Mohd Fadhli Khamis

Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model: micro-computed tomography and biomechanical evaluation.

Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone.

Micro-CT assessments of potential anti-osteoporotic agents

Bone quality assessment is important in assessments of potential agents for the prevention and treatment of osteoporosis. Bone density, microarchitecture and strength are important determinants in osteoporotic study which are widely studied using Dual-Energy X-ray Absorptiometry (DXA), histomorphometry and radiological imaging techniques. In recent years, high resolution micro-CT has become feasible for in vitro or in vivo evaluation of bone architecture. Three-dimensional images of micro-CT reflected high correlations with the conventional histomorphometry and DXA. In comparison to other imaging techniques, micro-CT is the most effective tool in detecting early bone changes for fracture prediction and assessments of potential anti-osteoporotic agents. It is crucial to define an ideal setting with safe radiation doses and appropriate methods for image reconstruction and segmentation to obtain high resolution images. Micro-CT evaluation provides a better insight of bone structure as well as non-metric parameters such as connectivity density, structural model index (SMI) and degree of anisotropy (DA). This non- invasive imaging technique is also equipped with finite element analysis for evaluation of bone biomechanical strength. Micro-CT allows a compressive understanding of the relationships between bone density, microarchitecture and strength which is fundamental to development of pharmacological interventions.

Bolton tooth size ratio and its relation with arch widths, arch length and arch perimeter: A cone beam computed tomography (CBCT) study

Abstract Objective. The prime aim of the study was to measure and compare the 3D CBCT Bolton tooth size ratio in relation to the upper and lower arch widths, arch length and arch perimeter. Materials and methods. The data source was CBCT high volumetric data from the archives. Tooth size, arch widths, arch length and arch perimeter were measured in maxilla and mandibular arches. The independent t-test and ANOVA were used for statistical analyses. Results. The female Bolton anterior ratio (BAR) (78.373) and Bolton overall ratio (BOR) (93.231) show a greater tooth size ratio in comparison to male BAR (77.162) and BOR (93.124), respectively. However, no significant difference was found in the sexual comparison of all the measurements. Tooth size ratio in arch width groups also showed no significant difference. Significant discrepancies in the arch length (p < 0.05) groups and overall ratio and in the arch perimeter groups (p < 0.05 and p < 0.01) and anterior ratio were revealed. Conclusions. Tooth size ratios during orthodontic treatment for different arch length and arch perimeter groups need to be evaluated carefully.

The effects of Labisia pumila on postmenopausal osteoporotic rat model: Dose and time-dependent micro-CT analysis.

BACKGROUND Postmenopausal osteoporosis is best treated and prevented by estrogen replacement therapy (ERT). Although effective, ERT may cause breast cancer, uterine cancer and cardiovascular problems. Labisia pumila var. alata (LP), a herb with phytoestrogenic, antioxidative and anti-inflammatory effects has potential as an ERT alternative. OBJECTIVE This study aimed to evaluate micro-CT analysis on the effects of LP supplementation on the trabecular microarchitecture of postmenopausal osteoporosis rat model. Micro-CT is an effective tool in detecting changes in trabecular bone structure and providing a three dimensional information which may replace other conventional bone analysis methods. METHODS Ninety-six female Sprague-Dawley rats (4 to 5 months old) were randomly divided into six groups of baseline group (BL) Sham-operated (Sham), ovariectomised control (OVXC), ovariectomised with 64.5 μg/kg of Premarin (ERT), ovariectomised with 20 mg/kg of LP (LP20) and ovariectomised with 100 mg/kg of LP at (LP100). The vehicle (deionized water), Premarin and LP were given via daily oral gavages for three, six and nine weeks of treatment periods. Rats in BL group were euthanized before the start of the study, while other rats were euthanized after completion of their treatments. Femora were dissected out and trabecular bone microarchitecture analysed with micro-CT. RESULTS Micro-CT analysis of OVXC rats revealed significant osteoporotic changes in connectivity density, trabecular bone volume, trabecular thickness, trabecular separation and trabecular number. Both ERT and LP were able to reverse all the OVX-induced bone changes with the best results seen with 100 mg/kg of LP for nine weeks duration of treatment. CONCLUSION Micro-CT provides accurate and reliable information on trabecular bone parameters which aid in the diagnosis and treatment of osteoporosis. LP supplementation at 100 mg/kg was more effective than ERT in reversing ovariectomy-induced bone changes. Further studies are required to explore the potential of LP as ERT alternative in the treatment and prevention of postmenopausal osteoporosis.

