The effect of radiation on the fracture repair process. A biomechanical evaluation of a closed fracture in a rat model

The effects of a single dose of irradiation on the biomechanical parameters of the fracture healing process were studied in a rat model. Intramedullary pinning was performed before production of a closed femoral midshaft fracture. The experimental group was exposed to 900 rad 3 days after fracture and was compared with a control group with a similar fracture that received no irradiation. Animals were killed at intervals ranging from 2-16 weeks after surgery and the bones were tested until failure in torsion. In the irradiated groups, a delay of 4 weeks was noted in the biomechanical parameters associated with fracture healing (torque to failure, torsional stiffness, angle to failure, and biomechanical stage). Despite this delay in the normal temporal progression, the staging and stiffness approached normal controls within an 8-week period. However, the torque to failure remained below normal levels at the conclusion of this study. These results differ from a previous study using an open fracture model.     

Low-dose X-irradiation promotes mineralization of fracture callus in a rat model

Objectives  This study investigated the hypothesized beneficial effect of low-dose irradiation (LDI) on fracture callus mineralization in a rat model. Methods  Seventy-two male Sprague–Dawley rats were averagely randomized into LDI group (rats treated with LDI) and SHAM group (rats treated with sham irradiation). Right after either LDI or sham irradiation, a standardized closed fracture on the right femur was established. At 2, 3 and 4 weeks postfracture, 12 rats in each group were euthanized. Fracture callus was assessed by using radiography and MicroCT for callus bridging, peripheral quantitative computed tomography (pQCT) for quantifying bone mineral content (BMC) and cross sectional area (CSA), confocal laser scanning microscopy for measuring area fraction of fluorescence labeling (AFFL) and four-point bending test for examining mechanical properties. Results  The CSA and AFFL were found to be 22 and 33% smaller in the LDI group compared to the SHAM group at 2 weeks (P < 0.05 for both), whereas the BMC and AFFL were 15 and 34% higher in the LDI group at 3 weeks (P < 0.05 for both). The changing patterns were consistent with the findings in 3-D MicroCT reconstructions. The mechanical parameters (Max-Load, Stiffness and Energy) were also 18, 30 and 24% higher in the LDI group than in the SHAM group at 3 weeks (P < 0.05 for all). At 4 weeks, there was no difference found for all assessments between the two groups. Conclusion  The results indicated LDI promoted mineralization at the stage of hard callus formation in a rat fracture model.     

A study of fracture callus material properties: relationship to the torsional strength of bone

This study was designed to quantitate the local material properties of fracture callus during gap healing and to relate these local properties to the torsional strength of bone in a canine model under external fixation. Bilateral tibial transverse osteotomies were performed in 32 dogs and stabilized using unilateral external skeletal fixators with a 2-mm gap. Dogs were divided into four equal groups and euthanized at either 2, 4, 8, or 12 weeks. The torsional properties of one bone of each pair were determined. In both bones of each pair, the indentation stiffness, calcium content, and histomorphometric properties of six sites of periosteal callus, six sites of endosteal callus, four sites of cortical bone, and two sites of gap tissue were determined. Each of the four types of tissue had a specific structural or material property change during the study period. The indentation stiffness of periosteal callus increased up to 8 weeks and then plateaued. Endosteal callus stiffness peaked at 8 weeks and then decreased by 12 weeks. Gap tissue stiffness increased linearly over time. Cortical bone stiffness decreased over time. Indentation stiffness was significantly associated with the calcium content of periosteal callus (R2 = 0.50, p less than 0.0001) and gap tissue (R2 = 0.66, p less than 0.0001). The local stiffnesses of gap tissue and periosteal callus were significantly associated with the maximum torque (gap, R2 = 0.50, p less than 0.0001; periosteal, R2 = 0.34, p less than 0.05) and the torsional stiffness (gap, R2 = 0.44, p less than 0.0001; periosteal, R2 = 0.65, p less than 0.0001) of the bone.(ABSTRACT TRUNCATED AT 250 WORDS)     

