Table B Excluded studies (posted as supplied by author)

References for tables of included and excluded studies
 

Table A Included studies (posted as supplied by author)
 

Study	Methods	Participants	Interventions	Outcomes	Notes	Allocation concealment
Ausili-Cefaro 1999 (w1)	Randomised controlled trial Open	(No patients recruited) Breast Cancer >70 yrs age Eligible for 2nd line hormone Tx or chemo  Painful bony metastases with no previous radiotherapy	A – Pamidronate  90 mg IV 2 hrs in 250 ml Nsaline x 9  (+ Radiotherapy) B – Control gp Radiotherapy	Protocol only – no results.  Pathological # SCC  Hypercalcaemia		B
Belch 1991 (w2)	Randomised controlled trial  Double blind	166 patients 104 M / 62 F Multiple myeloma No previous chemo (steroids or radiotherapy allowed)	A – Etidronate  5-20 mg/kg/day PO to death or withdrawal B – Placebo  Chemo, (melphalan, prednisolone)	Median time on study: 44.4 mths  Pathological # (C): A 20/92; B 21/74; p <0.368 Hypercalcaemia: A 23/92; B 14/74; p <0.453 Survival : NS	Also measured vertebral index (NS) Bone pain Progression of bony metastases	A
Berenson 1996 (w3) Berenson 1998(a) (w4) Berenson 1998(b) (w5)	Randomised controlled trial  Double blind	392 patients 217 M / 137 F Multiple myeloma Durie Salmon stage III, at least 1 osteolytic lesion Stratified by 1st line chemo or 2nd+ line chemo	A – Pamidronate  90 mg IV 4 hrs 500 ml 5% Dextrose every 4 wks x 9   B – Placebo  500 ml 5% Dextrose IV 4 hrs	Outcomes measured at: 3,6,9,12,15,18,21 mths  Pathological # (C,V): (C) 21 mths A 62/196; B 66/181; p < 0.330 (V) 21 mths A 31/196; B 49/181; p <0.008 Radiotherapy:  21 mths A 50/196; B 61/181; p <0.090 SCC: NS Ortho procedure:  NS  Hypercalcaemia: 21 mths A 18/196; B 16/181; p <1.000 Time to 1st SRE:  p <0.016 (log-rank test)  Survival [median]:  NS. 26 vs 24 mths, p <0.377	ECOG 9 mths QUAL (Spitzer index) 9 mths Pain and analgesic use 9 mths	A
Berenson 2001(a) (w6) Berenson 2001(b) (w7)	Randomised controlled trial  Double blind	280 patients 67 M / 213 F Breast cancer & multiple myeloma All pts at least 1 osteolytic lesion  Myeloma pts: previous SRE or failed 1st line chemo	A – Zoledronate  0.4 mg IV 5 mins in 50 ml Nsaline every 4 wks B – Zoledronate  2 mg IV 5 mins in 50 ml Nsaline every 4 wks C – Zoledronate  4 mg IV 5 mins in 50 ml Nsaline every 4 wks D – Pamidronate  90 mg IV 2 hrs in 250 ml Nsaline every 4 wks	Outcomes measured at:  10 mths Pathological # (C): A 19/68; B 16/72; C 14/67; D 15/73; p <0.723 Radiotherapy: A 16/68; B 14/72; C 14/67; D 13/73; p <0.857 SCC: A 1/68; B 0/72; C 2/67; D 2/73; p <0.545 Ortho procedure:  A 5/68; B 2/72; C 2/67; D 3/73; p <0.547 Hypercalcaemia:  A 5/68; B 2/72; C 0/67; D 2/73; p <0.103 Time to 1st SRE:  p <0.05 D vs A Survival: Not recorded	ECOG Pain and analgesic scores Bone mineral density	B
Brinker 1998 (w8)	Randomised controlled trial Double blind	304 patients  160 M / 140 F Multiple myeloma Stratified by: randomized to interferon, not randomized to interferon, not eligible for interferon	A – Pamidronate  300 mg/day PO to withdrawal, death or end of trial B – Placebo  Chemo (melphalan, prednisolone)	Median (range) time on study 544 (4-1702) vs 551 (2-1659) days Outcomes: number of EVENTS Pathological # (N,V):  (N) A 28/152; B 40/148;  p <0.098 (V) A 84/152; B 99/148;  p <0.044 Radiotherapy:  A 45/152; B 62/148; p <0.030 Ortho procedure:  A 5/152; B 11/148; p <0.129 Hypercalcaemia:  A 11/152; B 22/148; p <0.042 Time to 1st SRE [median]: NS 440 vs 414 days p <0.33 Survival [median]: NS 1183 vs 1063 days p <0.9	Progression of bony metastases Pain and analgesic use Height	B
