Calcifediol (25-hydroxyvitamin D) improvement and calcium-phosphate metabolism of alendronate sodium/vitamin D3 combination in Chinese women with postmenopausal osteoporosis: a post hoc efficacy analysis and safety reappraisal.

BACKGROUND: Vitamin D (VD) insufficiency or deficiency is a frequent comorbidity in Chinese women with postmenopausal osteoporosis (PMO). The present study aimed to investigate 25-hydroxyvitamin D [25(OH) D] improvement and calcium-phosphate metabolism in Chinese PMO patients treated with 70 mg of alendronate sodium and 5600 IU of vitamin D3 (ALN/D5600). METHODS: Chinese PMO women (n = 219) were treated with 12-month ALN/D5600 (n = 111) or calcitriol (n = 108). Changes in 25(OH) D at month 12 were post hoc analyzed by the baseline 25 (OH) D status using the longitudinal analysis. The main safety outcome measures included serum calcium and phosphate and 24-h urine calcium, and the repeated measures mixed model was used to assess the frequencies of the calcium-phosphate metabolic disorders. RESULTS: Absolute change in mean serum 25(OH) D level was the greatest in VD-deficient patients and least in VD-sufficient patients at months six and 12 (both, P < 0.01). Serum calcium level remained significantly lower in the ALN/D5600 treatment group than in the calcitriol treatment group throughout the 12 months. Mean 24-h urine calcium slightly increased in the ALN/D5600 treatment group and significantly increased in the calcitriol treatment group (+ 1.1 and + 0.9 mmol/L at months six and 12; both, P < 0.05). Calcitriol treatment was associated with more frequent hypercalciuria at month six (9.4% vs. 18.5%, P = 0.05), but not at month 12 (12.3% vs. 13.0%). CONCLUSION: Baseline VD status predicted 25(OH) D improvement in PMO patients on 12-month ALN/D5600 treatment. The daily use of 0.25 µg of calcitriol was associated with more frequent hypercalciuria at month six, compared to ALN/5600 treatment, necessitating the safety re-evaluation of calcitriol at a higher dosage.

[Association of Serum Vitamin D with Hand-grip Strength and Balance Ability: a Cross-sectional Study on Community-dwelling Women in Sichuan, China].

OBJECTIVE: To determine the relationship between serum levels of 25(OH)D and 1, 25(OH)2 D and the hand-grip strength and balance ability of women in Sichuan, China. METHODS: A cross-sectional study on a representative sample of 1 095 women aged 29-95 yr. in Sichuan Province was undertaken. Their hand-grip strength and balance ability were assessed using a hand-held dynamometer and the short physical performance battery (SPPB), respectively. The participants were divided into four groups according to the level of serum 25(OH)D: sufficient (>75 nmol/L), insufficient (51-75 nmol/L), deficiency (25-50 nmol/L), and serious deficiency (<25 nmol/L). General liner models were established to compare the differences of the four groups in balance ability. Logistic regression models were established to examine the associations of serum 25(OH)D and 1, 25(OH)2 D withhand-grip strength and physical performance. RESULTS: About 70.9% of the participants had vitamin D deficiency. Those with vitamin D insufficiency or deficiency were more likely to reside in a higher latitudinal area (P<0.001), spend less time in outdoor activities (P=0.013), and take less vitamin D supplements (P<0.001). Older women (≥65 years) had lower serum 25(OH)D (P=0.001) and were more likely to have ≤50 nmol/L 25(OH)D than their younger counterparts (74.6% vs. 68.9%, P=0.046). However, no significant age differences were found in serum 1, 25(OH)2 D. Serum levels of 25(OH)D and 1, 25(OH)2 D were not found to be associated with hand-grip strength and balance ability after adjusting for confounding factors. Hand-grip strength and balance ability decreased with age (OR=1.066, P<0.001; OR=1.111, P<0.001). Higher body mas was associated with higher hand-grip strength (OR=0.958, P<0.001). Higher serum albumin (OR=0.896, P=0.001) and longer walking time (OR=0.799, P=0.001) were associated with higher balance ability. CONCLUSION: Serum levels of 25(OH)D and 1, 25(OH)2D are not associated with hand-grip strength and balance ability.

