The nucleocytoplasmic shuttling protein CIZ reduces adult bone mass by inhibiting bone morphogenetic protein-induced bone formation.

Osteoporosis is a major health problem; however, the mechanisms regulating adult bone mass are poorly understood. Cas-interacting zinc finger protein (CIZ) is a nucleocytoplasmic shuttling protein that localizes at cell adhesion plaques that form where osteoblasts attach to substrate. To investigate the potential role of CIZ in regulating adult bone mass, we examined the bones in CIZ-deficient mice. Bone volume was increased and the rates of bone formation were increased in CIZ-deficient mice, whereas bone resorption was not altered. CIZ deficiency enhanced the levels of mRNA expression of genes encoding proteins related to osteoblastic phenotypes, such as alkaline phosphatase (ALP) as well as osterix mRNA expression in whole long bones. Bone marrow cells obtained from the femora of CIZ-deficient mice revealed higher ALP activity in culture and formed more mineralized nodules than wild-type cells. CIZ deficiency enhanced bone morphogenetic protein (BMP)-induced osteoblastic differentiation in bone marrow cells in cultures, indicating that BMP is the target of CIZ action. CIZ deficiency increased newly formed bone mass after femoral bone marrow ablation in vivo. Finally, BMP-2-induced bone formation on adult mouse calvariae in vivo was enhanced by CIZ deficiency. These results establish that CIZ suppresses the levels of adult bone mass through inhibition of BMP-induced activation of osteoblasts.

The anterior trochlear line as a reference for femoral component positioning in total knee arthroplasty.

PURPOSE: A new radiographic method using the anterior and posterior femoral condyles as a landmark to determine the rotational alignment of the femoral component in TKA had been developed. METHODS: The new radiograph presents an axial view of the distal femur. The patients were asked to lie in the supine position and flex the knee approximately 120° to 130°. Radiographs were applied at an inclination angle of 20° to 30°. The condylar twist angle (CTA), the external rotational angle between the posterior condylar (PC) line and the clinical transepicondylar axis (TEA), and the trochlear line angle (TLA), and the internal rotational angle between the anterior trochlear line and the clinical TEA were measured. Images were taken of 129 knees in 87 patients with osteoarthritis of the knee. The measurement values obtained using our method with those obtained using 3D reconstructed images from a 3-dimensional helical CT system (n = 35) were compared. RESULTS: The average CTA was 5.7° ± 2.8° and the average TLA was -5.6° ± 3.2°. The CTA was negatively correlated with the tibiofemoral angle (TFA). The average TLA was positively correlated with the TFA. The average difference between the TLA values obtained with this view and those obtained using the 3D-CT was 0.5° ± 1.6°. The relationship between the radiograph and 3D-CT in TLA was higher than that in CTA. CONCLUSIONS: This radiographic technique allows easy and simultaneous measurement of the CTA and TLA and may provide an alternative method for assessing the TEA of the femur during preoperative planning for TKA.

Effect of troglitazone on tumor growth and pulmonary metastasis development of the mouse osteosarcoma cell line LM8.

BACKGROUND: Osteosarcoma often develops micrometastases in the lung prior to diagnosis, causing a fatal outcome. Therefore, the prevention of pulmonary metastases is critical for the improvement of the prognosis of patients with osteosarcoma. The purpose of this study was to investigate whether troglitazone (TGZ) is considered as possible therapeutics in the treatment of growth and metastasis of osteosarcoma. METHODS: LM8 cells were treated for 3 days with various concentrations of TGZ. The effect of TGZ on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2'-deoxyuridine incorporation study. The assay of cell invasion and motility was performed using either the Matrigel-coated cell culture inserts or the uncoated cell culture inserts in the invasion chambers. The effect of TGZ on Akt signaling was assessed by Western blot analysis of Akt and p-Akt. The effects of oral administration of either TGZ (TGZ group) or ethanol (control group) on the growth of primary tumor and the development of pulmonary metastasis were examined in nude mice implanted with LM8 cells on their backs. The expression and activity of matrix metalloproteinase 2 (MMP-2) within the tumor were determined by immunohistochemistry and zymography. The microvessel density (MVD) within the tumor was determined by immunohistochemistry for CD34. RESULTS: TGZ dose-dependently inhibits cell proliferation. TGZ-treated cells were less invasive and less motile than untreated cells. The activity of MMP-2 secreted by TGZ-treated cells was lower than that secreted by untreated cells. TGZ decreased the level of p-Akt. The primary tumor mass was smaller in the TGZ group than in the control group. The TGZ group had less metastatic tumors in the lung compared with the control group. The expression and activity of MMP-2 within the tumor of the TGZ group were lower than those of the control group. The MVD within the tumor of the TGZ group was lower than that of the control group. CONCLUSIONS: Inhibition of Akt signaling by TGZ may decrease the secretion of MMP-2, resulting in the decrease of invasiveness and motility in LM8 cells. Treatment of tumor-bearing mice with TGZ decreases the expression and activity of MMP-2 within the tumor, and inhibits primary tumor growth and pulmonary metastasis development. TGZ may offer a new approach in chemotherapy for osteosarcoma.

