Bisphosphonate-Related Osteonecrosis of the Jaw

Abstract

Objectives Antiresorptive agents for bone pain were widely used to treat patients with advanced osteoporosis, multiple myeloma, and bone metastatic cancer. In recent years, however, bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been a rare but major complication of this therapy. Most patients with BRONJ undergo dental procedures during treatment with antiresorptive agents. However, BRONJ may also occur spontaneously. This study reports 13 BRONJ patient cases at Kaohsiung Veterans General Hospital, Taiwan, and their related treatments. We also compare patients with cancer with patients with osteoporosis in treatment outcomes. Methods Thirteen symptomatic patients with BRONJ were reviewed between 1985 and 2018 at Kaohsiung Veterans General Hospital. We included patients at advanced stage who were hospitalized for infection control of osteonecrosis of the jaw and excluded asymptomatic patients at stage 0 and stage 1. Four multiple myeloma, 3 patients with bone metastatic breast cancer and 6 patients with advanced osteoporosis (average ages, 63.57 ± 14.54 years in cancer patients and 79.5 ± 9.31 years in osteoporosis patients; average drug durations, 25.86 ± 27.23 months in cancer patients and 58.33 ± 23.87 months in osteoporosis patients; average follow-up times, 22.71 ± 14.46 months in cancer patients and 28.08 ± 36.35 months in osteoporosis patients) were included. Results Seven patients were defined as having stage 3 (53.8%) and 6 as having stage 2 (46.2%) medication-related osteonecrosis of the jaw, according to the American Association of Oral and Maxillofacial Surgeons classification. The complete response rate with totally healed mucosa was 61.5%. Four cancer patients received free fibular flap (FFF) reconstruction with a high complete response rate (100%). All of them had a relatively better performance status, and the average age was also younger than osteoporosis patients. Conclusion Free fibular flap with a high complete response rate may improve pain relief and infection control for patients with BRONJ. Younger age is seemed to be a great indicator for FFF, but poor self-care ability (Eastern Cooperative Oncology Group status >3) is not suitable for these surgical treatments.

Biological and Clinical Aspects of Metastatic Spinal Tumors

“…Furthermore, the risk of osteonecrosis development is directly proportional to the duration of antiresorptive treatment and the dosage used [ 200 ]. The current management algorithm varies from providing good oral care and eliminating risk factors such as periodontal disease or tobacco smoking [ 200 , 201 , 202 ] to intravenous antibiotics and radical oral surgery in advanced cases [ 203 , 204 ]. However, prophylactic and treatment guidelines have not been established; thus, treatment of this complication may be challenging.…”

Osteonecrosis of the jaw with the use of bisphosphonates and treatment with laser therapy and magnetotherapy: a concise systematic review

“…N-BPs have much stronger anti-bone resorptive effects than non-N-BP, and BRONJ is caused by N-BP. Findings suggest that BRONJ may be induced by mechanisms mediated by phosphate transporters and promoted by infection and that etidronate and clodronate may be useful for preventing and treating BRONJ [1][2][3].…”

“…The main property of BP is to inhibit calcium phosphate precipitation, decrease calcification, and bone resorption, and reduce osteoclastic action, by inducing apoptosis of these cells, which reabsorb bone tissue. These have a great affinity with bone tissue, long half-life in bones, inhibiting bone resorption, and can be administered orally or intravenously [2,3,14].…”

Clinical values of serum Semaphorin 4D (Sema4D) in medication‑related osteonecrosis of the jaw

“…Medication-related osteonecrosis of the jaw (MRONJ) is a rare clinical disease that mainly occurs in patients with osteoporosis, bone metastases and other bone-destructive diseases who receive bisphosphonate therapy [ 7 , 8 ]. The pathogenesis of MRONJ remains unclear [ 9 ]. Accumulating evidence has demonstrated that MRONJ may be associated with imbalances in bone remodeling, inhibition of angiogenesis, inflammatory response to infection, and soft tissue toxicity [ 9 , 10 ].…”

“…The pathogenesis of MRONJ remains unclear [ 9 ]. Accumulating evidence has demonstrated that MRONJ may be associated with imbalances in bone remodeling, inhibition of angiogenesis, inflammatory response to infection, and soft tissue toxicity [ 9 , 10 ]. Most of the current research shows that the treatment plan of MRONJ should comprehensively consider the disease stage and the patient's systemic condition [ 11 ].…”