bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of propranolol on bone metabolism in the rat
Authors: Minkowitz Barbara , Boskey Adele L. , Lane Joseph M. , Pearlman Hubert S. , Vigorita Vincent J.
Published: February 2005

Propranolol, a nonspecific β‐blocker, has many physiologic effects. Its effects on bone in vivo are unknown, although β receptor sites have been found on osteoblasts. In this study, the hypothesis tested was that low doses of propranolol could alter bone properties and enhance orthotopic endochondral bone formation. In a group of nonsurgical rats, propranolol treatment increased formation. In a group of nonsurgical rats, propranolol treatment increased femoral torsional strength on biomechanical testing. In the rat surgical model used, right femora were fixed to a polyethylene plate and then defects were created mid‐diaphysis and subsequently filled with demineralized bone matrix. These rats (defect rats) were randomly divided into groups that were given propranolol or a saline carrier for 19 consecutive days. In the defect rats, increased trabecular femoral metaphyseal mineral apposition rates were observed in propranolol‐treated groups. Densitometry and roentgenographic scoring of callus formation after 12 weeks in propranolol‐treated rats revealed increased callus and bone union. The results of this study indicate that propranolol treatment can significantly affect bone properties.
Telopeptide‐depleted bovine skin collagen as a carrier for bone morphogenetic protein
Authors: Takaoka Kunio , Koezuka Masahiro , Nakahara Haruhiko
Published: February 2005

The telopeptide of type I collagen is thought to be responsible for causing immunogenic response when introduced into xenogenic hosts. To eliminate this problem, solubilized bovine skin collagen was filtered through a millipore membrane, digested repeatedly with pepsin to remove telopeptides, and used as a carrier for a water‐soluble, partially‐purified fraction of bone morphogenetic protein (BMP) in mice. Composite implants of this telopeptide‐depleted collagen and the partially‐purified BMP fraction consistently elicited ectopic bone formation in mice 3 weeks postimplantation. When implanted alone, collagen or BMP failed to show this response. Collagens, prepared by use of conventional methods (acid‐solubilized collagen, or collagen‐digested once with pepsin) were also assessed as carriers for BMP, but were found to be inferior in terms of consistency of bone formation and amount of induced bone mass. The results suggest that telopeptide‐depleted collagen permitted a gradual release of purified BMP for induction of bone, with minimal immunogenic interference. Consequently, this collagen carrier represents an important development for future clinical application of BMP.
Fibronectin and keratan sulfate synthesis by canine articular chondrocytes in culture is modulated by dibutyryl cyclic adenosine monophosphate
Authors: Leipold Harry R. , Wurster Nancy Burton , Steinmeyer Juergen , Vernier‐Singer Margaret S. , Lust George
Published: February 2005

The ability of cyclic adenosine monophosphate (cAMP) to maintain differentiated properties of canine articular chondrocytes in culture is reported. Treatment with 0.5 mM dibutyryl cAMP (DBcAMP) caused the cells to adopt a more rounded morphology. This change in morphology seems to have no effect on the overall biosynthetic rates of the cells. After a pulse with 35S‐methionine, there was no difference in the concentration of labeled proteins between cultures treated with DBcAMP and control cultures. After 6 days, the amount of fibronectin (FN) in the media of DBcAMP‐treated cultures detected by an enzyme‐linked immunosorbent assay was specifically reduced by 30%. The amount of 35S‐FN purified by gelatin‐affinity chromatography decreased 33%. Moreover, the percentage of FN containing the extra domain A sequence was reduced from 19.4 ± 8.7% in control cultures to 9.6 ± 4.2%. Concomitant with the decrease in FN, there was an increase in the concentration of keratan sulfate in the media of DBcAMP‐treated cultures. After 6 days, treated cultures had 47% more keratan sulfate than controls did. These changes appear not to be the result of a change in the deposition of FN or keratan sulfate, because the amount of these molecules that could be extracted from the cell layer was typically below the limit of detection of the assays. Instead, it seems there is a phenotypic change in the chondrocytes pertaining to the production of FN and keratan sulfate.
Human growth plate development in the fetal and neonatal period
Authors: Rodriguez Jose I. , Razquin Socorro , Palacios Jose , Rubio Vicente
Published: February 2005

The development of the normal human upper tibial growth plate was studied at autopsy in 46 stillborns and 79 newborns of 20–41 weeks gestational age. During this time period, the histology of this plate evolves from a highly cellular structure with relatively poor columnar organization and matrix development to the well known structure seen later in postnatal life. The thickness of the growth plate, assessed in the area surrounding the longitudinal tibial axis, decreases continuously from 1.15 mm on the 20th week to 0.6 mm on the 38th week. This decrease results from losses of both matrix and cellular components, mostly of the latter. However, the relative fraction of area occupied by the matrix significantly increased (12%) and matrix area per cell increased 1.5 times over the last half of gestation, indicating a maturation process of the plate towards a more matrix‐oriented structure with age. In this maturation process the number of cells per unit area does not change and the average size of the cells appears to decrease. Plate thickness does not decrease further in the final 3 weeks of pregnancy and increases in early neonatal life; this has no apparent influence on the tibial growth rate. In the period under study the relative anatomical participation of the upper tibial growth plate decreases from ∼4% of the radiographic length of the tibia on the 20th week to < 1% at term. Present data will provide fetal and neonatal growth plate standards needed to obtain a better understanding of this structure during both normal and abnormal conditions.
Antagonist drugs and bone vascular smooth muscle
Authors: Dean Michael T. , Wood Michael B. , Vanhoutte Paul M.
Published: February 2005