Genetic heterogeneity in rheumatoid arthritis mouse models induced by extrinsic and intrinsic factors.

A cumulative effect of the susceptibility genes with polymorphic alleles may be responsible for rheumatoid arthritis (RA). The objective of this study was to clarify whether susceptibility to RA is under the control of common allelic loci between two different RA models induced by extrinsic and intrinsic factors, collagen-induced arthritis (CIA) in DBA/1 mice and arthritis in MRL/Mp (MRL) mice associated with the Fas deficient mutant gene, Fas(lpr), respectively. CIA was examined in mice of parental DBA/1 and MRL, (MRL x DBA/1) F1 and (MRL x DBA/1) F2 progenies. In genome-wide screening of the severity in the F2 using microsatellite markers, significant linkage was observed on chromosomes 5 and 17 at map position of D5Mit259 and H-2, respectively, associated with DBA/1 alleles, while there was no loci associated with arthritis of MRL-Fas(lpr) mice previously identified. In a quantitative trait locus (QTL) analysis, the locus on chromosome 5 showed the highest peak at map position 35 cM (LOD score 6.0). This study may indicate that the arthritis induced by extrinsic and intrinsic factors is under the control of a different combination of susceptibility genes with common and different alleles, possibly simulating the genetic heterogeneity of RA.

3-D MRI/CT fusion imaging of the lumbar spine.

OBJECTIVE: The objective was to demonstrate the feasibility of MRI/CT fusion in demonstrating lumbar nerve root compromise. MATERIALS AND METHODS: We combined 3-dimensional (3-D) computed tomography (CT) imaging of bone with 3-D magnetic resonance imaging (MRI) of neural architecture (cauda equina and nerve roots) for two patients using VirtualPlace software. RESULTS: Although the pathological condition of nerve roots could not be assessed using MRI, myelography or CT myelography, 3-D MRI/CT fusion imaging enabled unambiguous, 3-D confirmation of the pathological state and courses of nerve roots, both inside and outside the foraminal arch, as well as thickening of the ligamentum flavum and the locations, forms and numbers of dorsal root ganglia. Positional relationships between intervertebral discs or bony spurs and nerve roots could also be depicted. CONCLUSION: Use of 3-D MRI/CT fusion imaging for the lumbar vertebral region successfully revealed the relationship between bone construction (bones, intervertebral joints, and intervertebral disks) and neural architecture (cauda equina and nerve roots) on a single film, three-dimensionally and in color. Such images may be useful in elucidating complex neurological conditions such as degenerative lumbar scoliosis(DLS), as well as in diagnosis and the planning of minimally invasive surgery.

Arthroscopic technique for fragment fixation using absorbable pins for osteochondritis dissecans of the humeral capitellum: a report of 4 cases.

This is the first report to describe a method of arthroscopic osteochondral fixation using absorbable pins to treat osteochondritis dissecans (OCD) of the capitellum. Four adolescent baseball players with OCD of the capitellum were treated, and good short-term results were obtained. During this arthroscopic procedure, the elbow was maintained in the maximum flexed position, and posterolateral portals were used to visualize the lesion, perform drilling, and insert the pins. This procedure is less invasive and easier to perform than other fixation procedures that require harvesting or production of autologous bone pegs. This is an effective method of fragment fixation with absorbable pins.

Proposed novel unified nomenclature for range of joint motion: method for measuring and recording for the ankles, feet, and toes.

