Denosumab has shown to be noninferior to zoledronic acid for the prevention of skeletal-related events and provides an alternative .
Fewer adverse events related to renal toxicity have been noted with denosumab compared with zoledronic acid and may be preferred in this setting .
Purpose To up date guideline recommendations on the role of bone-modifying agents in multiple myeloma .
Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial.
BACKGROUND Compared with placebo , prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma . However , because of toxicity associated with long-term bisphosphonate treatment , establishing the lowest effective dose is important . This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma . METHODS This double-blind , r and omised , phase 3 trial was undertaken at 37 clinics in Denmark , Norway , and Sweden . Patients with multiple myeloma who were starting antimyeloma treatment were r and omly assigned in a 1:1 ratio to receive one of two doses of pamidronate ( 30 mg or 90 mg ) given by intravenous infusion once a month for at least 3 years . R and omisation was done by use of a central , computerised minimisation system . Primary outcome was physical function after 12 months estimated by the European Organisation for Research and Treatment of Cancer ( EORTC ) QLQ-C30 question naire ( scale 0 - 100 ) . All patients who returned question naires at 12 months and were still on study treatment were included in the analysis of the primary endpoint . This study is registered with Clinical Trials.gov , number NCT00376883 . FINDINGS From January , 2001 , until August , 2005 , 504 patients were r and omly assigned to  pamidronate 30 mg or 90 mg ( 252 in each group ) . 157 patients in the 90 mg group and 156 in the 30 mg group were included in the primary analysis  . Mean physical function at 12 months was 66 points ( 95 % CI 62·9 - 70·0 ) in the 90 mg group and 68 points ( 64·6 - 71·4 ) in the 30 mg group ( 95 % CI of difference -6·6 to 3·3 ; p=0·52 ) . Median time to first skeletal-related event in patients who had such an event was 9·2 months ( 8·1 - 10·7 ) in the 90 mg group and 10·2 months ( 7·3 - 14·0 ) in the 30 mg group ( p=0·63 ) . In a retrospective analysis , eight patients in the pamidronate 90 mg group developed osteonecrosis of the jaw compared with two patients in the 30 mg group . INTERPRETATION Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma . FUNDING Nordic Cancer Union and Novartis Healthcare
Denosumab has shown to be noninferior to zoledronic acid for the prevention of skeletal-related events and provides an alternative .
Fewer adverse events related to renal toxicity have been noted with denosumab compared with zoledronic acid and may be preferred in this setting .
Purpose To up date guideline recommendations on the role of bone-modifying agents in multiple myeloma .