Biomedical subjects

R F Zernicke

Publications and source records attributed to R F Zernicke.

At least 19 recordsLinked to original sources

PubMed2005

Structure, function and adaptation of bone-tendon and bone-ligament complexes.

Mechanical and physiological processes contribute to joint tissue adaptations during growth and exercise and after injury. Those adaptations are often in response to the mechanotransductive stimuli linked to the transmission of forces across these load-bearing structures. Muscle-tendon interactions have been explored during skeletal loading and describe the relation of sarcomere shortening at the expense of tendon lengthening(1,2). The effects of load transmission through the bone-tendon and bone-ligament complexes, however, have not been studied as extensively, although both disuse and exercise will alter the stiffness of these significant structures. Recently, however, renewed interest has emerged about the pathogenesis underlying enthesopathies and enthesitis, and investigators are beginning to reveal the intricacies of bone-tendon and bone-ligament complexes(3,4,5). Here, we summarize the structure and function of the types of entheses between bone-tendon and bone-ligament, and relate how mechanical loading leads to functional adaptation, and at times, entheseal pathophysiology.

Adaptation, Physiological↗

PubMed2004

Antiresorptive therapy conserves some periarticular bone and ligament mechanical properties after anterior cruciate ligament disruption in the rabbit knee.

The purpose of this study was to assess, in an osteoarthritic (OA) model, whether bisphosphonate (BP) antiresorptive therapy altered periarticular bone and bone-ligament biomechanics and OA progression. We surgically transected the anterior cruciate ligament (ACLX) in two groups of rabbits; the first group was dosed with BP (risedronate, 0.01 mg/kg s.c. daily for 6 wk), the second group remained untreated, and a third group of normal (unoperated) control rabbits was also evaluated. We measured distal femoral bone mineral density (BMD, Dual Energy X-ray Absorptiometry [DEXA]), medial collateral ligament (MCL) laxity, and bone mechanical function (bone cores mechanically tested in compression). These measures were related to cartilage/joint gross morphology, histology, and measures of vascular volume (gelatin-dye perfusion) for evidence of inflammatory angiogenesis and early OA. BMD by DEXA in 6 wk ACLX animals was 18% less than normal controls (p<0.05). In contrast, BP dosing conserved periarticular BMD; risedronate-treated rabbits had distal femoral BMD only 5% less and not significantly different than normal controls. When the same bone cores were compressed to failure, both ACLX and BP-dosed animals were significantly weaker than normal controls (p<0.05). However, the bone energy to failure and elastic modulus of BP-dosed animals was conserved and not significantly different from normal controls 6 wk after ACLX. Blocking bone resorption with BP also resulted in a significantly improved bone-ligament structural complex. MCL-complex laxity was significantly less in BP-dosed animals (1.2 times that of normal controls) compared to untreated ACLX animals (1.7 times that of normal controls; p<0.05). Blocking bone resorption with risedronate did not suppress osteophytosis and inflammatory angiogenesis, which were significantly increased in the periarticular bone of both untreated and BP treated ACLX animals. Thus, administering BP immediately after ACL loss conserved some periarticular bone and MCL-complex properties in an early OA model.

Animals↗

PubMed2003

Angiogenesis in the distal femoral chondroepiphysis of the rabbit during development of the secondary centre of ossification.

In the developing chondroepiphyses of long bones, the avascular cartilaginous anlage is invaded by numerous blood vessels, through the process of angiogenesis. The objective of this study was to investigate the chronology of this vascular invasion with the spontaneous calcification of the cartilaginous epiphysis during development of the secondary ossification centre in the rabbit distal femur. The time-course of chondroepiphyseal vascular invasion was determined histologically and standardized for eight gestational and four postnatal intervals by plotting kit body mass against crown-rump length. Similarly, microcomputed tomography (micro-CT) helped to visualize calcification at those same gestational and postnatal intervals. To confirm the angiogenic nature of the avascular chondroepiphysis, such samples were assayed on the chick chorio-allantoic membrane (CAM). Neovascular outgrowths from the CAM were apparent 48 h following introduction of an 18-day (gestational) chondroepiphyseal sample. Chondroepiphyseal samples were assayed for the potent developmental angiogenic factors bFGF and VEGF, with the mRNA expression for both these mediators being confirmed using RT-PCR. As angiogenesis and calcification during chondroepiphyseal development occur in a defined tissue environment initially devoid of blood vessels and mineral, those processes provided a unique opportunity to study their progression without complication of injury-related inflammation or extant vasculature and mineral. Furthermore, the discovery of angiogenic, angiostatic or mineral-regulating mediators specific to developing connective tissue may prove useful for analysing the regulation of vascular and mineral pathogenesis in articular tissues.