An ex vivo canine tibia model was used to quantitate the specific adrenergic subtype contribution in bone vasculature. Tibiae were obtained from mongrel dogs, the nutrient artery was catheterized, and the bone was placed in an ex vivo perfusion apparatus at constant flow. Perfusion was accomplished using oxygenated Krebs‐Ringer solution. A norepinephrine dose‐response curve was obtained by using incremental single bolus doses. Each bone was perfused with a vasoactive drug at a standard physiologic dosage. After 30 min of perfusion, a second norepinephrine dose‐response curve was generated. The degree of attenuation of the norepinephrine dose‐response curve, as determined by the total area under the curve, was interpreted as the relaxation effect of the drug on the smooth muscle of the vascular bed. Prazosin (α1‐receptor antagonist), rauwolszin (α2‐receptor antagonist), propranolol (β‐receptor antagonist), and diltiazem (calcium‐entry inhibitor) were evaluated. Our data suggest that α1 and α2 adrenergic receptor antagonism results in a quantitatively similar attenuation of norepinephrine‐induced vascular smooth muscle contraction. Calcium‐entry antagonism produced less, but significant, attenuation of smooth muscle contractility. Beta‐adrenergic receptor blockade yielded only a slight, although consistent, reduction in reactivity. Simple perfusion with Krebs‐Ringer solution had no effect.
Colony‐forming efficiency response of bone marrow stromal cells to acute blood loss
Authors: Lippiello L. , Chavda D. , Connolly J.
Published: February 2005

Colony‐forming efficiency (CFE) was used to monitor the proliferative response of alkaline phosphatase‐positive rabbit bone marrow stromal cells to acute blood loss. The CFE of animals subjected to a 1% blood loss was 0.97 compared with 0.06 (p < 0.01) in nonbled animals. Sera obtained from animals 10 days after an initial blood loss stimulated the CFE of marrow cultures from nonbled donors to the same degree as osteogenin. Erythropoietin and control sera (from nonbled animals) had no effect. Hence, acute blood loss and sera from bled animals stimulate proliferation of alkaline phosphatase‐positive marrow stromal cell colonies. The agent(s) responsible is unknown but it is present in serum in response to blood loss. Confirmation of a specific effect on osteoprogenitor cells may warrant the designation “osteopoietin”.
The early effects of joint immobilization on medial collateral ligament healing in an ACL‐deficient knee: A gross anatomic and biomechanical investigation in the adult rabbit model
Authors: Bray R. C. , Shrive N. G. , Frank C. B. , Chimich D. D.
Published: February 2005

In this study, the short‐term effects of immobilization on joint damage and medial collateral ligament (MCL) healing were investigated in unstable, anterior cruciate ligament (ACL)‐deficient knees in rabbits. Forty‐six 12‐month‐old female New Zealand white rabbits were separated into three groups. Animals from each group had surgery on their right knees: group I, sham controls (n = 9); group II, complete transection of the ACL and removal of a 4 mm segment (gap injury) of MCL midsubstance with no immobilization of the limb (n = 19); and group III, same injuries to the ACL and MCL (as group II) but with immobilization of the limb (n = 18). No surgical repair of disrupted ligaments was performed. Left knees served as unoperated contralateral controls. All animals were allowed unrestricted cage activity until sacrifice in subgroups at 3, 6, and 14 weeks of healing when biomechanical properties of all MCLs were measured. All knee joints were systematically examined for gross evidence of damage to articular cartilage, menisci, and periarticular soft tissues. To monitor relative in vivo loads on injured limbs during healing, hind‐limb weight bearing was assessed at biweekly intervals. Results indicate that animals in both groups II and III bore relatively lower loads (compared to preinjury values) on their injured hindlimbs. Mechanical testing of MCLs showed only minor changes in sham controls, while group II and III healing MCLs demonstrated significantly lower force and stress at MCL complex failure compared to contralateral controls. In specific comparisons of group III to group II animals, we noted that immobilization prevented joint damage over the early intervals studied. In addition, immobilization resulted in MCL laxity similar to contralateral control values but inhibited development of structural strength and stiffness in healing MCLs. These results suggest that in the rabbit, short‐term immobilization of an ACL‐deficient knee offers some advantages to the joint and to certain low load behaviors of the healing MCL, but it also results in a smaller quantity of scar tissue that is less able to resist higher loads. Longer‐term studies involving remobilization are necessary before the effects of brief immobilization on joint damage and MCL healing in this ACL‐deficient model can be fully defined.
Strain in the anteromedial bundle of the anterior cruciate ligament under combination loading
Authors: Berns Gregory S. , Hull M. L. , Patterson Hugh A.
Published: February 2005

