Impact of Bone Volume Upon Condylar Activity in Patients With Unilateral Condylar Hyperplasia.

PURPOSE: Unilateral condylar hyperplasia or hyperactivity (UCH) is a bone overgrowth disorder affecting the mandible. The purpose of this study was to determine the relations among age, condylar bone structure, condylar bone volume, and condylar bone activity on single-photon emission computed tomographic (SPECT) scans in patients with UCH. MATERIALS AND METHODS: This study included 20 patients with a clinical presentation of progressive mandibular asymmetry and a positive bone SPECT scan. A bone SPECT-derived standardized uptake value (bSUV) for the condylar region was determined. All patients underwent condylectomy to arrest further progression of the disease. The resected condyles were scanned with a micro-computed tomographic scanner (18-µm resolution). Bone architectural parameters were calculated with routine morphometric software. RESULTS: The mean bSUV of the condyle on the affected side was 15.32 (standard deviation [SD], 8.98) compared with 9.85 (SD, 4.40) on the nonaffected side (P = .0007). For trabecular bone structure, there was a nonsignificant correlation between the SUV of the affected condyle and the measured bone volume fraction (r = 0.13; P = .58) and trabecular thickness (r = 0.03; P = .90). CONCLUSION: No meaningful relation was found between condylar bone volume fraction and condylar activity on bone scan; therefore, the impact of bone volume fraction on the results of bone scans is limited. The measured condylar activity on SPECT scan seems to be primarily a reflection of the remodeling rate of bone.

Implications of high-dosage bisphosphonate treatment on bone tissue in the jaw and knee joint.

Bisphosphonates are bone antiresorptive agents traditionally used on a relatively large scale for treatment of bone metabolic diseases and on a smaller scale for bone metastasis treatment. A study on the effects of bisphosphonate treatment on healthy instead of diseased animals will give more insight into the basic mechanisms of bisphosphonates and their effects on different bone sites. We aimed to assess the effect of BP on the mouse knee and jaw joint. Three-month old female C57BL/6 mice were used (twenty-four and eighteen control and experimental group, respectively). At baseline and after treatment with zoledronic acid (ZA) for one, three or six months, we combined bone assessment via µCT and additional histology. Our results showed that, in the knee joint, ZA treatment increased TMD, bone volume, trabecular thickness but did not influence cortical thickness. In both control and ZA group, a higher trabecular TMD compared to cortical TMD was seen. Unseen in the knee joint, ZA treatment in the jaw joint resulted in bone-site specific changes in mineralization; a significant time-dependent higher TMD was evident in the subchondral bone compared to the most distal region of the condyle. MicroCT images revealed the presence of mineral in this region and histology showed that this region did not contain mature bone tissue but cartilage-like tissue. Our data indicate the possibility of site-specific negative side effects, i.e., disturbing normal mandibular development under the influence of bisphosphonate therapy.

A histomorphometric and micro-computed tomography study of bone regeneration in the maxillary sinus comparing biphasic calcium phosphate and deproteinized cancellous bovine bone in a human split-mouth model.

OBJECTIVE: The gain of mineralized bone was compared between deproteinized bovine bone allograft (DBA) and biphasic calcium phosphate (BCP) for dental implant placement. STUDY DESIGN: Five patients with atrophic maxillae underwent bilateral sinus elevation with DBA (Bio-Oss) and BCP (Straumann BoneCeramic). After 3 to 8 months, 32 Camlog implants were placed, and biopsies were retrieved. Bone and graft volume, degree of bone mineralization, and graft degradation gradient were determined using micro-computed tomography, and bone formation and resorption parameters were measured using histomorphometry. Implant functioning and peri-implant mucosa were evaluated up to 4 years. RESULTS: Patients were prosthetically successfully restored. All but one of the implants survived, and peri-implant mucosa showed healthy appearance and stability. Bone volume, graft volume, degree of bone mineralization, and osteoclast and osteocyte numbers were similar, but BCP-grafted biopsies had relatively more osteoid than DBA-grafted biopsies. CONCLUSIONS: The BCP and DBA materials showed similar osteoconductive patterns and mineralized bone, although signs of more active bone formation and remodeling were observed in BCP- than in DBA-grafted biopsies.

Condylar process contributes to mandibular asymmetry: In vivo 3D MRI study.

