Dsteoporosis influences the middle and late periods of racture healing in a rat osteoporotic model

OBJECTIVE: To evaluate the influence of osteoporosis on the middle and late periods of fracture healing process through observing the histomorphological changes, bone mineral density and biomechanical properties in ovariectomized rats. METHODS: Eighty-four female SD rats of 4 months old were randomly divided into osteoporosis group and sham operation group, 42 in each. Rats in osteoporosis group were performed ovariectomy operation while those in sham operation group were given sham operation. A midshaft tibia fracture model was established 10 weeks after ovariectomy. Tibias were harvested 2, 4, 6, 12, 18 weeks after fracture for bone mineral density, histomorphological and biomechanical evaluation. RESULTS: Compared with the sham operation group, callus bone mineral density was 12.8%, 18.0%, 17.0% lower in osteoporosis group 6, 12, 18 weeks after fracture, respectively (P<0.05); callus failure load was 24.3%, 31.5%, 26.6%, 28.8% lower in osteoporosis group, and callus failure stress was 23.9%, 33.6%, 19.1%, 24.9% lower in osteoporosis group 4, 6, 12, 18 weeks after fracture, respectively (P<0.05). In osteoporosis group, endochondral bone formation was delayed, more osteoclast cells could be seen around the trabecula, and the new bone trabecula arranged loosely and irregularly. CONCLUSIONS: Osteoporosis influences the middle and late periods of fracture healing in the rat osteoporotic model. The impairment is considered to be the result of combined effects of prolonged endochondral calcification, high activated osteoclast cell and the deceleration of the increase in bone mineral density.     

Relationship among bone mineral density, collagen composition, and biomechanical properties of callus in the healing of osteoporotic fracture

Objective： To study the change and relationship among bone mineral density （BMD）, collagen composition and biomechanical properties of the callus in the healing process of osteoporotic fracture. Methods： The osteoporotic rat model and fracture model were established through bilateral ovariectomy （OV＇X） and osteotomy of the middle shaft of the right hind tibiae, respectively. Ninety female SD rats were randomly divided into OVX group and sham group. With the samples of blood and callus, roentgenoraphic and histological observation were performed for the assessment of the healing progress of the fracture, and the serum concentration of TRAP-5b, proportion of type I collagen, BMD and biomechanical properties of the callus were measured. Results： The OVX group experienced a significant delay of fracture healing. The mean serum concentration of TRAP-5b of rats in the OVX group was much higher than that in the sham group after the operation （P 〈 0.05）, but the difference at the same time point after fracture was smaller than that before fracture （P 〈 0.05）. The BMD of the callus in both groups reached the peak value at the 6 th week after fracture while the proportion of the type I collagen and the biomechanical strength reached the peak at the 8th week. Conclusions. The deficiency of estrogen after the ovariectomy could induce the up-regulation of the osteoclasts activities, whereas the potency of further activation after fracture was depressed. Although the synthesis of collagen together with its mineralization determines the biomechanical properties of new bone, the accumulation of collagen could be assessed as an index in the prediction of biomechanical strength of bones independent of the bone mineral deposition.     

Early period of fracture healing in ovariectomized rats

Objective. To evaluate the effect of osteoporosis on fracture healing through observing the hlstomorphological changes, bone mineral density of callus and expression and distribution of transforming growth factor beta 1 (TGF-β1 ), basic fibroblast growth factor (bFGF)and bone morphogenetic protein.2 (BMP-2) in ovariectomized rats. Methods. Sixty female Sprague-Dawley rats ( aged 12 weeks and weighing 235 g on average ) were randomly divided into an ovariectomized (OVX) group (n =30) anda sham-operated (SO) group ( n = 30). Ovariectomy was performed in the OVX rats and same incision was made in the SO rats. Three months later, fracture of femoral shaft was made on all the rats. Then they were killed at different time points. Callus formation was observed with histological and imethods. Results: A reduction in callus and bone mineral density in the healing femur and a decrease of osteoblasts expressing TGF-β1 near the bone trabecula were observed in the OVX rats 3-4 weeks after fracture.Histomorphological analysis revealed a higher content of soft callus in the OVX rats than that in the SO rats.Immunohistochemistry results showed that no remarkable difference in expression and distribution of BMP-2 and bFGF between the OVX and SO groups was found. Conclusions: Osteoporosis influences the quantity and quality of callus during the early period of fracture healing. The effect of osteoporosis on fracture healing has no relationship with the expression of BMP-2 or bFGF. The decreased expression of TGF-I31 in osteoblasts may cause a decrease in quality of facture healing after osteoporosis.     

