Systematic review and Meta-analysis of Gusongbao preparation in treatment of primary osteoporosis / 中国中药杂志

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.

Association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride on bone mineral density and bone turnover markers in postmenopausal women with osteoporosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of bone metabolism related genes polymorphisms with the effect of raloxifene hydrochloride(RLX) on bone mineral density (BMD) and bone turnover markers in postmenopausal women with osteoporosis.</p><p><b>METHODS</b>A total of 68 unrelated postmenopausal women with osteoporosis of Han ethnicity aged 47-74 years were randomly divided into 2 groups of 34 women: RLX group (60 mg were given daily for 12 months) and placebo group. BMD and bone turnover markers were measured at baseline, 6 and 12 months after treatment. The polymorphisms of Xba I and Pvu II sites in estrogen receptor 1 gene(ESR1), Ras I site in ESR2 gene, and start codon (Fok I) and CDX2 binding sites in vitamin D receptor gene (VDR) were analyzed.</p><p><b>RESULTS</b>A total of 58 patients completed 12 months of study period. By the end of study, the increased percentage of BMD in lumbar spine 2-4 (L2-4), total hip, and trochanter were found significantly different between RLX group and placebo group(P<0.05), and the decreased percentage of C-telopeptide and osteocalcin were significantly different between the two groups (P<0.01). The BMD of total hip and trochanter of women with FF genotypes of VDR Fok I site were decreased by 1.98%+/-4.86% and 2.26%+/-4.73% respectively in the RLX group, but those of women with Ff/ff genotypes were increased by 2.52%+/-2.75% and 2.74 %+/-2.97%, respectively(P<0.05). Moreover, the total hip BMD of women with PP/Pp genotypes of ESR1 Pvu II site was increased by 2.12%+/-2.78%, and of women with pp genotype it was decreased by 1.34%+/-3.73%(P<0.05). However, no significant association was observed of the polymorphisms of five sites with the changes of BMD and bone turnover markers in the placebo group.</p><p><b>CONCLUSION</b>The effect of RLX on BMD in postmenopausal women with osteoporosis is regulated by the polymorphisms of Fok I of VDR gene and Pvu II of ESR1 gene. The study is valuable to select this drug according to genotype of patients in clinical.</p>

Relationship between the polymorphism of start codon and CDX2 site in vitamin D receptor gene and the effect of calcium supplementation on bone mineral density of postmenopausal women / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of polymorphisms of start codon (Fok I site) and CDX2 binding site in vitamin D receptor gene (VDR) concerned with the effect of calcium supplementation on bone mineral density (BMD) and bone turnover markers of postmenopausal women.</p><p><b>METHODS</b>Two hundreds unrelated postmenopausal women of Han ethnicity in Shanghai were randomly divided into 2 groups of 100 women: high calcium group (1000 mg element calcium and 400 units of vitamin D were given daily for 12 months) and low calcium group (300 mg element calcium and 300 units of vitamin D were given daily for 12 months). BMD and bone turnover markers were measured at baseline and 12 months after calcium supplementation. VDR gene Fok I and CDX2 polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific multiplex PCR, respectively.</p><p><b>RESULTS</b>One hundred and seventy-one women completed 12-month study period. The frequency of VDR Fok I genotypes was 48.0 % for Ff, 31.0 % for FF, and 21.0 % for ff, and the frequency of CDX2 genotypes was 56.7 % for AG, 25.7% for GG, and 17.6% for AA. The frequencies distribution of Fok I and CDX2 alleles in the entire population or in two subgroups all followed the Hardy-Weinberg equilibrium. No significant difference of baseline BMD and bone turnover markers in Fok I genotypes or CDX2 genotypes was observed in the entire population or in two subgroups. Moreover, regardless of calcium supplementation given for 12 months, no significant association was found between Fok I or CDX2 polymorphisms and the endpoint values or percentage changes of any BMD and bone turnover markers in either high calcium group or low calcium group.</p><p><b>CONCLUSION</b>There is no significant relationship between VDR gene Fok I or CDX2 polymorphisms and the effect of high or low doses calcium supplementation on BMD and bone turnover markers in Shanghai postmenopausal women of Han ethnicity.</p>

