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Association of decreased muscle mass with reduced bone mineral density in patients with Graves’ disease

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Abstract

Aim

This study aimed to determine the association of decreased muscle mass with reduced bone mineral density in patients with Graves’ disease.

Methods

A total of 758 patients with Graves’ disease at diagnosis (mean age 41.2 years) were enrolled for a cross-sectional study; of these, 287 were enrolled for a cohort study with a median follow-up of 24 months. Meanwhile, 1164 age- and sex-matched healthy controls were recruited. All participants underwent dual-energy x-ray absorptiometry and muscle mass index (ASMI) measurements. The changes in ASMI and bone mineral density (BMD) were calculated from the measurements made at a gap of 2 years.

Results

The BMD of patients with Graves’ disease was still significantly lower after normalizing serum thyroid hormone levels compared with that of healthy controls. ASMI positively correlated with BMD in patients with Graves’ disease (lumbar BMD, r = 0.210; femoral neck BMD, r = 0.259; hip BMD, r = 0.235; P < 0.001), and this relationship persisted after successful anti-thyroid therapy (lumbar BMD, r = 0.169; femoral neck BMD, r = 0.281; hip BMD, r = 0.394; P < 0.001). Low muscle mass was associated with low BMD (OR, 1.436; 95% CI, 1.026–2.010). Improving the muscle mass led to changes in the bone mass of the femoral neck (OR, 0.420; 95% CI, 0.194–0.911) and hip (OR, 0.217; 95% CI, 0.092–0.511) during the follow-up. However, this phenomenon was not observed in lumbar and bone turnover markers.

Conclusions

The recovery of bone mass might be related to the recovery of the muscle mass. Patients with Graves’ disease should be helped to regain their muscle mass and thus accelerate the recovery of bone mass while administering anti-thyroid therapy.

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References

  1. D.S. Ross, H.B. Burch, D.S. Cooper, M.C. Greenlee, P. Laurberg, A.L. Maia et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. Off. J. Am. Thyroid. Assoc. 26, 1343–1421 (2016). https://doi.org/10.1089/thy.2016.0229

    Article  Google Scholar 

  2. A.P. Delitala, A. Scuteri, C. Doria, Thyroid hormone diseases and osteoporosis. J. Clin. Med. 2020;9. https://doi.org/10.3390/jcm9041034

  3. P. Vestergaard, L. Mosekilde, Hyperthyroidism, bone mineral, and fracture risk-a meta-analysis. Thyroid. Off. J. Am. Thyroid. Assoc. 13, 585–593 (2003). https://doi.org/10.1089/105072503322238854

    Article  Google Scholar 

  4. K. Takedani, M. Notsu, Graves’ disease and vertebral fracture: possible pathogenic link in postmenopausal women. Clin. Endocrinol. 93, 204–211 (2020). https://doi.org/10.1111/cen.14208

    Article  CAS  Google Scholar 

  5. S.R. Cummings, M.C. Nevitt, W.S. Browner, K. Stone, K.M. Fox, K.E. Ensrud et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N. Engl. J. Med. 332, 767–773 (1995). https://doi.org/10.1056/nejm199503233321202

    Article  CAS  PubMed  Google Scholar 

  6. G.R. Williams, J.H.D. Bassett, Thyroid diseases and bone health. J. Endocrinological Investig. 41, 99–109 (2018). https://doi.org/10.1007/s40618-017-0753-4

    Article  CAS  Google Scholar 

  7. G.C. Isaia, C. Roggia, D. Gola, M.D. Stefano, G. Gallone, G. Aimo et al. Bone turnover in hyperthyroidism before and after thyrostatic management. J. Endocrinological Investig. 23, 727–731 (2000). https://doi.org/10.1007/bf03345061

    Article  CAS  Google Scholar 

  8. C. Szlejf, C.K. Suemoto, C. Janovsky, Thyroid function and sarcopenia: results from the ELSA-Brasil study. J. Am. Geriatrics Soc. 68, 1545–1553 (2020). https://doi.org/10.1111/jgs.16416

    Article  Google Scholar 

  9. K. Agbaht, M.F. Erdogan, R. Emral, N. Baskal, S. Gullu, Circulating glucagon to ghrelin ratio as a determinant of insulin resistance in hyperthyroidism. Endocrine 45, 106–113 (2014). https://doi.org/10.1007/s12020-013-9951-9

    Article  CAS  PubMed  Google Scholar 

  10. L. Cianferotti, M.L. Brandi, Muscle-bone interactions: basic and clinical aspects. Endocrine 45, 165–177 (2014). https://doi.org/10.1007/s12020-013-0026-8

