Alendronate sodium/vitamin D3 combination tablet versus calcitriol for osteoporosis in Chinese postmenopausal women: a 6-month, randomized, open-label, active-comparator-controlled study with a 6-month extension.

UNLABELLED: This study compares efficacy of ALN/D5600 versus that of calcitriol in osteoporotic Chinese postmenopausal women. ALN/D5600 produced greater bone mineral density (BMD) increases, greater bone turnover marker decreases, and less vitamin D insufficiency. This study provided detailed clinical information regarding ALN/D5600 treatment versus calcitriol 0.25 µg/day. The study did not evaluate fracture risk. INTRODUCTION: The aim of this study is to investigate efficacy of alendronate 70 mg/vitamin D3 5600 IU combination tablets (ALN/D5600) versus calcitriol in osteoporotic Chinese postmenopausal women. METHODS: This study is a 6-month, randomized, open-label, active-comparator study with 6-month extension (clinicaltrials.gov number NCT01350934) in postmenopausal women aged >55 years with osteoporosis (low bone mineral density (BMD) with/without prior fragility fracture). Patients were randomized to ALN/D5600 once weekly or calcitriol 0.25 µg daily. The primary efficacy end point of the base study was percent change from baseline in lumbar spine BMD (month 6). Hypercalcemia and hypercalciuria were safety events of special interest. RESULTS: A total of 219 patients (ALN/D5600 n = 111, calcitriol n = 108) were randomized. Baseline characteristics were similar, 30.3 % baseline 25-hydroxyvitamin D (25(OH)D) ≤15 ng/mL. At months 6 and 12, changes in lumbar spine BMD from baseline were 3.5 versus 1.6 % and 5.2 versus 2.3 % for ALN/D5600 versus calcitriol (between-group differences p < 0.001), respectively. Between-group differences for ALN/D5600 versus calcitriol were significant (p < 0.001) at months 6 and 12 for change from baseline in procollagen type 1 N-terminal propeptide (-59.1 versus -16.8 %, -68.1 versus -17.0 %) and serum C-telopeptides (-79.2 versus -27.2 %, -76.2 versus -24.2 %). Drug-related adverse events (AEs) and discontinuations due to drug-related AEs occurred in 15 (14.0 %) versus 8 (7.4 %) patients and 3 (2.8 %) versus 0 patients in the ALN/D5600 and calcitriol group, respectively. Hypercalciuria 12-month incidence (24-h urine Ca >300 mg) was 8.4 (ALN/D5600) versus 13.9 % (calcitriol) (p > 0.05). One patient (calcitriol) had hypercalcemia. CONCLUSIONS: ALN/D5600 produced greater increases in lumbar spine BMD and greater decreases in bone turnover markers versus calcitriol in osteoporotic Chinese women. It is not known whether the greater increase in BMD results in fewer fractures. ALN/D5600 was generally well tolerated in Chinese patients.

Reference intervals of bone turnover markers determined by using their curve-fitting valley for adult females in China.

SUMMARY: The reference values for bone turnover markers (BTMs) have a significant role in the diagnosis, monitoring, and treatment of metabolic bone disease. This study proposes that the peak value of bone mineral density and the trough value for the BTM curve can be used to determine the reference range of BTM. INTRODUCTION: The aim of this study is to determine the reference intervals of BTMs for adult females in China with an attempt to reference the peak bone mineral density (BMD) with the corresponding BTM valley. METHODS: This study included 546 premenopausal and 394 postmenopausal women. The levels of several BTMs were determined, and the BMD was measured using a dual-energy X-ray absorptiometry. RESULTS: The BTMs of postmenopausal women were 17-96 % higher than premenopausal women. The change of BTM with age presented an optimal goodness-of-fit according to the cubic regression model (R (2) = 0.074-0.346, all P = 0.000). All kinds of BTM levels were positively correlated with age in premenopausal women aged 27-56 years old (r = 0.167-0.502, P = 0.023-0.000). Except for uCTX, the BTM reference value determined using a curve-fitting valley was significantly lower than the reference values for premenopausal women. The BTM reference values determined in this study were also significantly different from the reference values given by the manufacturers of the reagents used. CONCLUSIONS: This study found that the changes of level with age of BTMs in Chinese women present an optimal goodness-of-fit according to the cubic regression model. The fitting valley corresponds to the BMD fitting peak and may possibly be an effective means of determining the BTM reference intervals.

