Skip to main content

Advertisement

SpringerLink
Log in

Teriparatide and exercise improve bone, skeletal muscle, and fat parameters in ovariectomized and tail-suspended rats

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Although teriparatide (TPTD) and exercise may improve osteoporosis, muscle atrophy, and fat metabolism during ageing, the effects of treatment with a combination of TPTD and exercise on these factors remain unclear. Therefore, this study examined the effects of TPTD and exercise on bone, skeletal muscle, and fat in ovariectomized and tail-suspended rats.

Materials and methods

Seven-month-old female Wistar rats were ovariectomized and subjected to tail suspension. The rats were then randomized into one of the following four groups (n = 20/group) after 4 weeks: control group, treated with TPTD vehicle and no exercise; TPTD group (30 µg/kg TPTD, 3 days/week); Exercise group (treadmill at 12 m/min, 60 min/day, 5 days/week); and Combined group treated with TPTD and treadmill exercise. After 1 and 8 weeks of treatment, bone, skeletal muscle, and fat tissue parameters were evaluated.

Results

TPTD improved bone mineral density (BMD), bone structure, bone strength at the femoral metaphysis, and the percentage of skeletal muscle mass, and decreased the percentage of fat mass and the adipose volume in the bone marrow. Treadmill exercise increased BMD, bone strength of cancellous bone, and the percentage of skeletal muscle mass, and decreased the percentage of fat mass as seen on dual-energy X-ray absorptiometry. Furthermore, combined treatment significantly affected BMD, bone structure, and bone strength of cortical bone at the femoral diaphysis.

Conclusion

TPTD or treadmill exercise improved bone, skeletal muscle, and fat mass. Combination therapy with TPTD and exercise had synergistic effects on BMD, structure, and bone strength in ovariectomized, tail-suspended rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Edwards MH, Dennison EM, Aihie Sayer A, Fielding R, Cooper C (2015) Osteoporosis and sarcopenia in older age. Bone 80:126–130. https://doi.org/10.1016/j.bone.2015.04.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Oliveira A, Vaz C (2015) The role of sarcopenia in the risk of osteoporotic hip fracture. Clin Rheumatol 34:1673–1680. https://doi.org/10.1007/s10067-015-2943-9

    Article  CAS  PubMed  Google Scholar 

  3. Larsson L, Degens H, Li M, Salviati L, Lee YI, Thompson W, Kirkland JL, Sandri M (2019) Sarcopenia: aging-related loss of muscle mass and function. Physiol Rev 99:427–511. https://doi.org/10.1152/physrev.00061.2017

    Article  PubMed  Google Scholar 

  4. Kawao N, Kaji H (2015) Interactions between muscle tissues and bone metabolism. J Cell Biochem 116:687–695. https://doi.org/10.1002/jcb.25040

    Article  CAS  PubMed  Google Scholar 

  5. Schwartz AV (2015) Marrow fat and bone: review of clinical findings. Front Endocrinol (Lausanne) 30(6):40. https://doi.org/10.3389/fendo.2015.00040

    Article  Google Scholar 

  6. Singhal V, Bredella MA (2019) Marrow adipose tissue imaging in humans. Bone 118:69–76. https://doi.org/10.1016/j.bone.2018.01.009

    Article  PubMed  Google Scholar 

  7. Wong AK, Chandrakumar A, Whyte R, Reitsma S, Gillick H, Pokhoy A, Papaioannou A, Adachi JD (2020) Bone marrow and muscle fat infiltration are correlated among postmenopausal women with osteoporosis: The AMBERS Cohort Study. J Bone Miner Res 35:516–527. https://doi.org/10.1002/jbmr.3910 (Epub 2019/11/20)

    Article  CAS  PubMed  Google Scholar 

  8. Miyakoshi N, Kasukawa Y, Linkhart TA, Baylink DJ, Mohan S (2001) Evidence that anabolic effects of PTH on bone require IGF-I in growing mice. Endocrinology 142:4349–4356. https://doi.org/10.1210/endo.142.10.8436

    Article  CAS  PubMed  Google Scholar 

  9. Hawke TJ (1985) Garry DJ (2001) Myogenic satellite cells: physiology to molecular biology. J Appl Physiol 91:534–551. https://doi.org/10.1152/jappl.2001.91.2.534

    Article  Google Scholar 

  10. Nozaka K, Miyakoshi N, Kasukawa Y, Maekawa S, Noguchi H, Shimada Y (2008) Intermittent administration of human parathyroid hormone enhances bone formation and union at the site of cancellous bone osteotomy in normal and ovariectomized rats. Bone 42:90–97. https://doi.org/10.1016/j.bone.2007.08.041 (Epub 2007/09/14)

