Seated whole body vibrations with high-magnitude accelerations--relative roles of inertia and muscle forces.

Reliable computation of spinal loads and trunk stability under whole body vibrations with high acceleration contents requires accurate estimation of trunk muscle activities that are often overlooked in existing biodynamic models. A finite element model of the spine that accounts for nonlinear load- and direction-dependent properties of lumbar segments, complex geometry and musculature of the spine, and dynamic characteristics of the trunk was used in our iterative kinematics-driven approach to predict trunk biodynamics in measured vehicle's seat vibrations with shock contents of about 4 g (g: gravity acceleration of 9.8m/s2) at frequencies of about 4 and 20 Hz. Muscle forces, spinal loads and trunk stability were evaluated for two lumbar postures (erect and flexed) with and without coactivity in abdominal muscles. Estimated peak spinal loads were substantially larger under 4 Hz excitation frequency as compared to 20 Hz with the contribution of muscle forces exceeding that of inertial forces. Flattening of the lumbar lordosis from an erect to a flexed posture and antagonistic coactivity in abdominal muscles, both noticeably increased forces on the spine while substantially improving trunk stability. Our predictions clearly demonstrated the significant role of muscles in trunk biodynamics and associated risk of back injuries. High-magnitude accelerations in seat vibration, especially at near-resonant frequency, expose the vertebral column to large forces and high risk of injury by significantly increasing muscle activities in response to equilibrium and stability demands.

Effect of zoledronate on bone quality in the treatment of aseptic loosening of hip arthroplasty in the dog.

Periprosthetic bone loss, which is a direct cause of aseptic loosening in total hip arthroplasty (THA), can be suppressed by bisphosphonates. It is unknown how the quality of this bone is affected in the presence of both wear debris (from implant) and bisphosphonates. The objective of this study was to evaluate the effect of zoledronate (ZLN) on bone quality in the presence of wear debris [polyethylene (PE) particles] in a canine model of uncemented THA. Thirty dogs underwent THA, and aseptic loosening was induced via implantation of PE particles packed into the femoral component. For 26 weeks until sacrifice, two groups (each n = 10) received weekly injections of ZLN (low dose 2 mug/kg, high dose 10 mug/kg) and the third group (control) received saline. Histological and radiographic examinations were performed to evaluate the degree of implant reaction. Histomorphometry (static/dynamic) was performed to evaluate bone turnover. Back-scattered electron imaging was used to quantify the newly formed bone and to evaluate the mineralization distribution. Density fractionation and X-ray diffraction were used to evaluate mineral properties, while four-point bending was used to determine mechanical properties. A dose-dependent presence of newly formed subperiosteal bone was found, which appeared to be less mineralized than the adjacent cortical bone. The high-dose ZLN group showed decreased cortical porosity and turnover and increased mineralization profile, failure strength, and modulus. We conclude that ZLN affects some of the material properties of cortical bone and allows the newly formed subperiosteal bone to remain and therefore affect the overall quality of the bone.

Immunoepidemiologic profile of Chlamydia trachomatis infection: importance of heat-shock protein 60 and interferon- gamma.

Epidemiological, animal, and in vitro investigations suggest that Chlamydia trachomatis infection engenders acquired immunity, the basis for which is incompletely defined, especially in humans. In a prospective cohort study of women at high risk for C. trachomatis infection, we found that, at baseline and after adjustment for age and other potential confounding variables, production of interferon- gamma by peripheral-blood mononuclear cells (PBMCs) stimulated with chlamydia heat-shock protein 60 strongly correlated with protection against incident C. trachomatis infection. This investigation supports a direct role for C. trachomatis-specific immune responses in altering the risk of infection and suggests immune correlates of protection that are potentially useful in vaccine development.

A live and inactivated Chlamydia trachomatis mouse pneumonitis strain induces the maturation of dendritic cells that are phenotypically and immunologically distinct.

