Table 1 Collection of MRONJ rodent models established by the classical method
From: Establishment and assessment of rodent models of medication-related osteonecrosis of the jaw (MRONJ)
Species | Age/week | Sex | Drug | Dose /(mg·kg−1) | Frequency | Administration route | Induction time/week | Times of administration | Extraction site | Interval | Total duration/week | MRONJ characteristics | Success rate | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Rat | 4 | F | ZA + DEX | ZA: 0.066 DEX: 5 | Thrice a week | SC | 6 | 36 | The right max M1 | TE after 2 weeks of drug administration | 6 | Exposed NB, incomplete epithelial continuity; EL; bone formation↓BV/TV↓ | 100% | |
Mouse | 8 | F | ZA | ZA: 0.5 | Weekly | SC | 8 | 8 | The right man M1, M2 | TE after 2 weeks of drug administration | 8 | Formation of EL | ND | |
Nude mouse | 8–10 | F | mAb | mAb: 10 | Thrice a week | IP | Approximately 4 | 12 | The left max M1 | TE conducted 1 week after the first antibody injection | Approximately 4 | Absence of OCs and accumulation of NB | ND | |
Rat | 12 | F | ZA | ZA: 0.035 | Once every 2 weeks | IV | 8 | 4 | The right man M1 | TE after 3 weeks of drug administration | 11 | NB area↑; number of stranded OCs↑ | 33.3% | |
Rat | 7 | ND | ZA | ZA:0.066 | Weekly | IP | 1–2 | 1/2/3 | Man M1, M2 of both sides | TE after 1 week of drug administration | Approximately 3 | Alveolar mucosal defects, granulation tissue, and exposed bone; BV/TV↓; osteonecrosis and EL↑; numbers of OCs↓ | ND | |
Rat | 12 | ND | ZA | ZA: 0.04 mg per rat | Weekly | TVI | 5 | 5 | The right max M1 | TE on the 7th week(drug induction has finished) | 15 | Exposed NB | 100% | |
Rat | 10–12 | F | ZA + DEX | ZA: 0.1 DEX: 1 | ZA:thrice a week for 4 weeks +ZA: 4 times a week, DEX: weekly for 3 weeks | IP | 7 | 27 | The right max molars | TE on the 11th week (drug induction has finished) | 14 | BE; number of EL↑; number of blood vessels↓ | 25% | |
ZA: 0.1 DEX: 1 | ZA: Thrice a week for 4 weeks +ZA: 4 times a week, DEX: Weekly for 3 weeks + additional ZA for 3 weeks | 10 | 39 | 50% | ||||||||||
Rat | 8 | F | ZA + DEX | ZA: 0.066 DEX: 5 | Thrice a week | SC | 4 | 24 | The left max M1 | TE after 2 weeks of drug administration | 4/6 | Exposed NB and EL; average number of OCs per linear bone perimeter↓; BV/TV, Tb.N, Tb.Th↓Tb.Sp↑ | 100% | |
Rat | 8 | M | ZA | ZA: 0.16 | 5 times at Weekly intervals | Jugular vein injection | 5 | 25 | The right max M1 | TE after 3 d after the third administration | 5 | BE; EL | 100% | |
Rat | 12 | F | ZA | ZA: 0.1 | Thrice a week | IP | 9 | 27 | The left max molars | TE after 7 weeks of drug administration | 11 | BE without abscess nor fistula; the number of osteocytes ↓EL↑; TNF-α and IL-1β in the gingival tissue↑ | 91.66% | |
Rat | 16–18 | F | ZA | ZA: 0.1 | Thrice a week | IP | 6/7 | 18/21 | The left man M1 | TE after 3 weeks of drug administration | 6/7 | Abscesses with purulent content; no clear signs of bone formation; EL | ND | |
Rat | 10 | M | ZA + DEX | ZA: 0.1 DEX: 1 | Twice a week | SC | 6 | 24 | The right max M1 | TE after 2 weeks of drug administration | 6 | Unhealed oral mucosa, exposed NB, number of polymorphonuclear cells, and EL↑ | 66.67% | |
Rat | 4 | F | ZA + DEX | ZA: 0.066 DEX: 5 | Thrice a week | Percutaneous injection | 4 | 24 | The right max M1 | TE after 2 weeks of drug administration | 4 | Exposed NB, incomplete epithelial continuity, insufficient formation of connective tissue, and infiltration of white blood cells | 100% | |
Rat | 9 | F | ZA + DEX | ZA: 0.035 DEX: 1 | ZA: Weekly DEX: Everyday | ZA: TVI DEX: IP | 3 | 24 | The left max molars | TE after 3 weeks of drug administration | 5/11 | The socket was not covered with mucosa; exposed alveolar bone; BV/TV↓ | ND | |
