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Bilateral defects (diameter 8 mm) in the medial tibial head of senile, osteopenic female sheep (n = 48; 9.63 ± 0.10 years; mean ± SEM) were treated with hydroxyapatite (HA)/beta-tricalcium phosphate (ß-TCP)/dicalcium phosphate dihydrate (DCPD; brushite) cylinders coated with BMP-2 (25 or 250 micrograms) or growth differentiation factor (GDF)-5 (125 or 1250 micrograms; left side); cylinders without BMP served as controls (right side). Three, 6, and 9 months post-operation (n = 6 each group), bone structure and formation were analyzed in vivo by X-ray and ex vivo by osteodensitometry, histomorphometry, and micro-computed tomography (micro-CT) at 3 and 9 months. Semi-quantitative X-ray evaluation showed significantly increasing bone densities around all implant cylinders over time. High-dose BMP-2-coated cylinders (3 and 9 months) and low-dose GDF-5-coated cylinders (3 and 6 months) demonstrated significantly higher densities than controls (dose-dependent for BMP-2 at 3 months). This was confirmed by osteodensitometry at 9 months for high-dose BMP-2-coated cylinders (and selected GDF-5 groups), and was again dose-dependent for BMP-2. Osteoinduction by BMP-2 was most pronounced in the adjacent bone marrow (dynamic histomorphometry/micro-CT). BMP-2 (and partially GDF-5) significantly increased the bone formation in the vicinity of HA/TCP/DCPD cylinders used to fill tibial bone defects in senile osteopenic sheep and may be suitable for surgical therapy of critical size, non-load-bearing bone defects in cases of failed tibial head fracture or defect healing.
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Durapatita , Osteogênese , Feminino , Animais , Ovinos , Durapatita/química , Regeneração Óssea , Fator 5 de Diferenciação de Crescimento , Microtomografia por Raio-X , Fosfatos de Cálcio/química , HidroxiapatitasRESUMO
INTRODUCTION: Existing osteoporosis models in sheep exhibit some disadvantages, e.g., challenging surgical procedures, serious ethical concerns, failure of reliable induction of substantial bone loss, or lack of comparability to the human condition. This study aimed to compare bone morphological and mechanical properties of old and young sheep, and to evaluate the suitability of the old sheep as a model for senile osteopenia. MATERIALS AND METHODS: The lumbar vertebral body L3 of female merino sheep with two age ranges, i.e., old animals (6-10 years; n = 41) and young animals (2-4 years; n = 40), was analyzed concerning its morphological and mechanical properties by bone densitometry, quantitative histomorphometry, and biomechanical testing of the corticalis and/or central spongious region. RESULTS: In comparison with young sheep, old animals showed only marginally diminished bone mineral density of the vertebral bodies, but significantly decreased structural (bone volume, - 15.1%; ventral cortical thickness, - 11.8%; lateral cortical thickness, - 12.2%) and bone formation parameters (osteoid volume, osteoid surface, osteoid thickness, osteoblast surface, all - 100.0%), as well as significantly increased bone erosion (eroded surface, osteoclast surface). This resulted in numerically decreased biomechanical properties (compressive strength; - 6.4%). CONCLUSION: Old sheep may represent a suitable model of senile osteopenia with markedly diminished bone structure and formation, and substantially augmented bone erosion. The underlying physiological aging concept reduces challenging surgical procedures and ethical concerns and, due to complex alteration of different facets of bone turnover, may be well representative of the human condition.
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Doenças Ósseas Metabólicas/patologia , Modelos Animais de Doenças , Ovinos/fisiologia , Animais , Fenômenos Biomecânicos , Densidade Óssea , Doenças Ósseas Metabólicas/fisiopatologia , Osso Esponjoso/patologia , Osso Esponjoso/fisiopatologia , Força Compressiva , Módulo de Elasticidade , Feminino , Vértebras Lombares/patologia , Vértebras Lombares/fisiopatologia , OsteogêneseRESUMO
BACKGROUND: Hip dysplasia is one of the most common malformations in childhood and has a significant impact on the further life of those affected. A distinction must be made between congenital and the much rarer acquired dysplasia. Early diagnosis and therapy are pivotal for further development of patients. OBJECTIVES: The paper gives an overview of current radiological possibilities of diagnosis with focus on congenital hip dysplasia supplemented by insights into therapeutic options. MATERIALS AND METHODS: Basic and review papers were analyzed. RESULTS: Clinical examination of the newborn has low sensitivity and specificity in the diagnosis of hip dysplasia. The introduction of Graf ultrasound screening has significantly improved the early detection of dysplastic hips. With the help of sonography, but also magnetic resonance imaging (MRI), the shape of the acetabulum and the position of the femoral head in the socket can be precisely and quickly determined, while Xray examinations have their place especially in the context of follow-up examinations after treatment from the age of 1 year and in the diagnosis of secondary dysplasia. Therapeutic options range from spreading treatment to open reduction with fixation in the newborn as well as conversion osteotomy in older children. CONCLUSION: Early detection of hip dysplasia is critical to the course of treatment. The right choice of examination method and correct performance are essential for further treatment.
