Effect of calcitriol supplementation and tail suspension on serum biomarkers of bone formation in rats

Journal of Diabetes & Metabolic Disorders

Farideh Razi³  Amir Khoshvaghti²  Ensiyeh Nasli Esfahani³  Mojtaba Rismanchi¹  Seyed Jafar Hashemian³ 

[1] Department of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran;Faculty of Aerospace and Sub-Aquatic Medicine, AJA University of Medical Sciences, Tehran, Iran;Diabetes Research Center, Endocrinology and Metabolism Clinical Science Institute, Tehran University of Medical Sciences, Tehran, Iran

关键词: Alkaline phosphatase (ALP);    Osteocalcin (OC);    Calcitriol;    Vitamin D;    Tail suspension model;   

Others  :  1144159
DOI  :  10.1186/s40200-015-0142-5

 received in 2014-07-04, accepted in 2015-02-28,  发布年份 2015

【 摘 要 】

Background

Calcitriol is documented to cause significant increase in bone mass densitometry counteracting osteoporosis.Promising results of calcitriol supplementation in studies aiming space flight induced osteoporosis is little and the effect of this hormone on biomarkers of bone metabolism is not examined yet in space flight models of osteoporosis in rats.

Methods

This was an interventional animal study being performed in a 1-month period. We included 21 Sprague Dawley strain rats (>200 gr, >6 week) who were randomly assigned to receive daily supplementation of oral 0.03μgr calcitriol and to be submitted to tail suspension model. Rats were followed for 1 month and were tested for serum osteocalcin (OC), alkaline phosphatase (ALP) and serum calcium at the beginning and the end of the study period. The results were analyzed and compared between groups.

Results

Although serum levels of osteocalcin and alkaline phosphatase biomarkers and total serum calcium were not significantly different within and between study groups, their levels were increased in tail suspension model compared to control group. The levels of these biomarkers were lower in those who were submitted to tail suspension model and received calcitriol supplementation compared to those who were only submitted to tail suspension (60.14 ± 11.73 ng/mL vs. 58.29 ± 2.69 ng/mL; p = 0.696 for osteocalcin and 381.86 ± 99.16 mU/mLvs. 362.57 ± 27.41 ng/mL; p = 0.635 for alkaline phosphatase).

Conclusion

Supplementation of daily diet with calcitriol in rats under weightlessness conditions may results in lower values for bone metabolic biomarkers of alkaline phosphatase and osteocalcin and serum calcium. This pattern of change in biomarkers of bone formation, may point to the capacity of calcitriol supplementation in preventing cellular process of osteoporosis. Thus calcitriol supplementation could be an available, economic and effective strategy for preventing bone metabolic changes related to weightlessness commonly encountered in space flight. The outcome of this study needs to be further studied in future trying to find more definite results.

