■前列腺癌(PC)的雄激素剥夺疗法(ADT)对肌肉骨骼系统和身体成分具有实质性的负面影响。许多研究集中在ADT对区域骨矿物质密度(aBMD)的影响,但是aBMD不能捕获骨强度和骨折风险的关键决定因素,例如体积骨密度(vBMD),几何图形,皮质厚度和孔隙率,小梁参数和重塑率。更多的专业成像技术,如高分辨率外周定量计算机断层扫描(HR-pQCT),已可用于评估这些参数。尽管以前已经证明,接受ADT的男性会发生骨骼微结构恶化,ANTELOPE研究的目的是检查骨骼微观结构的纵向变化以及一系列肌肉骨骼参数和虚弱,比较男性与PC单独接受ADT或ADT加化疗治疗转移性疾病,有一个健康的年龄匹配的人口。
■我们使用HR-pQCT来研究12个月的ADT对vBMD和微观结构参数的影响,辅以对aBMD变化的评估,血清骨转换标志物,性激素,身体成分,握力,身体和肌肉功能,虚弱和骨折的风险。我们研究了三组:A组-由于开始ADT而患有局部/局部晚期PC的男性;B组-新诊断为激素敏感的男性,转移性PC,与多西他赛化疗和类固醇一起开始ADT;C组-健康,年龄匹配的男人。主要终点是桡骨远端vBMD的变化(A组与C组)。
九十九名参与者接受了基线研究评估(A组:n=38,B组:n=30,C组:n=31)。75名参与者完成了所有研究评估(A组(29),B组(18)C组(28)。在基线,A组和C组的BMD或骨微结构结局均无显著差异.ADT治疗12个月后,与C组(平均12个月变化=-1.3mgHA/cm3,-0.4%)相比,A组(平均12个月变化=-13.7mgHA/cm3,-4.1%)的vBMD下降幅度更大(p<0.001),展示主要成果的成就。当比较B组(平均12个月变化=-13.5mgHA/cm3,-4.3%)和C组之间的vBMD变化时,观察到类似的效果。这些变化反映在aBMD中。ADT导致微观结构恶化,估计的骨强度降低和骨转换增加。有证据表明,在接受ADT治疗的患者中,总脂肪量和躯干脂肪量增加,上肢质量明显下降,随着BMI的增加。两个ADT组的虚弱增加,物理性能和力量下降,相对于健康对照组。
■研究表明,ADT对vBMD有深远的影响,aBMD,骨微观结构和强度以及身体组成,以及对虚弱和身体表现的重要影响。虽然DXA仍然是一个有价值的工具(aBMD的变化与vBMD的变化幅度相同),HR-pQCT应考虑用于评估抗雄激素和其他新型PC疗法对骨骼的影响,以及骨靶向药物的潜在缓解。
UNASSIGNED: Androgen Deprivation Therapy (
ADT) for prostate cancer (PC) has substantial negative impacts on the musculoskeletal system and body composition. Many studies have focused on the effects of
ADT on areal bone mineral density (aBMD), but aBMD does not capture key determinants of bone strength and fracture risk, for example volumetric bone density (vBMD), geometry, cortical thickness and porosity, trabecular parameters and rate of remodelling. More specialist imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) have become available to evaluate these parameters. Although it has previously been demonstrated that bone microarchitectural deterioration occurs in men undergoing
ADT, the aim of the ANTELOPE study was to examine longitudinal changes in bone microstructure alongside a range of musculoskeletal parameters and frailty, comparing men with PC receiving ADT alone or
ADT plus chemotherapy for metastatic disease, with a healthy age-matched population.
UNASSIGNED: We used HR-pQCT to investigate effects of 12 months of ADT on vBMD and microstructural parameters, complemented by assessment of changes in aBMD, serum bone turnover markers, sex hormones, body composition, grip strength, physical and muscle function, frailty and fracture risk. We studied three groups: Group A - men with localised/locally advanced PC due to commence
ADT; Group B - men with newly diagnosed hormone-sensitive, metastatic PC, starting ADT alongside docetaxel chemotherapy and steroids; Group C - healthy, age-matched men. The primary endpoint was change in vBMD (Group A vs Group C) at the distal radius.
UNASSIGNED: Ninety-nine participants underwent baseline study assessments (Group A: n = 38, Group B: n = 30 and Group C: n = 31). Seventy-five participants completed all study assessments (Group A (29), Group B (18), Group C (28). At baseline, there were no significant differences between Groups A and C in any of the BMD or bone microstructure outcomes of interest. After 12 months of ADT treatment, there was a significantly greater decrease in vBMD (p < 0.001) in Group A (mean 12-month change = -13.7 mg HA/cm3, -4.1 %) compared to Group C (mean 12-month change = -1.3 mg HA/cm3, -0.4 %), demonstrating achievement of primary outcome. Similar effects were observed when comparing the change in vBMD between Group B (mean 12-month change = -13.5 mg HA/cm3, -4.3 %) and Group C. These changes were mirrored in aBMD. ADT resulted in microstructural deterioration, a reduction in estimated bone strength and an increase in bone turnover. There was evidence of increase in total fat mass and trunkal fat mass in ADT-treated patients, with marked loss in upper limb mass, along with BMI gain. Frailty increased and physical performance and strength deteriorated in both ADT groups, relative to the healthy control group.
UNASSIGNED: The study showed that ADT has profound effects on vBMD, aBMD, bone microstructure and strength and body composition, and important impacts on frailty and physical performance. Whilst DXA remains a valuable tool (changes in aBMD are of the same magnitude as those observed for vBMD), HR-pQCT should be considered for assessing the effects of anti-androgens and other newer PC therapies on bone, as well as potential mitigation by bone-targeted agents.