Background
Methods
Search strategy
Selection criteria
Data extraction and quality assessment
Outcomes
Data synthesis and statistical analysis
Quality of evidence
Results
Study characteristics
Study | Follow-up | Country | No. of Patients | Female/Male | Intervention | Bisphosphonate Administration | N | Co-intervention | Immunosuppression |
---|---|---|---|---|---|---|---|---|---|
Smerud 2012 [18] | 12 months | Norway | 129 | 30/99 | ibandronate | 3 mg i.v. (every 3 months) | 66 | PO calcium 500 mg tweice daily+ calcitriol 0.25 mcg daily | corticosteroids, MMF, CsA or FK506 |
placebo | 63 | ||||||||
Coco 2012 [19] | 12 months | USA | 42 | 15/27 | risedronate | 35 mg p.o. (weekly) | 20 | PO calcitriol 0.25 μg daily (with or without calcium) | corticosteroids, MMF, FK506, rapamycin |
placebo | 22 | ||||||||
Torregrosa 2010 [20] | 12 months | Spain | 101 | 34/67 | risedronate | 35 mg p.o. (weekly) | 52 | PO calcium 1.5 g daily + vitamin D 400 IU daily | corticosteroids, FK506 with or without MMF |
no treatment | 49 | ||||||||
Torregrosa 2011 [21] | 12 months | Spain | 39 | 13/26 | pamidronate | 30 mg i.v. (between day 7 and 10 after KT and 3 months post-KT) | 24 | PO calcium 1 g daily + cholecalciferol 800 IU daily | corticosteroids, MMF, CsA |
placebo | 15 | ||||||||
Walsh 2009 [22] | 24 months | UK | 125 | 24/69 | pamidronate | 1 mg/kg i.v. (perioperatively and at month 1, 4, 8, 12) | 65 | PO calcium 500 mg daily + vitamin D 400 IU daily | corticosteroids, CsA |
no treatment | 60 | ||||||||
Lan 2008 [23] | 6 months | China | 46 | 27/19 | alendronate | 70 mg p.o. (weekly) | 23 | PO calcium 800 mg daily + calcitriol 0.25 μg daily | corticosteroids, MMF, CsA |
no treatment | 23 | ||||||||
Trabulus 2008 [24] | 12 months | Turkey | 64 | 19/40 | alendronate | 10 mg p.o. (daily) | 13 | PO calcium 1 g daily | corticosteroids, azathioprin or MMF, CsA or FK506 |
alfacalcidol | 0.5 μg p.o. (daily) | 25 | |||||||
alendronate + alfacalcidol | 17 | ||||||||
no treatment | 9 | ||||||||
Nayak 2007 [25] | 6 months | India | 50 | NA | alendronate | 35 mg p.o. (weekly) | 27 | PO calcium 1 g daily + vitamin D | NA |
no treatment | 23 | ||||||||
El-Agroudy 2005 [26] | 12 months | Egypt | 60 | 0/60 | alendronate | 5 mg p.o. (daily) | 15 | PO calcium 500 mg daily | corticosteroids, CsA |
alfacalcidol | 0.5 μg p.o. (daily) | 15 | |||||||
calcitonin | 100 μl intranasally (p.o.d and stopped for 1 month every 3 month) | 15 | |||||||
no treatment | 15 | ||||||||
Schwarz 2004 [27] | 36 months | Austria | 20 | 8/12 | zoledronic acid | 4 mg i.v. (week 2, month 3) | 9 | PO calcium 1 g daily | corticosteroids, MMF, CsA |
placebo | 10 | ||||||||
Jeffery 2003 [28] | 12 months | Canada | 117 | 26/71 | alendronate | 10 mg p.o. (daily) | 57 | PO calcium 500 mg daily | corticosteroids, CsA, azathioprin or MMF |
calcitriol | 0.25 μg p.o. (daily) | 60 | |||||||