Relationships between serum omentin-1, body fat mass and bone mineral density in healthy Chinese male adults in Changsha area.

PURPOSE: The present study is firstly designed to identify the relationship between serum omentin-1 concentration, body fat mass and bone mineral density in healthy Chinese male adults in Changsha city. METHODS: A total of 219 (20-80 years old) healthy subjects were enrolled in this cross-sectional study. Serum omentin-1, adiponectin, leptin, resistin and bone turn over biochemical markers were measured with enzyme-linked immunosorbent assay. Bone mineral density (BMD) and fat body composition were determined using dual-energy-X-ray absorptiometry. RESULTS: Serum omentin-1 levels in the overweight subjects were significantly lower than those of the subjects with normal weight (p < 0.05). Omentin-1 was negatively correlated with weight (r = -0.418), body mass index (BMI, r = -0.419), waist circumference (r = -0.402), waist-to-hip ratio (WHR, r = -0.355), fat body mass (FBM, r = -0.430), fat % (r = -0.408), trunk fat (-0.431). However, after controlling for age, BMI and FBM, no significant correlation was noticed between omentin-1 and BMD at different skeletal sites. Pearson's correlation coefficients and partial correlation coefficients after adjustment showed no significant correlations between omentin-1 and bone turn over biochemical markers, including bone-specific alkaline phosphatase and bone cross-linked N-terminal telopeptides of type I collagen. Multiple line stepwise regression analysis revealed that FBM, WHR, adiponectin were important variables affecting omentin-1. Moreover, lean tissue mass was the most important factor affecting BMD and explained 10.5-14.7 % of the variance. Omentin-1, leptin and resistin were not the predictors of BMD. CONCLUSIONS: Serum omentin-1 was negatively correlated with FBM and BMI in healthy Chinese male adults, It was not significantly correlated with bone turnover biochemical markers. Omentin-1 may exert ambiguous effects on BMD, which maybe caused by the complex interactions among adipokines, hormonal activity, and body composition and bone metabolism.

Omentin-1 exerts bone-sparing effect in ovariectomized mice.

UNLABELLED: Omentin-1 inhibited osteoblast differentiation in vitro. In co-culture systems of osteoblasts and osteoclast precursors, omentin-1 reduced osteoclast formation by stimulating osteoprotegerin (OPG) and inhibiting receptor activator for nuclear factor κB ligand (RANKL) production in osteoblasts. In vivo, adenovirus-mediated overexpression of omentin-1 suppressed bone turnover and restored bone mineral density (BMD) and bone strength in ovariectomized mice. INTRODUCTION: Omentin-1 (also intelectin-1) is a recently identified visceral adipose tissue-derived cytokine that is highly abundant in plasma. This study was undertaken to investigate the effects of omentin-1 on bone metabolism. METHODS: Osteoblast differentiation was assessed by measuring alkaline phosphatase activity, osteocalcin production and matrix mineralization. OPG and RANKL protein expression and secretion in osteoblasts were detected by Western blot and ELISA, respectively. The effect of recombinant omentin-1 on osteoclast formation was examined in co-culture systems of osteoblasts and osteoclast precursors. The effects of intravenous administration of adenoviral-delivered omentin-1 on bone mass, bone strength, and bone turnover were also examined in ovariectomized mice. RESULTS: In vitro, omentin-1 inhibited osteoblast differentiation, while it had no direct effect on osteoclast differentiation; it also reduced osteoclast formation in the co-culture systems through stimulating OPG and inhibiting RANKL production in osteoblasts. In vivo, adenovirus-mediated overexpression of omentin-1 partially restored BMD and bone strength in ovariectomized mice, accompanied by decreased levels of plasma osteocalcin and tartrate-resistant acid phosphatase-5b and lower serum RANKL/OPG ratios. CONCLUSION: The present study suggests that omentin-1 ameliorates bone loss induced by estrogen deficiency via downregulating the RANKL/OPG ratio.

Age-related bone mineral density, osteoporosis rate and risk of vertebral fracture in mainland Chinese women with type 2 diabetes mellitus.