Osteoporosis influences the early period of fracture healing in a rat osteoporotic model

Osteoporotic fractures commonly occur in the elderly. Although current therapies are aimed at the prevention and treatment of osteoporotic fractures, studies examing the fracture healing process in osteoporotic bone are limited. We produced an osteoporotic rat model by ovariectomy (ovx) and maintained a low calcium diet (LCD) in order to evaluate the influence of osteoporosis on fracture healing. Callus formation and strength was monitored over a 3 week period by histological and biomechanical assessment. Data collected simultaneously on a group of rats undergoing sham surgery (sx) were used for comparison. A 40% reduction in fracture callus cross-sectional area and a 23% reduction in bone mineral density in the healing femur of the ovx rats was observed on day 21 following fracture as compared with the sx group (p < 0.01). Biomechanical data from the healing femur of the ovx rats revealed a fivefold decrease in the energy required to break the fracture callus, a threefold decrease in peak failure load, a twofold decrease in stiffness and a threefold decrease in stress as compared with the sx group (p < 0.01, respectively). Histomorphological analysis revealed a delay in fracture callus healing with poor development of mature bone in the ovx rats. This study provides physical evidence of altered fracture healing in osteoporotic bone, which may have important implications in evaluating the effects of new treatments for osteoporosis on fracture healing.     

Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in rats.

The impact of age and ovariectomy on the healing of femoral fractures was studied in three groups of female rats at 8, 32 and 50 weeks of age at fracture. In the two older groups, the rats had been subjected to ovariectomy or sham surgery at random at 26 weeks of age. At fracture, all rats received unilateral intramedullary pinning of one femur and a middiaphyseal fracture. Rigidity and breaking load of the femora were evaluated at varying times up to 24 weeks after fracture induction by three-point bending to failure. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. In the youngest group, 8-week-old female rats regained normal femoral rigidity and breaking load by 4 weeks after fracture. They exceeded normal contralateral values by 8 weeks after fracture. In the middle group, at 32 weeks of age, fractures were induced, and the femora were harvested at 6 and 12 weeks after fracture. At 6 weeks after fracture there was partial restoration of rigidity and breaking load. At 12 weeks after fracture, only the sham-operated rats had regained normal biomechanical values in their fractured femora, while the fractured femora of the ovariectomized rats remained significantly lower in both rigidity and breaking load. In contrast, for the oldest group of rats, 50 weeks old at fracture, neither sham-operated nor ovariectomized rats regained normal rigidity or breaking load in their fractured femora within the 24 weeks in which they were studied. In all fractured bones, there was a significant increase in BMD over the contralateral intact femora due to the increased bone tissue and bone mineral in the fracture callus. Ovariectomy significantly reduced the BMD of the intact femora and also reduced the gain in BMD by the fractured femora. In conclusion, age and ovariectomy significantly impair the process of fracture healing in female rats as judged by measurements of rigidity and breaking load in three-point bending and by accretion of mineral into the fracture callus.     

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…     

Role of parathyroid hormone in the mechanosensitivity of fracture healing.

