Runyan Aliye L, Chhokar Vikram S, Sun Yao, Bhattacharya Syamal K, Runyan John W, Weber Karl T
Division of Cardiovascular Diseases, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Am J Med Sci. 2005 Jul;330(1):1-7. doi: 10.1097/00000441-200507000-00001.
We hypothesized that aldosteronism is accompanied by hypercalciuria and hypermagnesuria that lead to bone loss, which could be rescued by hydrochlorothiazide and spironolactone.
We monitored 24-hour urinary Ca and Mg excretion; plasma ionized [Ca]o and [Mg]o and plasma K; and bone mineral density of the femur. The following groups (n=5 in each group) were studied: age- and gender-matched, untreated controls; controls + 4 weeks hydrochlorothiazide; 4 weeks aldosterone/salt treatment (ALDOST, 0.75 mug/h and dietary 1% NaCl/0.4% KCl); 4 weeks ALDOST+hydrochlorothiazide (50 mg/kg in prepared food); and 4 weeks ALDOST+hydrochlorothiazide+spironolactone (200 mg/kg day in divided doses by twice-daily gavage).
ALDOST increased (P<0.05) urinary Ca and Mg excretion four- and twofold, respectively; hydrochlorothiazide co-treatment attenuated (P<0.05) Ca excretion in controls and during ALDOST without affecting augmented Mg excretion whereas hydrochlorothiazide+spironolactone normalized Ca and reduced Mg excretion (P<0.05). Compared with controls, plasma [Ca]o at 4 weeks of ALDOST was reduced (0.89+/-0.02 versus 0.83+/-0.03 mmol/L; P<0.05) but remained no different from levels in controls with hydrochlorothiazide and hydrochlorothiazide+spironolactone (0.88+/-0.04 and 0.97+/-0.03 mmol/L, respectively). Plasma [Mg]o fell (P<0.05) with ALDOST+hydrochlorothiazide (0.23+/-0.01 versus 0.34+/-0.01 mmol/L) and was prevented with spironolactone co-treatment (0.33+/-0.01 mmol/ dL). Hypokalemia (2.9+/-0.2 mmol/L) occurred in rats with ALDOST+hydrochlorothiazide but not with spironolactone co-treatment. At 4 weeks of ALDOST, plasma parathyroid hormone was increased (30+/-4 versus 11+/-3 pg/mL; P<0.05) and bone mineral density was reduced (0.153+/-0.006 versus 0.170+/-0.002 g/cm; P<0.05). Co-treatments with either hydrochlorothiazide or hydrochlorothiazide+spironolactone each prevented bone loss.
Hypercalciuria and hypermagnesuria accompany aldosteronism and account for a decline in their plasma ionized concentrations and secondary hyperparathyroidism with bone resorption. Attenuation of bone loss in aldosteronism can be achieved with hydrochlorothiazide; however, mono- and divalent cation homeostasis, together with bone integrity, are each preserved with the combination hydrochlorothiazide+spironolactone.
我们推测醛固酮增多症伴有高钙尿症和高镁尿症，进而导致骨质流失，而氢氯噻嗪和螺内酯可能会改善这种情况。
我们监测了24小时尿钙和尿镁排泄量、血浆离子钙（[Ca]o）和离子镁（[Mg]o）以及血钾水平，同时测量了股骨的骨密度。研究对象分为以下几组（每组n = 5）：年龄和性别匹配的未经治疗的对照组；对照组 + 4周氢氯噻嗪治疗；4周醛固酮/高盐治疗（ALDOST，0.75 μg/h，饮食中含1%氯化钠/0.4%氯化钾）；4周ALDOST + 氢氯噻嗪（在制备食物中加入50 mg/kg）；4周ALDOST + 氢氯噻嗪 + 螺内酯（200 mg/kg/天，分两次经口灌胃给药）。
ALDOST使尿钙和尿镁排泄量分别增加了4倍和2倍（P < 0.05）；联合使用氢氯噻嗪可减轻对照组和ALDOST治疗期间的尿钙排泄（P < 0.05），但不影响增加的尿镁排泄，而氢氯噻嗪 + 螺内酯可使尿钙排泄恢复正常并减少尿镁排泄（P < 0.05）。与对照组相比，ALDOST治疗4周时血浆[Ca]o降低（0.89 ± 0.02对0.83 ± 0.03 mmol/L；P < 0.05），但与氢氯噻嗪组和氢氯噻嗪 + 螺内酯组的对照组水平无差异（分别为0.88 ± 0.04和0.97 ± 0.03 mmol/L）。ALDOST + 氢氯噻嗪组血浆[Mg]o下降（P < 0.05）（0.23 ± 0.01对0.34 ± 0.01 mmol/L），而联合使用螺内酯可预防这种下降（0.33 ± 0.01 mmol/dL）。ALDOST + 氢氯噻嗪组大鼠出现低钾血症（2.9 ± 0.2 mmol/L），而联合使用螺内酯可预防。ALDOST治疗4周时，血浆甲状旁腺激素升高（30 ± 4对11 ± 3 pg/mL；P < 0.05），骨密度降低（0.153 ± 0.006对0.170 ± 0.002 g/cm；P < 0.05）。氢氯噻嗪或氢氯噻嗪 + 螺内酯联合治疗均可预防骨质流失。
醛固酮增多症伴有高钙尿症和高镁尿症，导致其血浆离子浓度下降及继发性甲状旁腺功能亢进和骨吸收。氢氯噻嗪可减轻醛固酮增多症患者的骨质流失；然而，氢氯噻嗪 + 螺内酯联合使用可同时维持一价和二价阳离子内环境稳定以及骨骼完整性。
