Multiple myeloma: bisphosponates reduced vertebral fractures and pain

Clinical bottom line (level 1a)

  1. Patients with multiple myeloma who take bisphosphonates compared with control are less likely to develop pathological vertebral fractures (NNT = 9 at months) and have less pain (NNT = 8 at months) .
  2. There is no clear difference in mortality, gastrointestinal symptoms or incidence of hypercalcaemia between the two groups.
Djulbegovic et al: Cochrane Library 2001; 4 : -
Expires May 2004

The study

Systematic review of all randomised trials of
  • Patients: multiple myeloma
  • Intervention: bisphosponates compared with placebo or no treatment
  • Outcome: pathological vertebral fractures, pain relief, death, hypercalcaemia

Articles found in ?all languages using Medline, LILCAS, Embase, Cochrnae Controlled Triasl Register, to June 2001 (search terms: deatiled in text ) and searching bibliographies of retrieved articles, and hand-searching relevant meetings proceedings from 1993 to 2000. Manufacturers of bisphosphonates and researchers in the field were contacted.

Selection criteria: by 2 independent reviewers - disagreements were resolved by consensus
Appraisal criteria: by 2 independent reviewers using Jadad scale
Articles excluded if:
  • duplicate reports or subgroup analysis of larger RCTs
  • other agents assessed
11 RCTs found involving 2183 patients; 4 on pamidronate, 4 on clodronate and 2 on etidronate and 1 on ibandronate
Study results for hypercalcaemia were significantly heterogeneous reflecting the small size of several of the studies.

The evidence

Outcome Time to outcome CER OR
(95% CI)		 NNT
(95% CI)
death months 549/1048
(52.4%)		 0.99
(0.88 to 1.12) 		400
(NNT = 31 to infinity;
NNH = 36 to infinity)
vertebral fractures months 188/541
(34.8%)		 0.59
(0.45 to 0.78) 		9
(6 to 19)
hypercalcaemia months 101/1002
(10.1%)		 0.76
(0.56 to 1.03) 		45
(NNT = 24 to infinity;
NNH = 370 to infinity)
reduction in pain months 318/624
(51.0%)		 0.59
(0.46 to 0.76) 		8
(5 to 15)
gastrointestinal symptoms months 83/836
(9.9%)		 1.28
(0.95 to 1.74) 		-41
(NNT = 220 to infinity;
NNH = 16 to infinity)

Citation

  1. Djulbegovic B, Wheatley K, Ross , et al: bisphosponates in multiple myeloma (Cochrane Review). Cochrane Library 2001; 4 : -
Search Terms: from ACP Journal Club other articles noted
Contributor: Chris Ball, May 2002
Reviewer:

Clinical Question.
Patient multiple myeloma
Intervention or Exposure bisphosphonates
Comparison control
Outcome death, hypercalcaemia, fractures, pain