Strain within the anteromedial bundle (AMB) of the anterior cruciate ligament (ACL) was measured in 13 human knee specimens in order to determine the combination of external loads most likely to cause injury. Using a load application system that allowed 5 df with the flexion angle being fixed, pure loads of anterior/posterior force, medial/lateral force, varus/valgus torque, and internal/external axial torque were applied at three flexion angles: 0°, 15°, 30°. Combined loads were applied in pairs at two flexion angles: 0° and 30°. Liquid mercury strain gauges were used to measure strain in the ACL. Anterior tibial force was the primary determinant of strain in the anteromedial bundle. This strain was significantly larger at 30° flexion than at 0°. The strain sensitivity of the AMB to medial force was approximately one‐half that to pure anterior force. The effect of anterior and medial forces was additive when applied in combination. Neither pure axial torque nor pure varus/valgus torque was observed to strain significantly the AMB at any of the flexion angles investigated. However, valgus torque in combination with anterior force resulted in a significantly larger strain than pure anterior force. Internal axial torque in combination with anterior force also resulted in a larger strain than pure anterior force.
Tensile properties of the inferior glenohumeral ligament
Authors: Bigliani Louis U. , Pollock Roger G. , Soslowsky Louis J. , Flatow Evan L. , Pawluk Robert J. , Mow Van C.
Published: February 2005

The tensile properties of the inferior glenohumeral ligament have been determined in 16 freshly frozen cadaver shoulders. The inferior gleno‐humeral ligament was divided into three anatomical regions: a superior band, an anterior axillary pouch, and a posterior axillary pouch. This yielded 48 bone‐ligament‐bone specimens, which were tested to failure in uniaxial tension. The superior band was consistently the thickest region, averaging 2.79 mm. The thickness of the inferior glenohumeral ligament decreased from antero‐superiorly to postero‐inferiorly. The resting length of all three anatomical regions was not statistically different. Total specimen strain to failure for all bone‐ligament‐bone specimens averaged 27%. Variations occurred between the three regions, with the anterior pouch specimens failing at a higher strain (34%) than those from the superior band (24%) or the posterior pouch (23%). Strain to failure for the ligament midsubstance (11%) was found to be significantly less than that for the entire specimen (27%). Thus, larger strain must occur near the insertion sites of the inferior glenohumeral ligament. Stress at failure was found to be nearly identical for the three regions of the ligament, averaging 5.5 MPa. These values are lower than those reported for other soft tissues, such as anterior cruciate ligament and patellar tendon. The anterior pouch was found to be less stiff than the other two regions, perhaps suggesting that it is composed of more highly crimped collagen fibers. Three failure sites were seen for the inferior glenohumeral ligament: the glenoid insertion (40%), the ligament substance (35%), and the humeral insertion (25%). In addition, significant capsular stretching occurred before failure, regardless of the failure mode.
Physicochemical properties of the aging and diabetic sand rat intervertebral disc
Authors: Ziv I. , Moskowitz R. W. , Kraise I. , Adler J. H. , Maroudas A.
Published: February 2005

Hydration, fixed charge density, (FCD) and hydration under various osmotic pressures were compared in young, old, and young diabetic sand rats. This rat is a desert animal that may develop diabetes when fed a regular diet; it is also known to have radiographic and histologic evidence of intervertebral disc (IVD) disease. Forty‐five rats and 180 IVD were used in this study; they were divided into three equal groups: young healthy, old healthy, and young diabetics. IVD, cancellous bone, and muscle were sampled from distal lumbar spines. The young diabetic rats (YD) were considerably heavier than the age‐matched controls, had higher insulin and glucose levels, and all YD had cataracts. The discs of the young diabetic animals demonstrated decreased hydration, FCD and ability to resist compression under osmotic pressures as compared with the young and healthy discs and were more similar to the discs from old rats. The IVD is the most affected musculoskeletal connective tissue in sand rats with aging and diabetes. The aged and diabetic discs in the sand rat demonstrated changes similar to human changes with regard to lower hydration, FCD, and ability to resist osmotic pressure. Therefore, the sand rat may be a suitable animal model for studying the pathogenesis of disc degeneration.
Spinal mobility and posture in 8‐ to 16‐year‐old children
Authors: Mellin Guy , Poussa Mikko
Published: February 2005

Spinal mobility and posture were measured in 294 8‐16‐year‐old boys and girls, divided into five age groups. The upper thoracic sagittal alignment was more vertical among girls, but the postural curves showed no significant age‐related differences for either sex. Among both boys and girls thoracic extension, lateral flexion, and rotation decreased significantly between the ages of 12 and 13, but with the exception of extension they returned to the previous level by age 16. Girls were significantly different from boys at 13 years of age. In the thoracic spine, girls had less kyphosis, and were stiffer in forward and lateral flexion, with more rotation to the right than to the left. In the lumbar spine, lateral flexion increased after the age of 10 in both sexes. Between the ages of 8 and 14 lumbar lateral flexion was significantly greater among girls than among boys, whereas extension and rotation was greater only at the ages of 8 and 10 years. With increasing age, a shift from left to right dominance in lumbar lateral flexion was found in girls only.
Tissue ingrowth into titanium and hydroxyapatite‐coated implants during stable and unstable mechanical conditions
Authors: Søballe Kjeld , Hansen Ebbe S. , B.‐Rasmussen Helle , Jørgensen Peter H. , Bünger Code
Published: February 2005