The mechanical environment at a fracture site can influence the course of healing. Intermittent parathyroid hormone (PTH) has been shown to accelerate fracture healing. Intact bone models show that mechanical loading and PTH have a synergistic beneficial effect on osteogenesis. We hypothesized that PTH and mechanical loading would have a similar synergistic effect on fracture healing. Eighty mice underwent surgical osteotomy and intramedullary nailing of the tibia. The mice were divided into four groups: one underwent daily loading, one received daily subcutaneous PTH injections (30 microg/kg/day), one received both loading and PTH, and a control group received sham loading and vehicle injection. Daily loading was applied to the ends of the tibia with an external loading device for 2 weeks. Fracture healing was assessed by microcomputed tomography, histology, and biomechanical testing. The group with both loading and PTH had increased osteoblast and osteoclast activity and was the only group with a significantly larger callus mineral density and bone volume fraction. The PTH only group had significantly more osteoid in the callus compared to the control group, indicating enhanced early osteoblast activity. This group also had a significantly higher bone mineral content and total bone volume compared to controls. The group that received loading as the only intervention had significantly greater osteoclast activity versus controls. The contribution of loading and PTH administration to the fracture healing cascade indicates a synergistic effect. This finding may be of potential clinical utility when weight bearing is utilized to stimulate lower extremity fracture healing.     

化瘀补肾方对卵巢切除小鼠骨折愈合的作用

目的观察化瘀补肾方对卵巢切除小鼠骨折愈合的作用。方法 3月龄雌性C57BL/6小鼠48只分为假手术组、模型组和化瘀补肾方组各16只。模型组和化瘀补肾方组小鼠采用双侧卵巢切除术(OVX)建立骨质疏松症模型。术后12周,各组小鼠建立左侧胫骨中段骨折模型。术后给予化瘀补肾方组小鼠化瘀补肾方灌胃,给予假手术组与模型组小鼠等体积生理盐水灌胃,至骨折术后4周取材。检测各组小鼠血清雌二醇水平,采用Micro-CT检测小鼠第4腰椎及左侧胫骨的骨密度,检测左侧胫骨最大应力,对左侧胫骨石蜡切片进行阿尔辛蓝/橙黄G染色,观察骨组织形态学变化。结果 OVX后4周开始,模型组小鼠体重明显升高,并持续高于假手术组(P0.01)。骨折术后4周,模型组小鼠血清雌二醇和第四腰椎骨密度(BMD)明显低于假手术组(P0.01),化瘀补肾方组小鼠血清雌二醇水平和第四腰椎BMD高于模型组(P0.01)。Micro-CT三维重建显示,模型组左侧胫骨仍有明显的骨折线,骨痂生长不明显,化瘀补肾方组骨折线模糊,骨痂形成明显。与假手术组相比,模型组小鼠的BV/TV(P0.01)、Tb.Th(P0.05)和Tb.N(P0.01)均明显降低,Tb.Sp明显升高,化瘀补肾方组小鼠的BV/TV(P0.05)、Tb.Th(P0.05)相较于模型组则显著升高,但Tb.N、Tb.Sp差异无统计学意义。与假手术组比较,模型组小鼠胫骨的最大应力在骨折术后28 d时显著低于假手术组(P0.01),化瘀补肾方组小鼠胫骨的最大应力显著高于模型组(P0.01)。阿尔辛蓝/橙黄G染色显示,假手术组和化瘀补肾方组骨痂组织处于塑形期,可见明显骨小梁结构,而模型组骨痂组织内见大量脂肪组织,骨小梁稀疏。结论化瘀补肾方能有效促进去卵巢小鼠的骨折愈合,改善愈合骨组织的生物力学性能。     

