Table 3.
Main results of the articles included in the present systematic review.
| Study | Fractures | LS BMD | TH BMD | FN BMD | Bone turnover biomarkers | Pain | Fatigue | Anxiety and Depression | Weakness | Lymphedema |
|---|---|---|---|---|---|---|---|---|---|---|
| Alendronate | ||||||||||
| Rhee et al. (40) | NR | 24 weeks: -3.5 ± 0.6% vs -0.5 ± 0.6%; p=0.05 | 24 weeks: -1.3 ± 0.5% vs -0.5 ± 0.4%; p=NS | NR | sCTx 24 weeks: 72.4%; p<0.05 OCN 24 weeks: 29.0%; p=NS |
NR | NR | NR | NR | NR |
| Denosumab | ||||||||||
| Ellis et al. (49) | 4% vs 2% p=NR |
12 months: 5.5%; p<0.0001
24 months: 7.6%; p<0.0001 |
12 months: p<0.0001 24 months: 4.7%; p<0.0001 |
12 months: p<0.0001 24 month: 3.6%; p<0.0001 |
1 month: sCTx 1 month: -9% vs -91%; p<0.0001 1 month: P1NP 1 month: -2% vs -29%; p<0.0001 |
Articular pain: 25% vs 24%; p=NR Back pain: 12.5% vs 14%; p=NR |
14.2% vs 13.2%; p=NR |
NR | NR | NR |
| Gnant et al. (34) | Incidence: 9.6% vs 5%; p=NR Time to first fracture: HR 0.5 [95% CI 0.39–0.65], p<0·0001 |
12 months: -1.81% vs +3.94%; p<0.0001 24 months: -2.44% vs +5.85%; p<0.0001 36 months: -2.75% vs +7.27%; p<0.0001 |
12 months: -1.20% vs +2.67%; p<0.0001 24 months: -2.5% vs +3.70%; p<0.0001 36 months: -3.32% vs +4.60%; p<0.0001 |
12 months: -1.08% vs +2.22%; p<0.0001 24 months: -2.33% vs +2.86%; p<0.0001 36 months: -3.10% vs +3.41%; p<0.0001 |
NR | Articular pain: 26% vs 26% p=NS Back pain: 9% vs 9% p=NS Bone pain: 7% vs 8% p=NS |
6% vs 6%; p=NS |
NR | NR | NR |
| Gnant et al. (35) | Incidence: 9.6% vs 5%; p=NR Time to first fracture: HR 0.5 [95% CI 0.39–0.65], p<0·0001 |
12 months: -1.81% vs +3.94%; p<0.0001 24 months: -2.44% vs +5.85%; p<0.0001 36 months: -2.75% vs +7.27%; p<0.0001 |
12 months: -1.20% vs +2.67%; p<0.0001 24 months: -2.5% vs +3.70%; p<0.0001 36 months: -3.32% vs +4.60%; p<0.0001 |
12 months: -1.08% vs +2.22%; p<0.0001 24 months: -2.33% vs +2.86%; p<0.0001 36 months: -3.10% vs +3.41%; p<0.0001 |
NR | Articular pain: 26% vs 26% p=NS Back pain: 9% vs 9% p=NS Bone pain: 7% vs 8% p=NS |
6% vs 6%; p=NS |
NR | NR | NR |
| Ibandronate | ||||||||||
| Lester et al. (41) | No fractures | 12 months: -3.19% vs +1.49%; p=0.012 24 months: -3.22% vs +2.98%; p=0.002 |
12 months: -2.27 vs +0.98; p=0.001 24 months: -3.90% vs +0.60%; p=0.003 |
NR | NTX 12 months: +39.5% vs -30.9%; p<0.001 sCTx 12 months: +34.9% vs -26.3%; p<0.001 bALP 12 months: +37.0% vs -22.8%; p<0.001 |
NR | NR | NR | NR | NR |
| Lester et al. (42) | 3 vs 4; p=NR | 60 months -2.88 vs 0.29%; p=NR |
60 months 1.18% vs -3.71%; p=NR |
NR | NR | NR | NR | NR | NR | NR |
