Improvement of bone mineral density and markers of proximal renal tubular function in chronic hepatitis B patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

Tenofovir alafenamide (TAF) is a novel prodrug that reduces tenofovir plasma levels by 90% compared to tenofovir disoproxil fumarate (TDF), resulting in decreased bone mineral density (BMD) loss and renal toxicity. We aimed to study changes in BMD and markers of renal function of chronic hepatitis B (CHB) patients previously treated with TDF who were switched to TAF in as early as 12 weeks. This was a prospective single‐arm open‐label study of 75 CHB patients treated with TDF 300 mg daily who were switched to TAF 25 mg daily and followed for 24 weeks. All patients had been treated with TDF for at least 12 months and had HBV DNA <21 IU/mL at the time of switch. BMD and markers of renal function were taken on the day of switch and repeated after 12 and 24 weeks of TAF treatment. Hip and spine bone mineral density significantly increased from baseline to week 12 (+12.9% and +2.4%, respectively, P < 0.01). There were significant decreases in urinary beta‐2‐microglobulin to creatinine and retinol‐binding protein to creatinine ratios by week 12 (P < 0.01 for both). Mean estimated glomerular filtration rate (GFR) did not change. Tubular reabsorption of phosphate was decreased at week 24 (P < 0.05). In conclusion, CHB patients previously treated with TDF experienced significant improvement in bone density and some markers of renal tubular function and as early as 12 weeks after switching to TAF. Bone density changes associated with TDF may not be entirely related to renal handling of phosphate.     

Bone turnover markers and bone mineral density in children with haemophilia

Summary. During childhood growth, bone undergoes modelling involving separate osteoblastic and osteoclastic processes. Markers of bone turnover circulate at high concentrations, parallel the childhood growth curve and correlate with height velocity. The aim of this study was to compare serum markers of bone turnover in children with haemophilia and normal bone mineral density (BMD) vs. those with low BMD. In a cross‐sectional study, 69 children with haemophilia were evaluated, 45 children with normal spine BMD vs. 24 with low BMD. Lumbar spine BMD was determined using dual X‐ray absorptiometry and Z‐scores were calculated. Serum samples of markers of bone turnover, osteocalcin (bone formation) and C‐telopeptide of type I collagen (bone resorption) were measured using ELISA. The mean BMD (g cm^?2) in the normal group was 0.656 ± 0.15 vs. 0.558 ± 0.12 in those with low BMD (P = 0.007), osteocalcin levels in children with normal BMD were 9.29 ± 4.97 vs. 7.06 ± 2.17 ng μL^?1 in the low BMD group (P = 0.012). C‐telopeptide levels in the normal group were 1.06 ± 1.4 vs. 0.74 ± 0.3 ng mL^?1 in the low BMD group (P = 0.169). Our results showed that low osteocalcin levels predominated in the group with low BMD, which indicates a diminished osteoblastic bone formation activity while there were no differences with regard to bone resorption markers. Moreover, osteocalcin levels explain 10% of the variation of lumbar spine Z‐score.     

中老年妇女骨转换生化指标和骨密度的变化

目的 探讨中老年妇女骨转换生化指标与骨密度随绝经的变化.方法 408名符合条件40 ～80岁的女性志愿者,同一时间段留取血清和晨尿,统一用酶免方法 测定血清骨碱性磷酸酶(BAP)、骨钙素和尿I型胶原氨基末端肽(uNTX);用舣能X线骨密度仪测定前后位腰椎1-4(L1-4)、左侧股骨颈的骨密度.结果 (1)BAP、骨钙素和uNTX与年龄、孕次、生育次数和绝经年限呈正相关(均P相似文献   

