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.

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.

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.

The correlation between mineralization degree and bone tissue stiffness in the porcine mandibular condyle.

The aim of this study was to correlate the local tissue mineral density (TMD) with the bone tissue stiffness. It was hypothesized that these variables are positively correlated. Cancellous and cortical bone samples were derived from ten mandibular condyles taken from 5 young and 5 adult female pigs. The bone tissue stiffness was assessed in three directions using nanoindentation. At each of three tested sides 5 indents were made over the width of 5 single bone elements, resulting in a total number of 1500 indents. MicroCT was used to determine the local TMD at the indented sites. The TMD and the bone tissue stiffness were higher in bone from the adult animals than from the young ones, but did not differ between cancellous and cortical bone. In the adult group, both the TMD and the bone tissue stiffness were higher in the center than at the surface of the bone elements. The mean TMD, thus ignoring the local mineral distribution, had a coefficient of determination (R(2)) with the mean bone tissue stiffness of 0.55, p < 0.05, whereas the correlation between local bone tissue stiffness and the concomitant TMD appeared to be weak (R (2) 0.07, p < 0.001). It was concluded that the mineralization degree plays a larger role in bone tissue stiffness in cancellous than in cortical bone. Our data based on bone from the mandibular condyle suggest that the mineralization degree is not a decisive determinant of the local bone tissue stiffness.

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.

The microstructural and biomechanical development of the condylar bone: a review.

BACKGROUND: Bone constantly strives for optimal architecture. Mandibular condyle, which is subjected to various mechanical loads forcing it to be highly adaptive, has a unique structure and a relatively high remodelling rate. Despite the eminent clinical relevance of mandibular condyle, literature on its structural and biomechanical development and on the mechanical role of its mineralized and non-mineralized bone components is scarce. OBJECTIVE: The aim of the present review is to provide a brief introduction to basic bone mechanics and a synopsis of the growth and development of human mandibular condyle. Subsequently, the current ideas on the relationship between the structural and biomechanical properties of bone in general and of mandibular condyle in particular are reviewed. Finally, up-to-date knowledge from fundamental bone research will be blended with the current knowledge relevant to clinical dentistry, above all orthodontics. METHODS: A comprehensive literature study was performed with an emphasis on recent and innovative work focusing on the interaction between microarchitectural and micromechanical properties of bone. CONCLUSIONS: Mandibular condyle is a bone structure with a high bone turnover rate. Mechanical properties of mandibular condyle improve during adolescence and are optimal during adulthood. Local mineralization degree might not be a decisive determinant of the local bone tissue stiffness as was believed hitherto. Bone collagen and its cross links play a role in toughness and tensile strength of bone but not in its compressive properties. Clinical procedures might affect mandibular condyle, which is highly reactive to changes in its mechanical environment.

Influence of botulinum toxin on rabbit jaw muscle activity and anatomy.

INTRODUCTION: Muscles can adapt their fiber properties to accommodate to new conditions. We investigated the extent to which a decrease in muscle activation can cause an adaptation of fiber properties in synergistic and antagonistic jaw muscles. METHODS: Three months after the injection of botulinum toxin type A in one masseter (anterior or posterior) muscle changes in fiber type composition and fiber cross-sectional areas in jaw muscles were studied at the microscopic level. RESULTS: The injected masseter showed a steep increase in myosin type IIX fibers, whereas fast fibers decreased by about 50% in size. Depending on the injection site, both synergistic and antagonistic muscles showed a significant increase in the size of their fast IIA fibers, sometimes combined with an increased number of IIX fibers. CONCLUSION: Silencing the activity in the masseter not only causes changes in the fibers of the injected muscle but also leads to changes in other jaw muscles.

The masticatory system under varying functional load. Part 2: Effect of reduced masticatory load on the degree and distribution of mineralization in the rabbit mandible.

