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Table 1 Study characteristics of the included studies. ALP activity: alkaline phosphatase activity, SrHA: strontium hydroxyapatite, and ZOLHA (zoledronate hydroxyapatite), BMP-2: bone morphogenetic protein 2

From: Effect of bisphosphonate treatment of titanium surfaces on alkaline phosphatase activity in osteoblasts: a systematic review and meta-analysis

Study ID

Year

Sample size per experiment

Time point of measurement

Cell type

Type of bisphosphonate

Amount / concentration

ALP activity (3 days)

ALP activity (4 days)

ALP activity (7 days)

ALP activity (10 days)

ALP activity (14 days)

ALP activity (18 days)

ALP activity (21 days)

Coating specificaiton

Bigi et al. [40]

2009

3

7, 14 days

MG-63 osteoblast like cells

Control

–

  

2.17 ± 1.21

 

4.81 ± 0.27

  

Hydroxyapatite

Bigi et al. [40]

2009

3

7, 14 days

MG-63 osteoblast like cells

Alendronate

7 mM

  

2.12 ± 0.20

 

4.72 ± 0.08

  

Hydroxyapatite

Bigi et al. [40]

2009

3

7, 14 days

MG-63 osteoblast like cells

Alendronate

28 mM

  

2.29 ± 0.45

 

5.23 ± 0.14

  

Hydroxyapatite

Boanini et al. [41]

2015

6

10, 21 days

MG-63 osteoblast like cells

Control

–

   

0.82 ± 0.12

  

0.99 ± 0.12

Strontium-substituted hydroxyapatite (SrHA)

Boanini et al. [41]

2015

6

10, 21 days

MG-63 osteoblast like cells

Zoledronat

Gradient composition C2 (SrHA and ZOLHA)

   

1 ± 0.15

  

1.09 ± 0.08

Strontium-substituted hydroxyapatite (SrHA)

Boanini et al. [41]

2015

6

10, 21 days

MG-63 osteoblast like cells

Zoledronat

Gradient composition C3 (SrHA and ZOLHA)

   

0.79 ± 0.1

  

0.92 ± 0.08

Strontium-substituted hydroxyapatite (SrHA)

Boanini et al. [41]

2015

6

10, 21 days

MG-63 osteoblast like cells

Zoledronat

Gradient composition C4 (SrHA and ZOLHA)

   

0.75 ± 0,1

  

0.86 ± 0.16

Strontium-substituted hydroxyapatite (SrHA)

Boanini et al. [41]

2015

6

10, 21 days

MG-63 osteoblast like cells

Zoledronat

ZOLHA

   

0,80 ± 0.06

  

0.92 ± 0,15

Strontium-substituted hydroxyapatite (SrHA)

Boanini et al. [42]

2015

6

14 days

Osteoblast derived from stem cells

Control

–

    

10.6 ± 2.1

  

Octacalcium phosphate

Boanini et al. [42]

2015

6

14 days

Osteoblast derived from stem cells

Alendronate

8 mM

    

16.3 ± 2.6

  

Octacalcium phosphate

Boanini et al. [42]

2015

6

14 days

Osteoblast derived from stem cells

Alendronate

20 mM

    

9.63 ± 2.30

  

Octacalcium phosphate

Hu et al. [44]

2013

5

14 days

MC3T3-E1

Control

–

    

0.41 ± 0.02

  

Precoated hydroxyapatite (CaP) layer

Hu et al. [44]

2013

5

14 days

MC3T3-E1

Alendronate

0.2 mg/ml solution

    

0.57 ± 0.04

  

Precoated hydroxyapatite (CaP) layer

Hu et al. [44]

2013

5

14 days

MC3T3-E1

Alendronate

0.5 mg/ml solution

    

0.59 ± 0.04

  

Precoated hydroxyapatite (CaP) layer

Hu et al. [44]

2013

5

14 days

MC3T3-E1

Alendronate

1 mg/ml solution

    

0.59 ± 0.63

  

Precoated hydroxyapatite (CaP) layer

Jeon et al [43]

2019

5

3 days

MG-63 osteoblast like cells

Control

–

1.11 ± 0.09

      

UV treatment

Jeon et al [43]

2019

5

3 days

MG-63 osteoblast like cells

Alendronate

10−3 M

1.16 ± 0.17

      

UV treatment

Kim et al. [45]

2013

5

7, 14, 21 days

MG-63 osteoblast like cells

Control

–

  

1.12 ± 0.03

 