    Article  CAS  PubMed  Google Scholar 

  11. M.D. Brennan, C. Powell, K.R. Kaufman, P.C. Sun, R.S. Bahn, K.S. Nair, The impact of overt and subclinical hyperthyroidism on skeletal muscle. Thyroid. Off. J. Am. Thyroid. Assoc. 16, 375–380 (2006). https://doi.org/10.1089/thy.2006.16.375

    Article  Google Scholar 

  12. A.J. Cruz-Jentoft, G. Bahat, J. Bauer, Y. Boirie, O. Bruyère, T. Cederholm et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 48, 16–31 (2019). https://doi.org/10.1093/ageing/afy169

    Article  PubMed  Google Scholar 

  13. F. Cosman, S.J. de Beur, M.S. LeBoff, E.M. Lewiecki, B. Tanner, S. Randall et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos. Int. 25, 2359–2381 (2014). https://doi.org/10.1007/s00198-014-2794-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. S.M. de la Monte, J.J. Kril, Human alcohol-related neuropathology. Acta Neuropathologica 127, 71–90 (2014). https://doi.org/10.1007/s00401-013-1233-3

    Article  CAS  PubMed  Google Scholar 

  15. F. Du, D. Birong, H. Changquan, W. Hongmei, Z. Yanling, Z. Wen et al. Association of osteoporotic fracture with smoking, alcohol consumption, tea consumption and exercise among Chinese nonagenarians/centenarians. J. Nutr. Health Aging 15, 327–331 (2011). https://doi.org/10.1007/s12603-010-0270-z

    Article  CAS  PubMed  Google Scholar 

  16. G.J. Cho, J.H. Shin, K.W. Yi, H.T. Park, T. Kim, J.Y. Hur et al. Serum ferritin levels are associated with metabolic syndrome in postmenopausal women but not in premenopausal women. Menopause 18, 1120–1124 (2011). https://doi.org/10.1097/gme.0b013e318217e172

    Article  PubMed  Google Scholar 

  17. J.S. Meengs, L.S. Roe, B.J. Rolls, Vegetable variety: an effective strategy to increase vegetable intake in adults. J. Acad. Nutr. Dietetics 112, 1211–1215 (2012). https://doi.org/10.1016/j.jand.2012.05.013

    Article  Google Scholar 

  18. E.Z. Movassagh, A.D.G. Baxter-Jones, S. Kontulainen, S. Whiting, M. Szafron, H. Vatanparast, Vegetarian-style dietary pattern during adolescence has long-term positive impact on bone from adolescence to young adulthood: a longitudinal study. Nutr J. 17, 36 (2018). https://doi.org/10.1186/s12937-018-0324-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. H.R. Kim, Y.S. Hong, S.H. Park, J.H. Ju, K.Y. Kang, Low bone mineral density predicts the formation of new syndesmophytes in patients with axial spondyloarthritis. Arthritis Res. Ther. 20, 231 (2018). https://doi.org/10.1186/s13075-018-1731-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. I.K. Blom-Høgestøl, S. Hewitt, M. Chahal-Kummen, C. Brunborg, H.L. Gulseth, J.A. Kristinsson et al. Bone metabolism, bone mineral density and low-energy fractures 10 years after Roux-en-Y gastric bypass. Bone 127, 436–445 (2019). https://doi.org/10.1016/j.bone.2019.07.014

    Article  PubMed  Google Scholar 

  21. R.A. Fielding, B. Vellas, W.J. Evans, S. Bhasin, J.E. Morley, A.B. Newman et al. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J. Am. Med. Dir. Assoc. 12, 249–256 (2011). https://doi.org/10.1016/j.jamda.2011.01.003

    Article  PubMed  Google Scholar 

  22. H.K. Kim, T. Suzuki, K. Saito, H. Yoshida, H. Kobayashi, H. Kato et al. Effects of exercise and amino acid supplementation on body composition and physical function in community-dwelling elderly Japanese sarcopenic women: a randomized controlled trial. J. Am. Geriatrics Soc. 60, 16–23 (2012). https://doi.org/10.1111/j.1532-5415.2011.03776.x

    Article  Google Scholar 

  23. Y. Zhang, X. Shen, L. He, F. Zhao, S. Yan, Association of sarcopenia and muscle mass with both peripheral neuropathy and nerve function in patients with type 2 diabetes. Diabetes Res. Clin. Pract. 162, 108096 (2020). https://doi.org/10.1016/j.diabres.2020.108096

    Article  PubMed  Google Scholar 

  24. M.L. Bouxsein, R. Eastell, L.Y. Lui, L.A. Wu, A.E. de Papp, A. Grauer et al. Change in bone density and reduction in fracture risk: a meta-regression of published trials. J. Bone Miner. Res. 34, 632–642 (2019). https://doi.org/10.1002/jbmr.3641