Conte 1996 (w9) Conte 1994 (w10) Ford 1996 (w11)	Randomised controlled trial  Open	295 (F) patients Breast Cancer Osteolytic or mixed metastases Progressive disease at entry and eligible for 1st line chemo. No restriction on amount of previous hormonal Tx	A – Pamidronate  45 mg IV 1 hr in 250 ml Nsaline every 3 wks until progressive disease B – Control  No treatment	Median follow-up 249 vs 168 days Outcomes: Number of EVENTS Pathological # (C):  A 34/143; B 32/152; p <0.580  Radiotherapy: A 66/143; B 83/152; p <0.163 Ortho procedure:  A 4/143; B 8/152; p <0.380 Hypercalcaemia:  A 8/143; B 13/152; p <0.371 Time to 1st SRE [median]:  NS, 533 vs 490 days Survival [median]:  NS, 592 vs 642 days	Performance status (WHO) Pain and analgesic use Time to progressive bony disease	A
Daragon 1993 (w12)	Randomised controlled trial Double blind	104 patients  44 M / 50 M Multiple myeloma Durie-Salmon stage II or III	A – Etidronate  10 mg/kg/day oral for 4 mths B – Placebo	Outcomes measured at: 4 mths Pathological # (C):  A 2/49; B 1/45; p <1.000 Hypercalcaemia: NS Survival [median]: NS, 43 vs 46 mths	Also measured vertebal index: NS Progression of bony metastases Pain and analgesic use Performance status (Karnofsky) Not included in meta-analysis as < 6 mths	B
Delmas 1982 (w13)	Randomised controlled trial Double blind	13 patients Multiple myeloma Excluded if >10 courses chemo on entry	A – Clodronate  1.6 g/day oral for 18 mths B – Placebo	Outcomes measured at: 6-18 mths (4 pts 6mths, 5 pts 12mths, 4 pts 18mths) Pathological # (N,V): (N) A 0/7; B 3/6; p <0.103 (V) A 1/7; B 4/6; p < 0.070 Hypercalcaemia:  A 1/7; B 0/6; p <1.000	Progression of bony disease Bone pain Bone Histomorpho-metry	B
Diel 1999 (w14)	Randomised controlled trial Open	361 patients Breast cancer	A – Clodronate 2.4 g/day oral  B –Clodronate 900 mg IV every 3 wks C – Pamidronate 60 mg IV every 3 wks	Median time on study: 18 mths Pathological # (V): A 11/112; B 19/103; C 16/103; p <0.183	Meeting Abstract  Bone pain	B
Elomaa 1983 (w15) Elomaa 1987 (w16) Elomaa 1988 (w17)	Randomised controlled trial  Double blind	34 (F) patients  Breast Cancer Pts with bone metastases that had progressed on hormone therapy and chemo	A – Clodronate  1.6-3.2 g/day oral for 3-9 mths B – Placebo	Outcomes measured at: 12 mths Pathological # (N):  A 1/17; B 4/17; p <0.335 Radiotherapy: A 3/17; B 10/17; p <0.032 Hypercalcaemia: A 1/17; B 4/17; p <0.335 Survival: NS. 14/17 vs 9/17 patients alive at 12 mths	Analgesic use Disease progression (new bone mets) (16) reports data on 1 yr follow-up period post Tx	B
Glover 1994 (w18)	Randomised controlled trial Open	61 (F) patients Breast Cancer Painful bony metastases Excluded pt with history of fracture, SCC, hypercalcaemia within 3 mths	A – Pamidronate  30 mg IV 4 hrs every 2 wks x 6 B – Pamidronate  60 mg IV 4 hrs every 4 wks x 3 C – Pamidronate 60 mg IV 4 hrs every 2 wks x 6 D – Pamidronate  90 mg IV 6 hrs every 4 wks x 3	Outcome measured at: 3 mths Pathological # (C):  NS, two events Radiotherapy: NS, one event Hypercalcaemia:  No events	Pain and analgesic use Progression of bony disease Not comparable with other studies – all patients on pamidronate at different dosing regimens for 3/12	B
Gomez-Pastrana 1996 (w19)	Randomised controlled trial Double blind	28 (F) patients Breast Cancer	A - Clodronate  300 mg/d IV for 5 d followed by 1600 mg/d oral for 6 mths B - Placebo	Outcomes measured at: 6 mths  Pathological #  Hypercalcaemia	Pain study No data on skeletal morbidity outcomes in text	A
