Earlier BMI rebound and lower pre-rebound BMI as risk of obesity among Japanese preschool children.

OBJECTIVES: Longitudinal growth data of children were analyzed to clarify the relationship between the timing of body mass index (BMI) rebound and obesity risk in later ages. SUBJECTS/METHODS: Of 54 558 children born between April 2004 and March 2005 and longitudinally measured in April and October every year in the preschool period, 15 255 children were analyzed wherein no longitudinal measurement is missing after 1 year of age. BMI rebound age was determined as the age with smallest BMI value across longitudinal individual data after 1 year of age. Rebound age was compared between overweight and non-overweight groups. The subjects were divided into groups based on the timing of rebound. The sex- and age-adjusted mean of the BMI, height and weight s.d. scores for age group, along with 6 months weight and height gain, were compared among groups using analysis of covariance. RESULTS: Among those who were overweight at 66-71 months of age, BMI rebound age obtained at approximately 3 years of age was compared with the non-overweight group, whose BMI rebound age was utmost 66 months or later (P<0.001). The comparison among BMI age group showed that earlier BMI rebound results in larger BMI (P<0.001) and larger weight and height gain after the rebound (P<0.001). Among the group with BMI rebound earlier than 30 months of age, low BMI was observed (P<0.001). Slight elevation of height and weight gain was observed before the BMI rebound among groups with rebound age earlier than 60 months of age (P<0.001). CONCLUSION: Earlier BMI rebound timing with pre-rebound low BMI leads to greater childhood obesity risk; hence, early detection and prevention is necessary for such cases.

Longitudinal changes in body mass index of children affected by the Great East Japan Earthquake.

BACKGROUND: The evacuation and disruption in housing caused by the 2011 Great East Japan Earthquake and following nuclear radiation may have influenced child health in many respects. However, studies regarding longitudinal childhood growth are limited. Therefore, in this study we aimed to explore the influence of the earthquake on longitudinal changes in body mass index in preschool children. METHODS: Participants were children from nursery schools who cooperated with the study in the Iwate, Miyagi and Fukushima prefectures. The exposed group consisted of children who experienced the earthquake during their preschool-age period (4-5 years old). The historical control group included children who were born 2 years earlier than the exposed children in the same prefectures. Trajectories regarding body mass index and prevalence of overweight/obesity were compared between the two groups using multilevel analysis. Differences in the changes in BMI between before and after the earthquake, and proportion of overweight/obesity was compared between the two groups. We also conducted subgroup analysis by defining children with specific personal disaster experiences within the exposed group. RESULTS: A total of 9722 children were included in the study. Children in the exposed group had higher body mass indices and a higher proportion of overweight after the earthquake than the control group. These differences were more obvious when confined to exposed children with specific personal disaster experiences. CONCLUSIONS: Children's growth and development-related health issues such as increased BMI after natural disasters should evoke great attention.

Incidence and prevalence of childhood-onset Type 1 diabetes in Japan: the T1D study.

AIMS: A majority of children with Type 1 diabetes in Japan are registered with the government-subsidized Specified Pediatric Chronic Disease Treatment Research Projects (SPCDTRP). In this study, the incidence and prevalence of childhood-onset (< 15 years) Type 1 diabetes in Japan were estimated by drawing on SPCDTRP data. METHODS: Data available for 2005-2012 from the SPCDTRP and Statistics Bureau, Ministry of Internal Affairs and Communications were used to estimate the incidence of Type 1 diabetes for 2005-2010, adjusted to cover those registered within 3 years of disease onset and stratified by sex, age at onset and period of onset. RESULTS: The incidence of Type 1 diabetes for 2005-2010 was 2.25/100,000 persons [95% confidence intervals (95% CI), 2.14-2.36] (boys: 1.91, 95% CI, 1.83-1.98; girls: 2.52, 95% CI, 2.34-2.69), with that for the age brackets 0-4, 5-9 and 10-14 years being 1.48 (95% CI, 1.29-1.66), 2.27 (95% CI, 2.08-2.47) and 3.00 (95% CI, 2.74-3.25), respectively. The onset of disease was shown to peak at age 13 among boys (3.28, 95% CI, 3.02-3.55) and at age 10 among girls (3.28, 95% CI, 3.02-3.55). The peak periods of disease onset were April/May and December. The number of children aged < 15 years with Type 1 diabetes for 2005-2012 was estimated to be 2326 (95% CI, 2202-2450) with the prevalence estimated as 13.53/100,000 persons (95% CI, 12.63-14.43). CONCLUSIONS: Study findings demonstrated no increase in the incidence of Type 1 diabetes, although suggesting, in agreement with earlier reports, that the onset of disease peaks in adolescence with a female predominance. In addition, the incidence of childhood-onset diabetes exhibited an annual bimodal pattern in this study.

