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The association between myasthenia gravis and risk of fracture: a systematic review and meta-analysis

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Abstract

Patients with myasthenia gravis (MG), because of their muscle weakness and exposure to corticosteroids treatment, are generally considered to be at increased risk for osteoporosis or fracture. However, clinical evidence of this issue is lacking. In this review, we systematically searched databases, including Cochrane Library, PubMed, Embase, and Airiti library from inception to the end of November 2023 for cohort studies that compared participants with MG and participants without MG for incidence of osteoporosis or fracture. We used the Newcastle–Ottawa Scale for quality assessment. In total, we included 3 studies with 34,865 participants. The pooled meta-analysis using the random effect model demonstrated no significant difference in risk of fracture in the MG group (odds ratio = 1.52; 95% confidence interval = 0.74 to 3.12; I2 = 93%; between-study variance [τ2] = 0.32) compared with that for the non-MG group. Due to limited studies, we could not perform a quantitative analysis for risk of osteoporosis. In conclusion, we found no robust evidence to support the proposition that patients with MG are at higher risk for fracture than general comparators. The explanations and underlying mechanisms of this finding remain unclear, we therefore conclude that additional studies are warranted.

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References

  1. Salari N, Fatahi B, Bartina Y, Kazeminia M, Fatahian R, Mohammadi P, Shohaimi S, Mohammadi M (2021) Global prevalence of myasthenia gravis and the effectiveness of common drugs in its treatment: a systematic review and meta-analysis. J Transl Med 19:516. https://doi.org/10.1186/s12967-021-03185-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Narayanaswami P, Sanders DB, Wolfe G et al (2021) International consensus guidance for management of Myasthenia Gravis: 2020 Update. Neurology 96:114–122. https://doi.org/10.1212/wnl.0000000000011124

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ruiter AM, Verschuuren J, Tannemaat MR (2020) Fatigue in patients with myasthenia gravis. A systematic review of the literature. Neuromuscul Disord 30:631–639. https://doi.org/10.1016/j.nmd.2020.06.010

    Article  PubMed  Google Scholar 

  4. Smith EL, Gilligan C (1991) Physical activity effects on bone metabolism. Calcif Tissue Int 49(Suppl):S50-54. https://doi.org/10.1007/bf02555089

    Article  PubMed  Google Scholar 

  5. Carter MI, Hinton PS (2014) Physical activity and bone health. Mo Med 111:59–64

    PubMed  PubMed Central  Google Scholar 

  6. Adami G, Saag KG (2019) Glucocorticoid-induced osteoporosis: 2019 concise clinical review. Osteoporos Int 30:1145–1156. https://doi.org/10.1007/s00198-019-04906-x

    Article  CAS  PubMed  Google Scholar 

  7. Lane NE (2019) Glucocorticoid-induced osteoporosis: New insights into the pathophysiology and treatments. Curr Osteoporos Rep 17:1–7. https://doi.org/10.1007/s11914-019-00498-x

    Article  PubMed  PubMed Central  Google Scholar 

  8. Wakata N, Nemoto H, Sugimoto H, Nomoto N, Konno S, Hayashi N, Araki Y, Nakazato A (2004) Bone density in myasthenia gravis patients receiving long-term prednisolone therapy. Clin Neurol Neurosurg 106:139–141. https://doi.org/10.1016/j.clineuro.2003.12.001

    Article  PubMed  Google Scholar 

  9. Braz NFT, Rocha NP, Vieira ÉLM, Gomez RS, Barbosa IG, Malheiro OB, Kakehasi AM, Teixeira AL (2017) Negative impact of high cumulative glucocorticoid dose on bone metabolism of patients with myasthenia gravis. Neurol Sci 38:1405–1413. https://doi.org/10.1007/s10072-017-2964-z

    Article  PubMed  Google Scholar 

  10. Guan Y, Lv F, Meng Y et al (2017) Association between bone mineral density, muscle strength, and vitamin D status in patients with myasthenia gravis: a cross-sectional study. Osteoporos Int 28:2383–2390. https://doi.org/10.1007/s00198-017-4041-0

    Article  CAS  PubMed  Google Scholar 

  11. Yeh JH, Chen HJ, Chen YK, Chiu HC, Kao CH (2014) Increased risk of osteoporosis in patients with myasthenia gravis: a population-based cohort study. Neurology 83:1075–1079. https://doi.org/10.1212/wnl.0000000000000804