阿仑膦酸钠和强骨胶囊单用与合用对大鼠骨质疏松性骨折骨愈合影响的实验研究

目的通过骨质疏松性骨折动物模型,观察阿仑膦酸钠、强骨胶囊单用及合用对骨折愈合的影响,以探讨中西医结合治疗骨质疏松性骨折的意义。方法 70只SD大鼠给予维甲酸灌胃,制造骨质疏松性骨折模型成功后分别予以阿仑膦酸钠、强骨胶囊及两药合用,于2周、4周和6周处死5只试验鼠,进行骨痂大小的测量及组织学研究。结果 2周时合用组骨痂大小较其他组无显著差异;4周时合用组骨痂大小较阿仑膦酸钠组小,较强骨胶囊组大;6周时各组骨痂大小无异。组织学检测发现阿仑膦酸钠组破骨细胞数目最少,骨小梁成熟较其他组缓慢;强骨胶囊组成骨细胞数目最多,小梁骨成熟最快;强骨胶囊联合阿仑膦酸钠组与对照组无差别。结论强骨胶囊与阿仑膦酸钠联合使用治疗维甲酸所致大鼠骨质疏松性骨折疗效并不显著。     

Alendronate prevents bone loss and improves tendon-to-bone repair strength in a canine model.

Previously we showed a loss of bone and a concomitant decrease in mechanical properties in the first 21 days after flexor tendon insertion site injury and repair in a canine model. The goal of this short-term study was to suppress bone loss after insertion site repair using alendronate in an attempt to prevent the reduction in biomechanical properties. Flexor tendons of the second and fifth digits of the right forelimbs of canines were injured and repaired. Dogs received a daily oral dose of alendronate (2 mg/kg). One digit in each dog also received a local dose of alendronate in the bone tunnel at the time of surgery. The repair was evaluated for bone mineral density (BMD) and biomechanical properties and compared to data from a previous study in which no alendronate was used. Alendronate was effective in protecting the distal phalanx from resorption during tendon-to-bone healing (BMD was 94 and 104% of control for systemic alendronate and for systemic plus local alendronate, respectively). Alendronate treatment prevented much of the decrease in ultimate load that occurs in the first 21 days. Without treatment, ultimate load was 42% of control. With systemic alendronate treatment and systemic plus local alendronate treatment, ultimate load was 78 and 69% of control, respectively. Failure mode was significantly different when comparing alendronate treatment to repair alone. A lower incidence of suture pull through was found in alendronate treated dogs, suggesting less tendon degeneration. Ultimate load can be improved in association with preventing the bone loss that normally occurs during the early period following tendon-to-bone repair. These initial short-term data demonstrate the potential for a clinical treatment that could enhance tendon-to-bone healing.     

Topical, single dose bisphosphonate treatment reduced bone resorption in a rat model for prosthetic loosening.

Fluid pressure, instability or particles have been suggested to cause peri-prosthetic bone resorption. High intracapsular pressures have been reported in hip joints with loose prosthetic components, and oscillating fluid pressure has been shown to cause dramatic bone resorption in animal models. Resorption can be reduced by systemic bisphosphonate treatment in rat models with oscillating fluid pressure, but this has required higher doses than needed to inhibit normal remodelling. Bisphosphonates have high affinity to bone mineral. Topical application of the drug is therefore feasible. We used a previously described rat model where oscillating fluid pressure causes bone resorption. Before pressurization, a 1 mg/ml solution of alendronate was applied onto the bone surface for 1 min, after which excess bisphosphonate was rinsed away. Bone resorption was measured on histological slides as soft tissue area at the interface. Rats treated with topical alendronate had soft tissue areas reduced by half. Topical bisphosphonate treatment before cementing a joint implant could possibly reduce the risk of later loosening.     

