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Effects of eldecalcitol on bone and skeletal muscles in glucocorticoid-treated rats

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Abstract

Glucocorticoids cause secondary osteoporosis and myopathy, characterized by type II muscle fiber atrophy. We examined whether a new vitamin D3 analogue, eldecalcitol, could inhibit glucocorticoid-induced osteopenia or myopathy in rats, and also determined the effects of prednisolone (PSL) and/or eldecalcitol on muscle-related gene expression. Six-month-old female Wistar rats were randomized into four groups: PSL group (10 mg/kg PSL); E group (0.05 µg/kg eldecalcitol); PSL + E group; and control group. PSL, eldecalcitol, and vehicles were administered daily for 2 or 4 weeks. Right calf muscle strength, muscle fatigue, cross-sectional areas (CSAs) of left tibialis anterior muscle fibers, and bone mineral density (BMD) were measured following administration. Pax7, MyoD, and myogenin mRNA levels in gastrocnemius muscles were also determined. Muscle strength was significantly higher in the PSL + E group than in the PSL group (p < 0.05) after 4 weeks, but not after 2 weeks. No significant difference in muscle fatigue was seen between groups at 2 or 4 weeks. CSAs of type II muscle fibers were significantly larger in the E group and the PSL + E group than in the PSL group at 4 weeks (p = 0.0093, p = 0.0443, respectively). Eldecalcitol treatment for 4 weeks maintained the same BMD as the PSL + E group. After 2 weeks, but not 4 weeks, eldecalcitol treatment significantly increased Pax7 and myogenin mRNA expression in gastrocnemius muscle, and PSL also stimulated myogenin expression. Eldecalcitol appears to increase muscle volume and to protect against femur BMD loss in PSL-administered rats, and it may also stimulate myoblast differentiation into early myotubes.

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References

  1. da Costa JA, Ribeiro A, Bogas M, Costa L, Varino C, Lucas R, Rodrigues A, Araújo D (2009) Mortality and functional impairment after hip fracture: a prospective study in a Portuguese population. Acta Reumatol Port 34:618–626

    PubMed  Google Scholar 

  2. Cooper C, Atkinson EJ, Jacobsen SJ, O’Fallon WM, Melton LJ 3rd (1993) Population-based study of survival after osteoporotic fractures. Am J Epidemiol 137:1001–1005

    CAS  PubMed  Google Scholar 

  3. Landi F, Liperoti R, Russo A, Giovannini S, Tosato M, Capoluongo E, Bernabei R, Onder G (2012) Sarcopenia as a risk factor for falls in elderly individuals: results from the ilSIRENTE study. Clin Nutr 31:652–658

    Article  PubMed  Google Scholar 

  4. Chan BK, Marshall LM, Winters KM, Faulkner KA, Schwartz AV, Orwoll ES (2007) Incident fall risk and physical activity and physical performance among older men: the Osteoporotic Fractures in Men Study. Am J Epidemiol 165:696–703

    Article  PubMed  Google Scholar 

  5. Pan HH, Li CY, Chen TJ, Su TP, Wang KY (2014) Association of polypharmacy with fall-related fractures in older Taiwanese people: age- and gender-specific analyses. BMJ Open 4:e004428

    Article  PubMed  PubMed Central  Google Scholar 

  6. Keller K, Engelhardt M (2014) Strength and muscle mass loss with aging process. Age and strength loss. Muscles Ligaments Tendons J 3:346–350

    PubMed  PubMed Central  Google Scholar 

  7. Johnell K, Fastbom J (2008) Multi-dose drug dispensing and inappropriate drug use: a nationwide register-based study of over 700,000 elderly. Scand J Prim Health Care 26:86–91

    Article  PubMed  PubMed Central  Google Scholar 

  8. Pereira RM, Freire de Carvalho J (2011) Glucocorticoid-induced myopathy. Joint Bone Spine 78:41–44

    Article  CAS  PubMed  Google Scholar 

  9. Larsson L, Sjödin B, Karlsson J (1978) Histochemical and biochemical changes in human skeletal muscle with age in sedentary males, age 22–65 years. Acta Physiol Scand 103:31–39

