Renal safety of zoledronic acid in patients with osteoporosis: a retrospective study.

INTRODUCTION: This study aimed to investigate the renal safety of Zoledronic Acid (ZOL) in patients with osteoporosis (OP). METHODS: A total of 1379 patients (baseline estimated glomerular filtration rate, eGFR ≥ 60 mL/min/1.73 m2) with primary OP who received ZOL from January 2008 to October 2020 at our hospital were retrospectively analyzed. Baseline and the changes in renal function within 1 year following infusions were collected, the incidence of renal impairment (eGFR < 60 mL/min/1.73 m2 or a > 25% reduction in the eGFR from baseline) was noted and the risk factors were analyzed. Furthermore, the changes in renal function between a 3-year consecutive infusion and a single infusion of ZOL were compared. RESULTS: Renal impairment occurred in 8.05% of patients, who with a significantly higher age, Charlson Comorbidity Index (CCI), smoking history, combination of hypertension or diabetes mellitus and worse renal function indicators (all P < 0.05). Binary logistic regression analysis showed that higher CCI (≥5) or smoking history or the baseline eGFR <90 mL/min/1.73 m2 were the risk factors for renal impairment (all P < 0.05). Patients of 3-year continuous infusion group had a significantly greater drop in the eGFR levels than the single infusion group after 1 year of infusion(s) (P < 0.05). CONCLUSION: Attention should be given to possible potential renal impairment following ZOL infusion in clinical practice for the management of OP, particularly in patients with higher CCI (≥5) or smoking history or the baseline eGFR <90 mL/min/1.73 m2. Continuous infusion of ZOL exerts a significant impact on renal function when compared to single infusion and intensive monitoring of renal function is necessary.

Astragaloside IV protects against oxidized low-density lipoprotein-induced injury in human umbilical vein endothelial cells via the histone deacetylase 9 (HDAC9)/NF-κB axis.

BACKGROUND: Atherosclerosis is a main cause of multiple cardiovascular diseases, and cell damage of human umbilical vein endothelial cells (HUVECs) was reported to participate in the development of atherosclerosis. In this study, we aimed to study the action of Astragaloside IV (ASV) on AS development using in vitro AS cell model. METHODS: MTT assay, EdU staining assay, and flow cytometry were utilized for detection of cell proliferation and apoptosis, respectively. The protein expression of histone deacetylase 9 (HDAC9), Bax, Bcl-2, p-P65, P65, p-IκBα, and IκBα was gaged using western blot. The angiogenesis was evaluated by tube formation assay. The inflammatory response was evaluated by ELISA kits. SOD activity and MDA level were detected using the matched commercial kits. RT-qPCR was used for HDAC9 mRNA expression measurement. RESULTS: Oxidized low-density lipoprotein (ox-LDL) significantly repressed cell proliferation, angiogenesis, and enhanced apoptosis, inflammation, and oxidative stress in HUVECs. ASV addition could alleviate ox-LDL-caused cell damage in HUVECs. Moreover, HDAC9 was overexpressed in AS patients and AS cell model. Functionally, HDAC9 knockdown also exhibited the protective role in ox-LDL-treated HUVECs. In addition, ASV treatment protected against ox-LDL-induced damage in HUVECs via targeting HDAC9. ASV could inactivate the NF-κB pathway via regulating HDAC9 in AS cell model. CONCLUSION: ASV exerted the protective effects on ox-LDL-induced damage in HUVECs through the HDAC9/NF-κB axis.

Curcumin ameliorates oxidized low-density lipoprotein (ox-LDL)-caused damage in human umbilical vein endothelial cells (HUVECs) through the miR-599/MYD88/NF-κB axis.

