Stability of proximal mandibular anatomical structures following bilateral sagittal split osteotomy.

The aim of this study was to investigate the stability of the proximal mandibular reference structures that have been proposed in the literature for superimposition. Forty proximal mandibular segments of 20 patients who underwent bilateral sagittal split osteotomy (BSSO) for advancement were reconstructed from a pair of pre- and postoperative (2 years) cone beam computed tomography scans, and spatially divided into the mandibular condyle, the coronoid process, and 20 mandibular ramus regions. To assess the stability of the anatomical regions, the volumetric and surface discrepancy between the superimposed pre- and postoperative regions were calculated. One-sample t-tests were applied to analyse the statistical stability of the individual regions. Two statistically stable (P < 0.05) structures in the proximal segment of the mandible following BSSO were identified: (1) the posterior part of the mandibular ramus above the gonial angle and below the condylar neck, and (2) the sub-coronoid area below the coronoid process/mandibular notch. Using these stable structures for superimposition resulted in an assessment discrepancy in the condylar displacement of up to 1.1 mm and in the volumetric change of up to 2.8%. Hence, it is suggested that these two identified stable structures are used as reference areas when assessing condylar displacement and change using superimposition.

Virtual surgical analysis: long-term cone beam computed tomography stability assessment of segmental bimaxillary surgery.

The assessment of the stability of orthognathic surgery is often time-consuming, relies on manual re-identification of anatomical landmarks, and has been based on short-term follow-up. The purpose of this study was to propose and validate a semi-automated approach for three-dimensional (3D) assessment of the long-term stability of segmental bimaxillary surgery. The approach was developed and validated using cone beam computed tomography scans obtained at 2 weeks and 2 years postoperative. The stability of the surgical outcome was calculated as 3D translational and rotational differences between the short- and long-term postoperative positions of the individual bone segments. To evaluate reliability, intra-class correlation coefficients were calculated at a 95% confidence interval on measurements of two observers. Ten class II and III patients (six male, four female; mean age 24.4 years), who underwent a combined three-piece Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty, were included in the study. Intra- and inter-observer reliability were excellent (range 0.82-0.99). The range of the mean absolute difference of the intra- and inter-observer translational and rotational measurements were 0.14 mm (0.13)-0.44 mm (0.50) and 0.20° (0.16)-0.92° (0.78). The approach has excellent reliability for 3D assessment of long-term stability of segmental bimaxillary surgery.

Virtual histology uncertainty in synchrotron x-ray micro-computed tomography evaluation.

A three-dimensional (3D) X-ray tomogram evaluation gives a full view of the bone distribution around an entire implant in contrast to the often-used two-dimensional (2D) histological methods. High-resolution X-ray absorption tomography was used to evaluate the 3D bone growth around dental implants in an experimental goat mandible reconstruction model. The tomograms allowed for the construction of virtual histological cross-sections that could be used to evaluate the statistical uncertainty of the histological methods, which was the purpose of this paper. The virtual 2D histological results showed a significantly higher uncertainty within the same sample than did the full 3D volume results.

Nerve lesions following apical extrusion of non-setting calcium hydroxide: a systematic case review and report of two cases.

We present two cases of apical extrusion of non-setting, calcium hydroxide paste which had been placed as an interappointment root canal dressing during routine endodontic treatment resulting in tissue necrosis of a large part of the mandible. Surgical intervention consisted of resections in both instances. In relation to the cases presented, a systematic review of similar cases in the literature between 1980 and April 2013 was conducted which resulted in eight cases meeting the criteria outlined. As with the two presented cases, half of these eight cases showed serious adverse effects and the use of an injectable system had most often been related to apical extrusion. Consequently, great care should be taken when applying the paste into the canal system.

Analgesic efficacy with rapidly absorbed ibuprofen sodium dihydrate in postsurgical dental pain: results from the randomized QUIKK trial.