仙灵骨葆胶囊联合阿仑膦酸钠对骨质疏松骨折大鼠骨痂血管形成的影响

目的探讨仙灵骨葆胶囊联合阿仑膦酸钠对骨质疏松性骨折大鼠骨痂血管形成及VEGF、BMP-2表达的影响。方法50只雌性SD大鼠随机分为假手术组(SHAM组)、模型组(MODEL组)、仙灵骨葆组(XLGB组)、阿仑膦酸钠组(ALLSN组)、联合药物组(LHYW组),10只/组,构建骨质疏松性骨折大鼠模型,放射性X线观察评估骨折愈合,双能X线检测骨密度,Mirco-CT检测骨结构形态学参数,番红O固绿染色观察骨痂组织形态学,免疫组化检测骨痂VEGF和BMP-2蛋白表达。结果所有实验大鼠均进入结果分析。与SHAM组比较,MODEL组大鼠骨折愈合评分、骨密度、骨组织形态学参数、骨痂VEGF和BMP-2表达均显著降低(P0.05),与MODEL组比较,XLGB组、ALLSN组和LHYY组骨折愈合评分、骨密度、骨组织形态学参数、骨痂VEGF和BMP-2表达均显著升高(P0.05),尤以LHYY组最高。SHAM组骨小梁结构正常,几乎均为骨性骨痂。MODEL组骨小梁明显稀疏、断裂,未见明显骨性骨痂。XLGB组和ALLSN组骨小梁增多,排列稍紊乱,大部分为骨性骨痂。LHYW组骨小梁明显增多,排列密集整齐,大量骨性骨痂。结论仙灵骨葆胶囊联合阿仑膦酸钠可能通过介导提高骨质疏松性骨折大鼠骨生长因子VEGF和BMP-2表达,促进骨痂血管形成,加速骨痂形成,增加骨密度,改善骨结构形态,促进骨折愈合。     

Changes of microstructure and mineralized tissue in the middle and late phase of osteoporotic fracture healing in rats

BACKGROUND: With osteoporosis emerged as one of the most important health issues, more and more investigations are focusing on osteoporotic fracture healing. However, there are few studies on the changes of microstructure and mineralized tissue of newly formed callus. OBJECTIVE: We established an osteoporotic fracture rat model to evaluate the changes of microstructure and mineralized tissue during osteoporotic fracture healing. MATERIALS AND METHODS: A mid-shaft femur fracture model was established 12 weeks after ovariectomy as an osteoporotic fracture group (OPF group). Femurs were then harvested at 4 weeks, 8 weeks and 12 weeks after fracture for peripheral quantitative computed tomography (pQCT), micro-computed tomography (MicroCT), histology and biomechanical test. A sham-operated group was used for comparison, i.e. the normal fracture group (NF group). RESULTS: The pQCT-derived total external callus area in the OPF group was smaller than that in the NF group at 4 weeks after fracture (P<0.05), whereas it was 21% larger in the OPF group than that in the NF group at 12 weeks after fracture (P<0.01). The pQCT-derived bone mineral density in the OPF group was significantly inferior to the NF group at all the time points (P<0.05 for all the time points, respectively). MicroCT data, at 12 weeks after fracture, showed the total callus, bony callus, and newly formed bone was approximately 20% lower in the OPF group than that in the NP group, and the total connectivity was 56% lower in the OPF group as compared to the NF group. Biomechanical test data, at 12 weeks after fracture, showed that the failure load of the left femur of OPF group was 17% less compared to that of the NF group (P<0.01), and 15% lower bending stiffness (P<0.05), 20% lower bending stress (P<0.01), and 28% lower energy at failure (P<0.01) were observed in the OPF group as compared to the NF group. CONCLUSION: The decrease in mineralized tissue and the not well connected microstructure in newly formed callus may explain the decline of mechanical impairment of fracture healing in the ovariectomized rats.     

