Systemic sclerostin antibody treatment increases osseointegration and biomechanical competence of zoledronic-acid-coated dental implants in a rat osteoporosis model.

Osseointegration of dental implants can be promoted by implant-surface modifications using bisphosphonate coatings. In addition, it is of clinical interest to promote peri-implant bone formation and to restore bony structure in low bone-mass patients. The present study evaluated a combination of an anti-resorptive zoledronic acid (ZOL) implant-coating and a systemically applied sclerostin antibody, a known bone anabolic treatment principle, versus sole sclerostin antibody treatment or ZOL implant-coating in a rat osteoporosis model. Uncoated reference surface implants or ZOL-coated implants (n = 64/group) were inserted into the proximal tibia of aged osteoporotic rats three months following ovariectomy. 32 animals of each group received once weekly sclerostin antibody therapy. Osseointegration was assessed 2 or 4 weeks post-implantation by ex vivo µCT, histology and biomechanical testing. Overall implant survival rate was 97 %. Histomorphology revealed pronounced bone formation along the entire implant length of ZOL-coated implants. At 4 weeks following implant insertion, bone-implant contact, cancellous bone mineral density and bone volume/tissue volume were significantly increased for the combination of ZOL and sclerostin antibody as compared to sclerostin antibody or ZOL implant-coating alone. Removal torque was also significantly increased in the combination therapy group relative to animals receiving only sclerostin antibody therapy or ZOL-coated implants. In an osteoporotic rat model, the combination of anti-resorptive ZOL implant-coating and systemically applied sclerostin antibody led to significantly increased peri-implant bone formation. Therefore, the combination of ZOL and the osteoanabolic sclerostin antibody was more effective than either agent alone.

Chondroitin sulfate and sulfated hyaluronan-containing collagen coatings of titanium implants influence peri-implant bone formation in a minipig model.

An improved osseous integration of dental implants in patients with lower bone quality is of particular interest. The aim of this study was to evaluate the effect of artificial extracellular matrix implant coatings on early bone formation. The coatings contained collagen (coll) in conjunction with either chondroitin sulfate (CS) or sulfated hyaluronan (sHya). Thirty-six screw-type, grit-blasted, and acid-etched titanium implants were inserted in the mandible of 6 minipigs. Three surface states were tested: (1) uncoated control (2) coll/CS (3) coll/sHya. After healing periods of 4 and 8 weeks, bone implant contact (BIC), bone volume density (BVD) as well as osteoid related parameters were measured. After 4 weeks, control implants showed a BIC of 44% which was comparable to coll/CS coated implants (48%) and significantly higher compared to coll/sHya coatings (37%, p = 0.012). This difference leveled out after 8 weeks. No significant differences could be detected for BVD values after 4 weeks and all surfaces showed reduced BVD values after 8 weeks. However, at that time, BVD around both, coll/CS (30%, p = 0.029), and coll/sHya (32%, p = 0.015), coatings was significantly higher compared to controls (22%). The osteoid implant contact (OIC) showed no significant differences after 4 weeks. After 8 weeks OIC for controls was comparable to coll/CS, the latter being significantly higher compared to coll/sHya (0.9% vs. 0.4%, p = 0.012). There were no significant differences in osteoid volume density. In summary, implant surface coatings by the chosen organic components of the extracellular matrix showed a certain potential to influence osseointegration in vivo.

Osseointegration of biochemically modified implants in an osteoporosis rodent model.

The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control) or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX) osteoporotic rats (n = 32/group). In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout). Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC), peri-implant bone area (BA), bone volume/tissue volume (BV/TV) and bone-mineral density (BMD) in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

Comparison of zirconia and titanium implants after a short healing period. A pilot study in minipigs.