The purpose of this study was to investigate the differences in mandibular morphology between the deviated and nondeviated sides in patients with noncongenital skeletal mandibular asymmetry. Divergences from control values were assessed to determine which region of the mandible contributes most to mandibular asymmetry. We measured various dimensions of the mandible in 20 young patients and 20 controls using noninvasive high-quality three-dimensional (3D) volumetric magnetic resonance imaging. Mandibular dimensions including the length of the condylar process were significantly greater on the nondeviated side of patients than the deviated side. Measurements of the deviated side were similar to control values, but measurements of the nondeviated side including condylar process length differed significantly from control values. These findings strongly suggest that overgrowth of the condylar process on the nondeviated side in these patients results in mandibular asymmetry, and therefore needs attention in orthodontic treatment, orthognathic surgery, and follow-up.

Osteoclast precursors in murine bone marrow express CD27 and are impeded in osteoclast development by CD70 on activated immune cells.

Osteoclasts (OCs) are bone-resorbing cells that are formed from hematopoietic precursors. OCs ordinarily maintain bone homeostasis, but they can also cause major pathology in autoimmune and inflammatory diseases. Under homeostatic conditions, receptor activator of nuclear factor kappa-B (RANK) ligand on osteoblasts drives OC differentiation by interaction with its receptor RANK on OC precursors. During chronic immune activation, RANK ligand on activated immune cells likewise drives pathogenic OC differentiation. We here report that the related TNF family member CD70 and its receptor CD27 can also mediate cross-talk between immune cells and OC precursors. We identified CD27 on a rare population (0.3%) of B220(-)c-Kit(+)CD115(+)CD11b(low) cells in the mouse bone marrow (BM) that are highly enriched for osteoclastogenic potential. We dissected this population into CD27(high) common precursors of OC, dendritic cells (DCs) and macrophages and CD27(low/neg) downstream precursors that could differentiate into OC and macrophages, but not DC. In a recombinant mouse model of chronic immune activation, sustained CD27/CD70 interactions caused an accumulation of OC precursors and a reduction in OC activity. These events were due to a CD27/CD70-dependent inhibition of OC differentiation from the OC precursors by BM-infiltrating, CD70(+)-activated immune cells. DC numbers in BM and spleen were increased, suggesting a skewing of the OC precursors toward DC differentiation. The impediment in OC differentiation culminated in a high trabecular bone mass pathology. Mice additionally presented anemia, leukopenia, and splenomegaly. Thus, under conditions of constitutive CD70 expression reflecting chronic immune activation, the CD27/CD70 system inhibits OC differentiation and favors DC differentiation.

Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength.

Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption.To shed light on the effect of uncoupling in adult mice with respect to bone strength, we transplanted irradiated three-month old normal mice with hematopoietic stem cells from control or oc/oc mice, which have defective acid secretion, and followed them for 12 to 28 weeks.Engraftment levels were assessed by flow cytometry of peripheral blood. Serum samples were collected every six weeks for measurement of bone turnover markers. At termination bones were collected for µCT and mechanical testing. An engraftment level of 98% was obtained. From week 6 until termination bone resorption was significantly reduced, while the osteoclast number was increased when comparing oc/oc to controls. Bone formation was elevated at week 6, normalized at week 12, and reduced onwards. µCT and mechanical analyses of femurs and vertebrae showed increased bone volume and bone strength of cortical and trabecular bone.In conclusion, these data show that attenuation of acid secretion in adult mice leads to uncoupling and improves bone strength.

Nonablative neonatal bone marrow transplantation rapidly reverses severe murine osteopetrosis despite low-level engraftment and lack of selective expansion of the osteoclastic lineage.

Infantile malignant osteopetrosis (IMO) is caused by lack of functional osteoclasts leading to skeletal abnormalities, blindness owing to compression of the optic nerves, bone marrow (BM) failure, and early death. In most patients, TCIRG1, a proton pump subunit essential for bone resorption, is mutated. oc/oc mice represent a model for IMO owing to a deletion in Tcirg1 and die around 4 weeks of age. To determine if hematopoietic stem cell transplantation without prior conditioning can reverse osteopetrosis, neonatal mice were transplanted intravenously with lineage-depleted BM cells. More than 85% of oc/oc mice transplanted with 5 × 10(6) cells survived long term with an engraftment of 3% to 5% in peripheral blood (PB). At 3 weeks, engraftment in the BM was 1% to 2%, but the cellularity had increased 60-fold compared with untreated oc/oc mice, and RANKL and macrophage colony-stimulating factor (M-CSF) expression in the BM was normalized. Histopathology and micro-computed tomography revealed almost complete reversal of osteopetrosis after 4 weeks. In vitro studies showed that bone resorption by osteoclasts from transplanted oc/oc mice was 14% of transplanted controls, and immunofluorescence microscopy revealed that resorption was mainly associated with osteoclasts of donor origin. Lineage analysis of BM, PB, and spleen did not provide any evidence for selective recruitment of cells to the osteoclastic lineage. The vision also was preserved in transplanted oc/oc mice, as determined by a visual tracking drum test. In summary, nonablative neonatal transplantation leading to engraftment of only a small fraction of normal cells rapidly reverses severe osteopetrosis in the oc/oc mouse model.