Effect of osteoporosis medications on fracture healing

Antiosteoporotic medications are often used to concurrently treat a patient’s fragility fractures and underlying osteoporosis. This review evaluates the existing literature from animal and clinical models to determine these drugs’ effects on fracture healing. The data suggest that these medications may enhance bone healing, yet more thorough prospective studies are warranted. Pharmacologic agents that influence bone remodeling are an essential component of osteoporosis management. Because many patients are first diagnosed with osteoporosis when presenting with a fragility fracture, it is critical to understand how osteoporotic medications influence fracture healing. Vitamin D and its analogs are essential for the mineralization of the callus and may also play a role in callus formation and remodeling that enhances biomechanical strength. In animal models, antiresorptive medications, including bisphosphonates, denosumab, calcitonin, estrogen, and raloxifene, do not impede endochondral fracture healing but may delay repair due to impaired remodeling. Although bisphosphonates and denosumab delay callus remodeling, they increase callus volume and result in unaltered biomechanical properties. Calcitonin increases cartilage formation and callus maturation, resulting in improved biomechanical properties. Parathyroid hormone, an anabolic agent, has demonstrated promise in animal models, resulting in accelerated healing with increased callus volume and density, more rapid remodeling to mature bone, and improved biomechanical properties. Clinical data with parathyroid hormone have demonstrated enhanced healing in distal radius and pelvic fractures as well as postoperatively following spine surgery. Strontium ranelate, which may have both antiresorptive and anabolic properties, affects fracture healing differently in normal and osteoporotic bone. While there is no effect in normal bone, in osteoporotic bone, strontium ranelate increases callus bone formation, maturity, and mineralization; forms greater and denser trabeculae; and improves biomechanical properties. Further clinical studies with these medications are needed to fully understand their effects on fracture healing in order to simultaneously treat fragility fractures and underlying osteoporosis.     

甲状旁腺激素联合阿仑膦酸钠对大鼠骨质疏松性骨折骨痂血管形成的影响

目的探讨甲状旁腺激素联合阿仑膦酸钠对大鼠骨质疏松性骨折骨痂血管形成及骨折愈合的影响。方法 75只雌性SD大鼠随机分为5组:假手术组、去势组、甲状旁腺素组、阿仑膦酸钠组、联合用药组,每组15只,首先行双侧卵巢切除术,术后4周行右侧股骨干骨折髓内固定术,以构建大鼠骨质疏松性骨折动物模型。观察并评估骨折愈合,检测骨痂生物力学和骨密度(bone mineral density,BMD),检测血清血管内皮生长因子(vascular endothelial growth factor,VEGF)和骨形成发生蛋白-2(bone morphogenetic protein-2,BMP-2)浓度,观察骨痂形态结构,检测骨痂VEGF表达。结果去势组较假手术组骨折愈合评分、骨痂生物力学强度、骨痂BMD、血清BMP-2和VEGF浓度、骨痂VEGF蛋白表达、骨痂微血管数均显著降低(P0.05),甲状旁腺素组、阿仑膦酸钠组、联合用药组较去势组上述指标均升高,其中以联合用药组升高最显著(P0.05)。结论甲状旁腺激素联合阿仑膦酸钠通过介导VEGF,上调BMP-2表达,促进骨质疏松性骨折大鼠骨痂血管形成,增加骨密度,改善生物力学强度及骨组织形态学,加快骨折愈合。     

Poor histological healing of a femoral fracture following 12 months of oestrogen deficiency in rats

Summary

Fractures in post-menopausal osteoporosis cause significant morbidity; however, animal models for post-menopausal fracture healing lack the effect of ageing. Therefore, we developed a model using aged animals with chronic oestrogen deficiency, which demonstrates inferior fracture repair (decreased healing histologically, bone mineral density and content and strength). This novel model may help develop molecular strategies for osteoporotic fracture repair.

Introduction

The femur is susceptible to damage by both systemic conditions such as osteoporosis and locally by traumatic injury. The capacity for fracture repair decreases with age, while the risk of fracture increases. As studies of osteoporotic fracture healing in rats traditionally use a period of 3 months or less of oestrogen deficiency prior to fracturing, we aimed to establish a osteoporosis model in rats with chronic oestrogen deficiency by 12 months to better mimic human female osteoporosis.

