Effects of a calcium/vitamin D/Zinc combination on anti-osteoporosis in ovariectomized rats |
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| Affiliation: | 1. School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, 510006 Guangzhou, Guangdong, China;2. Nutrition/Metabolism Laboratory, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA;3. Infinitus (China) Co., Ltd. R & D Center, 510653 Guangzhou, Guangdong, China;4. Foshan Allan Conney Biotechnology Co., Ltd. 523281 Foshan, Guangdong, China;1. Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany;2. Health Campus Immunology, Infection and Inflammation (GC-I3), Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany;3. Center of Health and Medical Prevention (CHaMP), Otto-von-Guericke University, Magdeburg, Germany;4. Hahnemannstr. 14, 39118 Magdeburg, Germany;1. Institute of Energy Metabolism and Health, Shanghai 10th People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China;2. Anhui Provincial Chest Hospital，Hefei 230022, Anhui Province, China;3. Department of Respiratory Medicine, No. 901 Hospital of the Chinese People’s Liberation Army Logistic Support Force, Hefei 230071, Anhui Province, China;4. Department of Respiratory Medicine, Shanghai 10th People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China;5. The Second People’s Hospital of HeFei, Hefei 230011, Anhui Province, China;1. Department of Neurosurgery, 5th Military Clinical Hospital with the SP ZOZ Polyclinic in Krakow, 30-901 Krakow, Poland;2. Department of Histology, Cytophysiology and Embryology, Faculty of Medicine in Zabrze, Academy of Silesia in Katowice, 41-800 Zabrze, Poland;3. Department of Neurosurgery, St. Raphael Hospital, 30-693 Krakow, Poland;4. Department of Neurosurgery, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski University, 30-705 Kraków, Poland;5. Department of Agricultural and Environmental Chemistry, University of Agriculture in Krakow, 31-120 Krakow, Poland;6. Department of Trauma and Orthopedic Surgery, 5th Military Clinical Hospital, Kraków, Poland;7. Department of Rehabilitation in Orthopedics, Faculty of Motor Rehabilitation Bronisław Czech University of Physical Education in Kraków, Poland;8. Department of Physiology, School of Medicine in Katowice, Medical University of Silesia, 40-752 Katowice, Poland;9. Department of Neurosurgery, Provincial Specialist Hospital No. 2 in Jastrzębie-Zdrój, 44-300 Jastrzębie-Zdrój, Poland;1. University of Life Sciences ”King Michael I”, Faculty of Veterinary Medicine, Timisoara, Romania;2. “Vasile Goldis” Western University of Arad, Institute of Life Sciences, Romania;1. NUS Graduate School’s Integrative Sciences & Engineering Programme (ISEP), National University of Singapore, University Hall, Tan Chin Tuan Wing, 119077, Singapore;2. Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore;3. Central Instrument Facility, Office of the Vice Chancellor for Research and Innovation, De La Salle University, 2401 Taft Avenue, Malate, Manila 1004, Philippines;4. Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore;1. Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Bacterial Vaccines Quality Control, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran |
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| Abstract: | 
BackgroundOsteoporosis is a major health problem in postmenopausal women, and characterized by deteriorated bone mass and micro-architecture. There have been some clinical trials demonstrating the beneficial effects of vitamin-D and some trace elements on calcium absorption and attenuation of osteoporosis development. However, effects of the combination of vitamin-D and zinc on calcium absorption and osteoporosis have not been adequately investigated.MethodsNetwork pharmacology was first performed to explore possible correlations between calcium/vitamin D/zinc and osteoporosis. Forty-nine female Sprague-Dawley rats (6 months old, 250 ± 20 g) were randomized into 7 experimental groups with 7 animals per group for the in vivo study, including one sham surgery control group, one ovariectomizing (OVX) group, and 5 OVX plus treatment groups. At the end of animal experiment, animal tibia and femur leg bones and blood were collected for H&E staining, bone microstructure analysis by a micro-CT, measurement of bone and serum Ca, P and Zn concentrations, and immunohistochemical detection of macrophage-colony stimulating factor receptor (M-CSFR) and receptor activator of nuclear factor-kappa B ligand (RANKL).ResultsThe network pharmacology analysis identified 57 candidate targets that were related to the osteoporosis-Ca/VitD/Zn interconnections. Further pathway analysis suggested that the combined treatment of Ca, VitD and Zn attenuated osteoporosis via modulation of metabolic pathways. We found that a therapy with Ca/VitD-M/Zn-M (73 mg/kg/day Ca, 0.6 g/kg/day VitD3 and 0.6 mg/kg/day zinc citrate) could significantly suppress the progression of osteoporosis in rats. After the Ca/VitD-M/Zn-M treatment, the ratio of bone volume/tissue volume, trabecular number and the trabecular thickness were all significantly elevated while the extent of trabecular separation was significantly reduced. Additionally, both serum calcium and bone calcium levels were significantly upregulated by the Ca/VitD/Zn treatment in a dose-dependent manner. The combination of Ca/VitD-M/Zn-M was superiou to either Ca/VitD-L/Zn-L or Ca/VitD-H/Zn-H treatment for such an effect. Moreover, the osteoporosis-associated M-CSFR and RANKL factors were both significantly downregulated by the Ca/VitD-M/Zn-M treatment in bone tissues of OVX rats.ConclusionsThe combined supplement of VitD and Zn facilitates the Ca(2 +) absorption and attenuates the development of osteoporosis via down-regulation of osteoporosis-associated factors M-CSFR and RANKL, thus potentially constitutes an alternative therapy for the postmenopausal osteoporosis. |
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| Keywords: | Calcium Vitamin D Zinc Osteoporosis Network pharmacology BV/TV |
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