Bone mineral density and bone turnover in patients with psoriatic arthritis

Psoriasis is a common inflammatory skin disease, and conflicting data have been published about osteoporosis and bone turnover markers in patients with psoriatic arthritis. The aim of this study was to assess bone mineral density (BMD) and bone turnover markers in psoriatic patients with and without peripheral arthritis and to investigate the relationship between clinical parameters and markers of bone turnover. Forty-seven patients (24 women, 23 men) with psoriasis were included to the study. Demographic data and clinical characteristics were recorded. Erythrocyte sedimentation rate and C-reactive protein were assessed as disease activity parameters. BMD was determined for lumbar spine and total hip by dual X-ray absorptiometry (DXA). Serum Ca, P, alkalen phosphatase (ALP), and serum type I collagen cross-linked C telopeptide (CTX) were measured as bone turnover markers in all patients. The patients were divided into two groups according to their peripheral arthritis status. The clinical and laboratory variables, as well as bone mass status of the groups, were compared with each other. Eighteen patients had peripheral arthritis. All the female patients were premenopausal. None of the patients had radiologically assessed axial involvement. There was no significant difference between the BMD levels of psoriatic patients with and without arthropathy. One patient (5%) had osteoporosis, and nine (50%) patients had osteopenia in arthritic group, while eight (27.5%) patients had osteopenia in patients without arthritis. Serum CTX, ALP, Ca, and P levels were not significantly different in arthritic than in non-arthritic patients (p > 0.05). In patients with psoriatic arthritis, the duration of arthritis was negatively correlated with BMD values of lumbar spine and total femur and serum CTX levels, suggesting an association of increased demineralization with the duration of joint disease. In conclusion, psoriatic patients with peripheral arthritis with longer duration of joint disease may be at a risk for osteoporosis, which can require preventative treatment efforts.     

Comparison of the effects of alendronate and risedronate on bone mineral density and bone turnover markers in postmenopausal osteoporosis

The aim of the study was to compare the effects of once-weekly alendronate sodium and daily risedronate sodium treatment on bone mineral density (BMD) and bone turnover markers in postmenopausal osteoporotic subjects. For this purpose, 50 patients were included in this study and randomly classified into two groups. Group I (n=25) received risedronate (5 mg/day) and group II (n=25) received alendronate Na (70 mg/week). The study duration was limited to 12 months. The efficacy of the treatment was evaluated by BMD measurements at spine and hip at 6th and 12th months of the treatment, as well as by the measurement of bone turnover markers such as serum osteocalcin (OC), bone-specific alkaline phosphatase (BASP), urine deoxypyridinoline (DPD) and calcium/creatine ratio in 24-h urine at 1st, 3rd, 6th and 12th months. The evaluation of the changes in BMD in all regions revealed a significant increase in BMD in both groups compared to baseline values except for spine (L2–L4) in alendronate group at 6th and 12th month and femoral neck in risedronate group at 6th month. However, the difference in percentage increase in BMD measurements was not statistically significant between the two groups at 6th and 12th months. In both groups, serum OC, BSAP and urine DPD were found to be significantly attenuated at 1st month of the treatment period, and continued to be lowered throughout the 3rd, 6th and 12th months (P<0.05). However, there was no statistically-significant difference between both groups of patients (P>0.05). In conclusion, our results suggest that both treatment protocols provide treatment options of similar efficiencyfor postmenopausal osteoporosis, and have almost-similar effects in enhancing the BMD and in slowing the bone turnover. Risedronate seems to havea more potent effect in the spinal region than that of alendronate, although this potency was not statistically significant.     

Comparison of the effects of denosumab with either active vitamin D or native vitamin D on bone mineral density and bone turnover markers in postmenopausal osteoporosis

Osteoporosis is a worldwide health concern. Although treatment with denosumab plus the active vitamin D alfacalcidol has been found to improve femoral neck (FN) and distal forearm bone mineral density (BMD), there have been no reports on the efficacy or adverse effects of denosumab plus eldecalcitol (ELD) in primary osteoporosis patients. Fifty-six treatment-naïve post-menopausal women with primary osteoporosis were recruited and divided into denosumab plus native vitamin D or denosumab plus ELD. Ultimately, 26 subjects in the native vitamin D group and 24 in the ELD group were analyzed. Lumbar and total hip BMD significantly increased in both groups. However, there was no significant difference in the percent increase of lumbar and total hip BMD between two groups. FN-BMD was significantly increased from 6 to 12 months in the ELD group compared with baseline. This study revealed that combination therapy with denosumab and ELD could improve FN-BMD more effectively than denosumab plus native vitamin D. Thus, the addition of ELD may enhance the effects of denosumab treatment for primary osteoporosis.     

