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重组人生长激素用于预防前交叉韧带重建术后肌肉无力的前瞻性随机安慰剂对照试验

The Use of Recombinant Human Growth Hormone to Protect Against Muscle Weakness in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Pilot, Randomized Placebo-Controlled Trial.

机构信息

Hospital for Special Surgery, New York, New York, USA.

Department of Physiology & Biophysics, Weill Cornell Medical College, New York, New York, USA.

出版信息

Am J Sports Med. 2020 Jul;48(8):1916-1928. doi: 10.1177/0363546520920591. Epub 2020 May 26.

Abstract

BACKGROUND

Anterior cruciate ligament (ACL) tears are common knee injuries. Despite undergoing extensive rehabilitation after ACL reconstruction (ACLR), many patients have persistent quadriceps muscle weakness that limits their successful return to play and are also at an increased risk of developing knee osteoarthritis (OA). Human growth hormone (HGH) has been shown to prevent muscle atrophy and weakness in various models of disuse and disease but has not been evaluated in patients undergoing ACLR.

HYPOTHESIS

Compared with placebo treatment, a 6-week perioperative treatment course of HGH would protect against muscle atrophy and weakness in patients undergoing ACLR.

STUDY DESIGN

Randomized controlled trial; Level of evidence, 2.

METHODS

A total of 19 male patients (aged 18-35 years) scheduled to undergo ACLR were randomly assigned to the placebo (n = 9) or HGH (n = 10) group. Patients began placebo or HGH treatment twice daily 1 week before surgery and continued through 5 weeks after surgery. Knee muscle strength and volume, patient-reported outcome scores, and circulating biomarkers were measured at several time points through 6 months after surgery. Mixed-effects models were used to evaluate differences between treatment groups and time points, and as this was a pilot study, significance was set at < .10. The Cohen was calculated to determine the effect size.

RESULTS

HGH was well-tolerated, and no differences in adverse events between the groups were observed. The HGH group had a 2.1-fold increase in circulating insulin-like growth factor 1 over the course of the treatment period ( < .05; = 2.93). The primary outcome measure was knee extension strength, and HGH treatment increased normalized peak isokinetic knee extension torque by 29% compared with the placebo group ( = .05; = 0.80). Matrix metalloproteinase-3 (MMP3), which was used as an indirect biomarker of cartilage degradation, was 36% lower in the HGH group ( = .05; = -1.34). HGH did not appear to be associated with changes in muscle volume or patient-reported outcome scores.

CONCLUSION

HGH improved quadriceps strength and reduced MMP3 levels in patients undergoing ACLR. On the basis of this pilot study, further trials to more comprehensively evaluate the ability of HGH to improve muscle function and potentially protect against OA in patients undergoing ACLR are warranted.

REGISTRATION

NCT02420353 ( ClinicalTrials.gov identifier).

摘要

背景

前交叉韧带(ACL)撕裂是常见的膝关节损伤。尽管在 ACL 重建(ACLR)后进行了广泛的康复,但许多患者仍存在持续性股四头肌无力,这限制了他们成功重返赛场的机会,并且患膝关节骨关节炎(OA)的风险也增加了。人体生长激素(HGH)已被证明可预防各种废用和疾病模型中的肌肉萎缩和无力,但尚未在接受 ACLR 的患者中进行评估。

假设

与安慰剂治疗相比,6 周的围手术期 HGH 治疗可预防 ACLR 患者的肌肉萎缩和无力。

研究设计

随机对照试验;证据水平,2 级。

方法

总共招募了 19 名计划接受 ACLR 的男性患者(年龄 18-35 岁),随机分配至安慰剂(n=9)或 HGH(n=10)组。患者在手术前 1 周开始每天接受 2 次安慰剂或 HGH 治疗,并持续接受 5 周治疗。在手术后 6 个月内的多个时间点测量膝关节肌肉力量和体积、患者报告的结局评分和循环生物标志物。使用混合效应模型评估治疗组和时间点之间的差异,由于这是一项初步研究,因此显著性水平设定为 <.10。使用 Cohen 来确定效应大小。

结果

HGH 耐受良好,两组之间未观察到不良反应的差异。HGH 组在治疗期间循环胰岛素样生长因子 1 增加了 2.1 倍( <.05; = 2.93)。主要结局指标为膝关节伸肌力量,与安慰剂组相比,HGH 治疗使膝关节等速向心伸肌峰值扭矩的归一化峰值增加了 29%( =.05; = 0.80)。基质金属蛋白酶 3(MMP3)被用作软骨降解的间接生物标志物,HGH 组降低了 36%( =.05; = -1.34)。HGH 似乎与肌肉体积或患者报告的结局评分的变化无关。

结论

HGH 改善了 ACLR 患者的股四头肌力量并降低了 MMP3 水平。基于这项初步研究,需要进一步的试验来更全面地评估 HGH 改善肌肉功能的能力,并有可能预防 ACLR 患者的 OA。

登记

NCT02420353(ClinicalTrials.gov 标识符)。

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