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阿仑膦酸钠联合钙尔奇D对糖尿病性骨质疏松症患者骨密度和骨代谢指标影响及疗效观察

杨群菲 张征宇




[摘要] 目的 探討阿仑膦酸钠联合钙尔奇D对糖尿病性骨质疏松症患者骨密度、骨代谢指标的影响及疗效观察。 方法 选取2017年1月~2018年4月在该院就诊的90例2型糖尿病性骨疏松症患者,随机分为观察组(n=45)与对照组(n=45)。两组患者均予以口服降糖药物或胰岛素控制血糖,并予以钙尔奇D 600 mg/次,1次/d,餐前口服。观察组加用阿仑膦酸钠70 mg/次,每周1次,口服,疗程6个月。观察两组治疗前和治疗6个月后骨密度、血清骨代谢指标[骨钙素N端中分子片段(N-MID)和骨特异性碱性磷酸酶(BALP)]水平的变化,并比较其临床疗效。结果 治疗6个月后,两组股骨颈、股骨粗隆及华氏三角区骨密度值较前均明显改善(P<0.05或P<0.01),且观察组改善幅度较对照组更明显(P<0.05);两组血清N-MID指标较前明显上升,BALP指标较前明显下降(P<0.05或P<0.01),且观察组变化幅度优于对照组(P<0.05);同时观察组临床总有效率(95.56%)明显高于对照组(82.22%)(χ2=4.05,P<0.05)。 结论 阿仑膦酸钠联合钙尔奇D治疗糖尿病性骨质疏松症的疗效较确切,能明显改善其疼痛症状,增加其骨密度值,作用机制可能与其能升高血清N-MID指标,降低BALP指标,抑制骨吸收和促进骨形成密切相关。

[关键词] 2型糖尿病;骨质疏松症;阿仑膦酸钠;钙尔奇D;骨密度;骨代谢指标

[中图分类号] R587.1          [文献标识码] B          [文章编号] 1673-9701(2020)03-0126-04

[Abstract] Objective To investigate the effect of alendronate sodium combined with Caltrate D on bone mineral density and bone metabolism in patients with diabetic osteoporosis and efficacy observation. Methods 90 cases of type 2 diabetic osteoporosis in the hospital from January 2017 to April 2018 were enrolled. The patients were randomLy divided into observation group (n=45) and control group (n=45). Both groups of patients were given oral hypoglycemic drugs or insulin to control blood sugar, and also given Caltrate D 600 mg/time, 1 time/d, oral before meals. The observation group was treated with alendronate sodium 70 mg/time, once a week, orally, for 6 months. Changes in the levels of bone mineral density, serum bone metabolism index (molecular fragment of osteocalcin N-terminus) and bone-specific alkaline phosphatase (BALP) before treatment and at 6 months after treatment, and their clinical efficacy was compared. Results After 6 months of treatment, the bone mineral density of the femoral neck, femur trochanter and Fahrenheit triangle were significantly improved(P<0.05 or P<0.01). And the improvement of observation group was more obvious than that of the control group (P<0.05). The serum N-MID index of the two groups was better than that before (P<0.05). BALP indicator was significantly lower than that before(P<0.05 or P<0.01). And the change of the observation group was better than that of the control group (P<0.05). At the same time, the clinical total effective rate of the observation group(95.56%) was significantly higher than that of the control group(82.22%) (χ2=4.05, P<0.05). Conclusion Lendronate sodium combined with Caltrate D in the treatment of diabetic osteoporosis has exact efficacy, which can significantly improve the pain symptoms, increase its bone density value. The mechanism of action may be closely related to its ability to raise serum N-MID, reduce BALP, inhibit bone resorption and promote bone formation.

[Key words] Type 2 diabetes; Osteoporosis; Alendronate sodium; Caltrate D; Bone mineral density; Bone metabolism index

糖尿病是臨床较常见的内分泌系统疾病,长期血糖控制不佳可并发骨质疏松,骨质疏松症是糖尿病较常见且严重的并发症之一,如不及时治疗可引起骨疼痛和功能障碍,严重可致残[1]。糖尿病性骨质疏松症患者随着病程的延长会出现骨代谢的变化,骨吸收增加,骨形成减低及骨密度的改变[2]。以往临床上常采用钙剂治疗糖尿病性骨质疏松症,但单纯的补钙治疗效果欠理想。阿仑膦酸钠(福善美)是常用的双膦酸盐类抗骨质疏松药,临床上常与钙剂合用治疗骨质疏松症,取得了较好的效果,但其对患者骨密度和骨代谢指标的影响国内外报道较少[4,5]。本研究观察了阿仑膦酸钠联合钙尔奇D对糖尿病性骨质疏松症患者骨密度和骨代谢指标的影响及疗效,现报道如下。

1 资料与方法

1.1 一般资料

选取2017年1月~2018年4月在我院骨科门诊治疗的2型糖尿病性骨质疏松症患者90例。纳入标准[6]:(1)符合中华医学会制定的《中国2型糖尿病防治指南(2007版)》中2型糖尿病的诊断标准[7];(2)符合1994年WHO推荐的骨质疏松症的诊断标准[8]。排除标准[9]:(1)合并骨折、骨肿瘤或骨结核等骨痛疾病;(2)长期服用激素类或肾上腺、甲状腺及甲状旁腺等其他影响骨代谢的药物。按照随机数字表法分为观察组与对照组的各45例。两组性别、年龄、BMI指数、空腹血糖、糖化血红蛋白及血钙水平等情况均衡可比(P>0.05)。见表1。