Actins↗

PubMed2001

Estimation of spinal deformity in scoliosis from torso surface cross sections.

STUDY DESIGN: Correlation of torso scan and three-dimensional radiographic data in 65 scans of 40 subjects. OBJECTIVES: To assess whether full-torso surface laser scan images can be effectively used to estimate spinal deformity with the aid of an artificial neural network. SUMMARY OF BACKGROUND DATA: Quantification of torso surface asymmetry may aid diagnosis and monitoring of scoliosis and thereby minimize the use of radiographs. Artificial neural networks are computing tools designed to relate input and output data when the form of the relation is unknown. METHODS: A three-dimensional torso scan taken concurrently with a pair of radiographs was used to generate an integrated three-dimensional model of the spine and torso surface. Sixty-five scan-radiograph pairs were generated during 18 months in 40 patients (Cobb angles 0-58 degrees ): 34 patients with adolescent idiopathic scoliosis and six with juvenile scoliosis. Sixteen (25%) were randomly selected for testing and the remainder (n = 49) used to train the artificial neural network. Contours were cut through the torso model at each vertebral level, and the line joining the centroids of area of the torso contours was generated. Lateral deviations and angles of curvature of this line, and the relative rotations of the principal axes of each contour were computed. Artificial neural network estimations of maximal computer Cobb angle were made. RESULTS: Torso-spine correlations were generally weak (r < 0.5), although the range of torso rotation related moderately well to the maximal Cobb angle (r = 0.64). Deformity of the torso centroid line was minimal despite significant spinal deformity in the patients studied. Despite these limitations and the small data set, the artificial neural network estimated the maximal Cobb angle within 6 degrees in 63% of the test data set and was able to distinguish a Cobb angle greater than 30 degrees with a sensitivity of 1.0 and specificity of 0.75. CONCLUSIONS: Neural-network analysis of full-torso scan imaging shows promise to accurately estimate scoliotic spinal deformity in a variety of patients.

Adolescent↗

PubMed2001

Evidence of chondrocyte repopulation in adult ovine articular cartilage following cryoinjury and long-term transplantation.

OBJECTIVE: To characterize the response of articular chondrocytes to a specific cryoinjury that leads to cluster formation following long-term transplantation. DESIGN: Osteochondral dowels from 20 adult sheep were cryopreserved to optimize the recovery of chondrocytes immediately after thawing. The dowels were transplanted as allografts and observed at 3 and 12 months. Chondrocyte distribution and viability was assessed using paravital dyes after transplantation. Chondrocyte phenotype was assessed by in situ hybridization and immunohistochemistry to detect type II collagen. An anticentrosome antibody was used to identify cells undergoing cell cycle progression towards mitosis. RESULTS: All cryopreserved grafts showed the presence of spheroidal clusters of chondrocytes 1 year after transplantation while the host cartilage adjacent to the graft appeared morphologically normal. The average size of the clusters increased from four cells at 3 months to 12 cells at 1 year. The chondrocytes in the clusters displayed newly formed type II collagen protein and mRNA. Some cells within clusters were observed with two centrosomes, indicative of cells progressing through the S phase of the cell cycle. CONCLUSION: Adult articular chondrocytes retain the ability to repopulate the matrix, an ability which is demonstrated with this specific cryoinjury. This may be an initial stage of cartilage regeneration.

Animals↗

PubMed2001

Physiological and mechanical adaptation of periarticular cancellous bone after joint ligament injury.