Methods

Seventy female Sprague–Dawley rats (10 weeks old) were ovariectomised or sham operated and housed for 12 months. The right femur was fractured by way of an open osteotomy and fixed with an intramedullary Kirschner wire. Animals were sacrificed at 1, 3 and 6 weeks for radiography, dual-energy X-ray absorptiometry, tensile testing and histology.

Results

Bone mineral density and bone mineral content were lower by 60 and 63 %, respectively, (p?<?0.05) in the bilaterally ovariectomized (OVX) groups than those in the sham groups at 6 weeks in the right fractured femurs. Maximum breaking force of the OVX group was lower than that of the sham group, with the greatest difference seen at 6 weeks following osteotomy. Histologically, the OVX groups demonstrated a delay in cellular differentiation within the fracture callus and the presence of bone resorption. The sham animals had a superior histological healing pattern with an Allen score of 4 at 6 weeks compared to a score of 1 for the OVX groups (p?<?0.01).

Conclusions

Long-term ovariectomy has a deleterious effect on fracture healing in a rodent model.     

Bolus or weekly zoledronic acid administration does not delay endochondral fracture repair but weekly dosing enhances delays in hard callus remodeling

INTRODUCTION: It has been widely assumed that osteoclasts play a pivotal role during the entire process of fracture healing. Bisphosphonates (BPs) are anti-catabolic agents commonly used to treat metabolic bone diseases including osteoporosis, minimizing fracture incidence. Yet, fractures do occur in these patients and the potential for negative effects of BPs on healing has been suggested. We aimed to examine the effect of different dosing regimes of the potent BP zoledronic acid (ZA) on early endochondral fracture repair and later callus remodeling in a normal bone healing environment. METHODS: Saline, a Bolus dose of 0.1 degrees mg/kg ZA or 5 weekly divided doses of 0.02 degrees mg/kg of ZA commenced 1 week post operatively in a rat closed fracture model. Samples at 1, 2, 4 and 6 weeks post fracture were used to analyze initial fracture union, and 12 and 26 weeks post fracture to investigate the progress of remodeling. RESULTS: ZA did not alter the rate of endochondral fracture union. All fractures united by 6 weeks, with no difference in the progressive reduction of cartilaginous soft callus between control and treatment groups over time. ZA treatment increased hard callus bone mineral content (BMC), volume and increased callus strength at 6 and 26 weeks post fracture. Hard callus remodeling commenced at 4 weeks post fracture with Bolus ZA treatment but was delayed until after 6 weeks in the Weekly ZA group. By 12 and 26 weeks, Bolus ZA had equivalent callus content of remodeled neo-cortical bone to the Saline controls, whereas Weekly ZA remained reduced compared to Saline controls at these times (P<0.01). Callus material properties such as peak stress were significantly reduced in both ZA groups at 6 weeks. At 26 weeks, Bolus ZA-treated calluses generated peak stress equivalent to control values, whereas Weekly ZA callus peak stress remained significantly reduced, indicating remodeling delay. CONCLUSIONS: Osteoclast inhibition with ZA does not delay endochondral fracture repair in healthy rats. Bolus ZA treatment increased net callus size and strength at 6 weeks while allowing hard callus remodeling to proceed in the long term, albeit more slowly than control. Prolonged bisphosphonate dosing during repair does not delay endochondral ossification but can significantly affect remodeling long after the drug is ceased.     