A reduction in mechanical loading of the mandible brought about by mastication of soft food is assumed to decrease the remodelling rate of bone, which, in turn, might increase the degree of bone mineralization. The effect of a reduction in masticatory functional load on the degree and distribution of mineralization of mandibular bone was investigated in male juvenile New Zealand White rabbits. The experimental animals (n=8) had been raised on a diet of soft pellets from 8 to 20 weeks of age, while the controls (n=8) had been fed pellets of normal hardness. The degree of mineralization of bone (DMB) was assessed at the attachment sites of various jaw muscles, the condylar head, and the alveolar process. Differences between groups and among sites were tested for statistical significance using a Student's t-test and one-way analysis of variance, respectively. The DMB did not differ significantly between the experimental and control animals at any of the sites assessed. However, in the rabbits that had been fed soft pellets, both cortical bone at the attachment sites of the temporalis and digastric muscles and cortical bone in the alveolar process had a significantly higher DMB than cortical bone at the attachment site of the masseter muscle, while there were no significant differences among these sites in the control animals. The results suggest that a moderate reduction in masticatory functional load does not significantly affect the remodelling rate and the DMB in areas of the mandible that are loaded during mastication but might induce a more heterogeneous mineral distribution.

The masticatory system under varying functional load. Part 1: Structural adaptation of rabbit jaw muscles to reduced masticatory load.

Skeletal muscle fibres can change their myosin heavy-chain (MyHC) isoform and cross-sectional area, which determine their contraction velocity and maximum force generation, respectively, to adapt to varying functional loads. In general, reduced muscle activity induces transition towards faster fibres and a decrease in fibre cross-sectional area. In order to investigate the effect of a reduction in masticatory load on three functionally different jaw muscles, the MyHC composition and the corresponding cross-sectional area of fibres were determined in the superficial masseter, superficial temporalis, and digastric muscles of male juvenile New Zealand White rabbits that had been raised on a soft diet (n=8) from 8 to 20 weeks of age and in those of normal diet controls (n=8). Differences between groups were tested for statistical significance using a Mann-Whitney rank sum test. The proportion and cross-sectional area of fibres co-expressing MyHC-I and MyHC-cardiac alpha were significantly smaller in the masseter muscles of the animals that had been fed soft food than in those of the controls. In contrast, the proportions and cross-sectional areas of the various fibre types in the temporalis and digastric muscles did not differ significantly between the groups. The results suggest that reducing the masticatory load during development affects the contraction velocity and maximum force generation of the jaw-closing muscles that are primarily responsible for force generation during chewing. These muscles adapt structurally to the reduced functional load with changes in the MyHC composition and cross-sectional area mainly within their slow fibre compartment.

Adaptation of rat jaw muscle fibers in postnatal development with a different food consistency: an immunohistochemical and electromyographic study.

The development of the craniofacial system occurs, among other reasons, as a response to functional needs. In particular, the deficiency of the proper masticatory stimulus affects the growth. The purpose of this study was to relate alterations of muscle activity during postnatal development to adaptational changes in the muscle fibers. Fourteen 21-day-old Wistar strain male rats were randomly divided into two groups and fed on either a solid (hard-diet group) or a powder (soft-diet group) diet for 63 days. A radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter, anterior belly of digastric and anterior temporalis muscles. The degree of daily muscle use was quantified by the total duration of muscle activity per day (duty time), the total burst number and their average length exceeding specified levels of the peak activity (5, 20 and 50%). The fiber type composition of the muscles was examined by the myosin heavy chain content of fibers by means of immunohistochemical staining and their cross-sectional area was measured. All muscle fibers were identified as slow type I and fast type IIA, IIX or IIB (respectively, with increasing twitch contraction speed and fatigability). At lower activity levels (exceeding 5% of the peak activity), the duty time of the anterior belly of the digastric muscle was significantly higher in the soft-diet group than in the hard-diet group (P < 0.05). At higher activity levels (exceeding 20 and 50% of the peak activity), the duty time of the superficial masseter muscle in the soft-diet group was significantly lower than that in the hard-diet group (P < 0.05). There was no difference in the duty time of the anterior temporalis muscle at any muscle activity level. The percentage of type IIA fibers of the superficial masseter muscle in the soft-diet group was significantly lower than that in the hard-diet group (P < 0.01) and the opposite was true with regard to type IIB fibers (P < 0.05). The cross-sectional area of type IIX and type IIB fibers of the superficial masseter muscle was significantly smaller in the soft-diet group than in the hard-diet group (P < 0.05). There was no difference in the muscle fiber composition and the cross-sectional area of the anterior belly of the digastric and anterior temporalis muscles. In conclusion, for the jaw muscles of male rats reared on a soft diet, the slow-to-fast transition of muscle fiber was shown in only the superficial masseter muscle. Therefore, the reduction in the amount of powerful muscle contractions could be important for the slow-to-fast transition of the myosin heavy chain isoform in muscle fibers.