Harris 1993 (w20)	Randomised controlled trial  Open	72 (F) patients Breast cancer	A – Pamidronate  30 mg IV every 3 wks for 3 mths B – Control gp	Outcomes measured at: 3 mths Pathological # (C):  A 3/36; B 3/36; p < 1.000 Radiotherapy: A 10/36; B 15/36; p <0.322 SCC:  A 2/36; B 2/36; p < 1.000 Hypercalcaemia:  A 2/36; B 0/36; p <0.493  Survival:  NS	Meeting Abstract Data not included in meta-analysis as < 6 mths	B
Heim 1995 (w21) Clemens 1993 (w22)	Randomised controlled trial Open	170 patients 77 M / 80 F Multiple myeloma Stratified by Durie-Salmon stage and presence of osteolytic metastases	A – Clodronate  1.6 mg/day oral for 12 mths B – Control gp	Outcomes measured: Pathological # Hypercalcaemia	Pain and analgesic use Progression of bony disease Data not extractable in format for this review therefore results not included	A
Holten-Verzantvoort 1993 (w23) Holten-Verzantvoort 1987 (w24) Cleton 1989 (w25) Holten-Verzantvoort 1991 (w26)	Randomised controlled trial Open	205 (F) patients Breast Cancer	A – Pamidronate  300-600 mg/day oral to death or withdrawal B – Control No treatment	Median (range) time in study: 18 (1-66) vs 21 (1-53) mths Pathological # (C): A 6/81; B 10/80 p <0.305  Radiotherapy:  A 22/81; B 43/80 p <0.001 Ortho procedure:  A 4/81; 8/80; p <0.247 Hypercalcaemia:  A 4/81; B 17/80; p <0.002 Time to 1st SRE [median]:  NS, 14 vs 11 mths, p <0.10 Survival [median]:  NS, 25 vs 24 mths, p <0.98	There were problems with study methodology and changes of dose in treatment group due to GI toxicity therefore data from this study not included in meta-analysis	B
Hortobagyi 1998 (w27) Hortobagyi 1996 (w28)	Randomised controlled trial  Double blind	382 (F) patients Breast Cancer Stage IV breast ca, on chemo, at least 1 osteolytic metastasis >1cm diameter Stratified by ECOG	A – Pamidronate  90 mg IV 2 hrs in 250 ml 5% Dextrose every 3-4 wks x 24 B – Placebo 250 ml 5% Dextrose IV 2 hrs every 3-4 wks x 24	Outcome measured at: 3,6,9,12,15,18,21,24 mths Pathological # (N,V,C): (N) 24 mths A 42/185; B 74/197; p <0.002 (V) 24 mths A 47/185; B 51/197; p <1.000 (C) 24 mths A 67/185; B 96/197; p <0.017 Radiotherapy: 24 mths A 51/185; B 88/197; p <0.001 SCC:  24 mths A 4/185; B 7/197;  p <0.545 Ortho procedure: 24 mths A 9/185; B 24/197;  p <0.017 Hypercalcaemia: 24 mths A 13/185; B 30/197; p <0.017 Time to 1st SRE [median]: 13.9 vs 7 mths p <0.001 Survival [median]:  NS, 14.8 vs 14.0 mths  p <0.82	ECOG QUAL Bone pain and analgesic use Radiological response in bone	A
Hultborn 1999 (w29) Hultborn 1996 (w30)	Randomised controlled trial  Double blind	404 (F) patients Breast Cancer Pts entered at diagnosis of skeletal spread or on change of systemic Tx due to disease progression	A – Pamidronate  60 mg IV 1 hr in 500 ml Nsaline every 3-4 wks x 24 B – Placebo  500 ml Nsaline IV 1 hr every 3-4 wks x 24	Median time on study: 12 vs 11.5 mths Pathological # (N): A 30/201; B 31/203; p <1.000 Radiotherapy: A 54/201; B 65/203; p <0.276 SCC: A 5/201; B 6/203; p <1.000 Ortho procedure: A 12/201; B 17/203; p <0.441 Hypercalcaemia: A 5/201; B 17/203; p <0.014 Time to 1st SRE [median]: 11.8 vs 8.4 mths p <0.006 Survival [median]: NS, 18.3 mths	Performance status (WHO) Pain and analgesic score	A
I – Kraj 2000 (a) (w31) I – Kraj 2000 (b) (w32)	Randomised controlled trial Open	46 patients 26 M / 20 F Multiple myeloma All receiving chemo	A – Pamidronate 60 mg IV over 4 hrs every 4 wks B – Control Standard chemo	Outcomes measured at: 12, 21 mths Pathological # : individual data not given Radiotherapy : individual data not given SCC : individual data not given Hypercalcaemia: NS Survival [median]: NS, 20 vs 19 mths p <0.45	ECOG Pain and analgesic use Progression of bone mets Mean SRE/yr (#,DXT,SCC) Sig p<0.013	B