The aim of this animal study was to investigate and compare the osseointegration of zirconia and titanium dental implants. 14 one-piece zirconia implants and 7 titanium implants were inserted into the mandibles of 7 minipigs. The zirconia implants were alternately placed submerged and non-submerged. To enable submerged healing, the supraosseous part was removed, using a diamond saw. The titanium implants were all placed submerged. After a healing period of 4 weeks, a histological analysis of the soft and hard tissue and a histomorphometric analysis of the bone-implant contact (BIC) and relative peri-implant bone-volume density (rBVD; relation to bone-volume density of the host bone) was performed. Two zirconia implants were found to be loose. All other implants were available for evaluation. For submerged zirconia and titanium implants, the implant surface showed an intimate connection to the neighbouring bone, with both types achieving a BIC of 53%. For the non-submerged zirconia implants, some crestal epithelial downgrowth could be detected, with a resultant BIC of 48%. Highest rBVD values were found for submerged zirconia (80%), followed by titanium (74%) and non-submerged zirconia (63%). The results suggest that unloaded zirconia and titanium implants osseointegrate comparably, within the healing period studied.

One-stage palate repair improves speech outcome and early maxillary growth in patients with cleft lip and palate.

There are several types of palatal surgery; each cleft centre chooses its own technique based on experience and treatment philosophy. The aim of this study was to compare speech outcome and maxillary growth in children with cleft lip and palate deformity after palate repair with either a one-stage or a two- stage procedure and to identify the better treatment protocol. In 24 children, speech outcome was assessed regarding resonance, nasal escape, compensatory articulations, facial grimace, and spontaneous speech. In addition, plaster models of 15 children were compared. In 12 children, a two-stage procedure was performed (group A): at the age of 9-12 months, an intravelar veloplasty for repair of the soft palate, and at the age of 24-36 months a bipedicled flap closure of the hard palate. In 12 children, the same techniques were used in a one-stage procedure, at the age of 9-12 months (group B). The children of group B showed less altered resonance and less nasal emission at 4 years of age compared to the children of group A. At 6 years, the children of group A had improved their speech skills, but they did not equal the results of group B. In the study models of group A at age 6 years, the transverse dimension (anterior and posterior width of the dental arch) was smaller than in the models of group B. The one-stage repair of cleft palate at the age of 9-12 months seems to have a more positive influence on speech development and early maxillary growth than the two-stage procedure.

INION compared with titanium osteosynthesis: a prospective investigation of the treatment of mandibular fractures.

We prospectively studied two groups of 30 patients to assess the outcome of treatment of mandibular fractures with the biodegradable INION system compared with osteosynthesis with titanium miniplates. The degree of occlusion, wound healing, and swelling, were noted preoperatively and at 1 week, 6 weeks, and 6 months postoperatively. All fractures healed uneventfully, both clinically and radiologically, and independently of the osteosynthesis used. We found no long-term disturbance of occlusion, but there were twice as many malocclusions in the INION group at one week. We now use a 3-5 day period of postoperative elastic intermaxillary fixation (IMF) to prevent material deformities. Both groups developed problems with wound healing; with INION adequate soft tissue closure combined with appropriate positioning of the plates prevented this. At 6 months a dense swelling developed in some patients in the INION group as a result of biodegradation of the plates. INION plates were biocompatible and strong enough to treat mandibular fractures.

Evaluation of osseointegration of dental implants coated with collagen, chondroitin sulphate and BMP-4: an animal study.

Various studies have shown type I collagen (coll) to increase bone-implant contact (BIC) compared to uncoated implants. The aim of this animal study was to test whether the integration of chondroitin sulphate (CS) and the growth factor rhBMP-4 into a collagenous coating could further increase the measured BIC compared to collagen coated implants alone. The experimental implants had two recesses along the length axis. 120 implants with the surface modifications: coll, coll/CS, coll/CS/rhBMP-4 were inserted into the mandible of 20 minipigs. Six months after implantation, BIC was measured histomorphometrically on the surface and within the recesses. Due to the specific animal model and strict criteria in placement, 39.2 % of the implants were considered as failure and not included in the analysis. Of the successfully gained 73 implants, the highest percentage of BIC was obtained for coll/CS (40%), followed by coll (30%) and coll/CS/rhBMP-4 (27%), P=0.013. BIC within the recesses was highest for coll/CS (51%), followed by coll (43%) and coll/CS/rhBMP-4 (34%), P=0.025. The result suggests that the inclusion of CS slightly increases the BIC compared to collagen coated implants. The further inclusion of a low amount rhBMP-4 had a detrimental effect on bone formation compared to coll/CS, P<0.05.

