White Helen D, Ahmad Aftab M, Durham Brian H, Peter Rajesh, Prabhakar V Karthik B, Corlett Pamela, Vora Jiten P, Fraser William D
Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Liverpool, United Kingdom.
J Bone Miner Res. 2007 Nov;22(11):1798-807. doi: 10.1359/jbmr.070715.
AGHD is associated with osteoporosis. We examined PTH circadian rhythmicity and PTH target-organ sensitivity in 23 patients with AGHD with low BMD and 20 patients with AGHD with normal BMD. Patients with low BMD had a blunted nocturnal rise in PTH concentration and reduced PTH target-organ sensitivity compared with patients with normal BMD; these factors may be important in the pathogenesis of AGHD-related osteoporosis.
Adult growth hormone deficiency (AGHD) is associated with decreased BMD. Reduced parathyroid gland sensitivity to changes in calcium and reduced PTH target-organ sensitivity may underlie the pathogenesis of AGHD-related osteoporosis. A blunted nocturnal PTH rise has been reported in AGHD and may contribute to the reduction in BMD. We examined the difference in PTH concentration and markers of bone metabolism in patients with AGHD with normal and low BMD.
Forty-three patients with AGHD consented to the study. Twenty-five patients were growth hormone (GH) naïve (GH-N, 13 had BMD femoral neck or lumbar spine T-score < -1.0), and 18 patients had received GH for >2 yr (GH-R, 10 had BMD T-score < -1.0). Patients were hospitalized for 24 h, where blood samples were collected every 0.5 h and urine samples were collected every 3 h for PTH, calcium, phosphate, NcAMP, 1,25-dihydroxyvitamin D [1,25(OH)(2)D], type-I collagen beta C-telopeptide (betaCTX), and procollagen type-I amino-terminal propeptide (PINP). Serum calcium was adjusted for albumin (ACa).
Low BMD GH-N and GH-R patients exhibited a reduced nocturnal rise in PTH concentration compared with patients with normal BMD (p < 0.001). GH-N low BMD patients had significantly higher 24-h mean PTH (p < 0.001) than GH-N normal BMD patients, with significantly lower 24-h mean NcAMP, ACa, and 1,25(OH)(2)D (p < 0.01), suggesting a reduction in renal PTH sensitivity. GH-R low BMD patients had significantly lower 24-h mean PTH, NcAMP, ACa, and 1,25(OH)(2)D (p < 0.01) than GH-R normal BMD patients, suggesting reduced renal PTH action. Lower PTH concentration in the presence of lower ACa may reflect reduced sensitivity of the parathyroid calcium-sensing receptor to changes in ACa concentration in the GH-R low BMD patients.
Low BMD in GH-N and GH-R AGHD patients may be a consequence of abnormalities in PTH circadian rhythmicity together with reduced parathyroid gland and target-organ sensitivity. Further studies are needed to determine the potential benefit of therapeutic manipulation of PTH rhythmicity and sensitivity on BMD.
成人生长激素缺乏症（AGHD）与骨质疏松症相关。我们对23例骨密度低的AGHD患者和20例骨密度正常的AGHD患者的甲状旁腺激素（PTH）昼夜节律性及PTH靶器官敏感性进行了研究。与骨密度正常的患者相比，骨密度低的患者夜间PTH浓度升高不明显，且PTH靶器官敏感性降低；这些因素可能在AGHD相关骨质疏松症的发病机制中起重要作用。
成人生长激素缺乏症（AGHD）与骨密度降低有关。甲状旁腺对钙变化的敏感性降低以及PTH靶器官敏感性降低可能是AGHD相关骨质疏松症发病机制的基础。据报道，AGHD患者夜间PTH升高不明显，这可能导致骨密度降低。我们研究了骨密度正常和低的AGHD患者PTH浓度及骨代谢标志物的差异。
43例AGHD患者同意参与本研究。25例患者未接受过生长激素（GH）治疗（GH初治组，13例股骨颈或腰椎骨密度T值＜-1.0），18例患者接受GH治疗＞2年（GH治疗组，10例骨密度T值＜-1.0）。患者住院24小时，每0.5小时采集一次血样，每3小时采集一次尿样，检测PTH、钙、磷、NcAMP、1,25-二羟维生素D [1,25(OH)₂D]、I型胶原β C末端肽（βCTX）和I型前胶原氨基端前肽（PINP）。血清钙校正白蛋白后为校正钙（ACa）。
与骨密度正常的患者相比，GH初治组和GH治疗组骨密度低的患者夜间PTH浓度升高不明显（p＜0.001）。GH初治组骨密度低的患者24小时平均PTH显著高于骨密度正常的患者（p＜0.001），而24小时平均NcAMP、ACa和1,25(OH)₂D显著低于骨密度正常的患者（p＜0.01），提示肾脏对PTH的敏感性降低。GH治疗组骨密度低的患者24小时平均PTH、NcAMP、ACa和1,25(OH)₂D显著低于骨密度正常的患者（p＜0.01），提示肾脏对PTH的作用降低。在ACa较低的情况下PTH浓度较低可能反映了GH治疗组骨密度低的患者甲状旁腺钙敏感受体对ACa浓度变化的敏感性降低。
GH初治组和GH治疗组AGHD患者骨密度低可能是PTH昼夜节律异常以及甲状旁腺和靶器官敏感性降低的结果。需要进一步研究以确定调节PTH节律性和敏感性对骨密度的潜在治疗益处。