Implications for Fracture Healing of Current and New Osteoporosis Treatments: An ESCEO Consensus Paper

Osteoporotic fracture healing is critical to clinical outcome in terms of functional recovery, morbidity, and quality of life. Osteoporosis treatments may affect bone repair, so insights into their impact on fracture healing are important. We reviewed the current evidence for an impact of osteoporosis treatments on bone repair. Treatment with bisphosphonate in experimental models is associated with increased callus size and mineralization, reduced callus remodeling, and improved mechanical strength. Local and systemic bisphosphonate treatment may improve implant fixation. No negative impact on fracture healing has been observed, even after major surgery or when administered immediately after fracture. Experimental data for denosumab and raloxifene suggest no negative implications for bone repair. The extensive experimental results for teriparatide indicate increased callus formation, improved biomechanical strength, and greater external callus volume and total bone mineral content and density. Case reports and a randomized trial have produced mixed results but are consistent with a positive impact of teriparatide on clinical fracture healing. Studies with strontium ranelate in models of fracture healing indicate that it is associated with improved bone microstructure, callus volume, and biomechanical properties. Finally, there is experimental evidence for a beneficial effect of some of the agents currently being developed for osteoporosis, notably sclerostin antibody and DKK1 antibody. There is currently no evidence that osteoporosis treatments are detrimental for bone repair and some promising experimental evidence for positive effects on healing, notably for agents with a bone-forming mode of action, which may translate into therapeutic applications.     

局部应用CPC/rhBMP-2复合材料对骨质疏松大鼠骨折愈合的影响

目的研究磷酸钙骨水泥（Calcium Phosphate Cement，CPC）与重组人骨形态发生蛋白-2（Recombinant Human Bone Morphogenefic Protein-2，rhBMP-2）复合材料对骨质疏松大鼠骨折愈合的影响。方法取4月龄雌性清洁大鼠106只，随机分成实验组96只，对照组10只。实验组行双侧卵巢切除术，对照组行假手术，术后行双能X线骨扫描确定骨质疏松动物模型形成。然后将实验组96只大鼠制作右侧股骨远端松质骨骨折，将上述动物随机分成3组，每组32只：（1）克氏针组，从髁间窝穿入直径1mm克氏针固定；（2）CPC组，将CPC从12号针头注入骨髓腔，手法固定至骨水泥凝固；（3）CPC-BMP组，将CPC与rhBMP-2复合材料用12号针头注入骨髓腔，手法固定至骨水泥凝固。术后第2、4、6、8wk三组各取8只动物处死，取手术侧股骨远端标本行压缩实验。结果在上述4个时间点，CPC-BMP组的骨折段最大载荷较克氏针组及CPC组增高（P〈0．05）；第2周CPC组骨折段最大载荷较克氏针组增高（P〈0．05）。结论（1）局部注射CPC-BMP复合材料可以促进骨质疏松大鼠骨折的愈合，提高骨折愈合后的强度；（2）CPC局部应用可以对骨折起到即时固定作用。     

蒙药蓝刺头抗绝经后骨质疏松症骨微观形态学计量研究

目的通过研究证实蒙药蓝刺头防治绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)的作用。基于蒙医药"补暖补精-清镇赫依-固骨质壮骨"经典理论,通过防治PMOP提供实验依据,揭示此理论、治法效应,为蒙医药现代化提供思路。方法分组:6月龄SD系SPF级健康雌性未孕大鼠84只,体重(250±20) g,随机分为假手术组(Sham)、去卵巢骨质疏松模型组(OVX)、蒙药蓝刺头高剂量组(Echinops-H)、中剂量组(Echinops-M)、低剂量组(Echinops-L)、中药对照组淫羊藿组(HEP)、西药对照组辅酶Q10组(Co-Q10) 7组。造模:采用双侧卵巢切除法(去势)制备绝经后骨质疏松模型,阴道上皮角化实验、骨密度检测、子宫病理学检查验证造模成功。给药:术后90 d,模型组、假手术组给予生理盐水灌胃,其余各组予相应药物灌胃。标本采集:末次灌胃后行标本采集。处死大鼠剔除右侧完整股骨并标记,4%多聚甲醛溶液固定保存。指标检测:右侧股骨采用骨密度仪测定离体骨骨密度(bone mineral density,BMD)(股骨近端BMD、股骨总BMD)检测,行Micro-CT骨微结构形态计量学测定。结果去卵巢术后各组大鼠BMD下降明显,表现为松质骨、皮质骨骨量相继减少,皮质骨变薄,BMD下降;去卵巢术后各组大鼠骨组织体积、骨小梁体积分数、骨小梁厚度、骨小梁宽度、骨小梁数目、骨小梁模块因素下降明显,骨小梁分离度升高明显;适当剂量蒙药蓝刺头可以明显提高大鼠骨组织体积、骨小梁体积分数、骨小梁厚度、骨小梁宽度、骨小梁数目、骨小梁模块因素,明显降低骨小梁分离度;其具明显抗PMOP作用。结论蒙药蓝刺头对PMOP模型大鼠具显著抗骨质疏松作用;蒙药蓝刺头能显著促进模型大鼠骨组织成骨分化、骨形成;降低PMOP模型大鼠骨代谢高转换指标,抑制骨吸收。     