Age-related changes in collagen properties and mineralization in cancellous and cortical bone in the porcine mandibular condyle.

Collagen is an important constituent of bone, and it has been suggested that changes in collagen and mineral properties of bone are interrelated during growth. The aim of this study was to quantify age-related changes in collagen properties and the degree of mineralization of bone (DMB). The DMB in cancellous and cortical bone samples from the mandibular condyle of 35 female pigs aged 0-100 weeks was determined using micro-computed tomography. Subsequently, the amount of collagen and the number of pentosidine (Pen), hydroxylysylpyridinoline (HP), and lysylpyridinoline (LP) cross-links were quantified by means of high-performance liquid chromatography. The amount of collagen increased with age in cancellous bone but remained unchanged in cortical bone. The number of Pen and LP cross-links decreased in both bone types. In contrast, the number of HP cross-links decreased only in cancellous bone. The sum of the number of HP and LP cross-links decreased with age in cancellous bone only. The DMB increased in cancellous and cortical bone. It was concluded that the largest changes in the number of mature collagen cross-links and the mineralization in porcine cancellous and cortical bone take place before the age of 40 weeks. The low number of mature cross-links after this age suggests that the bone turnover rate continues to be high and thereby prevents the development of mature cross-links.

Inhibitory regulation of osteoclast bone resorption by signal regulatory protein alpha.

Osteoclasts mediate bone resorption, which is critical for bone development, maintenance, and repair. Proper control of osteoclast development and function is important and deregulation of these processes may lead to bone disease, such as osteoporosis. Previous studies have shown that the cytosolic protein tyrosine phosphatase SHP-1 acts as a suppressor of osteoclast differentiation and function, but putative inhibitory receptors that mediate recruitment and activation of SHP-1 in osteoclasts have remained unknown. In the present study, we identify the SHP-1-recruiting inhibitory immunoreceptor signal regulatory protein (SIRP) alpha as a negative regulator of osteoclast activity. SIRPalpha is expressed by osteoclasts, and osteoclasts from mice lacking the SIRPalpha cytoplasmic tail and signaling capacity display enhanced bone resorption in vitro. Consequently, SIRPalpha-mutant mice have a significantly reduced cortical bone mass. Furthermore, osteoclasts from SIRPalpha-mutant mice show an enhanced formation of actin rings, known to be instrumental in bone resorption. SIRPalpha mutation did not significantly affect osteoclast formation, implying that the role of SIRPalpha was limited to the regulation of mature osteoclast function. This identifies SIRPalpha as a bona fide inhibitory receptor that regulates the bone-resorption activity and supports a concept in which osteoclast function is balanced by the signaling activities of activating and inhibitory immunoreceptors.

Functional characteristics of the rat jaw muscles: daily muscle activity and fiber type composition.