Lack of initial mechanical stability of cementless prostheses may be responsible for fibrous tissue fixation of prosthetic components to bone. To study the influence of micromovements on bony ingrowth into titanium alloy (Ti) and hydroxyapatite (HA)‐coated implants, a loaded unstable device producing movements of 500 μm during each gait cycle was developed. Mechanically stable implants served as controls. The implants were inserted into the weight‐bearing regions of all four femoral condyles in each of seven mature dogs. Histological analysis after 4 weeks of implantation showed a fibrous tissue membrane surrounding both Ti and HA‐coated implants subjected to micromovements, whereas variable amounts of bony ingrowth were obtained in mechanically stable implants. The pushout test showed that the shear strength of unstable Ti and HA implants was significantly reduced as compared with the corresponding mechanically stable implants (p < 0.01). However, shear strength values of unstable HA‐coated implants were significantly greater than those of unstable Ti implants (p < 0.01) and comparable to those of stable Ti implants. The greatest shear strength was obtained with stable HA‐coated implants, which was threefold stronger as compared with the stable Ti implants (p < 0.001). Quantitative determination of bony ingrowth agreed with the mechanical test except for the stronger anchorage of unstable HA implants as compared with unstable Ti implants, where no difference in bony ingrowth was found. Unstable HA‐coated implants were surrounded by a fibrous membrane containing islands of fibrocartilage with higher collagen concentration, whereas fibrous connective tissue with lower collagen concentration was predominant around unstable Ti implants. In conclusion, micromovements between bone and implant inhibited bony ingrowth and led to the development of a fibrous membrane. The presence of fibrocartilage and a higher collagen concentration in the fibrous membrane may be responsible for the increased shear strength of unstable HA implants. Mechanically stable implants with HA coating had the strongest anchorage and the greatest amount of bony ingrowth.
Fixation stability of femoral components in a canine hip replacement model
Authors: Vanderby Ray , Manley Paul A. , Kohles Sean S. , McBeath Andrew A.
Published: February 2005

A canine hip replacement model was used to compare fixation stability in cemented and cementless femoral components. Parameters of comparison were the load‐induced positional changes of each prosthesis relative to its proximal femoral cortex, hereafter called relative displacements. Identical femoral components, with the proximal third of their stem porous‐coated, were implanted in the right femurs of 10 large, mixed‐breed dogs. Five were tightly fit to allow porous ingrowth, and five were cemented into the medullary canal. Four months after implantation, all femurs were harvested. A prosthesis was implanted in the left (normal) femur of each dog ex vivo with fixation identical to the contralateral limb to simulate acute postoperative fixation. Eddy current transducers measured relative displacements under application of static loads, serially applied in the axial, mediolateral, and craniocaudal directions. Thereafter, the femurs were transversely sectioned and morphologically analyzed to correlate bony apposition at the implant surface with relative displacements. We observed no difference in relative displacements between acute and 4‐month‐cemented groups (e.g., 0.0059 ± 0.0021 vs. 0.0060 ± 0.0048 mm, respectively, for 100‐N axial loading measured at midstem). With cementless implantation, relative displacements of the acute group were significantly larger (p = 0.007) than those of the 4‐month group (e.g., 0.236 ± 0.257 vs. 0.097 ± 0.129 mm, respectively, for 100‐N axial loading measured at midstem). Cementless components implanted for 4 months were not significantly different than cemented components, but a trend suggested that they were still not as stable as cemented components, particularly for craniocaudal loads. Relative displacements of the 4‐month, porous ingrowth group were approximately proportional to the percentage of bony apposition raised to the ‐ 1.44 power (r = 0.94).
Histomorphometric analysis of the epiphyseal growth plate in rats after prenatal alcohol exposure
Authors: Miralles‐Flores Celia , Delgado‐Baeza Emilio
Published: February 2005

We studied the effect of prenatal alcohol exposure on growth in the proximal tibial growth plate in 0‐ and 15‐day‐old rats, using histomorphometric methods. Body weight and tibial length were reduced in all alcohol‐exposed rats. In 15‐day‐old rats, these parameters were lower than in the 15‐day‐old controls, thus showing a persistence of the effects of ethanol. The proximal tibial growth plate showed alterations, principally in 15‐day‐old rats. The most notable of these was a decrease in growth plate height produced by a significant reduction in hypertrophic zone height. Likewise, there were fewer cells in this zone in alcohol‐exposed rats than in controls. This work shows that prenatal ethanol exposure induces growth retardation which may be due to growth plate alterations that might reflect impaired cell function.
Meniscal repair by fibrocartilage? An experimental study in the dog
Authors: Klompmaker Jan , Jansen Henk W. B. , Veth René P. H. , Nielsen Hans K. L. , De Groot Jacqueline H. , Pennings Albert J. , Kuijer Roel
Published: February 2005

