盐酸氨基葡萄糖联合阿仑膦酸钠治疗老年膝骨关节炎的疗效及不良反应情况

目的 分析盐酸氨基葡萄糖联合阿仑膦酸钠治疗老年膝骨关节炎的疗效及不良反应情况.方法 选取本院2012年11月至2016年7月收治的70例老年膝骨关节炎患者,采用随机数字表法分为观察组(n=35)和对照组(n=35).两组均给予盐酸氨基葡萄糖治疗,观察组加用阿仑膦酸钠治疗,两组治疗周期均为7周.比较两组总有效率、治疗前和治疗7周后丙二醛(MDA)、超氧化物歧化酶(SOD)、lequesne指数评分及不良反应发生率.结果 观察组总有效率为88.57％(31/35),高于对照组的65.71％(23/35),差异具有统计学意义(x 2=5.185,P＜0.05);观察组治疗7周后MDA为(4.42±1.52) nmol/ml,SOD为(131.15±16.68) nU/ml,优于对照组[(6.87±1.84) nmol/ml、(112.24±14.24)nU/ml],差异具有统计学意义(P＜0.05);观察组治疗7周后行走能力、关节晨僵、关节肿胀、关节压痛、运动痛、休息痛评分分别为(1.02±0.42)分、(0.40±0.14)分、(0.36±0.11)分、(0.72±0.24)分、(1.16±0.31)分、(0.33±0.14)分,低于对照组[(1.87±0.49)分、(0.88±0.25)分、(0.72±0.26)分、(1.17±0.25)分、(2.00±0.49)分、(1.78±0.26)分],差异具有统计学意义(P＜0.05);对照组不良反应发生率8.57％(3/35),观察组14.29％(5/35),差异无统计学意义(P＞0.05).结论 盐酸氨基葡萄糖联合阿仑膦酸钠治疗老年膝骨关节炎可显著提高机体抗氧化能力,有效改善患者膝关节功能,安全性高,值得推广应用.     

Combined treatment with a traditional Chinese medicine, Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) and alendronate improves bone microstructure in ovariectomized rats

Ethnopharmacological relevance

Hachimi-jio-gan is one of the most common recipes in traditional Chinese, Japanese and Korean medicines and has been used for preventing and treating various diseases associated with aging, including osteoporosis.

Aim of the study

The present study was performed to examine the combined effects of a traditional Chinese medicine, Hachimi-jio-gan (HJG) and antiresorptive agent, alendronate (ALN) on ovariectomy-induced bone loss in rats.

Materials and methods

Six-month-old female Sprague-Dawley rats were underwent ovariectomy (OVX) or sham operation. Eight weeks later, the OVX rats were treated either with HJG or ALN alone or in combination of both. The skeletal response was evaluated using micro-computed tomography (micro-CT), image analysis software, and biochemical markers.

Results

This study demonstrated that treatment with HJG or ALN alone increased trabecular bone volume and bone mineral density (BMD), and partially improved bone microstructure of the proximal tibia and vertebra in OVX rats. Treatment with ALN to OVX rats resulted in significant reduction in both bone resorption and bone formation. Treatment with HJG to OVX rats inhibited bone resorption, with no marked effects on bone formation. Combined treatment of HJG and ALN significantly improved trabecular bone mass and bone microstructure, compared with either agent alone.

Conclusions

We conclude that the combined treatment with HJG and ALN has beneficial effects on trabecular bone mass, improving the structural properties of both tibia and vertebra in OVX rats.     

Clinical results of alendronate monotherapy and combined therapy with menatetrenone (VitK2) in postmenopausal RA patients

Objectives

We aimed to evaluate the clinical efficacy of monotherapy with alendronate and combined therapy with alendronate and menatetrenone (vitamin K2 [VitK2]) in postmenopausal rheumatoid arthritis (RA) patients with osteoporosis or osteopenia.

Methods

Sixty-two postmenopausal RA patients with untreated osteoporosis or osteopenia (lumbar spine bone density ≤80 % of young adult mean [YAM]) were enrolled: 39 had abnormal serum undercarboxylated osteocalcin (ucOC) levels (>4.5 ng/mL) and received combined therapy with alendronate (35 mg/week) and VitK₂ (45 mg/day) (ALN + K group); 23 had normal ucOC levels (≤4.5 ng/mL) and received alendronate monotherapy (35 mg/week) (ALN group). The clinical results for the 57 patients in both groups were evaluated after 1-year treatment.

Results

The mean baseline/follow-up (FU) lumbar spine bone density (%YAM) values were 73.0/76.8 % (P < 0.01) in the ALN + K group and 77.0/80.3 % (P < 0.01) in the ALN group; a significant increase was shown in both groups. Mean proximal femoral bone density values at baseline/FU were 71.4/73.8 (P < 0.01) in the ALN + K group and 71.4/71.6 % (not significant; NS) in the ALN group; a significant increase was shown in the ALN + K group only. Serum ucOC levels were normalized in the ALN + K group at FU. At FU, bone metabolism markers [bone-specific alkaline phosphatase (BAP) and N-terminal cross-linked telopeptides of type I collagen] were decreased in both groups. One patient in the ALN + K group and three in the ALN group suffered new fractures.

Conclusions

Combined therapy with alendronate and VitK₂ decreases bone metabolism marker levels and serum ucOC levels, and increases lumbar spine and femoral neck bone density in postmenopausal RA patients with abnormal ucOC levels and osteoporosis or osteopenia.     