The efficacy and safety of weekly 35-mg risedronate dosing regimen for Chinese postmenopausal women with osteoporosis or osteopenia: 1-year data.

AIM: Oral risedronate is effective in the treatment of postmenopausal osteoporosis when administered daily, weekly, or monthly. In this 1-year, randomized, double-blind, multicenter study we compared the weekly 35-mg and daily 5-mg risedronate dosing regimens in the treatment of Chinese postmenopausal women with osteoporosis or osteopenia. METHODS: Postmenopausal women with primary osteoporosis or osteopenia were randomly assigned to the weekly group or daily group (n=145 for each) that received oral risedronate 35 mg once a week or 5 mg daily, respectively, for 1 year. The subjects' bone mineral densities (BMDs), bone turnover markers (P1NP and ß-CTX), new vertebral fractures, and adverse events were assessed at baseline and during the treatments. RESULTS: All subjects in the weekly group and 144 subjects in the daily group completed the study. The primary efficacy endpoint after 1 year, ie the mean percent changes in the lumbar spine BMD (95% CI) were 4.87% (3.92% to 5.81%) for the weekly group and 4.35% (3.31% to 5.39%) for the daily group. The incidences of clinical adverse events were 48.3% in the weekly group and 54.2% in the daily group. CONCLUSION: The weekly 35-mg and daily 5-mg risedronate dosing regimens during 1 year of follow-up show similar efficacy in improving BMDs and biochemical markers of bone turnover in Chinese postmenopausal women with osteoporosis or osteopenia. Moreover, the two dosing regimens exhibit similar safety and tolerability.

[Optimal cut-off value of phalangeal radiographic absorptiometry to identify osteoporosis in postmenopausal women].

OBJECTIVE: To study the optimal cut-off value of phalangeal radiographic absorptiometry (RA) to identify osteoporosis in postmenopausal women. METHODS: A total of 650 postmenopausal women were recruited in this study. Bone mineral density (BMD) at lumbar spine and left proximal femur neck was measured by dual-energy X-ray absorptiometry (DXA) as the standard method to identify postmenopausal osteoprosis. Phalangeal bone density was estimated by the use of RA. Optimal cut-off value of phalangeal RA was determined using a ROC curve for screening the ostreoporosis cases. RESULTS: When the cut-off value of phalangeal RA was T score < or = -2.5, the sensitivity was 74.2%, the specificity was 72.9%. When the cut-off value was T score < or = -2.21, the sensitivity was 81.4%, the specificity was 62.0%. CONCLUSION: The cut-off value of phalangeal RA as T score -2.21. which has higher sensitivity could be optimal to identify postmenopausal osteoporosis.

[Risk factors of acute-phase response following the first-dose administration of zoledronic acid in the treatment of osteoporosis].

OBJECTIVE: To explore the risk factors of acute-phase response (APR) following the first-dose administration of zoledronic acid in the treatment of osteoporosis. METHODS: We reviewed the clinical data of the patients receiving the first use of zoledronic acid 5 mg treatment of osteoporosis from January 2009 to November 2012, and divided the patients into acute phase response group (APR+) and no response group (APR-). The age, body mass index (BMI), concomitant medications, comorbidities, laboratory parameters between the two groups were compared and analyzed. RESULTS: A total of 178 patients were eligible for inclusion in the study, of which 108 patients experienced APR. In APR group, there were 80 (44. 9%) patients developed fever, 14 (9. 6%) chills, 48 (27.0%) musculoskeletal pain, 19 (10.7%) gastrointestinal symptoms, 10 (5.6%) headache and dizziness, 7 (3.9%) palpitation,and 3 (1.7%) rash. APR was more common in the patients with higher baseline tartrate-resistant acid phosphatase 5b (TRACP-5b) and new-onset vertebral compression fractures (new-onset VCF). Stepwise logistic regression showed that the odds ratio (OR) of APR in higher baseline TRACP-5b and new VCF was 3. 3 and 2. 5 respectively. CONCLUSION: The first use of zoledronic acid in the treatment of osteoporosis appears high incidence of APR. High TRACP-5b levels and new vertebral fracture are risk factors for APR.