Rat | 9–11 | M | ALN + DEX | ALN: 0.2 DEX: 1 | Everyday | SC | ALN: 2 DEX: 4d | 18 | The unilateral M1, M2 | ALN injection once daily for 14 days, starting the day of TE, plus 1 mg·kg−1 DEX once daily for 4 d, starting 2 d before TE | Approximately 2 | Open wounds; erythema; exposed bone; infection and osteonecrosis | 84.62% | |
Mouse | 8–10 | F | ZA + DEX | ZA: 0.125 DEX: 5 | Weekly | TVI | 8 | 16 | Bilateral max M1 | TE after 2 weeks of drug administration | 10 | Inflammatory infiltration and unhealed mucosa; the NB; wound healing↓; BV/TV↓; numerous osteocytes with EL, inflammatory infiltrates, and the mucosa exposed chronically | Histopathologic: 78% Gross: 56% | |
Rat | 4 | F | ZA + DEX | ZA: 0.125 DEX: 5 | ZA: Twice a week DEX: Weekly | IP | 4 | 12 | The right man M1 | TE after 4 weeks of drug administration | 12 | Incomplete wound healing and the presence of exposed bone; BV/TV, Tb.N, BMD↓Tb.Sp↑; EL↑TRAP-positive cells↓ | 100% | |
Mouse | 8–12 | F | ZA + CY | ZA: 0.05 CY: 100 | Twice a week | ZA: SC CY: IP | Prevention:7 Treatment:5 | 20/28 | The max M1 | TE after 3 weeks of drug administration | 7/9 | Bone fill↓; EL↑ | ND | |
Mouse | 8 | F | ZA + CY | ZA: 0.05 CY: 150 | ZA: Twice a week CY: Twice and once a week before and after tooth extraction | ZA: SC CY: IP | 5/7 | 18/24 | The max M1 | TE after 3 weeks of drug administration | 5/7 | Exposed bone; wound open areas↑; OCs on bone surfaces of tooth extraction sockets↓; serum TRAcP5b levels↓; living bone and osteocyte density↓; NB and the number of EL↑; Tb.N, Tb.Th↓Tb.Sp↑ | 92.8% | |
mAb+CY | mAb: 5 CY: 150 | mAb: Once every 3 weeks CY: Twice and once a week before and after tooth extraction | mAb: SC CY: IP | 9/12 | 92.8% | |||||||||
ZA/CY/mAb | ZA: 0.05/ CY: 150/ mAb: 5 | ZA: Twice a week CY: Twice and once a week before and after tooth extraction mAb: Once every 3 wks | ZA: SC CY: IP mAb: SC | 1/2/8/10/14 | CY : 50% ZA: 0 | |||||||||
Rat | 8 | M | ZA + DEX | ZA: 0.125 DEX: 5 | ZA: Twice a week DEX: Weekly | IP | 5 | 15 | The left max M1 | TE after 1 week of drug administration | 5 | BE; soft tissue unhealed | 80% | |
Mouse | 8 | F | mAb+CY | mAb: 5 CY: 150 | mAb: Once every 3 weeks CY: Twice and once a week before and after tooth extraction | mAb:SC CY: IP | 5/7 | 9/11 | bilateral max M1 | TE after 3 weeks of drug administration | 5/7 | Open wounds with BE; Tb.N, Tb.Th↓Tb.Sp, BMD↑; living bone area, osteocyte density↓; the number of EL↑ | 5w: 87.5% | |
Rat | ND | M | ZA | ZA: 0.1 | Thrice a week | IP | 8 | 24 | The right max M1 | TE after 1 week rest at the end of the 8th week | 13/17 | Newly formed bone tissue↓ | ND | |
Rat | 8-12 | F | ZA | ZA: 0.1 | Thrice a week | IP | 9 | 27 | The right max molars | TE on the 8th week | 11 | Mucosal ulcerations at the teeth extraction site, frequent exposure of NB; formation of granulation tissue, inflammatory cell infiltrates, fibrosis, and sequestra | 33%(implantation of saline/β-TCP constructs) | |
Mouse | 8 | M | ZA | ZA: 0.125 | Twice a week | TVI | 4 | 8 | The max M1 | TE after 1 week of drug administration | 5 | Opened extraction site; delay in wound healing; discontinuous keratinized coverage with dead bone formation | 40% | |
Rat | 8 | M | ZA | ZA: 0.04 mg per rat | Twice a week | IP + TVI | 5 | 10 | The M1 (the left or right side was randomly determined) | TE on 2 weeks after completion of the drug administration | 8 | Several empty bone lacunae; marginal bone loss; teeth with necrotic pulps; numerous sequestrates (NBs) with infiltration of acute and chronic inflammatory cells | 87.5% | |
Rat | 6 | F | ZA | ZA: 2.25 | Everyday | IP | 3 | 21 | The left max molars | TE after 3 weeks of drug administration | Approximately 5/6 | Necrosis; new bone formation↓ | ND | |
