DNA demethylating agent decitabine increases AQP5 expression and restores salivary function.

Xerostomia is the symptom of oral dryness resulting most frequently, but not exclusively, from salivary gland hypofunction. Because the prevalence of xerostomia may increase with age, it has multiple oral health consequences in aging populations. In the present study, we demonstrate that the in vivo administration of 5-aza-2'-deoxycytidine (5-Aza-CdR; decitabine), a DNA demethylating agent, to the murine aging model C57BL/6CrSlc mice (24 wks old) increased the volumes of salivary flow compared with those of control mice. Western blot analysis and immunohistochemical staining demonstrated the augmented expression of AQP5 protein in the salivary glands of 5-Aza-CdR-treated mice compared with those of control mice. In addition, AQP5 protein expression levels in 5-Aza-CdR-treated old mice (27 wks old) were much higher than those in untreated and young mice (6 wks old). Global methylation levels in the salivary glands were significantly lower in the 5-Aza-CdR-treated mice than in the untreated mice. Moreover, the induction of demethylation in the AQP5 promoter of 5-Aza-CdR-treated mice was stronger than in the control mice. Analysis of our data therefore suggests that a DNA demethylating agent may be a useful drug for restoring hyposalivation in elderly individuals, thereby leading to the resolution of xerostomia.

Preservation of mitochondrial function may contribute to cardioprotective effects of Na+/Ca2+ exchanger inhibitors in ischaemic/reperfused rat hearts.

BACKGROUND AND PURPOSE: Na+/Ca2+ exchanger (NCX) inhibitors are known to attenuate myocardial reperfusion injury. However, the exact mechanisms for the cardioprotection remain unclear. The present study was undertaken to examine the mechanism underlying the cardioprotection by NCX inhibitors against ischaemia/reperfusion injury. EXPERIMENTAL APPROACH: Isolated rat hearts were subjected to 35-min ischaemia/60-min reperfusion or 20-min ischaemia/60-min reperfusion. NCX inhibitors (3-30 microM KB-R7943 (KBR) or 0.3-1 microM SEA0400 (SEA)) were given for 5 min prior to ischaemia (pre-ischaemic treatment) or for 10 min after the onset of reperfusion (post-ischaemic treatment). KEY RESULTS: With 35-min ischaemia/60-min reperfusion, pre- or post-ischaemic treatment with KBR or SEA neither enhanced post-ischaemic contractile recovery nor attenuated ischaemia- or reperfusion-induced Na+ accumulation and damage to mitochondrial respiratory function. With the milder model (20-min ischaemia/reperfusion), pre- or post-ischaemic treatment with 10 microM KBR or 1 microM SEA significantly enhanced the post-ischaemic contractile recovery, associated with reductions in reperfusion-induced Ca2+ accumulation, damage to mitochondrial function, and decrease in myocardial high-energy phosphates. Furthermore, Na+ influx to mitochondria in vitro was enhanced by increased concentrations of NaCl. KBR (10 microM) and 1 microM SEA partially decreased the Na+ influx. CONCLUSIONS AND IMPLICATIONS: The NCX inhibitors exerted cardioprotective effects during relatively mild ischaemia. The mechanism may be attributable to prevention of mitochondrial damage, possibly mediated by attenuation of Na+ overload in cardiac mitochondria during ischaemia and/or Ca2+ overload via the reverse mode of NCX during reperfusion.

Outcomes of hepatic artery infusion therapy for hepatic metastases from colorectal carcinoma after radiological placement of infusion catheters.

AIM: The aim of this study is to evaluate the safety and efficacy of hepatic artery infusion (HAI) of 5-fluorouracil (5FU) for patients with liver metastases from colorectal carcinoma after radiological placement of infusion catheters. METHODS: Forty-two patients with liver metastases from colorectal carcinoma received radiological placement of infusion catheters using the distal fixation method. They received continuous HAI of 5FU 1,000-1,500mg for 5h weekly or biweekly. Tumor status was assessed by chest-abdominal computed tomography (CT) scan after every 10 infusions. Hepatic perfusion was checked by CT arteriography via the infusion port after every 10 infusions. RESULTS: Radiological placements of catheters were performed successfully in all cases. Each patient received an average of 36 treatments (range: 10-98). Catheter failure was found in 3 patients (7.1%). Nine incidents of grade 1 toxicity were observed in 8 patients (19.0%). There was a complete response in 6 patients, partial remission in 18, stable disease in 9, and progression of disease in 9 (response rate: 57.1%). Overall median survival time was 29.1 months. Using Cox's proportional hazard model, lymph node metastases in primary colorectal carcinoma and pre-treatment serum CEA affected overall survival (P=0.011, P=0.005). CONCLUSIONS: HAI after radiological placement of infusion catheters is a safe and effective treatment particularly for patients with no lymph node metastasis in primary carcinoma or with a low pre-treatment serum CEA level.

