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Jaw osteonecrosis: 9 case reports Nine patients [see table for patient characteristics] developed jaw osteonecrosis during treatment with antineoplastics [duration of treatment not stated] and bisphosphonates for multiple myeloma.

Patient characteristics Patient Age Sex (years) 1 2 3

80 66 58

F M M

4

44

F

5

71

F

6 7 8 9

80 58 65 52

F M F F

Bisphosphonate, treatment duration Pamidronic acid (60 months) Pamidronic acid (42 months) Pamidronic acid /zoledronic acid (44 months) Pamidronic acid /zoledronic acid (10 months) Pamidronic acid /zoledronic acid (57 months) Zoledronic acid (10 months) Zoledronic acid (6 months) Zoledronic acid (17 months) Zoledronic acid (24 months)

1

patients 2, 6, 8 and 9, despite persistent bone exposure. However, patients 1 and 3 developed oroantral communication with suppurating cutaneous fistula of their necks. Patients 4, 5 and 7, who had areas of necrotic, exposed bone, without secondary infection, were followed up and received conservative treatment with local wound care and irrigations. Bone necrosis persisted in all patients for 4–9 months; none completely recovered. Author comment: "All patients included in our series developed [jaw osteonecrosis] after treatment with bisphosphonates. Nevertheless, as these patients. . . were simultaneously taking multiple drugs, including cancer chemotherapy and corticosteroids, both of which can affect wound healing, an exclusive role in inducing [jaw osteonecrosis] cannot be attributed to bisphosphonates." Capalbo S, et al. Jaw osteonecrosis associated with use of bisphosphonates and chemotherapy: paradoxical complication of treatment of bone lesions in multiple myeloma patients. International Journal of Hematology 83: 439-442, No. 5, Jun 2006 - Italy 801044237

Patients 1, 2, 3, 5 and 6 received monthly pulses of oral melphalan plus prednisone [dosages not stated], which was preceded in patient 6 by radiotherapy. The remaining patients received four courses of an IV combination of doxorubicin, vincristine and dexamethasone [dosages not stated]; this was followed by high-dose IV melphalan (200 mg/m2) in patients 4, 7, and 9. By the onset of jaw osteonecrosis, four patients had experienced a relapse of multiple myeloma: patients 2 and 8 required treatment with monthly pulses of oral melphalan plus prednisone [dosages not stated], patient 1 received IV cyclophosphamide plus dexamethasone 4-weekly [dosage not stated] and patient 4 received oral thalidomide daily [dosage not stated]. Four patients (patients 6–9) began receiving zoledronic acid alone [dosage not stated]; five patients began receiving IV pamidronic acid 90mg at monthly intervals which was then switched to IV zoledronic acid 4mg at monthly intervals in cases 3–5. All patients had recurrent dental abscesses, treated with antibacterials, and underwent tooth extraction prior to osteonecrosis onset. Osteonecrosis affected the mandible in patients 1–6, and the maxilla in patients 7, 8 and 9.The mean time from initiation of bisphosphonates to oral jaw osteonecrosis onset was