BACKGROUND: The role of curcumin in multiple human diseases was widely reported, including arteriosclerosis (AS). We aimed to investigate the correlation between curcumin and AS-related microRNAs (miRNAs) to find out more underlying mechanism of curcumin used in AS. METHODS: Cell proliferation and apoptosis were determined using CCK-8 assay, EdU staining assay, flow cytometry, and western blot for the detection of PCNA and Bax protein expression in human umbilical vein endothelial cells (HUVECs). Inflammation response was evaluated using ELISA kits, and oxidative stress was evaluated by detecting SOD activity and MDA level using the matched commercial kits. RT-qPCR analysis was applied for miR-599 and MYD88 mRNA level measurement. RESULTS: Curcumin treatment and miR-599 overexpression could promote cell proliferation, and inhibit cell apoptosis, inflammation response and oxidative stress, thereby alleviating ox-LDL-induced cell damage in HUVECs. Mir-599 was lowly expressed and MYD88 was highly expressed in AS patients and AS cell model. Curcumin could modulate miR-599 to exert the protective effect on ox-LDL-caused cell damage, and miR-599 directly targeted MYD88 to alleviate ox-LDL-caused cell damage in HUVECs. Curcumin targeted miR-599 to regulate MYD88 expression, thereby inactivating the NF-κB pathway in AS cell model. CONCLUSION: Our findings illustrated that curcumin exhibited anti-AS effect through the miR-599/MYD88 axis and thereby inhibiting the NF-κB pathway.

Poor Status of Vitamin D: A Survey of Area With Lowest Sunlight Radiation in Sichuan, China.

Objective: Vitamin D plays an important role in bone and mineral metabolism. Ultraviolet B (UVB) is the primary determinant for vitamin D synthesis. However, population-based data of vitamin D status was sparse in areas with sunlight deprivation in China. This study aimed to assess serum 25-hydroxyvitamin D [25(OH)D] levels among adult women in Sichuan basin with the lowest sunlight radiation in China, and the associations with sunlight exposure and age. Methods: In the context of the same ethnicity, similar latitude and lifestyle in sunlight-limited basin and sunlight-abundant plateau, 1,057 women in basin and 337 in plateau aged 29-95 years were included in this study, from November 2012 to February 2013. Daily sunlight exposure duration of previous month was obtained using questionnaires. Serum 25(OH)D was measured by enzyme-linked immunosorbent assay. Results: The prevalence of vitamin D severe deficiency [25(OH)D <30 nmol/L] and deficiency [30 ≤ 25(OH)D <50 nmol/L] was significantly higher in basin than plateau (21.85% vs. 10.09%, and 59.32% vs. 40.36%; P<0.0001). Women from basin exhibited lower serum 25(OH)D levels than those from plateau (40.66 ± 15.62 vs. 52.54 ± 19.94 nmol/L, P<0.0001). In basin, women more than 50 years old had higher 25(OH)D than younger counterparts, and 25(OH)D level of these groups was not associated with sunlight exposure duration. While in plateau, women younger than 60 years old had higher 25(OH)D than the older women. Furthermore, for those younger groups, women with long sunlight exposure (≥3 h daily) had higher 25(OH)D concentration than those with short sunlight exposure (<3 h daily). Serum PTH was negatively associated with 25(OH)D in basin, but not in plateau. Conclusions: Alarmingly high prevalence of vitamin D deficiency was observed in women in sunlight-deprived basin in Sichuan. Only the vitamin D status of younger women from plateau with adequate solar radiation could benefit from sunlight exposure. Vitamin D supplementation and vitamin D-fortified food should be encouraged to improve vitamin D status for women living in sunlight-limited areas, or with old age.

Association Between Bone Mineral Density and Lipid Profile in Chinese Women.

