Loss Of Trabeculae Research Articles

Development of a Preclinical Double Model of MandibularIrradiated Bone and Osteoradionecrosis in NewZealand Rabbits.

Radiotherapy (RT) plays a crucial role in head and neck (HN) cancer treatment. Nevertheless, it can lead to serious and challenging adverse events such as osteoradionecrosis (ORN). A preclinical rabbit model of irradiated bone and ORN is herein proposed, with the aim to develop a viable model to be exploited for investigating new therapeutic approaches. Nine New Zealand white rabbits were irradiated using a single beam positioned to the left of the mandible and directed perpendicular to the left mandible. A 10 × 10 mm2 region of interest (ROI) located below the first molar tooth on the left side was identified and irradiated with 7 Gy each fraction, once every 2 days, for five fractions. Dose distributions demonstrated that the corresponding ROI on the contralateral (right) mandibular side received approximately 5 Gy each fraction, thus bilateral irradiation of the mandible was achieved. ROIs were categorized as ROIH on the left side receiving the high dose and ROIL on the right side receiving the low dose. Rabbits were followed up clinically and imaged monthly. After 4 months, the irradiated bone was excised, and histological examination of ROIs was performed. Radiological signs suggestive for ORN were detected in the entire population (100%) 16 weeks after irradiation on ROIH, which consisted of cortical erosion and loss of trabeculae. ROIL did not show any radiological evidence of bone damage. Histologically, both sides showed comparable signs of injury, with marked reduction in osteocyte count and increase in empty lacunae count. A preclinical double model was successfully developed. The side receiving the higher dose showed radiological and histological signs of bone damage, resulting in an ORN model. Whereas the contralateral side, receiving the lower dose, presented with histological damage only and a normal radiological appearance. This work describes the creation of a double model, an ORN and irradiated bone model, for further study using this animal species.

Biopsies from patients with sacral insufficiency fracture are characterized by low bone matrix mineralization and high turnover.

Sacral insufficiency fractures are known to occur primarily in older women without adequate trauma. While an association with low bone mineral density (ie, osteoporosis) has been reported, more detailed information on local bone quality properties in affected patients is not available. In the present study, core biopsies were obtained from the S1 sacral ala in patients with a bilateral sacral insufficiency fracture (type IV according to the fragility fractures of the pelvis classification) who required surgical stabilization. Dual energy X-ray absorptiometry (DXA) and laboratory bone metabolism analyses were performed. For comparison, control biopsies were acquired from skeletally intact age- and sex-matched donors during autopsy. A total of 31 biopsies (fracture: n = 19; control: n = 12) were evaluated by micro-computed tomography, histomorphometry on undecalcified sections, and quantitative backscattered electron imaging (qBEI). DXA measurements showed mean T-scores in the range of osteoporosis in the fracture cohort (T-scoremin -2.6 ± 0.8). Biochemical analysis of bone metabolism parameters revealed high serum alkaline phosphatase and urinary deoxypyridinoline/creatinine levels. In the biopsies, a loss of trabecular microstructure along with increased osteoid values were detected in the fracture patients compared with controls (osteoid volume per bone volume 5.9 ± 3.5 vs. 0.9 ± 0.5%, p <.001). We also found evidence of microfractures with chronic healing processes (ie, microcallus) as well as pronounced hypomineralization in the biopsies of the fracture cohort compared with the controls as evidenced by lower CaMean measured by qBEI (22.5 ± 1.6 vs. 24.2 ± 0.5wt%, p =.003). In conclusion, this high-resolution biopsy study provides evidence of local hypomineralization in patients with sacral insufficiency fractures, pointing to reduced fracture resistance but also a distinct phenotype other than the predominant loss of trabeculae as in postmenopausal osteoporosis. Our data highlight the importance of therapies that promote bone mineralization to optimally treat and prevent sacral insufficiency fractures.

Seno cavernoso: anatomía, histología y terminología.