An experimental study of the biomechanical stability of ultrasound-activated pinned (SonicWeld Rx+Resorb-X) and screwed fixed (Resorb-X) resorbable materials for osteosynthesis in the treatment of simulated craniosynostosis in sheep.

We compared a conventional resorbable screw osteosynthesis with a resorbable, ultrasound-activated pin osteosynthesis, and studied mechanical load capacity and operative handling. This new form of osteosynthesis aims to reduce operation times, and to avoid torque loads and screw fractures to achieve stability. A sheep craniotomy model simulated an operation for dysmorphia on an infant skull. Two rectangular craniotomies of equal size were created in 13 lamb skulls, and each refixed by different means: the first by mesh and 20 screws, and the second by mesh with 20 pins inserted with ultrasound activation. All osteosynthesis material consisted of resorbable amorphous poly-(d,l)-lactide (PDLLA) (Resorb-X, KLS Martin, Tuttlingen, Germany). The insertion time was recorded. The animals were killed at different times, and areas of the healing skull including the plates and pins or screws were removed and divided into sections, which were then tested. In total 74 pin-fixed and 77 screw-fixed samples were obtained. Bending and tensile tests were used to simulate different forms of loading. The time required for the insertion of pins was significantly shorter than for screws. The mechanical tests showed differences in the stability of the bond between the osteosynthesis plate and bone that depended on the osteosynthesis system and the length of time it was in the animal. The pin osteosynthesis gave a stable mechanical load capacity, which was significantly different from that of screw osteosynthesis. Advantages of ultrasound-assisted, resorbable, pin osteosynthesis, include optimum operative handling, reduced insertion time, avoidance of fractures of the fixation elements and higher three-dimensional load capacity.

An experimental in vivo analysis of the resorption to ultrasound activated pins (Sonic weld) and standard biodegradable screws (ResorbX) in sheep.

We compared the healing and reaction in the mandibles of 11 sheep of a conventional bioresorbable screw osteosynthesis with the newly developed ultrasound-activated pin osteosynthesis. The thermal stress caused by insertion of the ultrasound-aided pins leads to no cellular reaction around the pin. There is neither clinical nor histological evidence of any initial inflammation that could have been induced by the insertion. Adequate attachment of fibrous tissue to the pin head and the absence of any inflammation are important preconditions for the introduction of this new method of osteosynthesis into clinical practice. Further advantageous characteristics are easy intraoperative handling and a reduction in operating time, because cutting the thread is not required. There must be sufficient interlinkage of the polymer and the trabecular structures to ensure stability.

[Transoral osteosynthesis of condylar neck fractures using a three-dimensional plate]. / Transorale operative Therapie von Kiefergelenkfrakturen mit einer 3D-Platte.

AIM: The transoral approach minimizes the risk of damaging the facial nerve. However, stable osteosynthesis with two miniplates at the proximal fragment is often not possible. To achieve a stable fixation also of condylar neck fractures a new delta-shaped plate was developed, which meets the biomechanical demands of this region. This plate was tested in a clinical study. PATIENTS AND METHODS: In total 11 patients suffering from 13 condyle fractures (Spiessl I: n=2, Spiessl II: n=10, Spiessl III: n=1, 3 bilateral fractures) were treated via a transoral approach and assessed clinically as well as radiologically in the follow-up period. Functional parameters and fracture alignment were assessed. RESULTS: After 6 months postoperative function had returned to normal with a mouth opening of 42 mm and pro- and laterotrusion of more than 5 mm. Postoperative radiographic controls showed a good fracture alignment in 7 of 8 patients respectively in 6 of 8 cases after 6 months. In 12 of 13 fractures directly postoperative and in 10 of 13 fractures 6 months postoperative, respectively, Towne's view radiographs showed an anatomical correct position. No plate fracture and no bending of plates were observed. Loosening of screws was found in 2 patients during plate removal. CONCLUSION: The newly developed three-dimensional plate was easy to handle, and a sufficiently stable osteosynthesis of condyle fractures was possible. This plate can be recommended for surgical fracture treatment via a transoral approach omitting extraoral scars and damage to the facial nerve.