Few data are available regarding bone mineral density (BMD) and the risk of vertebral fracture among mainland Chinese women with type 2 diabetes mellitus (T2DM). A decrease in the bone projective area (BPA) can be an indirect marker reflecting compressed vertebral fracture. We investigated age-related BMD, BPA, and the prevalence of osteoporosis in women with T2DM in mainland China. BMD and BPA of the posteroanterior lumbar spine (L1-L4) and hip were measured by dual-energy X-ray absorptiometry in 1253 women with T2DM and 1194 control subjects without diabetes aged 40-80 yr. BMD of the lumbar spine and hip decreased with age. BMD of the lumbar spine was higher in T2DM than controls (p<0.05-0.001), as was BPA at some vertebral bodies (p<0.05-0.001), whereas no significant intergroup differences in BPA were observed at the hip. The prevalence of osteoporosis in the women with T2DM increased with age: 0-2.58% at age 40-49 yr, 6.94-28.4% at age 50-59 yr, 32.7-76.7% at age 70-80 yr, with the range reflecting differences between skeletal sites. In subjects over 60 yr, the rates of osteoporosis at posteroanterior spine were significantly lower in T2DM patients than in controls (p<0.05-0.001). In conclusion, women with T2DM had higher BMD and lower risk of osteoporosis. Higher BPA of the vertebrae indicated that women with T2DM in mainland China would have a lower risk of vertebral fracture than non-diabetic women.

Age-related changes in biochemical markers of bone turnover and gonadotropin levels and their relationship among Chinese adult women.

UNLABELLED: The relationship between the levels of gonadotropic hormones and bone metabolism in Chinese adult women is unclear. Our research shows that a significant positive correlation exists between the levels of gonadotropic hormones and various bone turnover indicators. Follicle-stimulating hormone (FSH) has been found to have a greater influence on all types of bone turnover indicator than luteinizing hormone (LH). Further, FSH has a greater influence on bone formation indicators than on bone resorption indicators. INTRODUCTION: The aim of this study was to investigate the relationship between serum FSH and LH and biochemical markers of bone turnover in native Chinese adult women. METHODS: We conducted a cross-sectional study of 694 healthy Chinese women aged between 20 and 82 years. Serum FSH, LH, bone-specific alkaline phosphatase (BAP), osteocalcin (OC), N-terminal telopeptides of type I collagen, C-terminal telopeptides of type I collagen, urinary NTX, urinary CTX, and urinary deoxypyridinoline (uDPD) were determined. RESULTS: All types of bone turnover indicator were significantly positively correlated with FSH (r = 0.164-0.626, all P = 0.000) and LH (r = 0.130-0.618, all P = 0.013-0.000). The correlation coefficient between serum FSH and BAP was the highest (r = 0.626), and that between serum FSH and uDPD was the lowest (r = 0.164). The serum gonadotropic hormone levels were higher; concentrations of bone turnover indicators were higher. The extent of the influence of FSH on various bone turnover indicators was approximately seven to 20 times greater than that of LH on these indicators. FSH could explain 43% and 22% of the changes in BAP and OC, respectively; whereas, LH could explain only 2.1% and 1.1%, respectively. FSH could explain approximately 1.9-11.8% of the changes in bone resorption indicators; however, LH had almost no effect on them. CONCLUSIONS: Gonadotropic hormone levels are correlated with the rate of bone turnover in Chinese women: the higher the serum gonadotropic hormone levels in circulation, the higher the levels of bone turnover indicators. FSH has a greater influence on all types of bone turnover indicator than LH; moreover, it has a greater influence on bone formation indicators than on bone resorption indicators.

Relationships between serum adiponectin, apelin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in post-menopausal Chinese women.

BACKGROUND: Adiponectin, apelin, leptin, resistin, and visfatin, as the main circulating peptides secreted by adipose tissue, are potential contributors to bone metabolism. However, their association with bone mineral density (BMD) is unclear. AIM: The present study investigated whether these serum adipocytokines levels are associated with BMD and bone turnover markers. METHODS: Serum adiponectin, apelin, leptin, resistin, visfatin levels, bone turnover biochemical markers, and BMD were determined in 336 post-menopausal Chinese women (41-81 yr old). RESULTS: Adiponectin was negatively correlated with fat mass, while leptin had a positive correlation. In the multiple linear stepwise regression analysis, years since menopause, lean mass, estradiol, and adiponectin, but not fat mass, apelin, leptin, resistin, and visfatin, were independent predictors of BMD. The significant positive correlations between adiponectin and bone-specific alkaline phosphatase, bone crosslinked N-telopeptides of type I collagen were found. CONCLUSIONS: Adiponectin was an independent predictor of BMD in post-menopausal Chinese women, and positively correlated with bone turnover biochemical markers. It suggested that adiponectin may exert a negative effect on bone mass by promoting excessive bone resorption associated with bone loss in post-menopausal women.

