Osteonecrosis with bisphosphonates

Actonel contains risedronate sodium, a bisphosphonate. Osteonecrosis of the jaw has been reported in patients receiving oral bisphosphonates. Adequate oral hygiene should be maintained during and after treatment with bisphosphonates, including Actonel. Preventive dental treatment should be considered before starting bisphosphonates. Patient should be advised to maintain adequate oral hygiene during treatment. 

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g., cancer, chemotherapy, corticosteroid use, poor oral hygiene). While on bis-phosphonate treatment, patients with concomitant risk factors should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. 

Arduino PG, Menegatti E, Scoletta M et al (2011) Vascular endothelial growth factor genetic polymorphisms and haplotypes in female patients with bisphosphonate-related osteonecrosis of the jaws. J Oral Pathol Med 40 510-515... 

Katz J, Gong Y, Salmasinia D et al (2011) Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw. Int J Oral Maxillofac Surg 40 605-611... 

Bone marrow depression due to damage to the growing stem cells causes reduction in the blood white cell, platelet, and red cell counts. These, in turn, could cause susceptibility to infections, excessive bleeding, and anemia. In addition, certain drugs cause unique and serious bone damage, such as the osteonecrosis of the jaw associated with bisphosphonates [88]. 

In a 4-year study of 102 patients with osteonecrosis of the jaw associated with bisphosphonates, 24 had non-neoplastic diseases, and had used bisphosphonates mainly for postmenopausal osteoporosis (n = 20) [13 ]. The duration of therapy before the diagnosis of osteonecrosis was 11 0 months and the most common triggering event was dentoalveolar surgery. All were non-smokers six had multiple lesions and only three had possible co-morbidities. Surgical debridement was performed in 19 patients for a total of 22 lesions there was complete remission in 21 of the lesions. 

Tunick SJ, Huryn JM. Osteonecrosis of the maxilla and mandible in patients with advanced cancer treated with bisphosphonate therapy. Oncologist 2008 13(8) 911-20. 

La Verde N, Bareggi C, Garassino M, Borgonovo K, Sburlati P, Padretti D, Bianchi C, Perrone S, Mihali D, Cobelli S, Mantica C, Rizzo A, Farina G. Osteonecrosis of the jaw (ONJ), in cancer patients treated with bisphosphonates how the knowledge of a phenomenon can change its evolution. Support Care Cancer 2008 16(11) 1311-5. 

Bisphosphonates have been shown to be highly effective in osteoporosis, cancer bone metastasis, multiple myeloma, and Paget s disease of bone. While generally very well tolerated, these drugs do have potential adverse effects. Recently, the association of long-term high dose bisphosphonate treatment with osteonecrosis of the jaw has been described. This is a potentially serious side effect seen mostly in patients with multiple myeloma or... 

Bone disease is a common manifestation of multiple myeloma. Bisphosphonates should be initiated in symptomatic patients with bone lesions to slow osteopenia and reduce the fracture risk associated with the disease. Pamidronate and zolendronic acid have equivalent efficacy in the management of osteolytic lesions, but because of relative ease of administration, zolendronic acid is used most frequently.43 The use of zolendronic acid decreases pain and bone-related complications and improves quality of life. The suggestion that bisphosphonates have direct antimyeloma activity, based on the ability to inhibit NF-kB signaling, remains controversial. Recent cases of osteonecrosis of the jaw have been a major concern. Risk factors are unclear, but osteonecrosis of the jaw is more common in patients receiving intravenous administration of bisphosphonates and having dental procedures performed. It is recommended that patients... 

The most common bisphosphonate adverse effects are nausea, abdominal pain, and dyspepsia. Esophageal, gastric, or duodenal irritation, perforation, ulceration, or bleeding may occur when administration directions are not followed or when bisphosphonates are prescribed for patients with contraindications. The most common adverse effects of IV bisphosphonates include fever, flu-like symptoms, and local injection-site reactions. Osteonecrosis of the jaw occurs rarely if it develops, oral chlorhexidine washes, systemic antibiotics, and systemic analgesics are used based on severity. 

Sarasquete ME, Garcia-Sanz R, Marin L et al (2008) Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma a genome-wide single nucleotide polymorphism analysis. Blood 112 2709-2712... 