Longitudinal lesions in the avascular part of the dog's meniscus were repaired by implantation of a porous polyurethane. Ingrowing repair tissue was characterized by biochemical and immunological analysis. Histologically, repair tissue initially was composed of fibrous tissue containing type I collagen. After 3 months, fibrocartilaginous tissue developed inside the implants, whereas control defects only showed fibrous repair tissue. Both type I and II collagen, the major collagen types of normal meniscal fibrocartilage, could be detected in this newly formed fibrocartilage. It is concluded that fibrocartilage resembling normal meniscal tissue is formed and that longitudinal lesions can be healed after mensical repair by implantation of a porous polymer.
Slow release of anticancer drugs from porous calcium hydroxyapatite ceramic
Authors: Uchida A. , Shinto Y. , Araki N. , Ono K.
Published: February 2005

We have developed a new delivery system for sustained release of an anticancer drug (cis‐platinum) by enclosure into blocks of porous calcium hydroxyapatite ceramic. The slow release of this drug from this system was confirmed in in vitro experiments. When this system was implanted into normal back muscle, or the tibia, sustained release of cis‐platinum was observed during a 12‐week period after implantation. The diffusion rate of cis‐platinum into blood and other organs (liver, kidney, brain) was less than 10% of that at the implanted site. This delivery system placed into experimental tumors of mice also showed a uniform release of anticancer drug for more than 3 months. Inhibition of tumor growth was more marked after local implantation of this system than after intraperitoneal administration of cis‐platinum. These results indicate that this new approach to a drug delivery system may well have an important role in cancer chemotherapy. In bone tumors it is attractive because the mechanical strength of calcium hydroxyapatite ceramic permits partial surgical excision and replacement of the bone defect at the same time.
Immunological analysis of proteoglycan structural changes in the early stage of experimental osteoarthritic canine cartilage lesions
Authors: Pelletier Jean‐Pierre , Martel‐Pelletier Johanne , Mehraban Fuad , Malemud Charles J.
Published: February 2005

Specific modifications of the proteoglycan (PG) structure of osteoarthritic (OA) dog cartilage in relation to endogenous metalloprotease activity were examined using murine anti‐proteoglycan monoclonal antibodies (MoAbs). OA lesions were induced over a period of 8 weeks in crossbred dogs (Pond‐Nuki model). The articular cartilage was removed and homogenized in a Tris buffer, pH 7.5, and then divided into four groups: direct PG extraction, no addition, presence of 1 mM p‐aminophenyl mercuric acetate (APMA), and presence of 1 mM APMA and 10 mM o‐phenanthroline, incubated for 42 h at 37°C followed by PG extraction. MoAbs reactive with PG protein and carbohydrate epitopes included 1C6, 3B3, 5D4, D1B2, and m4D6. The results showed marked alterations induced by APMA activation of the endogenous metalloproteases. PG changes were apparent at at least three sites: one was either in the hyaluronic acid‐binding region or between the hyaluronic‐binding region and the G2 globular domain, another was between the keratan‐sulfate‐rich domain and the chondroitin sulfate‐attachment domain, and a third was in the chondroitin sulfate‐attachment domain. Constitutive metalloprotease activity resulted in less marked PG alterations with preservation of functional PG aggregation to hyaluronan.
Local stimulation of proteoglycan synthesis in articular cartilage explants by dynamic compression in vitro
Authors: Parkkinen Jyrki J. , Lammi Mikko J. , Helminen Heikki J. , Tammi Markku
Published: February 2005

Cultured bovine articular cartilage was subjected to 50 ms, 0.5–1.0 MPa compressions repeated at intervals of 2–60 s for 1.5 h and simultaneously labeled with 35SO4. The compression was delivered with a 4‐mm‐diameter nonporous loading head on an 8‐mm‐diameter cartilage explant. This method created directly compressed (central) and uncompressed (border) areas within the tissue. Analysis of the whole explant under a 0.5 MPa load showed significantly increased 35SO4 incorporation by compression repeated at 2‐ and 4‐s but not at 20‐ and 60‐s intervals. When the incorporation was studied separately in the border and central areas, a statistically significant stimulation was noticed in the central area with a 4‐s cycle, while the border area was stimulated with a 2‐s cycle. Autoradiography of the central area showed that the stimulation with 0.5 MPa and a 4‐s cycle occurred through the whole depth of the cartilage, while raising the pressure to 1 MPa or the frequency to 2 s reduced the stimulation, particularly in the superficial cartilage. In the border area the stimulation with 0.5 MPa and a 2‐s cycle was noted in the superficial zone only. The stimulation of proteoglycan synthesis is thus limited to certain loading frequencies and pressures and occurs in specific areas under and around the loaded site. Its rapid appearance suggests enhanced glycosylation or sulfation of core proteins or enhanced speed of posttranslational processing.
Chemotherapy and surgery in a murine osteosarcoma
Authors: Bell R. S. , Jacobs J.
Published: February 2005

