Prostaglandins control osteoblastic and osteoclastic function under physiological or pathological conditions and are important modulators of the bone healing process. The non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and consequently prostaglandins synthesis. Experimental and clinical evidence has indicated a risk for reparative bone formation related to the use of non-selective (COX-1 and COX-2) and COX-2 selective NSAIDs. Ketorolac is a non-selective NSAID which, at low doses, has a preferential COX-1 inhibitory effect and etoricoxib is a new selective COX-2 inhibitor. Although literature data have suggested that ketorolac can interfere negatively with long bone fracture healing, there seems to be no study associating etoricoxib with reparative bone formation. Paracetamol/acetaminophen, one of the first choices for pain control in clinical dentistry, has been considered a weak anti-inflammatory drug, although supposedly capable of inhibiting COX-2 activity in inflammatory sites. OBJECTIVE: The purpose of the present study was to investigate whether paracetamol, ketorolac and etoricoxib can hinder alveolar bone formation, taking the filling of rat extraction socket with newly formed bone as experimental model. MATERIAL AND METHODS: The degree of new bone formation inside the alveolar socket was estimated two weeks after tooth extraction by a differential point-counting method, using an optical microscopy with a digital camera for image capture and histometry software. Differences between groups were analyzed by ANOVA after confirming a normal distribution of sample data. RESULTS AND CONCLUSIONS: Histometric results confirmed that none of the tested drugs had a detrimental effect in the volume fraction of bone trabeculae formed inside the alveolar socket.

Epidemiological studies have suggested that cola beverage consumption may affect bone metabolism and increase bone fracture risk. Experimental evidence linking cola beverage consumption to deleterious effects on bone is lacking. Herein, we investigated whether cola beverage consumption from weaning to early puberty delays the rate of reparative bone formation inside the socket of an extracted tooth in rats. Twenty male Wistar rats received cola beverage (cola group) or tap water (control group) ad libitum from the age of 23 days until tooth extraction at 42 days and euthanasia 2 and 3 weeks later. The neoformed bone volume inside the alveolar socket was estimated in semi-serial longitudinal sections using a quantitative differential point-counting method. Histological examination suggested a decrease in the osteogenic process within the tooth sockets of rats from both cola groups, which had thinner and sparser new bone trabeculae. Histometric data confirmed that alveolar bone healing was significantly delayed in cola-fed rats at three weeks after tooth extraction (ANOVA, p = 0.0006, followed by Tukey's test, p < 0.01). Although the results of studies in rats cannot be extrapolated directly to human clinical dentistry, the present study provides evidence that cola beverage consumption negatively affect maxillary bone formation.

No presente trabalho analisou-se histometricamente a capacidade de um material de origem nacional em estimular o reparo ósseo alveolar de ratos. Uma mistura de BMPs bovinas purificadas adsorvidas à hidroxiapatita microgranular absorvível foi aglutinada com colágeno bovino e soro fisiológico e implantada na cavidade de extração de incisivos superiores. Os ratos implantados e controles (n=30 por grupo) foram sacrificados após 1, 2, 3 e 9 semanas, as hemi-maxilas contendo os alvéolos em reparação foram descalcificadas e processadas para inclusão em parafina e obtenção de cortes semi-seriados, corados com hematoxilina e eosina. O volume percentual de tecido ósseo reparacional foi estimado por um método de contagem diferencial de pontos, em imagens histológicas analisadas sob uma ocular contendo um retículo com 100 pontos eqüidistantes. Nos ratos controles e implantados o reparo seguiu o padrão descrito na literatura. No grupo implantado, o material não estimulou o reparo ósseo alveolar em nenhum dos períodos analisados. Os resultados sugerem que a mistura de BMPs adsorvidas à hidroxiapatita microgranular absorvível não tenha garantido sua incorporação a um sistema carreador de absorção lenta que propiciasse sua liberação num ritmo compatível com o da neoformação óssea, portanto, adequado à osteoindução.

The capacity of a commercially available pool of bovine bone morphogenetic proteins (BMPs) to stimulate osteogenesis in the rat alveolar healing was investigated by histometric analysis. Male rats were anesthetized and had their upper incisor extracted. A pool of purified bovine BMPs adsorbed to microgranular resorbable hydroxyapatite was agglutinated with bovine collagen and saline before implantation into the alveolar socket. The implanted and control rats (n=30 per group) were sacrificed 1 to 9 weeks postoperatively, the hemi-maxillae were decalcified, processed for paraffin embedding and semi-serial longitudinal sections were obtained and stained with hematoxylin and eosin. The volume fraction of alveolar healing components was estimated by a differential point-counting method in histologic images. The results showed that in both, control and implanted rats, the alveolar healing followed the histologic pattern usually described in the literature. Quantitative data confirmed that the BMPs mixture did not stimulate new bone formation in the alveolar socket of implanted rats. These results suggest that the pool of BMPs adsorbed to hydroxyapatite and agglutinated with bovine collagen did not warrant incorporation of the osteoinductive proteins to a slow-absorption system that would allow a BMPs release rate compatible to that of new bone formation, and thus more adequate to osteoinduction.