Effect of curcumin on bone healing: An experimental study in a rat model of femur fracture

ObjectiveTo determine the radiologic, histologic and biomechanical effects of curcumin on bone healing using a total rat femur fracture injury model.Materials and methodsSixty four male Wistar–Albino rats weighing 170–210 g were used in this study. The animals were randomly divided into eight groups and 5 or 6 animals were placed in each cage. A transverse femur shaft fracture model used. The animals in study groups received oral curcumin at a dose of 200 mg/kg for 14 days or 28 days. Remaining animals received only saline solution by oral gavage for a period of 14 days and 28 days as control groups. After sacrification the left femurs used for radiological, histological and biomechanical evaluation.ResultsThe groups treated with curcumin showed no significant difference in terms of radiological, histological and biomechanical evaluations in 14 days groups. Also there was no significant difference between curcumin and control groups for 28 days according to radiological, histological and biomechanical tests.ConclusionsAccording to our results, curcumin has no positive effect on fracture healing not only histologically but also radiologically and biomechanically. Curcumin’s antioxidant effect may be more noticeable with long term follow up investigation as it may have a positive effect in remodelling phase. Long term follow up designed studies may be planned to investigate its effect on remodelling phase of fracture healing.     

Effect of a single dose of pamidronate administered at the time of surgery in a rabbit posterolateral spinal fusion model

Spinal fusion is usually performed on patients who receive bisphosphonates (BP); however, limited data on their action on spinal fusion are available. Previous studies in animal models have shown that chronic administrations of BP reduced spinal fusion rates, and only one study has shown that a single dose administration of zolendronic acid increased fusion rate. The objective of the present study was to evaluate if pamidronate (PA), which was previously demonstrated to reduce spinal fusion rate when administered continuously for 8 weeks, would increase the spinal fusion rate if administered in a single dose at the time of surgery in a rabbit model. Thirty-two New Zealand rabbits underwent an L5–L6 posterolateral intertransverse fusion with iliac crest autograft. Animals were randomized to receive either PA 3 mg/kg in a single dose immediately after surgery, or normal saline. Animals were killed 8 weeks after surgery and fusion was determined by manual palpation and radiographic analysis. Fusion healing was obtained in eight rabbits (50%) in the PA group and in four animals (25%) in the control group, p = 0.137. In a rabbit model, a single dose of PA did not decrease lumbar spinal arthrodesis consolidation rates, but it obtained a nonsignificant higher spinal fusion rate.     

Effect of osteoporosis on bone mineral density and fracture repair in a rat femoral fracture model

Osteoporosis (OP) is one of the most prevalent bone diseases worldwide with bone fracture the major clinical consequence. The effect of OP on fracture repair is disputed and although it might be expected for fracture repair to be delayed in osteoporotic individuals, a definitive answer to this question still eludes us. The aim of this study was to clarify the effect of osteoporosis in a rodent fracture model. OP was induced in 3‐month‐old rats (n = 53) by ovariectomy (OVX) followed by an externally fixated, mid‐diaphyseal femoral osteotomy at 6 months (OVX group). A further 40 animals underwent a fracture at 6 months (control group). Animals were sacrificed at 1, 2, 4, 6, and 8 weeks postfracture with outcome measures of histology, biomechanical strength testing, pQCT, relative BMD, and motion detection. OVX animals had significantly lower BMD, slower fracture repair (histologically), reduced stiffness in the fractured femora (8 weeks) and strength in the contralateral femora (6 and 8 weeks), increased body weight, and decreased motion. This study has demonstrated that OVX is associated with decrease in BMD (particularly in trabecular bone) and a reduction in the mechanical properties of intact bone and healing fractures. The histological, biomechanical, and radiological measures of union suggest that OVX delayed fracture healing. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:384–393, 2008     

Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair.