Growth hormone-releasing hormone stimulates and somatostatin inhibits the release of a novel protein by cultured rat pituitary cells.

We have reported that the secretion of at least 17 distinct peptides [including rat (rGH)] GH by cultured rat pituitary cells was stimulated by GH-releasing hormone and inhibited by somatostatin, when analyzed by two-dimensional polyacrylamide gel electrophoresis. Three of these peptides (no. 23, 24, and 25) were not rGH immunoreactive. In order to determine whether these three peptides are fragments, degradation products or posttranscriptionally modified forms of rGH, rGH and peptide no. 23 were characterized structurally. From partial peptide maps of rGH and peptide no. 23 by V8 protease or chymotrypsin, it appeared that these peptides were not related to each other. By N-terminal microsequencing of two-dimensional polyacrylamide gel electrophoresis purified peptide, we have obtained the sequence of 24 N-terminal amino acid residues of peptide no. 23. This sequence has no significant homology with rGH or any other reported protein sequence. Antiserum was generated against a synthetic oligopeptide corresponding to amino acid residues 3-24 of peptide no. 23. The antiserum cross-reacted with peptides no. 23, 24, and 25 upon Western blot analysis. These results indicate that peptide no. 23 has a novel structure unrelated to other pituitary hormones. Since its secretion is influenced by GH-releasing hormone and somatostatin, peptide no. 23 may represent a previously unrecognized structurally unique growth factor.

Human growth hormone (GH)-releasing factor stimulates and somatostatin inhibits the release of rat GH variants.

Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) was used for the analysis of proteins secreted by male rat pituitary cells in monolayer culture in the presence of 10 nM human GH-releasing factor (hGRF) or 30 nM somatostatin (SRIF) or in the absence of these factors. More than 300 medium proteins were reproducibly detected either by fluorographic autoradiography or by silver staining. Immunoreactivity of each protein was examined after 2D PAGE followed by Western blotting and immunostaining with affinity-purified antirat GH (rGH) antibody. While there was a cluster of immunoreactive spots in the GH dimer range (40,000-50,000 mol wt), at least 16 medium proteins of mol wt 22,000 or less were also stained. Among these 16 proteins the release of 15 was stimulated and the release of 14 was inhibited by hGRF and SRIF, respectively. On the other hand, there were 3 proteins of approximate mol wt 16,000 whose secretion was regulated in a coordinate manner as rGH by the hypothalamic factors but which did not cross-react with anti-rGH antibodies. The increase or decrease in the radioactivity of each protein spot obtained from media after pituitary cells were incubated with [35S]methionine and hypothalamic factors was analyzed statistically. A pulse-chase study suggested that at least 7 of the hormonally regulated proteins, including rGH, were synthesized very rapidly. Finally, the 2D PAGE analysis of cell-free translation products of messenger RNA derived from male rat anterior pituitaries revealed the presence of about 40 rGH-immunoreactive proteins which included pre-GH. These data suggest that there are multiple forms of rGH-variants or rGH-related proteins. The biological significance(s) of all the rGH immunoreactive proteins and of the GRF- and SRIF-regulated pituitary proteins remains unclear. It is evident that a number of these proteins are synthesized and released rapidly by pituitary cells in culture. Furthermore, the presence of multiple genes for these rGH-related proteins is suggested by the large family of immunoreactive gene products identified after cell-free translation of messenger RNA derived from the pituitary.

Serum levels of 20-kilodalton human growth hormone (GH) are parallel those of 22-kilodalton human GH in normal and short children.

