Comparison of the effects of parathyroid hormone (1-34), alendronate sodium and simvastatin on osteoporotic rats

doi:10.3969/j.issn.2095-4344.2016.46.002

Abstract

Abstract:

BACKGROUND: Bone resorption drugs in the treatment of osteoporotic fracture are still controversial. The development of new drugs, especially drugs in the promotion of bone formation, become more important and urgent.
OBJECTIVE: To compare the effects of parathyroid hormone (1-34), alendronate sodium and simvastatin on bone loss in ovariectomized rats.
METHODS: Thirty female Sprague-Dawley rats aged 3 months were randomized into five groups of six animals in each group. All rats but those in sham group received dual ovariectomy (OVX) and treated by vehicle (OVX+V), parathyroid hormone (1-34) (5 days per week at a dose of 20 μg/kg, OVX+P), alendronate sodium (70 μg/kg/wk, OVX+A), simvastatin (5 mg/kg/d, OVX+S). Three months later, all rats were sacrificed. Dual energy X-ray method was used to measure bone density of L4 vertebra. Bone histomorphometry was utilized to analyze cancellous bone mass and bone microstructure. Compression test was performed on the L5 vertebra for the maximum loading and elastic modulus.
RESULTS AND CONCLUSION: (1) Bone density: The bone density from high to low levels was OVX+P group, sham group, OVX+A group, OVX+S group, and OVX+V group. No significant difference in bone density was detectable between the OVX+P and sham groups, but significant differences in bone density were determined between any other two groups (P < 0.05). (2) Bone histomorphometry: Relative volume of trabecular bone was significantly lower in the OVX+V group than in other groups. Relative volume of trabecular bone was remarkably higher in the OVX+P group than in the OVX+A group and OVX+S group. (3) Biomechanical properties: Biomechanical properties were noticeably lower in the OVX+V group than in other groups. Biomechanical properties were remarkably higher in the sham group and OVX+P group than in the OVX+S group and OVX+A group. (4) These findings indicated that under the dosage and intervention period used in the present study, parathyroid hormone (1-34), alendronate sodium and simvastatin showed anti-osteoporosis effect on OVX rats in a descending manner.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Osteoporosis, Ovariectomy, Bone Density, Tissue Engineering

Mu Shu-lin, Zhang Liu, Tian Fa-ming, Mu Shu-min, Sun Li-xia, Chu Li-ming. Comparison of the effects of parathyroid hormone (1-34), alendronate sodium and simvastatin on osteoporotic rats[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(46): 6854-6860.