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Luxação Congênita de Quadril , Luxação do Quadril , Recém-Nascido , Criança , Humanos , Luxação Congênita de Quadril/diagnóstico por imagem , Luxação Congênita de Quadril/terapia , Luxação do Quadril/complicações , Luxação do Quadril/patologia , Acetábulo/patologia , Acetábulo/cirurgia , Radiografia , Osteotomia/métodosRESUMO
(1) Background: Primary in-brace correction has been shown to be related to conservative adolescent idiopathic scoliosis (AIS) treatment outcome. The purpose of the study was to evaluate TLSO brace design changes over eight years regarding primary Cobb correction and de-rotation of the (major) curve. (2) Methods: This retrospective analysis included AIS patients treated with a full-time TLSO-brace in a single Orthopedic University hospital in 2012-2014 and 2017-2019. Brace design changes resulted from an evolutionary process, from a 3-point bending to a 3D TLSO. The brace parameters (presence of an anterior shoulder pad, posterior high-thoracic pad, thoracic space, and angle of the lumbar and thoracic pressure points) were analyzed regarding the primary (major) Cobb angle and apex rotation correction with a multivariate analysis. (3) Results: A total of 74 (63 female) patients were included in the study. The Cobb angle primary correction was significantly improved over the timeframe. The primary correction was significantly influenced by all design parameters and partially by its interactions with (curve specific) different effects on the Cobb correction and apex de-rotation. (4) Conclusions: Knowledge about the effects of brace design parameters on the curve's angle and rotation correction enables improvements in individualized brace design and the brace optimization process.
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Effects of hydroxyapatite (HA) particles with bone morphogenetic BMP-2 or GDF-5 were compared in sheep lumbar osteopenia; in vitro release in phosphate-buffered saline (PBS) or sheep serum was assessed by ELISA. Lumbar (L) vertebral bone defects (Ø 3.5 mm) were generated in aged, osteopenic female sheep (n = 72; 9.00 ± 0.11 years; mean ± SEM). Treatment was: (a) HA particles (2.5 mg; L5); or (b) particles coated with BMP-2 (1 µg; 10 µg) or GDF-5 (5 µg; 50 µg; L4; all groups n = 6). Untouched vertebrae (L3) served as controls. Three and nine months post-therapy, bone formation was assessed by osteodensitometry, histomorphometry, and biomechanical testing. Cumulative 14-day BMP release was high in serum (76-100%), but max. 1.4% in PBS. In vivo induction of bone formation by HA particles with either growth factor was shown by: (i) significantly increased bone volume, trabecular and cortical thickness (overall increase HA + BMP vs. control close to the injection channel 71%, 110%, and 37%, respectively); (ii) partial significant effects for bone mineral density, bone formation, and compressive strength (increase 17%; 9 months; GDF-5). Treatment effects were not dose-dependent. Combined HA and BMPs (single low-dose) highly augment long-term bone formation and biomechanical stabilization in sheep lumbar osteopenia. Thus, carrier-bound BMP doses 20,000-fold to 1000-fold lower than previously applied appear suitable for spinal fusion/bone regeneration and improved treatment safety.
