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PubMed2003

[A 36 month prospective study of 12 plate osteosyntheses of distal radius fractures].

INTRODUCTION: We performed a prospective study of 12 intra-articular distal radial fractures. The fractures were treated with an anterior plate together with posterior pinning. The aim of the study was to examine whether it was technically feasible to fix such fractures using this technique and to assess the stability of the fixation at follow up. METHOD: Twelve articular fractures were included with a mean age of 47.1 years. All patients were followed up from first admission to the 36th postop month with clinical and radiological checks. RESULTS: At follow up, we found 8 good and excellent clinical results, 3 fair and 1 poor. The combination of an anterior plate with posterior pinning allowed a good initial reduction but could not protect from secondary displacement particularly in the presence of a comminuted metaphysal fracture. DISCUSSION: This procedure gave clinically satisfactory results but did not control ulnar variance. This procedure should be combined with bone grafting in complex metaphysal fractures and epiphysal screws should be used whenever possible.

Bone Nails↗
PubMed2000

Heterogeneity of bone lamellar-level elastic moduli.

Advances in our ability to assess fracture risk, predict implant success, and evaluate new therapies for bone metabolic and remodeling disorders depend on our understanding of anatomically specific measures of local tissue mechanical properties near and surrounding bone cells. Using nanoindentation, we have quantified elastic modulus and hardness of human lamellar bone tissue as a function of tissue microstructures and anatomic location. Cortical and trabecular bone specimens were obtained from the femoral neck and diaphysis, distal radius, and fifth lumbar vertebra of ten male subjects (aged 40-85 years). Tissue was tested under moist conditions at room temperature to a maximum depth of 500 nm with a loading rate of 10 nm/sec. Diaphyseal tissue was found to have greater elastic modulus and hardness than metaphyseal tissues for all microstructures, whereas interstitial elastic modulus and hardness did not differ significantly between metaphyses. Trabecular bone varied across locations, with the femoral neck having greater lamellar-level elastic modulus and hardness than the distal radius, which had greater properties than the fifth lumbar vertebra. Osteonal, interstitial, and primary lamellar tissues of compact bone had greater elastic moduli and hardnesses than trabecular bone when comparing within an anatomic location. Only femoral neck interstitial tissue had a greater elastic modulus than its osteonal counterpart, which suggests that microstructural distinctions can vary with anatomical location and may reflect differences in the average tissue age of cortical bone or mineral and collagen organization.

Adult↗
PubMed2002

Thyroid status affects number and localization of thyroid hormone receptor expressing mast cells in bone marrow.

Thyroid hormone (T(3)) plays a key role in endochondral ossification. The process relies on the coordinated synthesis and degradation of cartilage matrix and is disrupted in juvenile hypothyroidism, leading to abnormal skeletal development. Mast cells synthesize and store matrix-degrading enzymes. We examined whether thyroid status influences skeletal mast cell distribution in growing rats to determine whether they might modulate the actions of T(3) in bone. Tibiae were collected for histological, histochemical, immunohistochemical, and immunofluorescence analysis. Mast cells were increased throughout the bone marrow in hypothyroid rats compared with euthyroid, thyrotoxic, and hypothyroid-thyroxine replaced animals. Large numbers were present in metaphyseal marrow adjacent to the growth plate in hypothyroid animals and cells were distributed evenly throughout the marrow. Very few mast cells were present in metaphyseal marrow in other groups, but their numbers increased with increasing distance from the growth plate. T(3) receptor alpha1 (TRalpha1) was expressed in the nucleus and cytoplasm of skeletal mast cells, whereas TRalpha2 and TRbeta1 were restricted to the cytoplasm. Localization of TRs was not affected by altered thyroid status. Thus, disrupted endochondral ossification in hypothyroidism may be mediated in part by skeletal mast cells, which express TR proteins and may function as T(3) target cells.

Animals↗
PubMed1996

Abnormalities in bone cell function and endochondral ossification in the osteopetrotic toothless rat.