骨质疏松性骨折愈合的细胞学观察

目的为了解骨质疏松性骨折愈合的过程及期问的细胞学变化情况。方法切除成年雌犬双侧卵巢，造成绝经后骨质疏松症模型，并人为造成胫骨骨折用螺钉内固定，以观察骨折愈合情况。结果发现骨质疏松性骨折后两周左右，骨折骨小梁表面及周围有大量大小不等的圆形细胞增殖，骨吸收陷窝内有胶原纤维形成，但比较稀疏、紊乱。在骨折塑形改造期，破骨细胞性骨吸收活动显得异常活跃，而成骨细胞性骨形成显得异常微弱。结论骨质疏松性骨折的治疗，不但要使骨折良好复位，坚强固定，而且在骨折塑形改造期，更应该促进成骨细胞的活性，降低破骨细胞活性，使骨形成增加，骨吸收减少。     

骨质疏松动物实验骨折风险性分析

目的:评价骨质疏松动物模型发生骨折的风险性.方法:健康雌性SD大鼠36只,随机分为实验组和对照组各18只.实验组切除双侧卵巢,对照组仅切开皮肤.于术后2、4、8周两组处死6只大鼠,作松质骨(腰椎)和皮质骨(股骨干)骨密度(BMD)组织形态学和力学测定.结果:与对照组相比,手术组松质骨BMD 2、4、8周均明显下降,2周皮质骨无明显差异,4、8周则明显下降;股骨中段骨皮质厚度变薄;骨小梁体积(TBV)占全部骨组织体积(TTV)的百分比明显减少;成骨细胞和破骨细胞明显增多;股骨最大弯曲载荷、腰椎最大压缩载荷下降.     

唑来膦酸对老年桡骨远端骨折术后疗效观察

目的观察唑来膦酸对老年桡骨远端骨折的术后疗效。方法分析自2012年1月1日至2012年12月31日行桡骨远端骨折手术患者136例接受手术治疗并纳入研究,118例获得随访(87%),分成唑来膦酸组(A组,59例)和对照组(B组,59例)。唑来膦酸组平均年龄(73.09±5.04)岁,男12例,女47例,术后2~7 d使用唑来膦酸抗骨质疏松治疗,并常规补充钙剂和骨化三醇;对照组平均年龄(73.25±6.96)岁,男14例,女45例,术后2~7 d使用针剂密盖息抗骨质疏松治疗,出院后继续使用密盖息鼻喷剂至术后3个月,常规补充钙剂和骨化三醇,术后4周、3个月随访骨折愈合的情况及术后1年复查骨密度的情况。结果老年桡骨远端骨折患者使用唑来膦酸抗骨质疏松药物后骨折愈合无明显影响且腕关节功能改善,术后1年骨密度较前增加。结论发生桡骨远端骨折的老年骨质疏松患者使用唑来膦酸药物后骨质疏松治疗效果好,同时对骨质疏松性桡骨远端愈合无明显不利影响。