A novel 'sandwich' assay for quantifying chemo-regulated cell migration within 3-dimensional matrices: wound healing cytokines exhibit distinct motogenic activities compared to the transmembrane assay.

The extracellular matrix profoundly affects cellular response to soluble motogens. In view of this critical aspect of matrix functionality, we have developed a novel assay to quantify chemo-regulated cell migration within biologically relevant 3-dimensional matrices. In this "sandwich" assay, target cells are plated at the interface between an upper and lower matrix compartment, either in the presence of an isotropic (uniform) or anisotropic (gradient) spatial distribution of test motogen. Cell migration in response to the different conditions is ascertained by quantifying their subsequent disposition within the upper and lower matrix compartments. The objective of this study has been to compare the motogenic activities of platelet-derived growth factor (PDGF-AB) and transforming growth factor-beta isoforms (TGF-beta1, -beta2 and -beta3) in the sandwich assay and the commonly employed transmembrane assay. As previously reported, dermal fibroblasts exhibited a motogenic response to isotropic and anisotropic distributions of all tested cytokines in the transmembrane assay. In contrast, only PDGF-AB and TGF-beta3 were active in the sandwich assay, each eliciting directionally unbiased (symmetrical) migration into the upper and lower type I collagen matrices in response to an isotropic cytokine distribution and a directionally biased response to an anisotropic distribution. TGF-beta1 and -beta2 were completely devoid of motogenic activity. These results are consistent with the reported differential bioactivities of PDGF and TGF-beta3 compared to TGF-beta1 and -beta2 in animal models of wound healing and suggest that the sandwich assay provides a means of obtaining physiologically relevant data regarding chemo-regulated cell migration.

Preliminary report of two-stage secondary alveolar bone grafting for patients with bilateral cleft lip and palate.

OBJECTIVE: To overcome the difficulties of one-stage secondary alveolar bone grafting for patients with bilateral cleft lip and palate (BCLP) who have a broad alveolar cleft, the value of two-stage alveolar bone grafting was examined. PATIENTS: Three patients (2 girls and 1 boy) with BCLP were treated by two-stage alveolar bone grafting. The procedure consisted of a first-stage surgery (mean age 8 year 6 months +/- 7.8 months), which consisted of alveolar bone grafting for one side of the BCLP, and second-stage surgery for the contralateral side several months later. For the postoperative assessment, radiographs of the operated site were examined. RESULTS: The average amount of implanted bone per operation and per patient was 6.8 +/- 1.1 g and 13.7 +/- 1.0 g, respectively. Postoperative clinical and radiographic examinations revealed that an appreciable alveolar bone ridge had formed, and there were no major complications. CONCLUSIONS: Two-stage alveolar bone grafting, which makes it possible to reduce the amount of implanted bone, could be an optional surgical procedure for patients with BCLP and a broad alveolar cleft.

Analysis of kinesiograph recordings and masticatory efficiency after treatment of non-reducing disk displacement of the temporomandibular joint.

The purpose of this study was to clarify the kinesiographs of chewing movement and masticatory efficiency before and after treatment in patients with non-reducing disk displacement of the temporomandibular joint (TMJ). Twenty patients who were diagnosed with unilateral non-reducing disk displacement of the TMJ were treated with pumping of the joint with injection of sodium hyaluronate. Chewing movement patterns in these patients were evaluated, using mandibular kinesiography (MKG) at their initial visit and at mean 19-month follow-up and the results were compared. Masticatory efficiency was also measured. As controls, 23 volunteers without TMJ dysfunction were employed. Far from the results of normal volunteers, chewing movement patterns of the patients on MKG did not show deviation to the chewing side in the TMJ-unaffected-side chewing in the horizontal plane. However, such patterns of the patients became similar to those of normal volunteers after treatment. Masticatory efficiency of the patients improved after treatment, though it was impaired at initial visit. The MKG and masticatory efficiency test appeared to be a useful method of comparing masticatory function before and after treatment in patients with non-reducing disk displacement of the TMJ.

