Efficacy data on teriparatide (parathyroid hormone) in patients with postmenopausal osteoporosis

Until recently, the only therapeutic agents available for postmenopausal osteoporosis acted by inhibiting bone resorption and decreased the fracture risk by no more than 50%. Teriparatide, the recombinant 1-34 fragment of human parathyroid hormone, is a bone formation enhancer that has recently been licensed for use in established postmenopausal osteoporosis. Intermittent parathyroid hormone administration preferentially stimulates bone formation. The resultant increase in bone mass and improvement in bone architecture translate into a large decrease in the fracture risk that constitutes a major advance in the treatment of postmenopausal osteoporosis. Further work is needed to define the role for teriparatide in the therapeutic strategy for postmenopausal osteoporosis and to determine whether this agent is best used alone or in synchronous or sequential combination with bone resorption inhibitors.     

Low serum albumin concentration is associated with increased risk of osteoporosis in postmenopausal patients with rheumatoid arthritis

BackgroundThe risk of osteoporosis in patients with rheumatoid arthritis (RA) is frequently overlooked, and investigating a simple indicator in routine care may be beneficial to motivate osteoporosis examination. The aim of this retrospective, case-controlled study was to identify the correlation between serum albumin concentrations and the prevalence of osteoporosis in postmenopausal patients with RA.MethodsThis study enrolled 197 patients who underwent dual-energy X-ray absorptiometry of lumbar spine (LS) and proximal femur without osteoporosis treatment [mean age, 67.5 years; disease duration, 12.8 years; Disease Activity Score assessing 28 joints with C-reactive protein, 2.0; prednisolone dose, 4.9 mg/day (usage, 42.6%); and LS T-score, ?1.9]. Patients were classified into 2 groups: osteoporosis, defined as ≥ 1 part bone mineral density T-score ≤ ?2.5 or history of fragility fracture of the vertebra or proximal femur (121 patients), and non-osteoporosis (76 patients). Groups were then matched by propensity score using clinical backgrounds affecting bone metabolism.ResultsIn non-matched model, serum albumin concentration was significantly associated with osteoporosis-related factors such as aging, inflammation, physical disability, and glucocorticoid dose. Multivariate logistic regression revealed that serum albumin concentration was independently and significantly associated with osteoporosis risk (odds ratio = 0.22, 95% confidence interval = 0.08, 0.61, p = 0.0033). After propensity score matching, 57 patients for each group showed that in addition to the LS and femoral neck T-scores (p < 0.001), serum albumin concentrations (p = 0.01) remained lower in the osteoporosis group compared to non-osteoporosis group. Receiver operating characteristic curve analysis in non-matched model revealed that when cut-off value of serum albumin concentration for indicating osteoporosis was set at 4.2 g/dl, the area under the curve was 0.69, sensitivity 0.74, and specificity 0.58.ConclusionsLow serum albumin concentration was significantly and independently associated with the prevalence of osteoporosis, which may be considered as one of the osteoporosis-related factors in postmenopausal patients with RA.     

Effect of teriparatide on bone mineral density and biochemical markers in Japanese women with postmenopausal osteoporosis: a 6-month dose-response study

