Osteogenic actions of metoprolol in an ovariectomized rat model of menopause.
Osteoporosis and hypertension are age-related chronic diseases with increased morbidity rates among postmenopausal women. Clinical epidemiological investigations have demonstrated that hypertensive patients treated with β1-selective β-blockers have a higher bone mineral density (BMD) and lower fracture risk. Nevertheless, no fundamental studies have examined the relationships between β1-selective β-blockers and these effects. The present study explored the effects and mechanisms of metoprolol in the in vitro treatment of osteoblasts and the in vivo treatment of ovariectomy-induced osteoporosis in rats.



Primary osteoblasts were obtained by digestion of the cranial bones of 24-hour-old Sprague-Dawley rats. After metoprolol treatment, cell proliferation and differentiation capacities were assessed at the corresponding time points. In addition, 3-month-old female Sprague-Dawley rats (200-220 g) were divided into a sham-operated group (n = 8) and three ovariectomized (OVX) (bilateral removal of ovaries) groups as follows: vehicle (OVX; n = 8), low-dose metoprolol (L-M, oral, 120 mg/kg/d; n = 8), and high-dose metoprolol (H-M, oral, 240 mg/kg/d; n = 8). After 12 weeks of metoprolol treatment, BMD, microarchitecture, and biomechanical properties were evaluated.



The results indicated that the treatments with 0.01 to 0.1 μM metoprolol increased osteoblast proliferation, alkaline phosphatase activity, and calcium mineralization, and promoted the expression of osteogenic genes. The in vivo study indicated that administration of metoprolol to OVX rats resulted in maintenance of the BMDs of the L4 vertebrae. Moreover, amelioration of trabecular microarchitecture deterioration and preservation of bone biomechanical properties were detected in the trabecular bones of the OVX rats.



Our findings indicate that metoprolol prevents estrogen deficiency-induced bone loss by increasing the number and enhancing the biological functions of osteoblasts, implying its potential use as an alternative treatment for postmenopausal osteoporosis in hypertensive patients.
1Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China 2Department of Orthopedics, 454 Hospital of PLA, Nanjing, Jiangsu Province, China 3Department of Orthopedics, 463 Hospital of PLA, Shenyang, Liaoning Province, China.
Yuan
Y
Zang
Quanchang
Q
Tan
Xiangyu
X
Ma
Xiong
X
Zhao
Wei
W
Lei
D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008593:Menopause / Q000187:drug effects; D008790:Metoprolol / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000209:etiology; D010052:Ovariectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D058671:Adrenergic beta-1 Receptor Antagonists; D008790:Metoprolol