Gα_s signaling controls intramembranous ossification during cranial bone development by regulating both Hedgehog and Wnt/β-catenin signaling

How osteoblast cells are induced is a central question for understanding skeletal formation. Abnormal osteoblast differentiation leads to a broad range of devastating craniofacial diseases. Here we have investigated intramembranous ossification during cranial bone development in mouse models of skeletal genetic diseases that exhibit craniofacial bone defects. The GNAS gene encodes Gαs that transduces GPCR signaling. GNAS activation or loss-of-function mutations in humans cause fibrous dysplasia(FD) or progressive osseous heteroplasia(POH) that shows craniofacial hyperostosis or craniosynostosis, respectively. We find here that, while Hh ligand-dependent Hh signaling is essential for endochondral ossification, it is dispensable for intramembranous ossification, where Gαsregulates Hh signaling in a ligand-independent manner. We further show that Gαscontrols intramembranous ossification by regulating both Hh and Wnt/β-catenin signaling. In addition, Gαsactivation in the developing cranial bone leads to reduced ossification but increased cartilage presence due to reduced cartilage dissolution, not cell fate switch. Small molecule inhibitors of Hh and Wnt signaling can effectively ameliorate cranial bone phenotypes in mice caused by loss or gain of Gnas function mutations, respectively. Our work shows that studies of genetic diseases provide invaluable insights in both pathological bone defects and normal bone development, understanding both leads to better diagnosis and therapeutic treatment of bone diseases.

Regulation of bone phosphorus retention and bone development possibly by BMP and MAPK signaling pathways in broilers

The bone morphogenetic protein(BMP)and mitogen-activated protein kinase(MAPK)signaling pathways play an important role in regulation of bone formation and development,however,it remains unclear that the effect of dietary different levels of non-phytate phosphorus(NPP)on these signaling pathways and their correlations with bone phosphorus(P)retention and bone development in broilers.Therefore,this experiment was conducted to investigate the effect of dietary P supplementation on BMP and MAPK signaling pathways and their correlations with bone P retention and bone development in broilers.A total of 800 one-day-old Arbor Acres male broilers were randomly allotted to 1 of 5 treatments with 8 replicates in a completely randomized design.The 5 treatments of dietary NPP levels were 0.15,0.25,0.35,0.45 and 0.55%or 0.15,0.22,0.29,0.36 and 0.43%for broilers from 1 to 21 days of age or 22 to 42 days of age,respectively.The results showed that extracellular signal-regulated kinase 1(ERK1)mRNA expression in the tibia of broilers on days 14 and 28,phosphorylated-ERK1(p-ERK1)on day 14,and BMP2 protein expression on days 28 and42 decreased linearly(P<0.04),while c-Jun N-terminal kinase 1(JNK1)mRNA expression on day 42 increased linearly(P<0.02)with the increase of dietary NPP level.At 14 days of age,total P accumulation in tibia ash(TP),bone mineral concentration(BMC),bone mineral density(BMD),bone breaking strength(BBS)and tibia ash were negatively correlated(r=-0.726 to-0.359,P<0.05)with ERK1 and JNK1 mRNA as well as p-ERK1;tibia alkaline phosphatase(ALP)and bone gal protein(BGP)were positively correlated(r=0.405 to 0.665,P<0.01)with ERK1 mRNA and p-ERK1.At 28 days of age,TP,BMC,BMD,BBS and tibia ash were negatively correlated(r=-0.518 to-0.370,P<0.05)with ERK1 mRNA and BMP2 protein,while tibia ALP was positively correlated(r=0.382 to 0.648,P<0.05)with them.The results indicated that TP,BMC,BMD,BBS or tibia ash had negative correlations,while tibia ALP and BGP had positive correlations with ERK1 and JNK1 mRNAs,BMP2 protein and p-ERK1,suggesting that bone P retention and bone development might be regulated by BMP and MAPK signaling pathways in broiler chickens.