The dose-response efficacy and safety with three doses of teriparatide and placebo was assessed, using oncedaily subcutaneous injections for 24 weeks, in Japanese postmenopausal women with osteoporosis at high risk of fracture for reasons of preexisting fracture(s), advanced age, and/or low bone mineral density (BMD). In this multicenter, randomized, placebo-controlled study, 159 subjects were randomized and 154 subjects were included for analysis. Teriparatide (10-μg, 20-μg, and 40-μg doses) showed a statistically significant increase with increasing treatment dose as assessed by the percent change of lumbar spine BMD from baseline to endpoint using Williams’ test when compared with placebo (P < 0.001). The mean (±SD) percent change in lumbar spine, femoral neck, and total hip BMD with the 20-μg dose from baseline to endpoint was 6.40% ± 4.76%, 1.83% ± 7.13%, and 1.91% ± 3.60%, respectively. Rapid and sustained increases in bone formation markers [type I procollagen N-terminal propeptide (PINP), type I procollagen C-terminal propeptide (PICP), and bone-specific alkaline phosphatase (BAP)], followed by late increases in a bone resorption marker [type I collagen cross-linked C-telopeptide (CTX)], were observed for the teriparatide treatment groups (20-μg, 40-μg), suggesting a persistent, positive, balanced anabolic effect of teriparatide. Optimal adherence was achieved by this daily self-injection treatment. Regarding safety, most of the adverse events were mild to moderate in severity. No study drug-or study procedure-related serious adverse events were reported during the treatment period. These results observed in Japanese patients may support the observation that teriparatide stimulates bone formation in patients with osteoporosis at a high risk of fracture.     

风湿活动度预测绝经后女性类风湿关节炎患者骨密度的研究

目的探讨能够预测绝经后女性类风湿关节炎(Rheumatoid Arthritis RA)患者骨质疏松的指标。方法收集100例绝经后女性RA患者一般临床资料包括年龄、病程、血沉、C反应蛋白、类风湿因子、抗环瓜氨酸肽抗体、关节疼痛数目、关节肿胀数目,采用双能量X线骨密度仪测量腰椎、股骨及全身总的平均骨密度,比较临床资料并分析可能影响骨密度的因素。结果1.绝经后女性类风湿关节炎患者骨质疏松比例为33%,骨量减少比例47%,骨量正常比例20%。2.骨质疏松组的年龄、病程、血沉、关节疼痛数目、DAS28均高于非骨质疏松组,且有统计学意义。3.采用Logistic回归分析结果显示,年龄和DAS28是绝经后女性RA患者骨密度的独立危险因素。4.骨密度T值为诊断骨质疏松的金标准绘制受试者工作曲线,计算DAS28、年龄诊断骨质疏松的切点为5.3分和59.5岁。结论风湿活动度和年龄对于绝经后女性RA患者有较强的骨质疏松预警作用。     

Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial.

We compared combination treatment with teriparatide plus raloxifene with teriparatide alone in women with postmenopausal osteoporosis in a 6-month double-blind, placebo-controlled trial that measured biochemical markers of bone turnover and BMD. Markers of bone formation and spine BMD increased similarly with teriparatide alone and combination therapy. However, combination therapy induced a significantly smaller increase in bone resorption versus teriparatide alone and significantly increased total hip BMD versus baseline. INTRODUCTION: The effects of combining two approved treatments for osteoporosis with different modes of action were examined by comparing teriparatide [rhPTH(1-34)] monotherapy with combination teriparatide and raloxifene therapy. MATERIALS AND METHODS: A 6-month randomized, double-blind trial comparing teriparatide plus raloxifene (n = 69) versus teriparatide plus placebo (n = 68) was conducted in postmenopausal women with osteoporosis. RESULTS: Bone formation (N-terminal propeptide of type 1 collagen [PINP]) increased similarly in both treatment groups. However, the increase in bone resorption (serum C-terminal telopeptide of type I collagen [CTx]) in the combination group was significantly smaller than in the teriparatide-alone group (p = 0.015). Lumbar spine BMD significantly increased 5.19 +/- 0.67% from baseline in the teriparatide-alone group. In the combination group, lumbar spine (6.19 +/- 0.65%), femoral neck (2.23 +/- 0.64%), and total hip (2.31 +/- 0.56%) BMD significantly increased from baseline to study endpoint, and the increase in total hip BMD was significantly greater than in the teriparatide-alone group (p = 0.04). In the teriparatide-alone group, mean serum calcium levels increased from baseline to endpoint (0.30 +/- 0.06 mg/dl, p < 0.001), whereas mean serum phosphate remained unchanged. In the combination group, mean serum calcium was unchanged, and mean serum phosphate decreased (-0.20 +/- 0.06 mg/dl, p < 0.001) from baseline to endpoint. Changes in serum calcium (p < 0.001) and phosphate (p < 0.004) were significantly different between treatment groups. The safety profile of combination therapy was similar to teriparatide alone. CONCLUSIONS: Combination therapy increased bone formation to a similar degree as teriparatide alone. However, the increase in bone resorption was significantly less and total hip BMD significantly increased for combination therapy compared with teriparatide alone. Combination treatment with raloxifene may thus enhance the bone forming effects of teriparatide. Further studies over longer treatment duration that include fracture endpoints are necessary to fully ascertain the clinical significance of combination raloxifene plus teriparatide therapy in postmenopausal osteoporosis.     

Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis

ObjectivesTo investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis.MethodsIn this prospective, observational, and multicenter study, treatment naïve patients (Naïve; n = 50) or patients previously treated with bisphosphonates (BP; n = 37) or denosumab (DMAb; n = 45) or teriparatide (TPTD; n = 16) (mean age, 75.0 years; T-scores of the lumbar spine [LS] ?3.2 and total hip [TH] ?2.6) were switched to ROMO due to insufficient effects of prior treatment. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 12 months.ResultsAt 12 months, changes in LS BMD were Naïve (18.2%), BP (10.2%), DMAb (6.4%), and TPTD (11.2%) (P < 0.001 between groups) and changes in TH BMD were Naïve (5.6%), BP (3.3%), DMAb (0.6%), and TPTD (4.4%) (P < 0.01 between groups), respectively. In all groups, the LS BMD significantly increased from baseline at 6 and 12 months, although only the DMAb group failed to obtain a significant increase in TH BMD during 12-month treatment. Mean values of N-terminal type I procollagen propeptide (PINP; μg/L) from baseline → 1 month → 12 months were Naïve (67.9 → 134.1 → 51.0), BP (32. 2 → 81.7 → 40.9), DMAb (30.4 → 56.2 → 75.3), and TPTD (97.4 → 105.1 → 37.1), and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; mU/dL) were Naïve (500.4 → 283.8 → 267.1), BP (273.4 → 203.1 → 242.0), DMAb (220.3 → 246.1 → 304.8), and TPTD (446.6 → 305.1 → 235.7), respectively. Multiple regression analysis revealed that the significant predictors of BMD change at 12 months were difference of prior treatment (r = ?2.8, P < 0.001) and value of PINP at 1 month (r = 0.04, P < 0.01) for LS, and difference of prior treatment (r = ?1.3, P < 0.05) and percentage change of TRACP-5b at 1 month (r = ?0.06, P < 0.05) for TH.ConclusionsThe early effects of ROMO on LS and TH BMD increase at 12 months were significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.     

类风湿关节炎继发骨质疏松症的临床分析

目的 探讨类风湿关节炎（rheumatoid arthrilis，RA)继发骨质疏松症（Osteoporosis，OP)的相关性，提高此类患者的生命质量。方法 选取RA患者和正常人群各60例分为观察组和对照组两组，检测两组的骨密度值，同时观察RA继发OP组及非OP组的临床症状及血沉（ESR)、类风湿因子（RF)、C反应蛋白（CRP)等实验室指标。结果 60例RA患者腰椎L1-4、髋部的骨密度检测均明显低于对照组，18例RA继发OP患者较非OP组（骨量正常、骨量减少），42例RA患者HAQ积分更高（P <0.01)，关节功能更差（P <0.01)，炎症指标更高（P <0.01)。结论 类风湿关节炎较正常人群的骨质疏松症的发生率明显升高，RA继发OP患者的HAQ评分、关节功能、炎症指标等较RA骨量正常者明显升高。     

