Table 1.
Characteristic of papers included
| References | Animals/surgical site | Biomaterials | Strontium | Number of defects per group and per time point | Implantation period | New bone formation (mean ± SD) |
Remaining material (mean ± SD) | Conclusion of bone repair | Conclusion of biomaterial resorption |
|---|---|---|---|---|---|---|---|---|---|
| Baier [22] | Rat/Osteoporosis/Femur | CPCa/SPC | NA | 10 | 1,3 and 6 months |
Histomorphometrical results 1 m: 0 (CPC) 0.157 ± 0.096 (SPC) 3 m: 0.331 ± 0.163 (CPC) 0.398 ± 0.247 (SPC) 6 m: 0.325 ± 0.193 (CPC) 3.789 ± 0.687 (SPC) |
NA | Sr-doping improved bone repair | NA |
| Carmo [23] | Rat/Healthy/Maxilla | CHA/SrCHA | NA | 5 | 1 and 6 weeks |
Histomorphometrical results 1w: 18.2 ± 2.04(CHA) 17 ± 1.7(SrCHA) 6w: 28.2 ± 3.82(CHA) 32 ± 4.15(SrCHA) |
Histomorphometrical results 1w:14.6 ± 2.50(CHA) 18.9 ± 1.69(SrCHA) 6w: 16.5 ± 2.41(CHA) 10.4 ± 2.33(SrCHA) |
Sr-doping did not improve bone repair | Sr-doping did not reduce biomaterial resorption |
| Cassino [24] | Rat/Albinoism/Tibia | HA/HASr/HAGa | NA | 10 | 7 days | NA | NA | NA | NA |
| Chandran [25] | Rat/Osteoporosis/Femur | Sham/HA/SrHA | 10 | 6 | 8 weeks |
Histomorphometrical results 0.68 ± 0.08(HA) 0.92 ± 0.04(SrHA) |
NA | Sr-doping improved bone repair | NA |
| Chandran [26] | Sheep/Osteoporosis/Femur |
SrHA—Ca9Sr1(PO4)6(OH)2 /HA–Ca10(PO4)6(OH)2 cHA/cSrHA |
10 | 2 | 2 months |
Histomorphometrical results 0.08 ± 0.03(HA) 0.24 ± 0.04(SrHA) 0.30 ± 0.06(cHA) 0.38 ± 0.04(cSrHA) |
NA | Sr-doping improved bone repair | NA |
| Cheng [27] | Rat/Osteoporosis/Femur | Sham/CPCa/Sr-CPC | NA | 7 | 6 weeks | NA | NA | NA | NA |
| Dagang [28] | Rabbit/Healthy/Femur | HAC/Sr-HAC | 5t%, 10% | 1 | 4, 8, 12 and 24 weeks | NA | NA | NA | NA |
| Elgali [29] | Rat/Healthy/Femur | DBB/HA/SrHA/Sham | 50% | 6 | 12 h, 3 and 6 days |
Histomorphometrical results 6d: 4.575 ± 1.018(HA) 7.401 ± 0.635(SrHA) |
NA | Sr-doping improved bone repair | NA |
| Ge [13] | Rabbit/NA/Femur | PLLA/HA/PLLA/Sr-HA/PLLA | NA | NA | 5 weeks | NA | NA | Sr-doping improved bone repair | NA |
| Gu [30] | Rabbit/Healthy/Mandible | HA/Sr-HA | 5t%, 10% | 4 | 1, 3 and 6 months | NA | NA | NA | NA |
| Gu [31] | Rabbit/Healthy/Radius | HA/CPP/SCPP | NA | 4 | 4, 8 and 16 weeks | NA | NA | Sr-doping improved bone repair | NA |
| Guo [32] | Rat/Osteoporosis/Femur | nano-HA/SrR nano-HA | 200 mM | 10 | 4 and 8 weeks |
Histomorphometrical results 4w: 4.632 ± 1.105(nano-HA) 6.533 ± 0.812(SrRnano-HA) 8w: 7.752 ± 0.39(nano-HA) 9.832 ± 0.585(SrRnano-HA) Micro-CT 4w: 48.934 ± 0.842(nano-HA) 49.871 ± 3.556(SrRnano-HA) 8w: 51.930 ± 1.871(nano-HA) 58.573 ± 4.866(SrRnano-HA) |
NA | Sr-doping improved bone repair | NA |
| Hu [33] | Rabbit/Healthy/Radius | Blank control/HA/Sr-HA | 5 wt% | 10 | 8 and 12 weeks | NA | NA | NA | NA |
| Kang [34] | Rabbit/Osteonecrosis/Femur | Autogenous cancellous bone/SrCPP/CPP | NA |
4 (4 and 8 weeks) 8 (12 weeks) |
4, 8 and 12 weeks | NA | NA | Sr-doping improved bone repair | Sr-doping reduced biomaterial resorption |
| Kaygili [35] | Rabbit/Healthy/Tibia | HA/SrHA | 0.45, 0.9, 1.35, 1.8, 2.25 at.% | 28 | 4 weeks | NA | NA | Sr-doping improved bone repair | NA |
