Porta-Sales, J., Garzón-Rodríguez, C., Llorens-Torromé, S., Brunelli, C., Pigni, A., & Caraceni, A. (2017). Evidence on the analgesic role of bisphosphonates and denosumab in the treatment of pain due to bone metastases: A systematic review within the European Association for Palliative Care guidelines project. Palliative Medicine, 31, 5–25.

STUDY PURPOSE: To critically appraise and synthesize evidence regarding the safety and effectiveness of bisphosphonates and denosumab for controlling pain from bone metastasis

TYPE OF STUDY: Systematic review

DATABASES USED: MEDLINE, EMBASE, Cochrane Collaboration, through January 2014

INCLUSION CRITERIA: RCT or meta analysis design, adult patients reported efficacy of pain reduction and/or side effects.

EXCLUSION CRITERIA: Abstracts, studies dealing only with prevention of skeletal-related events, economic or quality of life impact.

TOTAL REFERENCES RETRIEVED: 1,585

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: GRADE system used for study evaluation. Overall quality of evidence was rated as very low.

FINAL NUMBER STUDIES INCLUDED: 43 

TOTAL PATIENTS INCLUDED IN REVIEW: 15,064

SAMPLE RANGE ACROSS STUDIES: 9 to 5,544

KEY SAMPLE CHARACTERISTICS: Patients with bone metastases

PHASE OF CARE: Late effects and survivorship     

APPLICATIONS: Palliative care

Medications included clodronate, etidronate, pamidronate, ibandronate, zoledronic acid, and denosumab. Some of these had very few studies, and results comparing effectiveness of one over another for pain relief showed mixed findings. The authors concluded that evidence of any of these for direct pain relief is weak, mainly due to methodologic concerns.

Direct evidence for effectiveness of bone-modifying agents for relief of pain is weak; however, evidence suggests that these medications may help prevent pain by delaying onset of bone pain.

• Mostly low quality/high risk of bias studies
• High heterogeneity

Findings suggest that bisphosphonates and denosumab may benefit patients by delaying onset of bone pain, and that overall these medications are safe. Findings also suggest that this is probably most beneficial in patients with a relatively long life expectancy (months to years). Benefits may not be gained for patients with life expectancy of only weeks to months given the mechanism by which bone pain is affected.