Skeletal muscles have a heterogeneous fiber type composition, which reflects their functional demand. The daily muscle use and the percentage of slow-type fibers have been shown to be positively correlated in skeletal muscles of larger animals but for smaller animals there is no information. The examination of this relationship in adult rats was the purpose of this study. We hypothesized a positive relationship between the percentage of fatigue-resistant fibers in each muscle and its total duration of use per day. Fourteen Wistar strain male rats (410-450 g) were used. A radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter, deep masseter, anterior belly of digastric and anterior temporalis muscles. The degree of daily muscle use was quantified by the total duration of muscle activity per day (duty time) exceeding specified levels of the peak activity (2, 5, 20 and 50%). The fiber type composition of the muscles was examined by the myosin heavy chain content of the fibers by means of immunohistochemical staining. At lower activity levels (exceeding 2 and 5% of the peak activity), the duty time of the anterior belly of digastric muscle was significantly (P < 0.01) longer than those of the other muscles. The anterior belly of digastric muscle also contained the highest percentage of slow-type fibers (type I fiber and hybrid fiber co-expressing myosin heavy chain I + IIA) (ca. 11%; P < 0.05). By regression analysis for all four muscles, an inter-muscular comparison showed a positive relationship between the duty time (exceeding 50% of the peak activity) and the percentage of type IIX fibers (P < 0.05), which demonstrate intermediate physiological properties relative to type IIA and IIB fibers. For the jaw muscles of adult male rats, the variations of fiber type composition and muscle use suggest that the muscle containing the largest amounts of slow-type fibers (the anterior belly of digastric muscle) is mainly involved in low-amplitude activities and that the amount of type IIX fibers is positively related to the generation of large muscle forces, validating our hypothesis.

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.

Jaw-muscle activity changes after the induction of osteoarthrosis in the temporomandibular joint by mechanical loading.

AIMS: To examine the effect of mechanical loading on the induction of temporomandibular joint osteoarthrosis (TMJ OA). METHODS: Mechanical stress was applied to the rat TMJ by forced jaw opening of 3 hours a day for 5 days. The electromyographic (EMG) activity of the masseter and digastric muscles was continuously monitored by radio-telemetry. It was characterized by the total time each muscle was active (duty time), the number of bursts, and the average burst length. For histologic analysis, rats were sacrificed before, immediately after, and 3 weeks after the period of forced jaw opening. RESULTS: The condylar cartilage revealed OA-like lesions with a decrease in the number of chondrocytes immediately after forced jaw opening. Three weeks later, the OA-like lesions were repaired to some extent. After the forced jaw opening, the duty time of the masseter increased, whereas the duty time of the digastric decreased significantly (P < .01) at the 5% activity level. Three weeks later, the masseter duty time had decreased and the digastric duty time had slightly increased, returning to the levels observed before forced jaw opening. CONCLUSION: These results suggest that mechanical overloading of the TMJ induced OA-like lesions with a simultaneous influence on jaw muscle activity, especially at the low activity level. This might imply that muscle activity adapted to reduce the effects of (forced) joint overloading.

Heterogeneous postnatal transitions in myosin heavy chain isoforms within the rabbit temporalis muscle.

Postnatal changes in the fiber type composition and fiber cross-sectional area were investigated in the superficial (TEM1) and deep (TEM23) temporalis of male rabbits. It was hypothesized that, due to the transition from suckling to chewing during early postnatal development, the proportion of fast fiber types would decrease, while the proportion of fibers positive for myosin heavy chain (MyHC) cardiac alpha would increase, and that, due to the influence of testosterone during late postnatal development, the proportion of these alpha fibers would decrease again. Classification of the fibers types was performed by immunohistochemistry according to their MyHC content. The proportion of alpha fiber types significantly increased in both muscle portions from 2% and 8% for TEM1 and TEM23 at week 1 to 29% and 54% at week 8, respectively,. While in TEM1 the proportion of this fiber type did not change thereafter, it decreased again to 27% in TEM23 at week 20. The change for the fast fiber types was opposite to that of the alpha fiber types. Significantly more MyHC IIX fibers were found in TEM1 than in TEM23 in adult rabbits. In the first 8 weeks, the cross-sectional areas of all fibers increased. After this period, only MyHC cardiac alpha + I fibers continued to increase significantly. It was concluded that there are developmental differences in the myosin heavy chain transitions of the two portions of the temporalis muscle.