Differential expression of cornified cell envelope precursors in normal skin, intraorally transplanted skin and normal oral mucosa.

BACKGROUND: Skin flaps have routinely been used as substitutes for oral mucosa after extensive resection of oral tissues. However, it remains unknown how the transplanted skin flaps perform as a host defence in the new environment of the oral cavity. OBJECTIVES: To evaluate the expression of cornified cell envelope (CCE) precursors in pretransplanted (normal) skin, intraorally transplanted skin and normal oral mucosa, because CCEs are highly responsible for a protective barrier in each type of epithelium. METHODS: We used immunohistochemistry and immunoelectron microscopy to examine the expression of CCE precursors, small proline-rich protein (SPR) 2 and 3 and loricrin, in biopsy specimens of normal skin, transplanted skin and normal oral mucosa, including buccal and lingual (non-keratinized) mucosae, and palatal (keratinized) mucosa. RESULTS: Transplanted skin flaps were classified into two groups. About two-thirds of the transplanted skin flaps displayed a reddish appearance and were devoid of the stratum corneum (SC) together with a psoriasiform inflammatory tissue reaction. Others showed a native appearance, retaining the SC. While SPR2 expression was limited to the stratum granulosum (SG) in both normal and transplanted skin retaining the SC, it extended to the stratum spinosum (SS) of the transplanted skin lacking the SC and that of the normal oral mucosa. Although SPR3 expression was not found in normal skin or in the transplanted skin retaining the SC, it was strongly expressed in the SS of the transplanted skin lacking the SC and the non-keratinized oral mucosa, and in the SS and SG of the keratinized oral mucosa. Loricrin, which was expressed in the SG of normal skin, the transplanted skin retaining the SC and the keratinized oral mucosa, was not detected in the transplanted skin lacking the SC or in the non-keratinized oral mucosa. Immunoelectron microscopy confirmed the ultrastructural localization of SPR3 directly under the cytoplasmic membrane of keratinocytes of the transplanted skin lacking the SC and that of the oral mucosa. CONCLUSIONS: The altered expression of SPR2, SPR3 and loricrin reflects the possible adaptation of epidermal keratinocytes in the new environment of the oral cavity.

Analysis of post-treatment electromyographs in patients with non-reducing disc displacement of the temporomandibular joint.

The purpose of this study was to clarify the electromyographic property of chewing movement before and after treatment in patients with non-reducing disc displacement of the temporomandibular joint (TMJ). Twenty patients who were diagnosed with unilateral non-reducing disc displacement of the TMJ were treated by pumping and injection of sodium hyaluronate into the joint. Chewing movement in these patients was evaluated by electromyography (EMG) at the initial visit and at mean 19-month follow-up and the results were compared. Chewing movement in 23 normal controls were also examined. Duration of contraction, cycle time and integrated value at the initial visit which were different from those in the controls without TMJ dysfunction tended to be at the control level mean 19 months after treatment of pumping and injection of sodium hyaluronate into the joint in patients with non-reducing disc displacement of the TMJ. Electromyography appeared to be a method of documenting the chewing movement which was impaired at initial visit improved after treatment in patients with non-reducing disc displacement of the TMJ.

Changes of the elastic fibre network of the rabbit temporomandibular joint following discectomy.

Elastic fibres are thought to be very important for the function of various organs including the temporomandibular joint (TMJ). The current study was designed to examine changes in the elastic fibres of the TMJ following discectomy. The TMJs of six rabbits were surgically exposed, and the disc removed with a scalpel. Three untreated and three sham-operated rabbits were used as controls. Complete TMJs were removed in three rabbits 1 month and in three rabbits 3 months after discectomy and processed for histochemical demonstration of elastic fibres. In the TMJ 1 month after discectomy, osteoarthritic changes and a significant increase in the numbers of elastic fibres were observed in the condyle and articular eminence. In the TMJs 3 months after discectomy, they tended to revert to the levels in the condyle and articular eminence of the control TMJs. Our results show that after experimental discectomy, elastic fibres very often appear initially in the condyle and articular eminence, but they are destined to disappear later. This information may improve our understanding of the consequences of removal of the disc in clinical practice.

Implanted octacalcium phosphate is more resorbable than beta-tricalcium phosphate and hydroxyapatite.