PURPOSE: Atherosclerotic cardiovascular disease may share the risk factors for low bone mineral density (BMD), one of which is dyslipidemia. The association between serum cholesterol and BMD remains controversial. Thus, the correlation between serum lipids and BMD in women was explored in the current study. MATERIALS AND METHODS: This cross-sectional study included 1116 Chinese female participants. Serum samples were collected to evaluate total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and other laboratory markers. Dual-energy X-ray absorptiometry was used to assess lumbar spine, femoral neck, and total hip BMD. RESULTS: In the postmenopausal women, a non-linear relationship was detected between TC, LDL-C, HDL-C, and lumbar spine BMD. Using segmented linear regression, the inflection points were 5.86 mmol/L, 3.52 mmol/L, and 2.37 mmol/L, respectively. To the left of the inflection point, the higher the serum lipid level, the lower the value for lumbar spine BMD. To the right of the inflection point, the higher the serum level of TC and LDL-C, the higher the value for lumbar spine BMD. In the premenopausal women, the association between HDL-C and femoral neck BMD was non-linear. In addition, LDL-C had a positive association with BMD of the femoral neck and HDL-C had an inverse association with BMD of the femoral neck in postmenopausal women. CONCLUSION: In postmenopausal women, the relationship between TC, LDL-C, HDL-C, and lumbar spine BMD was non-linear. TC, LDL-C, and HDL-C were negatively associated with lumbar spine BMD when the values were less than 5.86 mmol/L, 3.52 mmol/L, and 2.37 mmol/L, respectively. The mechanisms of the association were unclear, and further research is warranted to clarify the relationship.

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.

New parathyroid function index for the differentiation of primary and secondary hyperparathyroidism: a case-control study.

BACKGROUND: Patients with primary hyperparathyroidism (PHPT) may be asymptomatic, and some may present with normocalcemic PHPT (NPHPT). Patients with vitamin D deficiency may also be asymptomatic, with normal calcium and elevated PTH concentrations. These latter patients are usually diagnosed with vitamin D deficiency-induced secondary hyperparathyroidism (VD-SHPT). Therefore, it is very difficult to distinguish PHPT and NPHPT from VD-SHPT based on calcium or PTH concentrations in clinical settings. In this case-control study, we aimed to verify the diagnostic power of a new parathyroid function index (PFindex = Ca*PTH/P). METHODS: This study enrolled 128 patients with surgically and pathologically confirmed PHPT, including 36 with NPHPT, at a hospital in West China between January 2009 and September 2017. Thirty-seven patients with VD-SHPT and 45 healthy controls were selected from the population of a cross-sectional epidemiological study as the SHPT and healthy groups, respectively. We used the PFindex to describe the characteristics of PHPT, NPHPT, and VD-SHPT.. Differences between the four groups were compared, and a receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic power of PFindex. RESULTS: The PHPT group had the highest PFindex (454 ± 430), compared to the other three groups (NPHPT: 101 ± 111; SHPT: 21.7 ± 6.38; healthy: 12.2 ± 2.98, all p < 0.001). A PFindex cut-off value of 34 yielded sensitivity and specificity rates of 96.9 and 97.6% and of 94.4 and 94.6% for the diagnoses of PHPT and NPHPT, respectively. The use of a PFindex > 34 to differentiate NPHPT from VD-SHPT yielded the highest positive likelihood ratio and lowest negative likelihood ratio. CONCLUSION: The PFindex provided excellent diagnostic power for the differentiation of NPHPT from VD-SHPT. This simple tool may be useful for guiding timely decision-making processes regarding the initiation of vitamin D treatment or surgery for PHPT.

Sinonasal hemangiopericytoma caused hypophosphatemic osteomalacia: A case report.

