Axial cortical involvement of metastatic lesions to identify impending femoral fractures; a clinical validation study.

BACKGROUND AND PURPOSE: Patients with advanced cancer may develop painful bone metastases, potentially resulting in pathological fractures. Adequate fracture risk assessment is of key importance to prevent fracturing and maintain mobility. This study aims to validate the clinical reliability of axial cortical involvement with a 30 mm threshold on conventional radiographs to assess fracture risk in femoral bone metastases. MATERIALS AND METHODS: All patients with bone metastases who received radiotherapy for pain included in two multicentre prospective studies were selected. Conventional radiographs obtained at a maximum of two months prior to radiotherapy were collected. Three experts independently measured lesions and scored radiographic characteristics. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were calculated. RESULTS: Hundred patients were included with a median follow-up of 23.0 months (95%CI: 10.6-35.5). Two fractures occurred in lesions with axial cortical involvement <30 mm, and 12 in lesions ≥30 mm. Sensitivity, specificity, PPV and NPV of axial cortical involvement for predicting femoral fractures were 86%, 50%, 20% and 96%, respectively. Patients with lesions ≥30 mm had a 5.3 times higher fracture risk than patients with smaller lesions. CONCLUSION: Our validation study confirmed the use of 30 mm axial cortical involvement to assess fracture risk in femoral bone metastases. Until a more accurate and practically feasible method has been developed, this clinical parameter remains an easy method to assess femoral fracture risk to aid patients and clinicians to choose the optimal individual treatment modality.

Can patient-specific finite element models better predict fractures in metastatic bone disease than experienced clinicians?: Towards computational modelling in daily clinical practice.

OBJECTIVES: In this prospective cohort study, we investigated whether patient-specific finite element (FE) models can identify patients at risk of a pathological femoral fracture resulting from metastatic bone disease, and compared these FE predictions with clinical assessments by experienced clinicians. METHODS: A total of 39 patients with non-fractured femoral metastatic lesions who were irradiated for pain were included from three radiotherapy institutes. During follow-up, nine pathological fractures occurred in seven patients. Quantitative CT-based FE models were generated for all patients. Femoral failure load was calculated and compared between the fractured and non-fractured femurs. Due to inter-scanner differences, patients were analyzed separately for the three institutes. In addition, the FE-based predictions were compared with fracture risk assessments by experienced clinicians. RESULTS: In institute 1, median failure load was significantly lower for patients who sustained a fracture than for patients with no fractures. In institutes 2 and 3, the number of patients with a fracture was too low to make a clear distinction. Fracture locations were well predicted by the FE model when compared with post-fracture radiographs. The FE model was more accurate in identifying patients with a high fracture risk compared with experienced clinicians, with a sensitivity of 89% versus 0% to 33% for clinical assessments. Specificity was 79% for the FE models versus 84% to 95% for clinical assessments. CONCLUSION: FE models can be a valuable tool to improve clinical fracture risk predictions in metastatic bone disease. Future work in a larger patient population should confirm the higher predictive power of FE models compared with current clinical guidelines.Cite this article: F. Eggermont, L. C. Derikx, N. Verdonschot, I. C. M. van der Geest, M. A. A. de Jong, A. Snyers, Y. M. van der Linden, E. Tanck. Can patient-specific finite element models better predict fractures in metastatic bone disease than experienced clinicians? Towards computational modelling in daily clinical practice. Bone Joint Res 2018;7:430-439. DOI: 10.1302/2046-3758.76.BJR-2017-0325.R2.

Estimating severity of sideways fall using a generic multi linear regression model based on kinematic input variables.

