Cranial bone flap resorption—pathological features and their implications for clinical treatment
Jennifer GöttscheKlaus C. MendeAnastasia SchramManfred WestphalMichael AmlingJan RegelsbergerThomas SauvignyMichael Hahn
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Abstract:
Abstract Cranioplasty following decompressive craniectomy (DC) has a primary complication when using the autologous bone: aseptic bone resorption (ABR). So far, risk factors such as age, number of fragments, and hydrocephalus have been identified but a thorough understanding of the underlying pathophysiology is still missing. The aim of this osteopathological investigation was to gain a better understanding of the underlying processes. Clinical data of patients who underwent surgical revision due to ABR was collected. Demographics, the time interval between craniectomy and cranioplasty, and endocrine serum parameters affecting bone metabolism were collected. Removed specimens underwent qualitative and quantitative histological examination. Two grafts without ABR were examined as controls. Compared to the controls, the typical layering of the cortical and cancellous bone was largely eliminated in the grafts. Histological investigations revealed the coexistence of osteolytic and osteoblastic activity within the necrosis. Bone appositions were distributed over the entire graft area. Remaining marrow spaces were predominantly fibrotic or necrotic. In areas with marrow cavity fibrosis, hardly any new bone tissue was found in the adjacent bone, while there were increased signs of osteoclastic resorption. Insufficient reintegration of the flap may be due to residual fatty bone marrow contained in the bone flap which seems to act as a barrier for osteogenesis. This may obstruct the reorganization of the bone structure, inducing aseptic bone necrosis. Following a path already taken in orthopedic surgery, thorough lavage of the implant to remove the bone marrow may be a possibility, but will need further investigation.Keywords:
Cranioplasty
Bone remodeling
Cancellous bone
ABSTRACT Strain magnitude has a controlling influence on bone adaptive response. However, questions remain as to how and if cancellous and cortical bone tissues respond differently to varied strain magnitudes, particularly at a molecular level. The goal of this study was to characterize the time‐dependent gene expression, bone formation, and structural response of the cancellous and cortical bone of female C57Bl/6 mice to mechanical loading by applying varying load levels (low: −3.5 N; medium: −5.2 N; high: −7 N) to the skeleton using a mouse tibia loading model. The loading experiment showed that cortical bone mass at the tibial midshaft was significantly enhanced following all load levels examined and bone formation activities were particularly elevated at the medium and high loads applied. In contrast, for the proximal metaphyseal cancellous bone, only the high load led to significant increases in bone mass and bone formation indices. Similarly, expression of genes associated with inhibition of bone formation (e.g., Sost ) was altered in the diaphyseal cortical bone at all load levels, but in the metaphyseal cortico‐cancellous bone only by the high load. Finite element analysis determined that the peak tensile or compressive strains that were osteogenic for the proximal cancellous bone under the high load were significantly greater than those that were osteogenic for the midshaft cortical tissues under the low load. These results suggest that the magnitude of the strain stimulus regulating structural, cellular, and molecular responses of bone to loading may be greater for the cancellous tissues than for the cortical tissues. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Strain (injury)
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Properly regulating the resorption rate of a resorbable bone implant has long been a great challenge. This study investigates a series of physical/chemical properties, biocompatibility and the behavior of implant resorption and new bone formation of a newly developed Ca/P/S-based bone substitute material (Ezechbone® Granule CBS-400). Experimental results show that CBS-400 is comprised majorly of HA and CSD, with a Ca/P/S atomic ratio of 54.6/39.2/6.2. After immersion in Hank's solution for 7 days, the overall morphology, shape and integrity of CBS-400 granules remain similar to that of non-immersed samples without showing apparent collapse or disintegration. With immersion time, the pH value continues to increase to 6.55 after 7 days, and 7.08 after 14 days. Cytotoxicity, intracutaneous reactivity and skin sensitization tests demonstrate the good biocompatibility features of CBS-400. Rabbit implantation/histological observations indicate that the implanted granules are intimately bonded to the surrounding new bone at all times. The implant is not merely a degradable bone substitute, but its resorption and the formation of new cancellous bone proceed at the substantially same pace. After implantation for 12 weeks, about 85% of the implant has been resorbed. The newly-formed cancellous bone ratio quickly increases to >40% at 4 weeks, followed by a bone remodeling process toward normal cancellous bone, wherein the new cancellous bone ratio gradually tapers down to about 30% after 12 weeks.
