Bisphosphonates for the relief of pain secondary to bone metastases

Bisphosphonates give some relief from pain caused by cancer that has invaded bones. Patients with cancer that has spread to the bone frequently have pain. Pain control is an important part of cancer management. Bisphosphonates are medicines that affect the way bone develops, and are proving useful in treating patients with cancer that has invaded the bone (metastasis). This review looked at the effect of bisphosphonates on pain caused by bone metastases. Bisphosphonates do have some effect but are not as useful as either strong analgesics (such as morphine) or radiotherapy. However, where other methods of pain relief are inadequate, the addition of bisphosphonates can be beneficial. Bisphosphonates can cause nausea and vomiting.

Authors' conclusions: 

There is evidence to support the effectiveness of bisphosphonates in providing some pain relief for bone metastases. There is insufficient evidence to recommend bisphosphonates for immediate effect; as first line therapy; to define the most effective bisphosphonates or their relative effectiveness for different primary neoplasms. Bisphosphonates should be considered where analgesics and/or radiotherapy are inadequate for the management of painful bone metastases.

Read the full abstract...

Bisphosphonates form part of standard therapy for hypercalcemia and the prevention of skeletal events in some cancers. However, the role of bisphosphonates in pain relief for bony metastases remains uncertain.


To determine the effectiveness of bisphosphonates for the relief of pain from bone metastases.

Search strategy: 

MEDLINE (1966 to 1999), EMBASE (1980 to 1999), CancerLit (1966 to 1999), T he Cochrane L ibrary (Issue 1, 2000) and the Oxford Pain Database were searched using the strategy devised by the Cochrane Pain, Palliative and Supportive Care Group with additional terms 'diphosphonate', 'bisphosphonate', 'multiple myeloma' and 'bone neoplasms'. (Last search: January 2000).

Selection criteria: 

Randomized trials of bisphosphonates compared with open, blinded, or different doses/types of bisphosphonates in cancer patients were included where pain and/or analgesic consumption were outcome measures. Studies where pain was reported only by observers were excluded.

Data collection and analysis: 

Article eligibility, quality assessment and data extraction were undertaken by both review authors. The proportions of patients with pain relief at 4, 8 and 12 weeks were assessed. The proportion of patients with analgesic reduction, the mean pain score, mean analgesic consumption, adverse drug reactions, and quality of life data were compared as secondary outcomes.

Main results: 

Thirty randomized controlled studies (21 blinded, four open and five active control) with a total of 3682 subjects were included. For each outcome, there were few studies with available data. For the proportion of patients with pain relief (eight studies) pooled data showed benefits for the treatment group, with an NNT at 4 weeks of 11[95% CI 6-36] and at 12 weeks of 7 [95% CI 5-12]. In terms of adverse drug reactions, the NNH was 16 [95% CI 12-27] for discontinuation of therapy. Nausea and vomiting were reported in 24 studies with a non-significant trend for greater risk in the treatment group. One study showed a small improvement in quality of life for the treatment group at 4 weeks. The small number of studies in each subgroup with relevant data limited our ability to explore the most effective bisphosphonates and their relative effectiveness for different primary neoplasms.