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AIMS: The aim of the present study was to answer the question whether curve morphology and location have an influence on rigid conservative treatment in patients with adolescent idiopathic scoliosis (AIS). METHODS: We retrospectively analyzed AIS in 127 patients with single and double curves who had been treated with a Chêneau brace and physiotherapeutic specific exercises (B-PSE). The inclusion criteria were the presence of structural major curves ≥ 20° and < 50° (Risser stage 0 to 2) at the time when B-PSE was initiated. The patients were divided into two groups according to the outcome of treatment: failure (curve progression to ≥ 45° or surgery) and success (curve progression < 45° and no surgery). The main curve type (MCT), curve magnitude, and length (overall, above and below the apex), apical rotation, initial curve correction, flexibility, and derotation by the brace were compared between the two groups. RESULTS: In univariate analysis treatment failure depended significantly on: 1) MCT (p = 0.008); 2) the apical rotation of the major curve before (p = 0.007) and during brace treatment (p < 0.001); 3) the initial and in-brace Cobb angles of the major (p = 0.001 and p < 0.001, respectively) and minor curves (p = 0.015 and p = 0.002); 4) major curve flexibility (p = 0.005) and the in-brace curve correction rates (major p = 0.008, minor p = 0.034); and 5) the length of the major curve (LoC) above (p < 0.001) and below (p = 0.002) the apex. Furthermore, MCT (p = 0.043, p = 0.129, and p = 0.017 in MCT comparisons), LoC (upper length p = 0.003, lower length p = 0.005), and in-brace Cobb angles (major p = 0.002, minor p = 0.027) were significant in binary logistic regression analysis. CONCLUSION: Curve size, location, and morphology were found to influence the outcome of rigid conservative treatment of AIS. These findings may improve future brace design and patient selection for conservative treatment. Cite this article: Bone Joint J 2021;103-B(2):373-381.
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Braquetes , Tratamento Conservador/métodos , Procedimentos Ortopédicos/métodos , Escoliose/patologia , Escoliose/terapia , Adolescente , Criança , Tratamento Conservador/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Procedimentos Ortopédicos/instrumentação , Radiografia , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Resultado do TratamentoRESUMO
Oil-based calcium phosphate cement (Paste-CPC) shows not only prolonged shelf life and injection times, but also improved cohesion and reproducibility during application, while retaining the advantages of fast setting, mechanical strength, and biocompatibility. In addition, poly(L-lactide-co-glycolide) (PLGA) fiber reinforcement may decrease the risk for local extrusion. Bone defects (diameter 5 mm; depth 15 mm) generated ex vivo in lumbar (L) spines of female Merino sheep (2-4 years) were augmented using: (i) water-based CPC with 10% PLGA fiber reinforcement (L3); (ii) Paste-CPC (L4); or (iii) clinically established polymethylmethacrylate (PMMA) bone cement (L5). Untouched (L1) and empty vertebrae (L2) served as controls. Cement performance was analyzed using micro-computed tomography, histology, and biomechanical testing. Extrusion was comparable for Paste-CPC(-PLGA) and PMMA, but significantly lower for CPC + PLGA. Compressive strength and Young's modulus were similar for Paste-CPC and PMMA, but significantly higher compared to those for empty defects and/or CPC + PLGA. Expectedly, all experimental groups showed significantly or numerically lower compressive strength and Young's modulus than those of untouched controls. Ready-to-use Paste-CPC demonstrates a performance similar to that of PMMA, but improved biomechanics compared to those of water-based CPC + PLGA, expanding the therapeutic arsenal for bone defects. O, significantly lower extrusion of CPC + PLGA fibers into adjacent lumbar spongiosa may help to reduce the risk of local extrusion in spinal surgery.
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To assess the clinical course of a sheep stifle joint model for osteochondral (OC) defects, medial femoral condyles (MFC) were exposed without patella luxation using medial parapatellar skin (3-4 cm) and deep incisions (2-3 cm). Two defects (7 mm diameter; 10 mm depth; OC punch) were left empty or refilled with osteochondral autologous transplantation cylinders (OATS) and explanted after six weeks. Incision-to-suture time, anesthesia time, and postoperative wound or impairment scores were compared to those in sham-operated animals. Implant performance was assessed by X-ray, micro-computed tomography, histology, and immunohistology (collagens 1, 2; aggrecan). There were no surgery-related infections or patellar luxations. Operation, anesthesia, and time to complete stand were short (0.5, 1.4, and 1.5 h, respectively). The wound trauma score was low (0.4 of maximally 4; day 7). Empty-defect and OATS animals reached an impairment score of 0 significantly later than sham animals (7.4 and 4.0 days, respectively, versus 1.5 days). Empty defects showed incomplete healing and dedifferentiation/heterotopic differentiation; OATS-filled defects displayed advanced bone healing with remaining cartilage gaps and orthotopic expression of bone and cartilage markers. Minimally-invasive, medial parapatellar surgery of OC defects on the sheep MFC allows rapid and low-trauma recovery and appears well-suited for implant testing.