OBJECTIVE: To evaluate the onset of analgesic effect for a new formulation of ibuprofen sodium dihydrate versus conventional ibuprofen (ibuprofen acid). MATERIALS AND METHODS: In this randomized, double-blind, double-dummy, crossover trial, patients requiring surgical removal of two impacted or partially impacted mandibular third molars received: ibuprofen sodium dihydrate 400 mg plus conventional ibuprofen placebo (Group 1); or conventional ibuprofen 400 mg plus ibuprofen sodium dihydrate placebo (Group 2) following the first surgery. Patients were then crossed over to the alternative treatment. RESULTS: 72 patients were enrolled in Group 1 and 72 patients in Group 2. Ibuprofen sodium dihydrate produced faster initial pain relief than conventional ibuprofen as assessed by time to first pain relief (24.6 vs. 30.5 minutes; p = 0.004), and patient-assessed pain relief at 15 minutes ("some" to "complete" pain relief: 43% vs. 29%; p < 0.001) and 30 minutes (82% vs. 63%; p < 0.001) and pain intensity at 30 minutes (p < 0.001). Substantial pain relief with ibuprofen sodium dihydrate was twice that of conventional ibuprofen at 30 minutes (11% vs. 5%; not significant); 29% and 33% of patients did not reach substantial pain relief at 120 minutes. There were no adverse events leading to treatment discontinuation and only two serious adverse events (oral abscess and facial paresis with conventional ibuprofen) considered unrelated to treatment. CONCLUSIONS: Ibuprofen sodium dihydrate was as effective as conventional ibuprofen, but had a faster onset of initial pain relief and significantly reduced pain intensity within the first 30 minutes after administration, providing rapid clinically meaningful pain relief for patients.

Stroke in relation to use of raloxifene and other drugs against osteoporosis.

UNLABELLED: Prior studies have associated fatal stroke with raloxifene. In a cohort study, we found no excess risk of stroke with raloxifene; whereas, an excess risk of stroke and fatal stroke was seen with alendronate and etidronate. However, the excess risks were small. PURPOSE: We aim to study the association between use of raloxifene and other drugs against osteoporosis and risk of stroke. METHODS: This is a nationwide cohort study from Denmark. All users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) as exposed group and three age- and gender-matched controls from the general population (n = 310,683). RESULTS: Before the drugs were started, patients later initiating alendronate or raloxifene had fewer strokes than the controls. In contrast, patients who later did start clodronate have more strokes. Among the later users of other bisphosphonates, strontium ranelate or parathyroid hormone, no change in the risk of stroke was present. Patients who started raloxifene neither had an excess risk of strokes nor of fatal strokes. No dose-response relationship was present. Among users of alendronate, a decreasing overall risk of stroke was seen with increasing dose. However, for fatal strokes, the risk increased with increasing dose of alendronate. Among users of etidronate, no trend with dose was present for overall stroke risk; whereas for fatal strokes, an increasing risk was seen with increasing dose of etidronate. CONCLUSIONS: Raloxifene does not seem associated with an excess risk of strokes. The increase seen for alendronate did not seem to be causal as no classical dose-response relationship was present. The dose-response relationship for fatal strokes with alendronate and etidronate needs further examination. However, the excess risks were small and may be due to the underlying disease.

Use of bisphosphonates and raloxifene and risk of deep venous thromboembolism and pulmonary embolism.