RATIONALE: Tumor-induced osteomalacia (TIO) is a rare, paraneoplastic syndrome featured with fibroblast growth factor 23 (FGF23) secretion primarily by benign mesenchymal tumors and sometimes by malignancies. TIO diagnosis and treatment is often delayed because TIO usually has nonspecific generalized bone pain and weakness, and location of TIO tumor is quite challenging. Very few TIO caused by sinonasal hemangiopericytoma have been reported in the literature. PATIENT CONCERNS: A 40-year-old Chinese woman presented with diffuse bone pain for more than 1 year. Laboratory examination showed hypophosphatemia, hyperphosphaturia, hypocalcemia, an elevated serum alkaline phosphatase (ALP) level and bone-specific ALP level. Imaging studies revealed low bone mineral density (BMD) and multiple pseudofractures at the ribs. F-18 fluorodeoxyglucose positron emission tomography was negative in searching for tumors. Because no tumor was located, the patient was treated with oral phosphate, calcium, and alfacalcidol, and achieved great relief in her symptoms and improvement in BMD. Six years later, the patient had breast cancer surgery and received chemotherapy, and still had hypophosphatemia. During this time, nasopharyngo-fiberscope showed nasal mass in her left nasal cavity. Then she had her nasal polyps removed and surprisingly the serum phosphate became normal. DIAGNOSES AND INTERVENTIONS: The patient had the nasal mass resected, and pathological diagnosis of the nasal mass was sinonasal hemangiopericytoma. Immunohistochemical analysis was positive for FGF23. Thus the final diagnosis was osteomalacia induced by sinonasal hemangiopericytoma. Phosphate supplementation and alfacalcidol were discontinued. OUTCOMES: The patient had normal serum phosphate after 6-month follow-up. LESSONS: By presenting this case, we hope to remind clinicians that in patients with osteomalacia with undetermined reason and intranasal polypoid mass, sinonasal hemangiopericytoma should be suspected.

[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.

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.

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.

The effect and safety of anacetrapib in the treatment of dyslipidemia: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease (CVD) is the major cause of morbidity and mortality worldwide. Anacetrapib may be a new treatment option that has a cardiovascular benefit for the management of dyslipidemia. OBJECTIVE: The aim of our current study was to perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) assessing the effect and safety of anacetrapib in the treatment of dyslipidemia. METHODS: We systematically searched PubMed, Embase, and Cochrane Library database from their inception to 5 October 2017, with the terms: 'anacetrapib' and 'placebo'. From 287 initial citations, 10 studies including 34781 patients with dyslipidemia were included in the final systematic review and meta-analysis. RESULTS: Pooled results showed that anacetrapib significantly increased high density lipoprotein cholesterol (HDL-C) [weighted mean differences (WMD) 53.07, 95% confidence interval (95% CI) 46.79 to 59.36] and apolipoprotein AI (ApoAI) (WMD 53.44, 95% CI 45.72 to 61.16). Our study also showed that anacetrapib significantly reduced low density lipoprotein cholesterol (LDL-C) (WMD -32.99; 95% CI -37.13 to -28.86), Non-HDL-C (WMD -39.19; 95% CI -52.22 to -26.16), triglycerides (TG) (WMD -9.97; 95% CI -10.54 to -9.41), apolipoprotein B (ApoB) (WMD -22.55; 95% CI -28.56 to -16.54) and lipoprotein a [LP(a)] (WMD -13.35; 95% CI -18.31 to -8.39). Our results demonstrated that there was no significant difference in all the following adverse events between the anacetrapib group and placebo group: [hepato-toxicity (OR 0.90, 95% CI: 0.75 to 1.07); musculoskeletal injury (OR 1.01, 95% CI: 0.88 to 1.15); drug-related adverse event (OR 1.00, 95% CI: 0.96 to 1.05); drug-related withdrawn (OR 1.01, 95% CI: 0.95 to 1.08)]. CONCLUSIONS: Although further studies are needed, our findings clearly offer support to the use of anacetrapib in the clinical management of patients with dyslipidemia.

Response to teriparatide in Chinese patients with established osteoporosis: osteocalcin and lumbar spine bone-mineral density changes from teriparatide Phase III study.