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人的一生不断进行着骨的新陈代谢。这是通过旧骨吸收和新骨形成来完成。在正常人两者紧密偶联,假如两者失偶联会引起骨量、骨结构和骨强度的改变。但体内骨结构和骨强度很难被检测。近代通过测定骨转换生化标志物了解是否存在骨代谢的失衡。文章介绍骨形成和骨吸收的生化标志物及其临床应用,由于无创伤,价较廉,正被推广应用。     

Bone mineral density and serum bone turnover markers in survivors of childhood acute lymphoblastic leukemia: comparison of megadose methylprednisolone and conventional-dose prednisolone treatments

During recent decades, the survival rate after childhood acute lymphoblastic leukemia (ALL) has improved substantially; consequently, the long-term side effects of ALL and its treatment have gained attention, of which osteoporosis is one of the most important. The purpose of the present study was to compare the influence of different treatment protocols that include high-dose methylprednisolone (HDMP) versus conventional-dose prednisolone (CDP) for remission-induction therapy on bone mineral density (BMD) and serum bone turnover markers in survivors of childhood ALL after cessation of chemotherapy. Thirty-six boy and 23 girl survivors, treated for ALL, were cross-sectionally studied, at a mean age of 11.7 years (range 6-19). Group 1 (n = 30) received CDP therapy (prednisolone, 2 mg/kg/day, orally) and group 2 (n = 29) received HDMP therapy (prednol-L, 900-600 mg/m2, orally). All other therapies were similar in both groups. Cranial irradiation was added for high-risk patients as soon as possible after consolidation therapy. We found that mean lumbar spine BMD z score value was -1.75 (0.83) SDS in group 1 and -1.66 (1.21) SDS in group 2. There is no difference between both groups (P = 0.736). The mean BMD z scores of prepubertal and pubertal patients were not significantly different in both groups. Comparison of serum bone turnover parameters of the patients revealed no difference between the two groups. Stepwise regression analysis revealed that lumbar spine BMD z scores was predicted by height SDS and the time past since cessation of therapy, but not age at diagnosis, BMI SDS, cranial radiotherapy, and puberty. Our study results showed that HDMP treatment did not deteriorate the bone mass any more than CDP treatment. These results proved that high-dose steroid therapy over a short period of time in remission-induction treatment would not affect the bone mass any more adversely than would conventional doses approximately 3 years after cessation of chemotherapy.     

The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

Abstract

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score ?1 to ?2.5) and 23 patients (27.7%) had osteoporosis (T < ?2.5). The body mass index of patients with normal BMD (T score ≥ ?1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score −1 to −2.5) and 23 patients (27.7%) had osteoporosis (T < −2.5). The body mass index of patients with normal BMD (T score ≥ −1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

胰岛素、胰岛素原对胰岛素抵抗状态下HepG2细胞PAI-1分泌的影响

目的研究胰岛素、胰岛素原对胰岛素抵抗状态下ＨｅｐＧ２细胞ＰＡＩ１分泌的影响。方法选择在合成ＰＡＩ１方面与肝细胞相似的ＨｅｐＧ２细胞，以高浓度胰岛素诱导胰岛素抵抗后，分别用生理浓度的胰岛素、胰岛素原刺激２４小时，以观察胰岛素抵抗状态下ＰＡＩ１活性的变化。结果基础状态下胰岛素抵抗ＨｅｐＧ２细胞与非胰岛素抵抗ＨｅｐＧ２细胞相比，ＰＡＩ１活性差异不明显；胰岛素、胰岛素原刺激后，胰岛素抵抗ＨｅｐＧ２细胞ＰＡＩ１活性明显高于非胰岛素抵抗ＨｅｐＧ２细胞。当培液中同时加入１０－４Ｍ二甲双胍后，胰岛素、胰岛素原介导的ＰＡＩ１过量分泌得到明显抑制。结论在胰岛素抵抗状态下，胰岛素、胰岛素原刺激后ＨｅｐＧ２细胞ＰＡＩ１活性明显增加，而二甲双胍可明显抑制此现象。     