The Ad Hoc Committee of Terminology of the Japanese Society for Surgery of the Foot (JSSF) proposes novel terminology for motion of the ankle, foot, and toe because there are some ambiguities in the current terminology. Articles were identified by searching the electronic databases of PubMed that compared definitions of American Orthopaedic Foot and Ankle Society (AOFAS), International Society of Biomechanics (ISB), and in the textbook of Kapandji as well as the American Academy of Orthopaedic Surgeons (AAOS). A total of 11 articles described the transverse (horizontal) plane motion in the hindfoot as external rotation/internal rotation and 10 as abduction/adduction. In all, 2 articles described the transverse (horizontal) plane motion in midfoot as external rotation/internal rotation and 10 as abduction/adduction. Another 4 articles described the transverse (horizontal) plane motion in the forefoot as external rotation/internal rotation and 8 as abduction/adduction. Altogether, 109 articles described the sagittal plane motion of the foot/ankle as dorsiflexion/plantarflexion and 20 as extension/flexion. In all, 99 articles described the frontal (coronal) plane motion of the foot/ankle as inversion/eversion and 4 as supination/pronation. Furthermore, 12 articles described the sagittal plane motion of toes as dorsiflexion/plantarflexion and 15 as extension/flexion. Another 16 articles described the frontal (coronal) plane motion of toes as supination/pronation and 1 as inversion/eversion. The transverse (horizontal) plane motion of the foot/ankle was defined as abduction/adduction in the hindfoot, midfoot, and forefoot; the sagittal plane motion of the foot/ankle was defined as dorsiflexion/plantarflexion; and the frontal (coronal) plane motion of the foot/ankle as inversion/eversion. The transverse (horizontal) plane motion of toes was defined as abduction/adduction; the sagittal plane motion of toes was defined as extension/flexion; and the frontal (coronal) plane motion of toes was defined as supination/pronation.

An Asian case of fibroblastic rheumatism: clinical, radiological, and histological features.

We report a case of fibroblastic rheumatism (FR) in a 61-year-old woman. The patient showed sclerodactyly and polyarthritis that involved both her hands and feet joints. Levels of C-reactive protein and matrix metallopeptidase-3 were within normal range. We diagnosed her condition as FR according to both the clinical features characterized with the destructive change of multiple joints and the histological sample. This is the first FR published case of FR in an Asian individual, and 23 published cases were reviewed.

Expression of sphingosine kinase 2 in synovial fibroblasts of rheumatoid arthritis contributing to apoptosis by a sphingosine analogue, FTY720.

Gene expression profiles in synovial tissues from rheumatoid arthritis (RA) patients have yielded useful information on the pathogenetic process of the synovitis. In one group of them, sphingosine kinase 2 (SPHK2), a nuclear protein regulating cell proliferation, seemed to be highly expressed, undergoing a different pathogenetic process of synovitis. In the present study it was clarified that SPHK2 was expressed in the synovial fibroblasts of the synovial tissues obtained from the knee joints of the RA patients. In the cultured synovial fibroblasts from these patients, SPHK2 was more highly expressed than that in the human macrophage cell line, THP-1 and human dermal fibroblasts. SPHK2 was expressed in and around the nucleus and transferred to the cytoplasm and cell surface by the administration of epidermal growth factor, associated with the increased expression of sphingosine-1-phosphate. A sphingosine analogue, FTY720, which is activated by phosphorylation specifically by SPHK2, mediated apoptotic signaling of the cultured synovial fibroblasts. These findings suggest that SPHK2 may regulate the autonomous proliferation of synovial fibroblasts as one of the predisposing genes to RA and could be a target for a novel therapeutic strategy for RA.

Laser-guided placement of the tibial guide in the transtibial technique for anterior cruciate ligament reconstruction.

In anterior cruciate ligament (ACL) reconstruction, it is important to determine the location and direction of the femoral bone tunnel when using the transtibial technique. Accurately identifying the anatomic location at which to make the femoral bone tunnel for double-bundle ACL reconstruction is not a straightforward procedure. We describe a new method in which the centrum of the femoral tunnel is marked with an awl and a laser beam-guided technique is used to place the tibial pin. This procedure allows us to mark the desired location of the femoral tunnel before drilling the tibial bone tunnel when using the transtibial technique. This is the first report of a laser-guided technique used in arthroscopic surgery. We used a laser beam to determine the location of the femoral tunnel--the anatomic site needed to perform the intra-articular drilling in the tibia. In this technique, a laser pointer is set at the tibial guide, which reflects the laser beam and illuminates the point where the femoral bone tunnel should be made. Our method offers an easy and accurate way to reconfirm the tibial placement before drilling.