| Livi et al. (29) | NR | 12 months: -2.29% vs +2.96%; p=0.021 24 months: -4.22% vs +6.09%; p<0.0001 |
12 months: -2.35% vs +3.11%; p<0.001 24 months: -1.51% vs +4.64%; p=0.09 |
NR | NR | NR | NR | NR | NR | NR |
| Risedronate | ||||||||||
| Greenspan et al. (38) | NR | 12 months: -1.2% vs +2%; p<0.0001 24 months: -1.7% vs +2.3%; p<0.0001 |
12 months: -1.6% vs +0.5%; p<0.0001 24 months: -2.7% vs +0.6%; p<0.0001 |
24 months: 2.6 ± 0.8%; p=0.0009 | sCTx 12 months: p<0.01 sCTx 24 months: p<0.01 P1NP 12 months: p<0.0001 P1NP 24 months: p<0.0001 |
NR | NR | NR | NR | NR |
| Markopoulos et al. (46) | No fractures |
12 months: 0% vs -0.4%; p=NS
24 months: -1.5% vs +5.7%; p=0.006 |
12 months: -1.3% vs 0%; p=NS
24 months: -3.9% vs +1.6%; p=0.037 |
NR | NR | NR | NR | NR | NR | NR |
| Van Poznak et al. (45) | 5 (2.1%) |
12 months: -1.2% vs +1.2%; p<0.0001
24 months: -1.8% vs +2.2%; p<0.0001 |
12 months: -0.4% vs +0.9%; p=0.0023 24 months: -1.1% vs +1.8%; p<0.0001 |
NR | sCTx 6 months: +8.2% vs -44.0%; p<0.0001 sCTx 12 months: +6.1% vs -43.8%; p<0.0001 P1NP 6 months: -1.5% vs -41.8%; p<0.0001 P1NP 12 months: -2.4% vs -44.3%; p<0.0001 bALP 6 months: +1.6% vs -21.6%; p<0.0001 bALP 6 months: +3.9% vs -22.7%; p<0.0001 |
Articular pain: 7.8% vs 5.2%; p=NR Bone pain: 1.3% vs 1.3%; p=NR |
NR | NR | No weakness | NR |
| Zoledronate | ||||||||||
| Brufsky et al. (52) | 2.1% vs 2.2%; p=NR | 12 months: 5.2%; p<0.0001 | 12 months: 3.5%; p<0.0001 | NR | NTX: 33.3%– 49%; p<0.0001 BSAP 30.3%– 48.9%; p<0.0001 |
Articular pain: 28.5% vs 31.7%; p=NR Back pain: 6.2% vs 5.6%; p=NR Bone pain: 5.9% vs 12.2%; p=NR |
NR | Depression: 6.7% vs 3.9%; p=NR | NR | NR |
| Brufsky et al. (48) | 6.3% vs 5.7% p=NS |
12 months: 4.3% p<0.0001
24 months: 6% p<0.0001 36 months: 6.7% p<0.0001 |
12 months: 3.2% p<0.0001 24 months: 4.6% p<0.0001 36 months: 5.3% p<0.0001 |
NR | NTX: p=NS BSAP: p=0.0045 |
Articular pain: 37% vs 36.3%; p=NS Back pain: 10.7% vs 9.3%; p=NS Bone pain: 6.7% vs 13%; p=0.01 |
22.3% vs 26%; p=NS | Anxiety: 6% vs 4.7%; p=NS Depression: 11.7% vs 8.7%; p=NS |
NR | 5.7% vs 5.3%; p=NS |
| Brufsky et al. (50) | 9.3% vs 11%; p=0.3803 | 48 months: p<0.0001 61 months: 8.9% p<0.0001 |
48 months: p<0.0001 61 months: 6.7% p<0.0001 |
NR | NTX: p=NS BSAP: p=0.0002 |
Articular pain: 47.0% vs 45.3%; p=NR; Back pain: 14.7% vs 17.3%; p=NR Bone pain: 16.0% vs 8.0%; p=NR Myalgia: 20.3% vs 15.7%; p=NR |
33.7% vs 29.3; p=NR | Depression: 11.7% vs 14.0%; p=NR | NR | 12.0% vs 10.0%; p=NR |
| Bundred et al. (24) | 1.7% vs 1.5%; p=NR | 12 months: 5.7%; p<0.0001 | 3.6%; p<0.0001 | NR | BSAP 12 months: 45.6%; p<0.0001 NTX: 33%; p<0.0001 |