| Kuang [36] | Rat/Healthy/Femur | CPCb/Sr-CPC | 5t%, 10% | 5 | 32 weeks | NA | NA | Sr-doping improved bone repair | Sr-doping accelerated biomaterial resorption |
| Li [14] | Rat/Osteoporosis/Femur | HA/SrHA | 10 mol% | 13 | 12 weeks |
Histomorphometrical results 35.753 ± 1.815(HA) 53.721 ± 10.98(SrHA) |
NA | Sr-doping improved bone repair | NA |
| Liao [37] | Rabbit/Healthy/Mandible | Blank/HA/Sr-HA | 5t%, 10% | 4 | 1, 3 and 6 months | NA | NA | NA | NA |
| Luo [38] | Rabbit/Healthy/Calvaria | HA/Sr-HA | NA | NA | 4, 8 and 12 weeks |
micro-CT: 12w:11.05 ± 1.11%(HA) 15.95 ± 3.23%(Sr-HA) |
NA | Sr-doping improved bone repair | NA |
| Machado [39] | Sheep/Healthy/Tibia | Blood clots/HA/SrHA | 1% (w/w) | 5 | 30 days |
Histomorphometrical results 31.2 ± 14.7%(HA) 26.2 ± 12.1%(SrHA) |
Histomorphometrical results 36.2 ± 8.5%(HA) 51.2 ± 14.1% (SrHA) |
Sr-doping did not improve bone repair | Sr-doping reduced biomaterial resorption |
| Masaeli [40] | Rat/Healthy/Calvaria | Control/CPCc/SrCPC | 3 wt% | 10 | 4 weeks | NA | NA | NA | NA |
| Reitmaier [41] | Sheep/Healthy/Femur and tibia | CPCa/SrCPC | NA | 7 | 6 and 26 weeks |
Histomorphometrical results 6w: Unoaded: 9.205 ± 2.092(CPC) 11.297 ± 5.021(SrCPC) Loaded: 11.715 ± 3.766(CPC) 13.389 ± 5.439(SrCPC) 26w: Unoaded: 13.158 ± 4.699(CPC) 29.323 ± 18.045(SrCPC) Loaded: 25.0 ± 5.827(CPC) 44.173 ± 4.511(SrCPC) |
Histomorphometrical results 6w: Unoaded: 58.779 ± 12.023(CPC) 41.984 ± 22.138(SrCPC) Loaded: 59.160 ± 12.977(CPC) 43.702 ± 17.176(SrCPC) 26w: Unoaded: 63.254 ± 10.42(CPC) 36.746 ± 16.271(SrCPC) Loaded: 59.415 ± 10.055(CPC) 41.133 ± 10.786(SrCPC) |
Sr-doping improved bone repair | Sr-doping accelerated biomaterial resorption |
| Salamanna [42] | Rat/Osteoporosis/Vertebra | HA/SrHA/HA-AL7/HA-AL28 | 3.1 atom%,6.9 atom% | 10 | 8 weeks | NA | NA | Sr-doping improved bone repair in osteoporotic bone | NA |
| Tao [10] | Rat/Osteoporosis/Femur | Control/CPCb/SrCPC/BSrCPC | SrCO3: 5 wt% | 5 | 8 weeks |
Histomorphometrical results 22.222 ± 2.963(CPC) 33.333 ± 3.704(SCPC) Micro-CT: 0.345 ± 0.084(CPC) 0.4 ± 0.084(SCPC) |
Histomorphometrical results 52.222 ± 7.037(CPC) 40.185 ± 5.741(SCPC) |
Sr-doping improved bone repair | Sr-doping accelerated biomaterial resorption |
| Tao [43] | Rat/Osteoporosis/Femur | Control/β-TCP/Srβ-TCP/Asp-Sr β-TCP | 10 wt% | 10 | 8w |
Histological results 30.573 ± 2.548(β-TCP) 45.223 ± 5.095(Sr /β-TCP) Micro-CT: 26.222 ± 2.667(β-TCP) 37.333 ± 3.556(Sr /β-TCP) |
Histomorphometrical results 29.968 ± 3.048(β-TCP) 25.016 ± 2.413(Sr /β-TCP) |
Sr-doping improved bone repair | Sr-doping accelerated biomaterial resorption |
| Thormann [44] | Rat/Osteoporosis/Femur/n = 15 | Sham/CPCa/SrCPC | NA | 15 | 6 weeks |
Histomorphometrical results 4.2 ± 3(CPC) 11 ± 1(SrCPC) |
NA | Sr-doping improved bone repair | NA |
| Tian [45] | Rabbit/Healthy/Radius | CPP/SrCPP | NA | 8 | 4, 8 and 16 weeks |
Histomorphometrical results 4w: 9.884 ± 0.401(CPP) 13.968 ± 0.560(SCPP) 8w: 19.012 ± 0.801(CPP) 27.179 ± 1.121(SCPP) 16w: 39.911 ± 1.121(CPP) 45.036 ± 1.361(SCPP) |
4w: 25.054 ± 1.125(CPP) 25.696 ± 0.858(SCPP) 8w: 20.125 ± 0.857(CPP) 19.964 ± 0.482(SCPP) 16w: 12.411 ± 0.643(CPP) 11.875 ± 0.75(SCPP) |