Our previous studies have suggested that synthetic octacalcium phosphate (OCP) could be resorbed and replaced by newly formed bone if implanted in rat skull defects. We hypothesized that the implanted OCP is more resorbable than other commonly used bone graft substitutes of calcium phosphate compounds, such as hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP). To test the hypothesis, the present study was designed to compare histomorphometrically resorption of the implanted OCP, HA, and beta-TCP, which were kept in the experimental cranial defect of rats for a long term. A full thickness of standardized trephine defect was made in the rat parietal bone, and the same volume of granules of OCP, HA, and beta-TCP were implanted into the defect. Five specimens of each group were fixed 6 months after implantation. The percentage of remaining implants (r-Imp%) and newly formed bone (n-Bone%) in the defect was analyzed histomorphometrically. The statistical analysis showed that the r-Imp% of OCP was significantly lower than that of HA and beta-TCP. In contrast, the n-Bone% of OCP was significantly higher than that of HA and beta-TCP. The present study has shown that the implanted OCP in the rat cranial defect is more resorbable than the implanted beta-TCP and HA, whereas the implanted OCP enhances bone formation more than the implanted beta-TCP and HA.

Comparison of reliability between the modified groin flap and the forearm flap in oral reconstruction.

OBJECTIVE: The groin flap has the advantage of minimum donor-site morbidity, while having the disadvantage of short vascular pedicle of small caliber. Modification of the groin flap has improved the former disadvantage, but the latter one remains. The purpose of this study was to compare the reliability of the modified groin flap with the forearm flap. STUDY DESIGN: Eleven modified groin flaps and 40 forearm flaps consecutively performed by a single surgeon in a hospital for patients with oral cancer were retrospectively reviewed. RESULTS: The rate of total flap loss in the modified groin flap group (8.3%) was higher than that in the forearm flap group (2.5%). The rates of partial flap loss in both flaps were similar to those of total flap loss. The failures of the modified groin flap and the forearm flap were due to arterial and venous complications, respectively. CONCLUSION: The modified groin flap appears to be a little less reliable than is forearm flap; nevertheless, it could be a good option for patients who desire less conspicuous postoperative scars.

Implantation of octacalcium phosphate nucleates isolated bone formation in rat skull defects.

OBJECTIVE: Our previous radiographic examinations have indicated that the synthetic octacalcium phosphate (OCP) may provide the core for nucleating multiple osteogenic sites in the experimentally created cranial defect. DESIGN: The present study was designed to confirm the possibility that the implanted OCP causes the osteoinduction as well as the osteoconduction in the rat cranial defect. MATERIALS AND METHODS: Standardized defects were created in male Wistar rat calvaria, and the OCP granules were implanted into the defect. The sham operated rats were processed in the same way except that nothing was implanted. The rats were fixed at 4 weeks after implantation of OCP or the sham operation. We examined bone formed on the implanted OCP, analyzing serial sections histologically combined with immunohistochemistry for the bone specific protein, osteocalcin. RESULTS: In the defects treated with OCP, the radiopacity was scattered throughout the defect besides being observed along the defect margin of the parietal bone. Examination of the serial sections showed that some of new bones on the implanted OCP were formed away from the defect margin of the parietal bone with regard to both histological identification and specific molecular marker. CONCLUSIONS: The present study suggested that the implanted OCP can serve as a core for initiating bone formation and cause the osteoinduction as well as the osteoconduction in the defect.

Loss of heterozygosity of nucleotide excision repair factors in sporadic oral squamous cell carcinoma using microdissected tissue.

The deficiencies of nucleotide excision repair (NER) factors are involved in rare genetic diseases such as xeroderma pigmentosum (XP) with increased risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NER factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (LOH) analysis, using the microdissected tissues, for the XPA, XPB, XPC, XPD, XPE, XPF, XPG and the transcription-coupled repair factor, Cockayne syndrome B (CSB) revealed that NER factors were abnormal in 30.0% (3/10 cases) of oral squamous cell carcinomas. Furthermore, 10.0% of oral carcinomas exhibited LOH for NER factors without LOH for tumor suppressor genes such as p53, FHIT, APC, BRCA1, BRCA2 and DCC. These observations raise the possibility that alterations of NER factors may be involved in carcinogenesis in human oral squamous cell carcinoma.

Implantation of octacalcium phosphate combined with transforming growth factor-beta1 enhances bone repair as well as resorption of the implant in rat skull defects.