Although the cavernous sinus (CS) has been studied since 1695, its anatomy and name are still under discussion. Anatomy and histology of 40 CS from human cadavers were studied, included both from a newborn specimen. Two walls limit the CS, an inferior medial one composed only of the dura's outer layer and a superior lateral one consisting of both dura's layers. Sinusoidal veins pass through the lateral wall of the CS as a transition between venous tributaries and the CS. An endothelial layer covers the inner surface of the CS and the outer surface of the internal carotid artery. The space within the CS shows trabeculae, which are rarer in adults compared to the newborn. The loss of trabeculae in the CS may be a natural process along with life. In conclusion, the CS is a real sinus, and the term "cavernous sinus" is appropriately applied.

Rapamycin attenuates pathological hypertrophy caused by an absence of trabecular formation

Cardiac trabeculae are mesh-like muscular structures within ventricular walls. Subtle perturbations in trabeculation are associated with many congenital heart diseases (CHDs), and complete failure to form trabeculae leads to embryonic lethality. Despite the severe consequence of an absence of trabecular formation, the exact function of trabeculae remains unclear. Since ErbB2 signaling plays a direct and essential role in trabecular initiation, in this study, we utilized the erbb2 zebrafish mutant as a model to address the function of trabeculae in the heart. Intriguingly, we found that the trabeculae-deficient erbb2 mutant develops a hypertrophic-like (HL) phenotype that can be suppressed by inhibition of Target of Rapamycin (TOR) signaling in a similar fashion to adult mammalian hearts subjected to mechanical overload. Further, cell transplantation experiments demonstrated that erbb2 mutant cells in an otherwise wildtype heart did not undergo hypertrophy, indicating that erbb2 mutant HL phenotypes are due to a loss of trabeculae. Together, we propose that trabeculae serve to enhance contractility and that defects in this process lead to wall-stress induced hypertrophic remodeling.

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis

BackgroudWhole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)–induced knee osteoarthritisrabbit model.MethodNinety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed.ResultsAfter 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group.ConclusionOur data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Effect Of Low-magnitude Different-frequency Whole-body Vibration On Subchondral

PURPOSE: To investigate the effects of different vibration frequencies of low-magnitude whole-body vibration (WBV) on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and jointpain in an anterior cruciate ligament transection (ACLT)-induced knee osteoarthritis(OA) rabbit model. METHODS: Ninety adult rabbits subjected to unilateral ACLT were divided into six groups:Group 1,ACLT control group;Group 2,WBV (5 Hz) + ACLT;Group 3,WBV (10 Hz) +ACLT;Group 4,WBV (20 Hz) + ACLT;Group 5,WBV (30 Hz);and Group 6,WBV (40Hz).Pain was tested via weight-bearing asymmetry.Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]).Serum bone-specific alkaline phosphatase,N-mid OC,cartilage oligometric protein,CPII,type I collagen,PIIANP,G1/G2 aggrecan levels, and urinary CTX-II were analyzed. RESULTS: After 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz group. CONCLUSIONS: Our data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women.

Clinical studies suggest that vitamin K2 protects against bone loss and fractures; however, its effect on bone quality has never been investigated. We investigated the effect of vitamin MK-7 on undercarboxylated osteocalcin (ucOC), and bone mass and quality. We conducted a randomised, placebo-controlled, double-blinded clinical trial. We investigated the effect of MK-7 375 µg for 12 months on bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA), bone microarchitecture measured by high-resolution peripheral quantitative computed tomography (HRpQCT) and biochemical bone turnover markers in 148 postmenopausal women with osteopenia. All of them were supplemented with calcium and vitamin D. ucOC decreased in the MK-7 group (-65.6 (59.1; 71.0) %) (median (CI)) compared with the placebo group (-6.4 (-13.5; 1.2) %) after 3 months (P < 0.01). HRpQCT after 12 months demonstrated that trabecular number in tibia was unchanged in the MK-7-group (-0.1 ± 1.9%) (mean ± s.d.) and decreased in the placebo group (-3.5 ± 2.2%), trabecular spacing was unchanged in the MK-7 group (+1.2 ± 8.0%) and increased in the placebo group (+4.5 ± 9.7%), and trabecular thickness was unchanged in the MK-7 group (+0.2 ± 1.7%) and increased in the placebo group (+4.0 ± 2.2%) (between-group changes for all: P < 0.05). There were no significant differences between the groups in HRpQCT-derived parameters at the radius or in BMD at any site. The changes in bone microarchitecture in the placebo group are consistent with the age-related deterioration of trabecular structure, with a loss of trabeculae and a greater mean thickness of the remaining trabeculae. This suggests that vitamin MK-7 preserves trabecular bone structure at the tibia.