Functional and radiological results of open and closed treatment of intracapsular (diacapitular) condylar fractures of the mandible.

The study was performed to evaluate and compare the results of open and closed treatments of diacapitular fractures of the mandible. Following open reduction and internal fixation (ORIF) 14 patients with 15 displaced condylar fractures, which had caused a shortening of the mandibular ramus, were examined clinically (Helkimo index), radiologically (Orthopantomogram, Clementschitsch [reversed Towne's] view, Submentovertex view) and axiographically (CARDIAX). These findings were compared to a group of 29 patients with 34 similar condylar fractures which had been treated using closed techniques. Following ORIF patients showed better radiological results with regard to the mandibular ramus height, resorption and pathological changes to the condyle, compared to the patient group after closed functional treatment. In both groups some signs of dysfunction persisted, although there were slightly better results in the ORIF group. In 30% of the closed treatment group, lateral deviation during mouth opening, crepitus and occlusal disturbances were noted. No cases of occlusal disturbance were observed in the ORIF group. The axiographic examinations revealed a significant limitation of movement of the fractured condyle in both groups. However, after open treatment, the temporomandibular joint displayed significantly less irregularities in the condylar paths. In cases of complex reconstruction of the mandibular condyle, ORIF appears to improve the function of fractured condyles, when combined with a postoperative therapeutic exercise regime.

Severe temporomandibular dysfunction and joint destruction after intra-articular injection of triamcinolone.

BACKGROUND: Steroid injections into joints are frequently used to control symptomatic pain. Risks associated with intra-articular steroid injections are not well documented. METHODS: We report the case of a 29-year-old woman who was referred to a dental surgeon because of a suspected relationship between persisting chronic back pain and an arthrosis of the temporomandibular joint (TMJ). RESULTS: The dental surgeon diagnosed capsulitis of the right TMJ and injected 40 mg triamcinolone into the joint. Within 4 months the patient developed progressive pain and trismus of the right TMJ and the intra-articular injection was repeated. An occlusal splint slightly improved the patients' symptoms but induced crepitus. Magnetic resonance imaging revealed a disk dislocation in the right TMJ and severe necrosis of the condyle. The patient had persisting pain and ankylosis. Surgical restoration of the TMJ revealed a bony apposition in the fossa deformed with the socket of the joint, extensive medial erosion of the condyle and complete destruction of the disk. CONCLUSION: This case report supports earlier observations that intra-articular glucocorticoid injections, if used in a wrong way, may cause severe destruction of a joint.

Subclassification of fractures of the condylar process of the mandible.

We present the definitions of various types of fracture of the condylar process, which have been adopted for the Strasbourg Osteosynthesis Research Group (SORG), in their Pan-European prospective randomised controlled trial into the management of such fractures. We think that this will assist people in their description of the various types of fracture of the condylar process.

[Custom moldable hydroxyapatite collagen composite for repair of osseous defects]. / Frei modellierbare Hydroxylapatit-Kollagen-Komposite zur Sanierung ossärer Defekte.

AIM: In the following study we evaluated the biological response of a new freely moldable bone substitute in an animal model. MATERIAL AND METHODS: Critically sized defects were created surgically in the lower jaw of ten adult minipigs. The drill defects were filled with hydroxyapatite collagen paste. After observation periods of 1, 3, 6, 12, and 18 months the mandibles were harvested without wound healing defects for histological evaluation of resorption and bone ingrowth with a sawing and grinding technique. RESULTS: The result of the remodeling process was a complete degradation of hydroxyapatite collagen implants after 12-18 months with reorganization of vital trabeculae oriented in a mature pattern. CONCLUSION: The hydroxyapatite collagen cement works as an osteoconductor and shows signs of direct osseointegration and resorption.