Coco 2003 [29] | 12 months | USA | 72 | 28/31 | pamidronate | 60 mg i.v. (< 48 h after KT, 30 mg i.v. at months 1, 2, 3, 6) | 36 | calcium + calcitriol | corticosteroids, CsA or FK506 |
no treatment | 36 | ||||||||
Hass 2003 [30] | 6 months | Austria | 20 | 8/12 | zoledronic acid | 4 mg i.v. (week 2, month 3) | 10 | PO calcium 1 g daily | corticosteroids, MMF, CsA |
placebo | 10 | ||||||||
Grotz 2001 [31] | 12 months | Germany | 80 | 24/48 | ibandronate | 1 mg i.v. (just before KT, 2 mg i.v. at month 3, 6, 9) | 36 | PO calcium 500 mg daily | corticosteroids, MMF, CsA |
no treatment | 36 | ||||||||
Nam 2000 [32] | 6 months | South Kore | 50 | 21/29 | pamidronate | 30 mg i.v. (every 4 weeks) | 15 | PO calcium 500 mg daily | NA |
calcitriol | 0.5 μg p.o. (daily) | 15 | |||||||
no treatment | 20 | ||||||||
Grotz 1998 [33] | 12 months | Germany | 46 | 17/29 | clodronate | 800 mg p.o. (daily) for 14 days, each followed by 75 days without treatment | 15 | PO calcium 500 mg daily | corticosteroids, CsA |
calcitonin | 100 IU intranasally twice a day | 16 | |||||||
no treatment | 15 | ||||||||
Giannini 2001 [34] | 12 months | Italy | 40 | 13/27 | alendronate | 10 mg p.o. (daily) | 20 | PO calcium 500 mg daily + calcitriol 0.5 μg daily | corticosteroids, CsA with or without azathioprin |
no treatment | 20 | ||||||||
Koc 2002 [35] | 12 months | Turkey | 35 | 10/25 | alendronate | 10 mg p.o. (daily) | 8 | PO calcium 1 g daily | corticosteroids, azathioprin, CsA |
calcitriol | 0.5 μg p.o. (daily) | 8 | |||||||
no treatment | 8 | ||||||||
Torregrosa 2007 [36] | 12 months | Spain | 84 | 42/42 | risedronate | 35 mg p.o. (weekly) | 39 | PO calcium 2.5 g daily + vitamin D | corticosteroids, CsA or FK506, with or without MMF |
no treatment | 45 |
Risk of Bias assessment result
Pairwise meta-analysis
Comparisons | No. of directed trials (participants) | Pairwise meta-analysis mean differences (95% CI) | Network meta-analysis mean differences (95% CrI) | Heterogeneity I2 | P-Value | Quality of evidence |
---|---|---|---|---|---|---|
Absolute BMD change at the femoral neck (536) | ||||||
Bis+Ca vs. Bis+Ca + Vit D | 1 (29) | – | − 0.01 (− 0.32, 0.29) | – | – | Low |
Bis+Ca vs. Ca | 5 (167) |
1.3 (0.92, 1.68)
| 0.19 (− 0.01, 0.38) | 94.70% | 0.000 | Low |
Bis+Ca vs. Ca + Vit D | 2 (176) | 0.26 (−0.04, 0.56) | 0.06 (− 0.15, 0.26) | 38.10% | 0.184 | Moderate |
Bis+Ca vs. Ca + Calcitonin | 2 (61) | 0.21 (−0.29, 0.72) | 0.06 (− 0.22, 0.36) | 24.60% | 0.249 | Moderate |
Bis+Ca + Vit D vs. Ca | – | – | 0.20 (−0.14, 0.53) | – | – | Very low |
Bis+Ca + Vit D vs. Ca + Vit D | 4 (206) |
0.36 (0.08, 0.64)
| 0.07 (−0.18, 0.30) | 67.60% | 0.026 | Low |
Bis+Ca + Vit D vs. Ca + Calcitonin | – | – | 0.07 (−0.34, 0.46) | – | – | Very low |
Ca vs. Ca + Vit D | 2 (46) |
−0.74 (−1.34, − 0.14)
| −0.13 (− 0.38, 0.13) | 0.00% | 0.403 | Low |
Ca vs. Ca + Calcitonin | 2 (60) |
−0.55 (−1.07, − 0.03)
| −0.12 (− 0.41, 0.19) | 60.20% | 0.113 | Low |