Resolution of intraspinal retro-odontoid cyst associated with os odontoideum after posterior fixation.

STUDY DESIGN: A case report and review of previous literature. OBJECTIVES: To describe the diagnosis and successful treatment of an intraspinal retro-odontoid cyst associated with an os odontoideum. SUMMARY OF BACKGROUND DATA: Retro-odontoid cysts associated with atlantoaxial instability are extremely rare. Direct excision of the cysts has commonly been performed for the surgical treatment of myelopathy. METHODS: A retro-odontoid cyst in a 58-year-old woman with os odontoideum was treated surgically by posterior fixation between C1 and C3 without resection of the retro-odontoid mass. The patient's history, clinical examination, imaging findings, and treatment are reported. RESULTS: The patient experienced walking difficulty, numbness in the upper and lower limbs, and hypesthesia in both hands. Congenital C2/3 fusion and atlantoaxial instability associated with an os odontoideum were found in the radiographs. Magnetic resonance imaging detected a round retro-odontoid mass, which compressed the spinal cord. The mass showed uniform low intensity on T1-weighted images and uniform high signal intensity on T2-weighted images. Gadolinium-diethylenetriaminepenta-acetic acid-enhanced T1-weighted images showed rim enhancement of the mass with no internal enhancement. Three months after the operation, the mass was no longer visible in a magnetic resonance imaging examination and the patient completely recovered motor function in her extremities. CONCLUSIONS: Posterior fixation without resection was successfully used to eliminate a retro-odontoid cyst associated with atlantoaxial instability.

The relationship between increased hip range of motion, wear, and locking mechanism failure in the Harris-Galante acetabular component.

We performed both clinical and radiographic evaluations of 178 patients (190 hips) who had undergone cementless total hip arthroplasties using Harris-Galante I/II porous cups after an average 12-year follow-up period (range, 8-18 years). We revised 15 Harris-Galante I/II porous cups (7.8%), and the locking mechanism was broken in 10 revised cups (67%). There was a significant association between locking mechanism failure and linear polyethylene wear. We observed a significant positive correlation between linear polyethylene wear and increased ranges of motion such as flexion, adduction, and external rotation at the last follow-up visit after the primary operation. Increased ranges of motion seen in Asians induced higher linear polyethylene wear and locking mechanism failure due to impingement of the neck and cup.

Correction of hallux valgus deformity using the center of rotation of angulation method.

BACKGROUND: To correct a hallux valgus (HV) deformity quantitatively and prevent unexpected postoperative deformity, the center of rotation of angulation (CORA) method was applied during HV surgery. To correct a hallux valgus (HV) deformity quantitatively and prevent unexpected postoperative deformity, the center of rotation of angulation (CORA) method was applied during HV surgery. METHODS: To create a normal foot model, radiographs of 64 normal female feet were measured. Points A and B were defined as the intersection of the intermetatarsal angle and the HV angle. CORA1 and CORA2 were defined as the intersection of the axes of the first metatarsal and the first proximal phalanx in the normal and HV models, respectively. Procedures to correct HV deformity using the CORA method were devised and were applied to HV feet, which underwent a focal dome osteotomy or medial wedge osteotomy. RESULTS: Point A was 2.3 times the length of the second metatarsal proximally from the top of the second metatarsal head, and point B was 0.17 times the length of the first metatarsal proximally from the top of the first metatarsal head. Two methods were used to correct the deformity. With one method, a focal dome osteotomy was performed at the first metatarsal on the circle at the CORA1 and the distal fragment was moved to the standard first metatarsal axis. The first proximal phalanx was then moved around the metatarsal head to the standard axis of the first proximal phalanx at the CORA2. With the other method, a medial wedge osteotomy was performed on or proximal to the CORA2, and the distal fragment was moved to the first standard metatarsal axis. CONCLUSIONS: We propose a preoperative plan to use the CORA method to correct deformities that prevent translation of the axis or an angulation deformity. HV deformity can be corrected effectively using the CORA method.

4-tert-octylphenol regulates the differentiation of C3H10T1/2 cells into osteoblast and adipocyte lineages.