Bone Micro-CT Assessments in an Orchidectomised Rat Model Supplemented with Eurycoma longifolia

Recent studies suggested that Eurycoma longifolia, a herbal plant, may have the potential to treat osteoporosis in elderly male. This study aimed to determine the effects of Eurycoma longifolia supplementation on the trabecular bone microarchitecture of orchidectomised rats (androgen-deficient osteoporosis model). Forty-eight-aged (10–12 months old) Sprague Dawley rats were divided into six groups of sham-operated (SHAM), orchidectomised control (ORX), orchidectomised + 7 mg/rat testosterone enanthate (TEN) and orchidectomised + Eurycoma longifolia 30 mg/kg (EL30), orchidectomised + Eurycoma longifolia 60 mg/kg (EL60), orchidectomised + Eurycoma longifolia 90 mg/kg (EL90). Rats were euthanized following six weeks of treatment. The left femora were used to measure the trabecular bone microarchitecture using micro-CT. Orchidectomy significantly decreased connectivity density, trabecular bone volume, and trabecular number compared to the SHAM group. Testosterone replacement reversed all the orchidectomy-induced changes in the micro-CT parameters. EL at 30 and 60 mg/kg rat worsened the trabecular bone connectivity density and trabecular separation parameters of orchidectomised rats. EL at 90 mg/kg rat preserved the bone volume. High dose of EL (90 mg/kg) may have potential in preserving the bone microarchitecture of orchidectomised rats, but lower doses may further worsen the osteoporotic changes.

Treatment Outcome of Bangladeshi UCLP Patients Based on Both Phenotype and Postnatal Treatment Factors Using Modified Huddart Bodenham (mHB) Index

Objective: To evaluate the dental arch relationship (DAR) of nonsyndromic unilateral cleft lip and palate (UCLP) and to explore the various phenotype and postnatal treatment factors that are responsible for poor DAR. Design: Retrospective study. Setting: School of Dental Science, Universiti Sains Malaysia. Subjects: Eighty-four Bangladeshi children with nonsyndromic UCLP who received cheiloplasty and palatoplasty. Main Outcome Measures: Dental models were taken at 5 to 12 years of age (man: 7.69), and dental arch relationships were assessed using modified Huddart/Bodenham index (mHB) by two raters. Kappa statistics was used to evaluate the intra- and interexaminer agreements, chi-square was used to assess the associations, and logistic regression analysis was used to explore the responsible factors that affect DAR. Results: The total mHB score (mean [SD]) was −8.261 (7.115). Intra- and interagreement was very good. Using crude and stepwise backward regression analysis, significant association was found between positive history of class III (P = .025, P = .030, respectively) and unfavorable DAR. Complete UCLP (P = .003) was also significantly correlated with unfavorable DAR. Conclusion: This multivariate study suggested complete type of UCLP and positive history of class III had a significantly unfavorable effect on the DAR.

Fracture resistance of over-flared root canals filled with MTA and resin-based material: an in vitro study

AIM: To measure the fracture resistance of over-flared roots filled with a variety of materials (gutta-percha-nano HA, resilon-epiphany, composite and mineral trioxide aggregate - MTA) using the Instron machine test and micro-computed tomography (Micro CT) Scan. In addition, scanning electron microscopy (SEM) images were used to illustrate the type of fracture patterns of the specimens. METHODS: One hundred and twenty extracted human mandibular single-rooted premolars were selected. A total of 105 out of the selected teeth were prepared to the working length and over-flared, leaving the apical 5 mm undisturbed. Fifteen samples had no treatment and were used as a positive control group (Group +ve). The 105 test teeth were further divided into 7 groups of 15 samples each. One of the 7 groups was designated as negative control (Group -ve) where teeth were over prepared and left without obturation. Remaining groups were filled with gutta-percha-nanoHA (Group1), gutta-percha-nano HA+composite (Group 2), gutta-percha-nano HA+MTA (Group 3), resilon-epiphany (Group 4), resilon-epiphany+composite (Group 5), and resilon-epiphany+MTA (Group 6). Fracture resistance of all samples was measured using the Instron testing machine. Three samples from each group had the depth of their fracture line measured by Micro CT Scan, and 2 samples from each group had their fracture pattern illustrated using SEM. RESULTS: The highest fracture resistance was observed in Group +ve, followed by Groups 3, 6, 5, 2, 4, 1, and Group -ve, with values (in N) of: 1598 (641.0), 1190.5(424.2), 1164.7 (489.4), 821.2 (220.9), 683.4(179), 658.4 (211.3), 658.4 (99.0), 158.3(49.3), respectively. Statistical analysis for root fracture resistance showed highly significant difference between all groups with p value < 001. CONCLUSIONS: Micro CT Scan and SEM analysis indicated the ability of MTA to withstand vertical force.

