Specific entities affecting the craniocervical region

INTRODUCTION: Osteogenesis imperfecta (OI) is an inheritable disorder of bone development caused by defective collagen synthesis. The attendant basilar impression or secondary basilar invagination is uncommon but can be devastating. CLINICAL MATERIALS AND METHODS: Fifty-two patients with osteochondrodysplasia (28 with OI, six with Hajdu-Cheney syndrome, six with Paget's disease, and 12 with spondyloepiphyseal dysplasia) with basilar impression were evaluated between 1985 and 2005. The male/female ratio in this cohort was 1:1. The mean age at presentation was 12.2 years. SYMPTOMS: Symptoms and signs included headache, lower cranial nerve dysfunction, dysphagia, respiratory embarrassment, weakness, and ataxia. TREATMENT: In the earlier part of the series (1985-1995), all patients with hydrocephalus were shunted and a ventral transoral decompression made for ventral compression of the pontomedullary junction followed by a dorsal occipitocervical fusion. As a result of this evaluation, it was felt that most patients would benefit by early bracing after the hydrocephalus was shunted if it existed. However, 20% of patients still required an anterior ventral decompression and the occipitocervical fusion. RESULTS: The results showed that the fusions were stable but over a period of time, there was progressive forward bending with osteogenesis imperfecta as well as with the Hajdu-Cheney syndrome. All patients with spondyloepiphyseal dysplasia had a good strong stable fusion which stood the test of time. CONCLUSION: In conclusion, we feel that early intervention with occipitocervical bracing can prevent the progressive march of significant basilar impression which leads to mortality.     

神经植入对大段组织工程骨成骨效果的一年观察

目的 观察在组织工程骨内植入神经束后大段组织工程骨的长期成骨效果.方法 新西兰大白兔64只,随机分为四组:A组,单纯组织工程骨组;B组,运动神经束植入组(股神经肌支);C组,感觉神经束植入组(隐神经);D组,感觉、运动神经束联合植入组.每只动物均在左侧股骨制作长1.5 cm的段缺性骨与骨膜缺损,钢板固定后在骨缺损处分别植入四种方法制备的组织工程骨.术后1、3、6、12个月行大体观察、X线和组织学定量观察成骨情况. 结果 术后1、3、6个月时,在组织工程骨内植入感觉神经或联合植入两种神经后,比单纯组织工程骨和运动神经束植入的修复效果均有明显提高.术后12个月时,各组骨再生情况基本一致,但新生骨组织出现一定程度的吸收,其外观较正常股骨细,新生骨组织与兔股骨牢固愈合,并开始塑形且出现髓腔再通. 结论 在组织工程骨内植入感觉神经可促进成骨,而植入运动神经未见促进作用;组织工程骨可以修复兔大段骨缺损;该实验新生骨组织的吸收可能与模型的制作方法有关.     

家兔自体骨髓移植对骨痂中钙镁铜含量的影响

目的 探讨新骨的形成在骨髓移植术后2周尤为显著现象的机制。方法 用34只家兔剥除双侧桡骨骨膜3cm，截除剥离骨膜后的桡骨中段1cm，1小时后去除骨缺损区血肿，从股骨大转子处抽取1ml骨髓，随机注入一侧桡骨缺损区作为实侧，另一侧注入等量生理盐水作为对照侧，术后2、4、6、8周分批做放射学、组织学和骨痂中钙、镁、铜含量的检查。结果 骨髓移植有肯定的成骨效果，术后2周实验侧骨痂中镁、铜及术后4周镁含量高于对照侧（P＜0．01）。结论 铜和镁在骨髓移植促进骨缺损愈合早期可能具有重要作用，移植术后的2周内补充铜和镁有可能提高骨髓移植的成骨能力。     

Synthesis and Discovery of Novel Pyrazole Carboxamide Derivatives as Potential Osteogenesis Inducers

