骨质疏松治疗仪对骨折愈合影响的研究

目的 回顾分析应用骨质疏松治疗仪治疗闭合性桡骨远端骨折,观察其在促进骨折愈合的作用.方法 2007年5月～2010年1月,选择69例闭合性桡骨远端骨折,年龄55岁～86岁,平均67.2岁.按就诊时间为序,单数进入实验组,双数进入对照组,将69例患者按序分配到实验组和对照组,实验组35例,对照组34例.实验组在手法复位石膏托外固定术后即开始连续16周应用天津希统生产的XT-2000B骨质疏松治疗仪治疗.2次/d,40 min/次.对照组在手法复位石膏托外固定术后不给予骨质疏松治疗仪治疗.其余康复治疗及预防感染,活血化淤,促进骨折愈合的药物等的应用完全相同.实验组和对照组分别在2w,6w,12w,16w复查X片.结果 所有患者获得4月的随访.实验组在6w,12w,X片上有明显骨痂生长,16w有大量骨痂生长,且有部分病例髓腔再通.对照组在12w,X片上有少量骨痂生长,16w骨痂生长明显.但未发现有髓腔再通的病例.结论 应用骨质疏松治疗仪治疗骨折具有促进骨折愈合,缩短骨折治疗时间的作用.     

MRI findings on healing process of vertebral fracture in osteoporosis

The healing process of vertebral fracture was investigated in 37 senile osteoporotic patients on serial magnetic resonance imagings (MRIs), including enhancement study with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA). The healing process was classified retrospectively into six categories in terms of the changes and recovery of T1 and T2 signal intensity and in terms of the local vascularity. Two types of damage foci were identified, and, in each type, three patterns of healing were noted. In the partial collapse type, the focus of damage in the fractured vertebral body was located near the cranial or caudal endplates; in the total collapse type, the focus was located at the center of the body. In each of these two types, fracture healing was smooth, belated, or resulted in nonunion. In the partial collapse type, vertebral fractures healed smoothly (smooth pattern) in 8 cases, belatedly (belated pattern) in 11, and resulted in nonunion (nonunion pattern) in 5. In the total collapse type, vertebral fractures healed smoothly (smooth pattern) in 6 cases, belatedly (belated pattern) in 4, and resulted in nonunion (nonunion pattern) in 3. The percent height of the anterior wall, central portion, and posterior wall was defined to allow accurate calculatation of the collapse of the fractured vertebral body. Chronological changes in the vertebral body height were investigated. Progressive collapse of the vertebral body was minimal in the smooth pattern cases, and most severe in the nonunion pattern cases. Statistical analysis indicated that prediction of the course of the fracture was difficult only with the height of the fractured vertebral body in acute phase. Enhancement study with Gd-DTPA showed that, in fractures with favorable prognosis, the ischemic area in the body tended to be smaller from the beginning, and restoration of vascularity was prompt. On the contrary, in fractures with unfavorable prognosis, the ischemic area was wider, and restoration of vascularity was poor.     

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。     

The influence of osteoporosis in femoral fracture healing time

Aim

In order to assess the effect of osteoporosis on healing time, the files of 165 patients with femoral shaft fractures that were treated in our institution with locked-reamed intramedullary nailing were retrospectively reviewed.

Patients and methods

Patients with open fractures, pathological fractures, revision surgery, severe brain injuries and prolonged ITU stay were excluded. In all patients the Singh-index score for osteoporosis and the canal bone ratio (CBR) were assigned. Sixty-six patients fulfilled the inclusion criteria. Patients were divided into two groups; group A (29 patients) consisted of patients over 65 years old with radiological evidence of osteoporosis and group B (37 patients) of patients between 18 and 40 years old with no signs of osteoporosis.

Results

In all group A patients Singh score ≤4 and CBR > 0.50 were assigned, suggesting the presence of osteoporosis, whereas all group B patients were assigned with Singh score ≥5 and CBR < 0.48. Fractures of group A healed in 19.38 ± 5.9 weeks (12-30) and in group B 16.19 ± 5.07 weeks (10-28), P = 0.02.