The relation between blood flow and bone mineral density (BMD) of periarticular bone was examined in an in vivo model of joint instability. Eighty mature New Zealand White rabbits were randomly assigned to experimental [anterior cruciate ligament transection (ACLX)], sham-operated control, or age-matched normal control groups. Experimental rabbits underwent unilateral transection of the right anterior cruciate ligament, and the nonoperated left [contralateral (Cntra)] limb was a within-animal control. BMD and blood flow to the periarticular bone in the femoral condyles were assessed in each group at 2, 4, 6, 14, and 48 wk postsurgery, using quantitative computed tomography scanning and entrapment of colored microspheres. BMD was significantly lower (5%) in the ACLX compared with Cntra limbs. Periarticular bone blood flow in the ACLX limbs was significantly greater than in the Cntra limb (29%) in the early stages (6 wk) after injury. Up to 48 wk post-ACLX, a significant correlation was found between increased blood flow and decreased BMD in the periarticular bone of the femoral condyles in the ACLX limbs. This correlation suggested that heightened blood flow may be linked to mechanisms of bone adaptation in joints after ligament injury.

Adaptation, Physiological↗

PubMed2001

Evaluation of laser-Doppler perfusion imaging for measurement of blood flow in cortical bone.

Most techniques currently available to measure blood flow in bone are time consuming and require destruction of the tissue, but laser-Doppler technology offers a less invasive method. This study assessed the utility of laser-Doppler perfusion imaging (LDI) to measure perfusion in cortical bone. Twelve mature New Zealand White rabbits were assigned to one of three groups: normal control, constriction (norepinephrine), or dilatation (nitroprusside). The left and right medial tibiae were consecutively scanned at red (634-nm) and near-infrared (810-nm) wavelengths to examine the repeatability of LDI output. The pharmacological intervention groups were injected with the respective drug, and LDI measurements at 810 nm were obtained concurrently with colored microsphere-determined flow in all of the groups. LDI effectively quantified blood flow in cortical bone and detected physiologically induced changes in perfusion. A significant positive correlation was found between microsphere-determined flow and LDI output (r = 0.6, P < 0.05). Repeatability of consecutive LDI measurements was within 5%. The effectiveness of LDI to measure perfusion in bone suggests this method has potential for investigating the role of blood flow in bone metabolism and remodeling.

Animals↗

PubMed2001

Periarticular cancellous bone changes following anterior cruciate ligament injury.

To understand more fully the early bone changes in an experimental model of osteoarthrosis, we quantified periarticular bone mineral density and bone mechanical properties in anterior cruciate ligament transected (ACLX) knee joints (4, 10, 32, and 39 wk post-ACLX) compared with contralateral joints and unoperated normal joints of skeletally mature animals. Maximal stress and energy were significantly reduced in ACLX cancellous bone from the medial femoral condyles at 4 wk postinjury. All mechanical properties (e.g., yield stress and elastic modulus) declined after 4 wk and were significantly reduced at 10 wk. ACLX bone mineral density was significantly reduced at all measured time points. Ash content was significantly reduced at 10 and 32 wk. Changes in the lateral condyles were similar but less pronounced than in the medial condyles. These bony changes accompanied the earliest articular cartilage molecular changes and preceded changes in the articular cartilage gross morphology. We suggest that these early changes in bone mechanical behavior contribute to the progression of osteoarthrosis and pathogenic changes in the joint.

Animals↗

PubMed2000

Dietary fish oil supplementation adversely affects cortical bone morphology and biomechanics in growing rabbits.