Kristensen 1999 (w33)	Randomised controlled trial  Open	100 (F) patients Breast cancer Untreated or 1st line treatment for <6 mths	A – Clodronate  1.6-3.2 g/day oral for 24 mths B – Control gp	Only recorded FIRST SRE for each patient. Pathological # (N, V, C): (C) A 3/49; B 13/51; p <0.013 Radiotherapy: A 8/49; B 4/51; p <0.230 Hypercalcaemia: A 3/49; B 4/51; p <1.000 Time to 1st SRE:  p <0.015 Survival [median (95%CI)]: NS, 18.3 (16.3-20.3) vs 18.0 (15.7-20.2) mths	WHO performance status QUAL – Eortc-30 + HADS Pain and analgesic use Time to progressive bony metastases Time to 1st SRE and survival included in analyses.	B
Lahtinen 1992 (w34) Laasko 1994 (w35)	Randomised controlled trial  Double blind	350 patients 166 M / 170 F Multiple myeloma Pts newly diagnosed, commenced on melphalan-prednisolone	A – Clodronate  2.4 g/day oral for 24 mths B – Placebo	Outcome measured at:  24 mths Pathological # (N,V): (N) A 26/108; B22/95;  p <1.000 (V) A 33/108; B 38/95;  p <0.185 Hypercalcemia NS	203/350 pts had baseline and follow-up x-rays therefore data not included in meta-analysis Pain and analgesic use Progression of bony lesion (35) is a subset analysis looking at cost data	B
Lipton 2000 (w36) Theriault 1996 (w37)	Randomised controlled trial  Double blind	754 (F) patients Breast Cancer			Pooled results from Hortobagyi 1998 and Theriault 1999 Trials considered individually as shown	A
Martoni 1991 (w38)	Randomised controlled trial Double blind for 1 wk then open	38 (F) patients  Breast cancer Progressive disease Stratified by type of bone metastases (osteolytic, osteoblastic, mixed), systemic treatment (chemo vs hormonal)	A – Clodronate  300 mg/day IV 3 hrs in 250 ml Nsaline for 1 wk, followed by 100 mg/day IM for 3 wks followed by 100 mg/alt days IM for 2 mths B – Control 250 ml/day Nsaline 3 hrs IV for 1 wk followed by standard care	Outcomes measured at: 3 mths  Pathological # (C):  A 0/17; B 2/16; p <0.103 Hypercalcaemia: A 1/17; B 3/16; p <0.335	Pain and analgesic use Number of bony metastases Data not included in meta-analysis as < 6 mths	B
McCloskey 1998 (w39)	Randomised controlled trial  Double blind	614 patients 318 M / 218 F Multiple myeloma Excluded if previous chemo	A – Clodronate  1.6 g/day oral for 24 mths B – Placebo	Median time on study 33.6 mths Pathological # (N,V):  (N) A 15/264; B 29/272;  p <0.041 (V) A 41/264; B 60/272;  p <0.060 Radiotherapy: NS  Hypercalcaemia:  A 39/264; B 48/272; p <0.413 Time to 1st SRE: NS Survival [median (95%CI)]:  NS, p <0.74, OR 0.97 2.9 (2.4-3.4) vs 2.8 (2.5-3.5) yr	Performance status QUAL Pain Height	A
Paterson 1993 (w40)	Randomised controlled trial  Double blind	173 (F) patients Breast cancer	A – Clodronate  1.6 g/day oral for 36 mths B – Placebo	Median time on study 14 vs 14.5 mths Pathological # (N, V): (N) A 19/85; B 24/88;  p <0.486 (V) A 38/85; B 46/88;  p <0.363 Radiotherapy: A 34/85; B 42/88; p <0.359 Hypercalcaemia: A 20/85; B 31/88; p <0.099 Time to 1st SRE: NS Survival: 35% vs 14% patients alive at 2 yrs		A
Robertson 1995 (w41)	Randomised controlled trial  Double blind	55 patients All cancer types Bone pain secondary to progressive bony disease, failed first line antitumour therapy	A – Clodronate  1.6 g/day oral B – Placebo	Median (range) time on study 8 (0.7-17.3) mths Pathological # (C):  A 4/27; B 2/28; p <0.422 SCC:  A 0/27; B 3/28; p <0.236 Hypercalcaemia:  A 0/27; B 2/28; p <0.491 Survival [median (range)]: NS, 240 (25-518) vs 240 (20-486) days		B