Epidemiological characteristics of hepatic echinococcosis, concurrent cerebral echinococcosis, and pulmonary echinococcosis in Ganzi County, Sichuan Province, China.

Human echinococcosis has become a major public health problem in most parts of the world. The objective of this article was to study the demographics of patients with hepatic echinococcosis in Ganzi County to elucidate the main risk factors, as well as to report the concurrent prevalence of cerebral echinococcosis and pulmonary echinococcosis.We recruited 195 patients with hepatic echinococcosis from the Datongma area of Ganzi County from January 2018 to November 2018. The patients' demographics, living environments, supported medical resources, knowledge of echinococcosis prevention and control, and hygienic practices were investigated and analyzed. The prevalence of cerebral echinococcosis and pulmonary echinococcosis were also investigated.The data were analyzed to identify risk factors for human echinococcosis. Our analysis showed that the herding Tibetan population within the 20 to 60 age group, and females, in particular, were at the highest risk of human echinococcosis infection. Having stray dogs around habitations and intimate activities with dogs and livestock were also behavioral risk factors. People with poor health literacy and low educational qualifications had possible risks of infection. In terms of hygiene, not using tap water as the drinking water source and lack of medical staff were significantly correlated with echinococcosis prevalence. Four patients were diagnosed with cerebral echinococcosis. Among them, 1 patient had both cerebral echinococcosis and pulmonary echinococcosis.Possible high-risk factors for echinococcosis were being female, herding population, in the 20 to 60 age group, having stray dogs around habitations, having activities with dogs and livestock, having poor health literacy, having low educational qualifications, and not using tap water as a drinking water source. The detection rate for brain echinococcosis in patients with hepatic echinococcosis was high (2.05%). Effective preventive strategies should be implemented in epidemic areas. Head CT scans should be applied for early detection of cerebral echinococcosis to carry out the treatment.

[The influence of different glucose concentrations on cellular activity of human osteosarcoma cell line MG63].

OBJECTIVE: In this research, we took an insight into the influence of different glucose concentrations on human osteosarcoma cell line MG63, hoping to give an explanation to the mechanism of the osteoporosis (OP) caused by diabetes mellitus (DM). METHODS: Four culture media of different glucose concentrations, 5.5 mmol/L, 10 mmol/L, 20 mmol/L, 40 mmol/L, were set up for this study. Human osteosarcoma cell line MG63 was cultured in these media successively for 21 d, and then the proliferation rate of cells, secretion of ALP and BGP, percentage of apoptosis cells and the formation of calcified nods were observed and measured. RESULTS: The elevated glucose concentration prompted the proliferation of MG63 cells, but the activities of MG63 cells were not correspondent with the cell number. On the contrary, the secretion of ALP, BGP and the mineralization of the MG63 cells were decreased. The apoptosis of the cells was promoted. CONCLUSION: From our study, we confirmed the toxicity of hyperglycemia to MG63 cells. It suggested that the tight control of the serum glucose can be a good method to prevent the occurrence of osteoporosis.

Clinical characteristics associated with bone mineral density improvement after 1-year alendronate/vitamin d3 or calcitriol treatment: Exploratory results from a phase 3, randomized, controlled trial on postmenopausal osteoporotic women in China.