Zoledronate reverses mandibular bone loss in osteoprotegerin-deficient mice.

UNLABELLED: To characterize the changes in osteoprotegerin-deficient (OPG-/-) mice mandibles and the possible mandibular bone loss prevention by zoledronate. This preventive effect in the mandible differed from that in the proximal tibia and was independent of the OPG pathway. INTRODUCTION: The study aimed to characterize both the changes in the mandible in osteoprotegerin-deficient (OPG-/-) mice and possible mandibular bone loss prevention by zoledronate. METHODS: Twenty-eight 6-week-old female mice (C57BL/6J), including OPG-/- (n = 21) and wild-type (WT) (n = 7) mice, were assigned to four groups after 2 weeks of acclimatization to local vivarium conditions: wild mice with vehicle (WT group); OPG-/- mice with vehicle (OPG-/- group); and OPG-/- mice that were subcutaneously injected with either 50 or 150 microg/kg zoledronate (Zol-50 and Zol-150 groups, respectively). Mice were sacrificed at 4 weeks after these treatments and after fasting for 12 h. Sera were harvested for biochemical analyses. The right mandible and tibia of each mouse were selected for microCT analysis. Student's t-test was performed for comparisons of bone parameters at different sites in the WT group. Analysis of variance (ANOVA) was used to compare the biomarkers and bone parameters in the different treatment groups. RESULTS: Serum bone-specific alkaline phosphatase (B-ALP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) were significantly decreased in WT mice as compared to the levels in the OPG-/- mice (P < 0.05). Zoledronate treatment decreased the high serum B-ALP activity observed in OPG-/- mice to the levels seen in WT mice, while serum TRACP-5b concentrations were decreased to levels even lower than those in WT mice. There were substantial variations in BMD and microstructure of the mandibular and proximal tibial trabeculae. Mandibular bone loss was less affected by OPG gene deprivation than the proximal tibia was. Both zoledronate groups showed greater BMD, trabecular BV/TV, Tb.Th, Tb.N, and Conn.D and a significant decrease in Tb.Sp and SMI as compared to the findings in OPG-/- mice (P < 0.05). However, higher apparent BMD and more compact plate-like trabeculae were observed in the mandible after treatment with zoledronate as compared to the findings in the proximal tibia. No significant differences were found in any parameter in both zoledronate groups. CONCLUSIONS: The present study showed that zoledronate could reverse the significant bone loss in mice mandibles that was induced by OPG gene deficiency. This preventive effect, which was accompanied with considerable inhibition of bone turnover, differed in the mandible and in the proximal tibia and was independent of the OPG pathway.

Effects of methylprednisolone on bone mineral density and microarchitecture of trabecular bones in rats with administration time and assessed by micro-computed tomography.

BACKGROUND: Little research exists on the dynamic effects of glucocorticoids on bone mineral density (BMD) and microarchitecture of trabecular bones of rats assessed by micro-computed tomography (micro-CT). PURPOSE: To investigate time-related changes in the BMD and microarchitecture of trabeculae in rats exposed to glucocorticoid. MATERIAL AND METHODS: Female Sprague-Dawley rats were recruited into a baseline group, glucocorticoid-treated groups, or control groups. Glucocorticoid-treated rats were given daily subcutaneous injections of methylprednisolone at a dosage of 3.5 mg/kg for 1 or 9 weeks. A high-resolution micro-CT was used to identify the densitometric and microarchitectural properties of trabeculae in both the proximal metaphysis of tibiae and the sixth lumbar vertebrae (L6). RESULTS: Compared with baseline rats, volumetric BMD, tissue BMD, bone volume fraction, trabecular number, and degree of anisotropy of trabeculae from tibiae or L6 increased in control rats and glucocorticoid-treated rats with time; however, changes in the latter group were smaller. Compared with control rats at each time point, a decrease occurred in volumetric BMD, tissue BMD, bone volume fraction, trabecular number, degree of anisotropy, and trabecular connectivity density in trabecular bones from tibiae or L6 in glucocorticoid-treated rats. The decrease was greater in week 9 compared to week 1. Contrarily, an increase was noted in trabecular thickness, trabecular separation, and structure model index in glucocorticoid-treated rats. A time-related analysis within glucocorticoid-treated groups in both skeletal regions showed a decline in bone volume fraction, trabecular connectivity density, trabecular number, and degree of anisotropy with time, but trabecular thickness and trabecular separation were elevated. CONCLUSION: Methylprednisolone can inhibit bone mineralization and bone mass gain with growth in rats. It can also deteriorate microarchitecture of trabeculae in a time-dependent or an accumulative dose-dependent manner. Further, the remaining trabeculae appear to thicken in order to adapt to altered stress.