The intracellular bacterial pathogen Chlamydia trachomatis is a major cause of sexually transmitted disease worldwide. While protective immunity does appear to develop following natural chlamydial infection in humans, early vaccine trials using heat-killed C. trachomatis resulted in limited and transient protection with possible enhanced disease during follow-up. Thus, immunity following natural infection with live chlamydia may differ from immune responses induced by immunization with inactivated chlamydia. To study this differing immunology, we used murine bone marrow-derived dendritic cells (DC) to examine DC maturation and immune effector function induced by live and UV-irradiated C. trachomatis elementary bodies (live EBs and UV-EB, respectively). DC exposed to live EBs acquired a mature DC morphology; expressed high levels of major histocompatibility complex (MHC) class II, CD80, CD86, CD40, and ICAM-1; produced elevated amounts of interleukin-12 and tumor necrosis factor alpha; and were efficiently recognized by Chlamydia-specific CD4+ T cells. In contrast, UV-EB-pulsed DC expressed low levels of CD40 and CD86 but displayed high levels of MHC class II, ICAM-1, and CD80; secreted low levels of proinflammatory cytokines; and exhibited reduced recognition by Chlamydia-specific CD4+ T cells. Adoptive transfer of live EB-pulsed DC was more effective than that of UV-EB-pulsed DC at protecting mice against challenge with live C. trachomatis. The expression of DC maturation markers and immune protection induced by UV-EB could be significantly enhanced by costimulation of DC ex vivo with UV-EB and oligodeoxynucleotides containing cytosine phosphate guanosine; however, the level of protection was significantly less than that achieved by using DC pulsed ex vivo with viable EBs. Thus, exposure of DC to live EBs results in a mature DC phenotype which is able to promote protective immunity, while exposure to UV-EB generates a semimature DC phenotype with less protective potential. This result may explain in part the differences in protective immunity induced by natural infection and immunization with whole inactivated organisms and is relevant to rational chlamydia vaccine design strategies.

Effect of strain rate on tensile properties of sheep disc anulus fibrosus.

We investigated the effect of loading rate on tensile properties of sheep bone-anulus-bone specimens in axial direction. Disc anulus Samples with adjacent bone attachments were prepared from lateral, posterior and anterior regions of sheep lumbar spinal segments. The specimens were then tested at different strain rates under non-destructive cyclic tensile loading followed by destructive tensile loading. Each specimen was prepared by embedding the bony parts in the polymethylmetacrylate (PMMA) exposing the anulus portion to support tension. The results of non-destructive cyclic tests indicated a decrease in the hysteresis energy loss as strain rate increased. In the destructive tests, no significant differences in ultimate stress, ultimate strain and strain energy density were observed at different strain rates or annulus locations. However, there was a significant increase in the modulus at linear region as strain rate increased. Two major modes of failure were observed; rupture in the anulus mid-substance and at the anulus-endplate junction. The former failure was more frequent with no clear pattern across strain rates and locations, while the latter failure at anulus-endplate junction occurred primarily at slow strain rates.

Differential effects of ovariectomy on the mechanical properties of cortical and cancellous bone in rat femora and vertebrae.

The purpose of this study was to evaluate the effects of ovariectomy on the mechanical properties of bone in the aged Sprague-Dawley rat model of osteoporosis. Eight female rats were sacrificed at the start of the study, at the age of four months. Twenty-four remaining rats were then bilaterally ovariectomized (OVX), and another twenty-four served as controls. Eight rats from each group were sacrificed at five, ten or fifteen weeks. The mean density of L1 vertebral bodies from OVX rats was lower than in their control counterparts, as was the compressive modulus, the ultimate compressive stress and the toughness. The second lumbar vertebra from each rat was cored to remove the bulk of the cancellous bone and tested in compression to failure. Ovariectomy did not affect the mechanical properties of the cored vertebrae, suggesting that the mechanically relevant changes take place in the cancellous bone. The gravimetric density and bone mineral density (measured by dual-energy x-ray absorptiometry) of whole femora were lower in OVX rats than control rats. However, the gravimetric density of the cortical bone was unchanged, and when femora were tested to fracture in three-point bending, the mechanical properties of the midshaft were found to be unaffected. This study suggests some limitations to the mature ovariectomized rat model of osteoporosis: mechanically significant loss of cancellous bone occurs in vertebrae much more rapidly than suggested by other studies. Further, there is little evidence of mechanically important bone loss in cortical bone within four months of ovariectomy.