    Article  CAS  PubMed  Google Scholar 

  11. Nomura S, Kitami A, Takao-Kawabata R, Takakura A, Nakatsugawa M, Kono R, Maeno A, Tokuda A, Isogai Y, Ishizuya T, Utsunomiya H, Nakamura M (2019) Teriparatide improves bone and lipid metabolism in a male rat model of type 2 diabetes mellitus. Endocrinology 160:2339–2352. https://doi.org/10.1210/en.2019-00239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bonaiuti D, Shea B, Iovine R, Negrini S, Robinson V, Kemper HC, Wells GA, Tugwell P, Cranney A (2002) Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD000333

    Article  PubMed  Google Scholar 

  13. Wallace BA, Cumming RG (2000) Systematic review of randomized trials of the effect of exercise on bone mass in pre- and postmenopausal women. Calcif Tissue Int 67:10–18. https://doi.org/10.1007/s00223001089

    Article  CAS  PubMed  Google Scholar 

  14. Binder EF, Brown M, Sinacore DR, Steger-May K, Yarasheski KE, Schechtman KB (2004) Effects of extended outpatient rehabilitation after hip fracture: a randomized controlled trial. JAMA 292:837–846. https://doi.org/10.1001/jama.292.7.837

    Article  CAS  PubMed  Google Scholar 

  15. Papaioannou A, Adachi JD, Winegard K, Ferko N, Parkinson W, Cook RJ, Webber C, McCartney N (2003) Efficacy of home-based exercise for improving quality of life among elderly women with symptomatic osteoporosis-related vertebral fractures. Osteoporos Int 14:677–682. https://doi.org/10.1007/s00198-003-1423-2 (Epub 2003/07/22)

    Article  CAS  PubMed  Google Scholar 

  16. Sakamoto K, Endo N, Harada A, Sakada T, Tsushita K, Kita K, Hagino H, Sakai A, Yamamoto N, Okamoto T, Liu M, Kokaze A, Suzuki H (2013) Why not use your own body weight to prevent falls? A randomized, controlled trial of balance therapy to prevent falls and fractures for elderly people who can stand on one leg for ≤15 s. J Orthop Sci 18:110–120. https://doi.org/10.1007/s00776-012-0328-3 (Epub 2012/11/09)

    Article  PubMed  Google Scholar 

  17. Ruas JL, White JP, Rao RR, Kleiner S, Brannan KT, Harrison BC, Greene NP, Wu J, Estall JL, Irving BA, Lanza IR, Rasbach KA, Okutsu M, Nair KS, Yan Z, Leinwand LA, Spiegelman BM (2012) A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 151:1319–1331. https://doi.org/10.1016/j.cell.2012.10.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kaji H (2016) Effects of myokines on bone. Bonekey Rep 5:826. https://doi.org/10.1038/bonekey.2016.48 (Epub 2016/07/20)

    Article  PubMed  PubMed Central  Google Scholar 

  19. Pedersen BK, Febbraio MA (2012) Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8:457–465. https://doi.org/10.1038/nrendo.2012.49 (Epub 2012/04/03)

    Article  CAS  PubMed  Google Scholar 

  20. Lombardi G, Sanchis-Gomar F, Perego S, Sansoni V, Banfi G (2016) Implications of exercise-induced adipo-myokines in bone metabolism. Endocrine 54:284–305. https://doi.org/10.1007/s12020-015-0834-0 (Epub 2015/12/30)

    Article  CAS  PubMed  Google Scholar 

  21. Shimada Y, Sakuraba T, Matsunaga T, Misawa A, Kawatani M, Itoi E (2006) Effects of therapeutic magnetic stimulation on acute muscle atrophy in rats after hindlimb suspension. Biomed Res 27:23–27. https://doi.org/10.2220/biomedres.27.23

    Article  CAS  PubMed  Google Scholar 

  22. Takakura A, Lee JW, Hirano K, Isogai Y, Ishizuya T, Takano-Kawabata R, Iimura T (2017) Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariectomized rats. Bone Res 5:17002. https://doi.org/10.1038/boneres.2017.2 (Epub 2017/04/25)

    Article  PubMed  PubMed Central  Google Scholar 

  23. Akagawa M, Miyakoshi N, Kasukawa Y, Ono Y, Yuasa Y, Nagahata I, Sato C, Tsuchie H, Nagasawa H, Hongo M, Shimada Y (2018) Effects of activated vitamin D, alfacalcidol, and low-intensity aerobic exercise on osteopenia and muscle atrophy in type 2 diabetes mellitus model rats. PLoS ONE 13:e0204857. https://doi.org/10.1371/journal.pone.0204857 (Epub 2018/10/17)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Miyakoshi N, Fujii M, Kasukawa Y, Shimada Y (2019) Impact of vitamin C on teriparatide treatment in the improvement of bone mineral density, strength, and quality in vitamin C-deficient rats. J Bone Miner Metab 37:411–418. https://doi.org/10.1007/s00774-018-0941-0 (Epub 2018/07/16)

