			Home About us Contact

Proximal Tibia (proximal + tibia)

Distribution by Scientific Domains

Medical Sciences	60%
Life Sciences	32%

Selected Abstracts

Postpubertal Architectural Developmental Patterns Differ Between the L3 Vertebra and Proximal Tibia in Three Inbred Strains of Mice,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2008
Helen R Buie
Abstract An understanding of normal microarchitectural bone development patterns of common murine models is needed. Longitudinal, structural, and mineralization trends were evaluated by in vivo ,CT over 12 time points from 6,48 wk of age at the vertebra and tibia of C3H/HeN, C57BL/6, and BALB/C mice. Longitudinal growth occurred rapidly until 8,10 wk, slowed as the growth plate bridged, and fused at 8,10 mo. Structural augmentation occurred through formation of trabeculae at the growth plate and thickening of existing ones. In the vertebrae, BV/TV increased rapidly until 12 wk in all strains. Between 12 and 32 wk, the architecture was stable with BV/TV deviating <1.1%, 1.6%, and 3.4% for the C57BL/6, BALB/C, and C3H/HeN mice. In contrast, the tibial architecture changed continuously but more moderately for BV/TV and TbTh compared with the vertebra and with comparable or larger changes for TbN and TbSp. Age-related trabecular deterioration (decreased BV/TV and TbN; increased TbSp and structure model index) was evident at both sites at 32 wk. In all strains, the cortex continued to develop after trabecular values peaked. The temporal plateau of BMD was variable across mouse strains and site, whereas tissue mineral density was attained at ,6 mo for all sites and strains. Geometric changes at the tibial diaphysis occurred rapidly until 8,10 wk, providing the C57BL/6 mice and C3H/HeN mice with the highest torsional and compressive rigidity, respectively. In summary, key skeletal development milestones were identified, and architectural topology at the vertebra was found to be more stable than at the tibia. [source]

Safety of, and biological and functional response to, a novel metallic implant for the management of focal full-thickness cartilage defects: Preliminary assessment in an animal model out to 1 year

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2006
Carl A. Kirker-Head
Abstract Focal full-thickness cartilage lesions of the human medial femoral condyle (MFC) can cause pain and functional impairment. Affected middle-aged patients respond unpredictably to existing treatments and knee arthroplasty may be required, prompting risk of revision. This study assesses the safety of, and biological and functional response to, a metallic resurfacing implant which may delay or obviate the need for traditional arthroplasty. The anatomic contour of the surgically exposed MFC of six adult goats was digitally mapped and an 11 mm diameter full-thickness osteochondral defect was created. An anchor-based Co,Cr resurfacing implant, matching the mapped articular contour, was implanted. Each goat's contralateral unoperated femorotibial joint was used as a control. Postoperative outcome was assessed by lameness examination, radiography, arthroscopy, synoviocentesis, necropsy, and histology up to 26 (n,=,3) or 52 (n,=,3) weeks. By postoperative week (POW) 4, goats demonstrated normal range of motion, no joint effusion, and only mild lameness in the operated limb. By POW 26 the animals were sound with only occasional very mild lameness. Arthroscopy at POW 14 revealed moderate synovial inflammation and a chondral membrane extending centrally across the implant surface. Radiographs at POWs 14 to 52 implied implant stability in the operated joints, as well as subchondral bone remodeling and mild exostosis formation in the operated and contralateral unoperated joints of some goats. By POW 26, histology revealed new trabecular bone abutting the implant. At POWs 26 and 52 MFC cartilage was metachromatic and intact in the operated and unoperated femorotibial joints. Proximal tibiae of some operated and unoperated limbs demonstrated limited subchondral bone remodeling and foci of articular cartilage fibrillation and thinning. The chondral membrane crossing the prosthesis possessed a metachromatic matrix containing singular and clustered chondrocytes. Our data imply the safety, biocompatibility, and functionality of the implant. Focal articular damage was documented in the operated joints at POWs 26 and 52, but lesions were much reduced over those previously reported in untreated defects. Expanded animal or preclinical human studies are justified. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source]

Donor site morbidity after harvesting of proximal tibia bone

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2006
Yuan-Chien Chen DDS
Abstract Background. Bone-grafting procedures are common in head and neck surgery. Donor site morbidity is an important factor in deciding the site for harvest of cancellous bone. The tibia has been recommended as a harvest site. Use of the proximal tibia as a donor site is associated with few complications. Our present study used proximal tibia bone grafts to reconstruct maxillofacial defects and augment bone volume for implantation. Methods. A retrospective study was undertaken to analyze 40 proximal tibia bone grafts in maxillofacial reconstruction. Minimal follow-up was 6 months. Results. There were no major complications during the follow-up period. Early minor complications (15%) included temporary sensory loss and ecchymosis. Late minor complication (2.5%) was gait disturbance for 2 months. Long-term minor complication (2.5%) was an unsightly scar. Conclusion. The procedure for proximal tibia bone graft is easy, has less operative risk, and results in a lower postoperative morbidity rate. Based on our findings, we believe the proximal tibia offers a reliable site for harvest of sufficient quantities of good-quality cancellous bone. © 2006 Wiley Periodicals, Inc. Head Neck 28:496,500, 2006 [source]

Morphological changes in the shape of the non-pathological bony knee joint with age: a morphometric analysis of the distal femur and proximal tibia in three populations of known age at death

INTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 4 2008
S. D. Stevens
Abstract This study examines possible morphological variation in the knee joint of Homo sapiens with increasing age in ostensively healthy and non-pathological distal femora and proximal tibiae. Throughout the lifetime of each individual, the hard tissue of the knee undergoes considerable remodelling as a response to biomechanical stresses, changes in bone microarchitecture and reduction of bone mineral content as a concomitant of ageing. The knee is also subject to greater levels of degenerative joint disease than any other joint. If death occurs whilst such diseases are in the earliest stages, initial bone changes may not be visually obvious in museum specimens. If such specimens are used for comparative analyses, it is hypothesised that changes might render it problematic if all ages are conglomerated into discrete samples. This study therefore investigates the degree to which the distal femur and proximal tibia change shape during ageing and, if changes are present, whether they are expressed similarly in males and females. It also examines whether changes are of greater magnitude than those morphological differences which might exist between populations. In an example population of African-Americans, results indicate that there is a statistically significant difference in shape between age groups and those differences become progressively greater between the youngest and oldest adults. Results also show that although morphological variation caused by ageing is apparent, those shape differences attributable to sexual dimorphism are more powerful. When two additional populations are analysed jointly with the African-Americans (Caucasian Americans and the European Spitalfields sample), results indicate that inter-population shape differences are considerably greater than differences caused by increasing age. Results imply that it is justifiable to combine specimens of all ages into discrete samples for comparative purposes. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Recovery of Trabecular and Cortical Bone Turnover After Discontinuation of Risedronate and Alendronate Therapy in Ovariectomized Rats

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008
Robyn K Fuchs
Abstract Alendronate (ALN) and risedronate (RIS) are bisphosphonates effective in reducing bone loss and fractures associated with postmenopausal osteoporosis. However, it is uncertain how long it takes bone turnover to be re-established after treatment withdrawal, and whether this differs between the two drugs. The objective of this study was to determine the time required to re-establish normal bone turnover after the discontinuation of ALN and RIS treatment in an animal model of estrogen-deficiency osteoporosis. Two hundred ten, 6-mo-old female Sprague-Dawley rats were ovariectomized and 6 wk later were randomized into baseline controls (n = 10) and four treatment groups (n = 50/group): vehicle-treated controls (CON; 0.3 ml sterile water), ALN (2.4 ,g/kg), low-dose RIS (RIS low; 1.2 ,g/kg), and high-dose RIS (RIS high; 2.4 ,g/kg). Treatments were administered 3 times/wk by subcutaneous injection. Baseline controls were killed at the initiation of treatment. Other groups were treated for 8 wk, and subgroups (n = 10/ treatment group) were killed 0, 4, 8, 12, and 16 wk after treatment was withdrawn. Static and dynamic histological analyses were performed for cortical (tibial diaphysis) and trabecular (proximal tibia and L4 vertebrae) bone. DXA and mechanical testing was performed on the L5 vertebra. After 8 wk of treatment, trabecular bone turnover rates were significantly suppressed in all drug-treated animals. Trabecular bone formation rate (BFR/BS) remained significantly lower than vehicle in bisphosphonate-treated animals through 12 wk. Sixteen weeks after treatment withdrawal, trabecular BFR/BS in the proximal tibia was re-established in animals treated with RIS but not in animals treated with ALN compared with controls. BMD of the fifth lumbar vertebra remained significantly higher than controls 16 wk after treatment withdrawal in ALN-treated animals but not in RIS-treated animals. Despite reductions in BMD and increases in bone turnover, ultimate force of the fifth lumbar vertebra remained significantly higher in all drug-treated animals through 16 wk after withdrawal. [source]

IGF-I Receptor Is Required for the Anabolic Actions of Parathyroid Hormone on Bone,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2007
Yongmei Wang
Abstract We showed that the IGF-IR,null mutation in mature osteoblasts leads to less bone and decreased periosteal bone formation and impaired the stimulatory effects of PTH on osteoprogenitor cell proliferation and differentiation. Introduction: This study was carried out to examine the role of IGF-I signaling in mediating the actions of PTH on bone. Materials and Methods: Three-month-old mice with an osteoblast-specific IGF-I receptor null mutation (IGF-IR OBKO) and their normal littermates were treated with vehicle or PTH (80 ,g/kg body weight/d for 2 wk). Structural measurements of the proximal and midshaft of the tibia were made by ,CT. Trabecular and cortical bone formation was measured by bone histomorphometry. Bone marrow stromal cells (BMSCs) were obtained to assess the effects of PTH on osteoprogenitor number and differentiation. Results: The fat-free weight of bone normalized to body weight (FFW/BW), bone volume (BV/TV), and cortical thickness (C.Th) in both proximal tibia and shaft were all less in the IGF-IR OBKO mice compared with controls. PTH decreased FFW/BW of the proximal tibia more substantially in controls than in IGF-IR OBKO mice. The increase in C.Th after PTH in the proximal tibia was comparable in both control and IGF-IR OBKO mice. Although trabecular and periosteal bone formation was markedly lower in the IGF-IR OBKO mice than in the control mice, endosteal bone formation was comparable in control and IGF-IR OBKO mice. PTH stimulated endosteal bone formation only in the control animals. Compared with BMSCs from control mice, BMSCs from IGF-IR OBKO mice showed equal alkaline phosphatase (ALP)+ colonies on day 14, but fewer mineralized nodules on day 28. Administration of PTH increased the number of ALP+ colonies and mineralized nodules on days 14 and 28 in BMSCs from control mice, but not in BMSCs from IGF-IR OBKO mice. Conclusions: Our results indicate that the IGF-IR null mutation in mature osteoblasts leads to less bone and decreased bone formation, in part because of the requirement for the IGF-IR in mature osteoblasts to enable PTH to stimulate osteoprogenitor cell proliferation and differentiation. [source]