Teriparatide is the first anabolic agent for osteoporosis, and this analysis aimed to understand responses to teriparatide in Chinese patients with established osteoporosis in subgroups. In this Phase III study of teriparatide in China, 362 patients were randomized at a 2:1 ratio to receive subcutaneous teriparatide (20 µg/day) or intranasal salmon calcitonin (200 IU/day) for 24 weeks. Teriparatide treatment produced a significantly greater increase in lumbar spine bone-mineral density (LS-BMD) in postmenopausal women than calcitonin at the 24-week end point. The relationship between osteocalcin (OCN) and LS-BMD was evaluated, and the greatest correlation was found between absolute OCN change at week 12 and percentage change in LS-BMD for patients in the teriparatide group (r=0.24, P<0.001). The correlation weakened at week 24 (r=0.16, P=0.02) and was negligibly negative for calcitonin-treated patients. Proportions of patients achieving >10 µg/L absolute OCN change from baseline in the teriparatide- and calcitonin-treated groups were 81% and 6% at week 12, respectively (P<0.001). Proportions of patients with increased LS-BMD ≥3% at week 24 from baseline were 71% and 35% in the teriparatide- and calcitonin-treated groups, respectively (P<0.001). Proportions of patients meeting both criteria were 63% for the teriparatide group and 1% for the calcitonin-treated group (P<0.001). Subgroup analysis suggested that significant increases in LS-BMD and OCN can be achieved in patients receiving teriparatide, regardless of baseline age, LS-BMD, and fracture times. The rate of treatment-emergent adverse events in each subgroup was similar to the overall analysis.

Generalized high bone mineral density on bone density scanning: a case of gastric carcinoma with bone metastasis.

Generalized high bone mineral density (BMD) on Dual-energy X-ray absorptiometry (DXA) scanning most commonly reflects metabolic bone disease. However, some malignancies could also stimulate the underlying processes. We reported that a 41-year-old female was referred for lumbago. She did not complain of any symptoms in the digestive system. DXA revealed high BMD in the lumbar vertebras. Marked increase in bone mass was observed in an X-ray of chest compared with one conducted 6 months previously. Additionally, an X-ray of the axial skeleton showed diffuse sclerotic change. Laboratory data revealed hypocalcemia and high osteoblastic activity. A bone biopsy of the pelvis confirmed metastatic undifferentiated adenocarcinoma. Further research for the primary site revealed gastric signet ring cell carcinoma via endoscopic biopsy. The patient refused treatment and died 2 months after the diagnosis. In clinical practice, high BMD could be the initial feature of gastric cancer. Due to its poor prognosis, adequate clinical management is of paramount value.

The effect and safety of diacerein in patients with type 2 diabetes mellitus : a systematic review and meta-analysis.

The Background: Diacerein has been proposed as a treatment option for management of type 2 diabetes due to its anti-inflammatory properties. PURPOSE: The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to examine the effect and safety of diacerein in patients with type 2 diabetes. DATA SOURCES AND STUDY SELECTION: We searched Pubmed, Embase, and Cochrane Library for RCTs published from database inception to September 2017. DATA EXTRACTION AND DATA SYNTHESIS: Among 44 studies that were initially identified, four were eligible and were included in the following analysis. Diacerein significantly reduced fasting glycemia [weighted mean differences (WMD) -0.66, 95% confidence interval (95% CI) -1.16 to -0.16] and glycated hemoglobin A1c (HbA1c ) (WMD -0.85, 95% CI -1.44 to -0.26). And the patients with a diacerein supplementation duration of ≤12 weeks had a greater decrease of fasting glycemia and HbA1c than the supplementation duration of >12 weeks. Furthermore, compared with placebo, diacerein revealed a significant increase in the relative risk (RR) of gastrointestinal symptoms (RR=2.50, 95% CI: 1.10 to 5.65), especially in the study subgroup with supplementation duration of >12 weeks (RR=4.01, 95% CI: 2.32 to 6.95). LIMITATIONS: The sample size was relatively small and the duration of included studies was short so that the treatment efficacy and safety for longer duration was unknown. CONCLUSIONS: Although further studies are needed, our findings clearly provide support to the use of diacerein in the clinical management of subjects with type 2 diabetes.

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.

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.

Primary hypertrophic osteoarthropathy with myelofibrosis and anemia: a case report and review of literature.