SUMMARY: Prior studies have associated raloxifene and strontium ranelate with deep venous thromboembolism and pulmonary embolism. In a cohort study, we observed an increased risk also with the bisphosphonates. However, the increase was present already before the start of bisphosphonates pointing at an effect of the underlying condition. INTRODUCTION: We seek to study the association between use of drugs against osteoporosis and risk of deep venous thromboembolism (DVT) and pulmonary embolism (PE). METHODS: Nationwide register-based cohort study from Denmark with all users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) as cases and three age- and gender-matched controls from the general population (n = 310,683). RESULTS: Before start of a drug against osteoporosis, an increased risk of DVT/PE was present in the crude analysis for alendronate, etidronate, and risedronate. However, upon adjustment, this increase in risk disappeared. Before start of raloxifene, a decreased risk of DVT/PE was present (odds ratio (OR) = 0.53, 95% confidence interval (CI), 0.39-0.71). After start of a drug, alendronate (HR = 1.20, 95% CI, 1.00-1.43), clodronate (HR = 4.06, 95% CI, 1.47-11.2), and etidronate (HR = 1-37, 95% CI, 1.23-1.51) were all associated with an increased risk of DVT/PE, while raloxifene was only borderline, significantly associated with risk of DVT/PE (HR = 1.64, 95% CI, 0.97-2.77). No dose-response relationship was present except for alendronate, where the risk was inversely associated with dose, i.e., the risk of DVT/PE decreased with increasing average daily dose. The HR for DVT/PE was higher with clodronate and etidronate than with alendronate. Alendronate and raloxifene carried the same risk for DVT/PE. CONCLUSION: Bisphosphonates seem associated with an increased risk of DVT/PE. However, the association does not seem to be causal.

Revascularisation of fresh compared with demineralised bone grafts in rats.

Revascularisation of bone grafts is influenced by both the anatomical origin and the pre-implantation processing of the graft. We investigated the revascularisation by entrapment of 141Ce (cerium)-labelled microspheres in large, fresh and demineralised syngeneic grafts of predominantly cancellous (iliac bone) or cortical (tibial diaphysis) bone three weeks after heterotopic implantation in rats. The mean (SD) 141Ce deposition index (counts per minute (cpm) of mg recovered implant/cpm of mg host iliac bone) was higher in fresh iliac bone grafts, 0.98 (0.46) compared to that of demineralised iliac bone, 0.32 (0.20), p < 0.001, and fresh tibial bone grafts, 0.51 (0.27), p = 0.007. We found no significant difference in the mean 141Ce deposition index between fresh tibial bone grafts and demineralised tibial bone grafts, 0.35 (0.42), p = 0.4, or between demineralised tibial grafts and demineralised iliac bone grafts, p = 0.8. The results suggest that whereas fresh cancellous grafts are revascularised more completely than fresh cortical grafts, there is no difference in the revascularisation of demineralised cancellous and cortical grafts. In addition, fresh cancellous bone is revascularised more completely than demineralised cancellous bone, whereas there is no difference between fresh and demineralised cortical bone.

The relationship between revascularisation and osteogenesis in fresh or demineralised bone grafts.

Bone formation generally depends on adequate blood flow. Failure of bone grafts has been attributed to delayed revascularisation of the graft. We compared the relationship between revascularisation and osteogenesis, evaluated as entrapment of (141)Ce-labelled microspheres and uptake of (85)Sr, respectively, in fresh or demineralised syngeneic bone grafts 3 weeks after heterotopic implantation in rats. Whereas a moderately high linear correlation between (85)Sr and (141)Ce radioactivity was found both in the (intact) host iliac bone (r = 0.75, p = 0.0001) and implanted fresh syngeneic grafts (r = 0.50, p = 0.001), no correlation could be demonstrated in demineralised grafts (r = 0.09, p = 0.6). The results may indicate differences in the mechanisms of vascularisation and osteogenesis in the grafts used fresh or after demineralization but are, at present, difficult to fully explain.

Histological evaluation of different biodegradable and non-biodegradable membranes implanted subcutaneously in rats.