We hypothesized that ZA treatment would bolster fracture repair. In a rat model for closed fracture healing, a single dose of ZA at 0, 1, or 2 wk after fracture significantly increased BMC and strength of the healed fracture. Delaying the dose (1 or 2 wk after fracture) displayed superior results compared with dosing at the time of fracture. INTRODUCTION: Bisphosphonates are known to increase bone strength and thus the resistance to fracture by decreasing osteoclastic bone resorption. These properties may enable bisphosphonates to also increase the strength of fracture repair. Zoledronic acid (ZA) is a potent bisphosphonate with a high affinity for bone mineral, allowing bolus intravenous dosing in a range of indications. In this study, we examined the application of bolus dose ZA in endochondral fracture repair. MATERIALS AND METHODS: Carbon-14 labeled ZA was used in a closed rat fracture model. Rats were divided into five treatment groups (n = 25 per group): saline control, local ZA (0.01 mg/kg), and three systemic bolus ZA groups (0.1 mg/kg) with different administration times: at fracture, 1 wk after fracture, and 2 wk after fracture. Rats were killed 6 wk postoperatively. Postmortem analyses included radiography, QCT, microCT, biomechanical testing, scintillation counting, autoradiography, and histology. RESULTS: Single-dose systemic ZA administration significantly increased callus volume, callus BMC, and mechanical strength. Perioperative treatment increased mechanical strength by 30% compared with controls (p < 0.05). Administering the systemic dose at 1 or 2 wk after fracture further increased mechanical strength compared with controls by 44% and 50%, respectively (p < 0.05). No significant differences in mechanical parameters were seen with local injection at the dose studied. Autoradiographic analysis indicated that ZA binds significantly to bone that is present at the time of administration. ZA quantification indicated that delayed administration significantly increased the uptake efficiency in the callus. Histological and microCT analysis showed that ZA treated calluses had a distinctive internal structure consisting of an intricate network of retained trabecular bone. CONCLUSIONS: The timing of a single systemic dose of ZA plays an important role in the modulation of callus properties in this rat fracture model; delaying the single dose produces a larger and stronger callus.     

Development of an atrophic nonunion model and comparison to a closed healing fracture in rat femur.

Although most fractures heal, some fail to heal and become nonunions. Many animal models have been developed to study problems of fracture healing. The majority of nonunion models have involved segmental bone defects, but this may not adequately represent the biologic condition in which nonunions clinically develop. The objective of the present study is to develop a nonunion model that better simulates the clinical situation in which there is soft tissue damage including periosteal disruption and to compare this model to a standard closed fracture model utilizing identical fracture stabilization, providing a similar mechanical environment. A total of 96 three month old Long Evans rats were utilized. A 1.25 mm diameter K-wire was inserted into the femur in a retrograde fashion, and a mid-diaphyseal closed transverse fracture was created using a standard three-point bending device. To create a nonunion, 48 of the rats received additional surgery to the fractured femur. The fracture site was exposed and 2 mm of the periosteum was cauterized on each side of the fracture. Fracture healing was evaluated with serial radiographs every two weeks. Animals were maintained for intervals of two, four, six or eight weeks after surgery. Specimens from each time interval were subjected to biomechanical and histological evaluation. None of the cauterized fractures healed throughout the eight weeks experimental duration. The radiographical appearance of nonunion models was atrophic. This investigation showed pronounced differences between the experimental nonunions and standard closed fractures both histologically and biomechanically. In conclusion, we have developed a reproducible atrophic nonunion model in the rat femur that simulates the clinical condition in which there is periosteal disruption but no bone defect.     

Intact fibula improves fracture healing in a rat tibia osteotomy model.

Rat tibia fractures are often used in fracture healing studies. Usually the fracture is stabilized with an intramedullary pin, which provides bending stiffness, but little torsional stiffness. The objective of this research was to determine the in vitro torsional rigidity of an osteotomized tibia with and without the fibula, and to determine if this difference influences the healing process in vivo. In vitro eleven rat tibias received an osteotomy, were stabilized with an intramedullary pin, and were tested in internal rotation to determine the torsional rigidity. The fibula was then manually broken and the torsional rigidity measured again. In vivo 18 rats received a tibial osteotomy, eight of which had an additional fractured fibula. After three weeks, the rats were sacrificed and the tibias were analyzed. Bone density in the fracture callus was measured with qCT. Bending rigidity and maximum breaking moment were determined in three-point bending. In vitro testing demonstrated that the torsional rigidity with an intact fibula was nearly two times higher than when the fibula was fractured. Though the torsional rigidity was still small in comparison with an intact bone, it resulted in a significantly different healing process in vivo. Rats with intact fibulas had significantly higher bone mineral density, bending rigidity, and maximum breaking moment compared to rats with a fractured fibula. These results indicate that torsional stability considerably affects the healing process. In a fracture model, it is critical to characterize the mechanical environment of the fracture.     

