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Table 8 In vivo studies using animal models that investigated the effect of NSAIDs on osseointegration
| Study (year) | Sample (size) | Treatment group (size) | Methodology | Parameter | Outcome |
|---|---|---|---|---|---|
| Cai et al. (2015) [22] | New Zealand white rabbits (n = 18). Implant inserted into calvaria (n = 18). | Control (n = 6) Diclofenac (n = 6) Parecoxib (n = 6) | Treatments were administered for 7 days: Diclofenac, 2 mg/kg/day orally Parecoxib, 1.5 mg/kg/day subcutaneous injection | Parameters observed at week 4 and 12 after implantation: Micro-CT: bone volume ratio, mean trabecular thickness, and mean trabecular separation. Histomorphometric: bone-to-implant contact. | No statistically significant differences between the three separate groups, nor between the different time points. |
| Chikazu et al. (2007) [30] | 9-week old male mice (n = 72). Implant inserted in femur (n = 72). | Mice with the original C57BL6/129S7 hybrid background were generated and maintained: Wild-type (n = 36) COX-2-knockout (n = 36) | No drug was administered | mRNA levels were observed at days 0, 1, 2, 4, 7, and 56 after implant insertion: expression of COX-2 and osteocalcin mRNA. Histomorphometric analysis at weeks 4 and 8: bone-to-implant contact. | Expression of COX-2 and osteocalcin mRNA was induced in bone surrounding implants in wild-type mice, but not in knockout mice. Bone-to-implant contact was minimal in knockout mice. |
| Goodman et al. (2002) [29] | New Zealand white rabbits (n = 8). Titanium bone harvest chamber inserted in tibia (n = 8). | Control Naproxen Rofecoxib | Treatments administered: Control: weeks 0–4 and 9–12. Naproxen, 110 mg/kg: weeks 5–8 orally. Rofecoxib, 12.5 mg/kg: week 13–16 orally. | Immunohistochemistry observed: total tissue area, total bone area, ratio of bone area, and total number of osteoblasts and osteoclast-like cells per section area | Naproxen and rofecoxib decreased bone ingrowth significantly. Rofecoxib decreased the area of osteoblasts per area compared with controls, and naproxen sodium did not reach statistical significance. |
| Goodman et al. (2005) [26] | New Zealand white rabbits (n = 8). Titanium bone harvest chamber implanted bilaterally in tibia (n = 16). | Control Rofecoxib | Treatments were administered for 6 weeks each: control-no drug; rofecoxib (12.5 mg/day) for the first 2 weeks of a 6-week trial, or the last 2 weeks or given continuously for all 6 weeks washout periods | Immunohistochemistry observed: total tissue area, total bone area, ratio of bone area, and the total number of osteoblasts and osteoclast-like cells per section area. | Rofecoxib given continuously for 6 weeks had less bone ingrowth, osteoclast-like cells and osteoblasts per area compared to the control treatment. Rofecoxib given for 2 of a 6-weeks cycle did not interfere with the parameters. |
| Pablos et al. (2008) [31] | Male Sprague-Dawley rats, 3-month-old, weighing 250-300 g (n = 30). Implant inserted in tibia (n = 30). | Control (n = 10) Diclofenac (n = 10) Meloxicam (n = 10) | Diclofenac, 1.07 mg/kg b.i.d. for 5 days. Meloxicam, 0.2 mg/kg daily for 5 days. | Histomorphometric analysis at 28 days after implant insertion: bone-to-implant contact, cortical bone area, and trabecular bone area within the implant threads | The bone-to-implant contact was lower in diclofenac compared with the meloxicam and control. The trabecular bone area was greater in diclofenac compared with meloxicam and control. |
| Ribeiro et al. (2006) [27] | Male Wistar rats, aged 10 weeks (n = 31). Implant inserted in tibia (n = 31). | Control (n = 14) Meloxicam (n = 17) | Daily subcutaneous injections for 60 days: control, 1 mL/kg of saline Meloxicam, 3 mg/kg | Histomorphometric analysis at 60 days after implant insertion: bone-to-implant contact, bone area, and bone density in the cortical and cancellous bone areas | Meloxicam reduced bone-to-implant contact, bone area, and bone density in both the cortical and cancellous bone areas. |
| Ribeiro et al. (2009) [28] | Male Wistar rats, aged 10 weeks (n = 30). Implant inserted in tibia (n = 30). | Control (n = 14) Meloxicam (n = 16) | Daily subcutaneous injections for 60 days: control, 1 mL/kg of saline Meloxicam, 3 mg/kg | Histomorphometric analysis at 60 days after implant insertion: bone-to-implant contact, bone area, and bone density in the cortical and cancellous bone areas | Blasting implant surface with aluminium oxide can increase bone-to-implant contact; however, it does not reverse the negative effects caused by a selective COX-2 inhibitor on bone healing around implants. |
| Salduz et al. (2017) [32] | New Zealand white rabbits, skeletally mature weighing 3.5–4 kg (n = 40). Titanium rods implanted bilaterally in femur (n = 80). | Control Diclofenac Celecoxib | Treatments were administered for 8 weeks: control, regular food Diclofenac, 5 mg/kg/day intramuscularly Celecoxib, 3 mg/kg/day orally | Biomechanical and histomorphometric analysis at 8 weeks after implant insertion: interface failure load, bone quality, bone implant interface, host reaction, total bone area, and bone-to-implant contact rate | No significant difference in the biomechanical and histological results between the groups. |