Surgical and chemotherapeutic effects on pulmonary metastatic disease were evaluated in the MGH‐OGS murine osteosarcoma. The tumor responded to three sequential injections of doxorubicin with prolonged growth delay but cisplatin administration (although given in doses sufficient to cause weight loss and significant mortality) was not effective in controlling local disease progression. Using a protocol with three injections of doxorubicin (0.006 mg/g of body weight), it was observed that disease‐free survival was enhanced when one of the three doses of doxorubicin was given at the time of surgery (perioperatively). By marginally resecting the primary tumor and permitting its regrowth, a model was developed with recurrent primary and metastic disease present simultaneously. It was observed in this model that amputation or resection of the recurrent primary lesion resulted in pulmonary metastatic growth acceleration. Using this recurrent primary tumor model, doxorubicin's effect on pulmonary metastatic lesions was enhanced when the drug was given at the time of amputation.
Bone formation near direct current electrodes with and without motion
Authors: Spadaro Joseph A. , Albanese Stephen A. , Chase Sharon E.
Published: February 2005

The osteogenesis induced in the medullary canal of rabbits by the implantation of moving and stationary wire electrodes was studied with and without the simultaneous application of 20‐μA constant direct cathodic current. After 3 weeks, the formation of new trabecular bone in the canal was studied and measured microscopically. Electrically stimulated osteogenesis was not observed at stationary electrodes. As in previous studies with this model, a movable electrode alone stimulated new bone formation whose area was 7–10% of the canal area. The amount of this bone was not statistically increased by the addition of cathode current. Movable, electrically active cathodes were associated, however, with fluid‐filled spaces incorporated within the new trabecular bone. When mechanical stimuli were controlled, we were not able to demonstrate that the direct current stainless steel cathode acts either as an inducer or a substantial enhancer of medullary osteogenesis.
Determination of bone mineral density by dual X‐ray absorptiometry in patients with uncemented total hip arthroplasty
Authors: Kiratli B. Jenny , Heiner John P. , McBeath Andrew A. , Wilson Michael A.
Published: February 2005

Bone remodeling is an expected sequela with total hip arthroplasty (THA). Although there are several methods of estimating bone response in THA patients from radiographs, there are no accurate and generally accepted methods for quantitative determinations in vivo. In this study, we describe an application of dual x‐ray absorptiometry (DXA) for measuring bone mineral content and bone mineral density in the proximal femur following THA. DXA is a noninvasive technique with minimal radiation exposure (<5 mrem). Various aspects of measurement error (accuracy and reliability) of this application of DXA were determined in a series of studies reported here. Accuracy error (how similar are the measured and actual values) was <1% determined in bone phantoms of four densities. Precision error (how reproducible are the measurements) was also <1% at all four densities in the phantoms and was only slightly elevated (0.9‐1.5%) in repeated measurements of implanted cadaver femora. Precision error in vivo, determined both from multiple replicates on five patients and from duplicate scans on 30 patients, was further elevated but remained <5%. Contributions to precision error, rotation of the leg, and interoperator variability were assessed; none was found to elevate precision error appreciably. We suggest that DXA is a feasible method for quantifying bone response following THA, and will allow discrimination of small changes (>5%) not previously measurable.
Effects of material properties of femoral hip components on bone remodeling
Authors: Weinans Harrie , Huiskes Rik , Grootenboer Henk J.
Published: February 2005

Bone loss around femoral hip stems is one of the problems threatening the long‐term fixation of uncemented stems. Many believe that this phenomenon is caused by reduced stresses in the bone (stress shielding). In the present study the mechanical consequences of different femoral stem materials were investigated using adaptive bone remodeling theory in combination with the finite element method. Bone‐remodeling in the femur around the implant and interface stresses between bone and implant were investigated for fully bonded femoral stems. Cemented stems (cobalt‐chrome or titanium alloy) caused less bone resorption and lower interface stresses than uncemented stems made from the same materials. The range of the bone resorption predicted in the simulation models was from 23% in the proximal medial cortex surrounding the cemented titanium alloy stem to 76% in the proximal medial cortex around the uncemented cobalt‐chrome stem. Very little bone resorption was predicted around a flexible, uncemented “iso‐elastic” stem, but the proximal interface stresses increased drastically relative to the stiffer uncemented stems composed of cobalt‐chrome or titanium alloy. However, the proximal interface stress peak was reduced and shifted during the adaptive remodeling process. The latter was found particularly in the stiffer uncemented cobalt‐chrome‐molybdenum implant and less for the flexible isoelastic implant.
Biomechanical effect of a two‐segment anterior cruciate ligament graft with separate femoral attachments and differing levels of prescribed load sharing
Authors: Chao Thomas T. H. , Lew William D. , Lewis Jack L. , Lindquist Conrad , Hong Boyang , Arendt Elizabeth
Published: February 2005