Twenty-kilodalton human GH (20K), which is one of the human GH (hGH) variants, is thought to be produced by alternative premessenger ribonucleic acid splicing. However, its physiological role is still unclear due to the lack of a specific assay. We have measured serum 20K and 22-kDa hGH (22K) by specific ELISAs to investigate the physiological role of 20K in children. The subjects were 162 normal children, aged 1 month to 20 yr; 12 patients with GH deficiency (GHD), aged 11 months to 13 yr; 57 children with non-GHD short stature, aged 2-17 yr; and 13 girls with Turner's syndrome, aged 5 months to 15 yr. Samples were collected at random from normal children and were collected after hGH provocative tests and 3-h nocturnal sleep from GHD, non-GHD short stature, and Turner's syndrome children. The mean basal serum concentrations of 22K and 20K were 2.4 +/- 2.8 ng/mL and 152.3 +/- 184.0 pg/mL in normal boys and 2.5 +/- 3.1 ng/mL and 130.6 +/- 171.5 pg/mL in normal girls, respectively. The percentages of 20K (%20K) were 5.8 +/- 2.1% and 6.0 +/- 3.2% in 83 normal boys and 79 normal girls, respectively. There was no significant difference in %20K either among ages or between the prepubertal stage and the pubertal stage in normal boys and girls. The mean %20K values in basal samples of provocative tests in 12 patients with GHD, non-GHD short stature, and Turner's syndrome were 6.5 +/- 2.4%, 6.5 +/- 3.8%, and 5.9 +/- 3.2%, respectively. There was no significant difference in %20K among normal children and these growth disorders, and there was no significant difference in %20K throughout the hGH provocative tests and 3-h nocturnal sleep in these growth disorders. There was also no significant correlation between the percentage of 20K and the height SD score or body mass index in either normal children or subjects with these growth disorders. In conclusion, the %20K is constant, regardless of age, sex, puberty, height SD score, body mass index, and GH secretion status. The regulation of serum 20K levels remains to be established.

A novel missense mutation of mineralocorticoid receptor gene in one Japanese family with a renal form of pseudohypoaldosteronism type 1.

Pseudohypoaldosteronism type 1 (PHA1) is a rare condition characterized by neonatal salt loss with dehydration, hypotension, hyperkalemia, and metabolic acidosis, despite elevated plasma aldosterone levels and PRA. Two modes of inheritance of PHA1 have been described: an autosomal dominant form and an autosomal recessive form. An autosomal recessive form manifests severe life-long salt wasting resulting from multiple mineralocorticoid target tissue such as sweat, salivary glands, the colonic epithelium, and lung. Contrary, an autosomal dominant PHA1 manifests milder salt wasting that gradually improves with advancing age. Recently, in one sporadic and four dominant cases, four different mutations including two frame shift mutations, two premature termination codons, and one splice site mutation in the mineralocorticoid receptor (MR) gene were identified. We studied the molecular mechanisms of one Japanese family with a renal form of PHA1. PCR and direct sequencing of the MR gene identified a heterozygous point mutation changing codon 924 Leu (CTG) to CCG (Pro) (L924P) in all affected members. COS-1 cells were transfected with expression vectors for either wild type or the mutant MR-L924P receptors, together with the reporter plasmid (glucocorticoid response element tk-CAT). Aldosterone increased CAT activity in cells expressing wild-type receptor, but had no effect in cells expressing the mutant receptors. These results suggest that mineralocorticoid resistance in this family is due to a missense mutation in the MR gene. To our knowledge, this is the first case of the missense mutation of the MR gene in renal PHA1.

Recent status in the occurrence of leukemia in growth hormone-treated patients in Japan. GH Treatment Study Committee of the Foundation for Growth Science, Japan.

The Foundation for Growth Science in Japan has monitored the safety and efficacy of GH treatment in GH-deficient patients since 1975. Data were collected from more than 32,000 patients up to December 31, 1997. New leukemia was observed in 14 patients and myelodysplastic syndrome (MDS) in one patient. The types of leukemia were acute lymphocytic leukemia (n = 6; 40%), acute myelocytic leukemia or MDS (n = 7; 47%), and chronic myelocytic leukemia (n = 2; 13%). Leukemia developed in 9 patients during GH treatment and in 6 after the cessation of GH treatment. Six patients had known risk factors for leukemia, such as Fanconi's anemia and previous radiation or chemotherapy. Patient-years of GH therapy was defined as the time from the first dose of GH to the date of the last visit during GH therapy, and patient-years of risk was defined as the time from the first dose of GH to December 31, 1997. The incidence of leukemia of patient-years of GH therapy and patient-years of risk in GH-treated patients without risk factors was 3.0/100,000 and 3.9/100,000, respectively, a figure similar to the incidence in the general population aged 0-15 yr. We conclude that the incidence of leukemia in GH-treated patients without risk factors is not greater than that in the general population aged 0-15 yr, and a possible increased occurrence of leukemia with GH treatment appears to be limited to patients with risk factors.