Minimally Invasive Techniques to Accelerate the Orthodontic Tooth Movement: A Systematic Review of Animal Studies

Objective. To evaluate various noninvasive and minimally invasive procedures for the enhancement of orthodontic tooth movement in animals. Materials and Methods. Literature was searched using NCBI (PubMed, PubMed Central, and PubMed Health), MedPilot (Medline, Catalogue ZB MED, Catalogue Medicine Health, and Excerpta Medica Database (EMBASE)), and Google Scholar from January 2009 till 31 December 2014. We included original articles related to noninvasive and minimally invasive procedures to enhance orthodontic tooth movement in animals. Extraction of data and quality assessments were carried out by two observers independently. Results. The total number of hits was 9195 out of which just 11 fulfilled the inclusion criteria. Nine articles were good and 5 articles were moderate in quality. Low level laser therapy (LLLT) was among the most common noninvasive techniques whereas flapless corticision using various instruments was among the commonest minimally invasive procedures to enhance velocity of tooth movement. Conclusions. LLLT, low intensity pulsed ultrasound (LIPUS), mechanical vibration, and flapless corticision are emerging noninvasive and minimally invasive techniques which need further researches to establish protocols to use them clinically with conviction.

Prevalence and patterning of maxillary premolar accessory ridges (MxPARs) in several human populations

We present new data on the prevalence and patterning of the maxillary premolar accessory ridge (MxPAR), a common but understudied morphological dental trait that is expressed as a linear elevation extending from the buccal cusp ridge to the medial sulcus of maxillary premolar teeth. A total of 579 sets of dental casts, representing six ethnic groups, were scored using the five-grade system proposed by Burnett et al. (2010). The frequency and distribution of the MxPAR were determined by tooth type, sex, side, locus and ethnicity, and the applicability of the scoring system was assessed. The MxPAR was found in approximately two-thirds of premolar teeth, more often on second than first premolars, and more often on the distal aspect of the occlusal surface than the mesial. There was some evidence that more pronounced forms of the feature occurred more often in males than females, and that there may be some directionality in its expression between sides. Variation was also noted in the frequency of occurrence and degree of expression of the MxPAR between ethnic groups. Intra- and inter-observer concordance rates for scoring the MxPAR were low, confirming that it was difficult to score the trait identically on two different occasions. Our findings have clarified the distribution of the MxPAR within the dentition and between ethnic groups, and highlighted the need for researchers to carry out thorough replicability studies and to decide on an appropriate breakpoint for determining presence or absence of this feature before embarking on genetic studies or bio-distance analyses.

New prediction equations for the estimation of maxillary mandibular canine and premolar widths from mandibular incisors and mandibular first permanent molar widths: A digital model study.

Objective The primary aim of the study was to generate new prediction equations for the estimation of maxillary and mandibular canine and premolar widths based on mandibular incisors and first permanent molar widths. Methods A total of 2,340 calculations (768 based on the sum of mandibular incisor and first permanent molar widths, and 1,572 based on the maxillary and mandibular canine and premolar widths) were performed, and a digital stereomicroscope was used to derive the the digital models and measurements. Mesiodistal widths of maxillary and mandibular teeth were measured via scanned digital models. Results There was a strong positive correlation between the estimation of maxillary (r = 0.85994, r2 = 0.7395) and mandibular (r = 0.8708, r2 = 0.7582) canine and premolar widths. The intraclass correlation coefficients were statistically significant, and the coefficients were in the strong correlation range, with an average of 0.9. Linear regression analysis was used to establish prediction equations. Prediction equations were developed to estimate maxillary arches based on Y = 15.746 + 0.602 × sum of mandibular incisors and mandibular first permanent molar widths (sum of mandibular incisors [SMI] + molars), Y = 18.224 + 0.540 × (SMI + molars), and Y = 16.186 + 0.586 × (SMI + molars) for both genders, and to estimate mandibular arches the parameters used were Y = 16.391 + 0.564 × (SMI + molars), Y = 14.444 + 0.609 × (SMI + molars), and Y = 19.915 + 0.481 × (SMI + molars). Conclusions These formulas will be helpful for orthodontic diagnosis and clinical treatment planning during the mixed dentition stage.