Conclusions

Fracture healing of nailed femoral diaphyseal fractures is significantly delayed in older osteoporotic patients. Further studies are required to clarify the exact impact of osteoporosis in the whole healing process.     

The effects of nail rigidity on fracture healing in rats with osteoporosis

Background and purpose Stress shielding from rigid internal fixation may lead to refracture after removal of the osteosynthesis material. We investigated the effect of a low-rigidity (Ti-24Nb-4Zr-7.9Sn) intramedullary nail regarding stress shielding and bone healing of osteoporotic fractures in the rat.

Methods 40 female Sprague-Dawley rats, aged 3 months, were divided into the following groups: sham-operation (SHAM) (n = 10), ovariectomized (OVX) (n = 10) and OVX-fracture (n = 20). 10 SHAM rats and 10 OVX rats were killed after 12 weeks to provide biomechanical data. Ovariectomy was performed 12 weeks before fracturing both femurs in 20 rats. The left fracture was stabilized with a high-rigidity titanium alloy pin (Ti-6Al-4V; elastic modulus 110 GPa) and the right with a low-rigidity (Ti-24Nb-4Zr-7.9Sn; elastic modulus 33 GPa). The bony calluses were examined by micro-CT at 6 and 12 weeks after fracture, bone volume (BV) and total volume (TV) were determined at the callus region (ROI1) and the total femur (ROI2). Subsequently, the bones were tested mechanically by a three-point bending test.

Results In the low-rigidity group, TV (ROI1) increased at 6 weeks, but BV (ROI1), BV (ROI2) were similar but maximum load increased. At 12 weeks, the maximum load and also BV (ROI1, ROI2) were increased in the low-rigidity group.

Interpretation The low-rigidity nail manufactured from Ti-24Nb-4Zr-7.9Sn showed better external callus formation, seemed to reduce effects of stress shielding, and reduced bone resorption better than the stiffer nail. The low-rigidity nail was strong enough to maintain alignment of the fracture in the osteoporotic rat model without delayed union.     

The effects of nail rigidity on fracture healing in rats with osteoporosis

Background and purpose Stress shielding from rigid internal fixation may lead to refracture after removal of the osteosynthesis material. We investigated the effect of a low-rigidity (Ti-24Nb-4Zr-7.9Sn) intramedullary nail regarding stress shielding and bone healing of osteoporotic fractures in the rat.Methods 40 female Sprague-Dawley rats, aged 3 months, were divided into the following groups: sham-operation (SHAM) (n = 10), ovariectomized (OVX) (n = 10) and OVX-fracture (n = 20). 10 SHAM rats and 10 OVX rats were killed after 12 weeks to provide biomechanical data. Ovariectomy was performed 12 weeks before fracturing both femurs in 20 rats. The left fracture was stabilized with a high-rigidity titanium alloy pin (Ti-6Al-4V; elastic modulus 110 GPa) and the right with a low-rigidity (Ti-24Nb-4Zr-7.9Sn; elastic modulus 33 GPa). The bony calluses were examined by micro-CT at 6 and 12 weeks after fracture, bone volume (BV) and total volume (TV) were determined at the callus region (ROI1) and the total femur (ROI2). Subsequently, the bones were tested mechanically by a three-point bending test.Results In the low-rigidity group, TV (ROI1) increased at 6 weeks, but BV (ROI1), BV (ROI2) were similar but maximum load increased. At 12 weeks, the maximum load and also BV (ROI1, ROI2) were increased in the low-rigidity group.Interpretation The low-rigidity nail manufactured from Ti-24Nb-4Zr-7.9Sn showed better external callus formation, seemed to reduce effects of stress shielding, and reduced bone resorption better than the stiffer nail. The low-rigidity nail was strong enough to maintain alignment of the fracture in the osteoporotic rat model without delayed union.     