Effect of dietary calcium or phosphorus deficiency on bone development and related calcium or phosphorus metabolic utilization parameters of broilers from 22 to 42 days of age

This experiment was conducted to investigate the effect of dietary calcium(Ca)or phosphorus(P)deficiency on bone development and related Ca or P metabolic utilization parameters of broilers from 22 to 42 days of age based on our previous study,which indicated that dietary Ca or P deficiency impaired the bone development by regulating related Ca or P metabolic utilization parameters of broilers from 1 to 21 days of age.A total of 504 one-day-old Arbor Acres male broilers were randomly assigned to 1 of 4 treatments with 7 replicates in a completely randomized design,and fed the normal control and Ca-or P-deficient diets from 1 to 21 days of age.At 22 days of age,the broilers were further fed the normal control diet(0.90%Ca+0.35%non-phytate P(NPP)),the P-deficient diet(0.90%Ca+0.18%NPP),the Ca-deficient diet(0.30%Ca+0.35%NPP)or the Ca and P-deficient diet(0.30%Ca+0.18%NPP),respectively.The results showed that dietary Ca or P deficiency decreased(P<0.05)tibia bone mineral density(BMD),bone breaking strength(BBS),ash content,tibia ash Ca content and serum P content on days 28 and 42,but increased(P<0.05)tibia alkaline phosphatase(ALP)activity of broilers on day 42 compared with the control group.Furthermore,the broilers fed the P-deficient diet had the lowest(P<0.05)tibia BMD,BBS,ash content,serum P content and the highest(P<0.05)serum Ca content on day 28 compared with those fed the Ca-deficient or Ca and P-deficient diets.The results from the present study indicated that the bone development and related Ca or P metabolic utilization parameters of broilers were the most sensitive to dietary P deficiency,followed by dietary Ca deficiency or Ca and P-deficiency;dietary Ca or P deficiency impaired the bone development possibly by regulating serum Ca and P contents as well as tibia Ca content and ALP activity of broilers from 22 to 42 days of age.

Role of fibroblast growth factor receptor 1 in the bone development and skeletal diseases

Accumulating data suggest that FGFs/FGFR1 plays essential roles in the bone development and human skeletal diseases. Conditional inactivation of fgfrl caused different phenotypes displaying in different cells or specific organs and revealed some novel functions of FGFR1 in bone development. Fgfrl mutation mainly induced 2 types of human skeletal diseases, craniosynostosis syndrome and dysplasias. Similar mutation of fgfrl in mouse model just mimicked the phenotype that happened in human. These fa- cilitate the investigation on the underlying mechanism of the diseases. Here we mainly focused on the ad- vance of FGFR1 function in the bone development and its mutation caused skeletal diseases.

Genetic and Environmental Effects on the Bone Development of the Hand and Wrist in Chinese Young Twins

We assessed genetic and environmental effectson bone development of the hand and wrist, andon key anthropometric measures in Chinese youngtwins. In total, 139 monozygotic and 95 dizygotictwin pairs aged from 5 to 18 years were recruited.The twin correlations of total hand and wrist scoresfor monozygotic （MZ） and dizygotic （DZ） twins were0.71 and 0.36, respectively. Bivariate modelanalysis showed moderate genetic correlations onlyfor total skeletal maturity vs. weight and totalskeletal maturity vs. waist circumference （r, 0.51and 0.46, respectively）. Our findings demonstratedthat genetic factors played important roles in bonedevelopment of the hand and wrist in Chineseyoung twins, and that these genetic effects mightbe distinct from those influencing anthropometricmeasures.

Skeletal stem cells in bone development,homeostasis,and disease

Tissue-resident stem cells are essential for development and repair,and in the skeleton,this function is fulfilled by recently identified skeletal stem cells(SSCs).However,recent work has identified that SSCs are not monolithic,with long bones,craniofacial sites,and the spine being formed by distinct stem cells.Recent studies have utilized techniques such as fluorescence-activated cell sorting,lineage tracing,and single-cell sequencing to investigate the involvement of ssCs in bone development,homeostasis,and disease.These investigations have allowed researchers to map the lineage commitment trajectory of ssCs in different parts of the body and at different time points.Furthermore,recent studies have shed light on the characteristics of ssCs in both physiological and pathological conditions.This review focuses on discussing the spatiotemporal distribution of ssCs and enhancing our understanding of the diversity and plasticity of ssCs by summarizing recent discoveries.

TGF-β and BMP signaling in osteoblast,skeletal development,and bone formation,homeostasis and disease

INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.

