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

다국어 초록 (Multilingual Abstract)

The effects of several antihypertensive drugs on bone mineral density (BMD) and microarchitectural 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 (20mg/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.

참고문헌 (Reference)

1 Rejnmark L, "Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case-control study" 24 : 581-589, 2006

2 Chobanian AV, "The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report" 289 : 2560-2572, 2003

3 Ilic K, "The relationship among hypertension, antihypertensive medications, and osteoporosis: a narrative review" 92 : 217-227, 2013

4 Bolland MJ, "The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women" 18 : 479-486, 2007

5 Riggs BL, "Sex steroids and the construction and conservation of the adult skeleton" 23 : 279-302, 2002

6 Solomon DH, "Risk of fractures in older adults using antihypertensive medications" 26 : 1561-1567, 2011

7 LaCroix AZ, "Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults: a randomized, double-blind, placebo-controlled trial" 133 : 516-526, 2000

8 Lalande A, "Indapamide, a thiazide-like diuretic, decreases bone resorption in vitro" 16 : 361-370, 2001

9 Broulik PD, "Impact of antihypertensive therapy on the skeleton: effects of enalapril and AT1 receptor antagonist losartan in female rats" 50 : 353-358, 2001

10 Reid IR, "Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomized controlled trial" 109 : 362-370, 2000

11 Melton LJ 3rd, "How many women have osteoporosis? JBMR Anniversary Classic: JBMR, volume 7, number 9, 1992" 20 : 886-892, 2005

12 Walsh JS, "Heart drugs that affect bone" 23 : 163-168, 2012

13 Bouxsein ML, "Guidelines for assessment of bone microstructure in rodents using micro-computed tomography" 25 : 1468-1486, 2010

14 Rejnmark L, "Fracture risk in perimenopausal women treated with beta-blockers" 75 : 365-372, 2004

15 Otto C, "Estradiol release kinetics determine tissue response in ovariectomized rats" 153 : 1725-1733, 2012

16 Ott SM, "Effects of three years of low-dose thiazides on mineral metabolism in healthy elderly persons" 19 : 1315-1322, 2008

17 Cauley JA, "Effects of thiazide diuretic therapy on bone mass, fractures, and falls: the Study of Osteoporotic Fractures Research Group" 118 : 666-673, 1993

18 Wiens M, "Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies" 260 : 350-362, 2006

19 Pierroz DD, "Combined treatment with a beta-blocker and intermittent PTH improves bone mass and microarchitecture in ovariectomized mice" 39 : 260-267, 2006

20 Liu YY, "Captopril improves osteopenia in ovariectomized rats and promotes bone formation in osteoblasts" 29 : 149-158, 2011

21 Pasco JA, "Beta-adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: geelong osteoporosis Study" 19 : 19-24, 2004

22 Reid IR, "Beta-Blocker use, BMD, and fractures in the study of osteoporotic fractures" 20 : 613-618, 2005

23 Yang S, "Association between beta-blocker use and fracture risk: the Dubbo Osteoporosis Epidemiology Study" 48 : 451-455, 2011

24 Lynn H, "Angiotensin converting enzyme inhibitor use is associated with higher bone mineral density in elderly Chinese" 38 : 584-588, 2006

25 Shimizu H, "Angiotensin II accelerates osteoporosis by activating osteoclasts" 22 : 2465-2475, 2008