Ca + Vit D vs. Ca + Calcitonin | 1 (30) | – | 0.00 (−0.30, 0.34) | – | – | Low |
Percent BMD change at the femoral neck (284) | ||||||
Bis+Ca vs. Bis+Ca + Vit D | 1 (29) | – | −4.60 (−18.07, 7.67) | – | – | Low |
Bis+Ca vs. Ca | 4 (152) |
1.14 (0.78, 1.51)
|
5.83 (1.61, 9.27)
| 91.10% | 0.000 | Moderate |
Bis+Ca vs. Ca + Vit D | 4 (46) |
1.55 (0.76, 2.35)
| −0.24 (5.62, 9.79) | 96.10% | 0.000 | Low |
Bis+Ca vs. Ca + Calcitonin | 1 (31) | – | −0.04 (−19.65, 18.12) | – | – | Low |
Bis+Ca + Vit D vs. Ca | – | – | 10.43 (−2.64, 23.31) | – | – | Very low |
Bis+Ca + Vit D vs. Ca + Vit D | – | – | 4.35 (−2.29, 11.37) | – | – | Very low |
Bis+Ca + Vit D vs. Ca + Calcitonin | – | – | 4.56 (−18.36, 19.16) | – | – | Very low |
Ca vs. Ca + Vit D | 3 (51) |
−1.53 (−2.18, −0.88)
| −6.07 (− 17.09, 4.47) | 79.30% | 0.028 | Low |
Ca vs. Ca + Calcitonin | 1 (30) | – | −5.87 (−20.01, 18.60) | – | – | Low |
Ca + Vit D vs. Ca + Calcitonin | 1 (30) | – | 0.20 (−19.15, 19.61) | – | – | Low |
Absolute BMD change at the lumbar spine (814) | ||||||
Bis+Ca vs. Bis+Ca + Vit D | 1 (29) | – | −0.01 (−0.06, 0.04) | – | – | Low |
Bis+Ca vs. Ca | 5 (167) |
0.51 (0.20, 0.82)
|
0.06 (0.02, 0.09)
| 0.00% | 0.571 | Moderate |
Bis+Ca vs. Ca + Vit D | 4 (176) | 0.19 (−0.11, 0.49) | 0.01 (−0.03, 0.06) | 0.00% | 0.866 | Moderate |
Bis+Ca vs. Ca + Calcitonin | 2 (61) | 0.49 (−0.02, 1.00) | 0.05 (−0.01, 0.11) | 24.60% | 0.250 | Moderate |
Bis+Ca + Vit D vs. Ca | 1 (30) | – |
0.07 (0.00, 0.13)
| – | – | Low |
Bis+Ca + Vit D vs. Ca + Vit D | 8 (484) |
0.38 (0.19, 0.57)
|
0.03 (0.00, 0.05)
| 92.10% | 0.000 | Moderate |
Bis+Ca + Vit D vs. Ca + Calcitonin | – | – | 0.06 (−0.01, 0.15) | – | – | Very low |
Ca vs. Ca + Vit D | 2 (46) | −0.40 (− 0.99, 0.18) | −0.04 (− 0.10, 0.02) | 0.00% | 0.960 | Moderate |
Ca vs. Ca + Calcitonin | 2 (60) | −0.04 (− 0.55, 0.47) | −0.01 (− 0.07, 0.06) | 0.00% | 0.874 | Moderate |
Ca + Vit D vs. Ca + Calcitonin | – | – | 0.04 (−0.04, 0.12) | – | – | Very low |
Percent BMD change at the lumbar spine (466) | ||||||
Bis+Ca vs. Bis+Ca + Vit D | – | – | −3.27 (−7.87, 0.84) | – | – | Very low |
Bis+Ca vs. Ca | 4 (152) |
1.17 (0.80, 1.54)
|
7.24 (3.73, 10.69)
| 91.70% | 0.000 | Moderate |
Bis+Ca vs. Ca + Vit D | 2 (46) |
1.53 (0.79, 2.27)
| 2.22 (−1.44, 5.73) | 94.10% | 0.000 | Low |
Bis+Ca vs. Ca + Calcitonin | 1 (31) | – | 3.13 (−2.51, 8.51) | – | – | Low |
Bis+Ca + Vit D vs. Ca | – | – |
10.50 (5.92, 15.34)
| – | – | Very low |
Bis+Ca + Vit D vs. Ca + Vit D | 3 (145) |
1.32 (1.02, 1.62)
|
5.48 (2.57, 8.42)
| 98.30% | 0.000 | Moderate |
Bis+Ca + Vit D vs. Ca + Calcitonin | – | – |
6.39 (0.55, 12.89)
| – | – | Low |
Ca vs. Ca + Vit D | 2 (51) |
−2.73 (−3.51, −1.95)
|
−5.02 (−8.84, − 1.20)
| 0.00% | 0.373 | Moderate |
Ca vs. Ca + Calcitonin | 1 (30) | – | −4.11 (−9.01, 0.72) | – | – | Low |
Ca + Vit D vs. Ca + Calcitonin | – | – | 0.91 (−4.38, 6.44) | – | – | Very low |