Ovariectomy-Induced Bone Loss Varies Among Inbred Strains of Mice,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005
Mary L Bouxsein PhD
Abstract There is a subset of women who experience particularly rapid bone loss during and after the menopause. However, the factors that lead to this enhanced bone loss remain obscure. We show that patterns of bone loss after ovariectomy vary among inbred strains of mice, providing evidence that there may be genetic regulation of bone loss induced by estrogen deficiency. Introduction: Both low BMD and increased rate of bone loss are risk factors for fracture. Bone loss during and after the menopause is influenced by multiple hormonal factors. However, specific determinants of the rate of bone loss are poorly understood, although it has been suggested that genetic factors may play a role. We tested whether genetic factors may modulate bone loss subsequent to estrogen deficiency by comparing the skeletal response to ovariectomy in inbred strains of mice. Materials and Methods: Four-month-old mice from five inbred mouse strains (C3H/HeJ, BALB/cByJ, CAST/EiJ, DBA2/J, and C57BL/6J) underwent ovariectomy (OVX) or sham-OVX surgery (n = 6-9/group). After 1 month, mice were killed, and ,CT was used to compare cortical and trabecular bone response to OVX. Results: The effect of OVX on trabecular bone varied with mouse strain and skeletal site. Vertebral trabecular bone volume (BV/TV) declined after OVX in all strains (,15 to ,24%), except for C3H/HeJ. In contrast, at the proximal tibia, C3H/HeJ mice had a greater decline in trabecular BV/TV (,39%) than C57BL/6J (,18%), DBA2/J (,23%), and CAST/EiJ mice (,21%). OVX induced declines in cortical bone properties, but in contrast to trabecular bone, the effect of OVX did not vary by mouse strain. The extent of trabecular bone loss was greatest in those mice with highest trabecular BV/TV at baseline, whereas cortical bone loss was lowest among those with high cortical bone parameters at baseline. Conclusions: We found that the skeletal response to OVX varies in a site- and compartment-specific fashion among inbred mouse strains, providing support for the hypothesis that bone loss during and after the menopause is partly genetically regulated. [source]

Capsaicin-Sensitive Sensory Neurons Contribute to the Maintenance of Trabecular Bone Integrity,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2005
Sarah C Offley
Abstract This investigation used capsaicin to selectively lesion unmyelinated sensory neurons in rats. Neuronal lesioning induced a loss of trabecular integrity, reduced bone mass and strength, and depleted neuropeptides in nerve and bone. These data suggest that capsaicin-sensitive sensory nerves contribute to trabecular bone integrity. Introduction: Familial dysautomia is an autosomal recessive disease in which patients suffer from unmyelinated sensory neuron loss, reduced BMD, and frequent fractures. It has been proposed that the loss of neurotransmitters synthesized by unmyelinated neurons adversely affects bone integrity in this hereditary syndrome. The purpose of this study was to determine whether small sensory neurons are required for the maintenance of bone integrity in rats. Materials and Methods: Ten-month-old male Sprague-Dawley rats were treated with either capsaicin or vehicle. In vivo DXA scanning and ,CT scanning, and histomorphometry were used to evaluate BMD, structure, and cellular activity. Bone strength was measured in distal femoral sections. Body weight and gastrocnemius/soleus weights were measured and spontaneous locomotor activity was monitored. Peroneal nerve morphometry was evaluated using light and electron microscopy. Substance P and calcitonin gene-related peptide (CGRP) content in the sciatic nerve and proximal tibia were determined by enzyme immunoassay (EIA). Substance P signaling was measured using a sciatic nerve stimulation extravasation assay. Results: Four weeks after capsaicin treatment, there was a loss of BMD in the metaphyses of the tibia and femur. In the proximal tibia, the osteoclast number and surface increased, osteoblast activity and bone formation were impaired, and trabecular bone volume and connectivity were diminished. There was also a loss of bone strength in the distal femur. No changes occurred in body weight, 24-h grid-crossing activity, weight bearing, or muscle mass after capsaicin treatment, indicating that skeletal unloading did not contribute to the loss of bone integrity. Capsaicin treatment destroyed 57% of the unmyelinated sensory axons, reduced the substance P and CGRP content in the sciatic nerve and proximal tibia, and inhibited neurogenic extravasation. Conclusion: These results support the hypothesis that capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity. Capsaicin-sensitive neurons have efferent functions in the tissues they innervate, effects mediated by transmitters released from the peripheral nerve terminals. We postulate that the deleterious effects of capsaicin treatment on trabecular bone are mediated by reductions in local neurotransmitter content and release. [source]