Many research groups have studied fall impact mechanics to understand how fall severity can be reduced to prevent hip fractures. Yet, direct impact force measurements with force plates are restricted to a very limited repertoire of experimental falls. The purpose of this study was to develop a generic model for estimating hip impact forces (i.e. fall severity) in in vivo sideways falls without the use of force plates. Twelve experienced judokas performed sideways Martial Arts (MA) and Block ('natural') falls on a force plate, both with and without a mat on top. Data were analyzed to determine the hip impact force and to derive 11 selected (subject-specific and kinematic) variables. Falls from kneeling height were used to perform a stepwise regression procedure to assess the effects of these input variables and build the model. The final model includes four input variables, involving one subject-specific measure and three kinematic variables: maximum upper body deceleration, body mass, shoulder angle at the instant of 'maximum impact' and maximum hip deceleration. The results showed that estimated and measured hip impact forces were linearly related (explained variances ranging from 46 to 63%). Hip impact forces of MA falls onto the mat from a standing position (3650±916N) estimated by the final model were comparable with measured values (3698±689N), even though these data were not used for training the model. In conclusion, a generic linear regression model was developed that enables the assessment of fall severity through kinematic measures of sideways falls, without using force plates.

Curved Beam Computed Tomography based Structural Rigidity Analysis of Bones with Simulated Lytic Defect: A Comparative Study with Finite Element Analysis.

In this paper, a CT based structural rigidity analysis (CTRA) method that incorporates bone intrinsic local curvature is introduced to assess the compressive failure load of human femur with simulated lytic defects. The proposed CTRA is based on a three dimensional curved beam theory to obtain critical stresses within the human femur model. To test the proposed method, ten human cadaveric femurs with and without simulated defects were mechanically tested under axial compression to failure. Quantitative computed tomography images were acquired from the samples, and CTRA and finite element analysis were performed to obtain the failure load as well as rigidities in both straight and curved cross sections. Experimental results were compared to the results obtained from FEA and CTRA. The failure loads predicated by curved beam CTRA and FEA are in agreement with experimental results. The results also show that the proposed method is an efficient and reliable method to find both the location and magnitude of failure load. Moreover, the results show that the proposed curved CTRA outperforms the regular straight beam CTRA, which ignores the bone intrinsic curvature and can be used as a useful tool in clinical practices.

Incorporating in vivo fall assessments in the simulation of femoral fractures with finite element models.

Femoral fractures are a major health issue. Most experimental and finite element (FE) fracture studies use polymethylmethacrylate cups on the greater trochanter (GT) to simulate fall impact loads. However, in vivo fall studies showed that the femur is loaded distally from the GT. Our objective was to incorporate in vivo fall data in FE models to determine the effects of loading position and direction, and size of simulated impact site on the fracture load and fracture type for a healthy and an osteoporotic femur. Twelve sets of loading position and angles were applied through 'near point loads' on the models. Additional simulations were performed with 'cup loads' on the GT, similar to the literature. The results showed no significant difference between fracture loads from simulations with near point loads distally from the GT and those with cup loads on the GT. However, simulated fracture types differed, as near point loads distally from the GT generally resulted in various neck fractures, whilst cup load simulations predicted superior neck and trochanteric fractures only. This study showed that incorporating in vivo fall assessments in FE models by loading the models distally from the GT results in prediction of realistic fracture loads and fracture types.

The assessment of the risk of fracture in femora with metastatic lesions: comparing case-specific finite element analyses with predictions by clinical experts.

Previously, we showed that case-specific non-linear finite element (FE) models are better at predicting the load to failure of metastatic femora than experienced clinicians. In this study we improved our FE modelling and increased the number of femora and characteristics of the lesions. We retested the robustness of the FE predictions and assessed why clinicians have difficulty in estimating the load to failure of metastatic femora. A total of 20 femora with and without artificial metastases were mechanically loaded until failure. These experiments were simulated using case-specific FE models. Six clinicians ranked the femora on load to failure and reported their ranking strategies. The experimental load to failure for intact and metastatic femora was well predicted by the FE models (R(2) = 0.90 and R(2) = 0.93, respectively). Ranking metastatic femora on load to failure was well performed by the FE models (τ = 0.87), but not by the clinicians (0.11 < τ < 0.42). Both the FE models and the clinicians allowed for the characteristics of the lesions, but only the FE models incorporated the initial bone strength, which is essential for accurately predicting the risk of fracture. Accurate prediction of the risk of fracture should be made possible for clinicians by further developing FE models.

Can martial arts techniques reduce fall severity? An in vivo study of femoral loading configurations in sideways falls.