Skeletal features and growth patterns in 14 patients with haploinsufficiency of SHOX: implications for the development of Turner syndrome.

We report on clinical features in 14 Japanese patients (4 males and 10 females) with partial monosomy of the short arm pseudoautosomal region involving SHOX (n = 11) or total monosomy of the pseudoautosomal region with no involvement of disease genes on the sex-differential regions (n = 3). Skeletal assessment showed that three patients had no discernible skeletal abnormalities, one patient exhibited short 4th metacarpals and borderline cubitus valgus, and the remaining 10 patients had Madelung deformity and/or mesomelia characteristic of Léri-Weill dyschondrosteosis (LWD), together with short 4th metacarpals and/or cubitus valgus. Skeletal lesions were more severe in females and became obvious with age. Growth evaluation revealed that patients without LWD grew along by the -2 SD growth curve before puberty and showed a normal or exaggerated pubertal growth spurt, whereas those with LWD grew along by the standard growth curves before puberty but exhibited an attenuated pubertal growth spurt and resultant short stature. Maturational assessment indicated a tendency of relatively early maturation in patients with LWD. There was no correlation between the clinical phenotype and the deletion size. These findings suggest that haploinsufficiency of SHOX causes not only short stature but also Turner skeletal anomalies (such as short 4th metacarpals, cubitus valgus, and LWD) and that growth pattern is primarily dependent on the presence or absence of LWD. Because skeletal lesions have occurred in a female-dominant and age-influenced fashion, it is inferred that estrogens exert a maturational effect on skeletal tissues that are susceptible to premature fusion of growth plates because of haploinsufficiency of SHOX, facilitating the development of skeletal lesions.

Eos: a novel member of the Ikaros gene family expressed predominantly in the developing nervous system.

We identified a novel member of the Ikaros gene family, which has critical roles in the development of lymphoid lineages. This gene, which we named Eos, was expressed predominantly in the developing central and peripheral nervous system. Eos protein could interact with itself and Ikaros protein through its C-terminal portion in the yeast two hybrid assay. These findings suggested that Eos may have important roles in neural development similarly to the Ikaros family in the development of hemolymphoid tissue.

Substrate adhesiveness and experimental metastatic potential of rat ascites hepatoma AH7974-derived variant sublines.

Cells of an adherent subline (74AD, adhesion greater than 95%) and a floating subline (74FL, adhesion less than 1%) of rat ascites hepatoma AH7974 produced substrates containing fibronectin (FN), laminin (LN) and type IV collagen (CL-IV), with 74AD cells producing higher levels of each component. 74AD cells possessed high adhesion affinities to LN and CL-IV substrates. By contrast, 74FL cells hardly adhered to these purified attachment proteins. The difference in adhesion between the two lines in vitro tended to increase on incubation of the cells in medium containing fetal bovine serum. However, 74FL and 74AD cells adhered avidly to the extracellular matrix (ECM) of vascular endothelial cells. Although the cell-ECM adhesion apparently was not inhibited by pretreatment of the ECM with anti-FN, anti-LN and anti-CL-IV antibodies, the 74FL cell-ECM adhesion was inhibited considerably by pretreatment of the ECM with a mixture of these antibodies, especially with a combination of anti-FN and anti-LN antibodies. The lung-colonizing potential of 74FL cells was greater than that of 74AD cells, but the liver-colonizing potential of 74FL cells was less than that of 74AD cells. These results suggest that rat ascites hepatoma cells with extremely reduced substrate adhesiveness retain an adhesion mechanism that binds to FN and LN in the ECM of vascular endothelial cells. This mechanism may be a minimum essential unit of tumor cell-ECM adhesion in lung colonization, but the unit is insufficient for liver colonization of these cells.

Clinical utility of insulin-like growth factor binding protein-3 in the evaluation and treatment of short children with suspected growth hormone deficiency.