类风湿关节炎患者骨密度及骨矿物质含量的变化及意义

目的探讨类风湿关节炎(RA)患者骨密度(BMD)及骨矿物质(BMC)含量的变化及意义。方法选择71例RA患者(RA组)及20例正常人(对照组),采用双能X线骨密度仪检测各组前臂BMD、BMC含量,魏氏法检测血沉(ESR),免疫比浊法检测血清C反应蛋白(CRP),速率散射比浊法检测类风湿因子(RF),ELISA法检测抗环瓜氨酸肽抗体(ACCP);同时进行X线分期,计算患者疾病活动分数(DAS28)。结果 RA组前臂BMD、BMC均低于对照组(P均<0.01),ESR、CRP、RF、ACCP均高于对照组(P均<0.01)。Pearson’s相关分析显示,前臂BMD与DAS28、ESR、RF呈负相关(r分别为-0.357、-0.390、-0.255,P<0.05或<0.01),前臂BMC与DAS28、ESR呈负相关(r分别为-0.344、-0.401,P均<0.01)。多元线性回归分析显示,前臂BMD与RF、年龄呈负相关(T分别为-7.544、-3.254,P均<0.01);前臂BMC与DAS28呈负相关(T=-4.44,P<0.01)。RA组中X线分期为Ⅰ期的有15例,其中BMD示骨质疏松6例、骨量减少2例。结论 RA患者BMD、BMC含量明显减少,其含量减少与RA活动密切相关;RF可能是导致RA骨量丢失的危险因素;BMD检测能更早反映RA患者的骨量丢失情况。     

老年男性各年龄组骨密度与骨代谢生化指标的关系

目的　测定老年男性不同年龄组骨密度及血、尿中与骨吸收和骨形成有关的生化指标 ,观察其与年龄的关系 ,探讨以上生化指标对早期诊断原发性骨质疏松的临床意义。方法　采用双能量 X线骨密度测定仪测定前臂骨密度 ;采用全自动生化分析法测定血清碱性磷酸酶(ALP)、尿钙 (Ca)、肌酐 (Cr) ;采用放免法测定骨钙素 (BGP)、抗酒石酸酸性磷酸酶 (TRAP)、尿羟脯氨酸 (HOP)。将年龄 60～ 95岁的老年男性 97例分为 60～ 69岁、 70～ 79岁和 80岁以上三组并与 60岁以下男性进行比较。再将其分为骨质疏松组与非骨质疏松组 ,比较其测定值。结果　老年男性骨密度及骨形成与骨吸收指标呈现随着年龄增长而降低的趋势。其中 ,骨质疏松组较非骨质疏松组骨钙素 (BGP)、抗酒石酸酸性磷酸酶 (TRAP)、尿羟脯氨酸 (HOP) ,明显下降 (P<0 . 0 5)。结论　老年男性骨质疏松属于低转换型 ,骨转换指标随增龄而呈下降趋势     