1.2 治疗方法

两组均予以口服降糖药物或胰岛素控制血糖,并予以钙尔奇D(惠氏制药有限公司,规格600 mg/片,国药准字H10950029)600 mg/次,1次/d,餐前口服。观察组加用阿仑膦酸钠片(杭州默沙东制药有限公司,规格70 mg/片,国药准字J20130085)70 mg/次,每周1次,口服,疗程为6个月。

1.3 观察指标

观察两组治疗前和治疗6个月后骨密度、血清骨代谢指标[骨钙素N端中分子片段(N-MID)和骨特异性碱性磷酸酶(BALP)]指标的变化,并比较其临床疗效。

1.3.1 骨密度测定  采用双能X线吸收法测定股骨颈、股骨粗隆及华氏三角区骨密度值。

1.3.2 骨代谢指标测定  采晨空腹静脉血约5 mL,常规离心提取血清,存于-70℃冰箱。采用酶联免疫吸附试验(ELISA)法测定血清N-MID与BALP指标。

1.3.3 疗效评估标准[10]  显效:治疗后疼痛基本消失,骨密度较前明显上升;有效:治疗后疼痛较前好转,骨密度较前有所改善;无效:治疗后疼痛与骨密度较前无明显改善或反而较前加重。总有效包括显效和有效。

1.4 统计学方法

采用SPSS18.0软件,计量资料以均数±标准差(x±s)表示,采用t检验,计数资料采用χ2检验,P<0.05为差异有统计学意义。

2 结果

2.1 两组治疗前后骨密度值比较

治疗前两组股骨颈、股骨粗隆及华氏三角区骨密度值比较,差异无统计学意义(P>0.05),治疗6个月后,两组股骨颈、股骨粗隆及华氏三角区骨密度值较前均明显改善(P<0.05或P<0.01),且治疗后观察组改善幅度较对照组更明显(P<0.05)。见表2。

2.2 两组血清N-MID与BALP指标比较

治疗前两组血清血清N-MID与BALP指标比较差异无统计学意义(P>0.05)。治疗6个月后,两组血清N-MID指标较前明显上升,BALP指标较前明显下降(P<0.05或P<0.01),且治疗后观察组变化幅度明显优于对照组(P<0.05)。见表3。

2.4 两组治疗后疗效比较

治疗6个月后,观察组临床总有效率(95.56%)明显高于对照组(82.22%)(χ2=4.05,P<0.05)。见表4。

3 讨论

糖尿病性骨质疏松症属于继发性,临床病理特征是以骨量下降和骨组织微结构发生破坏使得骨脆性增加。糖尿病性骨质疏松症的早期临床症状表现一般不明显,随着病情的加重,临床上多出现经常性腰背部、髋骨部疼痛或严重时出现持续性肌肉钝痛,严重者可导致腰椎、髋部等病理性骨折,严重影响其生活质量[11-13]。糖尿病性骨质疏松症是糖尿病患者骨骼系统上出现的慢性严重并发症,是引起长期严重骨痛和功能障碍的主要原因。糖尿病性骨质疏松症的发病机制较复杂,大多数学者认为其原因是血糖升高引起的渗透性利尿,降低钙、磷、镁浓度,引起继发性甲状旁腺激素分泌增加,致使溶骨增加,骨量明显减少;加上糖尿病严格控制饮食,钙摄入减少,骨生长所需营养物质缺乏,骨中钙质沉积减少[14-16]。

补钙是目前治疗糖尿病性骨质疏松症最常用方法,虽可有效缓解患者的骨密度和骨质量的流失,但单纯补钙治疗由于不能抑制骨吸收,减少骨钙吸收环节中的流失及破坏,往往疗效欠佳,患者骨质疏松症状难以快速纠正[17]。钙尔奇D是临床常用的补钙药物,其主要的作用在于有利肠道对磷、钙的吸收,稳定骨骼内的环境状况,有助于骨骼钙化和骨矿化,从而增加骨量[18,19]。阿仑膦酸钠是一种新型第三代双磷酸盐类骨代谢调节剂,其与骨内羟磷灰石有强亲和力,能抑制破骨细胞活性促进其凋亡以避免骨转化,有效抑制骨吸收,从而提高骨密度,加快骨形成[20-22]。谢树[23]研究发现阿仑膦酸钠联合钙尔奇D治疗糖尿病骨质疏松症疗效确切,能明显减轻疼痛症状及增加骨密度。本研究发现治疗6个月后,观察组患者的股骨颈、股骨粗隆及华氏三角区骨密度值改善幅度较对照组更明显;观察组患者血清N-MID指标上升幅度及BALP指标下降幅度明显优于对照组,且观察组临床总有效率明显高于对照组。提示阿仑膦酸钠联合钙尔奇D治疗糖尿病性骨质疏松症的疗效较确切,能明显改善其疼痛症状,增加其骨密度值,作用机制可能与其能升高血清N-MID指标降低BALP指标,抑制骨吸收和促进骨形成密切相关。我们推测2型糖尿病骨质疏松症在常规补钙治疗基础上加用阿仑膦酸钠治疗能通过有效地抑制破骨细胞的活性,促进其发生凋亡,可降低血清骨吸收标志物BALP水平,升高血清骨形成标志物N-MID水平,使得骨形成量明显多于骨吸收量,从而提高骨密度,增加患者骨量,减少患者的疼痛症状[24]。

總之,阿仑膦酸钠联合钙尔奇D治疗糖尿病性骨质疏松症的疗效较确切,能明显改善其疼痛症状,增加其骨密度值,作用机制可能与其能升高血清N-MID指标,降低BALP指标,抑制骨吸收和促进骨形成密切相关。

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(收稿日期:2019-04-25)

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