Static and dynamic finite element analyses of an idealized structural model of vertebral trabecular bone.

An idealized three-dimensional finite element model of a rodlike trabecular bone structure was developed to study its static and dynamic responses under compressive loading, considering the effects of bone marrow and apparent density. Static analysis of the model predicted hydraulic stiffening of trabecular bone due to the presence of bone marrow. The predicted power equation relating trabecular bone apparent elastic modulus to its apparent density was in good agreement with those of the reported experimental investigations. The ratio of the maximum stress in the trabecular bone tissue to its apparent stress had a high value, decreasing with increasing bone apparent density. Frequency analyses of the model predicted higher natural frequencies for the bone without marrow than those for the bone with marrow. Adding a mass relatively large compared to that of bone rendered a single-degree-of-freedom response. In this case, the resonant frequency was higher for the bone with marrow than that for the bone without marrow. The predicted vibrational measurement of apparent modulus was in good agreement with that of the static measurement, suggesting vibrational testing as a method for nondestructive measurement of trabecular bone elastic moduli.

Effects of different estrogen and progestin regimens on the mechanical properties of rat femur.

The purpose of this study was to examine the effects of estrogen replacement, in concert with three different progestin regimens, on the mechanical properties of rat femoral cortical bone. Ninety-two 11-month-old female Sprague-Dawley rats were randomly divided into six groups and were treated for a duration of 6 months. Group-1 rats were intact controls, group-2 rats were ovariectomized controls, and groups 3-6 were ovariectomized and given continuous doses of estrogen with 5% estradiol 17B silicone-rubber implants. Groups 4, 5, and 6 were also given different doses of progestin (norethindrone): group 4 received a continuous dose of 3 micrograms per animal per day, group 5 received a cyclic dose of 6 micrograms per animal per day for 14 days of a 28-day cycle, and group 6 received an interrupted dose of 3 micrograms per animal per day for 3 days of a 6-day cycle. Femurs from each group were mechanically tested. Bending stiffness was measured by nondestructive three-point bending tests and maximum torque capacity, by destructive torsion tests. Geometrical properties and apparent density of cortical bone were also measured. The significant differences were: the increases in elastic modulus (measured from the three-point bending stiffness) of group 5 (cyclic norethindrone) compared with those of group 2 (ovariectomized controls) and group 3 (estrogen only); the increases in the size represented by the moment of inertia, the moment of the area, and medial-lateral width of group 2 compared with those of group 5; and the increases in apparent density and decreases in moment of inertia of group 6 (interrupted norethindrone) compared with those of group 2. Cyclic or interrupted treatment of progestin along with continuous treatment of estrogen after ovariectomy likely improves material properties of cortical bone, increases its density, and reduces the size of the bone compared with ovariectomized rats.

Engineered bar design for a midface defect: a case report.

This case report describes the design process for engineering an implant-retained bar to support maxillary dental and facial prostheses for a patient missing his midface, including the maxilla, bilaterally. A computer-driven finite element analysis program was used to anticipate the forces and moments on each implant to distribute occlusal forces as evenly as possible. The implants, and later the prosthesis, were used to support the upper lip in the absence of bony support. The completed restorations greatly improved the patient's speech, eating, and appearance.

Lumbar vertebral density and mechanical properties in aged ovariectomized rats treated with estrogen and norethindrone or norgestimate.