The toothless (tl) rat is an osteopetrotic mutation whose excess skeletal mass is produced by a defect in its skeletal microenvironment. Its skeletal sclerosis fails to be cured by bone marrow transplantation but is largely reversed by exogenous administration of colony stimulating factor 1 which increases osteoclast neogenesis and resorptive activity. Recent studies have also indicated abnormalities in growth plate cartilage morphology and in osteoblast number and function in the tl rat. The present histomorphometric study examined static and kinetic parameters of bone cell and cartilage function in young (3-5-week-old) animals of tl stock for evidence of tissue level dysfunction. Mineralization of growth plate cartilage in mutants occurred only in the lateral regions of the growth plate, not in the central region, and longitudinal bone growth was significantly reduced (36%-61%) in mutants at the ages examined. Bone volume and trabecular thickness were greater in mutants despite significant reductions in their osteoblast populations and bone formation rates (two to threefold lower). Mutants also showed progressive age- and metaphyseal site-related decreases in osteoblast numbers which, compared to normal littermates, may relate to differences in osteoprogenitor cell pools, osteoblast lifespan, or resorption-derived skeletal growth factors locally available to support and maintain normal osteoblast phenotype. Osteoclast number per millimeter bone perimeter was reduced 96-fold in mutants and showed no age- or metaphyseal site-related changes. This study presents evidence in support of defects in chondrocyte and bone cell function in the tl rat and reveals the specific tissue locations where they occur.

Analysis of Variance↗
PubMed1997

Comparative effects of droloxifene, tamoxifen, and estrogen on bone, serum cholesterol, and uterine histology in the ovariectomized rat model.

The purpose of this study was to compare the effects of droloxifene (DRO), tamoxifen (TAM), and 17 alpha-ethynyl estradiol (EE) on bone mineral density, bone histomorphometry, total serum cholesterol, and uterine histology in the ovariectomized (ovx) rat model. Sprague-Dawley female rats at five months of age were sham-operated and treated orally with vehicle (n = 8), or ovx (n = 56) and treated (p.o.) with either vehicle, DRO at 0.1 or 1.0 mg/kg daily, TAM at 0.1 or 1 mg/kg daily, or EE at 3 or 30 micrograms/kg daily for 4 weeks. The uterine wet weight and uterine histologic parameters (cross-sectional tissue area, stromal thickness, and luminal epithelial thickness) were determined. Femoral and lumbar vertebral bone mineral density was determined ex vivo using dual energy x-ray absorptiometry. Static and dynamic cancellous bone histomorphometry was performed on double-labeled, undecalcified longitudinal sections from proximal tibial metaphyses. Furthermore, the changes in total serum cholesterol and body weight gain were also determined. Compared to sham controls, ovx for four weeks significantly decreased uterine weight (-72%), uterine cross-sectional tissue area (-74%), stromal thickness (-52%), and luminal epithelial thickness (-53%). ovx rats treated with EE at 30 micrograms/kg/day maintained these parameters at the levels of sham controls. Uterine weight and uterine cross-sectional tissue area in 3 micrograms/kg/day of EE treated ovx rats were higher than that of vehicle-treated ovx rats. In ovx rats treated with TAM at both 0.1 and 1 mg/kg/day, these parameters were significantly less than sham controls but significantly higher than ovx controls. DRO at 0.1 mg/kg/day had no effects on all above parameters. Uterine weight and cross-sectional tissue area in 1 mg/kg/day of DRO treated ovx rats was slightly but significantly higher than that in ovx controls. However, DRO at 1 mg/kg/day had no effects on uterine stromal thickness and luminal epithelial thickness compared to ovx controls. The ovx-induced decrease in femoral and lumbar vertebral bone mineral density was prevented by treatment with EE at 30 micrograms/kg/day, TAM at both 0.1 and 1 mg/kg/day, or DRO at 1 mg/kg/day. Similarly, the decrease in bone mass and the increase in bone resorption and bone turnover in proximal tibial metaphyses were prevented by treatment with EE at 30 micrograms/kg/day or TAM at both 0.1 and 1 mg/kg/day, or DRO at 1 mg/kg/day. Total serum cholesterol decreased significantly in ovx rats treated with either EE, DRO, or TAM at all dose levels compared to vehicle treated ovx controls (-32% to -56%). The ovx-induced body weight gain was completely prevented by EE at 30 micrograms/kg/day, and partially prevented by DRO at 1 mg/kg/day. TAM at both 0.1 and 1 mg doses caused a significant decrease in body weight compared to both sham and ovx controls. Our results indicated that DRO prevented ovx-induced bone loss and lowered total serum cholesterol with an ED50 less than 1 mg/kg/day. The bone protective and cholesterol lowering effects of DRO were comparable to those observed with TAM and EE. However, DRO differed from TAM and EE in its lack of significant estrogenic effects on uterine tissue at doses which were bone protective. These data suggest that DRO may be a significant alternative to EE and TAM for prevention and treatment of postmenopausal osteoporosis.