We have shown previously that serum insulin-like growth factor binding protein-3 (IGFBP-3) levels have good predictive value for complete, but not partial, growth hormone deficiency (GHD). In this study, we compare IGFBP-3 levels in short children previously divided into groups on the basis of their post-stimulation GH levels. Complete GHD (N = 59) included those children with peak post-stimulation GH < 5 micrograms/l. The partial GHD group (N = 49) had post-stimulation GH peaks of > 5 micrograms/l but < 10 micrograms/l. The normal children with short stature (N = 103) had post-stimulation GH peaks > 10 micrograms/l. Partial GHD and normal children with short stature also were divided into either low IGF-I or normal IGF-I subgroups. The clinical sensitivity of IGFBP-3 for complete GHD was 92%, whereas its sensitivity for partial GHD was 39%. For partial GHD, among those with low IGF-I (N = 19) 68% were also low for IGFBP-3, while 80% of those with normal IGF-I (N = 30) were also normal for IGFBP-3. The clinical specificity of IGFBP-3 for normal children with short stature was 69%. For these groups, among those with low IGF-I (N = 22) 73% also were low for IGFBP-3, while 80% of those with normal IGF-I (N = 81) also were normal for IGFBP-3. In addition, we tested whether IGFBP-3 can predict the response to GH treatment in prepubertal children by comparing pretreatment IGFBP-3 with the height gain achieved by 1 year of GH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression pattern of a novel death-promoting gene, DP5, in the developing murine nervous system.

We examined the expression patterns of the DP5 gene, which encodes a protein with apoptosis-inducing activity, in the developing nervous system of mice. This gene was primarily expressed in the spinal motor neurons and peripheral sensory ganglia of mouse embryos and transiently in the postnatal brain, particularly in the entorhinal cortex and hippocampus. These expression patterns suggest that the DP5 gene may be involved in the apoptosis, if not all, of the developing nervous system.

Identification of a novel gene, OASIS, which encodes for a putative CREB/ATF family transcription factor in the long-term cultured astrocytes and gliotic tissue.

Gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system (CNS). To study the mechanisms underlying gliosis, we performed differential display screening for genes specifically induced in long-term cultured astrocytes used as an in vitro gliosis model. We identified and characterized a gene (named OASIS, for old astrocyte specifically-induced substance) expressed in long-term cultured mouse astrocytes, or 'old astrocytes (OA)'. The OASIS gene encoded a putative transcription factor belonging to the cyclic AMP responsive element binding protein/activating transcription factor (CREB/ATF) gene family, with homology to box B-binding factor-2 (BBF-2), a Drosophila transcription factor. Its expression was developmentally regulated; OASIS mRNA was primarily expressed in the salivary gland and cartilage in the mouse embryo and it was transiently upregulated in the brain during postnatal two weeks. The expression became weaker in the adult brain. We also demonstrated that an expression of the OASIS mRNA was induced in response to the cryo-injury of the mouse cerebral cortex. The distribution pattern of the OASIS-positive cells in the injured cortex was very similar to that of the glial fibrillary acidic protein (GFAP)-positive cells. These results suggest that OASIS protein may play a role in gliotic events.

Localization of huntingtin-interacting protein-2 (Hip-2) mRNA in the developing mouse brain.

Huntingtin-interacting protein-2 (Hip-2) was identified as a human protein specifically associated with huntingtin in vitro, a gene product affected in patients with Huntington disease (HD). It is a ubiquitin-conjugating enzyme identical to the previously characterized bovine E2-25k. We identified the mouse Hip-2 homologue (mHip-2) and examined its distribution patterns in the developing mouse brain in order to gain an insight into the functional significance of the Hip-2 protein in the normal brain as well as in the pathogenesis of HD. As reported with huntingtin, the mHip-2 mRNA expression developed in parallel with neuronal maturation and became distributed widely in the postnatal mouse brain. This spatiotemporal pattern of mHip-2 mRNA expression resembled that of huntingtin. We further demonstrated that mHip-2 mRNA was colocalized with huntingtin-like immunoreactivity in a single neuron. These findings suggested that the Hip-2 interacted with huntingtin in vivo and played an important role in HD pathogenesis.

Functional reconstruction of the jaw bones using poly(l-lactide) mesh and autogenic particulate cancellous bone and marrow.