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Granule (geology)
Bone Formation
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Abstract Resorption cavities formed during bone remodeling may act as “stress risers” and impair cancellous bone strength, but biomechanical analyses of the effects of stress risers have been limited. To provide further insight, we assessed the theoretical biomechanical effects of virtually-added resorption cavities in cancellous bone specimens spanning a wide range of bone volume fraction (BV/TV = 0.05–0.36) and across different anatomic sites (hip and spine) and species (human and canine). Micro-CT scans of 40 cubes of cancellous bone were converted into nonlinear finite element models (voxel element size ∼ 20 µm) for strength assessment. In each model, uniform trench-like resorption cavities with nominal dimensions 500 µm (length) × 200 µm (width) × 40 µm (depth), were virtually added either at random locations throughout the specimen, or, preferentially at locations of high tissue-level strain. We found that cancellous bone strength (p < 0.0001) and its relation with BV/TV (p < 0.001) were both altered by the virtual addition of the resorption cavities. When the resorption cavities were added at random locations throughout the specimen, the reduction in strength did not depend on BV/TV or anatomic site or species. When the resorption cavities were instead added preferentially at locations of high tissue-level strain, the effect was accentuated and was greatest in low-BV/TV bone. We conclude that, in theory, uniform-sized resorption cavities can reduce cancellous bone strength over the full range of BV/TV and across species, and the effect is larger if the cavities occur at highly strained locations in low-BV/TV bone. © 2012 American Society for Bone and Mineral Research.
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Abstract Background : This study characterizes the changes in cortical and cancellous bone and cross sectional moment of inertia of the femoral neck from aging and ovariectomized (ovx'd) rats to determine their role in the previously reported ovx‐induced reduction of mechanical strength in the femoral neck. Methods : Undecalcified double‐fluorescent lableled cross sections of femoral neck of 3.5‐, 5.5‐, 6.5‐, and 8.5‐month‐old female rats and rats ovx'd at 3.5 months for 2, 3, and 5 months of 45 rats were studied. The estimated endocortical and trabecular surfaces, cortical and cancellous bone histomorphometry, and cortical moment of inertia were determined. Results : The femoral neck was adding cortical bone between 3.5 and 5.5 months of age by increasing cortical thickness and decreasing marrow cavity area. No change of cortical bone mass was found between 5.5 and 8.5 months and the same amount of cancellous bone was observed between 3.5 and 8.5 months of age. Ovariectomy‐induced cancellous, but not cortical bone loss. The loss was due to a transient ovx‐induced negative bone balance that by 5 months post‐ovx produced a 42% loss in trabecular bone while the histomorphometry profiles were the same as controls. The crosssectional moment of inertia increased with age but did not differ significantly between ovx'd and controls. Conclusions : Our findings suggest that the ovx‐induced cancellous bone loss could be a contributing factor to the reduced mechanical strength in the femoral neck of ovx'd rats reported previously. © 1995 Wiley‐Liss, Inc.
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Osteopenia
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There are substantial changes in maternal skeletal dynamics during pregnancy, lactation, and after lactation. The purpose of this study was to correlate changes in cortical and cancellous bone mass, structure, and dynamics with mechanical properties during and after the first reproductive cycle in rats. Rats were mated and groups were taken at parturition, end of lactation and 8 wk after weaning, and were compared with age-matched, nulliparous controls. Measurements were taken on femoral cortical bone and lumbar vertebral body cancellous bone. At the end of pregnancy, there was an increase in cortical periosteal bone formation and an increase in cortical volume, but a suppression of turnover in cancellous bone with no change in cancellous or cortical mechanical properties. Lactation was associated with a decrease in cortical and cancellous bone strength with a decrease in bone volume, but an increase in turnover on cancellous and endocortical surfaces. After lactation, there was a partial or full restoration of mechanical properties. This study demonstrates substantial changes in bone mechanics that correlate with changes in bone structure and dynamics during the first reproductive cycle in rats. The greatest changes were observed during the lactation period with partial or full recovery in the postlactational period.