The objective of this study was to analyze the biomechanical effect of varying the level of prescribed load sharing between two segments of an anterior cruciate ligament (ACL) graft, and of separating the femoral attachments of these segments. Total anterior‐posterior (AP) laxity was measured using an instrumented spatial linkage. Forces in graft segments were measured using buckle transducers. The two‐segment graft was formed using the middle third of the patellar tendon with bone blocks and a synthetic augmentation device. Proximal fixation was obtained using a fixture which allowed changing the individual locations of the femoral attachments of the tendon and augmentation segments. Distal fixation was achieved using a force‐setting device which allowed the loads in each segment to be set to prescribed levels. Total graft force, load sharing, and total AP laxity were recorded during the application of 100‐N AP tibial loads at 0°, 30°, 60°, 90°, and 110° flexion, for various combinations of load sharing set at extension and locations of femoral attachment sites. The load sharing, total graft force, and AP laxity during AP loading at the five test flexion angles were not significantly affected by changing the prescribed level of load sharing set at extension for a given femoral attachment configuration. However, varying the separate hole locations of the graft segments for a given level of load sharing significantly affected load sharing, total graft force, and AP laxity. If the tendon graft was located posteriorly (on the medial surface of the lateral femoral condyle) and the augmentation segment proximally, the augmentation carried a greater portion of the total force in flexion. If the augmentation segment was changed to a more posterosuperior location and the tendon posteroinferior, the tendon carried a higher percentage of the total force in flexion. AP laxity in most reconstruction states was significantly greater than in the normal joint with an intact ACL. The nature of the load sharing between the graft segments under AP tibial load over the flexion range can be controlled by the appropriate choice of the segments' femoral attachment locations.
The correlation between anterior‐posterior translation and cross‐sectional area of anterior cruciate ligament reconstructions
Authors: Grood E. S. , Walz‐Hasselfeld K. A. , Holden J. P. , Noyes F. R. , Levy M. S. , Butler D. L. , Jackson D. W. , Drez D. J.
Published: February 2005

Total anterior‐posterior translation is commonly used to assess the integrity of the cruciate ligaments and the success of reconstructive surgery. The purpose of this study was to determine, after surgical reconstruction of the anterior cruciate ligament with a biological graft, if total anterior‐posterior translation correlated with graft length, cross‐sectional area, or mechanical properties. These factors were investigated by analyzing data from three previous studies. These studies involved replacement of the anterior cruciate ligament in cynomolgus monkeys and goats, with free and vascularized patellar tendon autografts and both patellar tendon and anterior cruciate ligament allografts. Data were available at time periods of 6 and 12 months after surgery. We found statistically significant inverse correlations between the amount of anterior‐posterior translation and cross‐sectional area of a graft at the time of sacrifice. The Pearson correlation coefficients ranged from −0.966 (p < 0.002) to −0.830 (p < 0.05). We hypothesize that these correlations result from the following mechanism: the increased anterior translation reflects a slack graft; a slack graft is stress shielded by other structures about the knee; the reduced in vivo stresses on the graft modulate cellular metabolism in a way that over time produces a small cross‐sectional area.
Two processes of bone remodeling in plated intact femora: An experimental study in dogs
Authors: Uhthoff H. K. , Foux A. , Yeadon A. , McAuley J. , Black R. C.
Published: February 2005

Bone loss is known to occur under plates used for internal fixation. Its exact location and extent and its relationship to the plate‐bone contact area was investigated in 36 adult beagles. Plates with two different contact areas were fixed unilaterally to intact femora for periods of 8 and 24 weeks. After removal, the bones were assessed radiographically, histologically, histomorphometrically, and biomechanically. Two processes that affect the bone after plating became apparent. One is a short‐term process, possibly caused by the interference of the plate with the blood supply to the cortex. This is followed by necrosis, which induces porosis. The second independent process is caused by the tendency of the bone to adapt to the new state of mechanical loads that results from the load sharing by the plate. The first stage of this process is expressed through swift changes in the bone cross‐sectional area under the plate by remodeling in all three envelopes: haversian, periosteal, and endosteal. This stage is followed by a gradual remodeling towards a steady state, in which the final cross‐section of the bone is attained. Both processes affected the bone simultaneously during plate fixation. The process caused by the vascular interference ceases after some time, and only the process due to stress‐shielding prevails for a long period.
Complex balance reactions in different sensory conditions: Adolescents with and without idiopathic scoliosis
Authors: Byl Nancy N. , Gray John M.
Published: February 2005

We measured simple and complex balance responses with a force plate stabiliometer in 70 adolescents: 50 with idiopathic scoliosis (IS) and 20 controls. In stable static balance positions, the two groups performed similarly, but when the visual and somatosensory systems were challenged simultaneously, the IS group had a significantly higher mean body sway than the controls. Within the IS group, children with mild, nonprogressive curves that had not been operated on were significantly more likely to maintain their balance when the visual and somatosensory systems were challenged simultaneously than those with curves ≥40°, who had had surgery, and who had more rapid progression of the curve. These findings suggest that adolescents with IS have normal balance in static, stable positions but are not able to perform as well as normal adolescents in sensory‐challenged positions, particularly if they have a severe, progressive curve. Longitudinal studies are needed to determine whether balance dysfunction can be used to predict progression of the curve.
The effects of cisplatin on the incorporation of fresh syngeneic and frozen allogeneic cortical bone grafts
Authors: Zart David J. , Miya Leslie , Wolff David A. , Makley John T. , Stevenson Sharon
Published: February 2005

