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Pharmacologic Treatments to Preserve Bone and Muscle Mass in Osteosarcopenia

Current Osteoporosis Reports volume 18, pages 228–231 (2020)Cite this article

Abstract

Purpose of Review

We aim to recast the diagnosis of osteosarcopenia in light of its pathophysiology rather than of the age at which it is diagnosed. We will consider why we think the diagnosis of osteosarcopenia is missed in those who are not elderly and why pharmacologic treatment based on pathophysiology rather than age may provide a more comprehensive treatment for patients with the condition.

Recent Findings

We will present recent findings on the pathogenesis of osteosarcopenia from two distinct groups of patients which will highlight why pathophysiology is of paramount importance in designing treatment.

Summary

We will show that in patients with cancer and burns, muscle catabolic factors are released from bone on resorption, exert a paracrine effect on muscle to cause catabolism, and can be prevented with the use of anti-resorptive drugs. New uses for anti-resorptives may result from these findings.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. • Bauer J, Morley JE, Schols AMWJ, Ferrucci L, Cruz-Jentoft AJ, Dent E, et al. Sarcopenia: A time for action. An SCWD position paper. J Cachexia Sarcopenia Muscle. 2019;10(5):956–61. https://doi.org/10.1002/jcsm.12483This paper represents the latest consensus thinking onthe diagnosis of osteosarcopenia. Current findings and their potential therapeutic use should be judged in relation to the current thinking of experts in the field.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Klein GL, Herndon DN, Rutan TC, Sherrard DJ, Coburn JW, Langman CB, et al. Bone disease in burn patients. J Bone Miner Res. 1993;8(3):337–45. https://doi.org/10.1002/jbmr.5650080311.

    CAS  Article  PubMed  Google Scholar 

  3. Bauer J, Cruz-Jentoft AJ, Fielding RA, Kanis JA, Reginster JY, Bruyere O, et al. Is there enough evidence for osteosarcopenic obesity as a distinct entity? A critical literature review. Calcif Tissue Int. 2019;105(2):109–24. https://doi.org/10.1007/s00223-019-00561-w.

    CAS  Article  PubMed  Google Scholar 

  4. Millar SA, Anderson SI, O’Sullivan SE. Osteokines and the vasculature: A review of the effects of osteocalcin, fibroblast growth factor-23 and lipocalin-2. PeerJ. 2019;7:e7139. https://doi.org/10.7717/peerj.7139.eCollection2019.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Costamagna D, Costelli P, Sampaolesi M, Penna F. Role of inflammation in muscle homeostasis and myogenesis. Mediat Inflamm. 2015;2015:805172. https://doi.org/10.1155/2015/805172.

    CAS  Article  Google Scholar 

  6. Bonetto A, Ayodoglu T, Jin X, Zhang Z, Zhan R, Puzis L, et al. JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab. 2012;303:E410–21.

    CAS  Article  Google Scholar 

  7. Fleisch H, Russell RGG, Francis MD. Diphosphonates inhibit hydroxyapatite dissolution and bone resorption in tissue culture and in vivo. Science. 1969;165:1262–4.

    CAS  Article  Google Scholar 

  8. Heaney RP, Saville PD. Etidonate disodium in post-menopausal osteoporosis. Clin Pharmacol Ther. 1976;114:307–15.

    Google Scholar 

  9. Currow DC, Mattocks M, Cella D, Muscaritoli M. Efficacy of anamorelin , a novel non-peptide ghrelin analog, in patients with advanced small-cell lung cancer (NSCLC) and cachexia – Review and expert opinion. Int J Mol Sci. 2018;19(11):E3471. https://doi.org/10.3390/ijms19113471Review.

    CAS  Article  PubMed  Google Scholar 

  10. • Waning DL, Mohammad KS, Reiken S, Xie W, Andersson DC, John S, et al. Excess TGF-β mediates muscle weakness associated with bone metastases in mice. Nat Med. 2015;21(11):1262–71. https://doi.org/10.1038/nm.3961This was the first paper to demonstrate that anti-resorptives could prevent muscle wasting in cancer patients with bone metastases.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Hain BA, Jude B, Xu H, Smuin DM, Fox EJ, Elfar JC, et al. Zoledronic acid improves muscle function in healthy mice treated with chemotherapy. J Bone Miner Res published online 30 Oct 2019. https://doi.org/10.1002/jbmr.3890.

    Article  Google Scholar 

  12. Essex AL, Pin F, Huot JR, Bonewald LF, Plotkin LI, Bonetto A. Bisphosphonate treatment ameliorates chemotherapy-induced bone and muscle abnormalities in young mice. Front Endocrinol (Lausanne). 2019. https://doi.org/10.3389/fendo.2019.00809.