Chondrosarcoma in Association With Primary Hyperparathyroidism,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2004
Ajay Bhatia
Abstract We describe two female patients, 66 and 36 years of age, with both primary hyperparathyroidism and chondrosarcoma. Case 1 had a chondrosarcoma of the right scapula, and case 2 had chondrosarcoma of the left proximal tibia. Both patients underwent surgical resection of their chondrosarcoma and subsequent parathyroid surgery. Histological analysis of the excised parathyroid in case 1 showed a parathyroid carcinoma and in case 2 showed a parathyroid adenoma. Including these two patients, there is now a total of six cases that have been reported in the literature describing the association between hyperparathyroidism and bone malignancy. We believe that this small number makes it unlikely that there is an association between these two conditions, although we speculate that there may be an underlying genetic basis. [source]

Climbing Exercise Increases Bone Mass and Trabecular Bone Turnover Through Transient Regulation of Marrow Osteogenic and Osteoclastogenic Potentials in Mice,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 11 2003
Toshiharu Mori
Abstract To investigate the relationship between the effects of bone turnover and bone marrow cell development in bone cells, we developed a mouse voluntary climbing exercise model. Climbing exercise increased bone volume and transient osteogenic potential of bone marrow. This model would be suitable for investigating the mechanistic roles of mechanical loading. Introduction: The relationship between bone mass gain and local bone formation and resorption in mechanically loaded bone is not well understood. Materials and Methods: Sixty-five C57BL/6J mice, 8 weeks of age, were assigned to five groups: a baseline control and two groups each of ground control and climbing exercise mice for 2 and 4 weeks. Mice were housed in a 100-cm tower and had to climb toward a bottle placed at the top to drink water. Results: Compared with the ground control, bone mineral density of the left femur increased in the climbing mice at 4 weeks. At 2 and 4 weeks, bone formation rate (BFR/BS) of periosteal surface, the cross-sectional area, and moment of inertia were increased in the climbing mice, whereas BFR/BS and eroded surface (ES/BS) of endosteal surface did not differ. The trabecular bone volume (BV/TV) of the proximal tibia increased in climbing mice, and osteoclast surface (Oc.S/BS) and osteoclast number decreased at 2 weeks. At 4 weeks, there were increases in BV/TV and parameters of bone formation, including mineralized surface, mineral apposition rate, and bone formation rate. In marrow cell cultures from the tibia, the number of alkaline phosphatase+ colony forming units-fibroblastic and the area of mineralized nodule formation in climbing mice were increased, and the number of osteoclast-like TRACP+ multinucleated cells was lower at 2 weeks. At 4 weeks, these parameters recovered to the levels of the ground controls. Conclusion: Our results indicate that climbing increased trabecular bone volume and reduced bone resorption, with a subsequent increase in bone formation. Intermittent climbing downregulates marrow osteoclastogenic cells and upregulates osteogenic cells initially, but further exercise seemed to desensitize them. Cortical envelopes were enlarged earlier, but the response seems to differ from trabecular bone. [source]

Insulin-Like Growth Factor I Is Required for the Anabolic Actions of Parathyroid Hormone on Mouse Bone,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2002
Daniel D. Bikle M.D., Ph.D.
Abstract Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 ,g/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH. [source]

The Skeletal Structure of Insulin-Like Growth Factor I-Deficient Mice

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2001
Daniel Bikle
Abstract The importance of insulin-like growth factor I (IGF-I) for growth is well established. However, the lack of IGF-I on the skeleton has not been examined thoroughly. Therefore, we analyzed the structural properties of bone from mice rendered IGF-I deficient by homologous recombination (knockout [k/o]) using histomorphometry, peripheral quantitative computerized tomography (pQCT), and microcomputerized tomography (,CT). The k/o mice were 24% the size of their wild-type littermates at the time of study (4 months). The k/o tibias were 28% and L1 vertebrae were 26% the size of wild-type bones. Bone formation rates (BFR) of k/o tibias were 27% that of the wild-type littermates. The k/o bones responded normally to growth hormone (GH; 1.7-fold increase) and supranormally to IGF-I (5.2-fold increase) with respect to BFR. Cortical thickness of the proximal tibia was reduced 17% in the k/o mouse. However, trabecular bone volume (bone volume/total volume [BV/TV]) was increased 23% (male mice) and 88% (female mice) in the k/o mice compared with wild-type controls as a result of increased connectivity, increased number, and decreased spacing of the trabeculae. These changes were either less or not found in L1. Thus, lack of IGF-I leads to the development of a bone structure, which, although smaller, appears more compact. [source]

Moderate Alcohol Consumption Suppresses Bone Turnover in Adult Female Rats

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2001
R. T. Turner
Abstract Chronic alcohol abuse is a major risk factor for osteoporosis but the effects of moderate drinking on bone metabolism are largely uninvestigated. Here, we studied the long-term dose-response (0, 3, 6, 13, and 35% caloric intake) effects of alcohol on cancellous bone in the proximal tibia of 8-month-old female rats. After 4 months of treatment, all alcohol-consuming groups of rats had decreased bone turnover. The inhibitory effects of alcohol on bone formation were dose dependent. A reduction in osteoclast number occurred at the lowest level of consumption but there were no further reductions with higher levels of consumption. An imbalance between bone formation and bone resorption at higher levels of consumption of alcohol resulted in trabecular thinning. Our observations in rats raise the concern that moderate consumption of alcoholic beverages in humans may reduce bone turnover and potentially have detrimental effects on the skeleton. [source]