In our previous study, we reported that synthetic octacalcium phosphate (OCP) enhances bone repair if implanted in rat skull defects. We hypothesized that OCP can be used as an effective carrier for transforming growth factor-beta1 (TGF-beta1) to promote bone repair. We designed the present study to investigate histomorphometrically whether combination with recombinant human TGF-beta1 could promote bone repair caused by OCP per se (Control/OCP). A full-thickness standardized trephine defect was made in the rat parietal bone and OCP combined with recombinant human TGF-beta1 (TGF-beta1/OCP) or Control/OCP was implanted into the defect. Four rats from each group were fixed at 2, 4, and 8 weeks after implantation. Histomorphometrical analysis of the percentage of newly formed bone (n-Bone %) and remaining implants (r-Imp %) in the defect was performed. The statistical analysis showed the n-Bone % of TGF-beta1/OCP was significantly higher than that of the Control/OCP in week 4, whereas the r-Imp % of TGF-beta1/OCP was significantly lower than that of the Control/OCP. The present study demonstrated that OCP can be used as an effective carrier for TGF-beta1 and their combination enhances bone repair as well as resorption of the carrier OCP in the early stage of bone formation.

Immunohistochemical analysis of cell-cycle- and apoptosis-related factors in lining epithelium of odontogenic keratocysts.

We examined the immunohistochemical expressions of cell-cycle- and apoptosis-related factors to investigate the possible role of these factors in odontogenic keratocyst (OKC). Expression of cyclin D1 and p16 protein was detected in the basal and parabasal cells in lining epithelium of OKCs and was found more frequently in basal cell nevus syndrome (BCNS)-associated OKCs than in primary or recurrent OKCs. Positivity for p21 protein was detected in basal to superficial cells, whereas that for p27 protein was detected in parabasal to superficial cells in lining epithelium of OKCs. DNA topoisomerase IIalpha reacted with nuclei in basal and parabasal cells of the lining epithelium of OKCs, and positive cells were observed in BCNS-associated OKCs significantly more frequently than in primary or recurrent OKCs. Expression of Fas in suprabasal to superficial cells and expression of Fas-L in basal and parabasal cells were detected in lining epithelium of OKCs. Immunoreactivity for caspase-3 was detected in basal to suprabasal or superficial cells in lining epithelium of OKCs. Single stranded (ss)DNA-positive nuclei were detected in superficial cells in lining epithelium of OKCs. Fas was more broadly distributed in BCNS-associated OKCs than in primary OKCs, and ssDNA-positive cells were observed in BCNS-associated OKCs significantly more frequently than in primary or recurrent OKCs. These results suggest that BCNS-associated OKCs might be a distinguishable entity from solitary OKCs.

Pumping injection of sodium hyaluronate for patients with non-reducing disc displacement of the temporomandibular joint: two year follow-up.

OBJECTIVES: The purpose of the present study was to examine the long-term effect of pumping injection of sodium hyaluronate into the TMJ in patients with non-reducing disc displacement. PATIENTS: Sixty patients with non-reducing disc displacement underwent pumping injection of sodium hyaluronate (pumping group). Seventy-six patients with non-reducing disc displacements were observed without any active treatment (observation group). STUDY DESIGN: In both patient groups clinical signs and symptoms were observed periodically for 2 years. Variables such as age, range of maximum mouth opening, angle of posterior slope of the articular eminence and degenerative bony changes of the condyle at the initial visit were also examined. Cox hazards analysis was applied to examine the clinical outcome for such variables in addition to the results of pumping injection of sodium hyaluronate. RESULTS: Pumping injection of sodium hyaluronate seemed to have a favourable effect when compared with the control group (untreated) (p = 0.0002). However, the four background variables mentioned could not be explained as predictors of outcome. CONCLUSION: Pumping injection of sodium hyaluronate seems to be effective for non-reducing disc displacement of the temporomandibular joint.

Effect of pumping with injection of sodium hyaluronate and the other factors related to outcome in patients with non-reducing disk displacement of the temporomandibular joint.

We retrospectively examined the effect of pumping with injection of sodium hyaluronate into the temporomandibular joint (TMJ) and the other factors influencing outcome in patients with non-reducing disk displacement of the TMJ. Fifty-nine patients underwent pumping with injection of sodium hyaluronate into the TMJ. As control, 62 patients were observed without any treatment. Both groups were observed for 12 months. The relation between outcome and the following clinical characteristics was also studied: sex, age, range of motion for maximal mouth opening, TMJ pain, TMJ noise, tenderness of masticatory muscles, locking duration, intercuspal occlusions, angle of posterior slope of articular eminence and degenerative bony changes of the condyle. Logistic regression analysis revealed that pumping with injection of sodium hyaluronate was related to a good outcome. Clinical characteristics of presentation significantly related to a good outcome were a large maximal mouth opening, a short locking duration, and a steep posterior slope of articular eminence. We conclude that pumping with injection of sodium hyaluronate into the TMJ is an effective treatment method for non-reducing disk displacement of the TMJ and that some clinical characteristics also influence outcome.