    Article  CAS  PubMed  Google Scholar 

  10. Schakman O, Gilson H, Thissen JP (2008) Mechanisms of glucocorticoid-induced myopathy. J Endocrinol 197:1–10

    Article  CAS  PubMed  Google Scholar 

  11. Skelton DA, Kennedy J, Rutherford OM (2002) Explosive power and asymmetry in leg muscle function in frequent fallers and non-fallers aged over 65. Age Ageing 31:119–125

    Article  PubMed  Google Scholar 

  12. Gallagher JC, Fowler SE, Detter JR, Sherman SS (2001) Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab 86:3618–3628

    Article  CAS  PubMed  Google Scholar 

  13. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB (2004) Effect of Vitamin D on falls: a meta-analysis. JAMA 291:1999–2006

    Article  CAS  PubMed  Google Scholar 

  14. Dukas L, Schacht E, Mazor Z, Stähelin HB (2005) Treatment with alfacalcidol in elderly people significantly decreases the high risk of falls associated with a low creatinine clearance of <65 ml/min. Osteoporos Int 16:198–203

    Article  CAS  PubMed  Google Scholar 

  15. Kasukawa Y, Miyakoshi N, Maekawa S, Nozaka K, Noguchi H, Shimada Y (2010) Effects of alfacalcidol on muscle strength, muscle fatigue, and bone mineral density in normal and ovariectomized rats. Biomed Res 31:273–279

    Article  CAS  PubMed  Google Scholar 

  16. Miyakoshi N, Sasaki H, Kasukawa Y, Kamo K, Shimada Y (2010) Effects of a vitamin D analog, alfacalcidol, on bone and skeletal muscle in glucocorticoid-treated rats. Bio Med Res 31:329–336

    CAS  Google Scholar 

  17. Matsumoto T, Ito M, Hayashi Y, Hirota T, Tanigawara Y, Sone T, Fukunaga M, Shiraki M, Nakamura T (2011) A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures—a randomized, active comparator, double-blind study. Bone (NY) 49:605–612

    Article  CAS  Google Scholar 

  18. O’Donnell S, Moher D, Thomas K, Hanley DA, Cranney A (2008) Systematic review of the benefits and harms of calcitriol and alfacalcidol for fractures and falls. J Bone Miner Metab 26:531–542

    Article  PubMed  Google Scholar 

  19. Nakamura T, Takano T, Fukunaga M, Shiraki M, Matsumoto T (2013) Eldecalcitol is more effective for the prevention of osteoporotic fractures than alfacalcidol. J Bone Miner Metab 31:417–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hagino H, Takano T, Fukunaga M, Shiraki M, Nakamura T, Matsumoto T (2013) Eldecalcitol reduces the risk of severe vertebral fractures and improves the health-related quality of life in patients with osteoporosis. J Bone Miner Metab 31:183–189

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ito M, Nakamura T, Fukunaga M, Shiraki M, Matsumoto T (2011) Effect of eldecalcitol, an active vitamin D analog, on hip structure and biomechanical properties: 3D assessment by clinical CT. Bone (NY) 49:328–334

    Article  CAS  Google Scholar 

  22. Harada S, Takeda S, Uno A, Takahashi F, Saito H (2010) Eldecalcitol is less effective in suppressing parathyroid hormone compared to calcitriol in vivo. J Steroid Biochem Mol Biol 121:281–283

    Article  CAS  PubMed  Google Scholar 

  23. Sasaki H, Miyakoshi N, Kasukawa Y, Maekawa S, Noguchi H, Kamo K, Shimada Y (2009) Muscle strength and fatigue in glucocorticoid-treated rats. Akita J Med 36:195–202

    CAS  Google Scholar 

  24. Clarke HH, Shay CT, Mathews DK (1954) Strength decrement of elbow flexor muscles following exhaustive exercise. Arch Phys Med Rehabil 35:560–567

    CAS  PubMed  Google Scholar 

  25. Murata K, Yano E (2002) Medical statistics for evidence-based medicine with SPBS user’s guide. Nankodo, Tokyo

    Google Scholar 

  26. Compston J (2010) Management of glucocorticoid-induced osteoporosis. J Nat Rev Rheumatol 6:82–88

    Article  CAS  Google Scholar 

  27. Saito H, Kishimoto K, Okuno H, Tanaka M, Itoi E (2013) Effect of eldecalsitol on C2C12 cell. (in Japanese). Clin Calcium 23:142