Hormonal and Biochemical Parameters and Osteoporotic Fractures in Elderly Men

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2000
Dr. Jacqueline R. Center
Abstract Low testosterone has been associated with hip fracture in men in some studies. However, data on other hormonal parameters and fracture outcome in men is minimal. This study examined the association between free testosterone (free T) estradiol (E2), sex hormone-binding globulin (SHBG), 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and fracture in 437 elderly community-dwelling men. Age, height, weight, quadriceps strength, femoral neck bone mineral density (FN BMD), and fracture data (1989,1997) also were obtained. Fractures were classified as major (hip, pelvis, proximal tibia, multiple rib, vertebral, and proximal humerus) or minor (remaining distal upper and lower limb fractures). Fifty-four subjects had a fracture (24 major and 30 minor). There was no association between minor fractures and any hormonal parameter. Risk of major fracture was increased 2-fold for each SD increase in age, decrease in weight and height, and increase in SHBG, and risk of major fracture was increased 3-fold for each SD decrease in quadriceps strength, FN BMD, and 25(OH)D (univariate logistic regression). Independent predictors of major fracture were FN BMD, 2.7 (1.5,4.7; odds ratio [OR]) and 95% confidence interval [CI]); 25(OH)D, 2.8 (1.5,5.3); and SHBG, 1.7 (1.2,2.4). An abnormal value for three factors resulted in a 30-fold increase in risk but only affected 2% of the population. It is not immediately apparent how 25(OH)D and SHBG, largely independently of BMD, may contribute to fracture risk. They may be markers for biological age or health status not measured by methods that are more traditional and as such may be useful in identifying those at high risk of fracture. [source]

Generation of tendon-to-bone interface "enthesis" with use of recombinant BMP-2 in a rabbit model

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2007
Yusuke Hashimoto
Abstract The anatomical structure at bone-tendon and bone-ligament interfaces is called the enthesis. Histologically, the enthesis is characterized by a transitional series of tissue layers from the end of the tendon to bone, including tendon, fibrocartilage, calcified fibrocartilage, and bone. This arrangement yields stronger direct connection of the soft tissues to bone. In surgical repair, the enthesis has proven difficult to reproduce, and the success of ligament-bone bonding has depended on the fibrous attachment that forms after any ligament reconstructions. In this study, we attempted to generate a direct-insertion enthesis in two stages. First, recombinant human bone morphogenetic protein-2 (rhBMP-2) was injected into the flexor digitorum communis tendon in the rabbit hind limb to induce ectopic ossicle formation. In a second step, the resultant tendon/ossicle complex was then surgically transferred onto the surface of the rabbit tibia to generate a stable tendon-bone junction. One month following surgery, histomorphological examination confirmed direct insertion of tendon-bone structures in the proximal tibia of the rabbit. Ultimate failure loads of the BMP-2-generated tendon-bone junction were significantly higher than in the control group (p,<,0.01). These findings suggest that it is possible to successfully regenerate a direct tendon-to-bone enthesis. Use of this approach may enable successful reconstruction of joints rendered unstable after ligamentous rupture or laxity after anterior cruciate ligament injury. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1415,1424, 2007 [source]

Nonweight-bearing anterior knee laxity is related to anterior tibial translation during transition from nonweight bearing to weight bearing

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2006
Sandra J. Shultz
Abstract We examined the relationship between anterior knee laxity (AKL), evaluated while the knee was nonweight bearing, and anterior translation of the tibia relative to the femur (ATT), evaluated when the knee transitioned from nonweight-bearing to weight-bearing conditions in response to an applied compressive load at the foot. Twenty subjects with normal knees (10 M, 10 F; 25.2,±,4.1 years, 169.8,±,11.5 cm, 71.6,±,16.9 kg) underwent measurements of AKL and ATT of the right knee on 2 days. AKL was measured at 133N with the KT-2000Ô. ATT was measured with the Vermont Knee Laxity Device and electromagnetic position sensors attached to the patella and the anteromedial aspect of the proximal tibia. Three trials for each measure were averaged and analyzed. Measurement consistency was high for both AKL (ICC,=,0.97; SEM,=,0.44 mm) and ATT (ICC,=,0.88; SEM,=,0.84 mm). Linear regression revealed that AKL predicted 35.5% of the variance in ATT (p,=,0.006), with a prediction equation of YATT,=,3.20,+,0.543(XAKL). Our findings suggest that increased AKL is associated with increased ATT as the knee transitions from nonweight-bearing to weight-bearing conditions. The potential for increased knee joint laxity to disrupt normal knee biomechanics during activities such as landing from a jump, or the foot strike phase of gait deserves further study. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:516,523, 2006 [source]

Repair of porcine articular cartilage defect with autologous chondrocyte transplantation