Bone mineral density of the spine and femur in healthy Chinese men / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To establish bone mineral density (BMD) reference database in healthy Chinese men of Han ethnicity, and to estimate the prevalence of osteoporosis in the population.</p><p><b>METHODS</b>The BMD in the lumbar spine 1-4 (L1-4) and proximal femur was measured using dual energy X-ray absorptiometry in a total of 1 385 healthy Chinese men of Han ethnicity aged 20-89 years old in Shanghai.</p><p><b>RESULTS</b>The highly significant negative correlation between age and BMD at any sites of proximal femur was found in the studied population, wheras no correlation between age and BMD at lumbar spine was observed. The peak BMD of the lumbar spine and any sites of hip in Chinese men was defined as the mean BMD for the subjects aged 20-89 years. According to World Health Organization (WHO) criteria, the BMD cut-off values for osteoporosis of the L1-4, total hip, femoral neck, trochanter and intertrochanter in Chinese men are 0.719, 0.638, 0.575, 0.437 and 0.725 g/cm(2), respectively. Using the current Chinese reference data, the prevalence of osteoporosis at the L1-4, total hip, femoral neck, trochanter and intertrochanter is 5.4%, 3.8%, 6.3%, 1.8% and 2.8% in 1 084 men aged 50 years or older, respectively. However, using a database for US non-Hispanic white men (NHANES III), the prevalence of osteoporosis or osteopenia at any sites of the hip was significantly higher than that while using the current Chinese reference data.</p><p><b>CONCLUSION</b>The BMD reference database was established in healthy Chinese men of Han ethnicity, and will facilitate more accurate diagnosis of osteoporosis in Chinese men.</p>

CMV-hFasL transgenic mice prevent from experimental autoimmune thyroiditis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies showed that the role of Fas ligand (FasL) is not consistent in the pathogenesis of autoimmune thyroiditis. This study was designed to investigate the effects of FasL on the pathogenesis of experimental autoimmune thyroiditis (EAT) using CMV-human FasL (hFasL) transgenic mice.</p><p><b>METHODS</b>Transgenic mice ubiquitously expressing hFasL were used as an animal model of EAT by injection of porcine thyroglobulin (pTg). Expression of hFasL was detected by RT-PCR and Western blot. The activity of hFasL transgenic thyrocytes killing Jurket cells was determined. CMV-hFasL transgenic mice and wild type (WT) mice were immunized with pTg and killed 28 days later to evaluate the lymphocytic infiltration of their thyroids. The number of CD4+ and CD8+ lymphocytes from the spleen was detected using FACS. The serum interferon-gamma (IFN-gamma) concentration was measured by ELISA.</p><p><b>RESULTS</b>hFasL expression in the thyroid of CMV-hFasL transgenic mice was confirmed. After co-incubation of Jurket thymocytes with thyroid tissues of CMV-hFasL transgenic mice, the percentage of apoptotic cells in the CMV-hFasL transgenic thyroid group was significantly higher than that of the control WT thyroid group [(23.4 +/- 4.3)% vs (6.6 +/- 2.5)%, P < 0.01]. On day 28 after immunization with pTg, the infiltration index of lymphocytes in thyroids of the CMV-hFasL transgenic mice was significantly lower than that of the WT mice [(1.0 +/- 0.5) vs (2.1 +/- 0.7), P < 0.001]. Moreover, the number of CD4+ and CD8+ lymphocytes of the spleen and serum IFN-gamma concentration were significantly decreased in the CMV-hFasL transgenic mice.</p><p><b>CONCLUSIONS</b>FasL plays an important role in the pathogenesis of autoimmune thyroiditis. Transgenic mice ubiquitously expressing hFasL may strongly inhibit lymphocytic infiltration of the thyroid of EAT and ameliorate the course of this disease.</p>

Association of Xba I, Pvu II, and Bst U I polymorphisms of estrogen receptor-alpha gene with bone mass in men / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of polymorphism in estrogen receptor-alpha (ER-alpha ) gene with bone mineral density(BMD) in men.</p><p><b>METHODS</b>The ER-alpha Xba I, Pvu II and Bst UI genotypes were determined by PCR-restriction fragment length polymorphism (RFLP) in 388 unrelated healthy men who were 46-80 years old and were of Han nationalities in Shanghai city. Bone mineral densities (BMD, g/cm(2)) at lumbar spines 1-4 (L(1-4)) and at any sites of proximal femur, including femoral neck (Neck), trochanter (Troch) and Ward's triangle (Ward's) were measured by duel-energy X-ray absorptiometry.</p><p><b>RESULTS</b>The frequencies distribution of Xba I and Pvu II alleles and genotypes in this cohort all followed the Hardy-Weinberg equilibrium. No Bst UI polymorphic site in ER-alpha gene was found in total samples. All subjects were of BB genotype. No significant association was found between Xba I genotype and BMD at any skeleton sites. The significant association was found between Pvu II genotype and BMD at L(1-4) and Ward's triangle site (P< 0.05). Compared against men with PP and pp genotype, men with Pp genotype had significantly higher mean BMD at L(1-4) and Ward's triangle site (P< 0.05).</p><p><b>CONCLUSION</b>This study suggests that Bst UI polymorphism in ER-alpha gene may be absent or rare in Chinese Han population. Pvu II polymorphism possibly influences the loss of trabecular bone mass in old men.</p>