抗高血压药与骨质疏松症

骨质疏松症和高血压有共同的发病高危因素和病理生理机制,多见于老年人群。对于患者个体而言,二者往往同时存在。因此在进行抗高血压治疗的同时,有必要考虑抗高血压药物对骨密度和脆性骨折发生的影响。目前文献证实,除了袢利尿剂对骨量有负性作用外,噻嗪类利尿剂、血管紧张素转化酶抑制剂(ACEI)和血管紧张素II受体阻滞剂(ARB)、β受体阻滞剂和钙离子通道阻滞剂似乎都有一定骨保护作用,可增加骨密度和强度,降低骨质疏松骨折的发生几率。但尚需要双盲随机对照的临床试验和更多基础实验室证据支持骨质疏松症和高血压的相关性及抗高血压药物缓解骨丢失的作用。     

Antidepressant medications and osteoporosis

Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major types of bone cell (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the neuroendocrine system in bone. Observational studies indicate a complex relationship between depression, antidepressants, and fracture. First, the presence of depression itself increases fracture risk, in relation with decreased BMD and an increase in falls. A range of aspects of depression may operate, including behavioral factors (e.g., smoking and nutrition), biological changes, and confounders (e.g., comorbidities and concomitant medications). A substantial proportion of depressed patients receive antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). Some of these have been linked to decreased BMD (SSRIs) and increased fracture risk (SSRIs and tricyclic agents). Current use of SSRIs and tricyclics increases fracture risk by as much as twofold versus nonusers, even after adjustment for potential confounders. While there is a dose-response relationship for SSRIs, the effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. The increase in risk is the greatest in the early stages of treatment, with a dramatic increase after initiation, reaching a peak within 1 month for tricyclics and 8 months for SSRIs. Treatment-associated increased risk diminishes towards baseline in the year following discontinuation. The body of evidence suggests that SSRIs should be considered in the list of medications that are risk factors for osteoporotic fractures.     

Effect of smoking on tibial shaft fracture healing

Of 146 consecutive closed and Grade I open tibia shaft fractures treated with cast immobilization, external fixation, or intramedullary rod fixation during a 4-year period, 44 of 76 (58%) tibias of patients who smoked and 59 of 70 (84%) tibias of patients who did not smoke had followup to union or followup beyond 1 year. The demographics, fracture patterns, and treatments of the two groups were similar. Two of the 44 patients who smoked had nonunions at the 1-year followup, whereas none of the patients who did not smoke had nonunions. Of the 103 tibias with complete followup to union, the median time to clinical healing for patients who smoked (269 days) was significantly greater than that of patients who did not smoke (136 days). Likewise, there was a 69% delay in radiographic union in the group that smoked as interpreted by a radiologist blinded to the two groups. Statistical differences in clinical and radiographic healing rates between those who smoked and those who did not smoke were observed for patients receiving intramedullary fixation or external fixation. Statistical differences were not seen in the clinical and radiographic healing of tibias treated with cast immobilization, although tibias of patients who smoked took 62% longer to heal. The current data suggest that tibias of patients who smoke who require treatment with intramedullary nailing or external fixation require more time to heal than do those of patients who do not smoke.     

Effect of EHDP on fracture healing in dogs

Ethane-1-hydroxy-1,1-diphosphonate (EHDP) was administered subcutaneously to mature beagle dogs at dose levels of 0.1, 0.5, and 5.0 mg/kg/day for a 20 week period to determine the drug's effects on fracture healing. Uniform, transverse fractures of the midshaft radius were created in one limb and treated by external splintage. Drug-induced effects on fracture healing were monitored radiographically, histologically, and histomorphometrically; mechanical properties of the healing bones were determined in 4-point bending tests. At a dose of 0.1 mg/kg/day, ultimate load at failure and flexural rigidity of the fractured limbs equaled or exceeded that of saline control animals, and radiographic healing was normal. At a dose of 0.5 mg/kg/day ultimate load at failure and flexural rigidity of the fractured limbs proved inferior to saline control values, and radiographic healing appeared delayed. At a dosage of 5.0 mg/kg/day, there was obvious radiographic nonunion, and the callus of fractured radii had little inherent flexural rigidity or strength. Histomorphometrically, no differences were noted between control animals and the 0.1 or 0.5 mg/kg/day groups; however, mineralization activity appeared totally disrupted at the higher dosage level (5.0 mg/kg/day). In the 5.0 mg/kg/day group, EHDP-induced effects proved reversible with mineralization evident as early as 3 weeks following drug withdrawal. In mature beagle dogs EHDP proved to have dose-dependent and reversible inhibitory effects on secondary fracture healing.     