    Article  PubMed  Google Scholar 

  25. R. Eastell, P. Szulc, Use of bone turnover markers in postmenopausal osteoporosis. lancet Diabetes Endocrinol. 5, 908–923 (2017). https://doi.org/10.1016/s2213-8587(17)30184-5

    Article  PubMed  Google Scholar 

  26. K. Maratova, O. Soucek, J. Matyskova, Z. Hlavka, L. Petruzelkova, B. Obermannova et al. Muscle functions and bone strength are impaired in adolescents with type 1 diabetes. Bone 106, 22–27 (2018). https://doi.org/10.1016/j.bone.2017.10.005

    Article  PubMed  Google Scholar 

  27. M. Hayashi, K. Abe, M. Fujita, K. Okai, A. Takahashi, H. Ohira, Association between sarcopenia and osteoporosis in chronic liver disease. Hepatol. Res. 48, 893–904 (2018). https://doi.org/10.1111/hepr.13192

    Article  PubMed  Google Scholar 

  28. Apostu D., Lucaciu O., Oltean-Dan D., Mureșan A.D., Moisescu-Pop C., Maxim A., et al. The influence of thyroid pathology on osteoporosis and fracture risk: a review. Diagnostics. 2020;10: https://doi.org/10.3390/diagnostics10030149

  29. T. Grofte, T. Wolthers, N. Moller, J.O. Jorgensen, A. Flyvbjerg, H. Orskov et al. Moderate hyperthyroidism reduces liver amino nitrogen conversion, muscle nitrogen contents and overall nitrogen balance in rats. Eur. J. Clin. Investig. 27, 85–92 (1997). https://doi.org/10.1046/j.1365-2362.1997.00101.x

    Article  CAS  Google Scholar 

  30. P. Iglesias, J.J. Díez, Influence of thyroid dysfunction on serum concentrations of adipocytokines. Cytokine 40, 61–70 (2007). https://doi.org/10.1016/j.cyto.2007.10.001

    Article  CAS  PubMed  Google Scholar 

  31. N. Kubota, W. Yano, T. Kubota, T. Yamauchi, S. Itoh, H. Kumagai et al. Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake. Cell Metab. 6, 55–68 (2007). https://doi.org/10.1016/j.cmet.2007.06.003

    Article  CAS  PubMed  Google Scholar 

  32. C. Di Munno, R.A. Busiello, J. Calonne, A.M. Salzano, J. Miles-Chan, A. Scaloni et al. Adaptive thermogenesis driving catch-up fat is associated with increased muscle type 3 and decreased hepatic type 1 iodothyronine deiodinase activities: a functional and proteomic study. Front. Endocrinol. 12, 631176 (2021). https://doi.org/10.3389/fendo.2021.631176

    Article  Google Scholar 

  33. S. Judex, K.J. Carlson, Is bone’s response to mechanical signals dominated by gravitational loading? Med. Sci. Sports Exerc. 41, 2037–2043 (2009). https://doi.org/10.1249/MSS.0b013e3181a8c6e5

    Article  PubMed  Google Scholar 

  34. R.J. Wetzsteon, B.S. Zemel, J. Shults, K.M. Howard, L.W. Kibe, M.B. Leonard, Mechanical loads and cortical bone geometry in healthy children and young adults. Bone 48, 1103–1108 (2011). https://doi.org/10.1016/j.bone.2011.01.005

    Article  PubMed  PubMed Central  Google Scholar 

  35. G. Karsenty, E.N. Olson, Bone and muscle endocrine functions: unexpected paradigms of inter-organ communication. Cell 164, 1248–1256 (2016). https://doi.org/10.1016/j.cell.2016.02.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. L.H. Bogl, A. Latvala, J. Kaprio, O. Sovijärvi, A. Rissanen, K.H. Pietiläinen, An investigation into the relationship between soft tissue body composition and bone mineral density in a young adult twin sample. J. Bone Miner. Res. 26, 79–87 (2011). https://doi.org/10.1002/jbmr.192

    Article  PubMed  Google Scholar 

  37. G. Battafarano, M. Rossi, F. Marampon, S. Minisola, A. Del Fattore, Bone control of muscle function. Int. J. Mol. Sci. 2020;21, https://doi.org/10.1016/bs.acc.2019.07.010

  38. K. Tsang, H. Liu, Y. Yang, J.F. Charles, J. Ermann, Defective circadian control in mesenchymal cells reduces adult bone mass in mice by promoting osteoclast function. Bone 121, 172–180 (2019). https://doi.org/10.1016/j.bone.2019.01.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. S.C. Manolagas, R.L. Jilka, Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N. Engl. J. Med. 332, 305–311 (1995). https://doi.org/10.1056/nejm199502023320506

