[Bisphosphonate-related osteonecrosis of the jaw]. / Bisfosfonaatgerelateerde osteonecrose van de kaak.

Osteonecrosis of the jaw in association with long-term use of bisphosphonates (BRONJ) is a relatively rare but serious side effect that is difficult to treat. The incidence of BRONJ in patients treated for osteoporosis is low at 0.1%. The incidence in cancer patients treated with high doses of intravenous bisphosphonates is higher, ranging between 3% and 10%. Risk factors for BRONJ are invasive treatments such as tooth extractions, root canal procedures and the placement of dental implants, as well as trauma caused by pressure from poorly fitting dental prostheses. High-risk patients should be examined by a dentist or an oral surgeon and, if necessary, undergo dental treatment prior to treatment with bisphosphonates. All patients taking bisphosphonates should maintain good oral hygiene, receive regular dental examinations and see a dentist if any oral symptoms develop. Physicians who prescribe medication as well as the patient's dentist and oral surgeon should be aware of the use of bisphosphonates and BRONJ as a possible adverse reaction. This requires cooperation and the exchange of information between a patient's health care providers.

Effect of concomitant CYP2D6 inhibitor use and tamoxifen adherence on breast cancer recurrence in early-stage breast cancer.

PURPOSE: The use of cytochrome P450 2D6-inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Concomitant use of CYP2D6 inhibitors, such as selective serotonin reuptake inhibitors, as well as low tamoxifen adherence may negatively impact tamoxifen efficacy in patients with breast cancer. The objectives of this study were to relate concomitant CYP2D6 inhibitor use and tamoxifen adherence to breast cancer event-free time (EFT). PATIENTS AND METHODS: Data were from PHARMO and included a community pharmacy dispensing database; PALGA, a nationwide pathology database; and the Dutch Medical Register in the Netherlands. Patients with breast cancer treated with adjuvant tamoxifen between 1994 and 2006 were included. A Cox proportional hazards model with a time-dependent definition for concomitant CYP2D6 inhibitor exposure was used. Adherence calculated over the first year after tamoxifen initiation was related to breast cancer events in the following period. RESULTS: In total, 1,962 patients with breast cancer using tamoxifen were included, among whom 150 (7.6%) frequently used a CYP2D6 inhibitor during tamoxifen treatment. No association between concomitant CYP2D6 inhibitor use and breast cancer recurrence was observed (adjusted hazard ratio [HR], 0.87; 95% CI, 0.42 to 1.79; P = .69). Poor tamoxifen adherence was associated with lower EFT (adjusted HR, 0.987; 95% CI, 0.975 to 0.999; P = .029). CONCLUSION: This observational study did not show an association between concomitant CYP2D6 inhibitor use and breast cancer recurrence among patients treated with adjuvant tamoxifen despite the strong biologic rationale. This study shows, to the best of our knowledge for the first time, that poor tamoxifen adherence is associated with an increased risk of breast cancer events.