Terpenoids from the Chinese liverwort Odontoschisma grosseverrucosum and their antifungal virulence activity.

Eight undescribed terpenoids, namely, odongrossins A-H, together with two known terpenoids were isolated from Odontoschisma grosseverrucosum Stephani (Cephaloziaceae). Their structures were established based on NMR data, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction measurements. Odongrossin A and odongrossin G displayed moderate anti-virulence activities against CDR1-and CDR2-efflux-pump-deficient Candida albicans DSY654. Further investigation of odongrossin A revealed that it inhibited adhesion and biofilm formation on C. albicans DSY654. The results regarding the transcription levels of genes demonstrated that odongrossin A could regulate the expression of genes that are associated with the virulence of C. albicans DSY654.

Hip axis length changes in 10,554 males and females and the association with femoral neck fracture.

Hip axis length (HAL) has been proposed as an independent predictor of hip fracture risk in Caucasian females. There are, however, few data concerning its predictive risk in Chinese. The aim of this study was to investigate the changes of HAL in healthy Chinese population and the relationship between HAL and femoral neck fracture. The study population included 10,554 healthy Chinese people (8665 females, 1889 males) aged 20-97 yrs living in Shanghai. Cases were 106 patients (82 females, 24 males) aged 52 yrs old and over with femoral neck fracture. Controls were 106 age-matched healthy persons. All subjects were measured bone mineral density (BMD) at any site of proximal femur and HAL using dual-energy X-ray absorptiometry. HAL had significantly positive correlations with height and weight. After the adjustment of height and weight, HAL increased with age at 50 yrs of age and over in females, and no difference was found among the age groups in males. Males had longer HAL than females in all age groups. The peak BMD appeared in 30-44 yrs for females and 20-24 yrs for males and decreased thereafter, especially for females at 50 yrs old and over. HAL was similar in both fracture and control groups, whereas the BMD values at proximal femur were significantly lower in fracture group than in controls. There was no evidence that subjects with femoral neck fracture had longer HAL. Because of the limitations of retrospective study and relatively small fracture sample, prospective studies are required to determine the conclusions.

Estrogen receptor alpha gene polymorphisms and peak bone density in Chinese nuclear families.

PBD is an important determinant of osteoporotic fractures. Few studies were performed to search for genes underlying PBD variation in Chinese populations. We tested linkage and/or association of the estrogen receptor alpha gene polymorphism with PBD in 401 Chinese nuclear families. This study suggests the ER-alpha gene may have some minor effects on PBM variation in the Chinese population. Low peak bone density (PBD) in adulthood is an important determinant of osteoporotic fractures in the elderly. PBD variation is mainly regulated by genetic factors. Extensive molecular genetics studies have been performed to search for genes underlying PBD variation, largely in whites. Few studies were performed in Chinese populations. In this study, we simultaneously test linkage and/or association of the estrogen receptor alpha (ER-alpha) gene polymorphism with PBD in 401 Chinese nuclear families (both parents plus their female children) of 1260 subjects, with the 458 children generally between 20 and 40 years of age. All the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) at polymorphic PvuII and XbaI sites inside the ER-alpha gene. Bone mineral density was measured at the lumbar spine (L1-L4) and hip (femoral neck, trochanter, and intertrochanteric region). Raw bone mineral density values were adjusted by age, height, and weight as covariates. We detected marginally significant results for within-family association (transmission disequilibrium; p = 0.054) between the spine bone mineral density variation and the ER-alpha XbaI genotypes. For the hip bone mineral density variation, significant (p < 0.05) linkage results were generally found for the two intragenic markers. Analyses of the haplotypes defined by the two markers confer further evidence for linkage of the ER-alpha with the hip PBD variation. In conclusion, this study suggests that the ER-alpha gene may have minor effects on PBD variation in our Chinese population.

Effects of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis: a multi-center, randomized, placebo-controlled clinical trial.