Sideways falls onto the hip are a major cause of femoral fractures in the elderly. Martial arts (MA) fall techniques decrease hip impact forces in sideways falls. The femoral fracture risk, however, also depends on the femoral loading configuration (direction and point of application of the force). The purpose of this study was to determine the effect of fall techniques, landing surface and fall height on the impact force and the loading configuration in sideways falls. Twelve experienced judokas performed sideways MA and Block ('natural') falls on a force plate, both with and without a judo mat on top. Kinematic and force data were analysed to determine the hip impact force and the loading configuration. In falls from a kneeling position, the MA technique reduced the impact force by 27%, but did not change the loading configuration. The use of the mat did not change the loading configuration. Falling from a standing changed the force direction. In all conditions, the point of application was distal and posterior to the greater trochanter, but it was less distal and more posterior in falls from standing than from kneeling position. The present decrease in hip impact force with an unchanged loading configuration indicates the potential protective effect of the MA technique on the femoral fracture risk. The change in loading configuration with an increased fall height warrant further studies to examine the effect of MA techniques on fall severity under more natural fall circumstances.

Predictive value of femoral head heterogeneity for fracture risk.

Osteoporosis (OP) is characterized by low bone mass and weak bone structure, which results in increased fracture risk. It has been suggested that osteoporotic bone is strongly adapted to the main loading direction and less adapted to the other directions. In this study, we hypothesized that osteoporotic femoral heads have 1) an increased anisotropy; 2) a more heterogenic distribution of bone volume fraction (BV/TV) throughout the femoral head; and, 3) a more heterogenic distribution of the trabecular thickness (Tb.Th.) throughout the femoral head, as compared to non-osteoporotic bone. To test these hypotheses, we used 7 osteoporotic femoral heads from patients who fractured their femoral neck and 7 non-fractured femoral heads from patients with osteoarthrosis (OA). Bone structural parameters from the entire trabecular region were analyzed using microCT. We found that the degree of anisotropy was higher in the fractured femoral heads, i.e. 1.72, compared to a value of 1.61 in the non-fractured femoral heads. The BV/TV and Tb.Th. and their variations throughout the femoral head, however, were all significantly lower in the fractured group. Hence, the first hypothesis was confirmed, whereas the other two were rejected. Interestingly, the variation of Tb.Th. throughout the femoral head provided a 100% discrimination between the OP and OA groups, i.e. for the same BV/TV, all fractured cases had a less heterogenic distribution. In conclusion, our results suggest that bone loss in OP takes place uniformly throughout the femoral head, leading to an overall decrease in bone mass and trabecular thickness. Furthermore, the variation of Tb.Th. in the femoral head could be an interesting parameter to improve the prediction of fracture risk in the proximal femur.

Densitometry test of bone tissue: validation of computer simulation studies.

Bone densitometry measurements are performed to predict the fracture risk in bones. However, the sensitivity of these predictions are not satisfactory. One of the explanations is that densitometry ignores the (architectural) structural aspects of the bone. The effects of varying architectural parameters on the densitometry parameters can be effectively assessed by considering a 3-D image of a bone and vary the bone structure parameters in a controlled manner and determine the consequence of these changes on a simulated (virtual) densitometry analysis. In this paper we present such a computer simulation of densitometry analysis of bone. The simulation allows quantification of densitometry parameters, such as BMD and BMC, on the basis of computed tomography bone scans. The aim of the presented study is the evaluation of our method by comparing its results to the results from real densitometry (DEXA) tests. For the evaluation we selected three femoral bones. These items were CT scanned and individual computer models were created. In addition, the densitometry parameters of these items were assessed by a clinical DEXA scanner. The densitometry parameters obtained from the simulations were very close to the results from the DEXA densitometry measurements. We therefore conclude that our method can be employed in the research on the influence of changes in bone structure on densitometry test results.

Additional weight bearing during exercise and estrogen in the rat: the effect on bone mass, turnover, and structure.

