关键词: Addison’s disease Bone turnover markers Glucocorticoid substitution Osteoporosis Sclerostin

Mesh : Humans Bone Density / drug effects Female Addison Disease / drug therapy blood Male Middle Aged Glucocorticoids / adverse effects administration & dosage Adult Aged Osteoporosis / blood Biomarkers / blood Hormone Replacement Therapy Peptides / blood Osteocalcin / blood Adaptor Proteins, Signal Transducing Peptide Fragments / blood Procollagen / blood Alkaline Phosphatase / blood Bone Remodeling / drug effects Collagen Type I / blood Genetic Markers Absorptiometry, Photon Hydrocortisone / blood Intercellular Signaling Peptides and Proteins / blood Lumbar Vertebrae / diagnostic imaging drug effects Young Adult

来  源:   DOI:10.1007/s12020-024-03709-3

Abstract:
OBJECTIVE: Patients receiving long-term glucocorticoid (GC) treatment are at risk of osteoporosis, while bone effects of substitution doses in Addison\'s disease (AD) remain equivocal. The project was aimed to evaluate serum bone turnover markers (BTMs): osteocalcin, type I procollagen N-terminal propeptide (PINP), collagen C-terminal telopeptide (CTX), sclerostin, DKK-1 protein, and alkaline phosphatase (ALP) in relation to bone mineral density (BMD) during GC replacement.
METHODS: Serum BTMs and hormones were assessed in 80 patients with AD (22 males, 25 pre- and 33 postmenopausal females) on hydrocortisone (HC) substitution for ≥3 years. Densitometry with dual-energy X-ray absorptiometry covered the lumbar spine (LS) and femoral neck (FN).
RESULTS: Among BTMs, only PINP levels were altered in AD. BMD Z-scores remained negative except for FN in males. Considering T-scores, osteopenia was found in LS in 45.5% males, 24% young and 42.4% postmenopausal females, while osteoporosis in 9.0%, 4.0% and 21.1%, respectively. Lumbar BMD correlated positively with body mass (p = 0.0001) and serum DHEA-S (p = 9.899 × 10-6). Negative correlation was detected with HC dose/day/kg (p = 0.0320), cumulative HC dose (p = 0.0030), patient\'s age (p = 1.038 × 10-5), disease duration (p = 0.0004), ALP activity (p = 0.0041) and CTX level (p = 0.0105). However, only age, body mass, ALP, serum CTX, and sclerostin remained independent predictors of LS BMD.
CONCLUSIONS: Standard HC substitution does not considerably accelerate BMD loss in AD patients and their serum BTMs: CTX, osteocalcin, sclerostin, DKK-1, and ALP activity remain within the reference ranges. Independent predictors of low lumbar spine BMD, especially ALP activity, serum CTX and sclerostin, might be monitored during GC substitution.
摘要:
目的:接受长期糖皮质激素(GC)治疗的患者有患骨质疏松症的风险,而替代剂量对阿狄森氏病(AD)的骨骼影响仍然模棱两可。该项目旨在评估血清骨转换标志物(BTMs):骨钙蛋白,I型前胶原N端前肽(PINP),胶原蛋白C末端端肽(CTX),硬化蛋白,DKK-1蛋白,和碱性磷酸酶(ALP)与GC替代过程中的骨密度(BMD)有关。
方法:评估了80例AD患者的血清BTM和激素(22例男性,25名绝经前和33名绝经后女性)接受氢化可的松(HC)替代治疗≥3年。采用双能X线吸收法的光密度测定覆盖腰椎(LS)和股骨颈(FN)。
结果:在BTM中,AD中仅PINP水平发生改变。除男性FN外,BMDZ得分仍为阴性。考虑到T分数,在LS中,有45.5%的男性发现骨质减少,24%的年轻人和42.4%的绝经后女性,而骨质疏松占9.0%,4.0%和21.1%,分别。腰椎BMD与体质量(p=0.0001)和血清DHEA-S(p=9.899×10-6)呈正相关。与HC剂量/天/kg呈负相关(p=0.0320),累积HC剂量(p=0.0030),患者年龄(p=1.038×10-5),疾病持续时间(p=0.0004),ALP活性(p=0.0041)和CTX程度(p=0.0105)。然而,只有年龄,体重,ALP,血清CTX,硬化蛋白仍然是LSBMD的独立预测因子。
结论:标准HC替代不会显著加速AD患者及其血清BTM的BMD损失:CTX,骨钙蛋白,硬化蛋白,DKK-1和ALP活性保持在参考范围内。低腰椎BMD的独立预测因子,尤其是ALP活性,血清CTX和硬化蛋白,可能会在GC替换过程中进行监控。
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