The aim of this study was to investigate whether 4-tert-octylphenol (OP) affects the differentiation of multipotent C3H10T1/2 cells, a cell line established from mouse embryonic connective tissue, into osteoblast and adipocyte lineages. Confluent C3H10T1/2 cells were incubated for 7 days with (OP-treated cultures) or without (control cultures) 15 microg/ml of OP. The 7-day treatment of confluent cells with OP decreased alkaline phosphatase activity by 81%, inhibited the expression of transforming growth factor beta2, and inhibited the morphological changes in cells to an osteoblastic appearance. These results indicate that the 7-day treatment of confluent C3H10T1/2 cells with OP inhibited their differentiation into osteoblasts. Since this treatment strongly induced the expression of peroxisome proliferator-activated receptor r (PPARr) but did not stimulate triacylglycerol (TG) accumulation in cells, C3H10T1/2 cells in the control and OP-treated cultures were incubated for 2 days with a hormone mixture (insulin [INS], dexamethasone, and 1-methyl-3-isobutylxanthine) and incubated for an additional 5 days with INS alone. The TG and adiponectin contents of the OP-treated cultures were 4.2 and 4.1 times higher, respectively, than those of the control cultures. There were many more Oil Red O-staining cells in the OP-treated cultures than in the control cultures. The expression of PPARr in the OP-treated cultures was higher than that in the control cultures. These results indicate that the OP-treated cultures contained a larger number of adipocytes than the control cultures. In conclusion, treatment of C3H10T1/2 cells with OP inhibited osteoblast differentiation, causing a lineage shift toward adipocytes.

Effect of cortisol on cell proliferation and the expression of lipoprotein lipase and vascular endothelial growth factor in a human osteosarcoma cell line.

PURPOSE: The aim of this study is to investigate whether cortisol inhibited cell proliferation and the expressions of lipoprotein lipase (LPL), a key enzyme involved in the energy metabolism in tumor cells, and vascular endothelial growth factor (VEGF), a potent angiogenic factor in the tumor, in cultures of OST cells, a human osteosarcoma cell line. METHODS: OST cells were treated for 48 h with or without cortisol. To examine the effect of cortisol on cell proliferation, the expression of proliferating cell nuclear antigen (PCNA) was examined by Western blotting, and the amount of (3)H-thymidine incorporated into DNA during the last 30 min of the 48-h treatment period was measured. To examine the effect of cortisol on the expression of LPL, the activity and mass of LPL were measured in the extract of acetone/ether powder of cells, and the amount of (35)S-methionine incorporated into LPL during the last 2 h of the 48-h treatment period was measured by immunoprecipitation. The expression of VEGF was examined by immunohistochemistry and Western blotting. RESULTS: The amount of (3)H-thymidine incorporated into DNA and the level of PCNA were lower in the cortisol-treated cultures than in the untreated cultures, thus indicating that cortisol inhibited the proliferation of OST cells. The synthetic rate and activity of LPL were lower in the cortisol-treated cultures than in the untreated cultures but no difference in the specific activity of LPL between the two cultures was observed, thus indicating that cortisol inhibited LPL synthesis, thereby resulting in a decreased LPL activity. The expression of VEGF was lower in the cortisol-treated cultures than in the untreated cultures. CONCLUSION: Cortisol not only has the ability to inhibit cell proliferation but also the ability to inhibit the expressions of LPL and VEGF in cultures of OST cells.

Perinatal and postnatal exposure to 4-tert-octylphenol inhibits cortical bone growth in width at the diaphysis in female mice.

The aim of this study was to investigate the effects of 4-tert-octylphenol (OP) on bone growth in vivo. Pregnant mice were exposed to drinking water containing either 1microg/ml OP (LD group) or 10microg/ml OP (HD group) from gestational day 10 and throughout the lactation period. After weaning, the pups were allowed free access to drinking water containing the appropriate OP concentrations. The serum osteocalcin level of the females, but not the males, was significantly lower in the LD and HD groups than in the control group on postnatal day 31. The femurs of the females were analyzed by peripheral quantitative computed tomography and immunohistochemistry for alkaline phosphatase (ALP) was performed in the sections of the formalin-fixed femurs. The periosteal and endosteal circumferences of the cortical bone at the diaphysis were significantly smaller in the LD group, but not the HD group, than in the control group (4% and 6% smaller, respectively), while there were no differences in the cortical bone density, cortical bone area, or cortical thickness among the three groups. There were fewer ALP-positive cells on the periosteal surfaces at the diaphysis in the LD group than in the control group. The values of the strength strain index (xSSI, ySSI, and pSSI) decreased with decreasing the periosteal circumference. In conclusion, the exposure of female mice to OP during the perinatal and postnatal periods inhibited the periosteal bone formation in the cortical bone at the diaphysis of the femur, thereby causing a reduction in bone growth in width.