Mechanical loading and estrogen play important roles in bone homeostasis. The aim of this study was to evaluate the effects of mechanical loading on trabecular bone in the proximal femur of ovariectomized rats. We hypothesized that mechanical loading suppresses bone resorption and increases bone formation, which differs from the suppressive effects of estrogen on both resorption and formation. Furthermore, we expected to find changes in trabecular architecture elicited by the effects of mechanical loading and estrogen deficiency. Sixty female Wistar rats, 12 weeks old, were assigned to either the sedentary groups sham surgery (SED), ovariectomy (SED+OVX), and ovariectomy with estrogen replacement (SED+OVX+E2) or to the exercise groups EX, EX+OVX, EX+OVX+E2. Following ovariectomy, 5 microg 17beta-estradiol was given once weekly to the estrogen replacement groups. Exercise consisted of running with a backpack (load +/-20% of body weight) for 15 minutes/day, 5 days/week, for 19 weeks. Dual-energy X-ray absorptiometry (DXA) scans were performed before (T0), during (T6), and after (T19) the exercise period to obtain bone mineral content (BMC) and bone mineral density (BMD) data. After the exercise program, all rats were killed and right and left femora were dissected and prepared for micro-CT scanning and histomorphometric analysis of the proximal femoral metaphysis. After 19 weeks, increases in BMC (P = 0.010) and BMD (P = 0.031) were significant. At T19, mechanical loading had a significant effect on BMC (P = 0.025) and BMD (P = 0.010), and an interaction between mechanical loading and estrogen (P = 0.023) was observed. Bone volume and trabecular number decreased significantly after ovariectomy, while trabecular separation, mineralizing surface, bone formation rate, osteoclast surface, degree of anisotropy, and structure model index increased significantly after ovariectomy (P < 0.05). Trabecular bone turnover and structural parameters in the proximal femur were not affected by exercise. Estrogen deficiency resulted in a less dense and more oriented trabecular bone structure with increased marrow cavity and a decreased number of trabeculae. In conclusion, mechanical loading has beneficial effects on BMC and BMD of the ovariectomized rat. This indicates that the load in the backpack was high enough to elicit an osteogenic response sufficient to compensate for the ovariectomy-induced bone loss. The results confirm that estrogen suppresses both bone resorption and bone formation in the proximal metaphysis in the femoral head of our rat-with-backpack model. The effects of mechanical loading on the trabecular bone of the femoral head were not significant. This study suggests that the effect of mechanical loading in the rat-with-backpack model mainly occurs at cortical bone sites.

Different responsiveness to mechanical stress of bone cells from osteoporotic versus osteoarthritic donors.

INTRODUCTION: Osteoporosis (OP) and osteoarthritis (OA) are both common diseases in the elderly, but remarkably seldom coexist. The bone defects that are related to both diseases develop with increasing age, which suggests that they are related to some form of imperfect bone remodeling. Current opinion holds that the bone remodeling process is supervised by bone cells that respond to mechanical stimuli. An imperfect response of bone cells to mechanical stimuli might thus relate to imperfect bone remodeling, which could eventually lead to a lack bone mass and strength, such as in OP patients. MATERIALS: To investigate whether the cellular response to mechanical stress differs between OP and OA patients, we compared the response of bone cells from both groups to fluid shear stress of increasing magnitude. Bone cells from 9 female OP donors (age 60-90 year) and 9 female age-matched OA donors were subjected to pulsating fluid flow (PFF) of low (0.4+/-0.1 Pa at 3 Hz), medium (0.6+/-0.3 Pa at 5 Hz), or high shear stress (1.2+/-0.4 at 9Hz), or were kept under static culture conditions. RESULTS: We found subtle differences in the shear-stress response of the two groups, measured as nitric oxide (NO) and prostaglandin E2 (PGE2) production. The NO-response to shear stress was higher in the OP than the OA cells, while the PGE2-response was higher in the OA cells. CONCLUSIONS: Assuming that NO and PGE2 play a role in cell-cell communication during remodeling, these results suggest that slight differences in mechanotransduction might relate to the opposite bone defects in osteoporosis and osteoarthritis.

Cortical bone development under the growth plate is regulated by mechanical load transfer.

