Scoliosis in children with osteogenesis imperfecta: influence of severity of disease and age of reaching motor milestones

We studied the relationship between the age of reaching motor milestones, especially anti-gravity activities, and the age of development of pathological spinal curvatures in children with osteogenesis imperfecta (OI). We hypothesized that earlier achievement of anti-gravity motor milestones predicts a later development of pathological spinal curvatures. Ninety-six children participated in this retrospective study. The severity of the disease was classified according to Sillence into types I-IV. Spinal radiography was performed annually and spinal deformities were measured according to the Cobb angle. Scoliosis was defined as a Cobb angle exceeding 9°. Pathological thoracic kyphosis was defined as a Cobb angle exceeding 40°. The parents were asked to report the age at which the child achieved motor milestones, and data were checked against health care records. Thirty-seven of 96 children (39%) developed a scoliosis of more than 9°. Nine of 96 children (9%) developed a pathological kyphosis. The age of developing scoliosis was significantly lower than the age of development of the pathological kyphosis (P=0.01). Bone mineral density was measured by dual energy X-ray absorptiometry (DEXA) in 53 children, 28 of whom developed scoliosis, and 25 of whom did not. The mean DEXA Z-score of the 28 children with scoliosis was significantly lower than that of the 25 children without (-5.2, SD 1.3 vs -3.2, SD 1.9; P-value <0.001). Children with OI type IV, but particularly OI type III, reached motor milestones much later than children with OI type I. The motor milestone "supported sitting" showed a significant inverse association with time of the first presence of scoliosis with a Cobb angle greater than 9° (linear regression coefficient: -1.3, 95% confidence interval: -2.6 to -0.03). The age of achieving the motor milestones "lifting the head to 45° in prone position", "rolling", and "supported-" and "unsupported standing" were not significantly associated with age of the first presence of scoliosis with a Cobb angle greater than 9°. However, the directions of associations suggest that here, too, there is a tendency for later development of scoliosis in those who reach milestones at earlier ages. Multivariable analyses showed that the motor milestone "sitting with support" was significantly associated with age of first achieving scoliosis, independent of gender and type of OI (linear regression coefficient: -0.9, 95% confidence interval: -1.3 to -0.5). We conclude that in children with OI, the age of anti-gravity motor milestones was associated with the age of development of pathological spinal curvatures. Earlier achievement of the motor milestone "supported sitting" predicted significantly a later development of pathological spinal curvatures, independent of gender and type of OI.     

Early bisphosphonate treatment in infants with severe osteogenesis imperfecta

OBJECTIVE: To evaluate prospectively the efficacy of bisphosphonate treatment in infants with severe forms of osteogenesis imperfecta (OI). STUDY DESIGN: Of 10 children (6 females) with OI type III, 5 (group A) started treatment (2 mg/kg neridronate administered intravenously for 2 consecutive days, every 3 months) just after diagnosis at birth and 5 (group B) after 6 months. Ten untreated children, matched for sex, age, and clinical severity of OI, constituted a historical control group (group C). We measured weight, length, and number of fractures every 3 months and serum and urinary levels of calcium, phosphorus, creatinine, serum alkaline phosphatase, 25-hydroxyvitamin D, insulin-like growth factor I, parathyroid hormone, and osteocalcin, urinary type I collagen N-terminal telopeptide, and lateral radiography of vertebral column every 6 months. RESULTS: Group A had better growth and a lower incidence of fractures than groups B and C in the first 6 months of treatment. In the second 6 months, both groups A and B had lower fracture rates than group C. After 12 months of therapy, osteocalcin and insulin-like growth factor I levels significantly increased only in group A. The urinary Ca/Cr ratio and N-terminal telopeptide/Cr ratio significantly declined only in treated patients. Vertebral body area and the structure of vertebral bodies improved in all treated patients, but especially in group A. CONCLUSIONS: Cyclical neridronate treatment, started just after diagnosis at birth, had positive effects on growth and fracture rate.     

优化牙支持式上颌骨前部牵引成骨术与上颌骨Le FortⅠ型前徙术治疗唇腭裂患者的效果及对其腭咽部结构的影响分析

目的 探讨优化牙支持式上颌骨前部牵引成骨术与上颌骨Le FortⅠ型前徙术治疗唇腭裂患者的效果,以及对其腭咽部结构的影响.方法 将大连市口腔医院2017年1月—2020年1月收治的63例唇腭裂伴上颌骨发育不足患者纳入研究,依据随机数字表法分为观察组31例和对照组32例.对照组实施上颌骨Le FortⅠ型前徙术治疗,观察...     