应用特立帕肽对骨质疏松症腰椎融合手术疗效影响的研究进展

腰椎融合手术是治疗腰椎退行性疾病的主要方式之一。随着人口老龄化加剧,骨质疏松症在患有脊柱退行性疾病的患者中非常多见。腰椎融合手术的骨质疏松相关并发症包括内固定失败、假关节形成、邻近节段退变、继发椎体骨折、近端交界性后凸等。骨质疏松相关并发症严重影响腰椎融合手术的效果,而在腰椎融合术前后进行抗骨质疏松治疗可以有效地降低术后1年内发生骨质疏松相关并发症的概率。甲状旁腺激素（parathyroid hormone,PTH）是一种由甲状旁腺产生的多肽,参与维持钙和磷的稳态。特立帕肽（teriparatide）,即重组人PTH（1-34）[recombinant human PTH（1-34）,rhPTH（1-34）],是骨的合成代谢剂,其通过刺激细胞表面相应的受体,激活成骨细胞增殖和分化所必需的信号通路,促进新骨组织的形成,并抑制成骨细胞和骨细胞的凋亡。作为第一个促成骨类的药物,特立帕肽自2002年开始用于治疗骨质疏松症,提高骨质疏松患者骨密度。由于特立帕肽的骨合成代谢作用,已有研究报道在其他骨病中使用特立帕肽修复和改善骨的质量。脊柱融合术的目的是实现脊柱的实体关节融合,提高脊柱的稳定性。脊柱融合的成功取决于骨的质量和数量,骨质疏松会影响脊柱融合的效果。对骨质疏松患者可以采取有效的药物治疗策略,以提高骨密度并促进新的骨形成。研究表明,特立帕肽可以提高融合骨的体积和质量,并提高脊柱的融合率。特立帕肽改善骨质疏松症腰椎融合术后融合率已在许多动物模型和临床试验中得到证实。笔者就特立帕肽在骨质疏松症腰椎融合术动物模型和临床试验中的研究进展做一综述。     

绝经后女性类风湿关节炎患者骨质疏松影响因素的回顾性研究

目的 通过分析绝经后女性类风湿性关节炎(RA)患者骨密度与临床资料的相关性,探讨影响骨密度的相关因素。方法 收集64例绝经后女性RA患者一般临床资料、腰椎及股骨的平均骨密度（BMD)、骨代谢指标、实验室检查指标,根据骨密度分为骨质疏松组和非骨质疏松组,比较临床资料并分析可能影响骨密度的因素。结果 64例患者平均年龄(58. 47 ±5.81) 岁,平均病程5.5(2.0,12.0)年。骨质疏松比例为62.5% (40/64)。骨质疏松组的绝经时间、ESR、纤维蛋白原、DAS28高于非骨质疏松组,绝经年龄、体重、BMI、ALB、DMARDs及抗骨吸收药物使用率低于非骨质疏松组,病程2年以上的患者骨质疏松发病率较高,其炎症指标亦高于同病程非骨质疏松组。简单相关分析提示BMD与绝经年龄、体重、BMI、ALB正相关,与 DAS28负相关。Logistic回归分析提示绝经年龄（OR = 4. 750,95%CI：1. 30247. 327,P = 0. 018)是影响绝经后女性RA患者 BMD的独立因素。多重线性回归方程提示BMD与BMI正相关,与DAS28负相关。结论 绝经后RA患者BMD受绝经年龄、BMI、DAS28的影响。绝经年龄是影响绝经后女性RA患者BMD的独立因素。     

Adrenal effects of teriparatide in the treatment of severe postmenopausal osteoporosis

Summary  

The aim of our study was to investigate the effects of teriparatide on the hypophysis–adrenal axis in postmenopausal women. Treatment with teriparatide increased plasmatic and urinary levels of cortisol after 6 and 12 months. Our paper demonstrates a possible direct secretagogue effect of teriparatide on adrenals in osteoporotic postmenopausal women.     