Longitudinal growth of long bones takes place at the growth plates. The growth plate produces new bone trabeculae, which are later resorbed or merged into the cortical shell. This process implies transition of trabecular metaphyseal sections into diaphyseal sections. We hypothesize that the development of cortical bone is governed by mechanical stimuli. We also hypothesize that trabecular and cortical bone share the same regulatory mechanisms for adaptation to mechanical loads. To test these hypotheses, we monitored the development of the tibial cortex in growing pigs, using micro-computer tomography and histology. We then tested the concept that regulatory mechanisms for trabecular bone adaptation can also explain cortical bone development using our mechanical stimulation theory, which could explain trabecular bone (re)modelling. The main results showed that, from the growth plate towards the diaphysis, the pores of the trabecular structure were gradually filled in with bone, which resulted in increased density and cortical bone. The computer model largely predicted this morphological development. We conclude that merging of metaphyseal trabeculae into cortex is likely to be governed by mechanical stimuli. Furthermore, cortex development of growing long bones can be explained as a form of trabecular bone adaptation, without the need for different regulatory mechanisms for cortical and trabecular bone.

Trabecular architecture can remain intact for both disuse and overload enhanced resorption characteristics.

The paradigm that bone metabolic processes are controlled by osteocyte signals have been the subject of investigation in many recent studies. One hypothesis is that osteoblast formation is enhanced by these signals, and that osteoclast resorption is enhanced by the lack of them. Reduced, or absent, osteocyte signaling can be an effect of reduced mechanical loading (disuse) or of defects in the canalicular network, due to microcracks. This would mean that bone is resorbed precisely there where it is mostly needed. In our study, we addressed this apparent contradiction. The purpose was to investigate how alternative strain-based local stimuli for osteoclasts to resorb bone would affect remodeling and adaptation of the trabecular architecture. For this purpose, a computer-simulation model was used, which couples morphological and mechanical effects of local bone metabolism to changes in trabecular architecture and density at large. Six resorption characteristics were studied in the model: (I) resorption occurs spatially random, (II) resorption is enhanced or (III) strongly enhanced where there is disuse, (IV) resorption is enhanced or (V) strongly enhanced where there are high strains, i.e. overload, and (VI) resorption is enhanced where there is disuse and where there are high strains. Results showed that the rates of structural adaptation to alternative loading were higher for disuse-controlled resorption than for overload-controlled resorption. Architecture and mass remained stable for all cases except (V) in which the structure deteriorated as in osteoporotic bone. We conclude that, given the potential of osteoblasts to form bone in highly strained areas, based on signals from osteocytes, osteoclast resorption can normally be compensated for.

Additive effects of estrogen and mechanical stress on nitric oxide and prostaglandin E2 production by bone cells from osteoporotic donors.

Mechanical loading is thought to provoke a cellular response via loading-induced flow of interstitial fluid through the lacuno-canalicular network of osteocytes. This response supposedly leads to an adaptation of local bone mass and architecture. It has been suggested that loss of estrogen during menopause alters the sensitivity of bone tissue to mechanical load, thereby contributing to the rapid loss of bone. The present study aimed to determine whether estrogen modulates the mechanoresponsiveness of bone cells from osteoporotic women. Bone cell cultures from nine osteoporotic women (aged 62-90 years) were pre-cultured for 24 h with 10(-11) mol/l 17beta-estradiol (E2) or vehicle, and subjected to 1 h of pulsating fluid flow (PFF) or static culture. E2 alone enhanced prostaglandin E(2) (PGE(2)) and nitric oxide (NO) production by 2.8-fold and 2.0-fold, respectively, and stimulated endothelial nitric oxide synthase protein expression by 2.5-fold. PFF, in the absence of E2, stimulated PGE(2) production by 3.1-fold and NO production by 3.9-fold. Combined treatment with E2 and PFF increased PGE(2) and NO production in an additive manner. When expressed as PFF-treatment-over-control ratio, the response to fluid shear stress was similar in the absence or presence of E2. These results suggest that E2 does not affect the early response to stress in bone cells. Rather, E2 and shear stress both promote the production of paracrine factors such as NO and PGE(2) in an additive manner.