    Article  CAS  PubMed  Google Scholar 

  25. Segawa T, Miyakoshi N, Kasukawa Y, Aonuma H, Tsuchie H, Shimada Y (2016) Combined treatment with minodronate and vitamin C increases bone mineral density and strength in vitamin C-deficient rats. Osteoporos Sarcopenia 2:30–37. https://doi.org/10.1016/j.afos.2016.01.002 (Epub 2016/03/21)

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kasukawa Y, Miyakoshi N, Itoi E, Tsuchida T, Tamura Y, Kudo T, Suzuki K, Seki A, Sato K (2004) Effects of h-PTH on cancellous bone mass, connectivity, and bone strength in ovariectomized rats with and without sciatic-neurectomy. J Orthop Res 22:457–464. https://doi.org/10.1016/j.orthres.2003.08.017

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  28. Marędziak M, Śmieszek A, Chrząstek K, Basinska K, Marycz K (2015) Physical activity increases the total number of bone-marrow-derived mesenchymal stem cells, enhances their osteogenic potential, and inhibits their adipogenic properties. Stem Cells Int 2015:379093. https://doi.org/10.1155/2015/379093 (Epub 2015/06/16)

    Article  PubMed  PubMed Central  Google Scholar 

  29. Chen YJ, Huang CH, Lee IC, Lee YT, Chen MH, Young TH (2008) Effects of cyclic mechanical stretching on the mRNA expression of tendon/ligament-related and osteoblast-specific genes in human mesenchymal stem cells. Connect Tissue Res 49:7–14. https://doi.org/10.1080/03008200701818561

    Article  CAS  PubMed  Google Scholar 

  30. Bu S, Chen Y, Wang S, Zhang F, Ji G (2012) Treadmill training regulates β-catenin signaling through phosphorylation of GSK-3β in lumbar vertebrae of ovariectomized rats. Eur J Appl Physiol 112:3295–3304. https://doi.org/10.1007/s00421-011-2306-4

    Article  CAS  PubMed  Google Scholar 

  31. Shi R, Tian X, Feng Y, Cheng Z, Lu J, Brann DW, Zhang Q (2019) Expression of aromatase and synthesis of sex steroid hormones in skeletal muscle following exercise training in ovariectomized rats. Steroids 143:91–96. https://doi.org/10.1016/j.steroids.2019.01.00

    Article  CAS  PubMed  Google Scholar 

  32. Takao-Kawabata R, Isogai Y, Takakura A, Shimazu Y, Sugimoto E, Nakazono O, Ikegaki I, Kuriyama H, Tanaka S, Oda H, Ishizuka T (2015) Three-times-weekly administration of teriparatide improves vertebral and peripheral bone density, microarchitecture, and mechanical properties without accelerating bone resorption in ovariectomized rats. Calcif Tissue Int 97:156–168. https://doi.org/10.1007/s00223-015-9998-0 (Epub 2015/04/25)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Abboud M, Rybchyn MS, Liu J, Ning Y, Gordon-Thomson C, Brennan Speranza TC, Cole L, Greenfield H, Fraser DR, Mason RS (2017) The effect of parathyroid hormone on the uptake and retention of 25-hydroxyvitamin D in skeletal muscle cells. J Steroid Biochem Mol Biol 173:173–179. https://doi.org/10.1016/j.jsbmb.2017.01.001 (Epub 2017/01/16)

    Article  CAS  PubMed  Google Scholar 

  34. Ullman M, Oldfors A (1989) Effects of growth hormone on skeletal muscle. I. Studies on normal adult rats. Acta Physiol Scand 135:531–536. https://doi.org/10.1111/j.1748-1716.1989.tb08612.x

    Article  CAS  PubMed  Google Scholar 

  35. Brent MB, Brüel A, Thomsen JS (2018) PTH (1–34) and growth hormone in prevention of disuse osteopenia and sarcopenia in rats. Bone 110:244–253. https://doi.org/10.1016/j.bone.2018.02.017 (Epub 2018/02/20)

    Article  CAS  PubMed  Google Scholar 

  36. Kimura S, Yoshioka K (2014) Parathyroid hormone and parathyroid hormone type-1 receptor accelerate myocyte differentiation. Sci Rep 11(4):5066. https://doi.org/10.1038/srep05066