类风湿关节炎患者并发骨质疏松的临床研究

目的探讨类风湿关节炎(RA)患者骨密度(BMD)的变化和骨质疏松(OP)的发生情况及其与临床指标的相关性。方法 采用双能X线骨密度仪,测量了105例RA患者的腰椎和股骨颈的骨矿含量,并同时测定关节功能、X线分期、关节压痛数和肿胀数、C反应蛋白(CRP)、抗链球菌溶血素"O"(ASO)、血清类风湿因子(RF)、血沉(ESR)、抗瓜氨酸肽抗体(CCP)、血钙、磷、碱性磷酸酶等指标。结果105例RA患者中骨质疏松的发生率是47%,RA患者中OP组与非OP组比较在年龄(P0.001),病程(P0.01),ESR(P0.05),Ca(P0.05),AKP(P0.01),关节功能(P0.05)均具有显著差异,关节压痛数和肿胀数及RF、CRP、CCP、P、ASO、X线分期等指标比较无差异。RA患者中激素组与非激素组间发生率的比较差异有显著性(X2=11.021,OR=4.189,P=0.001)。股骨颈与腰椎BMD比较显示激素组与非激素组间均具有明显差异(P0.01)。激素使用小剂量组OP发生较非小剂量组多(P0.01),激素长时间用药组较短时间用药组的OP发生多(P0.01)。RA患者中免疫抑制剂组与非免疫抑制剂组间引起OP的比较无差异(X2=0.536 OR=1.333,P=0.464)。结论 确诊为RA的患者应进行BMD检测,以了解骨矿含量,在RA治疗过程中需早期发现、早期预防骨质疏松的发生。     

阿仑膦酸钠对类风湿关节炎合并骨质疏松患者骨强度的影响

目的 分析阿仑膦酸钠对类风湿关节炎（rheumatoid arthritis,RA）合并骨质疏松（osteoporosis,OP）患者骨强度的影响。方法 选取华北理工大学附属医院骨质疏松门诊2012年6月至2020年6月诊治的OP患者120例,分为RA+OP组（60例）和OP组（60例）,且均口服阿仑膦酸钠联合骨化三醇、钙尔奇D持续12个月。比较治疗前后表征髋部力学结构强度的参数值CSA、CSMI、Z、CT和BR值（分别代表股骨颈抗轴向压缩力、骨骼刚度、抗屈曲负荷系数、皮质骨厚薄及屈曲比）、骨密度（BMD）、骨折发生率、炎性指标及临床体征。结果 经治疗6月、12月后,除RA+OP组全髋部位BMD外,OP组全髋、两组患者腰椎、股骨颈BMD、CSA、CSMI、Z、CT值均高于治疗前（P＜0.05）,BR值均低于治疗前（P＜0.05）;治疗12月后,RA+OP组股骨颈、全髋BMD、CSA、CSMI、Z值均低于OP组（P＜0.05）,腰椎BMD、CT、BR值无差异;治疗6至12月期间,RA+OP组股骨颈、全髋BMD增长率低于OP组（P＜0.05）;RA+OP组治疗前骨折发生率显著高于OP组,所有RA患者疾病活动性控制良好。结论 阿仑膦酸钠联合骨化三醇和钙剂可明显提升RA患者骨密度及髋部骨强度,提高骨骼稳定性,这种提升随疗程延长比正常骨质疏松患者缓慢。     

Relationship between duration of teriparatide therapy and clinical outcomes in postmenopausal women with osteoporosis