Circadian variation and intermuscular correlation of rabbit jaw muscle activity.

The activation of jaw muscles varies with different tasks and must be coordinated to ensure proper function of the masticatory system. The activation patterns might differ in various muscles or over the time course. In order to evaluate the activation patterns and the intermuscular correlation during normal daily activity the electromyograms (EMG) of the superficial and deep masseter, medial pterygoid and digastric muscles were continuously recorded in rabbits and related to activity levels. Muscle use was assessed as the relative time per hour (duty time) during which predefined levels of the peak-EMG of the day were exceeded. Pearson's correlation of duty times was calculated for 6 muscle pairs at various activity levels. The duty times of the muscles differed significantly at levels exceeding 50% of the peak-EMG. The animals exhibited apparent intraday variations of duty times revealing a circadian covariant pattern of muscle use. These variations, however, were different in each individual animal. The activation of pairs of jaw-closing muscles was more highly correlated than that of pairs consisting of a jaw-closing and a jaw-opening muscle. The mutual dependence of hourly muscle activity among jaw-closers and among jaw-closers and jaw-openers varied with the activity level suggesting that those muscle groups might be independently controlled during non-powerful and powerful motor behaviors.

Effects of Decreased Occlusal Loading during Growth on the Mandibular Bone Characteristics.

BACKGROUND: Bone mass and mineralization are largely influenced by loading. The purpose of this study was to evaluate the reaction of the entire mandibular bone in response to decreased load during growth. It is hypothesized that decreased muscular loading will lead to bone changes as seen during disuse, i.e. loss of bone mass. METHODS AND FINDINGS: Ten 21-day-old Wistar strain male rats were divided into two groups (each n=5) and fed on either a hard- or soft-diet for 11 weeks. Micro-computed tomography was used for the investigation of bone mineralization, bone volume, bone volume fraction (BV/TV) and morphological analysis. Mandibular mineralization patterns were very consistent, showing a lower degree of mineralization in the ramus than in the corpus. In the soft-diet group, mineralization below the molars was significantly increased (p<0.05) compared to the hard diet group. Also, bone volume and BV/TV of the condyle and the masseter attachment were decreased in the soft-diet group (p<0.05). Morphological analysis showed inhibited growth of the ramus in the soft-diet group (p<0.05). CONCLUSION: Decreased loading by a soft diet causes significant changes in the mandible. However, these changes are very region-specific, probably depending on the alterations in the local loading regime. The results suggest that muscle activity during growth is very important for bone quality and morphology.

Higher number of pentosidine cross-links induced by ribose does not alter tissue stiffness of cancellous bone.

The role of mature collagen cross-links, pentosidine (Pen) cross-links in particular, in the micromechanical properties of cancellous bone is unknown. The aim of this study was to examine nonenzymatic glycation effects on tissue stiffness of demineralized and non-demineralized cancellous bone. A total of 60 bone samples were derived from mandibular condyles of six pigs, and assigned to either control or experimental groups. Experimental handling included incubation in phosphate buffered saline alone or with 0.2M ribose at 37°C for 15 days and, in some of the samples, subsequent complete demineralization of the sample surface using 8% EDTA. Before and after experimental handling, bone microarchitecture and tissue mineral density were examined by means of microcomputed tomography. After experimental handling, the collagen content and the number of Pen, hydroxylysylpyridinoline (HP), and lysylpyridinoline (LP) cross-links were estimated using HPLC, and tissue stiffness was assessed by means of nanoindentation. Ribose treatment caused an up to 300-fold increase in the number of Pen cross-links compared to nonribose-incubated controls, but did not affect the number of HP and LP cross-links. This increase in the number of Pen cross-links had no influence on tissue stiffness of both demineralized and nondemineralized bone samples. These findings suggest that Pen cross-links do not play a significant role in bone tissue stiffness.