BACKGROUND: Raloxifene has been approved for prevention and treatment of postmenopausal osteoporosis in Caucasian women. It also has some positive effects on serum lipids in Caucasians. The objective of this study was to determine the effect of raloxifene hydrochloride on lumbar spine and total hip bone mineral density (BMD), bone metabolism, and serum lipids in Chinese postmenopausal women with osteoporosis. METHODS: This was a multi-center, randomized, double-blind, placebo-controlled clinical trial in which 204 postmenopausal Chinese women with osteoporosis were assigned to receive raloxifene (60 mg) or placebo treatment daily for 12 months. BMD, serum bone metabolism markers, and serum lipids were measured before and after drug administration. BMD was measured by Dual-Energy X-Ray Absorptiometry (DEXA) and bone metabolism markers were analyzed by one-step enzyme-linked immunosorbent assay. Serum lipids were measured by enzymatic analysis. RESULTS: At the end of the 12-month study, lumbar spine BMD increased in both groups with a mean increase of (3.3 +/- 4.8)% in the raloxifene group and (1.0 +/- 4.9)% in the placebo group (P < 0.001). There was a mean increase in total hip BMD of (1.4 +/- 4.8)% in the raloxifene group and a mean decrease of (0.9 +/- 5.0)% in the placebo group (P < 0.001). No subject in the raloxifene group had a new vertebral fracture and 5 placebo subjects had new fractures (P > 0.05). In the raloxifene group, the median decreases in the biochemical markers of bone metabolism serum osteocalcin and C-telopeptide were 41.7% and 61.5%, respectively. These changes were statistically significant compared with those in the placebo group (10.6% and 35.6%, P < 0.001, respectively). Both total cholesterol and low-density lipoprotein cholesterol decreased significantly in the raloxifene group compared with those in the placebo group (P < 0.001, respectively) and there was no significant effect of raloxifene on high-density lipoprotein cholesterol and triglycerides compared with placebo. CONCLUSIONS: Raloxifene 60 mg/d for 12 months significantly increases lumbar spine and total hip BMD, significantly decreases bone turnover, and has favourable effects on serum lipids in Chinese postmenopausal women with osteoporosis.

[Effect of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis].

OBJECTIVE: To determine the effect of raloxifene hydrochloride (RLX) on the lumbar spine and total hip bone mineral density (BMD), bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis. METHODS: 204 Chinese postmenopausal women with osteoporosis from 3 hospitals in Beijing and Shanghai were randomly divided into 2 groups of 102 women: RLX group (RLX of the dosage of 60 mg/day was given for 12 months) and placebo group. In addition, 500 mg of elemental calcium and 200 units of vitamin D were given daily to all women. BMD, serum bone markers and lipids were measured before and after drug administration. The BMD of lumber spine and hip was measured by dual-energy X-ray absorptiometry (DEXA). Serum bone gamma-carboxyglutamic acid-containing protein (BGP) and C-teloppeptide were analyzed by one-step ELISA. Serum lipids were measured by enzymatic method. RESULTS: By the end of the 12-month study period, the lumbar spine BMD was increased by 3.3% +/- 4.8% in the RLX group and 1.0% +/- 4.9% in the placebo group (P < 0.001); the hip BMD was increased by 1.4% +/- 4.8%in the RLX group and decreased by 0.9% +/- 5.0% in the placebo group (P < 0.01). New vertebral fracture occurred in none of the subjects in the RLX group and in 5 subjects of the placebo group (P = 0.059). The serum BGP and CTX decreased by 41.7% and 61.5% respectively in the RLX group, both significantly more than those in the placebo group (10.6% and 35.6% respectively, both P < 0.001). Both the total cholesterol and low-density lipoprotein cholesterol were significantly lower in the RLX group than in the placebo group (both P < 0.001), however, there were no significant differences in high-density lipoprotein cholesterol and triglycerides between these two groups. One subject in the RLX group and 5 subjects in the placebo group discontinued the study due to adverse events. There were no differences in the number of subjects with hot flushes (3 in the RLX group and 1 in the placebo group) and the number of subjects with leg cramps (9 in the RLX group and 4 in the placebo group). No venous thromboembolic event was reported. CONCLUSION: RLX of the dosage of 60 mg/day for 12 months significantly increases the lumbar spine and total hip bone BMD, significantly decreases bone turnover and has favorable effects on serum lipids in Chinese postmenopausal women with osteoporosis.

Association of vitamin D receptor and estrogen receptor-alpha gene polymorphism with peak bone mass and bone size in Chinese women.

AIM: To investigate if vitamin D receptor (VDR) gene Apa I polymorphism and estrogen receptor-alpha (ER-alpha) gene Pvu II, Xba I polymorphisms are related to bone mineral density (BMD), bone mineral content (BMC) and bone size in premenopausal Chinese women. METHODS: The VDR Apa I genotype and ER-alpha Pvu II, Xba I genotype were determined by PCR-restriction fragment length polymorphism (RFLP) in 493 unrelated healthy women aged 20-40 years of Han nationality in Shanghai city. BMD (g/cm(2)), BMC (g), and bone areal size (BAS, cm(2) ) at lumbar spine 1-4 (L(1-4)) and proximal femur (femoral neck, trochanter and Ward's triangle) were measured by duel-energy X-ray absorptionmetry. RESULTS: All allele frequencies did not deviate from Hardy-Weinberg equilibrium. After phenotypes were adjusted for age, height, and weight, a significant association was found between VDR Apa I genotype and BMC variation at L(1-4) and Ward's triangle (P<0.05), but not in BMD or BAS at lumbar spine and proximal femur. ER-a Pvu II, Xba I genotype was not related to BMC, BMD, and BAS at all sites. CONCLUSION: The study suggested that Apa I polymorphism in VDR gene may influence on attainment and maintenance of peak bone mass in premenopausal Chinese women.