Summary  The extent to which fracture protection and safety varies with increasing time on teriparatide [rhPTH(1-34)] therapy is a clinically relevant unanswered question. In postmenopausal women with osteoporosis, increased duration of teriparatide versus placebo treatment was associated with a progressive decrease in the rates of nonvertebral fragility fractures and back pain. Introduction  The impact of duration of teriparatide [rhPTH(1-34)] therapy on patient outcomes is a relevant unanswered question. Methods  Postmenopausal women with osteoporosis were randomized to once-daily subcutaneous injection with placebo (N = 544), teriparatide 20 μg (TPTD20; N = 541), or teriparatide 40 μg (TPTD40; N = 552) plus calcium and vitamin D supplementation. The time to first nonvertebral fragility fracture and new or worsening back pain following treatment initiation was analyzed using Cox partial likelihood regression treating time on therapy as a linear, time-dependent covariate. Results  Compared with placebo, the relative hazard for nonvertebral fragility fractures decreased by 7.3% for each additional month of TPTD20 [hazard ratio = 0.927, 95% CI (0.876 to 0.982), p = 0.009] and by 7.6% for each additional month of TPTD40 [hazard ratio = 0.924, 95% CI (0.871 to 0.981), p = 0.009]. Clinical vertebral fractures appeared to increase over time in the placebo group and occurred primarily in the first time interval in the teriparatide treatment groups. Compared with placebo, the relative hazard of back pain was decreased by 8.3% for each additional month of TPTD20 [hazard ratio = 0.920, 95% CI (0.902 to 0.939), p < 0.001] and 8.7% for each additional month of TPTD40 [hazard ratio = 0.917, 95% CI (0.898 to 0.935), p < 0.001]. Conclusions  These findings suggest increased nonvertebral fracture protection, reduced back pain, and reduced occurrence of side effects with longer duration of teriparatide therapy. Some of these findings were presented at the 67th Annual Scientific Meeting of the American College of Rheumatology in Orlando, Florida, October 23–28, 2003 and at the 31st European Symposium on Calcified Tissues in Nice, France, June 5–9, 2004.     

Response rate of bone mineral density to teriparatide in postmenopausal women with osteoporosis

PURPOSE: It is desirable for clinicians to know what bone mineral density (BMD) response they can expect in women treated with osteoporosis therapies. The focus of this analysis was to determine what percentage of women attained a lumbar spine BMD response to teriparatide that equaled or exceeded the least significant change (LSC) value of 3%. METHODS: Data from three clinical trials involving postmenopausal women with osteoporosis were examined. The Fracture Prevention Trial was a double-blinded, placebo-controlled clinical trial examining the safety and efficacy of teriparatide 20 and 40 microg/day. The other two trials were double-blinded, head-to-head comparisons of alendronate 10 mg/day and teriparatide 20 or 40 microg/day, respectively. Only treatment-compliant women who had lumbar spine BMD measurements at all specified time points in these trials were included. For reference, we also examined the percentage of women with lumbar spine BMD responses to alendronate. Hip BMD responses that equaled or exceeded 3% were also examined. RESULTS: According to the LSC criteria, 91% of the teriparatide 20 microg/day group and 94% of the teriparatide 40 microg/day group were lumbar spine BMD responders at 18 months in the Fracture Prevention Trial. In the teriparatide 20 microg/alendronate head-to-head trial, 94% of women receiving teriparatide had a lumbar spine BMD response that equaled or exceeded the 3% criterion at 18 months compared to 75% of those receiving alendronate 10 mg/day (p < 0.01). In the teriparatide 40 microg/day group of the other head-to-head trial, 92% of women achieved the 3% criterion for the lumbar spine at 12 months compared to 69% of those receiving alendronate 10 mg/day (p < 0.01). The median 3-month change in amino-terminal extension peptide of procollagen type 1 [PINP] in women who had a lumbar spine BMD response to teriparatide at 18 months was larger than in women who did not have a lumbar spine BMD response. However, the median 3-month PINP change in lumbar spine BMD nonresponders still exceeded the LSC value of 10 microg/L. Although the percentage of teriparatide-treated women with a hip BMD response that met the 3% criterion was significantly greater than for placebo, there was no significant difference between the percentage of teriparatide 20 microg/day and alendronate 10 mg/day responders in the comparison trial. The baseline characteristics of teriparatide lumbar spine responders and nonresponders were similar. CONCLUSION: This analysis demonstrates that the vast majority of treatment-compliant postmenopausal women with osteoporosis and minimal prior bisphosphonate exposure have a lumbar spine BMD response to teriparatide that meets or exceeds the LSC. The characteristics of teriparatide responders and nonresponders were not significantly different; thus, we were unable to discern any characteristics that could be used to identify potential nonresponders.     