青壮年骨折与骨质疏松性骨折愈合机理及药物促愈机制研究进展

骨折愈合是一个复杂的组织学、生物学、内分泌及生物力学的动态过程,其机制非常繁杂.随着人口老龄化的发展和平均预期寿命的延长,骨质疏松症的发病率逐渐增加.骨质疏松性骨折是骨质疏松症最严重的后果,严重威胁着老年人的身心健康,降低生存期的生活质量.由于骨质疏松症本身的病理特点,决定了骨质疏松性骨折的愈合过程不同于正常骨折愈合过程.因此,鉴别认识骨质疏松性骨折的发病特点及机理,是预防骨质疏松性骨折的发生发展,是针对其病理本质进行靶向治疗的核心问题.笔者立足人体骨骼系统生理及疾病的病理生理过程,从组织学改变、细胞学机制及分子生物学机制等角度深入地阐述了骨折愈合的机制,提出临床药物治疗中要正确鉴别认识青壮年骨折与骨质疏松性骨折的特点,着眼两种不同骨折的愈合特点,把握其由内分泌因子、细胞因子、转录因子、受体及受体拮抗等分子调控的复杂信号传导通路机制,以拟定更科学的临床治疗方案,促进骨质疏松症研究的进一步深入.     

Effect of clodronate on fracture healing in denervated rats

The effect of clodronate on healing of the fracture of osteopenic bone was studied in rats. A total of 165 female rats (14 ± 1 weeks, 216 ± 2 g) were divided into five fracture groups (n = 30), and a neurectomized group (n = 15). Osteopenia (op) was induced by right sciatic neurectomy 4 weeks before the fracture. Nonosteopenic (nop) rats were not operated. A closed prepinned diaphyseal fracture of the right femur was done by three-point bending method both to op and nop rats, and the left femur served as an unoperated control. All the fracture groups were divided into treatment (clodronate 10 mg/kg/day sc) and control (saline sc) groups, and the administration was continued throughout the study. The op rats were killed 2, 4, 8, and 12 weeks and nop rats 8 weeks after the fracture. Fracture healing was examined by x-ray and bone-bending strength. Neurectomy reduced bone strength (p < 0.01) at 4 weeks. Clodronate did not affect the bending strength of healing callus of op rats at 2, 4, 8, or 12 weeks after fracture, but reduced the strength of healing callus in nop rats (p < 0.05) at 8 weeks. Radiologic callus width increased in clodronate-treated groups both in op (8 and 12 weeks, p < 0.001) and nop rats (8 weeks, p < 0.05) when compared with saline-treated groups. Clodronate did not affect normal bone strength.

In conclusion, clodronate did not affect the bending strength of op fracture nor the strength of the control bones. The remodeling of the fracture was delayed with clodronate.     