Comparou-se o efeito de dois protocolos experimentais (ovariectomia associada ou não à dieta pobre em Ca++) utilizados para promover osteoporose em maxila e metáfise proximal de ratas, nos períodos de 5 e 11 semanas pós-cirurgia. Ratas Wistar foram ovariectomizadas ou submetidas à cirurgia simulada. Metade das ratas ovariectomizadas recebeu dieta pobre em Ca++ (ovx*) e as demais (ovx), assim como as que sofreram falsa cirurgia, receberam dieta comercial. Foram coletados o osso maxilar (após extração dos molares) e a metáfise proximal da tíbia para medidas do peso seco (60ºC/12 h) e do da cinza óssea (700ºC/14 h), utilizada para dosagem de Ca++ (método colorimétrico). Cinco semanas após a cirurgia, não se observaram alterações nos parâmetros investigados no grupo ovx, enquanto no grupo ovx* houve redução da massa óssea da metáfise proximal (17%) e da maxila (35%). Após 11 semanas, o grupo ovx apresentou 14% de redução da massa óssea da metáfise proximal, mas não da maxila, enquanto no grupo ovx* observou-se diminuição de 30% em ambos os segmentos ósseos. A concentração de Ca++ na cinza não se alterou em nenhuma condição experimental. Os resultados mostram que apenas a deficiência de estrógeno não é suficiente para provocar osteoporose maxilar em ratas num período de até 11 semanas, mas que nesse período já se observa seu efeito deletério na massa da metáfise proximal. Quando se associa a ovariectomia à dieta pobre em Ca++, observa-se diminuição da massa óssea após 5 semanas, 2 vezes maior na maxila do que na metáfise proximal da tíbia.

The effects of two experimental protocols (ovariectomy associated or not with a low calcium diet) used to promote osteoporosis in the rat maxilla and proximal tibia were compared 5 and 11 weeks after surgery. Female Wistar rats were ovariectomized or sham-operated. Half of the ovariectomized rats were fed a low Ca++ diet (ovx*) and the remaining ovariectomized (ovx) and sham animals received a standard chow. At sacrifice, the proximal metaphysis was excised from the tibia and the molars were extracted from the hemi-maxilla. Dry (60°C overnight) and ash (700°C/14 h) weights were measured and the ashes were used for Ca++ measurement by means of a colorimetric method. After 5 weeks, ovx caused no alteration while ovx* decreased proximal metaphysis (17%) and maxilla (35%) bone mass. After 11 weeks, ovx caused a 14% bone mass reduction in the proximal metaphysis but not in the maxilla, while ovx* caused a comparable bone mass reduction (30%) in both bone segments. Calcium concentration was not altered in any experimental condition. The results show that estrogen deficiency is insufficient to cause maxillary osteoporosis in rats over an 11-week period and a long-term ovariectomy is needed to exert deleterious effect on proximal metaphysis bone mass. When a low Ca++ diet is associated with estrogen deficiency, however, a relatively precocious harmful effect is observed, twice as pronounced in the maxilla than in the proximal metaphysis. On a long-term basis, ovariectomy associated with a low Ca++ diet seems to be equally injurious to both proximal metaphysis and maxilla.

Os objetivos do presente trabalho foram: 1) testar a biocompatibilidade de uma resina natural, derivada do óleo de mamona, implantada na cavidade de extração dental de ratos, e 2) estudar a possível interferência do material na cronologia do reparo alveolar. O material (AUG-EX, Poliquil Araraquara Polímeros Químicos Ltda., Araraquara - SP) foi implantado no alvéolo imediatamente após a extração do incisivo superior direito e os ratos foram sacrificados de 1 a 6 semanas após a extração ou extração + implante. As hemimaxilas foram descalcificadas e processadas para inclusão em parafina e obtenção de cortes semi-seriados, corados com hematoxilina-eosina. Os flocos da resina, de forma irregular e tamanho variável, localizaram-se entre os terços alveolares médio e cervical, inicialmente circundados por tecido de granulação e a seguir por quantidade progressivamente maior de tecido ósseo, no geral com a presença de um tecido conjuntivo interposto, mas em algumas áreas estabelecendo aparente osseointegração direta. Não houve persistência da reação inflamatória, mas observou-se pequena quantidade de células gigantes aderidas à superfície do material, em todos os períodos. A análise histométrica (contagem diferencial de pontos) do terço apical mostrou um atraso de 13% a 20% no reparo alveolar dos ratos implantados, com menor neoformação óssea associada a maiores volumes percentuais de tecido conjuntivo e de remanescentes do coágulo sangüíneo.

The purposes of the present study were: 1) to investigate the biocompatibility of a natural resin (made of fatty acids extracted from Ricinus communis) implanted in the dental alveolus of rats and 2) to verify any possible interference of that material in the osseous healing following tooth extraction. The resin (AUG-EX, Poliquil Araraquara Polímeros Químicos LTDA, Araraquara - SP) was placed inside de alveoli immediately after extraction of the upper right incisors. The animals were sacrificed 1, 2, 3 and 6 weeks after extraction or extraction + implantation. The hemi-maxillae were decalcified and processed for paraffin embedding. Longitudinal 6-micrometer-thick semi-serial sections stained with hematoxylin and eosin were obtained. Histologic examination showed particles of irregular shape and variable size (700-1200 mum) localized in the medium/cervical alveolar thirds, with a scanty but persistent foreign body reaction. From the second week on, as the relative volume of bone trabeculae increased, it was seen in close contact with the surface of the implanted material in some regions. Histometric analysis (differential point counting method), used to quantify the healing process in the apical third, showed a small but significant decrease (13%-20%) in new bone formation in the implanted rats. In conclusion, the results show that, in spite of its biocompatible nature, the studied resin hinders the post-extration healing process.