【 授权许可】

   
2015 Hashemian et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Smith SM, Wastney ME, O’Brien KO, Morukov BV, Larina IM, Abrams SA: Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the mir space station. J Bone Miner Res 2005, 20:208-18.
• [2]Iwase S, Nishimura N, Mano T: Osteoporosis in Spaceflight, Topics in Osteoporosis. [http:/ / www.intechopen.com/ books/ topics-in-osteoporosis/ osteoporosis-in-spaceflight] webciteIn Tech Edited by Valdés-Flores M. 2013. doi:10.5772/54708. Available from: http://www.intechopen.com/books/topics-in-osteoporosis/osteoporosis-in-spaceflight
• [3]Vico L, Collet P, Guignandon A, Lafage-Proust MH, Thomas T, Rehaillia M, et al.: Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet 2000, 355:1607-11.
• [4]Sibonga JD: Spaceflight-induced bone loss: is there an osteoporosis risk? Curr Osteoporosis Rep. 2013, 11(2):92-8. doi:10.1007/s11914-013-0136-5
• [5]Orwoll ES, Adler RA, Amin S, Binkley N, Lewiecki EM, Petak SM, et al.: Skeletal health in long duration astronauts: nature, assessment, and management recommendations from the NASA bone summit. J Bone Miner Res 2013, 28:1243-55.
• [6]Holick MF: Microgravity-induced bone loss—will it limit human space exploration? Lancet 2000, 355:1569-70.
• [7]Cavanagh PR, Licata AA, Rice AJ: Exercise and pharmacological countermeasures for bone loss during long duration space flight. Gravit Space Biol 2007, 18:39-58.
• [8]Iwamoto J, Takeda T, Sato Y: Interventions to prevent bone loss in astronauts during space flight. Keio J Med 2005, 54:55-9.
• [9]Jee W, Yao W: Overview: animal models of osteopenia and osteoporosis. J Musculoskelet Neuronal Interact 2001, 1:193-207.
• [10]Morey-Holton E, Globus R: Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight. Bone 1998, 22:83S-8.
• [11]Morey-Holton ER, Globus RK: Hindlimb unloading rodent model: technical aspects. J Appl Physiol 2002, 92:1367-77.
• [12]Morey-Holton E, Globus RK, Kaplansky A, Durnova G: The hindlimb unloading rat model: literature overview, technique update and comparison with space flight data. Adv Space Biol Med 2005, 10:7-40.
• [13]Iwasaki Y, Yamato H, Murayama H, Sato M, Takahashi T, Ezawa I, et al.: Maintenance of trabecular structure and bone volume by vitamin K2 in mature rats with long-term tail suspension. J Bone Miner Metab 2002, 20:216-22.
• [14]Barou O, Lafage-Proust M-H, Martel C, Thomas T, Tirode F, Laroche N, et al.: Bisphosphonate effects in rat unloaded hindlimb bone loss model: three-dimensional microcomputed tomographic, histomorphometric, and densitometric analyses. J Pharmacol Exp Ther 1999, 291:321-8.
• [15]Wimalawansa SM, Chapa MT, Wei JN, Westlund KN, Quast MJ, Wimalawansa SJ, et al.: Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI. J Appl Physiol 1999, 86:1841-6.
• [16]Wronski T, Morey-Holton E: Skeletal response to simulated weightlessness: a comparison of suspension techniques. Aviat Space Environ Med 1987, 58:63-8.
• [17]Schneider V, Oganov V, LeBlanc A, Rakmonov A, Taggart L, Bakulin A, Huntoon C, Grigoriev A, Varonin L: Bone and body mass changes during space flight. Acta astronautica. 1995, 36:463-466.
• [18]Amblard D, Lafage‐Proust MH, Laib A, Thomas T, Rüegsegger P, Alexandre C, et al.: Tail suspension induces bone loss in skeletally mature mice in the C57BL/6J strain but not in the C3H/HeJ strain. J Bone Miner Res 2003, 18:561-9.
• [19]Szulc P, Bauer DC, Eastell R: Chapter 35 Biochemical markers of bone turnover in osteoporosis. In Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Eighth edition. Edited by Rosen CJ. John Wiley & Sons, Inc, Ames, Iowa; 2013:297-306.
• [20]Yap CY, Aw TC: Bone turnover markers. Proceedings of Singapore Healthcare 2010, 19:273-5.
• [21]Delmas PD: Biochemical markers of bone turnover for the clinical assessment of metabolic bone disease. Endocrinol Metab Clin North Am 1990, 19:1.
• [22]Brown JE, Cook RJ, Major P, Lipton A, Saad F, Smith M, et al.: Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst. 2005, 97:59-69.
• [23]Gallego‐Rojo FJ, Gonzalez‐Calvin JL, Muñoz‐Torres M, Mundi JL, Fernandez-Perez R: Bone mineral density, serum insulin‐like growth factor I, and bone turnover markers in viral cirrhosis. Hepatol 1998, 28:695-9.
• [24]Atteritano M, Sorbara S, Bagnato G, Miceli G, Sangari D, Morgante S, et al.: Bone mineral density, bone turnover markers and fractures in patients with systemic sclerosis: a case control study. PLoS One 2013, 8:e66991.
• [25]Lu H, Mai Z, Xu Y, Wang W, Ai H: Mechanical loading induced expression of bone morphogenetic protein-2, alkaline phosphatase activity, and collagen synthesis in osteoblastic MC3T3-E1 cells. Chin Med J (Engl) 2012, 125:4093-7.
• [26]Park JC, Kovesdy CP, Duong U, Streja E, Rambod M, Nissenson AR, et al.: Association of serum alkaline phosphatase and bone mineral density in maintenance hemodialysis patients. Hemodial Int 2010, 14:182-92.
• [27]Pearce S, Cheetham TD: Diagnosis and management of vitamin D deficiency. BMJ 2010, 340:b5664.
• [28]Lips P, Duong T, Oleksik A, Black D, Cummings S, Cox D, et al.: A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. J Clin Endocrinol Metab 2001, 86:1212-21.
• [29]Chen P, Satterwhite JH, Licata AA, Lewiecki EM, Sipos AA, Misurski DM, et al.: Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res 2005, 20:962-70.
• [30]Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al.: Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006, 354:669-83.
• [31]Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A: Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007, 370:657-66.
• [32]Takahashi M, Naitou K, Ohishi T, Kushida K, Miura M: Effect of vitamin K and/or D on undercarboxylated and intact osteocalcin in osteoporotic patients with vertebral or hip fractures. Clin Endocrinol (Oxf) 2001, 54:219-24.
• [33]O’Connor E, Mølgaard C, Michaelsen KF, Jakobsen J, Cashman KD: Vitamin D–vitamin K interaction: effect of vitamin D supplementation on serum percentage undercarboxylated osteocalcin, a sensitive measure of vitamin K status, in Danish girls. Br J Nutr 2010, 104:1091-1095.
• [34]Holick MF: Perspective on the impact of weightlessness on calcium and bone metabolism. Bone 1998, 22(5):105S-11.
• [35]Breslau NA, McGuire JL, Zerwekh JE, FRENKEL EP, PAK CY: Hypercalcemia associated with increased serum calcitriol levels in three patients with lymphoma. Ann Intern Med 1984, 100(1):1-7.
• [36]Donovan PJ, Sundac L, Pretorius CJ, d’Emden MC, McLeod DS: Calcitriol-mediated hypercalcemia: causes and course in 101 patients. J Clin Endocrinol Metab 2013, 98(10):4023-9.
• [37]Lems W, Jacobs J, Van Rijn H, Bijlsma J: Changes in calcium and bone metabolism during treatment with low dose prednisone in young, healthy, male volunteers. Clin Rheumatol 1995, 14:420-4.