    Article  CAS  PubMed  Google Scholar 

  40. K.M. Kim, E.Y. Lee, S. Lim, H.C. Jang, C.O. Kim, Favorable effects of skeletal muscle on bone are distinguished according to gender and skeletal sites. Osteoporos. Sarcopenia 3, 32–36 (2017). https://doi.org/10.1016/j.afos.2016.11.001

    Article  PubMed  Google Scholar 

  41. B.J. Ausk, P. Huber, S. Srinivasan, S.D. Bain, R.Y. Kwon, E.A. McNamara et al. Metaphyseal and diaphyseal bone loss in the tibia following transient muscle paralysis are spatiotemporally distinct resorption events. Bone 57, 413–422 (2013). https://doi.org/10.1016/j.bone.2013.09.009

    Article  PubMed  Google Scholar 

  42. M.K. Kwak, B.J. Kim, J.S. Kim, S.H. Lee, J.M. Koh, The local and systemic interactions between muscle and bone in postmenopausal Korean women. Calcif. Tissue Int. 105, 373–382 (2019). https://doi.org/10.1007/s00223-019-00585-2

    Article  CAS  PubMed  Google Scholar 

  43. C. Suetta, S.P. Magnusson, A. Rosted, P. Aagaard, A.K. Jakobsen, L.H. Larsen et al. Resistance training in the early postoperative phase reduces hospitalization and leads to muscle hypertrophy in elderly hip surgery patients-a controlled, randomized study. J. Am. Geriatrics Soc. 52, 2016–2022 (2004). https://doi.org/10.1111/j.1532-5415.2004.52557.x

    Article  Google Scholar 

  44. J.T. Cramer, A.J. Cruz-Jentoft, F. Landi, M. Hickson, M. Zamboni, S.L. Pereira et al. Impacts of high-protein oral nutritional supplements among malnourished men and women with sarcopenia: a multicenter, randomized, double-blinded, controlled trial. J. Am. Med. Dir. Assoc. 17, 1044–1055 (2016). https://doi.org/10.1016/j.jamda.2016.08.009

    Article  PubMed  Google Scholar 

  45. R.W. Lau, L.R. Liao, F. Yu, T. Teo, R.C. Chung, M.Y. Pang, The effects of whole body vibration therapy on bone mineral density and leg muscle strength in older adults: a systematic review and meta-analysis. Clin. Rehabil. 25, 975–988 (2011). https://doi.org/10.1177/0269215511405078

    Article  PubMed  Google Scholar 

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Acknowledgements

We are grateful to the patients for their help and willingness to participate in the study.

Funding

This work was financially supported by Joint Funds for the Innovation of Science and Technology, Fujian Province (No. 2019Y9110), Youth Scientific Research Project of Fujian Provincial Health Commission (No. 2020QNA057) and Natural Science Foundation of Fujian Province (No. 2018J01171) financially supported this work.

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Author notes

  1. These authors contributed equally: Yongze Zhang, Yuzhen Ke, Lingning Huang

Authors and Affiliations

  1. Department of Endocrinology, the First Affiliated Hospital of Fujian Medical University, 20 Cha Zhong Road, Fuzhou, 350005, Fujian, China

    Yongze Zhang, Yuzhen Ke, Lingning Huang, Ximei Shen, Sunjie Yan, Fengying Zhao, Yimei Li & Yuxi Lin

  2. Clinical Research Center for Metabolic Diseases of Fujian Province, the First Affiliated Hospital of Fujian Medical University, 20 Cha Zhong Road, Fuzhou, 350005, Fujian, China

    Yongze Zhang, Yuzhen Ke, Lingning Huang, Ximei Shen, Sunjie Yan, Fengying Zhao, Yimei Li & Yuxi Lin

  3. Diabetes Research Institute of Fujian Province, the First Affiliated Hospital of Fujian Medical University, 20 Cha Zhong Road, Fuzhou, 350005, Fujian, China

    Yongze Zhang, Yuzhen Ke, Lingning Huang, Ximei Shen, Sunjie Yan, Fengying Zhao, Yimei Li & Yuxi Lin

  4. Metabolic Diseases Research Institute, the First Affiliated Hospital of Fujian Medical University, 20 Cha Zhong Road, Fuzhou, 350005, Fujian, China

    Yongze Zhang, Yuzhen Ke, Lingning Huang, Ximei Shen, Sunjie Yan, Fengying Zhao, Yimei Li & Yuxi Lin

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Correspondence to Sunjie Yan.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).

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Informed consent was obtained from all patients for being included in the study. This study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University, and the participants gave informed consent.

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Zhang, Y., Ke, Y., Huang, L. et al. Association of decreased muscle mass with reduced bone mineral density in patients with Graves’ disease. Endocrine 75, 916–926 (2022). https://doi.org/10.1007/s12020-021-02960-2

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