Different types of biodegradable membranes have become available for guided tissue regeneration. The purpose of this study was to evaluate histologically three different biodegradable membranes (Bio-Gide, Resolut and Vicryl) and one non-biodegradable membrane (expanded polytetrafluoroethylene/e-PTFE) implanted subcutaneously in rats. Five subcutaneous pouches were created in each of 24 rats. One of the four test membranes was randomly placed in each of the four pouches and one pouch was left empty to serve as a control. Histological evaluation was performed after 4, 10 and 21 days which demonstrated that e-PTFE was well tolerated and encapsulated by a fibrous connective tissue capsule. There was capsule formation around Resolut and Vicryl and around Bio-Gide in the early phase there was a wide inflammatory zone already. e-PTFE and Vicryl were stable materials while Resolut and Bio-Gide fragmented in the early phase. In the late phase Vicryl was surrounded by an increasing amount of multinucleated macrophages and a thin capsule, whilst around Resolut and Bio-Gide a strong foreign body reaction was observed. Also granuloma formation was noted around the fragmented Resolut material in its capsule and a mild inflammatory reaction surrounding Bio-Gide within its thin capsule.

Comparative data from young men and women on masseter muscle fibres, function and facial morphology.

The primary aim was to relate information about masseter muscle fibres and function to aspects of facial morphology in a group of healthy young men. The secondary aim was to investigate possible sex differences using data previously obtained from a comparable group of age-matched, healthy women. Dental status and facial morphology were recorded in 13 male students aged 20-26 years. Functional examinations included bite-force measurements and electromyographic recordings of masseter activity. A biopsy was removed from the masseter of each participant during surgical extraction of a wisdom tooth, and the tissue examined for myosin ATPase activity. Further, the cross-sectional areas of the different fibre types were measured. In spite of using age-matched healthy men and women with a full complement of teeth, statistically significant sex differences were found among measures related to muscle function and some measures of facial morphology. Thus data from men and women should not be pooled uncritically. The greater bite force in men than women corresponded with the greater diameter and cross-sectional area of type II fibres. Further, the males had more anteriorly inclined mandibles and shorter anterior facial height, suggesting a relation between the greater muscle force and the shape of the face. However, linear regression analysis failed to demonstrate any significant association between bite force and facial morphology among men and women. Thus, craniofacial morphology could be a result of far more contributing factors than previously believed.

Incomplete bone regeneration of rabbit calvarial defects using different membranes.

The present study describes the use of a degradable and a non-degradable material for guided bone regeneration. Forty rabbits were divided into 5 groups. Bicortical defects 15 mm in diameter were prepared in rabbit calvaria. A titanium microplate was placed over the defect to prevent collapse of the membrane. The calvarial defects of 2 groups were covered by an outer expanded polytetrafluoroethylene (ePTFE) membrane respectively by a Polyglactin 910 membrane. Bicortical ePTFE membranes or Polyglactin 910 membranes were used in 2 other groups. The defects were not covered by membranes in the control group. Undecalcified sections were prepared for histologic evaluation after an observation period of 8 weeks. Complete bone healing of the defects was not observed in any of the specimens. The Polyglactin 910 material lacks physical strength, resulting in collapse of the membrane and brain tissue herniation into the defects. Subsequently, bone regeneration was impaired. The cellular reactions due to degradation of the material were minor and did not interfere with bone healing. Defects covered bicortically by ePTFE membranes revealed the largest amount of regenerated bone. The ePTFE membrane induced a severe cellular reaction, but no inhibition of bone regeneration was noted.

Osteoinductive potential of demineralized rat bone increases with increasing donor age from birth to adulthood.

Demineralized allogenic bone implanted in the subcutis or muscle of rodents causes formation of heterotopic bone by osteoinduction. The osteoinductive response may be weaker in primates than in rodents. It was suggested that the osteoinductive response of demineralized bone for clinical use could be enhanced by using young donors, because studies have indicated that the osteoinductive response is reduced in demineralized bone of old versus young donors. However, these findings may not represent a gradual decline in the osteoinductive property of bone matrix throughout the life span. We evaluated quantitatively, by uptake of strontium 85, the osteoinductive effect of demineralized bone matrix from newborn, 8-week-old (adolescent), and 8-month-old (adult) male Wistar rats implanted in the abdominal muscles of 8-week-old male Wistar rats. The osteoinductive response increased significantly with increasing donor age. The results of the present study, weighed with those of previous studies, indicate that the osteogenic potential of the bone matrix increases from newborn to adulthood but decreases in the aged rat. This may be due to changes in concentration of essential growth factors (e.g., bone morphogenetic proteins) resulting from maturational changes from birth to adulthood and osteoporotic changes occurring in later years. The results do not support the contention that young donors of demineralized bone are preferable to adult donors.

