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Ann R Coll Surg Engl 2010; 92: 489-494 489Bisphosphonate-related osteonecrosis of the jaws (BRONJ), first described by Marx, 1 is defined as jaw necrosis occurring either spontaneously or, more commonly, after simple dento-alveolar surgery in patients on bisphosphonates, commonly with the intravenous (i.v.) form of the drug. Bisphosphonates are non-metabolised analogues of pyrophosphate that localise to bone inhibiting the dissolution of hydroxyapatite crystals preventing bone resorption.2,3 Other effects include reducing blood flow and antiangiogenic properties, 4 contributing to the ischaemic changes noted in the affected jawbones. Bisphosphonates are preferentially deposited in bones with high turn-over rates, since the maxilla and mandible are sites of significant remodelling, it is possible that the levels of the drug within the jaw are selectively elevated.2 BRONJ is a multifactorial event with multicellular impairments, resulting in altered wound healing. 5Cancer patients with metastatic or primary bone lesions often develop sequential skeletal complications and hypercalcaemia of malignancy.6 Intravenous bisphosphonates are primarily used in the management of cancer-related hypercalcaemia and skeletal-related events associated with bone metastases including pain, pathological fracture, spinal cord compression, mostly with solid tumours such as breast, prostate and lung cancers.6 They are also effective in the management of lytic lesions in the setting of multiple myeloma; 7 multiple myeloma patients appear to have a uniquely elevated risk for the development of the condition as the disease itself is present in bone. 8 The most prevalent and common indication for oral bisphosphonates is osteoporosis. RESULTS Of the 41 patients, four developed BRONJ, two in maxilla, one in mandible and one bimaxillary. Patients with BRONJ were older; mean age was 69.3 ± 3.1 years compared to 62.8 ± 12.5 years (P = 0.022). Dental co-morbidities were more commonly present in patients with the disease (P = 0.038). Patients who developed BRONJ were on treatment for a longer duration of time; the mean duration of treatment was 23.5 ± 8.4 months compared to 11.9 ± 13.4 months (P = 0.10). CONCLUSIONS The results of this case series demonstrated that age and poor oral health status are significant risk factors of BRONJ for oncology patients on long-term frequent dosing schedule of i.v. bisphosphonates.

Background Serratiopeptidase has been clinically used in controlling surgical and non-surgical inflammatory conditions. This study was conducted to assess the therapeutic effect of Serratiopeptidase in patients undergoing surgical removal of impacted mandibular third molar. Methods This randomized clinical trial investigated the efficacy of Serratiopeptidase and Paracetamol after surgical removal of impacted third molar for 5 days (n = 67) as compared with an equivalent dose of placebo and Paracetamol (n = 66). Outcome measures were reported pain, trismus and swelling using Laskin method. All outcome measures were recorded on days 0, 1, 2, 4, and 5 post-surgeries. Results In this clinical trail 133 patients (mean age 23 years, 54% female) completed the study. Baseline characteristics were comparable across treatment groups. Serratiopeptidase significantly improved trismus compared with control on the 4th day (27.30 ± 7.3 mm and 32.06 ± 7.7 mm, respectively (P < 0.001) Swelling markedly improved, The distance from the lower edge of the earlobe to the midpoint of the symphysis for cases vs control were 111.49 ± 8.1 mm and 115.39 ± 9.9 mm, respectively (P < 0.001). Reported pain, showed no statistical significance difference. Conclusion Serratiopeptidase resulted in better inflammation improvement than placebo over 5 days. Further studies are warranted to assess longer-term and clinical outcomes, as well as safety. Clinical relevance Serratiopeptidase administered postoperatively helps in improving trismus and swelling after removal of impacted lower third molars. Trial registration The study was registered in ClinicalTrial.gov under the number NCT02493179. Registered 1st of June 2015, https://clinicaltrials.gov/ct2/results?cond=serratiopeptidase.

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