The synthesis and activity of lipoprotein lipase in the subcutaneous adipose tissue of patients with musculoskeletal sarcomas.

The purpose of this study was to explore the triacylglycerol (TG) deposition and lipoprotein lipase (LPL) activity in the adipose tissue of patients with muculoskeletal sarcoma. Subcutaneous adipose tissue was obtained from the thighs of 19 patients with musculoskeletal sarcomas (sarcoma group) and 20 patients with osteoarthritis of the hip joint (control group) at surgery. The adipose tissue was homogenized and aliquots of the homogenate were used to measure the TG content and to prepare an acetone/ether powder to measure the LPL activity. The TG content was higher, but not significantly, in the sarcoma group than in the control group. The LPL activity of the sarcoma group was significantly higher than that of the control group. The TG content of the sarcoma group correlated positively with the LPL activity. [35S]Methionine incorporation investigation showed that the rate of LPL synthesis was significantly higher in the sarcoma group than in the control group. These results indicated that LPL was up-regulated at the transcriptional/translational level, thus resulting in an increased TG deposition in the adipose tissue of patients with muculoskeletal sarcoma.

A complete remission of sclerosing rhabdomyosarcoma with multiple lung and bone metastases treated with multi-agent chemotherapy and peripheral blood stem cell transplantation (PBSCT): a case report.

A case of sclerosing rhabdomyosarcoma (RMS) in a young adult with multiple lung and skip bone metastases is reported. Complete remission was achieved with this patient by treatment with multi-agent chemotherapy and peripheral blood stem cell transplantation (PBSCT) based on the pathological diagnosis of RMS using a specimen obtained during an open biopsy at the first consultation. He is still alive and has been continuously disease free for 12 years after surgery. This is a very rare case with successful treatment using PBSCT for a sclerosing RMS that presented with multiple distant metastases at the first consultation.

Biomechanical study of optimum anchorage in dome-shaped high tibial osteotomy.

PURPOSE: There has been no report to date on any biomechanical study regarding the strength of fixation at the osteotomy site in dome-shaped high tibial osteotomy (HTO). In this study, we evaluated the biomechanical strength of a spacer that we improved and determined the medial site of HTO. METHODS: HTO correction angles of 15° and 20° were used in all experiments, which were performed on lower leg specimens from pigs ( n = 12). The osteotomy site was fixed by a locking plate and screws with a spacer. Compression (600 N/min until 1100 N) and extended cyclic loading (200 cycles at 1000-2000 N) were performed to compare initial displacements in HTO specimens with and without spacers. RESULTS: The reduction ratios of displacement with and without spacers at HTO correction angles of 15° and 20° were 37% and 27%, respectively. No effect of the spacer at the correction angle of 15° was observed in the cyclic loading; however, the maximum displacement and amplitude were reduced with the spacer at the correction angle of 20°. CONCLUSIONS AND CLINICAL RELEVANCE: When the HTO correction angle is small, the effect of the spacer is uncertain. However, the spacer is effective at an HTO correction angle of 20°.

Perinatal and postnatal exposure to bisphenol a increases adipose tissue mass and serum cholesterol level in mice.

AIM: To investigate whether the perinatal and postnatal exposure of mice to bisphenol A (BPA) caused the development of obesity and/or hyperlipidemia. METHODS: Pregnant mice were exposed to BPA in drinking water at concentrations of either 1 microg/mL (LD group) or 10 microg/mL (HD group) from gestation day 10 and throughout the lactating period. After weaning, the pups were allowed free access to drinking water containing the appropriate concentrations of BPA. The body weight, adipose tissue weight, and serum lipid levels were measured in the offspring at postnatal day 31. RESULTS: In females, the mean body weight increased by 13% in the LD group (p<0.05) and 11% in the HD group (p<0.05) compared with the control group. The mean adipose tissue weight increased by 132% in the LD group (p<0.01). The mean total cholesterol level increased by 33% in the LD group (p<0.01) and 17% in the HD group (p<0.05). In males, the mean body weight and mean adipose tissue weight increased by 22% (p<0.01) and 59% (p<0.01), respectively, in the HD group compared with the control group. The mean triacylglycerol level increased by 34% in the LD group (p<0.05). CONCLUSIONS: The continuous exposure of mice to BPA during the perinatal and postnatal periods caused the development of obesity and hyperlipidemia.