动态监测骨代谢标志物在诊治强直性脊柱炎中的意义

目的通过对血清骨代谢指标的动态检测探讨其与强直性脊柱炎(AS)发生发展的相关性,为AS的诊断预后及治疗提供客观依据。方法根据AS患者骶髂关节的病损程度分早期、进展期、晚期3期,选择各50例门诊及住院患者。对照组选择年龄及性别相匹配的50名健康对照者,取患者晨起空腹血样,采用电化学发光免疫(ECLIA)及酶联免疫吸附试验(ELISA)检测骨代谢相关指标:甲状旁腺素(PTH),总Ⅰ型前胶原氨基末端(N端)前肽(tPINP),骨钙素N端中分子片段(N-MID OT),I型胶原C端肽(β-CTX),25-羟基维生素D3[25-(OH)D3],Ⅰ型胶原交联羧基末端肽(ICTP)。对3期各组间数据进行比较及相关分析。结果①AS组血清中NMID OT、25-(OH)D3低于健康对照组,β-CTX、ICTP高于健康对照组,组间比较差异均有统计学意义(P<0.01);tPINP、PTH浓度水平在AS患者组与健康对照组组间无显著差异性(P>0.05)。②AS晚期组血清中N-MID OT、25-(OH)D3低于早期组,组间比较差异具有统计学意义(P<0.05);晚期组β-CTX、ICTP浓度水平高于早期组,组间比较差异均有统计学意义(P<0.05);晚期组与早期组tPINP、PTH在组间差异无统计学意义(P>0.05);随着AS疾病的进展,血清中N-MID OT、25-(OH)D3浓度水平逐渐降低,β-CTX、ICTP浓度水平显著升高。结论血清骨代谢指标在分期不同的AS患者中存在异常,不同指标参与了AS的骨吸收及骨转换过程,可为AS的诊断预后及治疗提供客观依据。     

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 .     

一罕见成骨不全Ⅳ型的基因诊断

目的对一疑似成骨不全Ⅳ型或其他类型的患儿实施基因诊断,以揭示患儿发病及频繁骨折的内在原因,为今后实施对症治疗和产前基因诊断创造必要的前提条件。方法对经症状、体征观察和X线检查初诊为成骨不全Ⅳ型或其他类型的患儿,在抽取外周血制备DNA模板后,采用PCR、DNA直接测序法,对患儿的COL1A1基因进行突变检测,然后对所发现的突变进行分析和鉴定。结果在COL1A1基因的编码区内发现一典型的错义突变(c.823G>C1/p.G275R),经查HGMD数据库证实为成骨不全Ⅳ型的致病性突变。结论先证者为一罕见的成骨不全Ⅳ型患儿,所发现的p.G275R突变为中国人群首次报道的病理性突变。     

珊瑚人工骨复合游离骨膜瓣的肌内植入试验

珊瑚人工骨复合游离骨膜植入兔腓肠肌内，所有试样均有新生骨骼和血管组织生成，３周时新骨量占试样的１３．３±７．０，６周时为２２．３±７．０％，新骨于植入５天后开始发生，并持续６周以上。而单纯人工骨或骨膜肌内植入均无新骨产生。全部植入物未发现炎症和排斥反应。     

复合型完全脱蛋白骨复合成骨细胞体内成骨的研究

目的　探讨复合型完全脱蛋白骨 (CFDB)作为成骨细胞支架材料体内植入的成骨作用。方法　将CFDB与人胚骨膜成骨细胞体外复合培养 1周后植入裸鼠体内 ,于术后 4周及 8周取出材料行ALP活性及常规组织学检查 ,了解其成骨作用。结果　CFDB复合成骨细胞体内植入 8周时ALP活性比 4周时强 ,并比单纯植入的材料强得多 ;实验侧 4周见有软骨形成 ,8周时有编织骨形成 ,并见有髓腔 ,且软骨或新骨形成增多 ,而对照侧未见软骨或骨形成。结论　CFDB复合成骨细胞体内植入后能形成软骨或骨 ,并随植入时间的延长 ,软骨或新骨形成增多 ;CFDB可用于成骨细胞的支架材料     

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.