Theriault 1999 (w42)	Randomised controlled trial Double blind	372 (F) patients Breast Cancer Pts on stable hormonal Tx 2 osteolytic metastases or 1 osteolytic (>1cm diameter) + extraskeletal metastases Stratified by ECOG score	A – Pamidronate  90 mg IV 2 hrs in 250 ml 5% Dextrose every 3-4 wks x 24 B – Placebo 250 ml 5% Dextrose IV 2 hrs every 3-4 wks x 24	Outcome measures at: 6,12,18,24 mths Pathological # (N, V, C): (N) 24 mths A 66/182; B 75/189; p <0.522 (V) 24 mths A 50/182; B 58/189; p <0.568 (C) 24 mths A 81/182; B 102/189; p <0.078 Radiotherapy: 24 mths A 56/182; B 76/189; p <0.065 SCC: 24 mths A 7/182; B 6/189;  p <0.783 Ortho procedure:  24 mths A 13/182; B 20/189; p <0.277  Hypercalcaemia: 24 mths A 8/182; B 19/189;  p <0.045 Time to 1st SRE [median]: 10.4 vs 6.9 mths p <0.049 Survival [median (95%CI)]:  23.2 (19.3-25.8) vs 23.5 (18.7-27.4) p <0.685	ECOG QUAL Bone pain and analgesic use	A
Tubiana-Hulin 2001 (w43) Hulin 1994 (w44)	Randomised controlled trial Double blind	144 (F) patients Breast cancer	A – Clodronate  1.6 g/day PO for 12 mths B – Placebo	Only recorded FIRST SRE for each patient Pathological # (C): A 8/73; B 7/71; p <1.000 Radiotherapy: A 7/73; B 13/71; p <0.153 Hypercalcaemia: A 0/73; B 4/71; p <0.057 Time to 1st SRE [median (range)]: 18.1 (1.2-12.2) vs 6 (1.1-12.2) mths  p <0.05	Time to progressive bony metastases Time to 1st SRE included in analyses.	B
Unpublished data A (w45) Rosen 2002 (w46)	Randomised controlled trial Double blind	773 patients Solid tumours excluding breast/prostate	A- Zoledronate 8/4mg IV every 3 wks for 9 mths B – Zoledronate 4mg IV every 3 wks for 9 mths C - Placebo	Outcome measured at: 9 mths Pathological # (N,V,C): (N) A 21/266; B 26/257; C 29/250 (V) A 13/266;B 20/257; C 30/250 (C) A 31/266; B 40/257; C 53/250 Radiotherapy: A 70/266; B 69/257; C 81/250 SCC: A 7/266; B 7/257; C 10/250 Ortho procedure: A 14/266; B 11/257; C 9/250 Hypercalcaemia: A 2/266; B 0/257; C 8/250 Time to 1st SRE [median]: A 7.2; B 7.56; C 5.1 mths	Performance status QUAL Bone pain and analgesic use	A
Unpublished data B (w47) Rosen 2001 (w48)	Randomised controlled trial Double blind	1648 patients Breast cancer and multiple myeloma	A – Zoledronate 8/4mg IV every 3-4 wks for 12 mths  B – Zoledronate 4mg IV every 3-4 wks for 12 mths C – Pamidronate 90mg IV every 3-4 wks for 12 mths	Outcome measured at: 13 mths Pathological # (N,V,C): (N) A 135/524; B 145/561; C 148/555 (V) A 84/524; B 109/561; C 108/555 (C) A 179/524; B 200/561; C 203/555 Radiotherapy: A 112/524; B 85/561; C 112/555 SCC: A 12/524; B 11/561; C 16/555 Ortho procedure: A 15/524; B 21/561; C 31/555 Hypercalcaemia: A 5/524; B 7/561; C 12/555 Time to 1st SRE [median]: A 11.54; B 12.26; C 11.70 mths, NS	Performance status QUAL Bone pain and analgesic use	A
Unpublished data C (w49) Saad 2002 (w50)	Randomised controlled trial Double blind	643 patients Prostate cancer	A – Zoledronate 8/4mg IV in 50-100mls Nsaline over 5-15 mins every 3 wks for 15 mths B - Zoledronate 4mg IV in 50-100 mls Nsaline over 5-15 mins every 3 wks for 15 mths C – Placebo	Outcome measured at: 15 mths Pathological # (N,V,C): (N) A 22/221; B 22/214; C 33/208 (V) A 17/221; B 8/214; C 17/208 (C) A 33/221; B 28/214; C 46/208 Radiotherapy: A 53/221; B 49/214; C 61/208 SCC: A 11/221; B 9/214; C 14/208 Ortho procedure: A 6/221; B 5/214; C 7/208 Hypercalcaemia: A 0/221; B 0/214; C 2/208 Time to 1st SRE [median]: A 11.93; B Not reached; C 10.55 mths	Performance status QUAL Bone pain and analgesic use	A