Sialoglycoprotein isolated from eggs of Carassius auratus promotes fracture healing in osteoporotic mice

In this study, open tibial fracture surgery was performed on mice with ovariectomy induced osteoporosis to investigate the effect of a treatment with sialoglycoprotein isolated from Carassius auratus eggs (Ca-SGP) on fracture healing. Dynamic histological analysis showed that Ca-SGP promoted the generation of cartilage callus on day 5 post-surgery, then facilitated the transformation of the cartilage callus to bony callus on days 11 and 24 post-surgery, and enhanced the remodeling of bony callus on 35 day post-surgery. Moreover, Ca-SGP significantly decreased the secretion of TNF-α and IL-1β in serum on day 5 post-surgery, thus inhibiting the negative spread of the inflammatory reaction. On day 11 post-surgery, Ca-SGP clearly decreased the serum level and the mRNA expression of Aggrecan but also increased the secretion and the expression of VEGF and MMP13, thus promoting the degradation of the cartilage matrix and vascular invasion. On day 24 post-surgery, Ca-SGP remarkably increased the mRNA expression of osteogenesis markers Col1a and OCN, and increased callus BV/TV and Tb.N, this facilitating the formation of woven bone. On day 35 post-surgery, Ca-SGP enhanced the transformation of woven bone into lamellar bone and improved the callus biomechanical property. In conclusion, Ca-SGP promoted fracture healing in osteoporotic mice by accelerating endochondral ossification.     

Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial

Objective

To assess the efficacy and safety of 18 months of subcutaneous abaloparatide (ABL-SC) or placebo (PBO) followed by 6 months of alendronate (ALN) (preplanned interim analysis).

Direct immunization of the abomasum or rectum of goats induces local lymph node responses against Haemonchus contortus mucosal antigens

We investigated several methods to immunize the abomasum (fourth and gastric stomach) of kid goats by direct (abomasal) or distal (rectal or nasal) routes utilizing mucosal antigens isolated from the abomasal parasite, Haemonchus contortus. Direct (ultrasound guided), immunization of the abomasal mucosa together with rectal immunization established lymphocyte proliferation responses in abomasal lymph nodes (ALNs), while distal methods, alone, produced equivocal results. The differential responses (cellular and antibody) induced by alternative immunization methods demonstrated an experimental system that can facilitate advances in mucosal immunization against H. contortus and other gastrointestinal pathogens of food animals.     

Breastfeeding for Primary Prevention of Stroke

A recent review by Zhang et al. published in the “Journal of the National Medical Association” focused on the major and emerging strategies for the prevention of stroke.We would highlight the evolving role of breastfeeding as an efficient intervention in primary prevention of such cardiovascular disease, including in black women.     

Preoperative prediction nomogram based on primary tumor miRNAs signature and clinical‐related features for axillary lymph node metastasis in early‐stage invasive breast cancer

More than half patients who undergo axillary lymph node (ALN) surgery are ALN negative in early‐stage invasive breast cancer (EIBC). Thus, to avoid excessive treatment, we aim to establish and validate a novel nomogram model for the preoperative diagnosis of ALN status in patients with EIBC. In total, 864 patients with EIBC from two independent centers were enrolled in our study. For the discovery set, miRNAs expression profiling with functional roles in ALN metastasis was discovered by microarray analysis and validated by quantitative polymerase chain reaction (PCR). For the training and validation cohorts, we used PCR to quantify miRNAs expression in a model development cohort and assessed miRNAs signature in an internal validation cohort and external independent validation cohort. Multivariable logistic regression analyses were used to establish a nomogram model for the likelihood of ALN metastasis from miRNAs signature and clinical variables. A signature of nine‐miRNA was significantly associated with ALN status. The predictive ability of our nomogram that included miRNAs signature and clinical‐related variables (age, tumor size, tumor location and axillary ultrasound‐reported ALN status) was significantly greater than a model that only considered clinical‐related factors (concordance index: 0.856, 0.796) and also performed well in the two validation cohorts (concordance index: 0.841, 0.747). Our nomogram is a reliable prediction method that can be conveniently used to preoperatively predict ALN status in patients with EIBC. Therefore, after further confirmation in prospective and multicenter clinical trial, omission of axillary surgery may be feasible for some patients with EIBC in the future.     

PLGA‐linked alendronate enhances bone repair in diaphysis defect model

Alendronate (ALN) is known as an anti‐resorptive drug for the treatment of osteoporosis. Recently, ALN was found to stimulate osteogenic differentiation in mesenchymal stem cells and enhance new bone formation in calvarial bone defects. Previous in vitro and in vivo studies found that the effective concentration of ALN was approximately 1–10   μm . In the present study, a poly (lactic‐co‐glycolic acid) (PLGA) cross‐linked ALN (PLGA‐ALN) with a short‐term controlled‐release property for local application to enhance bone repair was developed. An in vitro drug‐release kinetic test showed that PLGA‐ALN microspheres released an effective concentration (50–100 nm ) of ALN for 9 days. The effect of PLGA‐ALN on bone repair was tested in a rat femoral bone defect model. The biomechanical study results showed that the maximal strength, stiffness and energy absorption were significantly increased in the PLGA‐ALN group compared with the PLGA group. The microstructure of the newly formed bone at the defect site was analysed using microcomputed tomography. The PLGA‐ALN group significantly improved the trabecular bone volume at the defect site compared with the PLGA group. The fibril collagen and immunolocalized bone morphogenetic protein 2 were evident in the newly formed trabecular bone in the PLGA‐ALN group. Local use of newly developed PLGA‐ALN‐enhanced bone repair was attributable to increasing bone matrix formation, which improved the ultrastructure of the newly formed bone and thus increased the biomechanical properties of the repaired bone. It is suggested that PLGA‐ALN may be a potential bone graft substitute to enhance bone repair. Copyright © 2016 John Wiley & Sons, Ltd.