[Preoperative determination of the position of mandibular canal for planning sagittal ramus osteotomy of the mandible]. / Präoperative Lagebestimmung des Canalis mandibulae vor sagittaler Ramusosteotomie des Unterkiefers.

BACKGROUND: In the literature the incidence of permanent nerve lesions ranges from 3 to 39%. Therefore, we think that it is necessary to discuss the procedure of individual risk assessment and management. Standard imaging techniques for the preoperative planning and preparation of a sagittal split osteotomy usually include a panoramic radiograph and lateral cephalometric radiograph. If an assessment of the transversal thickness of the lower jaw and cortical substance is required, or the position of the inferior alveolar nerve needs to be determined for preoperative planning, computed tomography of the viscerocranium has to be performed. By employing the conventional computed tomographic X-ray imaging system CommCAT, we are able to determine preoperatively both the transversal thickness of the lower jaw including the cortical substance and the diameter of the ascending ramus of the mandible at the proximal osteotomy site. PATIENTS AND METHOD: We examined prospectively the value of these additional investigations and compared them with the intraoperative findings in 29 patients. With these tomograms, the relation between the position of the inferior alveolar nerve and the vestibular cortical bone was metrically evaluated. In 17 of 58 jaw sides we detected the nerve at a distance from the outer cortical bone of 2 mm or less. The situation for the upper osteotomy was critical in eight cases where the thickness of the mandibular ramus was only 3 mm. RESULTS: By using of the conventional computed tomography system CommCAT, we have the preoperative opportunity to determine the transversal thickness of the mandibular ramus as well as the exact position of the inferior alveolar nerve and its distance from the cortical bone of the mandibular corpus. By predicting the nerve's position and its relation to the osteotomy site, we are able to individualize the operation procedure so that a high standard of safety can be achieved.

[DiGeorge syndrome/velcardiofacial syndrome: oral and maxillofacial surgery]. / Das DiGeorge-Syndrom/velokardiofaziale Syndrom in der Mund-, Kiefer- und Gesichtschirurgie.

The DiGeorge syndrome/velocardiofacial syndrome is the most frequent chromosomal microdeletion syndrome. Partial deletion of chromosome 22q11 may lead to symptoms including facial dysmorphy, hypoparathyroidism, thymic aplasia, congenital heart disease, developmental retardation, and disturbance of speech development. According to the literature, 9% of patients have cleft palate, an additional 5% have a submucosal cleft, and a total of 32% show velopharyngeal insufficiency. We studied 64 children with a cleft, or with delayed speech development and a submucosal or occult cleft, for the presence of the 22q11deletion using fluorescent in situ hybridisation. Five patients had the 22q11 deletion. We conclude that patients presenting with nasal speech and additional anomalies should all be studied for the presence of submucosal or occult clefting and for the presence of the DiGeorge syndrome/velocardiofacial syndrome.

[Clinical, radiological and axiographic examination after conservative functional treatment of intracapsular temporomandibular joint fractures]. / Klinische, radiologische und axiographische Untersuchung nach konservativ funktioneller Behandlung diakapitulärer Kiefergelenkfrakturen.

PURPOSE: The different lines of intracapsular fractures of the mandibular condyle were studied and their influence on the prognosis following close treatment was evaluated. METHODS: In 40 patients with 50 intracapsular fractures of the mandibular condyle the following evaluation was carried out after close treatment: clinical, radiological and axiographical follow-up. The examinations were performed between 0.5-5 years following treatment. Three types of intracapsular fractures were distinguished. Type A = fractures through the medial condylar pole, type B = fractures through the lateral condylar pole with loss of vertical height of mandibular ramus, type M = multiple fragments, comminuted fractures. RESULTS: Moderate to serious dysfunction was observed in 33% of the cases. Radiological examination of fracture types B and M revealed a reduction in the height of the mandibular ramus by up to 13% as compared to the contralateral side. Also with regard to deformation of the condylar head these two fracture types resulted in the most prominent pathological findings. Axiography revealed irregular excursions and a clear limitation of condylar movement in comminuted fractures by up to 74% as compared to the non-fractured side. CONCLUSION: The findings emphasize the severity of lesions to the osseo-disko-ligamentous complex of the TMJ caused by intracapsular fractures of the mandibular condyle. The poor functional and radiological results encountered in the fracture types B and M demonstrated the limits of conservative functional treatment. With regard to fracture type B it may be discussed whether surgical therapy would improve the results.