Baseline and on-treatment characteristics, including age, obesity, calcium intake, and bone turnover markers, may predict the bone mineral density (BMD) response in women with postmenopausal osteoporosis (PMO) to 1 to 2 years of antiresorptive therapy and/or vitamin D supplementation. This study aimed to explore clinical characteristics associated with 12-month BMD improvement in Chinese women with postmenopausal osteoporosis (PMO).In this post hoc analysis of a previous phase 3 multicenter, randomized controlled trial, Chinese PMO women who were treated with once weekly alendronate 70 mg/vitamin D3 5600 IU (ALN/D5600) or once daily calcitriol 0.25 mcg, and had measurements of 1-year lumbar spine BMD (LS-BMD) and on-treatment bone turnover markers (BTMs) were included in the analysis.In Chinese PMO patients on ALN/D5600, 1-year LS-BMD change was negatively correlated with age (ß = -0.00084, P < .01), dietary calcium (ß = -0.0017, P = .07), and procollagen type 1 N-terminal propeptide (P1NP) change at month 6 (ß = -0.000469, P = .0016), but positively with body mass index (BMI) (ß = 0.00128, P = .08); baseline P1NP above the median was associated with a significantly greater BMD percentage change at the lumbar spine (P = .02) and the total hip (P = .0001). In the calcitriol group, a significant 1-year LS-BMD increase was associated with BMI (ß = 0.0023, P = .02), baseline P1NP (ß = 0.00035, P = .0067), history of prior vertebral fracture(s) (ß = 0.034, P < .0001) and baseline serum 25(OH)D level (ß = -0.00083, P = .02).The presented findings from Chinese postmenopausal osteoporotic women suggested clinically meaningful baseline and on-treatment characteristics predicting BMD improvement after 1 year of ALN/D5600 treatment, which differed from calcitriol treatment with baseline identifiable associations. The study remained exploratory and further accumulation of evidence is needed.

SOST polymorphisms and response to alendronate treatment in postmenopausal Chinese women with osteoporosis.

AIM: To investigate the association between SOST gene polymorphisms and response to alendronate treatment. MATERIALS & METHODS: 639 Chinese postmenopausal women with osteoporosis or osteopenia received alendronate treatment. Polymorphisms of SOST were analyzed. Bone mineral density (BMD), serum ALP and ß-CTX levels were measured. The correlation of SOST polymorphisms with changes of BMD and bone biomarkers after treatment was analyzed. RESULTS: rs1234612 and rs851054 polymorphisms were correlated to baseline lumbar spine BMD (p < 0.05). After 12 months of treatment rs1234612 and rs865429 polymorphisms were correlated to BMD changes at the lumbar spine (p < 0.05) or femoral neck (p < 0.05), respectively. CONCLUSION: The polymorphisms of SOST are genetic factors affecting bone health and response to alendronate in Chinese postmenopausal women.

LRP5 polymorphisms and response to alendronate treatment in Chinese postmenopausal women with osteoporosis.

AIM: To investigate the association between LRP5 gene polymorphisms and response to alendronate in Chinese osteoporotic women. MATERIALS & METHODS: Six hundred and thirty nine Chinese postmenopausal women with osteopenia or osteoporosis were included and received alendronate treatment. The A1330V polymorphism of LRP5 was investigated. Bone mineral density (BMD) and bone turnover markers (ALP and ß-isomerized carboxy-telopeptide of type I collagen [ß-CTX]) were measured before and after treatment. The correlation of LRP5 polymorphisms with changes in BMD and bone turnover biomarkers were analyzed after treatment. RESULTS: After 12 months of treatment, participants with CC and CT genotypes had a larger increase in lumbar spine BMD and a larger decrease in serum ß-CTX and ALP levels than those with TT genotype (all p < 0.001). No significant genotype-treatment interaction was found in hip BMD. CONCLUSION: The A1330V polymorphism of LRP5 is possibly correlated with response to alendronate treatment in Chinese women with osteoporosis, and the TT genotype could possibly predict a weak response to alendronate.

Effect of low-dose alendronate treatment on bone mineral density and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis.

