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Table 8 In vivo studies using animal models that investigated the effect of NSAIDs on osseointegration

From: The effect of non-steroidal anti-inflammatory drugs on the osteogenic activity in osseointegration: a systematic review

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.