Despite substantial evidence that fish oil-derived (n-3) polyunsaturated fatty acids (PUFA) may protect against cardiovascular disease, the effects of supplements containing (n-3) PUFA on the skeletal system are unknown. Here we investigated how a diet supplemented with 10 g/100 g fish oil affected tibial cortical morphology and mechanical properties in weanling rabbits. Rabbits were subdivided into a normal control (n = 10), a fish oil (n = 20), and a pair-fed (n = 20) group. The pair-fed group was energy restricted to match average body mass of the fish oil group. At completion of the 40 day dietary intervention, control rabbits were significantly heavier than the other two groups. Comparison between control and pair-fed rabbits revealed that energy restriction alone (30%) did not induce significant changes in tibial middiaphyseal morphology, but tibial longitudinal growth was significantly impaired. Most tibial mechanical properties were significantly degraded by energy restriction. Fish oil-supplemented rabbits had significantly smaller middiaphyseal areal properties and shorter tibiae than pair-fed rabbits. Tibial structural properties were significantly reduced in fish oil-fed rabbits, but tibial stress at the proportional limit (material property) was not significantly affected. Our data suggest that 10% fish oil supplementation in the presence of modest vitamin E supplementation can have detrimental effects on the skeleton of rapidly growing rabbits.

Animals↗

PubMed2000

Early morphometric and anisotropic change in periarticular cancellous bone in a model of experimental knee osteoarthritis quantified using microcomputed tomography.

OBJECTIVE: To quantify early stage microstructural changes of periarticular cancellous bone in a canine anterior cruciate ligament transection model for experimental osteoarthritis. DESIGN: Unilateral transection of the anterior cruciate ligament was performed in 10 animals. Bone structure changes were quantified in five animals at 3-week post-transection and five animals at 12-week post-transection. An additional two non-operated animals were used as controls. BACKGROUND: Changes in trabecular architecture of the periarticular cancellous bone in early stage post-traumatic osteoarthritis is not well understood. Previous studies have found alterations in bone mineral density in experimental osteoarthritis suggesting adaptation of the trabecular structure. Early change of the periarticular bone following a ligament injury may contribute to the long-term development of osteoarthritis. METHODS: ++. Bone cores from the medial condyles of the femoral and tibial pairs were scanned with a three-dimensional microtomographic system. Structural indices were quantified including bone volume ratio, bone surface ratio, trabecular thickness, trabecular separation, trabecular number, as well as structural anisotropy determined by the mean-intercept-length method.Results. Significant structural changes were observed at 3-week post-transection, and were more prominent at 12-week post-transection. These changes were accompanied by decreasing anisotropy. CONCLUSIONS: Periarticular cancellous bone microstructure is significantly altered in experimental osteoarthritis. These changes occurred as early as 3-week post-transection, and were large at 12-week post-transection. RELEVANCE: The pathogenesis of post-traumatic osteoarthritis is poorly understood, but it is clear that this disease involves the entire organ system of the joint, including the cartilages, synovium, ligaments, and bones. This study focuses on the changes that occur in the bones during the early stages following a joint injury, and contributes to a better overall understanding of the disease aetiology.

Animals↗

PubMed2000

Functional adaptation of bone to exercise and injury.

Bone adapts to altered physical stimuli, dietary changes, or injury. Dietary calcium and vitamins play important roles in maintaining skeletal health, but high-fat diets are pervasive in western cultures and may contribute to the increasing prevalence of osteoporosis and incidence of related hip fractures. Exercise helps maintain bone mass and counter osteoporosis, but exercise can also have detrimental effects-particularly for immature bone. Some negative exercise effects may also be linked to diet. For example, insufficient dietary protein during exercise can impair bone development and remodeling. Bone remodeling is a potent example of tissue repair. Chronically altered loading after a joint injury, however, can result in remodeling processes that can be detrimental to the joint. Anterior cruciate ligament injury, for example, commonly leads to osteoarthritis. Early changes in the periarticular cancellous bone may play a role in the development of knee osteoarthritis. Although these factors influence skeletal health, the mechanisms remain unclear by which bone interprets its environment and responds to mechanical stimuli or injury. To understand why different levels of exercise are beneficial or detrimental or why altered joint loading leads to changes in periarticular bone structure, underlying mechanisms must be understood by which bone interprets its mechanical environment.

Adaptation, Physiological↗

PubMed2000

Aging-induced osteopenia in avian cortical bone.