Infrequent genetic alterations of the tumor suppressor gene PTEN/MMAC1 in squamous cell carcinoma of the oral cavity.

BACKGROUND: Fifty tumor specimens from primarily untreated patients were analyzed to elucidate the involvement of the tumor suppressor gene PTEN/MMAC1 in the development of oral squamous cell cancer. METHODS: Eight microsatellite markers, spanning 10 cM of genomic DNA located centromeric, telomeric or intragenic of PTEN/MMAC1 were used for loss of heterozygosity (LOH) and breakpoint analysis. The microsatellite panel within or in close proximity (1 cM) to the 10q23.3 locus showed a LOH rate of 12%. Complete sequence analysis of the genes coding region was performed in all 10 cases that exhibited LOH in one of the eight microsatellite markers within or around the PTEN/MMAC1 gene. Comparative multiplex PCR reactions served to screen for homozygous deletions. RESULTS: There was no association between allelic loss of the gene, overall patient survival and recurrence-free survival. Sequencing did not reveal any mutation in the coding region of PTEN/MMAC1. Differential PCR analysis failed to detect any homozygous deletion. CONCLUSIONS: We conclude that PTEN/MMAC1 gene alterations do not play a key role in tumorigenesis of oral squamous cell cancers.

Cryosurgical treatment of genuine trigeminal neuralgia.

A newly developed cryoprobe for peripheral nerves allows surgeons to freeze branches of the trigeminal nerve at the infraorbital or the mandibular foramen without exposing the nerve or damaging the surrounding tissue. The probe has an outer diameter of 2.7mm, and a vacuum-insulated shaft to protect the adjacent tissue. It is designed to be inserted transmucosally. The cryoprobe was used in 19 patients to freeze the infraorbital nerve or the inferior alveolar nerve. At 4-8 months after cryotherapy sensation in the areas innervated by the treated nerve had returned, but pain was absent for at least 6 months. The pain recurred in 13 out of 19 patients within 6-12 months. However, it was possible to repeat the cryotherapy as the procedure was not stressful. Cryosurgery widens the range of methods available to treat trigeminal neuralgia.

Combination of microplate and miniplate for osteosynthesis of mandibular fractures: an experimental study.

Because of the limited space available in the mandible, especially in the mental foramen and apical region, miniature osteosynthesis material is desirable. Recently, metal deposition in the direct neighbourhood of osteosynthesis plates made of titanium or even in peripheral organs have been reported in the literature with increasing frequency. The size and amount of osteosynthesis material used should therefore be kept to a minimum. In an experimental study on 60 models, we examined load-carrying stability and in a second series, torsional strength of two-piece plastic models connected by either a single miniplate, two miniplates, or a titanium microplate plus a miniplate. In our test arrangement, the average loading capacity of the combination miniplate/miniplate was 470 N: that of the combination microplate/miniplate was only 267 N. The test group with the single miniplate had an average loading capacity of only 225 N. Masticatory loads on the plates exceeding 200 N occur only 3 months after osteosynthesis. At that time the fracture has largely consolidated. The torsional strength of the microplate/miniplate combination was similar to that of the miniplate/miniplate combination (1,000 Nmm resulting in a width of the gap measuring 0.8 mm and 0.5 mm, respectively). The single miniplate was considerably less stable (0.8 mm gap width as early as with 300 Nmm). According to Champy, rotational forces in the anterior region of the mandible amount to approximately 1,000 Nmm and need to be withstood by the osteosynthesis material. Our results suggest that treatment of fractures in the interforaminal region with a combination of microplate and miniplate will be stable enough for early mobilization.