Sobia Zafar

Antibiotic prophylaxis in third molar surgery: A randomized double-blind placebo-controlled clinical trial using split-mouth technique.

The use of prophylactic antibiotics to reduce postoperative complications in third molar surgery remains controversial. The study was a prospective, randomized, double blind, placebo-controlled clinical trial. 100 patients were randomly assigned to two groups. Each patient acted as their own control using the split-mouth technique. Two unilateral impacted third molars were removed under antibiotic cover and the other two were removed without antibiotic cover. The first group received antibiotics on the first surgical visit. On the second surgical visit (after 3 weeks), placebo capsules were given or vice versa. The second group received antibiotics with continued therapy for 2 days on the first surgical visit and on the second surgical visit (after 3 weeks) placebo capsules were given or vice versa. Pain, swelling, infection, trismus and temperature were recorded on days 3, 7 and 14 after surgery. Of 380 impactions, 6 sockets (2%) became infected. There was no statistically significant difference in the infection rate, pain, swelling, trismus, and temperature between the two groups (p>0.05). Results of the study showed that prophylactic antibiotics did not have a statistically significant effect on postoperative infections in third molar surgery and should not be routinely administered when third molars are removed in non-immunocompromised patients.

Bisphosphonate-induced osteonecrosis of the jaw: a medical enigma?

Bisphosphonates are used for the standard of care of patients with skeletal metastases and hypocalcemia of malignancy. Bisphosphonate-induced osteonecrosis (BION) is a serious complication. Clinically, BION presents as an area of exposed alveolar bone that occurs spontaneously or becomes evident following an invasive surgical procedure such as extraction of a tooth, periodontal surgery, apicoectomy, or oral implant placement. The mechanism by which bisphosphonates cause osteonecrosis is uncertain. There are no controlled trials to show a direct cause-effect relationship between bisphosphonates and osteonecrosis of the jaw. Oral bisphosphonate-induced necrosis is a rare clinical entity, less frequent, less aggressive, more predictable, and more responsive to treatment than IV forms of bisphosphonate-related osteonecrosis of the jaw. However, there have been reports of this complication with the less potent oral forms of bisphosphonates (0.007% to 0.01%). The morbidity of osteonecrosis of the jaw induced by IV bisphosphonates is significant, so prevention should receive prime importance. Patients should receive prophylactic dental examinations, and any necessary dental treatment before starting bisphosphonate therapy. Good communication among dentists, oral surgeons, physicians, and oncologists is of vital importance in providing care of these patients.

Knife inflicted penetrating injuries of the maxillofacial region: A descriptive, record-based study

UNLABELLED Penetrating knife injuries of the face are more common in South Africa than the rest of the world. These injuries can be life-threatening, especially where the major blood vessels of the face are involved. The approach to treatment should be multidisciplinary, beginning with the trauma unit to provide airway maintenance and haemodynamic stabilisation. An interventional radiologist may be consulted for angiography. The aim of the present study was to retrospectively analyse all cases of knife-inflicted penetrating injuries to the maxillofacial region with the knife in situ and subsequently develop a management protocol to be used by maxillofacial surgery registrars when presented with such cases. MATERIALS AND METHODS It was a retrospective, cross-sectional and record-based study, analysing all penetrating knife injuries reported at various hospitals for a period of 11 years. In this study, 24 cases of knife injuries were analysed. RESULTS Twenty-one patients (87.5%) in this series were male and three (12.5%) were female. Of these 24 patients, 13 (54.2%) were coloured and 11 (45.8%) were black. There were no white or Indian patients. Post-surgical recovery of all patients was rapid and uneventful, and there were no fatalities. CONCLUSION Patients with knife injuries to the face with no definite signs of vascular injury can thus be safely and accurately managed on the basis of physical examination and plain-film radiography. An angiogram is mandatory if the patient presents with excessive bleeding, an expanding haematoma or if the knife blade is in the region of any large vessels.

Zoledronic acid and geranylgeraniol regulate cellular behaviour and angiogenic gene expression in human gingival fibroblasts.

The mevalonate pathway (MVP) and the anti-angiogenic effect of bisphosphonates have been shown to play a role in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study determined the effect of the bisphosphonate, zoledronic acid and the replenishment of the MVP by geranylgeraniol on human gingival fibroblasts. Cell viability, apoptosis, morphological analysis using transmission electron microscopy, and gene expression for vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B, epiregulin and interferon-alpha were conducted. Results showed cellular viability was decreased in the presence of zoledronic acid and the co-addition of zoledronic acid with geranylgeraniol restored cell viability to control levels. Caspase 3/7 was detected in zoledronic-acid-treated cells indicating apoptosis. Transmission electron microscopy revealed dilation of the rough endoplasmic reticulum with zoledronic acid and the appearance of multiple lipid-like vesicles following the addition of geranylgeraniol. Zoledronic acid significantly (P < 0.05, FR > ± 2) up-regulated vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B and epiregulin at one or more time points but not interferon-alpha. Addition of geranylgeraniol resulted in a reduction in the expression of all five genes compared with zoledronic-acid-treated human gingival fibroblasts. The study concluded geranylgeraniol partially reversed the effects of zoledronic acid in human gingival fibroblasts both at the cellular and genetic levels, suggesting the regulation of these genes is mediated via the mevalonate pathway.