The adaptive response of jaw muscles to varying functional demands.

Jaw muscles are versatile entities that are able to adapt their anatomical characteristics, such as size, cross-sectional area, and fibre properties, to altered functional demands. The dynamic nature of muscle fibres allows them to change their phenotype to optimize the required contractile function while minimizing energy use. Changes in these anatomical parameters are associated with changes in neuromuscular activity as the pattern of muscle activation by the central nervous system plays an important role in the modulation of muscle properties. This review summarizes the adaptive response of jaw muscles to various stimuli or perturbations in the orofacial system and addresses general changes in muscles as they adapt, specific adaptive changes in jaw muscles under various physiologic and pathologic conditions, and their adaptive response to non-surgical and surgical therapeutic interventions. Although the jaw muscles are used concertedly in the masticatory system, their adaptive changes are not always uniform and vary with the nature, intensity, and duration of the stimulus. In general, stretch, increases neuromuscular activity, and resistance training result in hypertrophy, elicits increases in mitochondrial content and cross-sectional area of the fibres, and may change the fibre-type composition of the muscle towards a larger percentage of slow-type fibres. In contrast, changes in the opposite direction occur when neuromuscular activity is reduced, the muscle is immobilized in a shortened position, or paralysed. The broad range of stimuli that affect the properties of jaw muscles might help explain the large variability in the anatomical and physiological characteristics found among individuals, muscles, and muscle portions.

From movement to models: a tribute to professor Alan G. Hannam.

This tribute article to Professor Alan G. Hannam is based on 7 presentations for him at the July 1, 2008 symposium honoring 3 "giants" in orofacial neuroscience: Professors B. J. Sessle, J. P. Lund, and A. G. Hannam. This tribute to Hannam's outstanding career draws examples from his 40-year academic career and spans topics from human evolution to complex modeling of the craniomandibular system. The first presentation by W. Hylander provides a plausible answer to the functional and evolutionary significance of canine reduction in hominins. The second presentation, by A. McMillan, describes research activities in the field of healthy aging, including findings that intensity-modulated radiotherapy improves the health condition and quality of life of people with nasopharyngeal carcinoma in comparison to conventional radiotherapy. The developments in dental imaging are summarized in the third paper by E. Lam, and an overview of the bite force magnitude and direction while clenching is described in the fourth paper by M. Watanabe. The last 3 contributions by G. Langenbach, I. Staveness, and C. Peck deal with the topic of bone remodeling as well as masticatory system modeling, which was Hannam's main research interest in recent years. These contributions show the considerable advancements that have been made in the last decade under Hannam's drive, in particular the development of an interactive model comprising, in addition to the masticatory system, also the upper airways. The final section of the article includes a final commentary from Professor Hannam.

Daily jaw muscle activity in freely moving rats measured with radio-telemetry.

The jaw muscle activity of rats has been investigated for specific tasks. However, the daily jaw muscle use remains unclear. The purpose of the present study was to examine daily jaw muscle activity, and its variability over time, in the rat (n = 12) by the use of radio-telemetry. A telemetric device was implanted for the continuous recording of masseter muscle and digastric muscle activity. Daily muscle use was characterized by calculating the total time that each muscle was active (duty time), the number of bursts, and the average length of bursts. All parameters were estimated for activities exceeding various levels (5-90%) of the day's peak activity. Daily muscle use remained constant for 4 wk. At the low-activity level, the duty time and burst number of the digastric muscle were significantly (P < 0.01) higher than those of the masseter muscle, whereas the opposite was true at the high-activity level (P < 0.05). No significant intermuscular correlation was observed between the number of bursts of the masseter and digastric muscles, but the interindividual variation of both muscles changed, depending on the level of activation. These findings suggest that the masseter muscle and the digastric muscle show a differential active pattern, depending on the activity level.