Unbiased stereological methods used for the quantitative evaluation of guided bone regeneration.

The present study describes the use of unbiased stereological methods for the quantitative evaluation of the amount of regenerated bone. Using the principle of guided bone regeneration the amount of regenerated bone after placement of degradable or non-degradable membranes covering defects in rabbit calvaria was compared. Forty rabbits were divided into 5 groups. A titanium microplate was placed over the defect to prevent collapse of the membrane. The non-degradable expanded polytetrafluoroethylene membrane and the degradable Polyglactin 910 material were both placed unicortically and bicortically. Undecalcified sections were prepared for stereologic evaluation after an observation period of 8 weeks. Complete bone healing of the defects was not observed in any of the specimens. Unbiased stereologic estimates revealed 48% bone regeneration in defects covered by 2 ePTFE membranes, and 12% in defects covered by 2 Polyglactin 910 membranes. Defects covered by 1 ePTFE or 1 Polyglactin 910 membranes revealed 10% or 18% bone regeneration, respectively. The control group regenerated 14%. The major difference of the estimates was caused by real difference between specimens, i.e. biologic variation, whereas only minimal variance was added by the stereologic estimation procedure.

Oral cancer: a retrospective study of 100 Danish cases.

One hundred Danes with oral cancer who were collected consecutively from 1986 to 1991 were evaluated retrospectively. The study included subjective and objective observations in 56% men and in 44% women. M:F ratio was 1.2:1. Fifty percent of the patients were non-smokers. Nine percent were women who did not drink alcohol. Ten percent of the patients were between 40 and 49 years of age, 20% between 50 and 59 years, 35% were between 60 and 69 years and 20% between 70 and 79 years of age. This may reflect a tradition of early drinking and smoking. Doctor's delay was the cause of delayed referral in 14% of the cases while 72% of the patients were the cause themselves for the delayed referral.

Effect of platelet-derived growth factor-BB on bone formation in calvarial defects: an experimental study in rabbits.

The effect of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) on bone healing was examined in calvarial defects in rabbits. Bicortical circular (critical size) defects were prepared in the calvarial bone of 16 rabbits. The defects were closed on the dural side and covered externally with expanded polytetrafluoroethylene membranes to prevent interference with osteogenesis within the defect by the surrounding tissue and to keep the growth factor in place. A single dose of methylcellulose gel (4.4%) with (n = 8) or without rhPDGF-BB (50 micrograms/ml) (n = 8) was applied to the defects, and the bone formation was evaluated after 8 weeks. Healing of defects in both groups was characterized by the presence of newly formed bone along the edges of the original defect and by a central area of fibrous connective tissue. The newly formed bone in the rhPDGF-BB treated defects had a trabecular structure; in contrast, a more compact structure was found in the control defects. In the rhPDGF-BB-treated defects, the bone ingrowth was 51.8 +/- 7.1% compared to 30.5 +/- 3.3% in the control defects. Furthermore, the amount of mineralized tissue was increased 112% in the rhPDGF-BB group. The amount of bone marrow was increased 75% in the rhPDGF-BB-treated defect. The porosity of cortical lamella in the newly formed bone was 84% higher in the rhPDGF-BB-treated defects compared to the control. These results show that administration of a single dose of rhPDGF-BB stimulates bone formation in critical size calvarial defects.