Cortical bone loss contributes substantially to the degradation of skeletal integrity associated with aging. However, animal models that closely mimic age-related alterations in cortical bone are limited. The objective of this study was to determine if aged rooster cortical bone demonstrates phenotypic alterations similar to those observed in aged human cortical bone (i.e., expansion of the endocortical and periosteal envelopes and elevated cortical porosity). When compared with young adult roosters, aged roosters demonstrated significant expansion of the endocortical (16%) and periosteal (10%) envelopes, resulting in significantly increased cross-sectional moments of inertia. In addition, aged rooster bone demonstrated significantly elevated cortical porosity (51%) and average area of porosity (83%). We conclude that rooster bone demonstrates age-related adaptations similar to those of humans at both tissue and cellular levels, and may therefore represent a relatively useful, inexpensive animal model for investigating the mechanisms of age-related bone loss.

Age Factors↗

PubMed2000

Does the mechanical milieu associated with high-speed running lead to adaptive changes in diaphyseal growing bone?

Exercise during growth can be important for attaining optimal bone mass. High-intensity long-duration protocols, however, can have detrimental effects on immature bone morphology and mechanics. The underlying mechanisms are poorly understood. Here, we quantified the mechanical environment of the middiaphyseal rooster tarsometatarsus during high-speed running and examined whether short bouts of this exercise-related mechanical milieu can induce positive changes in cortical bone morphology, mechanics, and mineral ash content. At 9 weeks of age, roosters were assigned to controls (n = 9) and runners (n = 8). Treadmill running was applied in loading sessions of 5 min, three times per day (approximately 2600 cycles/day) for 8 weeks. Both controls and runners received double-fluorochrome labels during weeks 3 and 8 of the protocol. Middiaphyseal distributions of tarsometatarsal longitudinal normal strain, strain rate, and strain gradients engendered by walking and running were determined via in vivo strain gauges. Compared with walking, running elevated mean peak strain magnitude by 19%, peak strain rates by 136%, and peak strain gradients by approximately 18%. After 8 weeks of running, middiaphyseal areal and mechanical properties and normalized ash weight were no different between runners and controls. Transient and focal reductions in periosteal mineral apposition rates occurred during the exercise protocol. Our current data suggest that reducing the number of loading cycles can mitigate the adverse response previously observed in this model with long-duration running. This study also supports the tenet that the exercise-generated mechanical milieu must differ substantially from the habitual milieu to induce significant adaptations.

Adaptation, Physiological↗

PubMed2000

Reconstruction of laser-scanned 3D torso topography and stereoradiographical spine and rib-cage geometry in scoliosis.

Assessments of scoliosis are routinely done by means of clinical examination and full spinal x-rays. Multiple exposure to ionization radiation, however, can be hazardous to the child and is costly. Here, we explain the use of a noninvasive imaging technique, based on laser optical scanning, for quantifying the three-dimensional (3D) trunk surface topography that can be used to estimate parameters of 3D deformity of the spine. The laser optical scanning system consisted of four BIRIS laser cameras mounted on a ring moving along a vertical axis, producing a topographical mapping of the entire torso. In conjunction with the laser scans, an accurate 3D reconstruction of the spine and rib cage were developed from the digitized x-ray images. Results from 14 scoliotic patients are reported. The digitized surfaces provided the foundation data to start studying concordance of trunk surface asymmetry and spinal shape in idiopathic scoliosis.

Calibration↗

PubMed2000

High-impact exercise and growing bone: relation between high strain rates and enhanced bone formation.

We investigated whether high-impact drop jumps could increase bone formation in the middiaphyseal tarsometatarsus of growing rooster. Roosters were designated as sedentary controls (n = 10) or jumpers (n = 10). Jumpers performed 200 drop jumps per day for 3 wk. The mechanical milieu of the tarsometatarsus was quantified via in vivo strain gauges. Indexes of bone formation and mechanical parameters were determined in each of twelve 30 degrees sectors subdividing the middiaphyseal cortex. Compared with baseline walking, drop jumping produced large peak strain rates (+740%) in the presence of moderately increased peak strain magnitudes (+30%) and unaltered strain distributions. Bone formation rates were significantly increased by jump training at periosteal (+40%) and endocortical surfaces (+370%). Strain rate was significantly correlated with the specific sites of increased formation rates at endocortical but not at periosteal surfaces. Previously, treadmill running did not enhance bone growth in this model. Comparing the mechanical milieus produced by running and drop jumps revealed that jumping significantly elevated only peak strain rates. This further emphasized the sensitivity of immature bone to high strain rates.