Does mechanical stimulation really protect the architecture of trabecular bone? A simulation study.

Although it is beyond doubt that mechanical stimulation is crucial to maintain bone mass, its role in preserving bone architecture is much less clear. Commonly, it is assumed that mechanics helps to conserve the trabecular network since an "accidental" thinning of a trabecula due to a resorption event would result in a local increase of load, thereby activating bone deposition there. However, considering that the thin trabecula is part of a network, it is not evident that load concentration happens locally on the weakened trabecula. The aim of this work was to clarify whether mechanical load has a protective role for preserving the trabecular network during remodeling. Trabecular bone is made dynamic by a remodeling algorithm, which results in a thickening/thinning of trabeculae with high/low strain energy density. Our simulations show that larger deviations from a regular cubic lattice result in a greater loss of trabeculae. Around lost trabeculae, the remaining trabeculae are on average thinner. More generally, thin trabeculae are more likely to have thin trabeculae in their neighborhood. The plausible consideration that a thin trabecula concentrates a higher amount of strain energy within itself is therefore only true when considering a single isolated trabecula. Mechano-regulated remodeling within a network-like architecture leads to local concentrations of thin trabeculae.

Characterizing microarchitectural changes at the distal radius and tibia in postmenopausal women using HR-pQCT.

Limited prospective evidence exists regarding bone microarchitectural deterioration. We report annual changes in trabecular and cortical bone microarchitecture at the distal radius and tibia in postmenopausal women. Lost trabeculae with corresponding increase in trabecular thickness at the radius and thinning tibial cortex indicated trabecularization of the cortex at both sites. Osteoporosis is characterized by low bone mass and the deterioration of bone microarchitecture. However, limited prospective evidence exists regarding bone microarchitectural changes in postmenopausal women: a population prone to sustaining osteoporotic fractures. Our primary objective was to characterize the annual change in bone area, density, and microarchitecture at the distal radius and distal tibia in postmenopausal women. Distal radius and tibia were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 1 year later in 51 women (mean age ± SD, 77 ± 7 years) randomly sampled from the Saskatoon cohort of the Canadian Multicentre Osteoporosis Study (CaMos). We used repeated measures analysis of variance (ANOVA) with Bonferroni adjustment for multiple comparisons to characterize the mean annual change in total density, cortical perimeter, trabecular and cortical bone area, density, content, and microarchitecture. Significant changes were accepted at P < 0.05. At the distal radius in women without bone-altering drugs, total density (-1.7%) and trabecular number (-6.4%) decreased, while trabecular thickness (+6.0%), separation (+8.6%), and heterogeneity (+12.1%) increased. At their distal tibia, cortical area (-4.5%), density (-1.9%), content (-6.3%), and thickness (-4.4%) decreased, while trabecular area (+0.4%) increased. The observed loss of trabeculae with concomitant increase in trabecular size at the distal radius and the declined cortical thickness, density, and content at the distal tibia indicated a site-specific trabecularization of the cortical bone in postmenopausal women.

Endothelial Notch activity promotes angiogenesis and osteogenesis in bone

Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.

Role of family medicine in the early detection and management of osteoporosis

Objectives The aim was to study the epidemiology, pathophysiology, and risk assessment of osteoporosis among adults as a major health problem and clarify the role of the family physician in the prevention, screening, early detection, and management of osteoporosis. Data analysis Osteoporosis is a multifactorial skeletal disease characterized by reduction in bone mass and deterioration of the microarchitectural structure of bone tissue, with resulting increase in bone fragility and fracture risk. A decline in bone mineral density with age increases bone fragility because it reflects the progressive loss of bone mass and changes in the architecture of the bone, such as cortical thinning, cortical porosity, and thinning and loss of trabeculae with loss of connectedness of trabeculae. Bone loss is progressive and is not associated with symptoms until a fracture occurs - the main clinical feature of osteoporosis. Recent finding Worldwide, osteoporosis causes more than 8.9 million fractures annually, resulting in an osteoporotic fracture every 3 s. Osteoporosis is estimated to affect 200 million women worldwide. Egyptian studies show that 53.9% of postmenopausal women have osteopenia, whereas 28.4% have osteoporosis, and 21.9% of men aged 20-89 years have osteoporosis. Conclusion As the clinical outcome of osteoporosis is bone fracture, attention is now increasingly focused on the identification of patients at high risk for fracture rather than the identification of people with osteoporosis as defined by bone mineral density alone.