Allograft transplantation with concomitant chemotherapy has proven successful in the treatment of malignant bone tumors. However, these chemotherapeutic agents may delay tissue healing, resulting in clinical complications. To clarify the effects of cisplatin on the healing of bone grafts, we studied the incorporation of stably fixed massive diaphyseal femoral syngeneic and allogeneic grafts in rats treated with cisplatin. These data were compared with those of historical controls from animals that did not receive cisplatin. Rats that were to receive a fresh syngeneic graft or frozen allogeneic graft were given cisplatin every 4 weeks starting 9 weeks preoperatively and continuing until the time of death. The total bone area of the graft in animals that received cisplatin was smaller than that of the graft in untreated control rats that did not receive cisplatin. The area of the frozen allograft did not increase between 2 and 4 months. Revascularization was incomplete in cisplatin‐treated groups at 2 months, but by 4 months, vessel ingrowth in fresh syngeneic grafts approached control values. Frozen allografts remained poorly revascularized at 4 months. Host‐graft union was poor at 2 months in cisplatin‐treated rats compared with controls. In cisplatin‐treated rats, the host‐graft union of the frozen allograft remained inferior at 4 months while that of the syngeneic graft improved. Allogeneic cortical bone grafts are incorporated more slowly and incompletely than syngeneic grafts, and this handicap is exacerbated by the administration of cisplatin.
Healing of cancellous bone osteotomy in rabbits—Part II: Local reversal of arthritis‐induced osteopenia after osteotomy
Authors: Bogoch E. , Gschwend N. , Rahn B. , Moran E. , Perren S.
Published: February 2005

With use of the intravital bone label calcein, we previously identified, by histomorphometry, greatly increased new bone formation and juxtaarticular osteopenia (a high turnover state) in carrageenan‐induced experimental inflammatory arthritis of the knee in rabbits. In Part I of this paper, we showed that a large increase in new bone formation after a stable incomplete distal femoral condylar osteotomy of normal bone in the rabbit does not increase bone volume (BV) in normal tissue adjacent to the osteotomy (zone 1). In this study, we performed an osteotomy of bone made osteopenic by experimental inflammatory arthritis. After 4 weeks of healing, we examined new bone formation and BV in five zones around the osteotomy. In zone 0 (the osteotomy gap), new bone formation filled the gap to normal BV, as we found for the normal/osteotomy group. In zone 1 (adjacent to but excluding the osteotomy gap), we found greatly increased new bone formation and a return to normal BV, increased from the osteopenic level induced by experimental inflammatory arthritis. In this model, osteotomy apparently reversed the bone‐wasting process of inflammatory arthritis. This effect was not observed in other zones: the lateral condyle that had not been operated on, the metaphysis, or the diaphysis.
The proteoglycans of the cartilaginous end‐plate of the human intervertebral disc change after maturity
Authors: Bishop Paul B. , Pearce Richard H.
Published: February 2005

Lumbar spines collected postmortem were assigned to one of two groups: group 1—three spines with healthy discs, or group 2—three spines with severely degenerated discs. The proteoglycans (PGs) of the cartilaginous end‐plate (CEP) were extracted with 4 M guanidinium chloride containing protease inhibitors and were purified by caesium chloride density gradient ultracentrifugation. On Sepharose CL‐2B chromatography, the most dense 20% of the gradient (the A1 fraction) showed two subfractions, one eluting near the void volume and one partitioned by the gel. Both fractions resembled those of the nucleus pulposus and the anulus fibrosus in the number of components seen on agarose‐polyacrylamide gel electrophoresis. Both fractions changed with ageing/degeneration; the ratio of keratan sulphate to chondroitin sulphate, which was about 1 in group 1, increased to about 3 in group 2; the hydrodynamic volumes fell; the electrophoretically distinguishable component of lowest mobility disappeared while new, highly mobile components appeared; and the water content decreased slightly. Clearly, the PGs of the CEP of degenerated intervertebral discs differed from those of healthy discs; this supports the view that the CEP participates in the process of ageing/degeneration in the disc.
The effect of position of immobilisation on resting length, resting stiffness, and weight of the soleus muscle of the rabbit
Authors: Herbert Robert D. , Balnave Ronald J.
Published: February 2005

The extent of immobilisation‐induced adaptations of muscle length and muscle weight is known to be profoundly influenced by the position (or length) at which the muscle is immobilised. However, the effect of the full range of positions of immobilisation on subsequent adaptations of muscle length and weight has not yet been investigated. To examine further the effect of position of immobilisation, we used cast‐immobilisation of the hind limbs of 23 rabbits, in various positions between full plantar flexion and full dorsi‐flexion. Six muscles from non‐immobilised rabbits were used as the controls. After 10 days of immobilisation, the wet weight of the soleus muscle and the resting length and resting stiffness of the soleus muscle‐tendon unit were determined. Immobilisation in a shortened position was associated with a significantly greater decrease in length and weight than was immobilisation in a lengthened position. In addition, immobilisation produced significant increases in the resting stiffness of muscle‐tendon units, although there was no evidence of a position‐dependent increase in stiffness. Muscle weight was influenced by the position of immobilisation in a nonlinear way. The data support the views that the pre‐immobilisation resting length of the muscle represents a threshold length and that immobilisation at lengths longer than this retards immobilisation‐induced atrophy.