatment may offer benefit to selected patients with ONJ. |
|