A series of novel N‐aryl‐3‐aryl‐1‐arylmethyl‐1H‐pyrazole‐5‐carboxamide derivatives 4a – l was synthesized by the reaction of 3‐aryl‐1‐arylmethyl‐1H‐pyrazole‐5‐carbonyl chloride with substituted aniline in good to excellent yields. Structures of the compounds were determined by IR, ¹H NMR, and HR‐MS spectroscopy. The molecular structure was confirmed by the X‐ray crystal analysis of one compound ( 4j ) that was prone to crystallization. These compounds were used to induce mouse osteoblast precursors MC3T3‐E1 into osteoblasts and the induction was assessed by alkaline phosphatase (ALP) activity and the gene expression of bone sialoprotein (BSP). The results showed that the compounds 4a – d , 4g , 4h , and 4k could increase the ALP activity in comparison with the negative control group and compound 4h was the most effective one which could induce osteogenesis. Furthermore, mRNA expression of BSP which is a marker of osteogenesis was up‐regulated by the compound 4h .     

Treatment of chronic disruption of the patellar tendon in Osteogenesis Imperfecta with allograft reconstruction

We present a case of chronic disruption of the patellar tendon in a patient with Osteogenesis Imperfecta. This patient was treated with a customized extensor mechanism allograft. Results were excellent at 5 years follow up. To our knowledge this treatment has not previously been published in this situation. We present this as a reliable treatment option.     

The epitope characterisation and the osteogenic differentiation potential of human fat pad-derived stem cells is maintained with ageing in later life

Some clinical settings are deficient in osteogenic progenitors, e.g. atrophic nonunited fractures, large bone defects, and regions of scarring and osteonecrosis. These benefit from the additional use of bone marrow-derived mesenchymal stem cells, but these cells exhibit an age-related decline in lifespan, proliferation and osteogenic potential. Therapeutic approaches for the repair of bone could be optimised by the identification of a stem cell source that does not show age-related changes. Fat pad-derived stem cells are capable of osteogenesis, but a detailed study of the effect of ageing on their epitope profile and osteogenic potential has so far not been performed.Fat pad-derived cells were isolated from 2 groups of 5 patients with a mean age of 57 years (S.D. 3 years) and 86 years (S.D. 3 years). The proliferation, epitope profile and osteogenic differentiation potential of cells from the 2 groups were compared. Cells isolated from the fat pad of both groups showed similar proliferation rates and exhibited a cell surface epitope profile similar but not identical to that of bone marrow-derived stem cells. The cells from both groups cultured in osteogenic medium exhibited osteogenesis as shown by a significant upregulation of alkaline phosphatase and osteocalcin genes, and significantly greater alkaline phosphatase enzyme activity compared to cells cultured in the control medium. The cells cultured in the osteogenic medium also showed greater calcium phosphate deposition on alizarin red staining. There was no significant difference between the osteogenic potential of the two age groups for any of the parameters studied.The fat pad is a consistent and homogenous source of stem cells that exhibits osteogenic differentiation potential with no evidence of any decline with ageing in later life. This has many potential therapeutic tissue engineering applications for the repair of bone defects in an increasingly ageing population.     

牵张成骨术整复猕猴腭裂后胰岛素样生长因子-1与碱性磷酸酶表达研究

Objective To investigate the osteogenesis mechanism by analysis of the expression of insulin-like growth factor-I (IGF-1)and alkaline phesphatas (ALP)in the reconstruction of cleft palate(CP) with distraction osteogenesis (DO) in rhesus. Methods The CP animal models were established surgically. 21 rhesus in experimental group underwent DO to close the soft and bony defect, followed by consolidations. Every 3 animals were killed and the specimen were taken out after consolidation of 1, 2, 4, 6, 8, 12, 24 weeks. The mRNA of IGF-1 and ALP were detected with Real-time BT-PCB technique. The expression of IGF-1 and ALP was quantitatively analyzed by ELISA. The results were compared with those in control and sham groups (each of 2 animals), respectively. Results Since consolidation, the mRNA of IGF-1 and ALP increased significantly at one week and reached the peak at two weeks, but decrease to control level after 12 weeks of consolidation. The expression of IGF-1 also increased to peak level afiert two weeks of consolidation. The expression of ALT increased significantly since consolidation and reach the peak value after six weeks. They all decreased to nearly control level after 8 ～ 12 weeks. Conclusions The palate cleft can be successfully closed with new formed bone after DO. The mechanism of bone consolidation is intramembranons bone formation.     