Pre-emptive, early, and delayed alendronate treatment in a rat model of knee osteoarthritis: effect on subchondral trabecular bone microarchitecture and cartilage degradation of the tibia, bone/cartilage turnover, and joint discomfort

Bisphosphonates are considered potential disease modifying osteoarthritis (OA) agents. The present study investigated the efficacy of pre-emptive, early, and delayed alendronate (ALN) treatment initiation on subchondral trabecular bone and cartilage in low-dose monosodium iodoacetate (MIA)-induced knee OAin rats. Male rats received pre-emptive (n=12, day 0-end of week 2), early (n=12, end of week 2-end of week 6), or delayed (n=12, end of week 6-end of week 10) ALN treatment (30μg/kg/week). Pre-emptive ALN-treated rats were scanned using invivo micro-computed tomography (micro-CT) after 2 weeks and then sacrificed, early ALN-treated rats were scanned after 2 and 6 weeks and sacrificed, and the delayed ALN-treated rats were scanned after 2, 6, and 10 weeks of OA induction and sacrificed. After sacrifice, bone histomorphometry and histology of the tibia and biomarker analyses were undertaken. Changes in hind limb weight-bearing were assessed from day-1 until day 14. MIA-induced pathological features similar to progressive human OA in the cartilage and subchondral bone. Pre-emptive ALN treatment preserved subchondral trabecular bone microarchitecture, prevented bone loss, decreased bone turnover and joint discomfort. Pre-emptive ALN treatment had moderate effects on cartilage degradation. Early and delayed ALN treatments prevented loss of trabeculae and decreased bone turnover, but had no significant effect on cartilage degradation. ALN prevented increased bone turnover and preserved the structural integrity of subchondral bone in experimental OA. The time point of treatment initiation is crucial for treating OA. Treating both the subchondral bone and cartilage in OA would be clinically more beneficial.

A sclerostin-based theory for strain-induced bone formation

Bone formation responds to mechanical loading, which is believed to be mediated by osteocytes. Previous theories assumed that loading stimulates osteocytes to secrete signals that stimulate bone formation. In computer simulations this 'stimulatory' theory successfully produced load-aligned trabecular structures. In recent years, however, it was discovered that osteocytes inhibit bone formation via the protein sclerostin. To reconcile this with strain-induced bone formation, one must assume that sclerostin secretion decreases with mechanical loading. This leads to a new 'inhibitory' theory in which loading inhibits osteocytes from inhibiting bone formation. Here we used computer simulations to show that a sclerostin-based model is able to produce a load-aligned trabecular architecture. An important difference appeared when we compared the response of the stimulatory and inhibitory models to loss of osteocytes, and found that the inhibitory pathway prevents the loss of trabeculae that is seen with the stimulatory model. Further, we demonstrated with combined stimulatory/inhibitory models that the two pathways can work side-by-side to achieve a load-adapted bone architecture.

Automated quantitative microstructural analysis of metastatically involved vertebrae: Effects of stereologic model and spatial resolution