Absorptiometry, Photon↗
PubMed1998

Mechanics of avian fibrous periosteum: tensile and adhesion properties during growth.

We report the results of direct mechanical tests of the fibrous periosteum from the tibiotarsi of white leghorn chicks at 4, 6, 8, 9, 10, 11, 12, and 14 weeks of age using a newly developed sample isolation technique. Additionally, this technique allows the determination of the apparent in vivo load on the fibrous periosteum. The periosteum has a highly nonlinear stress-strain relationship at all ages. For loading below the in vivo level, the periosteum is pliant and mean tensile modulus is 3.35 MPa (+/- 1.84 SD, n = 75). For loading above the in vivo level, tensile stiffness is nearly two orders of magnitude greater. In the region of high stiffness, mean modulus is 229.5 MPa (+/- 89.6, n = 72). In vivo, the periosteum is loaded at the transition between these two stiffness regions. We interpret this as indicating that, in vivo, the collagen fibers of the periosteum are aligned, but subject to minimal loading. Stress levels in the periosteum corresponding to in vivo conditions indicate modest loading, and mean apparent in vivo stress levels are 0.92 MPa (+/- 0.37 SD, n = 67). A second technique demonstrated that the adhesion of the periosteum in the diaphyseal region (1-6 weeks of age) is minimal, but is substantial in the metaphyseal region. The metaphyseal adhesion will affect the transmission of load between the physes. These studies suggest that growth of the fibrous periosteum follows the longitudinal growth of the bone, rather than the periosteum having a direct mechanical influence on growth plate activity. Comparison of tensile properties over the course of growth indicates a substantial increase in periosteal stiffness in the early portion of the growth period, which reaches a maximum at approximately 9 weeks posthatching. There is also a marked decline in periosteal stiffness as growth rate declines in the latest stages of growth (14 weeks). This suggests that the basic properties of periosteal collagen may undergo a transition during the course of this tissue's brief functional lifetime; that is, during long bone growth.

Age Factors↗
PubMed1999

Differential effect of treadmill exercise on three cancellous bone sites in the young growing rat.

The aim of the present study was to examine cancellous bone changes induced by exercise on three different skeletal sites, the lumbar vertebra, the proximal, and the distal tibia, in the young growing rat. Forty 4-week-old female Sprague-Dawley rats were randomized into 4 groups of 10 animals each; 8 weeks exercise (8EX), 8 weeks sedentary control (8CON), 12 weeks exercise (12EX), and 12 weeks sedentary control (12CON). The exercise regimen consisted of treadmill running at 24 m/min 1 hr per day 5 days a week. After each period of exercise, the proximal and distal tibial metaphyses (PTM and DTM, respectively) and the fifth lumbar (L5) vertebral body were processed for histomorphometry of the cancellous bone (secondary spongiosa) and cortical periosteum. Eight and twelve weeks of exercise significantly increased the mineral apposition rate and bone formation rate in the PTM and DTM, and 12 weeks of exercise significantly increased the labeled perimeter in the DTM, compared with the age-matched controls. Eight and twelve weeks of exercise significantly increased cancellous bone volume in the PTM (mean +/- standard deviation, 8EX; 19.1 +/- 2.9% vs 8CON; 14.3 +/- 3.1%, P < 0.05 and 12EX; 18.8 +/- 3.5% vs 12CON; 15.2 +/- 3.3%, P < 0.05), and 12 weeks exercise significantly increased cancellous bone volume in the DTM, compared with age-matched control (12EX; 32.5 +/- 7.7%, 12CON; 22.2 +/- 4.8%, P < 0.05). The increase in cancellous bone volume by 12 weeks exercise was higher in the DTM than that in the PTM (43.4% and 24.0%, respectively). On the other hand, the exercise did not significantly affect cancellous bone volume and bone formation in the L5 vertebral body, although the cortical periosteal bone formation rate and the L5 vertebral bone mass were increased. These findings suggest that cancellous bone adaptation to treadmill exercise is site specific, and the effect may be influenced by factors such as mechanical loading and metaphyseal bone architecture in the young growing rat.