女性骨转换指标与年龄和腰椎骨密度的关系

目的观察20～80岁健康女性血清骨特异性碱性磷酸酶（sBAP）、血清和尿液中Ⅰ型胶原羧基末端肽（sCTX和uCTX）随年龄变化的规律及其与腰椎正位骨密度（BMD）之间的关系。方法用ELISA法测定sBAP、sCTX和uCTX，以自动分析仪测定血清总碱性磷酸酶（sTAP）和尿肌酐；同时用双能X线骨密度仪测定腰椎正位的BMD。结果（1）年龄与sBAP、sCTX、uCTX和sTAP之间均存在明显的相关性，决定系数（R^2）分别是0.371、0.130、0.121和0.333。（2）在校正年龄、体重及身高的影响之后腰椎正位的BMD与sBAP、sCTX、uCTX和sTAP明显负相关，其与骨转换指标的相关系数（r）分别为-0．37、-0．29、-0．26和-0．30（均P〈0.01）。（3）按腰椎正位的峰值骨量确定正常骨量、低骨量及骨质疏松的人群，发现sBAP、sCTX、uCTX和sTAP在3组之间差异存在统计学意义。结论sBAP、sCTX、uCTX随年龄而变化并与腰椎正位BMD间存在负相关。血清sBAP、sCTX和uCTX在低骨量和骨质疏松的人群中明显升高，提示其是健康女性确定骨转换率的敏感指标。     

The clinical utility of bone turnover markers in the evaluation of bone disease in patients with haemophilia A and B

Haemophilia A and B have been associated with increased prevalence of low bone mineral density (BMD). However, the utility of bone turnover markers (BTM) remains unknown. The aim of this study was to evaluate bone metabolism in men with haemophilia and to investigate associations between BTM and bone disease. Serum N‐ (NTX‐I), C‐terminal telopeptide of type I collagen (CTX‐I) and tartrate‐resistant acid phosphatase band‐5b (TRAP‐5b), as bone resorption markers, and osteocalcin (OC) and bone‐specific alkaline phosphatase (b‐ALP), as bone formation markers, were assessed. Seventy men with haemophilia A (n = 59) or B (n = 11) were studied. Patients with low BMD had significantly higher b‐ALP concentrations compared with those with normal BMD (12.8 ± 1.60 vs. 9.72 ± 0.58 μg/L, P = 0.009), without any differences in the other BTM. NTX‐I and CTX‐I concentrations were negatively associated with oestradiol levels and hip BMD and positively with human immunodeficiency virus infection, number of affected joints and arthropathy scores. B‐ALP and OC concentrations were negatively associated with hip BMD, severity of haemophilia and fracture history, and positively with the number of affected joints and testosterone concentrations. After multivariate analysis, NTX‐I levels remained negatively associated with oestradiol levels, whereas b‐ALP concentrations negatively correlated with the level of physical activity and positively with the number of affected joints. Increased bone metabolism exists in men with haemophilia and low BMD. Increased b‐ALP levels may identify patients at high risk for fracture. Increased number of target joints, low physical activity and low oestradiol concentrations are independently associated with increased bone metabolism.     

贵阳市部分成人代谢综合征对骨密度的影响

目的：了解代谢综合征及其组分对骨密度的影响。方法2009年11月至2010年2月贵阳市居民健康横断面调查的1512名20～79岁调查对象（男性636名,女性876名）纳入本研究,受试者平均年龄（45.3±14.4）岁。对所有受试者进行问卷调查及体格检查,用OLYMPUSAU5400全自动生化分析仪检测空腹静脉血糖及餐后2h血糖、三酰甘油、高密度脂蛋白胆固醇、血钙、血磷、血肌酐及血尿酸,用ROCHE化学发光法测定血清胰岛素;用双能X线检测股骨颈、全髋、Wards三角、粗隆及腰椎正位（L1-4）骨密度。结果完成血脂、尿酸、血糖、血钙、血磷、血肌酐、血胰岛素及骨密度检测者1216名,发现代谢综合征患者356例,患病率为29.3％,其中男性125例（35.1％）,女性231例（64.9％）;代谢综合征组骨折患病率为5.1％,非代谢综合征组为3.3％;代谢综合征患者全髋及粗隆骨密度较非代谢综合征者高[（0.95±0.15）g/cm2比（0.93±0.14）g/cm2;（0.76±0.13）g/cm2比（0.73±0.12）g/cm2;均P＜0.01];校正性别及年龄后,股骨颈、全髋、Wards三角、粗隆及L1-4骨密度值均随代谢综合征患者组份增加而增高（均P＜0.01）。结论代谢综合征患者有较高的全髋及粗隆骨密度,但其骨折率亦较高。