灌注造影显微CT三维重建研究骨痂微血管新生

目的 探讨灌注造影显微CT(MicroCT)扫描三维重建在研究大鼠骨折愈合时骨痂微血管变化的可行性及意义.方法 60只雄性Sprague-Dawley( SD)大鼠,随机分为实验组及对照组(每组30只),制作标准的右侧股骨中段闭合骨折模型,术后1、2、3、4、8周处死大鼠.实验组大鼠行腹主动脉远端血管造影后,使用MicroCT断层扫描标本,并选取同一兴趣区测定血管体积、体积分数和血管平均直径.对照组骨痂通过免疫组织化学染色法测定血管内皮生长因子(VEGF)及血管内皮生长因子受体2( VEGFR-2)的表达.结果 实验组血管体积、体积分数在术后第3周达到高峰,分别为(196.00±20.33) mm3和(6.70±0.74)％;而血管直径在第4周显著增加,为( 109.00±12.15) μm(P ＜0.05).对照组显示VEGF和VEGFR-2的表达在术后第2周明显增加,阳性细胞数分别为113.40±9.17和51.80±4.24(P ＜0.05).结论 灌注造影MicroCT扫描三维重建可无创提供直观的高分辨率三维微血管像,并精确定量微血管量与直径.     

Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodeling in fracture treatment: a biomechanical and histological study in rats

Bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor (TGF)-beta superfamily, is known to be a very potent osteoinductive growth factor. The purpose of this study was to investigate the effect of BMP-2 (5% [w/w], 50 microg on each nail), locally released from poly(D,L-lactide) (PDLLA)-coated intramedullary implants, on fracture healing. A closed fracture of the right tibia of 5-month-old Sprague-Dawley rats (n = 64) was intramedullary stabilized with uncoated vs. BMP-2-coated titanium Kirschner wires. X-ray examinations (posteroanterior and lateral) were performed throughout the experiment. At 28 and 42 days after fracture, the animals were killed and both tibiae were dissected for biomechanical torsional testing. For histological and histomorphometric evaluation, 5 microm sections were obtained, stained with Safranin-O/light green and von Kossa, and examined using an image analysis system. The radiological results demonstrated progressed callus consolidation in the BMP-2-treated groups compared with the uncoated groups at both timepoints. Histomorphometric evaluation showed progressed callus remodeling with significantly increased mineralization and less cartilage of the periosteal callus. Due to the BMP-2 treatment, increased mineralization of the cortices was detected at 28 and 42 days after fracture. Biomechanical testing revealed significantly elevated maximum load and torsional stiffness in the BMP-2-treated groups compared with controls at both timepoints. The results clearly demonstrate that local application of BMP-2 from PDLLA-coated implants is feasible and significantly accelerates fracture healing. Local administration of growth factors from coated implants could reduce clinical problems in fracture treatment without opening of the fracture, implantation of further devices, or injection with the risk of infection or side effects caused by other carriers.     