Sr-doping improved bone repair | Sr-doping accelerated biomaterial resorption |
| Tohidnezhad [46] | Mouse/Healthy/Femur | Sham/β-TCP/Srβ-TCP | NA | NA | 2 months |
Histological results 26.41% ± 1.31%(β-TCP) 61.93% ± 3.04%(β-TCP + Sr) |
NA | Sr-doping improved bone repair | NA |
| Valiense [47] | Rabbit/Healthy/Maxilla | CHA/SrCHA | NA | 6 | 4 and 12 weeks |
Histomorphometrical results 4w: 17.812 ± 9.423(CHA) 16.890 ± 9.797(SrCHA) 12w: 27.964 ± 4.863(CHA) 31.368 ± 2.614(SrCHA) |
Histomorphometrical results 4w: 14.620 ± 5.186(CHA) 18.241 ± 9.389(SCHA) 12w: 17.168 ± 7.869(CHA) 10.317 ± 6.36(SCHA) |
NA | Sr-doping accelerated biomaterial resorption |
| Vestermark [48] | Dog/Healthy/Humerus | HA/SrHA/Allograft | NA | 10 | 4 weeks |
Histomorphometrical results 28 ± 5.1(HA) 36 ± 3.06(SrHA) |
NA | NA | NA |
| Xie [15] | Rabbit/Healthy/Calvaria | CPP/SrCPP | NA | 3 | 4, 8 and 12 weeks |
Histomorphometrical results 8w: 18.938 ± 0.486(CPP) 25.475 ± 0.56(SCPP) 16w: 26.745 ± 1.344(CPP) 36.307 ± 0.198(SCPP) |
NA | Sr-doping improved bone repair | NA |
| Yu [49] | Rat/Healthy/Calvaria | Coll scaffold/(APMs/coll scaffold)/(SrAPMs/coll Scaffold) | 10 mol% | 12 | 8 weeks |
Micro-CT-BV/TV- 20.64 ± 7.33%(APMs/coll) 48.30 ± 11.75%(SrAPMs/coll) |
NA | Sr-doping improved bone repair | NA |
| Yuan [17] | Rat/Osteoporosis/Femur | HA/SrHA/(HA/G3-K PS)/(SrHA/G3-K PS) | 15% | 6 | 8 weeks |
Micro-CT: 17.558 ± 3.786(HA) 18.491 ± 3.567(15SrHA) |
NA | NA | |
| Zarins [11] | Rabbit/Osteoporosis/Femur | Sham/(HA /TCP)/Sr + (HA/TCP) | NA | 7 | 12 weeks | NA | NA | Sr-doping improved bone repair | NA |
| Zhao [16] | Rat/Osteoporosis/Femur | WCP/SrWCP/Sr-Ran + WCP | NA | 12 | 1, 8 and 12 weeks |
Histological results 8w:10.267 ± 3.850(WCP) 19.037 ± 4.92(SrWCP) 16w:11.337 ± 3.422(WCP) 23.102 ± 3.422(SrWCP) Micro-CT: 8w:20.315 ± 0.945(WCP) 21.417 ± 2.205(SrWCP) 16w:21.889 ± 2.205(WCP) 26.457 ± 1.889(SrWCP) |
NA | Sr-doping improved bone repair | NA |
CPC: calcium phosphate cement; SPC: Sr-doping calcium phosphate cement; HA: hydroxyapatite; CHA: Carbonated hydroxyapatite; CPP: calcium polyphosphate; TCP: tricalcium phosphate; Sr: Strontium; HAC: hydroxyapatite cement; DBB: Deproteinized bovine bone; Sham: without graft materials; PLLA: poly( l—lactic acid); SCPP: strontium-doped calcium polyphosphate; Asp-Sr/β-TCP: strontium-doped β-tricalcium phosphate (Sr/β-TCP) modified with aspirin; BSrCPC: strontium-doped calcium phosphate cement combined with single-dose local administration of BMP-2;Coll: collagen; APMs: amorphous calcium phosphate porous microspheres; HA/G3-K PS: hydroxyapatite gel modified by integrating branched poly(epsilon-lysine) dendrons with third-generation branches exposing phosphoserine; WCP: hydroxyapatite whiskers; Sr-Ran: strontium ranelate; NA: not available
aTricalcium phosphate (Ca3(PO4)2, TCP), calcium hydrogenphosphate (CaHPO4), calcium carbonate (CaCO3), and hydroxyapatite (HAp)
bEquimolar tetracalcium phosphate (Ca4(PO4)2O, TTCP) and anhydrous dicalcium phosphate (CaHPO4, DCPA)
cTetracalcium phosphate (Ca4P2O9, TTCP), dicalcium phosphate dihydrate