Adaptation, Physiological↗
PubMed2001

Mind over matter? I: philosophical aspects of the mind-brain problem.

OBJECTIVE: To conceptualize the essence of the mind-body or mind-brain problem as one of metaphysics rather than science, and to propose a formulation of the problem in the context of current scientific knowledge and its limitations. METHOD AND RESULTS: The background and conceptual parameters of the mind-body problem are delineated, and the limitations of brain research in formulating a solution identified. The problem is reformulated and stated in terms of two propositions. These constitute a 'double aspect theory'. CONCLUSIONS: The problem appears to arise as a consequence of the conceptual limitations of the human mind, and hence remains essentially a metaphysical one. A 'double aspect theory' recognizes the essential unity of mind and brain, while remaining consistent with the dualism inherent in human experience.

Brain↗
PubMedDate not supplied

An in vitro comparison of hollow ground and trocar points on threaded positive-profile external skeletal fixation pins in canine cadaveric bone.

OBJECTIVE: To compare the microstructural damage created in bone by pins with lathe-cut and rolled-on threads, and to determine the peak tip temperature and damage created by positive-profile external fixator pins with either hollow ground (HG) or trocar (T) tips during insertion. STUDY DESIGN: An acute, in vitro biomechanical evaluation. SAMPLE POPULATION: Twenty-seven canine tibiae. METHODS: Lathe-cut thread design with T point (LT-T), rolled-on thread design with T point (RT-T), and rolled-on thread design with HG point (RT-HG) pins were evaluated. Twenty pins of each type were inserted under constant drilling pressure into 12 canine tibiae (12 diaphyseal and 8 metaphyseal sites per pin type). Peak pin tip temperature, drilling energy, end-insertional pin torque, and pullout force were measured for each pin. For the histologic study, five pins of each type were inserted into cortical and cancellous sites in 15 additional tibiae. Entry and exit damage, and thread quality were assessed from 100 micron histologic sections by using computer-interfaced videomicroscopy. RESULTS: T-tipped pins reached higher tip temperature in both diaphyseal and metaphyseal bone compared with HG-tipped pins. RT-T pins had higher pullout strength (diaphyseal) and end-insertional torque compared with other combinations. No differences in drilling energy or insertional bone damage was found between the three pin types (P < .05). CONCLUSIONS: T-tipped pins mechanically outperformed HG-tipped pins. Pin tip and thread design did not significantly influence the degree of insertional bone damage. CLINICAL RELEVANCE: T-tipped pins may provide the best compromise between thermal damage and interface friction for maximizing performance of threaded external fixator pins.

Animals↗
PubMed2001

Load transfer and stress shielding of the hydroxyapatite-ABG hip: a study of stem length and proximal fixation.

We questioned whether the excellent clinical results reported for the hydroxyapatite-coated ABG hip are consistent with results of preclinical computer simulation methods for the prediction of strain-adaptive bone remodeling patterns around implants. We also investigated whether a further improvement of the results can be expected if complete proximal load transfer is enforced by reducing stem length to the metaphyseal area only. Resorption patterns predicted were in good agreement with radiographic clinical findings. Mechanical failure of the bone-implant interface was judged based on a Hoffman interface stress criterion, which was low. Reducing stem length hardly increased interface failure probability, but it did not reduce stress shielding, either. From a mechanical point of view, reducing stem length to the metaphyseal area only is not advantageous.