  13. Klein GL, Herndon DN, Goodman WG, Langman CB, Phillips WA, Dickson IR, et al. Histomorphometric and biochemical characterization of bone following acute severe burns in children. Bone. 1995;17(5):455–60. https://doi.org/10.1016/8756-3282(95)00279-1.

    CAS  Article  PubMed  Google Scholar 

  14. Klein GL, Bi LX, Sherrard DJ, Beavan SR, Ireland D, Compston JE, et al. Evidence supporting a role of glucocorticoids in the short-term bone loss in burned children. Osteoporos Int. 2004;15(6):468–74. https://doi.org/10.1007/s00198—003-1572-3.

    CAS  Article  PubMed  Google Scholar 

  15. Klein GL, Wimalawansa SJ, Kulkarni G, Sherrard DJ, Sanford AP, Herndon DN. The efficacy of the acute administration of pamidronate on the conservation of bone mass following acute severe burn injury in children: a double-blind, randomized, controlled study. Osteoporos Int. 2005;16:631–5. https://doi.org/10.1007/s00-198-004-1731-1.

    CAS  Article  PubMed  Google Scholar 

  16. Klein GL, Herndon DN, Langman CB, Rutan TC, Young WE, Pembleton G, et al. Long-term reduction in bone mass after severe burn injury in children. J Pediatr. 1995;126:252–6. https://doi.org/10.1016/s0022-3476(95)-70553-8.

    CAS  Article  PubMed  Google Scholar 

  17. Mayes T, Gottschlich MM, Khoury J, Kagan RJ. Investigation of bone health subsequent to vitamin D supplementation in children following burn injury. Nutr Clin Pract. 2015;30:830–7. https://doi.org/10.1177/0884533615587220.

    CAS  Article  PubMed  Google Scholar 

  18. Porter C, Sousse LE, Irick R, Schryver E, Klein GL. Interactions of phosphate metabolism with severe injury, including burns. JBMR Plus. 2017;1(2):59–65. https://doi.org/10.1002/jbm4.10011.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Porro LJ, Herndon DN, Rodriguez NA, Jennings K, Klein GL, Mlcak RP, et al. Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial of safety and efficacy. J Am Coll Surg. 2012;214:489–502. https://doi.org/10.1016/j.jamcollsurg.2011.12.038.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Reeves PT, Herndon DN, Tanksley JD, Jennings K, Klein GL, Mlcak RP, et al. Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial. Shock. 2016;45:367–74. https://doi.org/10.1097/SHK.0000000000000517.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. Przkora R, Herndon DN, Sherrard DJ, Chinkes DL, Klein GL. Pamidronate preserves bone mass for at least 2 years following acute administration for pediatric burn injury. Bone. 2007;41:297–302. https://doi.org/10.1016/j.bone.2007.04.195.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Borsheim E, Herndon DN, Hawkins HK, Suman OE, Cotter M, Klein GL. Pamidronate attenuates muscle loss after pediatric burn injury. J Bone Miner Res. 2014;29:1369–72. https://doi.org/10.1002/jbmr.2162.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. • Pin F, Bonetto A, Bonewald LF, Klein GL. Molecular mechanisms responsible for the rescue effects of pamidronate on muscle atrophy in pediatric burn patients. Front Endocrinol (Lausanne). 2019. https://doi.org/10.3389/fendo.2019.00543This paper confirmed the original findings of muscle sparing in pediatric burn patients and provided evidence that bone resorption was instrumental in causing muscle loss in widely disparate groups of patients.

  24. Klein GL. The role of the musculoskeletal system in post-burn hypermetabolism. Metabolism. 2019;97:81–6. https://doi.org/10.1016/j.metabol.2019.06.001.

    CAS  Article  PubMed  Google Scholar 

  25. Bonnet N, Bourguin L, Bivet E, Douni E, Ferrari S. RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass. J Clin Invest. 2019;129:3214–23. https://doi.org/10.1172/JCI.125915.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported in part by a grant from the National Institutes of Health 1P50 GM60338 (protocol 4) 2000-2005. The author warrants that he has no conflicts of interest, financial or otherwise.

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  1. Department of Orthopaedic Surgery and Rehabilitaton, University of Texas Medical Branch, Galveston, TX, 77555-0165, USA

    Gordon L Klein

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  1. Gordon L Klein
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Correspondence to Gordon L Klein.

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This article is part of the Topical Collection on Muscle and Bone

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Klein, G.L. Pharmacologic Treatments to Preserve Bone and Muscle Mass in Osteosarcopenia. Curr Osteoporos Rep 18, 228–231 (2020). https://doi.org/10.1007/s11914-020-00576-5

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  • DOI: https://doi.org/10.1007/s11914-020-00576-5

Keywords

  • Bone
  • Muscle
  • Osteosarcopenia
  • Bisphosphonates
  • Muscle catabolic factors