OBJECTIVE: This study was designed to investigate the effects of estrogen alone or combined with two different progestins, norethindrone or norgestimate, on bone density and compressive mechanical properties in an aged rat model. STUDY DESIGN: Twenty 11-month-old female Sprague-Dawley rats were sham operated (intact control) and 80 wee ovariectomized. Three groups of 20 ovariectomized rats were implanted with Silastic silicon rubber (Dow Corning, Midland, Mich.) capsules containing 5% estradiol (wt/wt) in cholesterol. All rats in the intact control (group 1) and the ovariectomized (group 2) and the first of the ovariectomized plus estrogen (group 3) groups were injected subcutaneously daily for 6 months with corn oil (vehicle). Two other groups of rats with estrogen capsules received daily injections of norethindrone (3 micrograms/rat/day) or norgestimate (1.5 micrograms/rat/day) in corn oil for 3 days out of every 6 days (interrupted progestin). The effects of these various treatments on bone mineral content and bone mineral density in the vertebrae were measured by dual energy x-ray absorptiometry. The L4 vertebral bodies were also tested to failure in compression. RESULTS: The ovariectomized rats receiving corn oil alone had the lowest bone mineral density compared with intact controls. Estrogen treatment alone resulted in a lower bone mineral density than in the intact controls. In contrast, both interrupted progestin regimens resulted in vertebral bone mass index at the same level as the intact controls. Compression tests revealed that ovariectomized controls also had the lowest modulus of elasticity of all groups. However, unlike bone mineral density, estrogen alone resulted in mechanical properties similar to intact controls, whereas the vertebrae in both interrupted progestin groups had variable mechanical properties compared with the ovariectomized and intact control groups. CONCLUSIONS: We conclude that in this experimental model hormone replacement therapy with estrogen and an androgenic (norethindrone) or nonadrogenic (norgestimate) progestin result in similar bone mineral density and mechanical properties. In addition, both interrupted progestin regimens had a better effect than estrogen alone on vertebral bone density.

The effect of pamidronate in a new model of immobilization in the dog.

Bone loss resulting from immobilization or disuse has been shown in humans following paralysis or bedrest. We have developed a new model of immobilization in the dog which is reversible and we have studied the effect of pamidronate (APD) in this model. Twelve mature beagle dogs were fitted with specially designed mesh jackets. These jackets were used to bind the left forelimb against the body of the dog, thereby preventing weight bearing on that limb. The experimental group (n = 6) was treated with an I.V. dose of 0.45 mumol/kg/day APD (pamidronate) for 7 days followed by 3 weeks without treatment. This cycle was repeated 3 times for a total of 12 weeks. The control group (n = 6) followed the same pattern, but received only saline injections. At the end of the experiment, the dogs were sacrificed and the humeri and radii cleaned of soft tissues. Mineralization profiles, which determine the distribution of mineralization densities of the cortical and trabecular bone were obtained and the main fractions were analyzed chemically. Static histomorphometric parameters were determined on 5 microns undecalcified sections from the distal humerus and on 50 microns section of the humeral shaft. Three point bending and torsional testing were performed on the radius. Immobilization induces hypomineralization in cortical and cancellous bone but is prevented by APD treatment in cancellous. Immobilization in this model induces osteopenia and increases turnover in cancellous bone. These effects are counteracted by APD. Finally, cortical bone density and stiffness are reduced by immobilization but this is prevented by APD treatment. This experiment shows that the mature dog model is useful to study the immobilization-induced increase of bone turnover and concomitant decrease in bone density, stiffness and mineralization. It also shows that these effects of immobilization can be prevented by treatment with the bisphosphonate pamidronate.

The effects of androgens on the mechanical properties of primate bone.

Feral adult female cynomolgus monkeys were divided into three groups and treated for two years: (1) normal controls; (2) weak androgenic treatment (androstenedione+estrone); and (3) strong androgenic treatment (testosterone). The tibiae and the trabecular bone of femoral head from each group were tested mechanically. There were no significant changes in the elastic modulus and shear modulus of the tibiae, measured by three point bending and torsion tests, among the three groups. Significant increases in energy absorption capacity (+45% for testosterone) and maximum shear stress (+19.4% for androstenedione and +39% for testosterone) of the tibiae, measured by torsion tests, and the cortical bone density (+5.5% for androstenedione and +8.7% for testosterone), were observed. Testosterone treatment significantly increased torsional rigidity (+23%) and bending stiffness (+15%) of the tibiae while androstenedione did not change any of these structural properties. The results of compression tests of the trabecular bone samples indicated significant increases in their elastic modulus after androstenedione (+88%) or testosterone (+107%) treatment. The maximum compressive stress of the testosterone treated samples was significantly higher than those of both normal (+28%) and androstenedione treated groups (+26%). The trabecular bone density increased after both androgenic treatments. This increase was significant for the testosterone treated group (+8.6%). We conclude that in the young cynomolgus monkey, long-term androgenic treatment significantly improves some of the mechanical properties of both cortical and trabecular bones, increases bone density, and the stronger the androgen, likely, the more pronounced is the effect.