Arthroplasty, Replacement, Hip↗
PubMed2000

[Pseudarthroses after distal radius fractures. What is the role of the distal radioulnar joint?].

Non-union following distal radial fracture is extremely rare. Therefore, the patterns are not completely understood. Recently, it was suggested that an associated distal ulna shaft fracture increases the risk to develop a non-union for comminuted fractures of the distal radius. The purpose of this study was to review our 15 cases with this condition to investigate the role of an associated distal ulna shaft fracture and/or an associated lesion of the distal radioulnar joint. The second goal was to evaluate the success of the surgical treatment in relation to the extent of the metaphyseal subchondral bone supporting the articular surface distal to the site of the non-union. We reviewed our 15 cases which were operated on for non-union of the distal radius since 1992. In all cases, the radiographs could be reviewed. Twelve patients could actually be re-examined. The investigated criteria were: initial, pre- and postoperative X-ray findings, other medical conditions, range of motion, grip strength, and pain relief. Clinical outcome was evaluated using the DASH-questionnaire. According to the AO classification system, there were two type A3 and 13 type C3 fractures. There were seven associated distal ulna fractures. The distal radioulnar joint was involved in twelve cases. The other medical conditions in the patients with non-union after distal radial fracture included allergy, hypothyroidism, diabetes mellitus, peripheral neuropathy, and bronchial asthma. Four patients were tobacco smokers. Only one patient was initially treated non-operatively. In all cases, the distal radius was restored preserving wrist motion. Bony union was achieved in 14 cases. The range of motion has improved in all planes. Grip strength increased but still remained over 50% below the level of the opposite side. Postoperatively, the majority of patients was pain free. In four cases, complications were seen postoperatively. Three of these patients had less than 6 mm of metaphyseal subchondral bone beneath the articular surface. Three of the four patients were tobacco smokers. Inadequate treatment of a comminuted distal radial fracture associated with a special local situation--such as an additional distal ulna shaft fracture and/or an associated lesion of the distal radioulnar joint--combined with a general medical condition, adversely affects fracture healing, increasing the risk for non-union. From the review of the records of these 15 cases, we recommend that non-union with more than 5 mm of subchondral bone supporting the articular surface distal to the non-union site undergo reconstruction of the radius. Non-union with less than 5 mm subchondral bone supporting the articular surface requires an individual decision. A good bone stock and stable fixation allows for reconstruction of the radius, otherwise wrist fusion is a useful salvage procedure.

Adult↗
PubMedDate not supplied

[Load shift-total hip replacement--numerical and clinical evaluation of a new concept of adaptive stem fixation].

AIM: The new load-shift fixation concept pursues the goal of an adaptive change of geometrical characteristics of the in-situ hip replacement. In this study a preclinical and clinical evaluation was performed. METHODS: By three-dimensional, dynamic finite element calculation the biomechanical properties of the prosthesis were analyzed in the early postoperative and long-term configuration. By clinical (20 +/- 10 months) and radiological (18 +/- 10 months) follow-up of a first series of implants (n = 20) the primary functional status of the prosthesis was examined in vivo. RESULTS: The preclinical results revealed that the metaphyseal micromotions are reduced significantly with the diaphyseal fit of the stem postoperatively. By absorption of a biodegradable element (spreader) integrated into the tip of the stem a change of stem geometry associated with loss of the diaphyseal fit occurs. This results in a complete shifting of load transmission into the metaphyseal area. In the clinical situation the postoperative Harris hip score averaged 92.9 +/- 10.5 points. Only in two patients did reversible episodes of thigh pain occur. The radiological analysis of bone remodeling phenomena pointed to a physiological load transmission. There was no evidence of loosening or osteolysis. On radiology, stem tapering could be demonstrated. CONCLUSION: On the basis of these promising preclinical and early clinical results the innovative load-shift prosthesis should now be further evaluated in prospective long-term studies.