 

Table B Excluded studies (posted as supplied by author)
 

Study	Reason for exclusion
Abdulkadyrov 1993 (w51)	Russian paper. On translation, did not fulfil criteria for a randomised controlled trial
Abildgaard 1998 (w52)	Histomorphometric study of a subset of patients from Brinker et al(w8)
Adami 1989 (w53)	Pain study; did not measure any of the primary outcome measures of this review
Arican 1999 (w54)	Pain study; did not measure any of the primary outcome measures of this review
Attardo-Parrinello 1987 (w55)	Not a randomised controlled trial
Ausgabe 1997 (w56)	German paper. This review mentions recruitment for a RCT of hormone resistant prostate cancer, patients randomised to one of three arms: epirubicin, clodronate, or epirubicin + clodronate. Study centre contacted for update on progress. No reply received.
Body 1999 (w57) [meeting abstract]	Outcomes measured as events/year. Further data not available from authors.
Cascinu 1998 (w58)	Pain study; did not measure any of the primary outcome measures of this review
Coleman 1997 (w59)	Pain study; did not measure any of the primary outcome measures of this review
Coleman 1998 (w60)	Pain study; did not measure any of the primary outcome measures of this review
Coleman 1999 (w61)	Study measuring bone resorption markers. No measurement of any of the primary outcome measures of this review
Conte 1991 (w62)	Study measuring bone resorption markers. No measurement of any of the primary outcome measures of this review
Costa 1993 (w63)	Portuguese paper. On translation, did not fulfil criteria for a randomised controlled trial
Dearnaley 2001 (w64)	Meeting Abstract. Did not report any of the primary outcome measures of this review
Diel 1999 (w65)	Meeting Abstract. Pain and quality of life study; did not measure any of the primary outcome measure of this review
Elomaa 1992 (w66)	Pain study; did not measure any of the primary outcome measures of this review
Elomaa 1996 (w67)	Bone resorption marker study; did not measure any of the primary outcome measures of this review
Ernst 1992 (w68)	Pain study; did not measure any of the primary outcome measures of this review
Ernst 1997 (w69)	Pain study; did not measure any of the primary outcome measures of this review
Fernandez-Conde 1997 (w70)	Histomorphometric study; did not measure any of the primary outcome measures of this review
Gessner 2000 (w71)	Economic study; costs of terminal care for patients with osteolytic bone disease treated with pamidronate
Jung 1983 (w72)	Calcium kinetics study; did not measure any of the primary outcome measures of this review
Koeberle 1999 (w73)	Pain study; did not measure any of the primary outcome measures of this review
Kylmala 1993 (w74)	Pain study; did not measure any of the primary outcome measures of this review
Kylmala 1997 (w73)	Pain study; did not measure any of the primary outcome measures of this review
Lipton 1994 (w76)	Pain study; did not measure any of the primary outcome measures of this review
Lipton 1996 (w77)	Not a randomised controlled trial
Lipton 1998 (w78)	Not a randomised controlled trial
Merlini 1990 (w79)	Not a randomised controlled trial
Moiseyenko 1998 (w80)	Russian paper. On translation, pain study, no measurement of any of the primary outcome measures of this review
O’Rourke 1995 (w81)	Pain study; did not measure any of the primary outcome measures of this review
Peest 1996 (w82)	Primary outcome, measurement of bone resorption markers. Did not measure any of the primary outcome measures of this review
Piga 1998 (w83)	Pain study; did not measure any of the primary outcome measures of this review
Poliakov 1999 (w84)	Russian paper. On translation, not a RCT, pain study, no measurement of any of the primary outcome measures of this review
Rinenberg 1987 (w85)	Maintenance of normocalcaemia study; included mixed haematological malignancies
Schiller 1987 (w86)	Maintenance of normocalcaemia study
Slaby 1997 (w87)	Czech paper. Measured bone resorption markers
Smith 1989 (w88)	Pain study; did not measure any of the primary outcome measures of this review
Strang 1997 (w89)	Pain study; did not measure any of the primary outcome measures of this review
Taube 1993 (w90)	Histomorphometric study; did not measure any of the primary outcome measure of this review
Taube 1994 (w91)	Histomorphometric study; did not measure any of the primary outcome measures of this review
Terpos 2000 (w92)	Pain study; did not measure any of the primary outcome measures of this review
Thurlimann 1994 (w93)	Not a randomised controlled trial
Vinholes 1996 (w94)	Not a randomised controlled trial
Vinholes 1997 (w95)	Pain study; did not measure any of the primary outcome measures of this review
Vinholes 1999 (w96)	Measured bone resorption markers; did not measure any of the primary outcome measures of this review
Zhang 1997 (w97)	Chinese paper. On translation, pain study, no measurement of any of the primary outcome measures of this review
Zhang 1999 (w98)	Chinese paper. On translation, pain study, no measurement of any of the primary outcome measures of this review