OBJECTIVE: The aim of this study was to evaluate the effect of low-dose alendronate (ALN) treatment on bone mineral density (BMD) and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis. METHODS: This study was a large-sample, randomized, open-label, prospective, multicenter, clinical trial with a 12-month follow-up. A total of 639 postmenopausal women (aged 62.2 ± 7.0 y) with osteopenia or osteoporosis were randomized into two groups: low-dose ALN (70 mg every two weeks) and standard-dose ALN (70 mg weekly). All patients were also supplemented with calcium (600 mg) and vitamin D3 (125 IU) daily. BMD (measured by dual-energy x-ray absorptiometry; Hologic and Lunar) and levels of serum bone turnover markers (bone resorption marker, carboxy-telopeptide of type I collagen; bone formation marker, alkaline phosphatase) were assessed at baseline and at 3, 6, and 12 months of treatment. BMD and bone turnover markers were compared between the baseline and the end of treatment, and the changes in BMD and bone turnover markers were also compared between the low-dose ALN group and the standard-dose ALN group. RESULTS: No significant differences in age, years since menopause, body mass index, BMD, 25-hydroxy vitamin D level, and serum biochemical markers were found at baseline between the two dose groups. A total of 558 (87.3%) and 540 (84.5%) women completed the treatment at the 6th and 12th months, respectively. After the 12-month treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly in both of the treatment groups (P < 0.01), and no differences in percentage changes in BMD at the lumbar spine, femoral neck, and hip were found between the low-dose group (5.60%, 3.87%, and 3.28%, respectively) and the standard-dose group (5.07%, 2.93%, and 3.80%, respectively; P > 0.05). However, levels of serum alkaline phosphatase and carboxy-telopeptide of type I collagen in the standard-dose group decreased moderately compared with those in the low-dose group (P < 0.05 and P < 0.01). The women tolerated the two doses of ALN quite well. Adverse effects were similar in the two groups. CONCLUSIONS: Treatment with low-dose ALN (70 mg every two weeks) in women with postmenopausal osteopenia or osteoporosis effectively increases lumbar spine and hip BMD, similar to treatment with standard-dose ALN. Low-dose ALN may be a cost-effective and safe protocol for treating osteopenia or osteoporosis in Chinese women.

Systematic review of soy isoflavone supplements on osteoporosis in women.

OBJECTIVE: To clarify the effect of soy isoflavones on prevention of osteoporosis, and the effective dosage of soy isoflavones and its duration. METHODS: Random control trials that investigated the association of soy isoflavones and osteoporosis were included in the meta-analysis by researching MEDLINE, EMBASE and the Chinese Biomedical Database up to October 2011. The Rev Man software was used for all of the statistical analysis. RESULTS: The present meta-analysis found that soy isoflavones significantly increased the bone mineral density by 54% and decreased the bone resorption marker urinary deoxypyridinoline (DPD) by 23% compared to baseline in women. Using random effects model, the effect of isoflavones on bone mineral density (BMD) regarding menopausal status and isoflavone dose revealed higher weighted mean difference changes were found in postmenopausal women and isoflavone dose above 75 mg/d. Subgroup analysis of trials with menopausal status, supplement type, isoflavone dose and intervention duration that used soy isoflavone extracts resulted in significant different overall effect of DPD using by random effects model. Sensitivity analysis indicated that the effect of soy isoflavones on BMD and DPD was robust. CONCLUSIONS: The present meta-analysis reveals that soy isoflavone supplements significantly increase bone mineral density and decrease the bone resorption marker urinary DPD. It shows no significant effect on bone formation markers serum bone alkaline phosphatase. The significant effect of soy isoflavones on BMD and urinary DPD is relative to menopausal status, supplement type, isoflavone dose and intervention duration.

Efficacy of intravenous zoledronic acid in the prevention and treatment of osteoporosis: a meta-analysis.

OBJECTIVE: To compare the effect of zoledronic acid in treatment and prevention of osteoporosis with placebo. METHODS: Random control trials regarding zoledronic acid in treatment of osteoporosis were retrieved by selecting Medline, EMbase and Pubmed databases till April 2012. The RevMan software was used for all of the statistical analysis. RESULTS: A total of 9 trials were included in this meta-analysis. The pooled effect showed that zoledronic acid could increase the bone mineral density by 2.98 times compared with placebo, and reduce the rate of fracture in patients by 32%. The results should the zoledronic acid intervention had significantly less serious adverse events than controls, and the odds ratio was 0.81 (0.76-0.87). The longer term intervention, more than 12 months intervention, could gain a better prevention effect for osteoporosis (OR, 95%CI for BMD was 3.35, 2.77-3.92; for fracture was 0.67, 0.54-0.82). CONCLUSIONS: This present study shows that zoledronic acid could be effective approach in the prevention of osteoporosis, and could increase the bone mineral density and reduce the risk of fracture.