L-carnitine protects against apoptosis of murine MC3T3-E1 osteoblastic cells.

L-carnitine (LC), an amino acid with a major role in cellular energy metabolism, has positive effects on bone metabolism. However, the effect of LC on apoptosis of osteoblast in vitro has not been reported. The aim of this study was to investigate the action of LC on apoptosis of mouse osteoblastic cell line MC3T3-E1. Cell apoptosis was measured by sandwich-enzyme-immunoassay. Release of cytochrome c from mitochondria into cytosol and Bcl-2, Bax protein levels were determined by Western blot analysis. The enzyme substrate was used to assess the activation of caspase-3 and caspase-9. LC inhibited MC3T3-E1 cell apoptosis induced by serum deprivation. Our study also shows that LC decreased cytochrome c release and caspase-3 and caspase-9 activation in serum-deprived MC3T3-E1 cells. Furthermore, LC protected against MC3T3-E1 cell apoptosis induced by the glucocorticoid (GC) dexamethasone (Dex).

Recombinant tissue metalloproteinase inhibitor-3 protein induces apoptosis of murine osteoblast MC3T3-E1.

Tissue inhibitor of metalloproteinases (TIMPs) plays an essential role in the regulation of bone metabolism. Here we report that recombinant tissue metalloproteinase inhibitor-3 (TIMP-3) protein induces the apoptosis of MC3T3-E1 osteoblasts. Cell apoptosis was detected by sandwich-enzyme-immunoassay. Fas and Fasl protein levels were determined by Western blot analysis. The enzyme substrate was used to assess the activation of caspase-3 and caspase-8. The phosphorylation of JNK, p38 and ERK1/2 was examined by Western blot analysis. The ELISA suggested that TIMP-3 promoted MC3T3-E1 cell apoptosis. TIMP-3 treatment induced the expression of Fas and Fasl proteins, and the activation of caspase-8 and caspase-3. TIMP-3 treatment induced p38 and ERK phosphorylation. SB203580 and PD98059, the inhibitor of p38 and ERK, respectively, abolished the TIMP-3 effect on osteoblast apoptosis. In conclusion, the signal pathway through which TIMP-3 induces MC3T3-E1 cell apoptosis, mediated by Fas and involves the p38 and ERK signal transduction pathways.

Bone mineral content and bone mineral density at lumbar spine and forearm in Chinese girls aged 6-18 years.

We investigated the age-related bone mineral content (BMC), bone mineral density (BMD) and the tempo of growth in BMC and BMD at lumbar spine and forearm in 455 Chinese girls aged 6-18 yr. BMC and BMD at the anteroposterior lumbar spine (LS), the left forearm (radius+ulna ultradistal, R+UUD) and one-third region (R+U1/3) were measured using a dual-energy X-ray bone densitometer (DXA). BMC and BMD exhibited different change patterns with the age changes. There were significant correlations between age, height, weight and BMC and BMD at LS, R+UUD and R+U1/3 sites. BMC and BMD increased significantly with increments in pubertal stages at LS, R+UUD and R+U1/3 sites. In conclusion, our study showed that Tanner stage had a significant positive association with BMC and BMD of the lumbar spine and forearm. The differences were found in the growth tempo of BMC and BMD within a region and between the spine and forearm. Both BMD and BMC were recommended to evaluate the bone health in children and adolescents.

Age-related variation in quantitative ultrasound at the tibia and prevalence of osteoporosis in native Chinese women.