Aged↗
PubMed2004

Displaced fractures of the proximal humerus in children require open/closed reduction and internal fixation.

Fractures of the proximal humerus in children are rare and constitute only 3% of all epiphyseal injuries. From 1992 to 2002 sixteen patients aged 4 - 15 years with a displaced fracture of the proximal humerus were treated at our level I trauma unit. The mean follow-up of the patients was 23.8 months (8 - 72). Ten children had a metaphyseal fracture and six a Salter and Harris Type II injury. Only one metaphyseal fracture was treated conservatively; the other patients underwent surgery (ORIF [= open reduction internal fixation] in ten patients, CRIF [= closed reduction internal fixation] in five patients). Follow-up examination showed no shortening or major angulation of the humerus in any of the sixteen cases. Fifteen children showed excellent and good results. There was only one average result in a polytraumatized child with additional injuries in both upper extremities. Based on the results of this study we suggest performing ORIF/CRIF in displaced fractures of the proximal humerus in children.

Child↗
PubMed2004

[Osseous abnormalities and CT findings in Stueve-Wiedemann-Syndrome (SWS)].

PURPOSE: Analysis of typical conventional radiological and CT findings in our group of patients with the rare skeletal dysplasia Stueve-Wiedemann-Syndrome (SWS) and comparison with published data. MATERIALS AND METHODS: In 16 newborns with clinically dysmorphic features, dwarfism, and bowed limbs, radiographs of the chest and skeleton were obtained for classification of the underlying skeletal dysplasia. For the first time, computed tomography was performed for further investigation of midface hypoplasia. The early diagnosis of SWS could be made by correlation of the radiological and clinical findings. For evaluation of progression, follow-up radiological examinations of the skeleton were performed in four children surviving infancy. RESULTS: Clinically, the newborns with SWS showed dwarfism, midface hypoplasia, bowed extremities with contractures and had severe problems with respiration, feeding, and swallowing as well as episodes of hyperthermia. Skeletal radiographs revealed bowing of the long tubular bones, most pronounced at the lower extremities. Additional findings were internal triangular cortical diaphyseal thickening at the concave side of the bowing, wide metaphyses with abnormal trabecular pattern and radiolucencies. Four patients survived infancy. Clinically, they suffered from recurrent aspiration pneumonia and recurrent episodes of hyperthermia as well as form cutaneous and mucosal infections. The follow-up radiographs showed progressive bowing of the long tubular bones as well as progressive metaphyseal decalcification. CONCLUSIONS: Skeletal abnormalities in SWS are so characteristic that an early post partum diagnosis can be made. However, a close cooperation between radiologists, clinicians, and geneticists is required for correlation of clinical and radiological findings. The few cases that survive infancy have progressing orthopaedic problems.

Abnormalities, Multiple↗
PubMedDate not supplied

[Midterm results and revisions of the thrust plate prosthesis (TPP)].

AIM: Although already in use for 20 years, the concept of the metaphyseal anchored thrust plate prosthesis has not yet gained general acceptance. Clinical and radiological follow-up examinations were carried out 5 to 8 years after implantation of a TPP. We tried to answer the question if the metaphyseal anchorage of the cement-less TPP is equal to a diaphyseal anchorage of a cement-less stem prosthesis and to define the advantages of the TPP. METHODS: We included 170 of the patients from our clinic with an implanted TPP in this study. Furthermore we reviewed the results of 30 revision hip arthroplasties of the TPP. The clinical examination were carried out using the Harris hip score while the radiological examinations were performed on the basis of predefined criteria. RESULTS: We found good clinical results. The preoperative Harris score of 48.7 increased to 93.7 at 24 months postoperatively. Radiolucencies were detected and were of varying relevance in dependence on their localization. The Kaplan-Meier survival analysis at 8 years was 90.5 %. The clinical results after changing the TPP were also good to excellent. The mean Harris hip score was 87.3. CONCLUSION: Our study suggests that in spite of a slightly higher aseptic loosening rate in comparison to the cement-less stem prosthesis, the thrust plate prosthesis proved to be worthwhile. On the basis of previous experience we assume that the TPP is a good alternative implant especially for young patients.