One-Piece Zirconia Ceramic versus Titanium Implants in the Jaw and Femur of a Sheep Model: A Pilot Study

Reports have documented titanium (Ti) hypersensitivity after dental implant treatment. Alternative materials have been suggested including zirconia (Zr) ceramics, which have shown predictable osseointegration in animal studies and appear free of immune responses. The aim of the research was to investigate the bone-to-implant contact (BIC) of one-piece Zr, compared with one-piece Ti implants, placed in the jaws and femurs of domestic sheep. Ten New Zealand mixed breed sheep were used. A One-piece prototype Ti (control) and one Zr (test) implant were placed in the mandible, and one of each implant (Ti and Zr) was placed into the femoral epicondyle of each animal. The femur implants were submerged and unloaded; the mandibular implants were placed using a one-stage transgingival protocol and were nonsubmerged. After a healing period of 12 weeks, %BIC was measured. The overall survival rate for mandibular and femur implants combined was 87.5%. %BIC was higher for Zr implants versus Ti implants in the femur (85.5%, versus 78.9%) (p = 0.002). Zirconia implants in the mandible showed comparable %BIC to titanium implants (72.2%, versus 60.3%) (p = 0.087). High failure rate of both Zr and Ti one-piece implants in the jaw could be attributed to the one-piece design and surface characteristics of the implant that could have influenced osseointegration. Further clinical trials are recommended to evaluate the performance of zirconia implants under loading conditions.

The bisphosphonate zoledronic acid regulates key angiogenesis-related genes in primary human gingival fibroblasts

BACKGROUND Osteonecrosis of the jaws is recognised as a serious complication for patients receiving bisphosphonates. The anti-angiogenic effects of bisphosphonates have been implicated in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The purpose of this study was to determine the effects of zoledronic acid on cultured human gingival fibroblasts in relation to the modulation of genes associated with angiogenic regulation. METHODS Primary cultures of fibroblasts were developed from gingival tissues excised during crown-lengthening surgery from three patients. Cells were cultured with and without 30μM zoledronic acid for 6, 12 and 24h and cellular proliferation and migration investigated using CellTiter-Blue and scratch wound assays, respectively. Gene expression was determined using semi-quantitative PCR array technology that allowed the analysis of 84 pathway-focused genes known to be important in the regulation of angiogenesis. RESULTS Zoledronic acid increased the proliferation of the gingival fibroblasts in a dose dependent manner with 12 and 24h of exposure. Scratch wounding of the human gingival fibroblasts and treatment with increasing doses and time exposure to zoledronic acid (ZA) inhibited their migration. Statistically significant increases in gene expression were found for RHOB, VEGFA, CD55 and BMP2 (p≤0.05) in response to 30μM zoledronic acid. CCL2 and IL6 genes were significantly downregulated (p≤0.05). CONCLUSIONS The regulation of the prenylated protein RHOB in this study was consistent with the known effects of zoledronic acid on the mevalonate pathway. The down regulation of CCL2 and IL6 and the upregulation of CD55 may be associated with suppression of inflammation. An increase in VEGFA and BMP2 gene expression suggests that fibroblasts respond to zoledronic acid by producing a proangiogenic environment.

Quantitative Real-Time Gene Profiling of Human Alveolar Osteoblasts

The use of quantitative real-time reverse transcriptase PCR (qRT2-PCR) for the identification of differentially regulated genes is a powerful technology. The protocol presented here uses qRT2-PCR gene arrays to investigate the regulation of 84 angiogenic related genes in human primary alveolar osteoblasts following treatment with the bisphosphonate, zoledronic acid (ZA), and geranylgeraniol (GGOH). GGOH has potential as a therapeutic agent for Bisphosphate-Related Osteonecrosis of the Jaw (BRONJ), a serious side-effect resulting from the treatment for metastatic cancer (Zafar et al., J Oral Pathol Med 43:711-721, 2014; Ruggiero, Ann NY Acad Sci 1218:38-46, 2011). The isolation of the primary osteoblast cells follows the methods previously described (Dillon et al., Methods Mol Biol 816:3-18, 2012) with a new RNA extraction technique described fully. The method highlights the importance of obtaining high-quality RNA which is DNA-free. Relative levels of gene expression are normalized against selected housekeeping genes (HKG) and a number of examples of how fold regulation (2-∆∆Cq) and gene expression level (2-∆Cq) data can be presented are given.