Role of dual energy X-ray absorptiometry in monitoring fracture healing in a rat femoral fracture model

Earlymobilizationandweightbearingplayimportantrolesinminimizingtheamountofbonelosstoachievegoodhealingafterbonefracture.1Areliableandnoninvasivemethodforevaluatingfracturehealingcannotonlyhelpdecidewhentostarweightbearing, butalsohelpdetecttheimpairedboneunionearlytopreventdelayedunionsornonunions.However, objectivequantitativemethodsforearlyevaluationoffracturehealinghavenotbeendevelopedyet. DualenergyX rayabsorptiometry(DEXA)isoneofthemostaccuratemethodsformeasuringbonemassinvivo. Itismain…     

Different effects of mechanical vibration on bone ingrowth into porous hydroxyapatite and fracture healing in a rabbit model

The effects of mechanical vibration on bone ingrowth into porous hydroxyapatite implants and fracture healing were examined radiographically, histomorphometrically, and biomechanically in a rabbit model. Fifty-three female NZW rabbits were used in this study. These rabbits were divided into four separate studies to assess the effects of 20 and 60 min of vibration/day in both implant and osteotomy models as compared with the respective non-vibrated controls. For the implant model, coral hydroxyapatite goniopora rods were implanted bilaterally into tibiae and for the osteotomy model, bilateral fibulae were osteotomized. A resonant frequency of 25 Hz mechanical vibration was used. After periods of 2, 3, 4, and 6 weeks of vibration, the rabbits were killed and examined. For the implant model, there was no significant difference between control, 20, or 60 min of vibration/day with respect to the rate or amount of new bone ingrowth. For the fracture model, 60 min of vibration/day produced a significantly larger callus as compared with the non-vibrated controls (p less than 0.05), whereas 20 min of vibration/day did not. Although biomechanical testing demonstrated a general trend for increased strength in the vibrated animals, it failed to reach significance. These results suggest that the mechanical vibration used in the present study had a beneficial effect on callus volume, possibly due to the stimulation of secondary bone healing processes, but does not appear to promote bone ingrowth into a porous hydroxyapatite implant.     

A reliable externally fixated murine femoral fracture model that accounts for variation in movement between animals.

Fifty-two CFLP mice had an open femoral diaphyseal osteotomy held in compression by a four-pin external fixator. The movement of 34 of the mice in their cages was quantified before and after operation, until sacrifice at 4, 8, 16 or 24 days. Thirty-three specimens underwent histomorphometric analysis and 19 specimens underwent torsional stiffness measurement. The expected combination of intramembranous and endochondral bone formation was observed, and the model was shown to be reliable in that variation in the histological parameters of healing was small between animals at the same time point, compared to the variation between time-points. There was surprisingly large individual variation in the amount of animal movement about the cage, which correlated with both histomorphometric and mechanical measures of healing. Animals that moved more had larger external calluses containing more cartilage and demonstrated lower torsional stiffness at the same time point. Assuming that movement of the whole animal predicts, at least to some extent, movement at the fracture site, this correlation is what would be expected in a model that involves similar processes to those in human fracture healing. Models such as this, employed to determine the effect of experimental interventions, will yield more information if the natural variation in animal motion is measured and included in the analysis.     

Adenoviral-mediated transfer of human BMP-6 gene accelerates healing in a rabbit ulnar osteotomy model.