Tissue reaction and material characteristics of four bone substitutes.

The aim of the present study was to qualitatively and quantitatively compare the tissue reactions around four different bone substitutes used in orthopedic and craniofacial surgery. Cylinders of two bovine bone substitutes (Endobon and Bio-Oss) and two coral-derived bone substitutes (Pro Osteon 500 and Interpore 500 HA/CC) were implanted into 5-mm bur holes in rabbit tibiae. There was no difference in the amount of newly formed bone around the four biomaterials. Interpore 500 HA/CC resorbed completely, whereas the other three biomaterials did not undergo any detectable biodegradation. Bio-Oss was osseointegrated to a higher degree than the other biomaterials. Material characteristics obtained by diffuse reflectance infrared Fourier transform spectrometry analysis and energy-dispersive spectrometry did not explain the differences in biologic behavior.

Healing of experimentally created defects: a review.

Within cranio-maxillofacial surgery and orthopedic surgery a bone graft or a bone substitute is required to recontour or assist bony healing in repair of osseous congenital deformities, or in repair of deformity due to trauma or to surgical excision after elimination of osseous disease processes exceeding a certain size. An autogenous bone graft is the optimal material of choice, however its use is problematic due to donor site morbidity, sparse amounts and uncontrolled resorption. Immunological responses and risk of viral contamination of allogenous and xenogenous bone materials make the use of these materials questionable. Healing and degradation of alloplastic materials are inconsistent with subsequent restricted use. The principle of guided tissue regeneration excluding soft tissue cells from a certain area is not alone sufficient to insure complete bony healing. Recombinant bone morphogenetic proteins have with success been added as adjuncts to already known biomaterials. In the future, inductive materials together with a suitable carrier and a biodegradable membrane may be the choice of bone substitute used within cranio-maxillofacial and orthopaedic surgery.

Osseointegration of subperiosteal implant via guided tissue regeneration. A pilot study.

The principle of guided tissue regeneration was applied in an attempt to generate bone to cover a subperiosteal implant. Titanium frame works, casted on individual impressions of the anterior surface of the tibia of 4 Copenhagen White rabbits, were stabilized to the tibia by microscrews, and half of them were covered by an expanded polytetrafluoroethylene augmentation membrane. The observation period was 12 weeks. Guided bone regeneration partly covering the implants was seen at all experimental sides; on the control sides the implants were mainly embedded in fibrous tissue. Studies are in progress with the aim of reducing marked marrow space formation observed in all the regenerated areas.

Local delivery of indomethacin by a polyorthoester inhibits reossification of experimental bone defects.

Inhibition of orthotopic reossification after surgical removal of bone is sometimes indicated and may be accomplished by implantation of interpositional materials or by systemic administration of indomethacin. However, implantation of nonresorbable foreign material may induce a chronic inflammation and predispose to infections; and systemic administration of indomethacin may induce systemic adverse effects. We studied the effect of local delivery of indomethacin by a bioerodible polyorthoester on the reossification of segmental defects of the radius in rats. We divided 45 Wistar rats into three groups, A-C. A 3.5 mm-long middiaphyseal osteoperiosteal resection of the right radius was made in each rat. The defect was filled with 15 mg of polyorthoester with 5% indomethacin in group A and 15 mg of polyorthoester without drug in group B. No material was implanted in the defects in the group C rats. The rats were killed 50 days postoperatively. The mean area of the residual defects were greater in the defects with the polyorthoester with 5% indomethacin compared with defects with polyorthoester without drug or without implant as judged by computer-assisted area measurements on radiographs. By light microscopy, no inflammation was seen and only traces of the polyorthoester could be detected in the defects filled with the polyorthoester with or without indomethacin. The results of this study suggest that the polyorthoester may be used as a bioerodible system for local delivery of indomethacin to inhibit reossification of skeletal defects without tissue reaction, unabsorbed carrier, or systemic effects.