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2005
Hongsen Chiang
Abstract Articular cartilage is known to have poor healing capacity after injury. Autologous chondral grafting remains the mainstay to treat well-defined, full-thickness, symptomatic cartilage defects. We demonstrated the utilization of gelatin microbeads to deliver autologous chondrocytes for in vivo cartilage generation. Chondrocytes were harvested from the left forelimbs of 12 Lee-Sung pigs. The cells were expanded in monolayer culture and then seeded onto gelatin microbeads or left in monolayer. Shortly before implantation, the cell-laden beads were mixed with collagen type I gel, while the cells in monolayer culture were collected and re-suspended in culture medium. Full-thickness cartilage defects were surgically created in the weight-bearing surface of the femoral condyles of both knees, covered by periosteal patches taken from proximal tibia, and sealed with a porcine fibrin glue. In total, 48 condyles were equally allotted to experimental, control, and null groups that were filled beneath the patch with chondrocyte-laden beads in gel, chondrocytes in plain medium solution, or nothing, respectively. The repair was examined 6 months post-surgery on the basis of macroscopic appearance, histological scores based on the International Cartilage Repair Society Scale, and the proportion of characteristic chondrocytes. Tensile stress-relaxation behavior was determined from uniaxial indentation tests. The experimental group scored higher than the control group in the categories of matrix nature, cell distribution pattern, and absence of mineralization, with similar surface smoothness. Both the experimental and control groups were superior to the null group in the above-mentioned categories. Viable cell populations were equal in all groups, but the proportion of characteristic chondrocytes was highest in the experimental group. Matrix stiffness was ranked as null > native cartilage > control > experimental group. Transplanted autologous chondrocytes survive and could yield hyaline-like cartilage. The application of beads and gel for transplantation helped to retain the transferred cells in situ and maintain a better chondrocyte phenotype. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source]

The distal superficial femoral arterial branch to the sartorius muscle as a recipient vessel for soft tissue defects around the knee: Anatomic study and clinical applications

MICROSURGERY, Issue 6 2009
Fernando A. Herrera M.D.
Complex wounds surrounding the knee and proximal tibia pose a significant challenge for the reconstructive surgeon. Most of these defects can be managed using local or regional flaps alone. However, large defects with a wide zone of injury frequently require microvascular tissue transfers to aid in soft tissue coverage and closure of large cavities. We describe a unique recipient vessel for microvascular anastomosis for free flap reconstruction involving the knee and proximal tibia through anatomic and clinical studies. © 2009 Wiley-Liss, Inc. Microsurgery 2009. [source]

Patterns in ontogeny of human trabecular bone from SunWatch Village in the Prehistoric Ohio Valley: General features of microarchitectural change

AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2009
James H. Gosman
Abstract Although adult skeletal morphological variation is best understood within the framework of age-related processes, relatively little research has been directed towards the structure of and variation in trabecular bone during ontogeny. We report here new quantitative and structural data on trabecular bone microarchitecture in the proximal tibia during growth and development, as demonstrated in a subadult archaeological skeletal sample from the Late Prehistoric Ohio Valley. These data characterize the temporal sequence and variation in trabecular bone structure and structural parameters during ontogeny as related to the acquisition of normal functional activities and changing body mass. The skeletal sample from the Fort Ancient Period site of SunWatch Village is composed of 33 subadult and three young adult proximal tibiae. Nondestructive microCT scanning of the proximal metaphyseal and epiphyseal tibia captures the microarchitectural trabecular structure, allowing quantitative structural analyses measuring bone volume fraction, degree of anisotropy, trabecular thickness, and trabecular number. The microCT resolution effects on structural parameters were analyzed. Bone volume fraction and degree of anisotropy are highest at birth, decreasing to low values at 1 year of age, and then gradually increasing to the adult range around 6,8 years of age. Trabecular number is highest at birth and lowest at skeletal maturity; trabecular thickness is lowest at birth and highest at skeletal maturity. The results of this study highlight the dynamic sequential relationships between growth/development, general functional activities, and trabecular distribution and architecture, providing a reference for comparative studies. Am J Phys Anthropol, 2009. © 2008 Wiley-Liss, Inc. [source]

Hindlimb adaptations in Ourayia and Chipetaia, relatively large-bodied omomyine primates from the Middle Eocene of Utah

AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2006
Rachel H. Dunn
Abstract North American omomyids represent a tremendous Eocene radiation of primates exhibiting a wide range of body sizes and dietary patterns. Despite this adaptive diversity, relatively little is known of the postcranial specializations of the group. Here we describe hindlimb and foot bones of Ourayia uintensis and Chipetaia lamporea that were recovered from the Uinta B member (early Uintan Land Mammal Age), Uinta Formation, Utah. These specimens provide insights into the evolution of postcranial adaptations across different body sizes and dietary guilds within the Eocene primate radiation. Body mass estimates based on talar measurements indicate that Ourayia uintensis and Chipetaia lamporea weighed about 1,500,2,000 g and 500,700 g, respectively. Skeletal elements recovered for Ourayia include the talus, navicular, entocuneiform, first metatarsal, and proximal tibia; bones of Chipetaia include the talus, navicular, entocuneiform, and proximal femur. Both genera had opposable grasping big toes, as indicated by the saddle-shaped joint between the entocuneiform and first metatarsal. Both taxa were arboreal leapers, as indicated by a consistent assemblage of characters in all represented bones, most notably the somewhat elongated naviculars, the high and distinct trochlear crests of the talus, the posteriorly oriented tibial plateau (Ourayia), and the cylindrical head of the femur (Chipetaia). The closest resemblances to Ourayia and Chipetaia are found among the Bridger omomyines, Omomys and Hemiacodon. The results of our comparisons suggest that the later, larger, more herbivorous omomyines from Utah retained a skeletal structure characteristic of earlier, smaller North American omomyids. Am J Phys Anthropol, 2006. © 2006 Wiley-Liss, Inc. [source]

Age- and site-specific decline in insulin-like growth factor-I receptor expression is correlated with differential growth plate activity in the mouse hindlimb