Surgical blood loss during femoral rodding in children with osteogenesis imperfecta

Background  Historically, patients with osteogenesis imperfecta (OI) have been reported to be at risk for significant surgical bleeding secondary to abnormalities in platelet function. By reviewing the operative blood loss in OI patients undergoing femoral osteotomies and rodding, we hoped to identify risk factors for excessive bleeding. Methods  A retrospective review of 22 patients with 52 inserted femoral rods was conducted under Institutional Review Board approval. Information concerning patients and procedures was collected. Associations with mean blood loss were made for categorical variables using the unpaired t-test and for continuous variables using correlation. Multivariate linear regression was used to test the influence of potential risk factors for excessive bleeding. Results  The mean blood loss was 197 cc (standard deviation [SD] 129 cc, range 10–500 cc). The adjusted mean blood loss (ratio of actual blood loss divided by the total predicted blood volume [Custer and Rau in “The Harriet Lane Handbook,” 18th edn. Mosby-Elsevier, Philadelphia, p 382, 2009]) was 0.16 (SD 0.13, range 0.01–0.44). Six blood transfusions were required out of 42 cases for a transfusion rate of 14%. The mean blood loss in those patients who were transfused was 279 cc compared with 182 cc for those not transfused. There were no differences in the adjusted mean blood loss between acute fracture treatment versus elective reconstruction (P = 0.08), nor between primary rodding versus revision rodding (P = 0.66). Older patients tended to have lower adjusted mean blood loss, though this was not significant (P = 0.07). Increasing number of osteotomies tended to lead to increased adjusted mean blood loss (P = 0.05). There was no association between operative time and adjusted mean blood loss (P = 0.36). When adjusting for procedure characteristics, increasing age was associated with decreasing adjusted mean blood loss (P = 0.008). Conclusion  Predicting blood loss for femoral rodding in patients with OI is difficult, with no differences between revision and primary procedures or elective versus trauma cases. The blood loss in our patients undergoing femoral rodding was manageable, and the transfusion rate was reasonably low. Although massive blood loss has been described in patients with OI in the literature, we found that femoral rodding did not pose excessive risk of transfusion in our OI population.     

Nitric oxide production during the osteogenic differentiation of human periodontal ligament mesenchymal stem cells

The critical tissues that require regeneration in the periodontium are of mesenchymal origin; therefore, the ability to identify, characterize and manipulate mesenchymal stem cells within the periodontium is of considerable clinical significance. In particular, recent findings suggest that periodontal ligament cells may possess many osteoblast-like properties. In the present study, periodontal ligament mesenchymal stem cells obtained from healthy volunteers were maintained in culture until confluence and then induced to osteogenic differentiation. Intracellular calcium ([Ca²⁺]_i) concentration and nitric oxide, important signalling molecules in the bone, were measured along with cell differentiation. Alkaline phosphatase activity was assayed and bone nodule-like structures were evaluated by means of morphological and histochemical analysis. Our results showed that the periodontal ligament mesenchymal stem cells underwent an in vitro osteogenic differentiation, resulting in the appearance of active osteoblast-like cells together with the formation of calcified deposits. Differentiating cells were also characterized by an increase of [Ca²⁺]_i and nitric oxide production. In conclusion, our data show a link between nitric oxide and the osteogenic differentiation of human periodontal ligament mesenchymal stem cells, thus suggesting that local reimplantation of expanded cells in conjugation with a nitric oxide donor could represent a promising method for treatment of periodontal defects.     

常染色体隐性遗传性成骨不全症的分子遗传学研究进展

成骨不全症(osteogenesis imperfecta,OI)又称脆骨症,由于遗传缺陷而引起Ⅰ型胶原结构或功能异常,表现为全身骨骼等结缔组织异常.临床特点是多发性骨折,同时可伴有巨头畸形、蓝巩膜、耳聋、牙齿改变和脊柱后侧凸等.成骨不全症不仪临床表型变异度大,而且遗传异质性高,以常染色体显件或隐性遗传方式传递,本文就常染色体隐性遗传性成骨不全症的分子遗传学研究进展加以综述.