title: Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results.
abstract: Bisphosphonates are recommended in patients with osteolytic lesions secondary to multiple myeloma. We report on the safety of bisphosphonate therapy with long-term follow-up in the Medical Research Council Myeloma IX study. Patients with newly diagnosed multiple myeloma were randomised to zoledronic acid (ZOL; 4 mg intravenously every 21-28 d) or clodronate (CLO; 1600 mg/d orally) plus chemotherapy. Among 1960 patients (5.9-year median follow-up), both bisphosphonates were well tolerated. Acute renal failure events were similar between groups (ZOL 5.2% vs. CLO 5.8% at 2 years; incidence plateaued thereafter). The overall incidence of confirmed osteonecrosis of the jaw (ONJ) was low, but higher with ZOL (ZOL 3.7% vs. CLO 0.5%; P < 0.0001). ONJ events were generally low grade and most occurred between 8 and 30 months (median time to ONJ, 23.7 months). Among 10 patients with ONJ recovery data, four patients in the ZOL group completely recovered, two patients improved, and three patients experienced no improvement; one CLO patient experienced no improvement. Dental surgery or trauma preceded ONJ in six ZOL patients. The incidence of renal adverse events was similar for ZOL and CLO. ONJ incidence remained low and was lower with CLO compared to ZOL. We have seen no further ONJ cases to date.
authors.affiliation: University of Newcastle, Newcastle-upon-Tyne, UK.
authors.forename: Graham H
authors.initials: GH
authors.lastname: Jackson
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Walter M
authors.initials: WM
authors.lastname: Gregory
authors.forename: Sue E
authors.initials: SE
authors.lastname: Bell
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szubert
authors.forename: Nuria
authors.initials: N
authors.lastname: Navarro Coy
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.forename: Roger G
authors.initials: RG
authors.lastname: Owen
authors.forename: Sylvia
authors.initials: S
authors.lastname: Feyler
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ashcroft
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Ross
authors.forename: Jennifer
authors.initials: J
authors.lastname: Byrne
authors.forename: Huw
authors.initials: H
authors.lastname: Roddie
authors.forename: Claudius
authors.initials: C
authors.lastname: Rudin
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Boyd
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Osborne
authors.forename: Gordon
authors.initials: G
authors.lastname: Cook
authors.forename: J Anthony
authors.initials: JA
authors.lastname: Child
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000453:epidemiology / Q000209:etiology*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004002:Clodronic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004739:England / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D010014:Osteolysis / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D004002:Clodronic Acid; D000077211:Zoledronic Acid
keywords: clodronate; myeloma; osteonecrosis; renal injury; zolendronic acid