Summary of background data Preclinical models of spinal metastases allow for the application of micro-image based structural assessments, however, large data sets resulting from high resolution scanning motivate a need for robust automated analysis tools. Accurate assessment of changes in vertebral architecture, however, may depend both on the resolution of images acquired and the models used to represent the structural data. Objective To apply a recently developed automated μCT based analysis tool to quantify the effect of diffuse metastatic disease on rat vertebral architecture at multiple resolutions. It was hypothesized that automated methods could accurately quantify differences in vertebral microstructure and that diffuse metastatic disease could be shown to have significant negative architectural effects on trabecular bone independent of stereologic model and resolution. Methods μCT images acquired at 14 μm 3 of healthy and metastatcially involved whole lumbar rat vertebrae were analyzed at high, medium and low (8.725, 17.45, and 34.9 μm 3) resolutions using an automated algorithm to yield micro-structural measures of the trabecular centrum and cortical shell. The images analyzed at different resolutions were obtained via up/downsampling of the acquired image data. Trabecular thickness was evaluated with the Parfitt and Hildebrand models, and anisotropy was evaluated through calculation of mean intercept length. Results Significant differences in microstructural parameters measured in comparing healthy and metastatically involved vertebrae were affected by resolution, however, relative anisotropy was maintained. The Parfitt and Hilderbrand models yielded similar structural differences between healthy and metastatic vertebrae, however, the Hildebrand model was limited due to segmentation accuracy required for its automated application. Conclusions Differences in microstructural parameters generated through automated analysis at high resolution suggest that diffuse MT1 osteolytic destruction in whole rat vertebrae results primarily in loss of trabeculae in the metastatic vertebrae, as opposed to trabecular thinning. The sensitivity of the bony architectural parameters to resolution motivates the need for high resolution scanning or post-processing of images.

Mechanobiological regulation of the remodelling cycle in trabecular bone and possible biomechanical pathways for osteoporosis

Background The rapid loss of trabeculae as observed during osteoporosis is attributed to pathological changes in the bone remodelling process. In this study, it is proposed that osteoporosis is due to altered signals resulting from either (i) a decrease in the mechanosensitivity of the sensor cells or (ii) an increase in the bone tissue elastic modulus. Methods To test these hypotheses, a mechanobiological algorithm was developed and applied to simulate the remodelling cycle in a realistic trabecular strut. The model is based on the supposition that bone resorption is initiated either to remove damaged tissue or when strains fall below a lower threshold; bone formation is triggered when strains exceed an upper threshold. Findings Applying this algorithm to a realistic trabecula, resorption and subsequent refilling of a cavity was simulated. Results showed that decreases in the mechanosensitivity (simulated by increasing the upper strain threshold) led to under-refilling of cavities. A critical sensitivity was found to exist, above which perforation of the strut due to osteoclastic resorption occurred. It was also found that increases in the bone tissue elastic modulus lead to an increased propensity for trabecular perforation. Interpretation It may be concluded that if cells become less mechanosensitive, or if increases in the elastic modulus of trabecular bone tissue occurs, the possibility of trabecular perforation and therefore the rapid loss of bone mass increases. If this is true, the preservation of the bone mineral content or maintenance of bone cell mechanosensitivity are potential therapeutic strategies for the prevention of osteoporosis.

Estrogen and Fracture Risk in Men

Estrogen and Fracture Risk in Men

Sarcomere Mutations in Cardiomyopathy, Noncompaction, and the Developing Heart

In this issue of Circulation , Klaassen and colleagues1 describe mutations in the genes encoding myosin heavy chain (MHC), cardiac actin, and troponin T in patients with left ventricular noncompaction (LVNC). LVNC, defined as excessive and unusual trabeculation of the mature left ventricle, is thought to reflect a developmental failure of the heart to form fully the compact myocardium during the later stages of cardiac development. Previously, mutations in sarcomeric genes have been linked extensively to the development of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The finding of similar, but not identical, mutations in patients with LVNC suggests a continuum of cardiomyopathy that includes LVNC and further supports the essential role for normal sarcomere function during cardiac development. Article p 2893 Noncompaction of the ventricular myocardium is characterized by a spongy morphological appearance of the myocardium occurring primarily in the left ventricle and most evident in the apical portion.2 Noncompaction often is visualized as deep recesses within the thickened apex, and these sinusoids communicate with the ventricular cavity. During heart development, the myocardium is initially trabeculated during a period before coronary artery development and is thought to be an adaptation to provide blood flow to the developing myocardium. The development of the coronary vasculature is associated temporally with the loss of trabeculae and the full maturation of the compact myocardium. Between embryonic weeks 5 and 8, the trabeculae regress as the compact myocardium develops from base to apex. Isolated LVNC is defined as occurring in the absence of other cardiac structural malformation. Nonsyndromic LVNC refers to the absence of other extracardiac developmental disorders. In 2006, the American Heart Association scientific statement on classification of cardiomyopathies reclassified LVNC as its own disease entity.3 Klaassen et al now link genetic sarcomere defects to both familial and sporadic isolated, …

Loss of trabeculae by mechano-biological means may explain rapid bone loss in osteoporosis.