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 4 2007
Maria A. Serrat
Abstract The proximal and distal growth plates of the principal long bones do not contribute equally to longitudinal growth. Most forelimb elongation occurs at the shoulder and wrist, while most hindlimb growth occurs at the knee. This study examined whether insulin-like growth factor-I (IGF-I), a potent growth regulator, could underlie this variation via differential receptor expression. The spatiotemporal distribution of the IGF-I receptor (IGF-IR) was mapped in hindlimb growth plates (overall and within regional zones) from immature mice using immunohistochemistry. Growth activity was assessed by size/morphology of the growth plate and proliferating cell nuclear antigen (PCNA) expression. Both IGF-IR and PCNA staining declined considerably with age in the proximal femur and distal tibia (hip and ankle), but expression remained high in the more active distal femur and proximal tibia (knee) throughout growth. Growth plate size decreased with age in all sites, but the absolute and relative decline in IGF-IR in the hips and ankles of older mice indicated a site-specific loss of IGF-I sensitivity in these less active regions. These results suggest that regulation of the IGF-IR may at least partially mediate differential long bone growth, thereby providing a local mechanism for altering skeletal proportions absent modification of systemic hormone levels. Anat Rec, 2007. © 2007 Wiley-Liss, Inc. [source]

Proliferative remodeling of the spatial organization of human superficial chondrocytes distant from focal early osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 2 2010
Bernd Rolauffs
Objective Human superficial chondrocytes show distinct spatial organizations, and they commonly aggregate near osteoarthritic (OA) fissures. The aim of this study was to determine whether remodeling or destruction of the spatial chondrocyte organization might occur at a distance from focal (early) lesions in patients with OA. Methods Samples of intact cartilage (condyles, patellofemoral groove, and proximal tibia) lying distant from focal lesions of OA in grade 2 joints were compared with location-matched nondegenerative (grade 0,1) cartilage samples. Chondrocyte nuclei were stained with propidium iodide, examined by fluorescence microscopy, and the findings were recorded in a top-down view. Chondrocyte arrangements were tested for randomness or significant grouping via point pattern analyses (Clark and Evans Aggregation Index) and were correlated with the OA grade and the surface cell densities. Results In grade 2 cartilage samples, superficial chondrocytes were situated in horizontal patterns, such as strings, clusters, pairs, and singles, comparable to the patterns in nondegenerative cartilage. In intact cartilage samples from grade 2 joints, the spatial organization included a novel pattern, consisting of chondrocytes that were aligned in 2 parallel lines, building double strings. These double strings correlated significantly with an increased number of chondrocytes per group and an increased corresponding superficial zone cell density. They were observed in all grade 2 condyles and some grade 2 tibiae, but never in grade 0,1 cartilage. Conclusion This study is the first to identify a distinct spatial reorganization of human superficial chondrocytes in response to distant early OA lesions, suggesting that proliferation had occurred distant from focal early OA lesions. This spatial reorganization may serve to recruit metabolically active units as an attempt to repair focal damage. [source]

Morphological changes in the shape of the non-pathological bony knee joint with age: a morphometric analysis of the distal femur and proximal tibia in three populations of known age at death

Modulation of vertebral and tibial growth by compression loading: Diurnal versus full-time loading

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2005
Ian A. Stokes
Abstract Purpose: This study was designed to determine whether the amount of endochondral growth response to mechanical compression and the underlying growth mechanism differed with night-time or day-time loading, relative to full-time loading. Methods: Mechanical compression (nominally 0.1 MPa stress) was applied across tibial and tail vertebral growth plates of growing Sprague,Dawley rats. Four groups of animals (five per group) were used: 24/24 h (full-time loading); 12/24 h (day-loading); 12/24 h (night-loading); and 0/24 h (sham instrumented). Contralateral tibiae and adjacent vertebrae served as within-animal controls. The animals were euthanized after eight days. Growth plates were processed for quantitative histology to measure 24-h growth, total and BrdU-positive proliferative zone chondrocyte counts, and hypertrophic chondrocytic enlargement in the growth direction. Results: Growth as a percentage of within-animal control averaged 82% (full-time); 93% (day-loading); 90% (night-loading); 100% (sham) for vertebrae. For proximal tibiae it averaged 70% (full-time); 84% (day-loading); 86% (night-loading); 89% (sham). Reduced amount of hypertrophic chondrocytic enlargement explained about half of this effect in full-time loaded growth plates, but was not significantly altered in half-time loaded growth plates. The remaining variation in growth was apparently explained by reduced total numbers of proliferative zone chondrocytes. These findings indicate that sustained compression loading suppressed growth more than intermittent loading at both anatomical locations. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source]

Patterns in ontogeny of human trabecular bone from SunWatch Village in the Prehistoric Ohio Valley: General features of microarchitectural change

Effects of a novel calcium titanate coating on the osseointegration of blasted endosseous implants in rabbit tibiae