Relationship of msp AI polymorphism in cytochrome P450c 17alpha gene with bone mass and bone size in Shanghai men of Han nationality / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the relationship of Msp AI polymorphism in the promoter region of cytochrome P450c 17alpha (CYP17) gene with bone mass and bone size in Shanghai men of Han nationality.</p><p><b>METHODS</b>The CYP17 Msp AI genotype was determined by polymerase chain reaction-restriction fragment length polymorphism in 397 unrelated men (324 healthy men, 73 osteoporosis patients) aged 46-80 years of Han nationality in Shanghai. Bone mineral density (BMD), bone mineral content (BMC), and bone cross-section area (CSA) at lumber spine 1-4 and at any sites of proximal femur, including femoral neck, trochanter and Ward's triangle were measured by duel-energy X-ray absorptiometry.</p><p><b>RESULTS</b>Frequency distributions of CYP17 genotype were TC (51.1%), CC (33.8%), and TT (15.1%). The allele frequencies T and C were 40.7% and 59.3%, respectively. Allele frequencies did not deviate from Hardy-Weinberg equilibrium. The frequencies of CYP17 Msp AI genotype did not show difference between osteoporosis cases and healthy controls. In group of all population, or in subgroups of osteoporosis patients and healthy men, CYP17 Msp AI genotype was not significantly associated with BMD, BMC, and CSA at lumber spine 1-4 and at any sites of proximal femur after having been adjusted for age, weight, and height with analysis of covariance.</p><p><b>CONCLUSION</b>Msp AI polymorphism of CYP17 gene is not a genetic factor that influence the variation of bone mass and bone size in Shanghai men of Han nationality.</p>

Association of Apa I polymorphism of vitamin D receptor gene with bone mass in men / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the association of Apa I polymorphism in vitamin D receptor (VDR) gene with bone mass in men.</p><p><b>METHODS</b>The VDR Apa I genotype was determined by PCR-restriction fragment length polymorphism (RFLP) in 388 unrelated healthy men aged 46-80 years of Han nationality in Shanghai city. Bone mineral density (BMD) and bone mineral content (BMC) at lumber spine 1-4 (L1-4) and at any sites of proximal femur including to femoral neck (Neck), trochanter (Troch) and Ward's striangle (Ward's) were measured by duel-energy X-ray absorptiometry.</p><p><b>RESULTS</b>Frequencies distribution of VDR Apa I genotype were aa for 48.1%, Aa for 44.2% and AA 7.7%. The allele frequencies of Apa I polymorphism were in Hardy-Weinberg equilibrium. No significant association was found between Apa I genotype and BMD or BMC in group of all population or in subgroup of men below 60 years. In men above 60 years, the significant association was found between VDR Apa I genotype and BMD or BMC at L1-4, Neck and Ward's (P < 0.05, P < 0.01) and compared with Aa and aa genotype, AA genotype had significantly higher mean BMD and BMC at L1-4, Neck and Ward's (P < 0.05, P < 0.01). But Apa I genotype is not associated with BMD and BMC at Troch.</p><p><b>CONCLUSIONS</b>Apa I polymorphism is associated with bone mass in men above 60 years, and AA genotype has higher bone mass. Apa I polymorphism in VDR gene possibly influence loss of trabecular and cortical bone mass in old men.</p>

Association of polymorphisms of vitamin D receptor gene start codon and 3'-end region with bone mineral density in postmenopausal women / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine whether vitamin D receptor(VDR) gene start codon polymorphisms and 3'-end region polymorphisms exerted a combined influence on bone mineral density(BMD) in Han postmenopausal women in Beijing area.</p><p><b>METHODS</b>The VDR Fok I and 3'-end region genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 110 unrelated postmenopausal women. BMD was measured at the lumbar spine (L(2-4)), femoral neck(Neck), Ward's triangle(Ward's) and trochanter (Troch) using duel-energy X-ray absorptiometry.</p><p><b>RESULTS</b>The frequencies distribution of Fok I, Apa I, Bsm I and Taq I alleles in this cohort all followed the Hardy-Weinberg equilibrium. No significant association of Fok I, Apa I or Taq I genotype with BMD in postmenopausal women was found when these polymorphisms were considered independently, except for Bsm I genotype. When a combined analysis of VDR gene Fok I and 3'-end region polymorphisms was carried out, cross-genotyping Fok I and Apa I polymorphisms was significantly associated with BMD at the L(2-4) (P<0.001), and cross-genotype of Fok I and Taq I was also significantly associated with BMD at the Neck and Troch sites (P<0.05). However, cross-genotyping Fok I and Bsm I polymorphisms was not significantly associated with BMD. Cross-genotyping Apa I and Bsm I or Taq I polymorphisms was not associated with BMD in postmenopausal women, either.</p><p><b>CONCLUSION</b>Although Fok I polymorphisms of VDR gene were not significantly associated with BMD in postmenopausal women, VDR gene Fok I and 3'-region polymorphisms (Apa I and Taq I) had a combined effect on the BMD in postmenopausal women.</p>