Effect of tenoxicam on fracture healing in rat tibiae

BACKGROUND: Nonsteroidal anti-inflammatory drugs have been implicated in the development of delayed unions and nonunion after fractures in animal models. Previous investigations have identified two important factors as determinants of delayed fracture healing: early drug administration and a dose-dependent effect. OBJECTIVE: The purpose of this investigation was to study the effect of tenoxicam, a nonsteroidal anti-inflammatory drug, on the fracture healing process in rat tibiae. METHODS: Fifty-eight Wistar rats were randomly divided in four groups (I, II, III, and IV). Group I (control group, n=12) was given 0.1ml saline solution per day intramuscularly. Groups II (n=12), III (n=12), and IV (n=12) were administered 10mg per kg per day of tenoxicam intramuscularly. Administration of substances was begun on a week before to 48h after the fracturing procedure and continued during the entire experiment. Callus formation was studied histologically and histomorphologically, using light microscopy. In addition, a histologic grading based on the morphologic stage of fracture healing was carried out at 4 weeks, according to the criteria proposed by Allen et al. RESULTS: There was a significant difference in treatment effect between Group I (saline solution) and Groups II, III, and IV (tenoxicam) (P=0.07). Histologically and histomorphologically, there were qualitative and quantitative delay in callus formation at all tenoxicam groups. This was more pronounced the earlier the nonsteroidal anti-inflammatory drug was started, although no significant difference could be detected between Groups II, III, and IV (P>(alpha=10%)). Four weeks after fracture, Group I (n=3) showed complete osseous union, Groups II (n=3) and III (n=3), complete cartilaginous union, and Group IV (n=3), incomplete osseous union, according to Allen et al. By using this rating scale, the difference between control and drug-treated groups was statistically significant (P<0.1). CONCLUSION: Under studied conditions, this investigation shows that administration of tenoxicam intramuscularly delays fracture healing process in rat tibiae. These results suggest the hypothesis that early drug administration may delay bone healing after experimental fractures in animals, although it could not be detected statistically significant.     

长期应用双膦酸盐类药物对老年性骨质疏松骨折愈合过程的影响

目的探讨长期应用双膦酸盐类药物(阿仑膦酸钠)治疗老年性骨质疏松症所引起的骨质疏松骨折的可行性以及长期应用双膦酸盐类药物在骨质疏松骨折愈合过程中对于骨组织的影响,为临床正确应用抗骨吸收药物治疗原发性骨质疏松症提供科学理论根据。方法选择90只12月龄雌性SD大鼠,常规饲养至15月龄左右。每组于骨折造模前2周以及骨折造模后并开始给药后的2周、4周、8周、12周5个时间点,进行X线、组织形态、骨代谢生化标志物以及micro-CT的检测。结果 X线:实验组A早期有明显的梭形外骨痂,但12周未愈合。组织形态学:实验组A早期见大量软骨细胞,愈合晚期虽有改建后成熟骨小梁和新生血管,但骨折处未愈合。骨代谢生化标志物:BAP:实验组A于12周的成骨活性均低于实验组B和实验组C;CTX-1:实验组A于8周后其水平逐渐增高。Micro-CT:实验组A的骨小梁厚度、骨小梁数量减少;骨小梁分离度增加。(统计数据均利用SPSS16.0进行统计分析,P<0.05)。结论长期应用双膦酸盐药物治疗老年性骨质疏松引起的骨折会导致骨折断端愈合延迟甚至不愈合。     

脑源性神经营养因子在大鼠胫骨骨折愈合中的作用研究

目的通过研究脑源性神经营养因子(BDNF)对骨折愈合的影响,探讨神经营养因子在骨组织工程和临床治疗中的应用前景。方法使用SD大鼠胫骨横行骨折髓内针内固定模型,术后处理组每隔一天皮下注射BDNF,对照组注射生理盐水,分别在第2、3、4、5周取胫骨对骨折愈合行大体比较、力学测试和扫描电镜观察。结果术后2周两组骨折均为结缔组织连接;3周处理组已有编织骨愈合,对照组仍有明显的骨折端活动;4周两组均呈骨性愈合,但处理组的骨痂、成角畸形较小;5周时处理组骨折塑型好,对照组骨折端仍有较大骨痂。处理组骨折矢状面成角在第3、4、5周小于对照组(P<0.05)。各阶段处理组抗折应力均优于对照组(P<0.05)。结论早期应用BDNF对骨折愈合的各阶段均可能有促进作用。     

脑外伤后体液因素对骨折愈合的影响

在骨科临床实践中经常见到一个奇怪的现象，在合并脑外伤的骨折病人中，骨痂生长快、数量多，甚至会出现异位骨化，似乎脑外伤会加速骨折愈合，事实是否如此呢?如果是的话，可能的机制会是什么?此机制对骨折愈合及异位骨化的产生作用是否一致?是什么将大脑和骨骼联系起来的?以上这些问题数十年来引起人们极大的兴趣，各国学者作了许多研究，