The mechanical consequences of mineralization in embryonic bone.

The purpose of this study was to examine the effect of mineralization on the mechanical properties of embryonic bone rudiments. For this purpose, four-point bending experiments were performed on unmineralized and mineralized embryonic mouse ribs at 16 and 17 days of gestational age. Young's modulus was calculated using force-displacement data from the experiment in combination with finite element analysis (FEA). For the unmineralized specimens, a calculated average for the Young's modulus of 1.11 (+/- 0.62) MPa was established after corrections for sticking to the four-point bending device and aspect ratio, which is the ratio between the length of the bone and its diameter. For the mineralized specimens, the value was 117 (+/- 62) MPa after corrections. Hence, Young's moduli of embryonic bone rudiments increase by two orders of magnitude within 1 day, during endochondral ossification. As an effect, the hypertrophic chondrocytes in the calcifying cartilage experience a significant change in their mechanical environment. The chondrocytes are effectively stress shielded, which means that they do not carry stresses since stresses are supported by the stiffest parts of the tissue, which are in this case the diaphyseal cortex and the calcified matrix. The deformability of the hypertrophic chondrocytes is, therefore, severely reduced. Since the transition is so sudden and enormous, it can be seen as a process of 'catastrophic' proportion for the hypertrophic chondrocytes. The subsequent resorption of calcified cartilage and the expansion of the marrow cavity could be consequential to stress shielding.

The influence of microcomputed tomography threshold variations on the assessment of structural and mechanical trabecular bone properties.

In this study, we investigate how morphological parameters and mechanical properties derived from microcomputed tomography (microCT) are affected by small errors in threshold value when variable bone structures and different bone volume fractions are involved. For this purpose, biopsies of vertebrae of 6-, 23-, and 230-week-old female pigs were scanned using microCT. For each specimen, five threshold values were determined within the range of thresholds that an observer could select realistically, in steps of 0.5%. The scans were converted to microfinite-element (microFE) models, used to determine the elastic moduli. A variation of 0.5% in threshold resulted in a 5% difference in bone volume fraction and 9% difference in maximal stiffness for bone cubes with a volume fraction of <0.15. When the volume fraction was >0.2, these differences were only 2% and 3%, respectively. For all bone cubes, the differences for trabecular thickness and bone surface density were <3%. The effects on morphological anisotropy and trabecular number were negligible for threshold variations of 0.5%. These findings suggest that threshold selection is important for the accurate determination of volume fraction and mechanical properties, especially for low bone volume fractions; the architectural directionality is less sensitive to changes in threshold.

Increase in bone volume fraction precedes architectural adaptation in growing bone.

In mature trabecular bone, both density and trabecular orientation are adapted to external mechanical loads. Few quantitative data are available on the development of architecture and mechanical adaptation in juvenile trabecular bone. We studied the hypothesis that a time lag occurs between the adaptation of trabecular density and the adaptation of trabecular architecture during development. To investigate this hypothesis we used ten female pigs at 6, 23, 56, 104, and 230 weeks of age. Three-dimensional morphological and mechanical parameters of trabecular bone samples from the vertebra and proximal tibia were studied using microcomputed tomography and micro-finite element analysis. Both bone volume fraction and stiffness increased rapidly in the initial growth phase (from 6 weeks on), whereas the morphological anisotropy started increasing only after 23 weeks of age. In addition, the anisotropy reached its highest value much later in the development than did bone volume fraction. Hence, the alignment of trabeculae was still progressing at the time of peak bone mass. Therefore, our hypothesis was supported by the time lag between the increase in trabecular density and the adaptation of the trabecular architecture. The rapid increase of bone volume fraction in the initial growth phase can be explained by the enormous weight increase of the pigs. The trabeculae aligned at later stages when the increase in weight, and thus the loading, was slowed considerably compared with the early growth stage. Hence, the trabecular architecture was more efficient in later years. We conclude that density is adapted to external load from the early phase of growth, whereas the trabecular architecture is adapted later in the development.