Primary hypertrophic osteoarthropathy (PHO) is a rare and usually benign disorder of bone and connective tissue growth. Here we present a 28-year-old male patient presenting to our hospital with PHO and symptomatic anemia. Bone marrow biopsy suggested myelofibrosis, a serious complication of PHO, which is often neglected upon admission, but may lead to life-threatening anemia.

Growth and aging of proximal femoral bone: a study with women spanning three generations.

Osteoporotic hip fracture is a serious clinical event associated with high morbidity and mortality. Understanding femoral growth patterns is important for promoting bone health in the young and preventing fractures in later life. In this study, growth patterns of areal bone mineral density (aBMD) and geometric properties of the proximal femur were measured by dual-energy X-ray absorptiometry. They were studied in 251 girls from premenarche (11.2 ± 0.7 years) to late adolescence (18.3 ± 1.1 years) and compared with their premenopausal mothers (n = 128, aged 44.9 ± 4.1 years) and postmenopausal grandmothers (n = 128, aged 70.0 ± 6.3 years). Hip axis length (HAL) was the first to reach peak growth velocity (-10.5 months before menarche), followed by neck diameter (ND) and neck cross-sectional area (CSA), (-7.1 and -4.1 months before menarche, respectively). Both neck-shaft angle (NSA) and aBMD of neck and total hip peaked at menarche. At 18 years (7-year follow-up), girls already had higher femoral neck aBMD but similar HAL and NSA compared with their mothers. Grandmothers had the longest HAL, narrowest NSA, widest ND but lowest aBMD and CSA. Hip strength index (HSI), an index of femoral neck strength during a fall, dropped rapidly after menarche in girls but thereafter remained relatively constant. Grandmothers had lower HSI than either mothers or girls. In conclusion, differences in proximal femoral bone mass and structure in adulthood are largely established before menarche, indicating that heritable factors are responsible for most of the individual variance. The development of geometric properties precedes aBMD in puberty, resulting in relatively constant hip strength after menarche. This asynchronous growth leads to adaptation of bone strength to the imposed loads, avoiding fractures in a biologically efficient manner. Both deterioration of aBMD and inadequate compensatory change in bone geometry after menopause contribute to the increased fracture risk later in life.

The associations of serum serotonin with bone traits are age- and gender-specific.

CONTEXT: Serotonin plays a potential role in bone metabolism, but the nature and extent of this relationship is unclear and human studies directly addressing the skeletal effect of circulating serotonin are rare. OBJECTIVE: The study aimed to investigate the associations between serum serotonin and bone traits at multiple skeletal sites in women and men. SUBJECTS AND METHODS: Subjects were part of the CALEX-family study and comprised 235 young women, 121 premenopausal women, 124 postmenopausal women, and 168 men. Body composition was assessed using DXA, as was areal bone mineral density (aBMD) of spine, femur and whole body. In addition, pQCT was used to determine bone properties at tibial midshaft and distal radius. Fasting serum serotonin concentration was assessed using a competitive enzyme-linked immunosorbent assay. RESULTS: Serum serotonin declined with advancing age both in females and males (all p<0.01). Serotonin was negatively correlated with weight, BMI, lean and fat mass in women (r = -0.22 to -0.39, all p<0.001), but positively with height and lean mass in men (all p<0.01). In the premenopausal women, serotonin was negatively correlated with lumbar spine aBMD (r = -0.23, p<0.05) but the statistical significance disappeared after adjustment for weight. Conversely, in postmenopausal women, serotonin was positively correlated with whole body and femur aBMD, as well as with distal radius bone mineral content and volumetric BMD (r = 0.20 to 0.30, all p<0.05), and these associations remained significant after adjustment for weight. In men, no significant associations were found between serotonin and bone traits. CONCLUSION: Serum serotonin is positively associated with bone traits in postmenopausal women, but not in premenopausal women or men. This partially supports the idea of circulating serotonin playing a role in the regulation of bone metabolism, but also indicates the importance of gender and age specific factors.