References for tables of included and excluded studies

w1 Ausili-Cefaro G, Capirci C, Crivellari D, Fontana V, Mandoliti G, Olmi P, et al. Radiation therapy vs radiation therapy + pamidronate (Aredia) in elderly patients with breast cancer and lytic bone metastases: A GROG-GIOGER randomized clinical trial. Rays 1999;24(suppl 2):49-52.

w2 Belch AR, Bergsagel DE, Wilson K, O’Reilly S, Wilson J, Sutton D, et al. Effect of daily etidronate on the osteolysis of multiple myeloma. J Clin Oncol 1991;9:1397-402.

w3 Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. N Engl J Med 1996;334(8):488-93.

w4 Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S, et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. J Clin Oncol 1998;16(2):593-602.

w5 Berenson JR. The efficacy of pamidronate disodium in the treatment of osteolytic lesions and bone pain in multiple myeloma. Rev Contemp Pharmacother 1998;9:195-203.

w6 Berenson JR, Rosen LS, Howell A, Porter L, Coleman RE, Morley W, et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer 2001;91:1191-200.

w7 Berenson JR. Zoledronic acid in cancer patients with bone metastases: results of phase I and II trials. Semin Oncol 2001;28(suppl 6):25-34.

w8 Brincker H, Westin J, Abildgaard N, Gimsing P, Turesson I, Hedenus M, et al. Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: a double-blind placebo-controlled trial. Danish-Swedish co-operative study group. Br J Haematol 1998;101:280-6.

w9 Conte PF, Giannessi PG, Latreille J, Mauriac L, Koliren L, Calabresi F, et al. Delayed progression of bone metastases with pamidronate therapy in breast cancer patients: a randomized, multicenter phase III trial. Ann Oncol 1994;5(suppl 7):S41-4.

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