Influence of muscular activity on local mineralization patterns in metatarsals of the embryonic mouse.

This study addressed the theory that local mechanical loading may influence the development of embryonic long bones. Embryonic mouse metatarsal rudiments were cultured as whole organs, and the geometry of the primary ossification center was compared with that of rudiments that had developed in utero. The mineralization front in vivo was found to be nearly straight, whereas in vitro it acquired a more convex shape due to a slower mineralization rate at the periphery of the mineralized cylinder. A poroelastic finite element analysis was performed to calculate the local distributions of distortional strain and fluid pressure at the mineralization front in the metatarsal during loading in vivo as a result of muscle contractions in the embryonic hindlimbs. The distribution of fluid pressure from the finite element analysis could not explain the difference in mineralization shape. The most likely candidate for the difference was the distortional strain, resulting from muscle contraction, which is absent in vitro, because its value at the periphery was significantly higher than in the center of the tissue. Without external loads, the mineralization process may be considered as pre-programmed, starting at the center of the tissue and resulting in a spherical mineralization front. Strain modulates the rate of the mineralization process in vivo, resulting in the straight mineralization front. These results confirm that disturbances in muscle development are likely to produce disturbed mineralization patterns, resulting in a disordered osteogenic process.

Why does intermittent hydrostatic pressure enhance the mineralization process in fetal cartilage?

The purpose of this study was to determine which factor is the most likely one to have stimulated the mineralization process in the in vitro experiments of Klein-Nulend et al. (Arth. Rheum., 29, 1002-1009, 1986), in which fetal cartilaginous metatarsals were externally loaded with an intermittent hydrostatic pressure, by compressing the gas phase above the culture medium. Analytical calculations excluded the possibility that the tissue was stimulated by changes in dissolved gas concentration, pH or temperature of the culture medium through compression of the gas phase. The organ culture experiments were also mechanically analyzed using a poroelastic finite element (FE) model of a partly mineralized metatarsal with compressible solid and fluid constituents. The results showed that distortional strains occurred in the region where mineralization proceeded. The value of this strain was, however, very sensitive to the value of the intrinsic compressibility modulus of the solid matrix (Ks). For realistic values of Ks the distortional strain was probably too small (about 2 microstrain) to have stimulated the mineralization. If the distortional strain was not the factor to have enhanced the mineralization process, then the only candidate variable left is the hydrostatic pressure itself. We hypothesize that the pressure may have created the physical environment enhancing the mineralization process. When hydrostatic pressure is applied, the balance of the chemical potential of water across cell membranes may be disturbed, and restored again by diffusion of ions until equilibrium is reached again. The diffusion of ions may have contributed to the mineralization process.

Effects of prosthesis surface roughness on the failure process of cemented hip implants after stem-cement debonding.

Retrieval studies suggest that the loosening process of the cemented femoral components of total hip arthroplasties is initiated by failure of the bond between the prosthesis and the cement mantle. Finite element (FE) analyses have demonstrated that stem-cement debonding has stress-producing effects in the cement mantle. High interface friction, which corresponds to a degree of surface roughness, reduces these stresses. In experiments, however, debonded rough stems produced more cement damage than polished ones; in the Swedish Hip Register polished stems were clinically superior with respect to stems with a mat surface finish. The purpose of the present study was to investigate this contradiction. For this purpose, global and local FE models with debonded stem-cement interfaces were used to study the effects of prosthesis surface roughness on the cement stresses on a global scale and microscale, respectively. Similar to earlier numerical studies, the global FE model predicted that an increased surface roughness of the stem reduced the stresses in the cement mantle. The local model provided insight in the load-transfer mechanism on a microscale and could explain the experimental and clinical findings. The local cement peak stresses around the asperities of the surface roughness profile increased with increasing surface roughness and decreased again beyond a particular roughness value. Cement abrasion is caused by localized stresses in combination with micromotion. From this study it can be concluded that to minimize cement abrasion, debonded stems should either have a polished microstructure to minimize the local cement stresses or have a profiled macrostructure to minimize micromotions at the stem-cement interface.