Alendronate disturbs femoral growth due to changes during immunolocalization of transforming growth factor-β1 and bone morphogenetic protein-2 in epiphyseal plate

BACKGROUND The epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone.Despite the abovementioned atractive reasons for alendronate’s use,few data on the effect of alendronate during epiphyseal growth exist.AIM Verify the effect of alendronate on the growth epiphyseal plate,and compare its effect with the size of the femur during the double-staining of the immunolocalization of transforming growth factor-β1(TGF-β1)and bone morphogenetic protein-2(BMP2)in endochondral ossifing in specimens that have received alendronate.METHODS Forty newborn rats were randomly divided into two groups:a control group(were given applications of 1 mg/kg physiologic saline)and a group that received Alendronate(a dose of 2.5 mg/kg).These groups were then divided into two subgroups for euthanasia in two and 12 d of life.After euthanasia,the femurs were removed,and the femoral bones were measured linearly between the apex of the greater trochanter until the lower intercondylar midlle face to verify the probable bone growth between 3 and 12 d in control and alednroanto treated rats.Posteriorly,the surgical pieces were also sent to the histopathology laboratory to produce histological slides.The obtained slides were stained with hematoxylin and eosin to measure each of the cartilage zones in endochondral development.and other slides were immunohistochemically tested for anti-TGF-β1 and BMP-2 antibodies to investigate the immunolocalization of these proteins in the epiphyseal plaque area.RESULTS On the third day,some diferences between the control group and specimens treated with alendronate were verified.Macroscopiccaly,we found similarities in size between the femoral bones when we compared the control group with the specimens that received alendronate.On the 12^th day,the bone size of the mice receiving the drug was significantly smaller than those of the control group.These results coincide with changes in the TGF-β1 and BMP-2 expression.In the specimens that received alendronate,the TGF-β1 was expressed in some sites of trabecular bone that was neoformed,peripherally to the bone marrow area.The BMP-2 was also positive in proliferative chondrocytes and hypertrofic chondrocytes.On the 12^th day,all layers of chondrocytes exhibited positivity for BMP-2 in the specimens that received alendronate.In the interface between the trabecular bone and cartilage,an area of disorganized bone deposition was evident.Neoformed bone also appeared to be different at 12 d.In the control group,BMP-2 was positive in an intense area of bone trabeculae,whereas the alendronate-treated group showed TGF-β1 positive trabeculae and a greater bone area.CONCLUSION Alendronate alters the immunolocalization of TGF-β1 and BMP-2 simultaneously,a condition that changes the usual histological aspects of the cartilage zone and impairs epiphysis growth and femur growth.

Cloning, expression profiling and promoter functional analysis of bone morphogenetic protein 2 in the tongue sole(Cynoglossus semilaevis)

BMP2 plays crucial roles in vertebrate developmental process and acts as a bone inducer during osteogenesis. We present here the molecular cloning of bmp2 cDNA from the marine flatfish Cynoglossus semilaevis, and the analysis of bmp2 expression profiling and promoter function. The full length of bmp2 cDNA sequence is 2 048 bp,which encodes a protein of 422 amino acids. Tissue expression distribution of bmp2 was examined in 14 tissues of mature individuals by quantitative real time PCR（qRT-PCR）. The results revealed that bmp2 was expressed ubiquitously, and the highest expression level was detected in the spinal cord. Moreover, bmp2 expression levels were detected at 15 sampling time points of early developmental stages（egg, larva, juvenile and fingerling stages）.The highest expression level of bmp2 was observed at the gastrula stage, which was about ten times higher than those at the other three embryo stages. Whole-mount in situ hybridization showed that the bmp2 signal was strongly detected at the location of the crown-like larval fin, heart and liver, and slightly expressed in the notochord at one day post hatch（dph）; then the expression of bmp2 started to be concentrated in notochord at three dph. Subsequently, we characterized the 5′-flanking region of bmp2 by testing the promoter activity by Luciferase reporter assays. Positive regulatory region was detected at the location of –179 to ＋109. The predicted transcription factor binding sites（E-box binding factors, zinc finger transcription factor, etc.） in this region might participate in the transcriptional regulation of the bmp2 gene.