This study evaluated healing of rabbit bilateral ulnar osteotomies 6 and 8 weeks after surgery in response to percutaneous injection of transgenic adenoviral (Ad) bone morphogenetic protein-6 (BMP-6) vector or green fluorescent protein vector control (Ad-GFP) administered 7 days after surgery compared to untreated osteotomy controls. The amount, composition and biomechanical properties of the healing bone repair tissue were compared among groups and to historical data for intact rabbit ulnae obtained from similar studies at the same institution. Quantitative computed tomography was used to determine area, density and mineral content of the mineralized callus in the harvested ulnae. Maximum torque, torsional stiffness, and energy absorbed to failure were determined at 1.5 degrees /s. Calcified sections of excised ulnae (5 microm) were stained with Goldner's Trichrome and Von Kossa, and evaluated for callus composition, maturity, cortical continuity, and osteotomy bridging. Radiographic assessment of bone formation indicated greater mineralized callus in the ulnae injected with Ad-hBMP-6 as early as 1 week after treatment (2 weeks after surgery) compared to untreated osteotomy ulnae (p < 0.006) and Ad-GFP treated osteotomy ulnae (p < 0.002). Quantitative computed tomography confirmed greater bone area and bone mineral content at the osteotomy at 6 weeks in Ad-BMP-6 treated osteotomy as compared to untreated osteotomy ulnae (p < 0.001) and Ad-GFP treated osteotomy ulnae (p < 0.01). Ad-BMP-6 treated osteotomy ulnae were stronger (p < 0.001 and 0.003) and stiffer (p < 0.004 and 0.003) in torsion at 6 weeks than untreated osteotomy ulnae or Ad-GFP treated osteotomy ulnae, respectively. Maximum torque, torsional stiffness, and energy absorbed to failure were greater in Ad-BMP-6 treated osteotomy ulnae compared to their respective untreated contralateral osteotomy ulnae at 8 weeks [p < 0.03]. Maximum torque and torsional stiffness in the Ad-BMP-6 treated osteotomy ulnae were not different to intact ulnae values at 6 and 8 weeks. These experiments confirm that BMP-6 can be potently osteoinductive in vivo resulting in acceleration of bone repair.     

去势对骨折早期愈合过程的影响

目的 通过对去势大鼠股骨骨折模型愈合早期骨痂的组织学、骨密度以及转化生长因子β1(Transforming growth factor beta 1.TGF-β1)、碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF）、骨形态发生蛋白-2(bone morphogenetic proteins-2，BMP-2)合成变化的观察．探讨骨质疏松骨折早期愈合过程的变化。方法 将60只雌性SD大鼠分为去势组和对照组，3个月后制成股骨干骨折模型．伤后不同阶段处死．分别进行组织学、骨密度以及TGF-β1,bFGF,BMP-2免疫组化染色方法观察。结果 大鼠去势后3个月全身骨密度检查证实去势组骨质疏松形成。骨折后第3d两组均开始形成原始骨痂；第4～6周，去势组骨痂比对照组少，且软骨痂比例较高．骨密度较低，免疫组化染色显示，在两组间bFGF、BMP-2的表达与分布、高峰出现与持续时间差异无显著性．去势组骨小梁附近表达TGF-β1的成骨细胞数目减少，结论 骨质疏松使大鼠骨折早期骨痂的数量与质量降低，自软骨性骨痂至骨性骨痂演变过程减缓．对骨折愈合过程的影响与BMP-2、bFGF的表达无明显关联。TGF-β1在成骨细胞中的表达减少可能是引起骨质疏松骨折愈合质量下降的因素之一．     

Zoledronic acid improves femoral head sphericity in a rat model of perthes disease.

We hypothesized that the bisphosphonate zoledronic acid (ZA) could improve femoral head sphericity in Perthes disease by changing the balance between bone resorption and new bone formation. This study tests the effect of ZA in an established model of Perthes disease, the spontaneously hypertensive rat (SHR). One hundred and twenty 4-week old SHR rats were divided into three groups of 40: saline monthly, 0.015 mg/kg ZA weekly, or 0.05 mg/kg ZA monthly. At 15 weeks DXA measurements documented that femoral head BMD was increased by 18% in ZA weekly and 21% in ZA monthly compared to controls (p<0.01). Femoral head sphericity in animals with osteonecrosis was improved in ZA-treatment groups (p<0.01) as measured by epiphyseal quotient (EQ). The proportion of "flat" heads (EQ0.40) was significantly reduced from 32% in saline-treated animals to 12% in weekly ZA and 3% in monthly ZA (p<0.01). Histologically there was a similar prevalence of osteonecrosis in all groups. The prevalence of ossification delay was significantly reduced by ZA treatment (p<0.01). Zoledronic acid favorably altered femoral head shape in this spontaneous model of osteonecrosis in growing rats. Translation of these results to Perthes disease could mean that deformity of the femoral head may be modified in children, perhaps reducing the need for surgical intervention in childhood and adult life.