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Abstract The vertebrate skeleton is an adaptive structure that responds to mechanical stimuli by increasing bone mass under increased mechanical loads. Although experimental animal models have shown the anabolic cortical bone response to applied load decreases with age, no consensus exists regarding whether this adaptive mechanism is affected by age in cancellous bone, the tissue most impacted by age-related bone loss. We used an established murine in vivo tibial loading model to characterize the load-induced cancellous, cortical, and whole bone responses to mechanical stimuli in growing and mature female mice at 6, 10, and 16wks of age. The effects of applied load on tibial morphology and stiffness were determined using microcomputed tomography and in vivo bone strains measured at the medial tibial midshaft during applied loading. At all ages, two weeks of applied load produced larger midshaft cortical cross-sectional properties (+13-72%) and greater cancellous bone volume (+21-107%) and thicker trabeculae (+31-68%) in the proximal metaphyses of the loaded tibiae. The relative anabolic response decreased from 6wks to 16wks of age in both the cancellous and cortical envelopes. Load-induced tibial stresses decreased more in 6wk old mice following loading, which corresponded to increased in vivo tibial stiffness. Stiffness in the loaded tibiae of 16wk old mice decreased despite moderately increased cortical cross-sectional geometry, suggesting load-induced changes in bone material properties. This study shows that the cancellous and cortical anabolic responses to mechanical stimuli decline with age into adulthood and that cortical cross-sectional geometry alone does not necessarily predict whole bone functional stiffness.
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X-ray microtomography
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Palytoxin, a nonphorbol ester-type tumor promoter, stimulated the production of prostaglandin E2 (PGE2) and bone resorption in neonatal mouse calvariae in organ culture. The action of palytoxin on bone resorption occurred at extraordinarily low concentrations; enhanced resorption was regularly observed at 0.5 pg/ml, and the ED50 was 1-2 pg/ml (-3 × 10-13 M). Palytoxin-induced formation of PGE2 and bone resorption were inhibited completely by indomethacin (200 ng/ ml). Concentrations of palytoxin above 10 pg/ml led to progressively decreasing enhancement of bone resorption; by 100–250 pg/ml no stimulation of resorption was observed despite continued high production of PGE2. Treatment with high concentrations of palytoxin (100 or 250 pg/ml) for 24–72 h inhibited cAMP accumulation stimulated by exogenous PGE2 or PTH and inhibited bone resorption induced by PGE2, PTH, or an analog of cAMP. Thus, palytoxin exhibited a biphasic doseresponse curve for enhanced bone resorption, with stimulation at low concentrations (0.5–10 pg/ml) and toxic inhibition at high concentrations (>50 pg/ml). Palytoxin is one of the most potent stimulators of bone resorption yet identified. (Endocrinology120: 1338–1345,1987)
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Biomechanics
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Objective: Scanning telescope was used to observe bone resorption carried out on the surface of cancellous bone and it's relationship with the change of biomechanical strength of the cancellous bone.Methods: 6 months-old SD rats were ovariectomized and the left tibias were obtained after 3 months.JEOL JSM 840 scanning telescope was used to observe the resorption pits on the surface of cancellous bone and colagen distribution on the bottom of the pits.The right tibias were also obtained to measure the biomechanical strength of its' upper end.Results: Cancellous bone was rich inside the upper tibias of the normal rats,the surface of the bone was smooth and collagen distribution was in order.Cancellous bone decreased after ovariectomy,resorption pits increased and deepened,collagen in the bot tom of the pits was distributed irregularly.Resorption pits could also be seen at the top of the arched trabecula.The biomechanical strength of the upper tibias was decreased obviously after ovariectomy.Conclusion: Ovariectomy enchances bone resorption on the surface of cancellus of the rats,especially the resorption carried out at the top of arched trabecula affects the cancellous bone strength mostly.
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Trabecula (gastropod)
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