Rat | ND | M | ZA | ZA: 0.035 | Every 15 days | TVI | 8 | 4 | The right max incisors | TE after the 4th dose | Approximately 9 | BE(suppuration and bone sequestration); areas of osteolysis and fracture or loss of socket integrity | 40% | |
Rat | 16 | M | ZA | ZA: 0.1 | Weekly | SC | 8 | 8 | All left man molars | TE on the 7th week of drug administration | 8 | pseudo-epitheliomatous epithelium overlying exposed and/or unexposed bone with osteolytic lesions and clusters of EL | 76.9% | |
Rat | 9–10 | ND | ZA | ZA: 0.1 | At week 2 and 5 | IV | 5 | 2 | The right man M1 | TE on the 5th week (drug induction has finished) | 13 | Nonvital bone and EL; bone volume↓ | 100% | |
Rat | 8 | F | ZA | ZA: 0.1 | Thrice a week | IP | 9 | 27 | The right max molars | TE after 9 weeks of drug administration | 13/17 | Osteonecrosis(10 adjacent EL) | 13w: 83.3% 17w: 63.6% | |
Rat | 13 | F + M | ZA | ZA: 0.0075 | Weekly | SC | 11 | 11 | Bilateral max M1 | TE on the 3rd week of drug administration | 11 | Clinically exposed bone or a fistula; epithelium discontinuation with fragments of non-vital bone surrounded by non-specific inflammatory infiltrate | 25% | |
DEX | DEX: 1 | 11 | 0 | |||||||||||
ZA + DEX | ZA: 0.0075 DEX: 1 | 22 | 50% | |||||||||||
Mouse | 8–12 | F | ZA + CY | ZA: 0.05 CY: 150 | ZA: Twice a week CY: Twice and once a week before and after tooth extraction | ZA: SC CY: IP | 5 | 18 | Max M1 | TE after 3 weeks of drug administration | 5 | Open wounds; EL, living bone↓; the number of OCs↓ | 92.8% | |
Mouse | 7–10 | F | ZA | ZA: 0.1, 0.3, 0.5, 0.7 or 0.9 | A bolus IV injection | IV | Once | 1 | The left max M1 | TE after 1 week of drug administration | 3 | Abnormal oral mucosa swelling; osteonecrosis area↑ | ND | |
Rat | 10 | F | ZA | ZA: 0.06 | Weekly | TVI | 2 | 2 | The unilateral man M1 | TE on the 2nd week of drug administration(1 wk after the first dose) | 4/9 | Discolored, brownish exposed bone, sometimes with accompanying pus discharge; small bone fragments suggestive of sequestra; EL | 4w: 85.7% 9w: 57.1% | |
Rat | 20 | M | ZA | ZA: 0.06 | Weekly | IV | 6 | 7 | The right man M1 | TE after 1 week after the last drug administration | 15 | Extraoral signs of osteonecrosis; BE or fistula | 78.3% | |
Rat | 8 | F | ZA | ZA: 0.08 | Weekly | TVI | 10 | 10 | The right max M1, M2 | TE after 2 weeks of drug administration | 10 | Exposed bone; BV/TV↓; open sockets with unhealed mucosa and the connective tissue collapsed; large amounts of NBs, empty bone lacunae; inflammatory cell infiltration and few OCs | 61.5% | |
Rat | 5 | F | ZA + DEX | ZA: 0.0075 DEX: 7 | ZA: 2/4/7 times within 14 days DEX: Everyday | SC | 2 | 16/18/21 | Three right molars | TE after the end of drug administration | 4 | Unhealed wound areas; ulcerated connective tissue; thin trabeculae, lined with multinuclear OCs; marrow spaces infiltrated with the inflammatory cells | 2-ZA/DX: 20% 4/7-ZA/DX: 100% | |
Rat | 5 | M | ZA + DEX | ZA: 0.1 DEX: 1 | Thrice a week | ZA: IP DEX: IM | 10 | 60 | Bilateral max M1 | TE after 9 weeks of drug administration | 10 | Newly-formed woven bone inside the socket↓; areas of NB which were not lined by OCs; NB↑ | ND | |
Rat | 6–8 | F | ZA + DEX | ZA: 0.2 DEX: 5 | ZA: Weekly DEX: Thrice a week | ZA: TVI DEX: SC | 8 | 32 | The right max M1 | TE after 8 weeks of drug administration | 16 | Incomplete mucosal healing and BE; destruction of cortical bone; the NB areas with EL | 100% | |
Rat | 12 | F | ZA | ZA: 0.066 | Thrice a week | IP | 6/8/12 | 18/24/36 | The right man and max M1 | TE after 4 weeks of drug administration | 6/8/12 | BE; osteonecrosis (continued EL up to 5 in a row) | ND |
