J Korean Med Sci.  2013 Aug;28(8):1139-1144. 10.3346/jkms.2013.28.8.1139.

The Effects of Antihypertensive Drugs on Bone Mineral Density in Ovariectomized Mice

• Kang KY
• Kang Y
• Kim M
• Kim Y
• Yi H
• Kim J
• Jung HR
• Park SH
• Kim HY
• Ju JH
• Hong YS

• KMID: 1793017
• DOI: http://doi.org/10.3346/jkms.2013.28.8.1139

Abstract

The effects of several antihypertensive drugs on bone mineral density (BMD) and micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight-week-old female C57/BL6 mice were used for this study. Three days after ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg), telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all mice was confirmed to evaluate estrogen deficiency state. BMD and micro-architectural analyses were performed on tibial proximal ends by micro-computed tomography (micro-CT). When OVX mice with uterine atrophy were compared with mice without atrophy, BMD decreased (P < 0.001). There were significant differences in BMD loss between different antihypertensive drugs (P = 0.005). Enalapril and propranolol increased BMD loss in mice with atrophied uteri compared with control mice. By contrast, thiazide increased BMD in mice with uterine atrophy compared with vehicle-treated mice (P = 0.048). Thiazide (P = 0.032) and telmisartan (P = 0.051) reduced bone loss and bone fraction in mice with uterine atrophy compared with the control. Thiazide affects BMD in OVX mice positively. The reduction in bone loss by thiazide and telmisartan suggest that these drugs may benefit menopausal women with hypertension and osteoporosis.

Keyword

Antihypertensive Agents; Osteoporosis; Ovariectomized Mice; Thiazides; Telmisartan

MeSH Terms

Animals
Antihypertensive Agents/*pharmacology
Atrophy
Benzimidazoles/pharmacology
Benzoates/pharmacology
Bone Density/*drug effects
Enalapril/pharmacology
Female
Mice
Mice, Inbred C57BL
Ovariectomy
Propranolol/pharmacology
Thiazides/pharmacology
Tibia/radiography
Tomography, X-Ray Computed
Uterus/anatomy & histology/pathology
Antihypertensive Agents
Benzimidazoles
Benzoates
Thiazides
Enalapril
Propranolol

Figure

• 

  Fig. 1 The effects of antihypertensive drugs on BMD in OVX mice. (A) Comparison of BMD by multiple comparison. (B) Comparison of BMD in thiazide-treated mice vs. control mice. Data represent means ± SE. Each group consisted of n=8.

• 

  Fig. 2 Comparison of BMD based on uterine atrophy. (A) BMD in mice with uterine atrophy (n=28) vs mice without uterine atrophy (n=16). (B) Differences in BMD based on uterine atrophy. BMD difference is the mean BMD of mice with atrophied uteri minus the mean BMD of mice with normal uteri. BMD in mice treated with telmisartan (C) or thiazide (D) vs vehicle-treated mice. Data represent medians with inter-quartile, minimum and maximum.

• 

  Fig. 3 The effects of antihypertensive drugs on bone in OVX mice. (A) A micro-CT three-dimensional image of the trabecular architecture of a tibial proximal end from a control mouse and thiazide treated mice with normal uterine size or uterine atrophy. (B) Bone fraction of tibial proximal ends from OVX mice analyzed by micro-CT. (C) Differences in bone fraction based on uterine atrophy. Data represent medians with inter-quartile, minimum and maximum. BV, bone volume; TV, total volume.

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