Macrophage-derived chemokine (MDC/CCL22) and CCR4 are involved in the formation of T lymphocyte-dendritic cell clusters in human inflamed skin and secondary lymphoid tissue.

Our previous study demonstrated formation of T cell-dendritic cell (DC) clusters in inflamed dermis of intraorally autotransplanted skin flaps. Such T cell-DC clusters are supposed to be important for close interactions between T cells and DCs including the specific antigen presentation. Here we show the involvement of the macrophage-derived chemokine (MDC/CCL22) and its specific receptor CC chemokine receptor 4 (CCR4) in the formation of T cell-DC clusters. Reverse transcriptase-polymerase chain reaction analysis revealed high levels of mRNA expression for MDC and CCR4 in inflamed skin and neck lymph nodes (LNs), but not in normal skin. Immunohistochemically, MDC(+) cells and CCR4(+) cells were mainly located within the T cell-DC clusters both in the dermis of inflamed skin and the T cell area of LNs. MDC(+) cells were identified to be DCs both in inflamed skin and LNs. The majority of CCR4(+) cells were CD4(+) T cells, accounting for approximately one-third of total CD4(+) T cells in the inflamed skin. Our data suggest that the MDC-CCR4 system plays an important role in the formation of T cell-DC clusters both in inflamed skin and LNs.

Effect of a mutant form of IkappaB-alpha on 5-fluorouracil-induced apoptosis in transformed human salivary gland cells.

Increasing evidence indicates that transcription factor NF-kappaB may play a role in cell survival, and that some chemotherapeutic agents activate NF-kappaB, while inhibition of NF-kappaB renders cells sensitive to these drugs. 5-Fluorouracil (5-FU) exerts its cytotoxic effect through the induction of apoptosis. However, it still remains uncertain whether 5-FU treatment in combination with the inhibition of NF-kappaB largely exerts an anti-proliferative effect on the growth of neoplastic human salivary gland cells. Thus, we investigated whether NF-kappaB suppression in transformed human salivary gland (NS-SV-AC) cells leads to a marked reduction in cell growth in response to 5-FU treatment. Our results demonstrated that under unstimulated conditions, the ability of cell growth in the super-repressor form of IkappaB-alpha (srIkappaB-alpha) cDNA-transfected cell clones (ACMT-6 and -7) was significantly lower than that in the empty vector-transfected cell clone (ACpRc-1). In addition, the growth inhibition caused by 5-FU was greatly enhanced in ACMT-6 and -7 as compared to ACpRc-1. Based on fractional inhibition analysis, this growth inhibition was due to an additive effect of both inhibitors. Electrophoretic mobility shift assay revealed that NF-kappaB activity in these cell clones was not affected by treatment with 5-FU. Accordingly, our data provide evidence that the combination of 5-FU and NF-kappaB suppression cooperatively functions in the growth inhibition of NS-SV-AC cells.

Structural equation modeling of the relationship of bone mineral density and its risk factors in Japanese women.

Several factors have been reported as risk factors for the development of osteoporosis. In this study, we aimed to examine the relationship among lifestyle factors, biologic factors, and bone mineral density (BMD) using structural equation modeling (SEM). The subjects in the present study consisted of 866 postmenopausal Japanese women aged between 40 and 80 years old. In the analysis by the SEM, we employed a multiple basic model. As the structural variables, lifestyle factors and biologic factors were selected.The goodness of fit index (GFI) of the final model was 0.991 and the Akaike's information criteria (AIC) showed the lowest value in the peripheral models. The degree of association between biologic factors and BMD was -0.576 (direct association), 0.012 (indirect association), and -0.564 (total association). With regard to the correlation between lifestyle factors and BMD, the degrees of association were 0.085, -0.084, and 0.001, respectively.This study defined a pilot model for factors influencing BMD. Although is remains necessary to conduct further analyses with more valid measurements and constructs, this model indicated that the correlation between BMD and lifestyle factors was lower than that between BMD and biologic factors.