CLINICAL ORAL IMPLANTS RESEARCH, Issue 3 2007
Jo-Young Suh
Abstract Objective: The purpose of this study was to investigate the effects of a nanostructured calcium coating on the surfaces of blasted Ti implants on peri-implant bone formation in the rabbit tibiae. Material and methods: Threaded implants (3.75 mm in diameter, 6 mm in length) were roughened by hydroxyapatite (HA) blasting (control; blasted implants). The implants were then hydrothermally treated in a Ca-containing solution for 24 h to prepare Ca-incorporated Ti surfaces (experimental; blasted/Ca implants). Surface characterizations were performed by scanning electron microscopy and stylus profilometry before and after Ca coating. Forty-two implants (21 control and 21 experimental) were placed in the proximal tibiae of seven New Zealand White rabbits. Each rabbit received six implants. To evaluate the effects of the nanostructured Ca coating on the peri-implant bone-healing response, removal torque tests and histomorphometric analyses were performed 6 weeks after surgery. Results: The Ca coating did not significantly change the surface properties produced by blasting at the micron level. Histologically, active bone apposition was observed in the blasted/Ca implants in the marrow space. Compared with the blasted implants, the blasted/Ca implants showed significantly increased bone-to-implant contact over the total implant length (P<0.01) and greater mean removal torque values (P<0.05). Discussion and conclusion: The nanostructured, Ca-incorporated surface significantly enhanced the peri-implant bone-healing response of HA-blasted Ti implants. It may be concluded that the use of nanostructured, Ca-coated surfaces may have synergic effects in enhancing osseointegration of blasted Ti implants due to their micron-scaled surface properties and biologically active surface chemistry. [source]

A Vacuolar ATPase Inhibitor, FR167356, Prevents Bone Resorption in Ovariectomized Rats With High Potency and Specificity: Potential for Clinical Application,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005
Kazuaki Niikura MS
Abstract FR167356, a novel inhibitor of vacuolar ATPase, has high potency against osteoclast V-ATPase and low potency against lysosomal V-ATPase. FR167356 is the first compound of this nature to be tested. It has the potential to be useful for clinical application. Introduction: It has been suggested that the key issue regarding the therapeutic usefulness of V-ATPase inhibitors is their selectivity. Materials and Methods: In in vitro and in vivo studies, we compared FR167356 with other vacuolar ATPase (V-ATPase) inhibitors, bafilomycin A1 and SB242784. H+ transport by various membrane vesicles was assayed by measuring uptake of acridine orange. Inhibitory activity against in vitro bone resorption was examined by measuring the Ca2+ release from cultured calvariae. In vivo, hypercalcemia was induced by retinoic acid in thyroparathyroidectomized-ovariectomized rats, and the effect on serum Ca2+ level was assessed. Ovariectomized rats were treated with FR167356 or SB242784. One week after surgery, free deoxypyridinoline levels in 24-h urine samples, which were collected from 6 h after administration of FR167356, were measured by ELISA. After 4 weeks of treatment, plasma biochemical parameters were analyzed. BMD of the distal femur metaphysis was measured with pQCT. Histomorphometric analysis of the proximal tibias was performed. Blood gases of rats treated with FR167356 were measured with a blood gas analyzer for estimating the effect of FR167356 on in vivo function of renal V-ATPase. Results: FR167356, which is distinctly different from other V-ATPase inhibitors, has a high potency against osteoclast V-ATPase and low potency against lysosomal V-ATPase. Similarly, FR167356 inhibited bone resorption in vitro when stimulated by PTH, IL-1, and IL-6. FR167356 reduced retinoic acid-induced hypercalcemia in thyroparathyroidectomized-ovariectomized rats in a dose-dependent manner. Moreover, FR167356 was shown to restore BMD of ovariectomized rats caused by the inhibition of bone resorption. Ovariectomized rats treated with FR167356 did not show adverse symptoms, whereas SB242784 caused a decrease in body weight gain and significant changes in two plasma biochemical parameters. Interestingly, FR167356 treatment did not affect blood acid-base balance; however, FR167356 inhibited renal V-ATPase with a similar potency as for osteoclast V-ATPase inhibition. Conclusion: Comparison of FR167356 with SB242784 implies that the characteristics of FR167356 may be more appropriate for clinical application as a V-ATPase inhibitor. [source]

Role of Inducible Nitric Oxide Synthase in Skeletal Adaptation to Acute Increases in Mechanical Loading,,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2002
Makoto Watanuki M.D.
Abstract To clarify the role of nitric oxide (NO) in regulation of bone metabolism in response to skeletal loading, we examined inducible NO synthase (iNOS) gene knockout mice in the tail-suspension model. Histomorphometric analyses of proximal tibias revealed that 7 days of tail suspension decreased the bone volume (BV/TV) and bone formation rate (BFR/BS) and increased the osteoclast surface (Oc.S/BS) in mice with all iNOS genotypes. Both iNOS+/+ and iNOS+/, mice responded to subsequent 14-day reloading, with increases in BV/TV and BFR/BS and a decrease in Oc.S/BS, whereas these responses were abolished in iNOS,/, mice. The osteoblasts flattened after tail suspension appeared cuboidal during subsequent reloading. Immunoreactivity for iNOS was detected in these osteoblasts and osteocytes by immunohistochemistry. These defective responses after reloading were rescued in iNOS,/, mice by treatment with an NO donor nitroglycerine (NG). Conversely, the responses in iNOS+/+ mice were inhibited by treatment with an NOS inhibitor aminoguanidine (AG). In bone marrow cell cultures, mineralized nodules derived from iNOS,/, mice after reloading were significantly reduced. Taken together, our results suggest that NO generated by iNOS in osteoblasts plays a critical role in adjusting bone turnover and increasing osteogenic activity in response to the acute increase in mechanical loading after tail suspension. [source]