Bisphosphonates and osteonecrosis of the jaw: cause and effect or a post hoc fallacy? (original) (raw)
Related papers
Bisphosphonate-related osteonecrosis of the jaws: a single-center study of 101 patients
Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons, 2009
Osteonecrosis of the jaw (ONJ) is a devastating side effect of long-term bisphosphonate (BP) use. We present the largest case series from a single department. This case series included 101 ONJ patients. Data on demographics, medical background, type and duration of BP use, possible triggering events, mode of therapy, and outcome were recorded. ONJ was associated with intravenous BPs in 85 patients and with oral BPs in 16 patients. It was diagnosed after 48, 27, and 67 months of pamidronate, zoledronic acid, and alendronate use, respectively. Long-term antibiotics and minimal surgical procedures resulted in complete or partial healing in 18% and 52% of the patients, respectively; 30% had no response. There was no association between ONJ and diabetes, steroid and antiangiogenic treatment, or underlying periodontal disease. Diagnostic biopsies aggravated lesions without being informative about pathogenesis. A conservative regimen is our treatment of choice. Solutions for decreasing mor...
Bisphosphonate-induced osteonecrosis of the jaw: a medical enigma?
Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 2009
Bisphosphonates are used for the standard of care of patients with skeletal metastases and hypocalcemia of malignancy. Bisphosphonate-induced osteonecrosis (BION) is a serious complication. Clinically, BION presents as an area of exposed alveolar bone that occurs spontaneously or becomes evident following an invasive surgical procedure such as extraction of a tooth, periodontal surgery, apicoectomy, or oral implant placement. The mechanism by which bisphosphonates cause osteonecrosis is uncertain. There are no controlled trials to show a direct cause-effect relationship between bisphosphonates and osteonecrosis of the jaw. Oral bisphosphonate-induced necrosis is a rare clinical entity, less frequent, less aggressive, more predictable, and more responsive to treatment than IV forms of bisphosphonate-related osteonecrosis of the jaw. However, there have been reports of this complication with the less potent oral forms of bisphosphonates (0.007% to 0.01%). The morbidity of osteonecrosis of the jaw induced by IV bisphosphonates is significant, so prevention should receive prime importance. Patients should receive prophylactic dental examinations, and any necessary dental treatment before starting bisphosphonate therapy. Good communication among dentists, oral surgeons, physicians, and oncologists is of vital importance in providing care of these patients.
Bisphosphonates and jaw osteonecrosis: The UAMS experience
Otolaryngology - Head and Neck Surgery, 2007
BACKGROUND: Over the past year at least 10 case series and several case reports on osteonecrosis of the jaw (ONJ) have been published with most found in the oral surgery literature. This clinical entity is largely unknown to head and neck surgeons. METHODS: Retrospective chart review. RESULTS: A total of 479 charts were reviewed, identifying 25 individuals meeting inclusion criteria. Mean age was 63.4 (standard deviation, 9.9) years; 40% were female. Multiple myeloma was the most common comorbidity. Twenty-five patients were treated with bisphosphonates for 4.4 years (range, 1 to 8 years); most commonly pamidronate before ONJ diagnosis. Forty-two percent (10) took steroids within the month before diagnosis. Fifty-two percent (11) underwent dental work before developing ONJ. CONCLUSION: These data reflect the importance of awareness of the possibility of ONJ with bisphosphonate therapy.
Bisphosphonates and Osteonecrosis of the Jaw
Annals of Internal Medicine, 2006
Osteonecrosis of the jaw (ONJ) is an important but uncommon side effect of bisphosphonate therapy. ONJ may result in disabling and sometimes disfiguring complications that may affect the quality of life of patients. ONJ occurs more frequently in patients on intravenous nitrogen-containing forms of bisphosphonates and is thought to be time and dose dependent. Currently, there is no recognized effective treatment apart from controlling pain and accompanied infection. Prevention of this complication is therefore important. In this article, some of the key issues of bisphosphonate-associated ONJ are being reviewed.
Oral Diseases
Objectives: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. Subjects and methods: Retrospective analysis of data from 22 secondary care centres in 7 countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. Results: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in cancer patients treated with zoledronate.