Articular pain: 29% vs 32.6%; p=NR Back pain: 6.5% vs 5.7%; p=NR Bone pain: 6.9% vs 12.3%; p=NR |
11.4% vs 11.2%; p=NR |
Depression: 5.3% vs 2.8%; p=NR | NR | NR |
| Eidtmann et al. (47) | 6% vs 5% p=NS |
12 months: 5.27% p<0.0001
24 months: 7.94% p<0.0001 36 months: 9.29% p<0.0001 |
NR p<0.0001 |
NR | NR | Articular pain: 40.7% vs 42.2%; p=NR Back pain: 11.4% vs 10.5%; p=NR Bone pain: 10.1% vs 15.3%; p=NR |
15.1% vs 16%; p=NR | Depression: 6.5% vs 4.8%; p=NR | NR | 5.4% vs 6.5%; p=NR |
| Coleman et al. (39) | NR | 60 months: -5.4% vs +4.3%; p<0.0001 | 60 months: -4.2% vs +1.6%; p<0.0001 | NR | NR | Articular pain: 46.9% vs 49% p=NR Back pain: 15.1% vs 15% p=NR Bone pain: 12.1% vs 18.5% p=NR |
17.8% vs 17.7%; p=NR |
NR | NR | NR |
| Llombart et al. (44) | 1.9% vs 0.8%; p=NR |
12 months: 5.43%; p<0.0001 | 12 months: 3.31%; p<0.0001 | NR | NR | Articular pain: 38.9% vs 37.7%; p=NS Back pain: 7% vs 5.2%; p=NS Bone pain: 4.1% vs 8.3%; p=NS p<0.05 Shoulder pain: 5.9% vs 4%; p=NS |
18.5% vs 15.1%; p=NS |
Anxiety: 5.2% vs 3.6%; p=NS Depression: 5.6% vs 2%; p=NS |
7.8% vs 9.1%; p=NS |
4.1% vs 5.6%; p=NS |
| Safra et al. (51) | 0 vs 0 p=NS |
24 months: 0.84; p<0.0001
48 months: 0.76; p<0.0001 |
24 months: 0.96; p=0.0041 48 months: 0.77; p=0.52 |
NR | NR | Articular pain: 26% vs 21%; p=NR |
17% vs 8%; p=NR | 4% vs 0%; p=NR | NR | NR |
| Takahashi et al. (43) | No fractures | 12 months: 4.9%; p<0.0001 | 12 months: 4.4%; p<0.0001 | NR | NTX 6 months: +21.8 vs -6.5%; p=NR NTX 12 months: +9.4% vs -23.6%; p=NR BSAP 6 months: +14.9% vs -33.6%; p=NR BSAP 12 months: +10.2% vs -39.4%; p=NR |
Articular pain: 48.5% vs 51.6% p=NS | 11,3% vs 9.6% p=NS |
NR | NR | NR |
| Hines et al. (36) | NR |
12 months: 3.66%
vs -1.66%; p<0.001 24 months: 4.94% vs -2.28%; p<0.001 |
12 months: 1.02% vs -1.41%; p<0.001 24 months: 1.22% vs -3.34%; p<0.001 |
12 months: 2.08% -0.09%; p<0.001 24 months: 3.36% vs 0.54%; p<0.001 |
NR | 12 months: Back pain: 25% vs 23%; p=0.67 Myalgia: 7% vs 5%; p=0.53 Articular pain; 13% vs 11%; p=0.59 |
12 months: 5% vs 2%; p= 0.038 |
NR | NR | NR |
| Wagner-Johnston et al. (37) | 25 vs 24; p= 0.84 |
> 5% BMD differences:
10.2% vs 41.2%; p<0.0001 |
> 5% BMD differences in both TH and FN BMD: 7.6% vs 45.8%; p<0.0001 |
NR | NR | NR | NR | NR | NR | |
bALP, bone isoforms of alkaline phosphatase; BSAP, bone-specific alkaline phosphatase; CG, control group; C-telopeptide I (sCTx); FN, femoral neck; IG, intervention group; LS, lumbar spine; NR, not reported; NS, not significant; NTx, N-telopeptide; OCN, osteocalcin; P1NP, procollagen type I N-terminal peptide; TH, total hip.
Primary outcomes of the study included were marked in bold.