    Article  PubMed  Google Scholar 

  12. Kassardjian C, Widdifield J, Paterson JM, Kopp A, Nagamuthu C, Barnett C, Tu K, Breiner A (2021) Fracture risk in patients with myasthenia gravis: A population-based cohort study. J Neuromuscul Dis 8:625–632. https://doi.org/10.3233/jnd-200612

    Article  PubMed  Google Scholar 

  13. Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71

    Article  PubMed  PubMed Central  Google Scholar 

  14. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605. https://doi.org/10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  15. Lo CK, Mertz D, Loeb M (2014) Newcastle-Ottawa scale: comparing reviewers’ to authors’ assessments. BMC Med Res Methodol 14:45. https://doi.org/10.1186/1471-2288-14-45

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rstudio software. Available online: Https://www.Rstudio.Com/products/rstudio/download. Accessed 15 November 2023

  17. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  18. Pouwels S, de Boer A, Javaid MK, Hilton-Jones D, Verschuuren J, Cooper C, Leufkens HG, de Vries F (2013) Fracture rate in patients with myasthenia gravis: the general practice research database. Osteoporos Int 24:467–476. https://doi.org/10.1007/s00198-012-1970-5

    Article  CAS  PubMed  Google Scholar 

  19. Chiu HC, Vincent A, Newsom-Davis J, Hsieh KH, Hung T (1987) Myasthenia gravis: population differences in disease expression and acetylcholine receptor antibody titers between Chinese and Caucasians. Neurology 37:1854–1857. https://doi.org/10.1212/wnl.37.12.1854

    Article  CAS  PubMed  Google Scholar 

  20. Gregson CL, Armstrong DJ, Bowden J et al (2022) UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 17:58. https://doi.org/10.1007/s11657-022-01061-5

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chowdhury SR, Chandra Das D, Sunna TC, Beyene J, Hossain A (2023) Global and regional prevalence of multimorbidity in the adult population in community settings: a systematic review and meta-analysis. EClinicalMedicine 57:101860. https://doi.org/10.1016/j.eclinm.2023.101860

    Article  PubMed  PubMed Central  Google Scholar 

  22. Clynes MA, Harvey NC, Curtis EM, Fuggle NR, Dennison EM, Cooper C (2020) The epidemiology of osteoporosis. Br Med Bull 133:105–117. https://doi.org/10.1093/bmb/ldaa005

    Article  PubMed  Google Scholar 

  23. Kutsal FY, Ergin Ergani GO (2021) Vertebral compression fractures: Still an unpredictable aspect of osteoporosis. Turkish J Med Sci 51:393–399. https://doi.org/10.3906/sag-2005-315

    Article  Google Scholar 

  24. Alsoof D, Anderson G, McDonald CL, Basques B, Kuris E, Daniels AH (2022) Diagnosis and management of vertebral compression fracture. Am J Med 135:815–821. https://doi.org/10.1016/j.amjmed.2022.02.035

    Article  PubMed  Google Scholar 

  25. Lin CW, Chen TC, Jou JR, Woung LC (2018) Update on ocular myasthenia gravis in Taiwan. Taiwan J Ophthalmol 8:67–73. https://doi.org/10.4103/tjo.tjo_39_17

    Article  PubMed  PubMed Central  Google Scholar 

  26. Kanis JA, Johansson H, Oden A et al (2004) A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 19:893–899. https://doi.org/10.1359/jbmr.040134

    Article  PubMed  Google Scholar 

  27. Canalis E, Mazziotti G, Giustina A, Bilezikian JP (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 18:1319–1328. https://doi.org/10.1007/s00198-007-0394-0

    Article  CAS  PubMed  Google Scholar 

  28. Sato AY, Peacock M, Bellido T (2018) Glucocorticoid excess in bone and muscle. Clin Rev Bone Miner Metab 16:33–47. https://doi.org/10.1007/s12018-018-9242-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Safipour Z, van der Zanden R, van den Bergh J, Janssen P, Vestergaard P, de Vries F, Driessen JHM (2022) The use of oral glucocorticoids and the risk of major osteoporotic fracture in patients with myasthenia gravis. Osteoporos Int 33:649–658. https://doi.org/10.1007/s00198-021-06101-3

    Article  CAS  PubMed  Google Scholar 

  30. Konno S, Suzuki S, Masuda M, Nagane Y, Tsuda E, Murai H, Imai T, Fujioka T, Suzuki N, Utsugisawa K (2015) Association between glucocorticoid-induced osteoporosis and Myasthenia Gravis: A cross-sectional study. PLoS One 10:e0126579. https://doi.org/10.1371/journal.pone.0126579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787. https://doi.org/10.1007/s001980200108

