Experimental osteonecrosis: development of a model in rodents administered alendronate

Abstract

Abstract:The main objective of this study was to cause bisphosphonate-related osteonecrosis of the jaws to develop in a rodent model. Adult male Holtzman rats were assigned to one of two experimental groups to receive alendronate (AL; 1 mg/kg/week; n = 6) or saline solution (CTL; n = 6). After 60 days of drug therapy, all animals were subjected to first lower molar extraction, and 28 days later, animals were euthanized. All rats treated with alendronate developed osteonecrosis, presenting as ulcers and necrotic bone, associated with a significant infection process, especially at the inter-alveolar septum area and crestal regions. The degree of vascularization, the levels of C-telopeptide cross-linked collagen type I and bone-specific alkaline phosphatase, as well as the bone volume were significantly reduced in these animals. Furthermore, on radiographic analysis, animals treated with alendronate presented evident sclerosis of the lamina dura of the lower first molar alveolar socket associated with decreased radiographic density in this area. These findings indicate that the protocol developed in the present study opens new perspectives and could be a good starting model for future property design.

The effects of sodium alendronate on socket healing after tooth extraction: a systematic review of animal studies

“…After reading the titles, 63 articles remained, and after careful abstract assessement, 44 reports were excluded (Table 2) due to the following reasons: reports that did not have a pure alendronane group; and studies that did not perform tooth extraction. The full text of the remaining 19 studies was retrieved 10,11,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] and included in this systematic review.…”

“…In summary, from the 19 eligible studies, five 39,42,45,[52][53] were considered to have "low' risk of bias in the SYRCLE's RoB tool, three studies 40,43,49 were considered to have "unclear" risk of bias, and 11 studies were considered to have "high" risk of bias. 10,11,37,38,41,44,[46][47][48]50,51 Twelve studies reported the randomization process for group allocation, but the sequence generation and the allocation concealment were not described in any of them. 11,37,39,40,42,44,45,[47][48][49][52][53] In five 39,42,45,[52][53] studies, the authors described the characteristics of the animals in sufficient detail to consider the experimental groups to be similar at baseline and to judge the study as having "low"' risk of bias.…”

“…Eleven articles did not report any processes to create and conceal allocation sequence, so they were considered to be unclear and to have a "high" risk in the selection bias domain. 10,11,37,38,41,44,[46][47][48]50,51 The authors did not provide information about the random placement of cages or animals within the animal room/facility. So, all of them received an unclear score in this domain.…”

“…Only two studies 37,42 reported that the investigator was blinded to the treatment allocation, and five studies stated that the outcome evaluator was blinded. 11,37,39,41,47 The incomplete outcome data were adequately addressed in only three studies. 10,39,50 All reports were unclear about selective outcome reporting, and four studies 39,43,45,49 were apparently free of other problems that could result in high risk of bias.…”

“…The characteristics of the 19 selected studies 10,11,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] are listed in Tables 3A and 3B. A total of 798 animals had been included in all eligible articles, distributed as 157 Spraguey-Dawley rats, 259 Wistar rats, 176 Holtzmann rats, 141 C57BL/6 mice, 12 mongrel dogs, 15 beagle dogs, and 38 New Zealand rabbits.…”