Cartilage and bone tissue engineering using adipose stromal/stem cells spheroids as building blocks

Scaffold-free techniques in the developmental tissue engineering area are designed to mimic in vivo embryonic processes with the aim of biofabricating,in vitro,tissues with more authentic properties.Cell clusters called spheroids are the basis for scaffold-free tissue engineering.In this review,we explore the use of spheroids from adult mesenchymal stem/stromal cells as a model in the developmental engineering area in order to mimic the developmental stages of cartilage and bone tissues.Spheroids from adult mesenchymal stromal/stem cells lineages recapitulate crucial events in bone and cartilage formation during embryogenesis,and are capable of spontaneously fusing to other spheroids,making them ideal building blocks for bone and cartilage tissue engineering.Here,we discuss data from ours and other labs on the use of adipose stromal/stem cell spheroids in chondrogenesis and osteogenesis in vitro.Overall,recent studies support the notion that spheroids are ideal"building blocks"for tissue engineering by“bottom-up”approaches,which are based on tissue assembly by advanced techniques such as three-dimensional bioprinting.Further studies on the cellular and molecular mechanisms that orchestrate spheroid fusion are now crucial to support continued development of bottom-up tissue engineering approaches such as three-dimensional bioprinting.

Ⅳa型黏多糖贮积症枕颈部畸形的诊断和外科治疗现状

J黏多糖贮积症(MPS)是一种溶酶体贮积性疾病,是由于编码糖胺聚糖(GAGs)降解酶的基因突变引起的,导致包括骨骼、关节、心脏、呼吸系统和中枢神经系统等多器官和系统受累。根据所缺乏或缺陷的酶的性质不同,MPS可细分为Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,Ⅶ,Ⅸ型7种类型,其中Ⅲ型又分为Ⅲa、Ⅲb、Ⅲc和Ⅲd亚型,Ⅳ型分为Ⅳa和Ⅳb亚型^([1])。

自体股骨头结构植骨重建髋臼辅助THA在改良CROWE Type ⅣB型DDH中的临床疗效分析

目的:分析和总结自体股骨头结构植骨重建髋臼辅助全髋关节置换术(total hip arthroplasty,THA)治疗改良Crowe TypeⅣB型成人髋关节发育不良性脱位(developmental dysplasia of the hip,DDH)患者的临床疗效。方法:按照改良Crowe分型,选取山东大学齐鲁医院德州医院关节外科2015年8月至2023年3月收治的TypeⅣB型DDH患者26例,其中男25例,女1例,采用自体股骨头结构植骨重建髋臼辅助THA,记录患者手术时间、术中失血量、术中术后输血量、术后血红蛋白、手术相关并发症和骨愈合时间等,并行骨盆正位X线片了解假体位置、假体骨长入、假体松动以及骨愈合情况等,采用视觉模拟评分表(visual analogue scale,VAS)评价髋关节的疼痛不适,采用髋关节Harris评分和Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)来评价髋关节功能及临床疗效。结果:所有患者的平均随访时间(9.73±8.35)个月,术中出血平均为(715.38±143.37) mL,术中平均输血(415.38±282.41) mL,手术时间平均为(118.62±18.27) min,术后平均输血为(192.31±236.51) mL。所有患者转子下骨端、自体股骨头和假臼之间均骨愈合良好。髋关节VAS评分从术前6.73±0.45,至术后末次随访时VAS评分1.73±0.53,差异有统计学意义(P=0.000),髋关节活动度均较术前明显改善,髋关节Harris评分从术前24.27±1.66,至术后末次随访时Harris评分74.77±2.89,差异有统计学意义(P=0.000),WOMAC术前术后评分分别为130.08±5.72和67.85±3.23,差异均有统计学意义(P=0.000)。结论:自体股骨头结构植骨重建髋臼辅助THA治疗改良Crowe TypeⅣB型DDH,具有操作相对简单、固定牢固、手术相对安全和疗效确切的优点。