Figures/Tables 3

References

[1] Tian FM,Zhang L, Zhao HY, et al. An increase in the incidence of hip fractures in Tangshan, China. Osteoporos Int. 2014;25(4): 1321-1325.
[2] Tao ZS, Zhou WS, Tu KK, et al. The effects of combined human parathyroid hormone (1-34) and simvastatin treatment on osseous integration of hydroxyapatite-coated titanium implants in the femur of ovariectomized rats. Injury. 2015; 46(11):2164-2169.
[3] Arita S, Ikeda S, Sakai A, et al. Human parathyroid hormone (1-34) increases mass and structure of the cortical shell, withresultant increase in lumbar bone strength, in ovariectomized rats. J Bone Miner Metab. 2004;22(6):530-540.
[4] Han SL, Wan SL. Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta-analysis of randomised controlled trials. Int J Clin Pract.2012;66(2):199-209.
[5] Cao Y, Mori S, Mashiba T, et al.Raloxifene, estrogen and alendronate affect the processes of fracture repair differently in ovariectomized rats. J Bone Miner Res. 2002; 17 (12): 2237-2246.
[6] Manabe T, Mori S, Mashiba T, et al. Eel calcitonin (elcatonin) suppressed callus remodeling but did not interfere with fracture healing in the femoral fracture model of cynomolgus monkeys. J Bone Miner Metab. 2009;27(3): 295-302.
[7] Mundy G, Garrett R, Harris S, et al. Stimulation of bone formation in vitro and in rodents by statins. Science. 1999;286(5446):1946-1949.
[8] Geesink RG,Hoefnagels NH,Bulstra SK.Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibulas defect.J Bone Joint Surgery.1999; 81(4):710-718.
[9] Sugiyama M,Kodama T, Konishi K,et al.Compacting and simvastatin,but not pravastatin,induce bone morphogenetic protein 2 in human osteosarcoma cell.Biochem Biopsy Res Common.2000;271(13): 688-692.
[10] Song CL, Guo ZQ, Ma QJ, et al. Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. Biochem Biopsy Res Common.2003;308(3): 458-462.
[11] Oxlund H, Andreassen TT. Simvastatin treatment partially ovariectomy-induced bone loss while increasing cortical bone formation. Bone. 2004;34(4): 609-618.
[12] Chung YS, Lee MD ,Lee SK, et al. HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients.J Clin Endocrinol Metab.2000;85(3): 1137-1142.
[13] Wang PS, Solomon DH, Mogun H, et al. HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. JAMA.2000;283(24):3211-3216.
[14] Maritz FJ, Conradie MM, Hulley PA,et al. Effects of statins on bone mineral density and bone histomorphometry in rodents.Arterioscler Thromb Vasc Biol.2001;21(10):1636-1641
[15] Von Stechow D, Fish S, Yahalom D, et al. Does simvastatin stimulate bone formation in vivo？BMC Musculoskelet Disord. 2003;4: 8
[16] Sehmisch S, Galal R, Kolios L, et al. Effects of low-magnitude, high-frequency mechanical stimulation in the rat osteopenia model. Osteoporos Int. 2009;20(12): 1999-2008.
[17] Khan K, Sharan K, Swarnkar G, et al. Positive skeletal effects of cladrin, a naturally occurring dimethoxydaidzein, in osteopenic rats that were maintained after treatment discontinuation. Osteoporos Int.2013; 24(4):1455-1470.
[18] Luo Y, Zhang L, Wang WY, et al. Alendronate retards the progression of lumbar intervertebral disc degeneration in ovariectomized rats. Bone.2013; 55(2): 439-448.
[19] Luo Y, Zhang L, Wang WY, et al. The inhibitory effect of salmon calcitonin on intervertebral disc degeneration in an ovariectomized rat model. Eur Spine J.2015; 24(8):1691-1701.
[20] Tian FM, Yang K, Wang WY, et al. Calcitonin suppresses intervertebral disk degeneration and preserves lumbar vertebral bone mineral density and bone strength in ovariectomized rats. Osteoporos Int.2015;26(12):2853-2861.
[21] Khajuria DK, Razdan R, Mahapatra DR. Additive effects of zoledronic acid and propranolol on bone density and biochemical markers of bone turnover in osteopenic ovariectomized rats. Rev Bras Reumatol. 2015;55(2):103-112.
[22] Khan K, Sharan K, Swarnkar G, et al.Positive skeletal effects of cladrin, a naturally occurring dimethoxydaidzein, in osteopenic rats that were maintained after treatment discontinuation. OsteoporosInt. 2013;24(4):1455-1470.
[23] Durão SF, Gomes PS, Colaço BJ, et al. The biomaterial-mediated healing of critical size bone defects in the ovariectomized rat.OsteoporosInt. 2014; 25(5):1535-1545.
[24] Qiu C, Liu X, Wang J, et al.Estrogen increases the transcription of human α2-Heremans-Schmid- glycoprotein by an interplay of estrogen receptor α and activator protein-1. OsteoporosInt. 2014;25(4): 1357-1367.
[25] 郑杰, 张柳, 韩大成.辛伐他汀体内给药部分阻止大鼠去卵巢导致的骨丢失[J]. 中国骨质疏松杂志, 2008, 14(9): 654-658.
[26] 卜建龙, 徐亮, 张品一, 等. 不同用药方案阿仑磷酸钠治疗老年性骨质疏松症的临床疗效分析[J]. 中国骨质疏松杂志, 2014, 20(2): 181-184+224.
[27] Haddad PT, Salazar M, Hernandes L. Histomorphometry of the organic matrix of the femur in ovariectomized rats treated with sodium alendronate. Rev Bras Ortop.2014;50(1):100-104.
[28] Khan A,Dubois S,Khan AA, et al.A randomized, double-blind, placebo-controlled study to evaluate the effects of alendronate on bone mineral density and bone remodelling in perimenopausal women with low bone mineral density. J Obstet Gynaecol Can. 2014; 36(11): 976-982
[29] Hassler N, Gamsjaeger S, Hofstetter B, et al. Effects of long-term alendronate treatment on postmenopausal osteoporosis bone material properties. Osteoporos Int. 2015; 26 (1):339-352.
[30] Black DM, Rosen CJ. Clinical Practice. Postmenopausal Osteoporosis. N Engl J Med. 2016; 374 (3): 254-262..
[31] Rugpolmuang L, Waikakul S. Effect of a Short-Term Treatment with Once-A-Week Medication of Alendronate 70 Mg on Bone Turnover Markers in Postmenopausal Women with Osteoporosis. J Med Assoc Thai. 2015; 98 Suppl 8:S70-75.
[32] Tella SH, Gallagher JC. Prevention and treatment of postmenopausal osteoporosis. J Steroid Biochem Mol Biol. 2014;142:155-170.
[33] Serrano AJ, Begoña L, Anitua E, et al. Systematic review and meta-analysis of the efficacy and safety of alendronate and zoledronate for the treatment of postmenopausal osteoporosis. 2013; 29(12): 1005-1014.
[34] Paggiosi MA, Peel N, McCloskey E, et al. Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study. Osteoporos Int. 2014; 25(12): 2729-2741.
[35] Naylor KE, Jacques RM, Paggiosi M, et al. Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study. Osteoporos Int. 2016; 27(1): 21-31.
[36] Gossiel F, Hoyle C, McCloskey EV, et al. The effect of bisphosphonate treatment on osteoclast precursor cells in postmenopausal osteoporosis: The TRIO study. Bone. 2016; 92:94-99.
[37] Li M, Zhang ZL, Liao EY, et al. Effect of low-dose alendronate treatment on bone mineral density and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis. Menopause. 2013; 20(1): 72-78.
[38] Eiken P, Vestergaard P. Treatment of osteoporosis after alendronate or risedronate. Osteoporos Int. 2016; 27(1): 1-12.
[39] Amugongo SK,Yao W,Jia J,et al.Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats. Bone. 2014; 67: 257-268.
[40] Kalea?as?o?lu F,Olcay E,Olgaç V. Statin-induced calcific Achilles tendinopathy in rats: comparison of biomechanical and histopathological effects of simvastatin, atorvastatin and rosuvastatin. Knee Surg Sports Traumatol Arthrosc,2015 Aug 15. [Epub ahead of print]