10年前后RA患者骨质疏松发生情况的横断面对比研究

目的横断面对比10年前后类风湿关节炎(RA)患者骨密度(BMD)的变化和骨质疏松(OP)的发生情况,分析其发生的原因。方法采用DEXA法测定2011年确诊的120例RA患者和120例正常人股骨和腰椎部位BMD,详细记录RA患者各临床及实验室资料。同时与2001年53例RA患者的BMD等资料进行横断面对比。结果①正常人、2001年RA及2011年RA患者3组间OP发生率有明显差别(15.0%、22.6%、34.2%;x2=17.218,P=0.002)。②2001年53例RA患者中,非OP患者的年龄(43.73±15.06 vs 59.25±14.75,t=3.154,P=0.003)、CRP(35.35±31.91 vs 58.74±31.81,t=2.235,P=0.030)明显低于OP组。③2011年120例RA患者中,非OP患者的年龄(48.94±11.98 vs 56.66±14.26,t=3.135,P=0.002)、HAQ(1.39±0.67 vs 1.66±0.73,t=2.067,P=0.041)明显低于OP组。④2001年发生OP与非OP的RA患者中,服用糖皮质激素的患者比例无差别(P>0.05)。2011年发生OP的RA患者中服用糖皮质激素的患者比例为73.2%(30/41),明显高于非OP患者中的53.2%(42/79)(x2=4.501,P=0.034)。⑤与2001年RA相比,2011年RA患者的DAS28更低(6.77±1.38 vs 5.97±1.30,t=3.613,P<0.0001)、关节功能更好(1:18:22:12 vs 9:57:50:3,x2=20.690,P<0.0001),但关节X线分期更差(7:26:12:8 vs 13:27:53:23,x2=13.302,P=0.004)。⑥Logistic Regression分析发现:年龄(OR=1.093,P=0.010,95%CI:1.022～1.169)和CRP(OR=1.025,P=0.037,95%CI:1.002～1.48)为2001年RA患者发生OP的危险因素;年龄(OR=1.047,P=0.012,95%CI:1.010～1.085)和HAQ评分(OR=2.040,P=0.046,95%CI:1.013～4.111)为2011年RA患者发生OP的危险因素。结论 10年前后的横断面对比研究提示,RA患者OP发生率明显高于正常人,且呈上升趋势;高龄和RA疾病活动性是两个不同年度的横断面资料中RA患者发生OP的相同的危险因素。RA患者中糖皮质激素的使用比例的增高,可能是其关节炎症表现好转,但关节X线分期更差及OP发生率更高的原因之一。     