3.44 ± 0.14

 

4.01 ± 0.09

Heparin-coated

Kim et al. [45]

2013

5

7, 14, 21 days

MG-63 osteoblast like cells

Alendronate

1 mg/ml solution

  

1.19 ± 0.04

 

5.29 ± 0.06

 

4.41 ± 0.12

Heparin-coated

Kim et al. [45]

2013

5

7, 14, 21 days

MG-63 osteoblast like cells

Control

–

  

1.31 ± 0.05

 

5.86 ± 0.23

 

4.65 ± 0.13

BMP-2/Heparin-coated

Kim et al. [45]

2013

5

7, 14, 21 days

MG-63 osteoblast like cells

Alendronate

1 mg/ml solution

  

1.41 ± 0.04

 

6.65 ± 0.27

 

5.36 ± 0.13

BMP-2/Heparin-coated

Kim et al. [46]

2017

3

7 days

MG-63 osteoblast like cells

Control

–

  

1.49 ± 0.23

    

without UV treatment

Kim et al. [46]

2017

3

7 days

MG-63 osteoblast like cells

Alendronate

10−6 M

  

4.08 ± 0.23

    

without UV treatment

Kim et al. [46]

2017

3

7 days

MG-63 osteoblast like cells

Control

–

  

3.49 ± 0.34

    

with UV treatment

Kim et al. [46]

2017

3

7 days

MG-63 osteoblast like cells

Alendronate

10−6 M

  

6.22 ± 0.78

    

with UV treatment

Moon et al. [47]

2011

3

7, 14, 21 days

MC3T3-E1

Control

–

  

2.56 ± 0.17

 

3.60 ± 0.06

 

3.48 ± 0.13

Heparin-coated

Moon et al. [47]

2011

3

7, 14, 21 days

MC3T3-E1

Alendronate

1 mg

  

3.55 ± 0.10

 

5.35 ± 0.17

 

4.36 ± 0.11

Heparin-coated

Moon et al. [47]

2011

3

7, 14, 21 days

MC3T3-E1

Alendronate

5 mg

  

4.24 ± 0.29

 

7.80 ± 0.21

 

5.35 ± 0.15

Heparin-coated

Mu et al. [48]

2018

5

7 days

Osteoblasts from neonate rat calvaria

Control

–

  

0.53 ± 0.05

    

Hyaluronan

Mu et al. [48]

2018

5

7 days

Osteoblasts from neonate rat calvaria

Alendronate

500 mg

  

0.63 ± 0.06

    

Hyaluronan

Yoshinari et al. [49]

2000

6

7 days

Osteoblastic cells from calvariae of Sprague-Dawley rats

Control

–

  

51.7 ± 5.9

    

Hydroxyapatite

Yoshinari et al. [49]

2000

6

7 days

Osteoblastic cells from calvariae of Sprague-Dawley rats

Pamidronate disodium

10−2 M

  

65.4 ± 9.7

    

Hydroxyapatite

Zheng et al. [50]

2016

3

4,7,10,14,18 days

MC3T3-E1

Control

–

 

1.19 ± 0.15

1.81 ± 0.20

3.27 ± 0,38

3.30 ± 0.27

2.66 ± 0.25

 

Plasma treated titanium

Zheng et al. [50]

2016

3

4,7,10,14,18 days

MC3T3-E1

Alendronate

2.5 mg/ml solution

 

1.59 ± 0.13

2.36 ± 0.27

3.58 ± 0.20

3.66 ± 0.28

2.65 ± 0.25

 

Plasma treated titanium

Zheng et al. [50]

2016

3

4,7,10,14,18 days

MC3T3-E1

Control

–

 

1.20 ± 0.16

1.95 ± 0,26

3.26 ± 0.16

3,3 ± 0.13

2.62 ± 0.36

 

Plasma treated, silane-treated

Zheng et al. [50]

2016

3

4,7,10,14,18 days

MC3T3-E1

Alendronate

0.5 mg/ml solution

 

1.52 ± 0.16

2.66 ± 0,16

3.93 ± 0.26

4.32 ± 0.30

3.18 ± 0.24

 

Plasma treated, silane-treated

Zheng et al. [50]

2016

3

4,7,10,14,18 days

MC3T3-E1

Alendronate

1 mg/ml solution

 

1.62 ± 0.12

3.39 ± 0,23

4.99 ± 0.28

3.70 ± 0.13

3.05 ± 0.14

 

Plasma treated, silane-treated