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BACKGROUND CONTEXT: Targeted delivery of osteoinductive bone morphogenetic proteins (eg, GDF5) in bioresorbable calcium phosphate cement (CPC), potentially suitable for vertebroplasty and kyphoplasty of osteoporotic vertebral fractures, may be required to counteract augmented local bone catabolism and to support complete bone regeneration. The biologically optimized GDF5 mutant BB-1 may represent an attractive drug candidate for this purpose. PURPOSE: The aim of the current study was to test an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming CPC containing low-dose BB-1 in a sheep lumbar osteopenia model. STUDY DESIGN/ SETTING: This is a prospective experimental animal study. METHODS: Bone defects (diameter 5 mm) were generated in aged, osteopenic female sheep and were filled with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages of BB-1 (L5; CPC+fibers+BB-1; 5, 100, and 500 µg BB-1; n=6 each). The results were compared with those of untouched controls (L1). Three and 9 months after the operation, structural and functional effects of the CPC (±BB-1) were analyzed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (BV/TV) (assessed by micro-CT and histomorphometry), trabecular thickness (Tb.Th), and trabecular number (Tb.N); (3) bone formation, that is, osteoid volume/bone volume (OV/BV), osteoid surface/bone surface (OS/BS), osteoid thickness, mineralizing surface/bone surface (MS/BS), mineral apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. RESULTS: Compared with untouched controls (L1), CPC+fibers (L4) and/or CPC+fibers+BB-1 (L5) significantly improved all parameters of bone formation, bone resorption, and bone structure. These effects were observed at 3 and 9 months, but were less pronounced for some parameters at 9 months. Compared with CPC without BB-1, additional significant effects of BB-1 were demonstrated for BMD, bone structure (BV/TV, Tb.Th, and Tb.N), and bone formation (OS/BS and MS/BS). The BB-1 effects on bone formation at 3 and 9 months were dose dependent, with 100 µg as the potentially optimal dosage. CONCLUSIONS: BB-1 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. A single local dose as low as 100 µg BB-1 was sufficient to augment middle- to long-term bone formation. A CPC containing the novel GDF5 mutant BB-1 may thus represent an alternative to the bioinert, supraphysiologically stiff polymethylmethacrylate cement presently used to treat osteoporotic vertebral fractures by vertebroplasty and kyphoplasty.
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Cimentos Ósseos/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Regeneração Óssea/efeitos dos fármacos , Fator 5 de Diferenciação de Crescimento/uso terapêutico , Ácido Láctico/uso terapêutico , Osteogênese/efeitos dos fármacos , Ácido Poliglicólico/uso terapêutico , Vertebroplastia/métodos , Animais , Densidade Óssea/efeitos dos fármacos , Força Compressiva , Modelos Animais de Doenças , Feminino , Fator 5 de Diferenciação de Crescimento/administração & dosagem , Ácido Láctico/administração & dosagem , Região Lombossacral , Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polimetil Metacrilato/administração & dosagem , Polimetil Metacrilato/uso terapêutico , Estudos Prospectivos , OvinosRESUMO
BACKGROUND CONTEXT: Injectable, brushite-forming calcium phosphate cements (CPC) show potential for bone replacement, but they exhibit low mechanical strength. This study tested a CPC reinforced with poly(l-lactide-co-glycolide) acid (PLGA) fibers in a minimally invasive, sheep lumbar vertebroplasty model. PURPOSE: The study aimed to test the in vivo biocompatibility and osteogenic potential of a PLGA fiber-reinforced, brushite-forming CPC in a sheep large animal model. STUDY DESIGN/SETTING: This is a prospective experimental animal study. METHODS: Bone defects (diameter: 5 mm) were placed in aged, osteopenic female sheep, and left empty (L2) or injected with pure CPC (L3) or PLGA fiber-reinforced CPC (L4; fiber diameter: 25 µm; length: 1 mm; 10% [wt/wt]). Three and 9 months postoperation (n=20 each), the structural and functional CPC effects on bone regeneration were documented ex vivo by osteodensitometry, histomorphometry, micro-computed tomography (micro-CT), and biomechanical testing. RESULTS: Addition of PLGA fibers enhanced CPC osteoconductivity and augmented bone formation. This was demonstrated by (1) significantly enhanced structural (bone volume/total volume, shown by micro-CT and histomorphometry; 3 or 9 months) and bone formation parameters (osteoid volume and osteoid surface; 9 months); (2) numerically enhanced bone mineral density (3 and 9 months) and biomechanical compression strength (9 months); and (3) numerically decreased bone erosion (eroded surface; 3 and 9 months). CONCLUSIONS: The PLGA fiber-reinforced CPC is highly biocompatible and its PLGA fiber component enhanced bone formation. Also, PLGA fibers improve the mechanical properties of brittle CPC, with potential applicability in load-bearing areas.