The effect of different hormone replacement therapy regimens on the mechanical properties of rat vertebrae.

The purpose of this study was to examine the effects of estrogen replacement, in concert with three different progestin regimens, on the mechanical properties of rat lumbar vertebrae. Ninety-two Sprague-Dawley rats (11 months old) were divided into six groups for treatment. The first group was an intact control, the second group (OVX) was ovariectomized only, and the third group (estrogen-only) was ovariectomized and received continuous estrogen through a 17 beta-estradiol implant. The remaining groups were ovariectomized and received estrogen and progestin (norethindrone, NET) therapy; 3 micrograms of NET was injected daily (estrogen plus continuous NET), or 6 micrograms of NET was injected for 14 consecutive days of a 28-day cycle (estrogen plus cyclic NET), or for 3 consecutive days of a 6-day cycle (estrogen plus interrupted NET). The animals were sacrificed after 6 months, and the vertebrae were dissected out. The vertebral processes of the fourth lumbar vertebrae were removed, and the density of the vertebral bodies was determined. They were then subjected to compression testing. We found that all three estrogen/progestin regimens maintain bone density and all mechanical properties at a level indistinguishable from the control. However, the cyclic and continuous NET treatment results were, with the exception of density, also indistinguishable from those of the ovariectomized group. The estrogen plus interrupted NET group on the other hand, has a significantly greater compressive modulus and density than the ovariectomized group. In conclusion, with respect to the ovariectomized group, the estrogen plus interrupted NET treatment resulted in a superior density and compressive modulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery from pamidronate (APD): a two-year study in the dog.

The goal of this study was to find out if bone can recover after long-term administration of bisphosphonate. Disodium pamidronate (APD) was given orally by gavage to mature beagle dogs at doses of 0, 2.5, 12.5, and 25 mg/kg/day for 1 year (0.1% concentration) and the animals were allowed to recover for another year. At sacrifice, the os ilium was used to determine bone mineralization profile and, subsequently, each density fraction was analyzed chemically. The ribs were used to determine the lattice parameters and the size of the apatite crystals of bone. The sternum was used to determine selected morphometric parameters using image analysis of specimen X-ray films and, subsequently, to determine bone mechanical properties using a 3-point bending technique. We found that the 12.5 and 25 mg/kg/day doses exhibit a significant shift towards greater mineralization versus control, whereas the lower dose (2.5 mg/kg/day) was indistinguishable from the controls. The lattice parameters and crystal size of bone apatite remained unchanged. The image analysis shows a dose-related increase in trabecular volume and thickness. The connectivity increased with dose but the anisotropy of bone remained unchanged. Both the elastic modulus and the maximum stress of bone remain unaffected by APD. We conclude that when dogs are treated with APD for 1 year, their bones can reestablish their physical-chemical characteristics (mineralization profile, chemistry, and crystal size/strain) after 1 year of recovery, provided that the treatment dose is 2.5 mg/kg/day. In addition, the mechanical properties of the bone remained unaffected and the gains in trabecular volume and thickness are maintained.

Effect of long-term ovariectomy on bone mechanical properties in young female cynomolgus monkeys.

Feral adult female cynomolgus monkeys were divided into two groups: normal controls and ovariectomized. Tibiae and trabecular bones from the femoral head, from each group, were tested using a materials testing machine. The bending stiffness of the tibiae was measured by nondestructive three-point bending tests and their maximum torque capacity by destructive torsion tests. The compressive strength of the trabecular bones was measured by compression tests. Ovariectomy caused significant decreases in elastic modulus of the tibiae (p < 0.008), measured by three-point bending tests, and in shear modulus (p < 0.015), failure shear stress (p < 0.01), and failure torque (p < 0.001) of the tibiae, measured by torsion tests. It caused a significant decrease in cortical bone density (p < 0.005), but no significant changes in tibial cross-sectional area and in cortical shaft external and internal diameters. The differences in elastic modulus, maximum compressive strength, and density of femoral trabecular bone samples between the two groups were not significant.