The Challenge for the Dental Community-Bisphosphonate-Related Osteonecrosis of the Jaw
Bisphosphonates are a synthetic analogue of inorganic pyrophosphates, a potent inhibitor of osteoclast activity. They are used for the treatment of diseases characterized with a high level of bone resorption/multiple myeloma, osteolytic bone metastases, Paget’s disease of bone, fibrous dysplasia, McCune-Albright syndrome, hypercalcemia of tumour origin, etc. They feature slow intestinal absorption; they are excreted by the kidneys and have high affinity to hydroxyapatite crystals. They incorporate into skeletal bones without being degraded. Bisphosphonates attach to calcium in areas of high bone resorption and remain integrated in the bone for more than ten years/for example, the half-life of Alendronate is 12 years. Once administered, they trigger a cascade of biochemical processes resulting in loss of the ability of osteoclasts to resorb bone, or even to apoptosis of osteoclasts. Bisphosphonate therapy may cause some adverse effects/ kidney failure, arthralgia, fever, muscle pain, hypocalcemia and others. Bisphosphonate-related Osteonecrosis of the Jaw (BRONJ) is a severe, group-specific complication associated with the use of bisphosphonates. Most reported cases were caused by intravenous administration of bisphosphonates. There are a few case reports of osteonecrosis of the jaw caused by continuous oral administration. Marx RE [1], was the first to report 36 cases of “painful bone exposure of the lower and upper jaw in patients treated with bisphosphonates - pamidronate and zoledronate”.
Osteonecrosis of the Jaw and the Role of Bisphosphonates: A Critical Review
The American Journal of Medicine, 2009
Osteonecrosis of the jaw (ONJ), a condition characterized by necrotic exposed bone in the maxillofacial region, has been reported in patients with cancer receiving bisphosphonate therapy, and rarely in patients with postmenopausal osteoporosis or Paget disease of bone receiving such therapy. In the absence of a uniform definition, the American Academy of Oral and Maxillofacial Surgeons (AAOMS), the American Society for Bone and Mineral Research (ASBMR), and other groups have established similar diagnostic criteria for bisphosphonate-related ONJ, which is more commonly reported in patients with advanced malignancies with skeletal metastases who receive higher doses, and is more rarely reported in patients with osteoporosis and Paget disease who receive lower doses. However, a critical review of the literature reveals that the etiology of ONJ remains unknown, and to date no direct causal link to bisphosphonates has been established. Despite an increased awareness of ONJ and recent improvements in preventive strategies, patients and physicians alike continue to express concern about the potential risks of bisphosphonate treatment in both oncologic and nononcologic settings. Although much remains to be learned about this condition, including its true incidence in various patient populations, its pathophysiology, and optimal clinical management, evidence to date suggests that the positive benefits of bisphosphonates in patients with malignant bone disease, osteoporosis, or Paget disease outweigh the relatively small risk of ONJ.
Pathophysiology of osteonecrosis of the jaw in patients treated with bisphosphonate
Collegium antropologicum, 2013
Apart from the well-known mechanism of bisphosphonates' cellular effect, embryonic development and the specific features of alveolar bone homeostasis have been discussed. The unique ethiopathogenic mechanism which relates osteonecrosis of the jaw and bisphosphonates treatment has not been explained. The emphasis lies on the toxicological effects of bisphosphonates on the physiology of the alveolar bone and on the lasting effect of tooth extraction followed by an infection of the extraction wound and consequent progression into deeper layers of osseous tissue. Epithelial infection includes microbiological findings of Actinomyces species. The risk is pronounced in oncological patients treated with bisphosphonates intravenously in relatively large doses and during a longer period of time, especially with highly potent nitrogen-containing bisphosphonates pamidronate and zoledronate. This review of bisphosphonate-related osteonecrosis of the jaw stresses the significance of some othe...
Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases
Journal of Cancer Research and Clinical Oncology, 2010
Purpose Bisphosphonates (BPs) are bone-remodeling inhibitors that are used to manage bone metastases and osteoporosis. Osteonecrosis of the jaw, however, can occur during treatment. This complication is poorly understood and is called ''bisphosphonate-induced osteonecrosis of the jaw'' (BIOJ). Methods We performed a PubMed-based review of all of the described cases of BIOJ from January 2003 (the year of the first description) to September 2009. Issues of clinical relevance, such as the primary diagnosis and type of treatment, were evaluated for each patient case. Results We retrieved 2,408 cases, 88% of which were associated with intravenous therapy, primarily with zoledronate. Of the total number of cases, 89% were associated with the treatment of a malignant condition, particularly multiple myeloma (43% of the cases). Of all the BIOJ cases, 67% were preceded by tooth extraction and only 35% of patients were cured. Conclusion Prevention is better than treatment, and the establishment of meticulous oral hygiene and surgical procedures prior to commencing BP treatment is important for preventing BIOJ. Our review summarizes the current knowledge about this severe complication. Future studies, especially basic research studies, are needed to better understand this devastating disease.