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Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results

Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results
Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results
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.
myeloma, osteonecrosis, renal injury, clodronate, zolendronic acid
0007-1048
109-117
Jackson, Graham H.
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Morgan, Gareth J.
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Davies, Faith E.
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Wu, Ping
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Gregory, Walter M.
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Bell, Sue E.
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Szubert, Alexander J.
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Navarro Coy, Nuria
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Drayson, Mark T.
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Owen, Roger G.
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Feyler, Sylvia
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Ashcroft, Andrew J.
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Ross, Fiona M.
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Byrne, Jennifer
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Roddie, Huw
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Rudin, Claudius
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Boyd, Kevin D.
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Osborne, Wendy L.
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Cook, Gordon
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Child, J. Anthony
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Jackson, Graham H.
82e8cc2d-7530-4b02-8f92-176f47451839
Morgan, Gareth J.
d285dcf8-ac2c-4fe0-acf9-4787eb025939
Davies, Faith E.
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Wu, Ping
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Gregory, Walter M.
4a7a4c5a-0a88-4ba2-8f08-0c035dd0b6db
Bell, Sue E.
4a926468-0ec4-4191-9842-5e9117d07883
Szubert, Alexander J.
f83d6436-08ec-46ea-878a-14fa54b27dc0
Navarro Coy, Nuria
fced386a-f467-4852-813f-d7e81cc9e716
Drayson, Mark T.
282a00f4-8edf-4075-a83c-272ffcce53e8
Owen, Roger G.
5846329e-f7a0-44d9-ac7a-717fb76ff9b5
Feyler, Sylvia
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Ashcroft, Andrew J.
cd992e39-ba82-44b8-a3c9-249b85f14042
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Byrne, Jennifer
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Roddie, Huw
1196845f-22f3-4240-bc41-2a2035721c9d
Rudin, Claudius
187e4beb-781d-4ffc-b8a1-83df6ed306e8
Boyd, Kevin D.
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Osborne, Wendy L.
c8ba0fc6-58eb-4ce3-ab6a-cf97b9beae01
Cook, Gordon
4fe17be9-5e4e-4a58-a09a-b76f07f410f4
Child, J. Anthony
1a7a739b-5295-4818-a455-3c67d9020abc

Jackson, Graham H., Morgan, Gareth J., Davies, Faith E., Wu, Ping, Gregory, Walter M., Bell, Sue E., Szubert, Alexander J., Navarro Coy, Nuria, Drayson, Mark T., Owen, Roger G., Feyler, Sylvia, Ashcroft, Andrew J., Ross, Fiona M., Byrne, Jennifer, Roddie, Huw, Rudin, Claudius, Boyd, Kevin D., Osborne, Wendy L., Cook, Gordon and Child, J. Anthony (2014) Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results. British Journal of Haematology, 166 (1), 109-117. (doi:10.1111/bjh.12861). (PMID:24673708)

Record type: Article

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.

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More information

Accepted/In Press date: 27 March 2014
Published date: July 2014
Keywords: myeloma, osteonecrosis, renal injury, clodronate, zolendronic acid
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 364168
URI: http://eprints.soton.ac.uk/id/eprint/364168
ISSN: 0007-1048
PURE UUID: b44df13b-d9d8-4b11-a246-17e428269e7d

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Date deposited: 07 Apr 2014 16:19
Last modified: 14 Mar 2024 16:31

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Contributors

Author: Graham H. Jackson
Author: Gareth J. Morgan
Author: Faith E. Davies
Author: Ping Wu
Author: Walter M. Gregory
Author: Sue E. Bell
Author: Alexander J. Szubert
Author: Nuria Navarro Coy
Author: Mark T. Drayson
Author: Roger G. Owen
Author: Sylvia Feyler
Author: Andrew J. Ashcroft
Author: Fiona M. Ross
Author: Jennifer Byrne
Author: Huw Roddie
Author: Claudius Rudin
Author: Kevin D. Boyd
Author: Wendy L. Osborne
Author: Gordon Cook
Author: J. Anthony Child

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