婴儿发育性髋关节发育不良与骨密度和维生素D的相关性研究

目的探究钙和维生素D缺乏对婴儿髋关节发育情况有无影响,以提高孕产妇及家庭对发育性髋关节发育不良(DDH)的正确认识,降低DDH的发病率,提高人口素质。方法对2021年3月—2023年3月对兰州市妇幼保健院儿童保健科体检的1107名3月龄婴儿,先进行临床检查,记录髋关节的发育状况、外部形态及运动状态,然后行超声检查,采用Graf法测量评估髋关节发育状况。同时检测婴儿骨密度相关参数、骨碱性磷酸酶和25-羟基维生素D[25-(OH)-D]的含量,采用相关分析和多因素Logistic回归分析探究婴儿骨密度和维生素D水平对髋关节发育情况有无影响。结果1107例受检婴儿中,髋关节发育正常990例,存在单侧或双侧髋关节发育不良117例,DDH检出率为10.6%;DDH组左侧和右侧α角均小于正常组,差异有统计学意义(P<0.05);2组间左侧和右侧β角之间的差异均无统计学意义(P>0.05);两侧α角、β角与骨密度、超声传导速度、z值和25-(OH)-D均无线性相关关系(P>0.05);DDH组骨密度、超声传导速度、z值和25-(OH)-D均低于正常组,差异有统计学意义(P<0.05);增加骨密度和25-(OH)-D含量为DDH发病的保护因素。结论婴儿期适当补充钙和维生素D有助于降低DDH的发病率。

NFIX基因变异导致一对同卵双胞胎Marshall-Smith综合征并文献复习

该文报道了一对NFIX基因变异导致Marshall-Smith综合征(Marshall-Smith syndrome,MRSHSS)的同卵双胞胎临床及遗传学特点并对相关文献进行复习。2例患儿均表现为全面发育落后、高额头、浅眼眶、漏斗胸。基因检测提示2例患儿均存在NFIX杂合剪接位点变异c.697+1G>A,父母该位点为野生型,根据美国医学遗传学与基因组学学会指南判定为可能致病性变异,该位点突变既往未见文献报道。复习文献共发现32例MRSHSS患者,突变类型为剪切/移码突变。骨骼成熟加速、中至重度全面发育迟缓/智力障碍是MRSHSS患者最主要的临床表现。基因检测结果是该病重要的诊断依据。

团头鲂肌间骨发育的形态学观察

研究利用整体骨骼染色、形态学解剖和X光透射的方法,对团头鲂(Megalobrama amblycephala)仔稚鱼肌间骨的出现时期、形态以及成鱼肌间骨数目、形态、分布和长度变化进行了观察与分析。结果表明:团头鲂的肌间骨在孵出后20d(体长为1.33 cm)骨化出现,首先出现在尾部,然后向头部方向依次出现,到第40天(体长为2.36 cm)基本全部出现;肌间骨出现与分化的时间受生长发育的影响大于日龄的影响。团头鲂肌间骨数目在108—129,平均为119根,其中躯干部轴上肌中的肌间骨数目最多(40—45根),尾部轴上肌与轴下肌中的肌间骨数目相近(32—39根)。肌间骨形态包括"1"形、"卜"形、"y"形、一端多叉形、两端多叉形和"("形6种类型,各种形态的肌间骨均是从"1"形发展而来;肌间骨越靠鱼体前端形态越复杂。团头鲂躯干轴上肌中的肌间骨显著长于尾部肌肉中的肌间骨(P<0.05),躯干轴下肌中的肌间骨最短,并且肌间骨长度与个体体重与体长呈正相关。研究结果为今后揭示团头鲂肌间骨发生与发育的分子机制,抑制团头鲂肌间骨骨化,培育无肌间骨的团头鲂提供了形态学基础。

髋臼旋转截骨术治疗髋臼发育不良

目的 :报告 1组成年人髋臼发育不良 (DDD)患者行髋臼旋转截骨术 (RAO)的疗效。方法 :采用王金成改良Ollier髋外侧入路 ,行大粗隆截骨 ,截骨块连同臀中肌一起向近端反转 ,在关节囊外距髋臼骨性边缘约 1.5cm处做穹隆状截骨 ,将整个髋臼以球形方式截断并向前、外、下方旋转 ,覆盖股骨头。结果 :12例患者经平均 2 .5年的随访 ,疗效满意。结论 :RAO手术是治疗成年人DDD行之有效的方法 ,可有效改善临床症状 ,恢复髋关节的生物力学及生理特点 ,明显降低患髋的病残率。