The goal of the reconstruction of jaw bone defects should be not only to recover deformities, but also to reconstruct the jaw with which the patient can perform normal functions. To achieve this purpose, it is essential that a method of promoting regeneration of physiological bone is developed so that dentures can be accommodated. In this report a new method of functional reconstruction using fresh autogenous particulate cancellous bone and marrow and a poly(L-lactide) mesh tray is presented. This method will make physiological reconstruction of the jaw possible. In the future this method is also expected to assist in the development of simultaneous functional reconstruction of the jaw bone and oral rehabilitation when dental implants are included in the tray.

Apoptosis induced in the spinal cord and dorsal root ganglion by infection of herpes simplex virus type 2 in the mouse.

After inoculation of a highly neuro-invasive strain of herpes simplex virus (HSV) type 2 (186) into the mouse hind-paw planter skin, many virus-positive neurons and glial cells were detected in the dorsal root ganglia (DRGs) and lumbar spinal cord by immunohistochemistry for HSV-2 antigen. A number of apoptotic cells were also observed in the spinal cord and DRGs by the terminal dUTP nick-end-labeling (TUNEL) method. Double labeling with the immunohistochemistry for HSV-2 and the TUNEL method revealed further that some glial and neuronal cells in the spinal cord, either infected or non-infected by HSV-2, showed apoptotic signs. In DRGs, however, apoptosis was detected in no neuronal cells, although some of HSV-2 -infected glial cells were apoptotic.

Retropharyngeal neuroblastoma causing airway obstruction in a newborn--survival with surgical treatment alone.

Neuroblastoma is known to occur occasionally in newborns, but very few are of cervical origin. We have encountered a newborn with retropharyngeal neuroblastoma causing airway obstruction, and successfully treated it by surgical removal alone.

High-dose growth hormone (GH) treatment in prepubertal GH-deficient children.

Two clinical studies were conducted to determine the effect of different doses of growth hormone (GH) on prepubertal growth in GH-deficient boys. In one study, GH doses of 1.0 and 1.5 IU/kg/week (0.33 and 0.5 mg/kg/week) were given to groups of five children and compared with a conventional Japanese dose of 0.5 IU/kg/week (0.17 mg/kg/week) in 15 children. A significant dose-dependent increase in height velocity occurred in the first year of treatment, but differences between doses were not significant thereafter. In a second study, GH was administered to ten boys at a dose of 0.5 IU/kg/week for the first year, 0.75 IU/kg/week for the second year, 1.0 IU/kg/week for the third year and 0.5 IU/kg/week for the fourth and subsequent years (0.17, 0.25, 0.33 and 0.17 mg/kg/week, respectively). During the second and third years of GH treatment, these boys had significantly higher growth rates than controls, who were given GH at 0.5 IU/kg/week (0.17 mg/kg/week) throughout, indicating successful reduction in 'waning' of the treatment effect. At the end of the fourth year, the different protocols from the two studies had both resulted in a greater height SDS than the controls, and did not advance bone maturation. In conclusion, these protocols may be effective in increasing prepubertal height gain in children with GH deficiency.

[Studies on biocompatibility of apatite-silicone composite material and investigation of its clinical application].

As reconstructive and prosthetic material of the bone or soft tissue, the author developed a hydroxyapatite composite with silicone (HA-Si composite and studied its biocompatibility to the bone and investigated its clinical application. Si and HA-Si composite containing 30wt%, 50wt%, 70wt% of HA particles were implanted into the rabbit femurs and 2, 4, 12 weeks after, the histological observation was performed. On the surface of the Si fibrous tissue was formed directly, but with the composite, of with the higher HA content, new trabecula were formed from the cortical bone 2 weeks after and the bone developed and contacted the surface directly 4 weeks after and then progressed along the surface. Twelve weeks after the remodeling of the bone progressed and the lamellar structure was recognized. In the bone marrow region new bone formation was observed along the composite and the lamellar structure was recognized. The 70wt% composite showed a good affinity like hydroxyapatite. This composite had elasticity and good handling and biocompatibility to the bone, and it was suggested to be potentially useful for implantation. The 70wt% composite was applied in the clinical cases: mandibular reconstruction (8 cases), additional implantation for deformity of the face (3 cases), alveolar ridge augmentation (3 cases) and supporting of the retention of facial prosthesis (2 cases). The results in the cases of mandibular reconstruction were not satisfactory, however those in the other cases were good so far now. Therefore it was considered that the 70wt% HA-Si composite could be useful in the statical condition.