Outcomes	Definition	Used by
Primary
Skeletal Related Eventsa	Radiation therapy or surgery to bone, spinal cord compression event or a pathologic bone fracture event Not specified	Scagliotti[37-39], Francini[25], Rosen (Hirsh [6, 7, 27] Zaragoulidis[31, 35], Hirai[36], Kritikos[34]
Painb
	Visual analogue scale (0-10) 4 categories: 0 = no pain, 1-3 mild, 4-6 moderate, 7-10= severe BPI	Zaragoulidis[31, 35], Guo[26]
	Verbal rating scale for analgesia effects 6-point McGill-Melzack pain questionnaire (reponses: no pain, mild pain, discomforting/moderate pain, distressing/severe pain, horrible/extremely severe pain, excruciating/life threatening pain)	Rosen (Hirsh)[6, 7, 27] Zheng[32] Francini[25], Li[28]
	Subjectively evaluated by patients and by analgesic needs (permanent pain, night- time pain, pain only occurring during movement) with 4 categories: no pain = no pain and no analgesics, mild pain = patient cannot rest, but needs no analgesics moderate pain = patient cannot rest and needs analgesics, severe pain = patient cannot sleep and needs nacotics.	Su[30], Zhang[29]
Pain control	‘Significant improvement’ = pain decreased by 2 levels; ‘Effective control’ = pain decreased by 1 level; ‘No effect ‘= no change	Francini[25], Guo[26], Zhang[29], Zheng[32]
	Complete remission = 100% of pain alleviated; Partial remission = ≥ 50% of pain alleviated; No improvement = pain was not effectively controlled	Su[30]
	No change = no pain improvement; Effective control = pain decreased by ≥1 level; Exacerbation = patients experience worse pain	Li[28]
Overall Survival	Days since beginning bisphosphonate therapy	Scagliotti[37-39], Zaragoulidis[31, 35], Rosen (Hirsh)[6, 7, 27]
	From the days of diagnosis to the date of death due to any cause (up to 1 year) Not Specified	Pandya[33] Hirai[36]
Secondary
Time to the First Skeletal Related Event	The time from randomization to the date of occurrence of the first SRE	Scagliotti[37-39]
	The time from the date of the first dose of study drug to the first documentation of bone metastasis	Pandya[33]
	Not Specified	Hirai[36], Kritikos[34]
Biomarkers	S-CTX and B-ALP NTx nM BCE	Francini[22] Zaragoulidis[28, 32], Rosen (Hirsh)[5, 6, 24]
Bone lesion progression	CT scan (measurement of lesions approximately every 3 months)	Rosen (Hirsh)[6, 7, 27]
Overall disease progression	Response Evaluation Criteria in Solid Tumors (RECIST), CT scans and then new symptom occurrence	Pandya[33], Francini[25]
	Modified Southwest Oncology Group	Rosen (Hirsh)[6, 7, 27]
Time to disease progression	The time from the date of the first dose of intervention to the date of first documented progression death due to underlying cancer, or date to loss of follow-up	Pandya[33], Zaragoulidis[31, 35],
	Not Specified	Hirai[36]
Performance status	ECOG	Rosen (Hirsh)[6, 7, 27]
Quality of life	FACT-G	Rosen (Hirsh)[6, 7, 27]
Serious Adverse Events	Not specified	Zheng[32], Zaragoulidis[31, 35]

^aPercentage of participants with >1event;

^bAll studies used 3 levels for pain categorization, we therefore, defined “pain not controlled” for categories with no improvement, exacerbation or no effect and we defined “pain controlled” for categories defining effective control, significant improvement, complete or partial remission