English BC, Baum CE, Adelberg DE et al (2010) A SNP in CYP2C8 is not associated with the development of bisphosphonate-related osteonecrosis of the jaw in men with castrate-resistant prostate cancer. Ther Clin Risk Manag 6 579-583... 

Osteonecrosis of the jaw Osteonecrosis of the jaw is a well-known adverse reaction to bisphosphonates in patients with multiple myeloma or other malignancies. Its incidence is still undetermined, and only a few cases in patients taking bisphosphonates for non-oncological diseases have been reported. The EIDOS and DoTS descriptions of this reaction are shown in Figure 1. 

Osteonecrosis of the jaw can occur after treatment with any kind of bisphosphonate, whether alkylbisphosphonates or aminobis-phosphonates, as reflected by the case of a patient taking clodronate, an alkylbisphospho-nate A systematic literature review... 

Most cases of bisphosphonate-related osteonecrosis occur after intravenous administration of bisphosphonate treatment for malignant bone disease and metastatic cancer. As the incidence of osteonecrosis caused by oral administration is low, it is believed that bisphosphonates are relatively safe and effective in preventing the complications of osteoporosis, such as hip or spine fractures. Osteonecrosis caused by oral bisphosphonates has been described in five Asian women aged over 65 years [15 ]. Three had also used glucocorticoids for rheumatoid arthritis. Irrespective of race, the elderly women undergoing glucocorticoid therapy have an increased incidence of osteonecrosis even with oral bisphosphonates. 

The CHMP has defined osteonecrosis related to bisphosphonates as an area of exposed or dead bone in the jaw that has lasted for more than 8 weeks in a patient who has been exposed to a bisphosphonate and has not had radiation to the jaw. The CHMP noted that the risk of osteonecrosis is greater in patients with cancers receiving intravenous bisphosphonates than in patients with other indications, such as osteoporosis. The risk is low in patients taking bisphosphonates by mouth, though the most important susceptibility factors seem to be the potency of the bisphosphonate, the dose, and how it is given. Finally, the Committee has recommended that... 

The prevalence of osteonecrosis of the jaw has been studied in 75 patients with breast cancer taking bisphosphonates for osseous metastases [14 ]. Four patients (5.3%) developed osteonecrosis three had used zoledronate only and one had first used pamidronate followed by zoledronate and ibandronate. Tooth extraction was identified as a trigger factor for osteonecrosis in two patients. 

The incidence and susceptibihty factors in cases of bisphosphonate-induced osteonecrosis of the jaw have been studied in patients with breast cancer and gynecological mahgnancies [16 ]. Of 345 patients, 10 (2.9%) developed osteonecrosis while taking bisphosphonates. Six had a history of... 

Susceptibility factors for osteonecrosis of the jaw have been sought in 34 cases [17 ]. The most frequently used bisphosphonate was zoledronic acid (n = 29). Microbiological data obtained in 25 patients showed that 72% of these were infected or colonized by an actinomycete. Eight of the 14 patients who received only medical treatment were cured. Of the 20 patients who underwent surgical treatment, only four were completely cured. Osteonecrotic lesions smaller than 1 cm were associated with a better prognosis in terms of treatment outcomes. Local treatments combined with long-term antibiotics also correlated with a better prognosis. 

A 74-year-old woman, who was referred for evaluation of pain and persistently abnormal exposure of jaw bone after extraction of teeth, had been using weekly oral alendronate for osteoporosis for about 5 years. She had the clinical features of bisphosphonate-associated osteonecrosis of the mandible, which was precipitated by extraction of teeth 14 months before she was referred for assessment. She had multiple susceptibility factors for osteonecrosis of the jaw, including older age, type 2 diabetes mellitus, and a long duration of bisphosphonate therapy. The mandibular lesions did not improve despite repeated operations over 14 months. Bisphosphonate therapy was withdrawn and parathyroid hormone therapy was started after 2 months the oral mucosa had healed, after 4 months the pain had completely subsided, and after 6 months the patient s eating and drinking habits had returned. The serum concentration of osteocalcin, a marker of bone formation, which was initially suppressed, increased by 174% from baseline after 6 months of treatment with parathyroid hormone. 

Song KE, Myn YK, Lee JK, Lee KB, Joo HI, Kwack KS, Chung YS. A probable case of oral bisphosphonate-associated osteonecrosis of the jaw and recovery with parath5froid hormone treatment. Curr Ther Res Clin Exp 2008 69(4) 356-62. 

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