This study investigated the variations in age-related speed of sound (SOS) at the tibia and prevalence of osteoporosis in native Chinese women, and establishment of a reference database by quantitative ultrasound. SOS at the right midtibia was measured using a quantitative ultrasound device (SoundScan 2000, Myriad Ultrasound Systems, Israel) in 1596 healthy Chinese women ranging from 12 years to 96 years of age. Healthy women were selected on the basis of (1). a detailed questionnaire about their medical history, (2). face to face questioning about their medical history, and (3). a physical examination. Women with a medical condition that required medication that affected bone metabolism or those who had had a pathologic or moderate traumatic fracture were excluded. We followed the diagnostic criteria provided by the instrument's manufacturer and equivalent to the WHO criteria (using the T-score cut-off that diagnoses 30% of the post-menopausal women aged >or =50 years with osteoporosis) as the diagnostic criteria for osteoporosis in this group of women. Data were analyzed in age groups divided by intervals of 5 years. The peak SOS at the tibia of 3991+/-68 m s(-1) (mean+/-SD) occurred in the 35-39 year age group and the T-score precision was 0.99 T-score units. The SOS value increased with age up to 34 years of age and then declined with age after 40 years of age with the rate of decrease at 9.68 m s(-1) per year. The curve representing the SOS change according to age is best fitted by the regression analysis of cubic model, and the cubic equation for SOS=3383+39.9 (age)-0.78 (age)(2)+0.0039 (age)(3) (R(2)=0.505, p=0.000). The T-score cut-off that diagnoses 30% of the post-menopausal women (n=559, mean age 63.2+/-8.97 years) aged >or=50 years with osteoporosis was SOSor=80 years, the prevalences of osteoporosis detected using equivalent to the WHO criteria were 0.39%, 9.27%, 30.3%, 58.4% and 69.0%, respectively. The prevalences detected following the manufacturer's diagnostic criteria (cut-off value: SOS

Effects of projective bone area size of the spine on bone density and the diagnosis of osteoporosis in healthy pre-menopausal women in China.

The aim of this study was to understand the effects of projective bone area (BA) size of the spine on bone density and the diagnosis of osteoporosis. Measurements of BA, bone mineral content (BMC), areal bone density (aBMD) and volumetric bone density (vBMD) at the posteroanterior (PA) lumbar spine (vertebrae L2-L4) followed by a paired PA/lateral spine (L2-L4) were made using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 1436 healthy pre-menopausal women aged from 20 to 56-years-old. At the PA and lateral lumbar spine, there was a significant positive correlation between BA and BMC (r=0.762 and 0.762, p=0.000) and aBMD (r=0.370 and 0.352, p=0.000), but not vBMD (r=0.000 and 0.102, p=0.813 and 0.063). When BA at the PA spine changed by one standard deviation (SD), BMC and aBMD correspondingly changed by 12.6% and 4.3% on the basis of their respective means while vBMD indicated no change. When a variation of 1 SD was observed in BA at the lateral spine, BMC, aBMD and vBMD correspondingly changed by 13.8%, 4.4% and 1.73% on the basis of their respective means. Through an intercomparison among large, intermediate and small BA groups, significant differences were found in the means of subject's height, weight, BMC and aBMD at the PA and lateral spine as well as the detection rate of osteoporosis by aBMD (p=0.000). Detection rates of osteoporosis by aBMD at the PA, lateral spine and vBMD in healthy pre-menopausal women aged from 40 years to 56 years were 4.5%, 16.4% and 9.7%, respectively, in the small BA group; 1.3%, 6.4% and 7.3%, respectively, in the intermediate BA group; and 0, 0 and 5.5%, respectively, in the large BA group. No significant differences were found in the detection rates of osteoporosis by vBMD among the groups. The results of multiple linear regression revealed that the major factors influencing BA of the lumbar spine was height. In healthy pre-menopausal women of the same race and age, the BA size of the lumbar spine would have significant influence upon aBMD and the diagnosis of osteoporosis, i.e. the larger the BA, the greater the aBMD and the lower the osteoporosis detection rate while conversely, the smaller the BA, the smaller the aBMD and the higher the osteoporosis detection rate. Though vBMD does not change with BA sizes of the lumbar spine, it is a sensitive marker for diagnosing osteoporosis.

[The diagnosis and management of adrenal "incidentaloma"].

We reported seven patients with adrenal "incidentaloma", diagnosed with ultrasonography and/or computed tomography and confirmed by operation and pathological examination. Three of them were pathologically diagnosed as pheochromocytoma and one each as mixed cell adenoma, bilateral adrenocortical adenoma, leiomyoma and adrenocortical carcinoma. Only one "incidentaloma" had cortisol-secreting function. The diagnosis and management of adrenal "incidentaloma" were discussed.

