Experimental investigation of relationship between trauma and bisphosphonate-related osteonecrosis.

BACKGROUND: Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) disease is rare, but there are serious side-effects of BP therapy in patients. In some patients, surgery is needed and could not be cured. A standard test is not available showing the risk of jaw osteonecrosis in routine use. The measurement of serum C-terminal telopeptide (CTX) levels has been used in diseases of BRONJ resorption and antiresorptive therapy. AIM: This paper is aimed at investigating the relationship between traumatic procedures and presence of BP-related osteonecrosis. MATERIALS AND METHODS: Thirty male Wistar albino rats with weighing 200 ± 20 g were used for the experimental procedures. Rats were randomly divided into three groups each containing 10 rats as follows: Group 1 (traumatic extraction group), Group 2 (atraumatic extraction group), and Group 3 (control group). All groups, zoledronic acid (ZA) (0.3 mg/kg/week) [1] was diluted with physiological saline and given subcutaneously for 2 months. After the 2 months, Group 1 was subjected to traumatic extraction of right first lower molars, and Group 2 was subjected to atraumatic extractions of the right first lower molars. Group 3 was subjected to no extractions as a control group. Animals were euthanized 32 days after tooth extractions, and the ZA administration protocol was maintained until the animals' death. After sacrifice, blood samples were collected for C-terminal cross-linking telopeptide of type I collagen (CTX-1) levels, clinical and radiological findings were recorded. RESULTS: The bone resorption marker CTX-1 showed a significant difference among the groups. CTX-1 was measured significantly higher in blood samples of Group 2 (4.15 ± 0.34; P = 0.001) than Group 1 (3.77 ± 0.34; P = 0.0001). No, statistically significant changes were found between Groups 1 and 2 as for clinical and radiological assessment. CONCLUSION: This study provides preliminary observations for the development of an animal model of BRONJ. Although clinical and radiological findings were not relevant, serum CTX values are reliable biochemical markers for predicting BRONJ and also atraumatic surgical procedures are important to prevent BRONJ.

Influence of caffeic acid phenethyl ester on bone healing in a rat model.

OBJECTIVE: To examine the effects of caffeic acid phenethyl ester (CAPE; a component of honey bee-hive propolis with antioxidant, anti-inflammatory, antiviral and anticancer properties) on bone regeneration and fibrotic healing in a rat model. METHODS: Male Sprague-Dawley rats (n = 63; mean age 7 weeks; weight 280-490 g) were randomly divided into three groups: A, cranial defect with no bone healing treatment (n = 21); B, cranial defect treated with CAPE (n = 21); C, cranial defect treated with CAPE and ß-tricalcium phosphate/hydroxyl apatite (n = 21). Rats were anaesthetized with ketamine (8 mg/100 g) by intraperitoneal injection and a cranial critical size bone defect was created. Following surgery, CAPE (10 µmol/kg) was administered by daily intraperitoneal injection. Seven rats in each group were killed at days 7, 15 and 30 following surgery. Bone regeneration, fibrotic healing and osteoblast activity were evaluated by histopathology. RESULTS: Statistically significant differences in healing were found between all groups. There were no statistically significant within-group differences between day 7 and 15. At day 30, bone healing scores were significantly higher in groups B and C compared with group A. CONCLUSION: CAPE significantly improved bone-defect healing in a rat model, suggesting that CAPE has beneficial effects on bone healing.

Effects of mesenchymal stem cells in critical size bone defect.

BACKGROUND AND OBJECTIVES: The aim of this study was to compare culture-expanded, bone marrow-derived mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) loaded to biphasic calcium phosphate (BCP) bone ceramic in the repair of rat calvarial bone. MATERIALS AND METHODS: Critical-size (7 mm dia.) calvarial defects were prepared in the frontal-parietal bones of 90 adult female Sprague-Dawley rats. Rats were randomly divided into 5 groups, according to defect filling, as follows: Group I (n = 21), BCP; Group II (n = 21), BCP+PRP; Group III (n = 21), BCP+MSC; Group IV (n = 21), BCP+PRP+MSC; Group V (n = 6) (control), no treatment. Animals were sacrificed at 2, 8 and 12 weeks postsurgery and bone regeneration was evaluated both histologically and immunohistochemically. RESULTS: Statistically significant differences were observed in bone osteoblastic activity in calvarial defects among the groups (p < 0.05). PRP and MSC used in combination with BCP as a defect filling resulted in greater osteoblastic bone formation activity when compared to the use of BCP alone. CONCLUSIONS: The combination of mesenchymal stem cells, platelet rich plasma and synthetic bone substitute was found to be more effective in inducing new bone formation (osteogenesis) than the use of platelet rich plasma combined with synthetic bone substitute and the use of synthetic bone substitute alone.

Phosphodiesterase-5 inhibitors may facilitate bone defect recovery.

BACKGROUND AND OBJECTIVES: Bone healing is still one of the most important problems of the oral and maxillofacial surgery procedures. This study was designed to evaluate the effect of sildenafil citrate (which is used for erectile dysfunction) on bone defect healing in an experimental animal model. MATERIALS AND METHODS: A total of 42 male Wistar-albino rats were randomly assigned to the control group (n=21) or the study group (n=21). The control group was fed on a standard laboratory diet until 12 h before surgery, whereas the study group received Sildenafil citrate via orogastric tube 10 mg/kg once a day for 30 days. Under anaesthesia, a 3 x 3 x 2 mm depth defect was made on tibia of each rat. 7 animals from each group were euthanised on postoperative days 7,15 and 30. Bone samples were taken for examination, histologically on day 7, by 3D dental tomography on day 15, and for bone strength resistance on day 30. RESULTS: Statistically significant differences were determined between the groups from the inflammatory and repair phase, with the healing process being more advanced in the Sildenafil group. CONCLUSIONS: Sildenafil citrate can be used as a supporting factor to accelerate the healing process of bone. In future comprehensive studies will need to demonstrate the Sildenafil citrate affect on bone defect healing.