男性类风湿关节炎患者骨量减低的相关研究

目的探讨男性类风湿关节炎(rheumatoid arthriti,RA)患者骨量减低的相关情况及合并骨质疏松的危险因素。方法收集2013年8月至2019年5月在苏州大学附属常州市肿瘤医院诊治的男性类风湿关节炎患者38例,年龄(64. 39±9. 44)岁,对照组为40例健康正常人群,年龄(63. 53±8. 14)岁。通过双光能X线骨密度仪测定正位腰椎(L1～4)及左侧股骨近端(包括FN、Troch、Ward、Total)骨密度;运用电化学发光免疫分析法检测BAP、BGP、CTX;记录RA患者的ESR、CRP、关节肿胀及压痛数、RF以及CCP等情况。分析比较两组骨密度及骨生化指标的差异,并采用单因素分析和多因素Logistic回归分析调查类风湿关节炎患者合并骨质疏松的危险因素。结果两组间年龄、体质量指数(body mass index,BMI)差异无统计学意义(P0. 05)。类风湿关节炎组左侧股骨颈、整体髋骨BMD测量值较对照组减低(P0. 05);且类风湿关节炎组骨量减少、骨质疏松发生率较对照组显著增高(P0. 05);在骨生化指标方面,类风湿关节炎组CTX水平高于对照组(P0. 05)。单因素分析显示BMI、CRP、DAS28-ESR及CTX与男性类风湿关节炎患者继发骨质疏松相关(P0. 05);多因素Logistic回归分析显示,BMI 18. 5 kg/m2(OR=0. 014),DAS28-ESR5. 1(OR=21. 433)及CTX0. 7 ng/m L(OR=25. 875)是男性类风湿关节炎继发骨质疏松的独立危险因素(P0. 05)。结论男性类风湿关节炎患者同样易合并骨质疏松的发生,BMI、DAS28及CTX等危险因素应高度重视。     

特立帕肽预防骨质疏松患者腰椎融合术后椎弓根螺钉 松动的前瞻性研究

目的观察特立帕肽在预防绝经后骨质疏松患者腰椎融合术后椎弓根螺钉松动治疗中的作用。方法 72名绝经后骨质疏松患者,诊断为腰椎退行性滑脱,随机分为3组:特立帕肽组(n=24,每日行皮下注射20μg teriparatide),双磷酸盐组(n=24,每日口服2.5mg利塞膦酸risedronate),空白对照组(n=24)。所有患者均接受腰椎管减压及1个节段后外侧融合手术,术后12月运用摄片、CT、临床体检等方法判断椎弓根螺钉松动及临床疗效。结果术后12月随访时,特立帕肽组螺钉松动率:X线摄片为7%,CT为12%;利塞膦酸组分别为13%和25%;空白对照组为14%和25%。特立帕肽组椎弓根螺钉松动率明显低于利塞膦酸组及空白对照组(P0.05),而利塞膦酸组椎弓根螺钉松动率与空白对照组无明显差别(P0.05)。末次随访时三组间临床评分无显著差异(P0.05)。结论特立帕肽能够增强腰椎椎体松质骨及椎弓根皮质骨强度,降低螺钉松动发生率。     

Comparison of osteoclast precursors in peripheral blood mononuclear cells from rheumatoid arthritis and osteoporosis patients

Osteolytic disorders cause serious problems for quality of life with aging. Osteolysis is performed by osteoclasts of the hematopoietic lineage that share some characteristics with monocytes and macrophages. As osteoclast precursors (pOCs) are present in peripheral blood, their characterization in osteolytic diseases may help us to understand risk factors. Although essential factors for osteoclastogenesis have been reported, the effective induction from pOCs in human peripheral blood mononuclear cells (PBMCs) to mature osteoclasts in culture requires further improvement. The aim of this study was development of an efficient culture system for human osteoclastogenesis and providing a simple system for the enrichment of pOCs from PBMCs. We employed coculturing of human PBMCs with a mouse stromal cell line. Significant numbers of tartrate-resistant acid phosphatase-positive (TRAP⁺) multinucleated osteoclasts (MNCs), which could resorb dentine slices, were efficiently induced in this culture condition. pOCs were enriched in an anti-CD16 antibody column-passed anti-CD14 antibody-bound cell population isolated by magnetic cell sorting. We compared the percentage of the CD14^high CD16^dull cell population, which mainly contained pOCs in PBMCs, from age-matched patients with rheumatoid arthritis (RA) and osteoporosis (OP), but it was comparable. However, the mean number of TRAP⁺ MNCs generated in cultures from PBMCs of RA was higher. In contrast, the frequency of pOCs in PBMCs from OP was relatively higher. These results suggest the characteristics of pOCs from RA and OP may be different, because single pOCs from OP gave rise to lower numbers of osteoclasts than those from RA.