Osteoporosis is characterized by rapid and irreversible loss of trabecular bone tissue leading to increased bone fragility. In this study, we hypothesize two causes for rapid loss of bone trabeculae; firstly, the perforation of trabeculae is caused by osteoclasts resorbing a cavity so deep that it cannot be refilled and, secondly, the increases in bone tissue elastic modulus lead to increased propensity for trabecular perforation. These hypotheses were tested using an algorithm that was based on two premises: (i) bone remodelling is a turnover process that repairs damaged bone tissue by resorbing and returning it to a homeostatic strain level and (ii) osteoblast attachment is under biochemical control. It was found that a mechano-biological algorithm based on these premises can simulate the remodelling cycle in a trabecular strut where damaged bone is resorbed to form a pit that is subsequently refilled with new bone. Furthermore, the simulation predicts that there is a depth of resorption cavity deeper than which refilling of the resorption pits is impossible and perforation inevitably occurs. However, perforation does not occur by a single fracture event but by continual removal of microdamage after it forms beneath the resorption pit. The simulation also predicts that perforations would occur more easily in trabeculae that are more highly mineralized (stiffer). Since both increased osteoclast activation rates and increased mineralization have been measured in osteoporotic bone, either or both may contribute to the rapid loss of trabecular bone mass observed in osteoporotic patients.

Cancellous bone changes in hip osteoarthritis: a short-term longitudinal study using fractal signature analysis

To quantify changes to the trabecular structure in the femoral heads of patients with hip osteoarthritis (OA). Patients with OA (n=14; F=7), mean (standard deviation age) 50.6 (10.1) years, had macroradiographs at approximately x4 magnification at baseline and 18 months later using a standardized protocol. Following digitization, computerized measurement was obtained of minimum hip joint space width and fractal signature analysis (FSA) measured longitudinal changes separately in the principal compressive (vertical) and horizontal trabeculae at the region of interest within the centre of the head. The patient group had mean annual rate of joint space narrowing of 0.14+/-0.36 mm/yr. FSA detected no significant changes in horizontal trabeculae, whereas the larger principal compressive (vertical) trabeculae (0.96 mm to 1.02 mm) increased significantly in thickness and the fine to medium trabeculae (0.18 mm to 0.54 mm) decreased significantly in number. The increased thickness of the larger trabeculae within the compressive structural element of the femoral head is a response to the increase in stress associated with an overall loss of trabeculae in this region, suggesting the presence of an osteoporosis within the femoral head in OA patients.

Perforation of cancellous bone trabeculae by damage-stimulated remodelling at resorption pits: A computational analysis

Loss of trabeculae in cancellous bone is often attributed to a general decline in the bone mass leading to fracture of the thin trabeculae. It has never been investigated whether trabecular perforation may have any other biomechanical mechanism. In this paper, an alternative hypothesis is proposed and tested using a computational model. Taking it as given that osteoclastic resorption is targeted to microdamage, it is hypothesised that the creation of a resorption cavity during normal bone remodelling could cause a stress-concentration in the bone tissue. If the resorption cavities were excessively deep, as is seen during osteoporosis, then this stress concentration may be sufficient to generate more microdamage so that osteoclasts "chase" newly formed damage leading to perforation. If this were true then we should find that, for a given trabecular thickness, there is a critical depth of resorption cavity such that smaller cavities refill whereas deeper cavities cause microdamage accumulation, continued osteoclast activity, and eventual trabecular perforation. Computer simulation is used to test this hypothesis. Using a remodelling stimulus calculated from both strain and damage and a simplified finite element model of a trabeculum with cavities of different sizes, it is predicted that such a critical depth of resorption cavity does indeed exist. Therefore we suggest that an increase in resorption depth relative to the thickness of trabeculae may be responsible for trabecular perforation during osteoporosis, rather than simply trabecular fracture due to insufficient strength.