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Cimentos Ósseos/química , Regeneração Óssea , Osteogênese , Vertebroplastia/métodos , Animais , Cimentos Ósseos/efeitos adversos , Fosfatos de Cálcio/química , Feminino , Ácido Láctico/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ovinos , Vertebroplastia/efeitos adversosRESUMO
BACKGROUND CONTEXT: Bioresorbable calcium phosphate cement (CPC) may be suitable for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures. However, additional targeted delivery of osteoinductive bone morphogenetic proteins (BMPs) in the CPC may be required to counteract the augmented local bone catabolism and support complete bone regeneration. PURPOSE: This study aimed at testing an injectable, poly (l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing low-dose bone morphogenetic protein BMP-2 in a sheep lumbar osteopenia model. STUDY DESIGN/ SETTING: This is a prospective experimental animal study. METHODS: Bone defects (diameter 5 mm) were generated in aged, osteopenic female sheep and filled with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages of BMP-2 (L5; CPC+fibers+BMP-2; 1, 5, 100, and 500 µg BMP-2; n=5 or 6 each). The results were compared with those of untouched controls (L1). Three and 9 months after the operation, structural and functional effects of the CPC (±BMP-2) were analyzed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (assessed by micro-computed tomography [micro-CT] and histomorphometry), trabecular thickness, and trabecular number; (3) bone formation, that is, osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralizing surface/bone surface, mineral apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. RESULTS: Compared with untouched controls (L1), CPC+fibers (L4) and/or CPC+fibers+BMP-2 (L5) significantly improved all parameters of bone formation, bone resorption, and bone structure. These effects were observed at 3 and 9 months, but were less pronounced for some parameters at 9 months. Compared with CPC without BMP-2, additional significant effects of BMP-2 were demonstrated for bone structure (bone volume/total volume, trabecular thickness, trabecular number) and formation (osteoid surface/bone surface and mineralizing surface/bone surface), as well as for the compressive strength. The BMP-2 effects on bone formation at 3 and 9 months were dose-dependent, with 5-100 µg as the optimal dosage. CONCLUSIONS: BMP-2 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. A single local dose as low as ≤100 µg BMP-2 was sufficient to augment middle to long-term bone formation. The novel CPC+BMP-2 may thus represent an alternative to the bioinert, supraphysiologically stiff polymethylmethacrylate cement presently used to treat osteoporotic vertebral fractures by vertebroplasty/kyphoplasty.