    Google Scholar 

  28. Tanaka K, Kanazawa I, Yamaguchi T, Yano S, Kaji H, Sugimoto T (2014) Active vitamin D possesses beneficial effects on the interaction between muscle and bone. Biochem Biophys Res Commun. doi:10.1016/j.bbrc.2014.05.145

    Google Scholar 

  29. Seale P, Sabourin LA, Girgis-Gabardo A, Mansouri A, Gruss P, Rudnicki MA (2000) Pax7 is required for the specification of myogenic satellite cells. Cell 102:777–786

    Article  CAS  PubMed  Google Scholar 

  30. Nabeshima Y, Hanaoka K, Hayasaka M, Esumi E, Li S, Nonaka I, Nabeshima Y (1993) Myogenin gene disruption results in perinatal lethality because of severe muscle defect. Nature (Lond) 364:532–535

    Article  CAS  Google Scholar 

  31. Smith CK 2nd, Janney MJ, Allen RE (1994) Temporal expression of myogenic regulatory genes during activation, proliferation, and differentiation of rat skeletal muscle satellite cells. J Cell Physiol 159:379–385

    Article  CAS  PubMed  Google Scholar 

  32. Perez-Ruiz A, Ono Y, Gnocchi VF, Zammit PS (2008) β-Catenin promotes self-renewal of skeletal-muscle satellite cells. J Cell Sci 121:1373–1382

    Article  CAS  PubMed  Google Scholar 

  33. Ceglia L, Rivas DA, Pojednic RM, Price LL, Harris SS, Smith D, Fielding RA, Dawson-Hughes B (2013) Effects of alkali supplementation and vitamin D insufficiency on rat skeletal muscle. Endocrine 44:454–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lieu FK, Powers SK, Herb RA, Criswell D, Martin D, Wood C, Stainsby W, Chen CL (1993) Exercise and glucocorticoid-induced diaphragmatic myopathy. J Appl Physiol 75:763–771

    CAS  PubMed  Google Scholar 

  35. Dong Y, Pan JS, Zhang L (2013) Myostatin suppression of Akirin1 mediates glucocorticoid-induced satellite cell dysfunction. PLoS One 8:e58554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. te Pas MF, de Jong PR, Verburg FJ (2000) Glucocorticoid inhibition of C2C12 proliferation rate and differentiation capacity in relation to mRNA levels of the MRF gene family. Mol Biol Rep 27:87–98

    Article  Google Scholar 

  37. de Rekeneire N, Visser M, Peila R, Nevitt MC, Cauley JA, Tylavsky FA, Simonsick EM, Harris TB (2003) Is a fall just a fall: correlates of falling in healthy older persons. The Health, Aging and Body Composition Study. J Am Geriatr Soc 51:841–846

    Article  PubMed  Google Scholar 

  38. Iwamoto J, Sato Y (2014) Eldecalcitol improves chair-rising time in postmenopausal osteoporotic women treated with bisphosphonates. Ther Clin Risk Manag 10:51–59

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant No. 25462284).

Conflict of interest

Drs. Kinoshita, Miyakoshi, Kasukawa, Segawa, Ohuchi, Fujii, Sato, and Shimada have no conflicts of interest. Drs. Shiraishi and Sakai are current employees of Chugai Pharmaceutical Co., Ltd.

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan

    Hayato Kinoshita, Naohisa Miyakoshi, Yuji Kasukawa, Toyohito Segawa, Kentaro Ohuchi, Masashi Fujii, Chie Sato & Yoichi Shimada

  2. Product Research Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka, 412-8513, Japan

    Sadaoki Sakai

  3. Medical Plan Management Department, Chugai Pharmaceutical Co., Ltd., 1-1 Nihonbashi-Muromachi 2-Chome, Chuo-ku, Tokyo, 103-8324, Japan

    Ayako Shiraishi

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  1. Hayato Kinoshita
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  2. Naohisa Miyakoshi
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Correspondence to Naohisa Miyakoshi.

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Kinoshita, H., Miyakoshi, N., Kasukawa, Y. et al. Effects of eldecalcitol on bone and skeletal muscles in glucocorticoid-treated rats. J Bone Miner Metab 34, 171–178 (2016). https://doi.org/10.1007/s00774-015-0664-4

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  • DOI: https://doi.org/10.1007/s00774-015-0664-4

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