PIKE mediates EGFR proliferative signaling in squamous cell carcinoma cells.

One of the key drivers for squamous cell carcinoma (SCC) proliferation is activation of the epidermal growth factor receptor (EGFR), a known proto-oncogene. However, the mechanism of EGFR-dependent SCC proliferation remains unclear. Our previous studies indicate that epidermal growth factor (EGF)-induced SCC cell proliferation requires the SH3 domain of phospholipase C-γ1 (PLC-γ1), but not its catalytic activity. The SH3 domain of PLC-γ1 is known to activate the short form of nuclear phosphatidylinositol 3-kinase enhancer (PIKE) that enhances the activity of nuclear class Ia phosphatidylinositol 3-kinase (PI3K) required for proliferation. However, PIKE has been described for more than a decade to be present exclusively in neuronal cells. In the present study, we found that PIKE was highly expressed in malignant human keratinocytes (SCC4 and SCC12B2) but had low expression in normal human keratinocytes. Immunohistochemical analysis showed strong nuclear staining of PIKE in human epidermal and tongue SCC specimens but little staining in the adjacent non-cancerous epithelium. Treatment of SCC4 cells with EGF-induced translocation of PLC-γ1 to the nucleus and binding of PLC-γ1 to the nuclear PIKE. Knockdown of PLC-γ1 or PIKE blocked EGF-induced activation of class Ia PI3K and protein kinase C-ζ and phosphorylation of nucleolin in the nucleus as well as EGF-induced SCC cell proliferation. However, inhibition of the catalytic activity of PLC-γ1 had little effect. These data suggest that PIKE has a critical role in EGF-induced SCC cell proliferation and may function as a proto-oncogene in SCC.

Effects of the sample size of reference population on determining BMD reference curve and peak BMD and diagnosing osteoporosis.

UNLABELLED: Establishing reference databases generally requires a large sample size to achieve reliable results. Our study revealed that the varying sample size from hundreds to thousands of individuals has no decisive effect on the bone mineral density (BMD) reference curve, peak BMD, and diagnosing osteoporosis. It provides a reference point for determining the sample size while establishing local BMD reference databases. INTRODUCTION: This study attempts to determine a suitable sample size for establishing bone mineral density (BMD) reference databases in a local laboratory. METHODS: The total reference population consisted of 3,662 Chinese females aged 6-85 years. BMDs were measured with a dual-energy X-ray absorptiometry densitometer. The subjects were randomly divided into four different sample groups, that is, total number (Tn) = 3,662, 1/2n = 1,831, 1/4n = 916, and 1/8n = 458. We used the best regression model to determine BMD reference curve and peak BMD. RESULTS: There was no significant difference in the full curves between the four sample groups at each skeletal site, although some discrepancy at the end of the curves was observed at the spine. Peak BMDs were very similar in the four sample groups. According to the Chinese diagnostic criteria (BMD >25% below the peak BMD as osteoporosis), no difference was observed in the osteoporosis detection rate using the reference values determined by the four different sample groups. CONCLUSIONS: Varying the sample size from hundreds to thousands has no decisive effect on establishing BMD reference curve and determining peak BMD. It should be practical for determining the reference population while establishing local BMD databases.

Taurine promotes connective tissue growth factor (CTGF) expression in osteoblasts through the ERK signal pathway.

Taurine is found in bone tissue, but its function in skeletal tissue is not fully understood. The present study was undertaken to investigate regulation of gene expression of connective tissue growth factor (CTGF), and the roles of mitogen-activated protein kinases (MAPKs) in murine osteoblast MC3T3-E1 cells treated with taurine. Western blot analysis showed taurine stimulated CTGF protein secretion in a dose- and time-dependent manner. Taurine induced activation of extracellular signal-regulated kinase (ERK), but not p38 and c-jun N-terminal Kinase (JNK), in osteoblasts. Furthermore, pretreatment of osteoblasts with the ERK inhibitor PD98059 abolished the taurine-induced CTGF production. These data indicate that taurine induces CTGF secretion in MC3T3-E1 cells mediated by the ERK pathway, and suggest that osteoblasts are direct targets of taurine.