    Article  CAS  Google Scholar 

  37. Yoon S, Grynpas M, Mitchell J (2019) Intermittent PTH treatment improves bone and muscle in glucocorticoid treated Mdx mice: A model of Duchenne Muscular Dystrophy. Bone 121:232–242

    Article  CAS  Google Scholar 

  38. Schafer A, Sellmeyer D, Schwartz A, Rosen C, Vittinghoff E, Palermo L, Bilezikian J, Shoback D, Black D (2011) Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1–84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J Clin Endocrinol Metab 96:E1982-1989. https://doi.org/10.1210/jc.2011-0587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Brahm H, Piehl-Aulin K, Ljunghall S (1997) Bone metabolism during exercise and recovery: the influence of plasma volume and physical fitness. Calcif Tissue Int 61:192–198. https://doi.org/10.1007/s002239900322

    Article  CAS  PubMed  Google Scholar 

  40. Iwamoto J, Shimamura C, Takeda T, Abe H, Ichimura S, Sato Y, Toyama Y (2004) Effects of treadmill exercise on bone mass, bone metabolism, and calciotropic hormones in young growing rats. J Bone Miner Metab 22:26–31. https://doi.org/10.1007/s00774-003-0443-5

    Article  CAS  PubMed  Google Scholar 

  41. Scott JPR, Sale C, Greeves JP, Casey A, Dutton J, Fraser WD (2011) The role of exercise intensity in the bone metabolic response to an acute bout of weight-bearing exercise. J Appl Physiol 110:423–432. https://doi.org/10.1152/japplphysiol.00764.2010

    Article  CAS  PubMed  Google Scholar 

  42. Sugiyama T, Saxon LK, Zaman G, Moustafa A, Sunters A, Price JS, Lanyon LE (2008) Mechanical loading enhances the anabolic effects of intermittent parathyroid hormone (1–34) on trabecular and cortical bone in mice. Bone 43:238–248. https://doi.org/10.1016/j.bone.2008.04.012 (Epub 2008/05/01)

    Article  CAS  PubMed  Google Scholar 

  43. Chow JW, Fox S, Jagger CJ, Chambers TJ (1998) Role for parathyroid hormone in mechanical responsiveness of rat bone. Am J Physiol 274:E146-154. https://doi.org/10.1152/ajpendo.1998.274.1.E146

    Article  CAS  PubMed  Google Scholar 

  44. Gardinier JD, Mohamed F, Kohn DH (2015) PTH Signaling during exercise contributes to bone adaptation. J Bone Miner Res 30:1053–1063. https://doi.org/10.1002/jbmr.2432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Asahi Kasei Pharma Corporation for providing TPTD and Ms. Matsuzawa and Ms. Kudo for their support of our experiments.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

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

    Chiaki Sato, Naohisa Miyakoshi, Yuji Kasukawa, Koji Nozaka, Hiroyuki Tsuchie, Itsuki Nagahata, Yusuke Yuasa, Kazunobu Abe, Hikaru Saito, Ryo Shoji & Yoichi Shimada

Authors
  1. Chiaki Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naohisa Miyakoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuji Kasukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Koji Nozaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroyuki Tsuchie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Itsuki Nagahata
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yusuke Yuasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazunobu Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hikaru Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ryo Shoji
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yoichi Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Chiaki Sato: Investigation, Validation, Visualization. Writing—original draft Itsuki Nagahata: Investigation, Validation. Yusuke Yuasa: Investigation, Validation. Kazunobu Abe: Investigation. Hikaru Saito: Investigation. Ryo Shoji: Investigation. Hiroyuki Tsuchie: Investigation, Formal analysis. Koji Nozaka: Investigation, Formal analysis. Yuji Kasukawa: Conceptualization, Methodology, Writing—review & editing. Naohisa Miyakoshi: Conceptualization, Methodology, Project administration. Writing—review & editing. Yoichi Shimada: Conceptualization, Funding acquisition, Supervision.

Corresponding author

Correspondence to Naohisa Miyakoshi.

Ethics declarations

Conflict of interest

Naohisa Miyakoshi has received payments for lectures from Asahi Kasei Pharma Corporation. The other authors declare that they have no conflicts of interest.

Ethical approval

The protocols for all animal experiments were approved in advance by the Animal Research Committee of our institute, and all subsequent animal experiments adhered to the “Guidelines for Animal Experimentation” of our university (approval number: a-1-2935).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (JPEG 133 KB)

Supplementary file1 (DOCX 14 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sato, C., Miyakoshi, N., Kasukawa, Y. et al. Teriparatide and exercise improve bone, skeletal muscle, and fat parameters in ovariectomized and tail-suspended rats. J Bone Miner Metab 39, 385–395 (2021). https://doi.org/10.1007/s00774-020-01184-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-020-01184-0

Keywords

Search

Navigation