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Cimentos Ósseos/química , Doenças Ósseas Metabólicas/tratamento farmacológico , Proteína Morfogenética Óssea 2/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Região Lombossacral/patologia , Animais , Cimentos Ósseos/uso terapêutico , Densidade Óssea , Proteína Morfogenética Óssea 2/administração & dosagem , Proteína Morfogenética Óssea 2/farmacologia , Fosfatos de Cálcio/química , Força Compressiva , Feminino , Polimetil Metacrilato/química , OvinosRESUMO
BACKGROUND CONTEXT: Biodegradable calcium phosphate cement (CPC) represents a promising option for the surgical treatment of osteoporotic vertebral fractures. Because of augmented local bone catabolism, however, additional targeted delivery of bone morphogenetic proteins with the CPC may be needed to promote rapid and complete bone regeneration. PURPOSE: In the present study, an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing the bone morphogenetic protein GDF5 was tested in a sheep lumbar osteopenia model. STUDY DESIGN/SETTING: This is a prospective experimental animal study. METHODS: Defined bone defects (diameter 5 mm) were placed in aged, osteopenic female sheep. Defects were treated with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages of GDF5 (L5; CPC+fibers+GDF5; 1, 5, 100, and 500 µg GDF5; n=5 or 6 each). The results were compared with those of untouched controls (L1). Three and 9 months postoperation, structural and functional effects of the CPC (±GDF5) were assessed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (assessed by micro-computed tomography and histomorphometry), trabecular thickness, and trabecular number; (3) bone formation, that is, osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralized surface/bone surface, mineral apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. RESULTS: Compared with untouched controls (L1), both CPC+fibers (L4) and CPC+fibers+GDF5 (L5) numerically or significantly improved all parameters of bone formation, bone resorption, and bone structure. These significant effects were observed both at 3 and 9 months, but for some parameters they were less pronounced at 9 months. Compared with CPC without GDF5, additional significant effects of CPC with GDF5 were demonstrated for BMD and parameters of bone formation and structure (bone volume/total volume, trabecular thickness, and trabecular number, as well as mineralized surface/bone surface). The GDF5 effects were dose-dependent (predominantly in the 5-100 µg range) at 3 and 9 months. CONCLUSIONS: GDF5 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. The results indicated that a local dose as low as ≤100 µg GDF5 may be sufficient to augment middle to long-term bone formation. The novel CPC+GDF5 combination may thus qualify as an alternative to the bioinert, supraphysiologically stiff poly(methyl methacrylate) cement currently applied for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures.
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Cimentos Ósseos/química , Doenças Ósseas Metabólicas/tratamento farmacológico , Regeneração Óssea , Fator 5 de Diferenciação de Crescimento/uso terapêutico , Animais , Cimentos Ósseos/uso terapêutico , Densidade Óssea , Fosfatos de Cálcio/química , Força Compressiva , Feminino , Fator 5 de Diferenciação de Crescimento/administração & dosagem , Região Lombossacral/patologia , Polimetil Metacrilato/química , OvinosRESUMO
BACKGROUND CONTEXT: Large animal models are highly recommended for meaningful preclinical studies, including the optimization of cement augmentation for vertebral body defects by vertebroplasty/kyphoplasty. PURPOSE: The aim of this study was to perform a systematic characterization of a strictly minimally invasive in vivo large animal model for lumbar ventrolateral vertebroplasty. STUDY DESIGN/ SETTING: This is a prospective experimental animal study. METHODS: Lumbar defects (diameter 5 mm; depth approximately 14 mm) were created by a ventrolateral percutaneous approach in aged, osteopenic, female sheep (40 Merino sheep; 6-9 years; 68-110 kg). L1 remained untouched, L2 was left with an empty defect, and L3 carried a defect injected with a brushite-forming calcium phosphate cement (CPC). Trauma/functional impairment, surgical techniques (including drill sleeve and working canula with stop), reproducibility, bone defects, cement filling, and functional cement augmentation were documented by intraoperative incision-to-suture time and X-ray, postoperative trauma/impairment scores, and ex vivo osteodensitometry, microcomputed tomography (CT), histology, static/fluorescence histomorphometry, and biomechanical testing. RESULTS: Minimally invasive vertebroplasty resulted in short operation times (28±2 minutes; mean±standard error of the mean) and X-ray exposure (1.59±0.12 minutes), very limited local trauma (score 0.00±0.00 at 24 hours), short postoperative recovery (2.95±0.29 hours), and rapid decrease of the postoperative impairment score to 0 (3.28±0.36 hours). Reproducible defect creation and cement filling were documented by intraoperative X-ray and ex vivo conventional/micro-CT. Vertebral cement augmentation and osteoconductivity of the CPC was verified by osteodensitometry (CPC>control), micro-CT (CPC>control and empty defect), histology/static histomorphometry (CPC>control and empty defect), fluorescence histomorphometry (CPC>control; all p<.05 for 3 and 9 months), and compressive strength measurements (CPC numerically higher than control; 102% for 3 months and 110% for 9 months). CONCLUSIONS: This first-time systematic clinical assessment of a minimally invasive, ventrolateral, lumbar vertebroplasty model in aged, osteopenic sheep resulted in short operation times, rapid postoperative recovery, and high experimental reproducibility. This model represents an optimal basis for standardized evaluation of future studies on vertebral augmentation with resorbable and osteoconductive CPC.