Systematic review of role of bisphosphonates on skeletal morbidity in metastatic cancer
BMJ 2003; 327 doi: https://doi.org/10.1136/bmj.327.7413.469 (Published 28 August 2003) Cite this as: BMJ 2003;327:469
Data supplement
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 chemoPainful 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 mthsPathological # (C):
A 20/92; B 21/74; p <0.368
Hypercalcaemia:
A 23/92; B 14/74; p <0.453Survival :
NSAlso 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 <0.090SCC:
NSOrtho procedure:
NSHypercalcaemia:
21 mths A 18/196; B 16/181; p <1.000Time to 1st SRE:
p <0.016 (log-rank test)Survival [median]:
NS. 26 vs 24 mths, p <0.377ECOG 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 mthsPathological # (C):
A 19/68; B 16/72; C 14/67; D 15/73; p <0.723Radiotherapy:
A 16/68; B 14/72; C 14/67; D 13/73; p <0.857SCC:
A 1/68; B 0/72; C 2/67; D 2/73; p <0.545Ortho procedure:
A 5/68; B 2/72; C 2/67; D 3/73; p <0.547Hypercalcaemia:
A 5/68; B 2/72; C 0/67; D 2/73; p <0.103Time to 1st SRE:
p <0.05 D vs ASurvival: 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 <0.030Ortho procedure:
A 5/152; B 11/148; p <0.129Hypercalcaemia:
A 11/152; B 22/148; p <0.042Time to 1st SRE [median]:
NS 440 vs 414 days p <0.33Survival [median]:
NS 1183 vs 1063 days p <0.9Progression 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 <0.580Radiotherapy:
A 66/143; B 83/152; p <0.163Ortho procedure:
A 4/143; B 8/152; p <0.380Hypercalcaemia:
A 8/143; B 13/152; p <0.371Time to 1st SRE [median]:
NS, 533 vs 490 daysSurvival [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 mthsPathological # (C):
A 2/49; B 1/45; p <1.000Hypercalcaemia:
NSSurvival [median]:
NS, 43 vs 46 mthsAlso 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 <0.183Meeting 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 mthsPathological # (N):
A 1/17; B 4/17; p <0.335Radiotherapy:
A 3/17; B 10/17; p <0.032Hypercalcaemia:
A 1/17; B 4/17; p <0.335Survival:
NS. 14/17 vs 9/17 patients alive at 12 mthsAnalgesic 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 mthsPathological # (C):
NS, two eventsRadiotherapy:
NS, one eventHypercalcaemia:
No eventsPain 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 mthsPathological #
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 mthsPathological # (C):
A 3/36; B 3/36; p < 1.000Radiotherapy:
A 10/36; B 15/36; p <0.322SCC:
A 2/36; B 2/36; p < 1.000Hypercalcaemia:
A 2/36; B 0/36; p <0.493
Survival:
NSMeeting 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 <0.305Radiotherapy:
A 22/81; B 43/80 p <0.001Ortho procedure:
A 4/81; 8/80; p <0.247Hypercalcaemia:
A 4/81; B 17/80; p <0.002Time to 1st SRE [median]:
NS, 14 vs 11 mths, p <0.10Survival [median]:
NS, 25 vs 24 mths, p <0.98There 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 <0.001SCC:
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 <0.017Time to 1st SRE [median]:
13.9 vs 7 mths p <0.001Survival [median]:
NS, 14.8 vs 14.0 mthsp <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 mthsPathological # (N):
A 30/201; B 31/203; p <1.000
Radiotherapy:
A 54/201; B 65/203; p <0.276SCC:
A 5/201; B 6/203; p <1.000Ortho procedure:
A 12/201; B 17/203; p <0.441
Hypercalcaemia:
A 5/201; B 17/203; p <0.014Time to 1st SRE [median]:
11.8 vs 8.4 mths p <0.006Survival [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 mthsPathological # : individual data not given
Radiotherapy : individual data not given
SCC : individual data not given
Hypercalcaemia:
NSSurvival [median]:
NS, 20 vs 19 mths p <0.45ECOG 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 <0.013Radiotherapy:
A 8/49; B 4/51; p <0.230Hypercalcaemia:
A 3/49; B 4/51; p <1.000Time to 1st SRE:
p <0.015Survival [median (95%CI)]:
NS, 18.3 (16.3-20.3) vs 18.0 (15.7-20.2) mthsWHO 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 mthsPathological # (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 mthsPathological # (C):
A 0/17; B 2/16; p <0.103Hypercalcaemia:
A 1/17; B 3/16; p <0.335Pain 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:
NSHypercalcaemia:
A 39/264; B 48/272; p <0.413Time to 1st SRE:
NSSurvival [median (95%CI)]:
NS, p <0.74, OR 0.972.9 (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 <0.359Hypercalcaemia:
A 20/85; B 31/88; p <0.099Time to 1st SRE:
NSSurvival:
35% vs 14% patients alive at 2 yrsA 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 <0.422SCC:
A 0/27; B 3/28; p <0.236Hypercalcaemia:
A 0/27; B 2/28; p <0.491Survival [median (range)]:
NS, 240 (25-518) vs 240 (20-486) daysB 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 <0.065SCC:
24 mths A 7/182; B 6/189;p <0.783
Ortho procedure:
24 mths A 13/182; B 20/189; p <0.277Hypercalcaemia:
24 mths A 8/182; B 19/189;p <0.045
Time to 1st SRE [median]:
10.4 vs 6.9 mths p <0.049Survival [median (95%CI)]:
23.2 (19.3-25.8) vs 23.5 (18.7-27.4) p <0.685ECOG 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 <1.000Radiotherapy:
A 7/73; B 13/71; p <0.153Hypercalcaemia:
A 0/73; B 4/71; p <0.057Time to 1st SRE [median (range)]:
18.1 (1.2-12.2) vs 6 (1.1-12.2) mthsp <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 mthsPathological # (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 81/250SCC:
A 7/266; B 7/257; C 10/250Ortho procedure:
A 14/266; B 11/257; C 9/250Hypercalcaemia:
A 2/266; B 0/257; C 8/250Time 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 mthsPathological # (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 112/555SCC:
A 12/524; B 11/561; C 16/555Ortho procedure:
A 15/524; B 21/561; C 31/555Hypercalcaemia:
A 5/524; B 7/561; C 12/555Time to 1st SRE [median]:
A 11.54; B 12.26; C 11.70 mths, NSPerformance 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 mthsPathological # (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 14/208Ortho procedure:
A 6/221; B 5/214; C 7/208Hypercalcaemia:
A 0/221; B 0/214; C 2/208Time to 1st SRE [median]:
A 11.93; B Not reached; C 10.55 mthsPerformance 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.
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