Effects of intermittent administration of pamidronate on the mechanical properties of canine cortical and trabecular bone.

The mechanical properties of cortical and trabecular bones from beagles treated with the bisphosphonate pamidronate (administered intermittently 1 week every month for 3 months, at a dosage of 0.45 mumol/kg/day) were assessed. The mechanical properties of cortical bone were measured by four-point bending tests on femoral quadrants, in order to measure their elastic modulus and ultimate stress. The structural properties of whole tibias were measured in torsion to determine the torsional stiffness and failure torque. The elastic modulus and maximum compressive stress of the trabecular bone samples were measured by compression tests of trabecular cores. Intermittent treatment with pamidronate did not change the pattern of mechanical properties that occurs naturally around the femur or the torsional stiffness and failure torque of the tibias. By contrast, pamidronate did significantly increase the modulus of elasticity (by 19%) and maximum compressive stress (by 33%) of vertically aligned cylindrical trabecular specimens taken from the vertebrae of the beagles.

Effect of pamidronate on the mechanical properties of canine bone.

Pamidronate (Aredia) has been used in the treatment of hypercalcemia of malignancy, in Paget's disease of bone, and in osteoporosis to prevent bone resorption. In a 3-month study, intermittent intravenous infusions of pamidronate in dogs did not change the mechanical properties of cortical bone, either in torsion or bending. However, such treatment increased the compressive stiffness and torsional strength of trabecular specimens taken from vertebrae. In a 1-year study, oral administration of pamidronate at various doses produced a linear increase in the elastic modulus of trabecular bone with the square root of the dose and no change in cortical bone. Finally, in a 2-year study (1 year on pamidronate followed by 1 year recovery), no differences were found in the mechanical properties of whole bone whatever dose was given.

Dynamics of human lumbar intervertebral joints. Experimental and finite-element investigations.

To improve our understanding of the dynamic characteristics of the human lumbar spine, both experimental and finite-element methods are required. The experimental methods included measurement of the axial steady state response, resonant frequencies, and damping of seven lumbar motion segments under an upper-body mass of 40 kg. The influence of the presence of posterior elements and different magnitudes of compression preload on the response was also studied. To supplement the measurements, linear and nonlinear, axisymmetric, and three-dimensional finite-element models of a L2-L3 disc-vertebra unit were developed to predict the free and forced-vibration responses. The step and harmonic loadings in the axial direction were considered for the forced-vibration analysis. The effect of the presence of the body mass and compression preloads were also examined. The results of experimental and finite-element studies were in good agreement with each other. They indicated that the system resonant frequencies are reduced considerably with the addition of a body mass of 40 kg and increase significantly (P less than .005) as the compression preload increases. The compliance at both low and resonant frequencies decreases with increasing compression preload. Under preloads of not more than 680 N, removal of the facet joints tends to decrease slightly the segmental resonant frequencies irrespective of the magnitude of compression preload (P less than .1). The finite-element model studies show quasi-static response under harmonic loads with periods much larger than the fundamental period of the segment and under step loads with slow rising times. Under a step load without the body mass, the nucleus pressure varies with both location and time and reaches a maximum of about 2.5 times that under equivalent static load. The addition of a 40-kg mass, in this case, renders a single degree-of-freedom response, with the pressure remaining nearly constant with location inside the nucleus. The stresses and strains throughout the segment in this case increase approximately twofold in comparison with equivalent static values. Partial or complete removal of the disc nucleus considerably decreases the resonant frequency and increases the corresponding segmental response amplitude (ie, compliance). The results indicate that the most vulnerable element under axial vibration loads is the cancellous bone adjacent to the nucleus space. Fatigue fracture of bone as a cumulative trauma and the subsequent loss of nucleus content likely initiates or accelerate the segmental degenerative processes. The annulus fibers do not appear to be vulnerable to rupture when the segment is subjected to pure axial vibration.