进行性假性类风湿发育不良症的临床分析

目的提高对进行性假性类风湿发育不良症的认识。方法对2例进行性假性类风湿发育不良症进行分析，并通过文献复习对本病的临床表现及影像学改变进行分析总结。结果2例患者均为幼年起病，以双手近端指间关节肿胀为突出表现，逐渐出现外周大小关节进行性受累，并伴有脊柱的异常。结合文献报道的51例分析发现，本病男女患病率相仿，发病年龄多为1～10岁，其中77％为3～5岁。外周大小关节均可受累，依次累及双手小关节、髋、膝、踝、腕、肩等，早发骨关节炎改变是致残的主要原因，38％的患者脊柱受累可出现短躯干畸形。影像学特点均表现为普遍性扁平椎并椎体终板不规则、骨骺增大、继发性退行性变和关节周围骨质疏松。本病临床症状与类风湿关节炎相似，但不同的是无滑膜炎和其他炎性改变、X线无破坏性改变。目前无特异的治疗方法。结论进行性假性类风湿发育不良症是一种少见的常染色体隐性遗传性疾病，临床特点及典型的影像学表现有助于诊断。

Bernese手术治疗先天性髋臼发育不良

目的 :介绍Bernese截骨术治疗先天性髋臼发育不良。方法 :1998年 4月～ 2 0 0 1年 12月 ,共有 2 9例 ( 30髋 )髋臼发育不良患者接受Bernese截骨术治疗。患者年龄 14～ 35岁 ,术前按Merled’Aubigne评分标准积分 6～ 15分 ,平均 13分 ,X线片示CE角 -5～ 2 0° ,平均 -0 .1° ,sharp角 42～ 6 0° ,平均 5 0° ,股骨头覆盖指数 10 %～ 6 0 % ,平均47.2 %。结果 :Merled’Aubigne评分从术前平均 13( 6～ 15 )分提高到术后平均 17( 12 .5～ 18)分 ,术后CE角平均 40°( 2 8～ 5 0°) ,sharp角平均 36°( 2 5～ 38°) ,股骨头覆盖指数 90 % ( 81%～ 10 0 % ) ,术后关节活动范围较术前在各方向上均有减少 ,术后并发症包括下肢深静脉血栓形成 1例 ,股外侧皮神经损伤 2例 ,髋关节半脱位加重 1例 ,浅表液化 2例。结论 :Bernese术具有其它截骨术不可比拟的优势 ,是目前治疗青少年及成年髋臼发育不良的最佳选择。

发育性髋脱位髋臼软骨细胞凋亡的实验研究

目的探讨发育性髋脱位（DDH）髋关节结构内髋臼软骨细胞凋亡与髋臼软骨发育不良的关系。方法选取出生4周的新西兰大耳白兔20只，雌雄兼用，采用兔后肢屈髋伸膝位管型石膏固定制作DDH大耳白兔模型，右后肢管型石膏固定为实验侧，左后肢不作处理作为对照侧。固定前和固定8周摄骨盆正位X线片，根据实验侧Shenton线不连续及股骨头脱位于Perkin方格外下及外上象限判定是否造模成功。观察造模成功的12只大耳白兔双侧髋臼形态、软骨细胞变化、细胞凋亡以及Bel-2表达情况。结果DDH造模成功率60％（12／20），实验侧髋关节X线片显示，髋臼上缘变钝，股骨头向Perkin方格外下或外上象限脱位，实验侧髋臼指数较对照侧明显增大（P〈0．05）。实验侧髋臼变窄且有较多软组织填充，髋臼软骨色暗。软骨细胞稀疏，排列混乱。电镜下细胞染色质边集、固缩，核形不规整，细胞质内出现空泡结构。实验侧髋臼软骨细胞凋亡率高于对照侧（P〈0．05），实验侧髋臼软骨细胞中Bcl-2较对照侧呈低表达（P〈0．05）且细胞凋亡率与Bcl-2低表达呈正相关。结论DDH髋关节结构内髋臼软骨过度细胞凋亡和凋亡因子Bcl-2低表达可能参与了DDH髋臼软骨发育不良。

不同类型氟骨症影响因素的研究

在环境流行病学调查的基础上，用病区粮食及燃煤进行大鼠氟中毒模型的复制，探讨不同类型氟骨症的影响因素及发病机制，为制订有针对性的防治措施提供科学依据。实验表明：除对照组外，其余各组均出现氟斑牙；骨骼Ｘ线摄片及病理组织学检查发现，高氟组出现骨疏松，并伴有骨转换征象，加营养可减轻骨病变程度；呼吸道吸入氟也可引起氟骨症，但病变较轻。引起不同类型氟骨症的主要因素是总摄氟量高、营养低下（蛋白质及钙摄入不足）和铝元素增多等。