Adolescent↗
PubMed1981

[Lesions of the epiphyses - classification - therapy - prognosis (author's transl)].

Between 1970 and 1980 53 children with epiphyseal injuries were treated. Analysing these 53 cases we found that metaphyseal lesions of the epiphyseal plate (i.e. epiphyseolysis, separation of the epiphysis with triangular metaphyseal fragment) heal completely, even in those cases in whom an open reduction was necessary. Conservatively treated epiphyseal injuries (i.e. fracture of the epiphysis, crushing of the epiphyseal plate) showed bad results. Contrary to these results 80% of open reduced injuries showed good results. We can conclude that epiphyseal injuries do not necessarily end in disturbances of growth or malformation if surgical correction of the injury is done as early as possible and if the injured extremity is immobilised at least 3 to 5 weeks. Destruction of the epiphyseal vascular system can only be avoided by surgical reposition of the epiphyseal injury.

Child↗
PubMed2000

Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene.

Tumor necrosis factor-related, activation-induced cytokine (TRANCE), a tumor necrosis factor family member, mediates survival of dendritic cells in the immune system and is required for osteoclast differentiation and activation in the skeleton. We report the skeletal phenotype of TRANCE-deficient mice and its rescue by the TRANCE transgene specifically expressed in lymphocytes. TRANCE-deficient mice showed severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibited profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae. These mice had marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes. Transgenic overexpression of TRANCE in lymphocytes of TRANCE-deficient mice rescued osteoclast development in two locations in growing long bones: excavation of marrow cavities permitting hematopoiesis in the marrow spaces, and remodeling of osteopetrotic woven bone in the shafts of long bones into histologically normal lamellar bone. However, osteoclasts in these mice failed to appear at the chondroosseous junction and the metaphyseal periosteum of long bones, nor were they present in tooth eruption pathways. These defects resulted in sclerotic metaphyses with persistence of club-shaped long bones and unerupted teeth, and the growth plate defects were largely unimproved by the TRANCE transgene. Thus, TRANCE-mediated regulation of the skeleton is complex, and impacts chondrocyte differentiation and osteoclast formation in a manner that likely requires local delivery of TRANCE.

Animals↗
PubMed2001

Dose-dependent bone-sparing effects of dietary isoflavones in the ovariectomised rat.

The dose-dependent bone-sparing effects of dietary isoflavones (IF) were investigated in adult (7-month-old) Wistar rats. Forty animals were ovariectomised, allocated into four groups of ten rats each, and immediately treated orally with IF at 0 (OVX), 20 (IF20), 40 (IF40) or 80 (IF80) microg/g body weight per d for 91 d; ten sham-operated (SH) controls received the same diet without added IF. Animals were killed on day 91. Both femoral failure load and total femoral, diaphyseal or metaphyseal bone mineral densities (BMD) were lower in OVX animals than in SH animals. Urinary deoxypyridinoline (DPD) excretion, a marker of bone resorption, and plasma osteocalcin (OC) levels, a marker of osteoblast activity, were higher in OVX animals than in SH animals. Total femoral and diaphyseal BMD and femoral failure load were similar in IF-treated rats and SH rats. Although metaphyseal BMD in IF40 or IF80 rats was similar to that in SH rats, its value was lower in IF20 rats than in controls. The day 91 urinary DPD excretion in IF40 and IF80 rats, but not in IF20 rats, was similar to that in SH rats. Day 91 plasma OC concentrations in IF-treated rats were similar to day 45 values, but were decreased in OVX and SH rats. Thus, daily IF consumption prevented ovariectomy-induced bone loss, both by depressing bone resorption and stimulating osteoblast activity. Moreover, as only the highest IF level induced a weak uterotrophic activity, the optimal IF dose which preserves both cancellous and cortical bone, but exhibits no oestrogen-like effects on the uterus, was 40 microg/g body weight per d.

Amino Acids↗