Animals↗

PubMed2000

Early regional adaptation of periarticular bone mineral density after anterior cruciate ligament injury.

The present study measured early-stage adaptation of bone mineral (BMD) in the periarticular cancellous bone of the canine knee (stifle) joint after anterior cruciate ligament (ACL) transection (ACLX). Regional changes in BMD in the tibia and femur were analyzed by using quantitative computed tomography (qCT) at 3 wk and 12 wk after unilateral ACLX to determine whether there were focal points for BMD changes and whether these changes occurred early after the induced knee injury. BMD decreased rapidly after ACLX, and the more pronounced response was in the femur. In the 3-wk group, there were decreases in BMD in the tibia and the femur, and these changes were significant in the posterior-medial region of the femur, which showed a decrease of BMD in the ACLX limb (-0.048 +/- 0.011 g/cm(3)). In the 12-wk group, all regions in the tibia and femur exhibited significant decreases in BMD, and the average decrease was greatest in the posterior-medial region of the femur (-0.142 +/- 0.021 g/cm(3)). The regions of pronounced periarticular cancellous BMD adaptation corresponded to observed focal cartilage defects. Early decreases in BMD in the injured knee may be related to altered loading and kinematics in the knee and may be an important link in the pathogenesis of posttraumatic osteoarthritis.

Adaptation, Physiological↗

PubMed1999

Dynamic measurement of bone blood perfusion with modified laser Doppler imaging.

Although the mechanisms are not clearly defined, blood flow may play an important role in moderating skeletal adaptation. Most techniques currently available to measure blood flow in bone are time-consuming and require destruction of the tissue, but laser Doppler technology offers a less invasive method. The present study assessed whether laser Doppler perfusion imaging could detect changes in perfusion in cortical bone. By use of modified laser Doppler perfusion imaging with an adjustable, incorporated, near infrared-laser gain photodetection system, perfusion of blood in the mid-diaphyseal tibial cortex of New Zealand White rabbits (n = 5) was measured before, during, and after occlusion of the femoral artery. During occlusion, perfusion decreased 69% compared with control levels; removal of the arterial clip caused flux values to return to near normal. Laser Doppler perfusion imaging provides a two-dimensional image related to blood flow, and the results of this pilot study suggest that it may be an effective technique for imaging in vivo dynamic changes in perfusion in cortical bone.

Animals↗

PubMed1999

Transplantation of cryopreserved osteochondral Dowel allografts for repair of focal articular defects in an ovine model.

The purpose of this study was to test whether successful cryopreservation of osteochondral tissue is possible and whether, with the appropriate surgical procedure, it can be used for the successful repair of focal articular defects within joints. Fresh (nonfrozen) and snap-frozen (plunged in liquid nitrogen and thawed in a water bath at 37 degrees C, repeated three times) autografts were used as positive and negative controls, respectively. Snap-frozen, frozen (fresh tissue placed in a freezer at -80 degrees C), and cryopreserved (immersed in 10% dimethyl sulfoxide for 30 minutes and then frozen at 1 degrees C/min to -80 degrees C) allografts were transplanted into the knees of adult sheep. Outcomes were evaluated 3, 6, and 12 months after transplantation. The morphological, histological, biochemical, and biomechanical behaviors and characteristics of the graft cartilage, the host cartilage adjacent to the grafts, and the opposing tibial cartilage were assessed. Freezing protocols that yielded poor chondrocyte recovery after thawing (frozen and snap-frozen) resulted in poor overall graft outcome. The cryopreservation protocol, however, resulted in intermediate recovery (50%) of chondrocytes and in intermediate overall graft outcome compared with fresh autografts. The membrane integrity of the allograft chondrocytes immediately following cryopreservation was identified as the most reliable predictor of long-term outcome of the graft. Further improvements in cryopreservation technique may lead to an effective method of banking osteochondral tissue for successful transplantation for the repair of focal defects and larger joint reconstructions.

Animals↗