    Article  PubMed  Google Scholar 

  32. Chotiyarnwong P, McCloskey EV (2020) Pathogenesis of glucocorticoid-induced osteoporosis and options for treatment. Nat Rev Endocrinol 16:437–447. https://doi.org/10.1038/s41574-020-0341-0

    Article  PubMed  Google Scholar 

  33. En-Nosse M, Hartmann S, Trinkaus K, Alt V, Stigler B, Heiss C, Kilian O, Schnettler R, Lips KS (2009) Expression of non-neuronal cholinergic system in osteoblast-like cells and its involvement in osteogenesis. Cell Tissue Res 338:203–215. https://doi.org/10.1007/s00441-009-0871-1

    Article  CAS  PubMed  Google Scholar 

  34. Sato T, Abe T, Chida D et al (2010) Functional role of acetylcholine and the expression of cholinergic receptors and components in osteoblasts. FEBS Lett 584:817–824. https://doi.org/10.1016/j.febslet.2010.01.001

    Article  CAS  PubMed  Google Scholar 

  35. Ma Y, Elefteriou F (2020) Brain-derived acetylcholine maintains peak bone mass in adult female mice. J Bone Miner Res 35:1562–1571. https://doi.org/10.1002/jbmr.4024

    Article  CAS  PubMed  Google Scholar 

  36. Cunningham J (2005) Posttransplantation bone disease. Transplantation 79:629–634. https://doi.org/10.1097/01.tp.0000149698.79739.ef

    Article  PubMed  Google Scholar 

  37. Kuppachi S, Cheungpasitporn W, Li R et al (2022) Kidney transplantation, immunosuppression and the risk of fracture: Clinical and economic implications. Kidney Med 4:100474. https://doi.org/10.1016/j.xkme.2022.100474

    Article  PubMed  PubMed Central  Google Scholar 

  38. Vestergaard P, Rejnmark L, Mosekilde L (2006) Methotrexate, azathioprine, cyclosporine, and risk of fracture. Calcif Tissue Int 79:69–75. https://doi.org/10.1007/s00223-006-0060-0

    Article  CAS  PubMed  Google Scholar 

  39. Dodd KC, Clay FJ, Forbes AM, Keh YS, Miller JAL, Sussman J, Lilleker JB (2023) Rituximab for myasthenia gravis. Cochrane Database Syst Rev 2023(4):CD014574. https://doi.org/10.1002/14651858.CD014574

    Article  PubMed Central  Google Scholar 

  40. Alhaidar MK, Abumurad S, Soliven B, Rezania K (2022) Current treatment of Myasthenia Gravis. J Clin Med 11. https://doi.org/10.3390/jcm11061597

  41. Upadhyay J, Farr OM, Mantzoros CS (2015) The role of leptin in regulating bone metabolism. Metabolism 64:105–113. https://doi.org/10.1016/j.metabol.2014.10.021

    Article  CAS  PubMed  Google Scholar 

  42. Humphrey MB, Russell L, Danila MI et al (2023) 2022 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatol (Hoboken, NJ) 75:2088–2102. https://doi.org/10.1002/art.42646

    Article  Google Scholar 

  43. Morren JA, Li Y (2023) Myasthenia gravis: Frequently asked questions. Cleve Clin J Med 90:103–113. https://doi.org/10.3949/ccjm.90a.22017

    Article  PubMed  Google Scholar 

  44. Ebeling PR, Nguyen HH, Aleksova J, Vincent AJ, Wong P, Milat F (2022) Secondary osteoporosis. Endocr Rev 43:240–313. https://doi.org/10.1210/endrev/bnab028

    Article  PubMed  Google Scholar 

  45. Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA 3rd, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–739. https://doi.org/10.1359/jbmr.2000.15.4.721

    Article  CAS  PubMed  Google Scholar 

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We would like to thank Enago (www.enago.com) for editing and proofreading this manuscript.

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Correspondence to Kuan-Yu Lin.

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Chien-Ju Lin, Yu-Shan Lee, Jiann-Horng Yeh, Shu-Jung Liu, and Kuan-Yu Lin declare that they have no conflict of interest.

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Lin, CJ., Lee, YS., Yeh, JH. et al. The association between myasthenia gravis and risk of fracture: a systematic review and meta-analysis. Osteoporos Int (2024). https://doi.org/10.1007/s00198-024-07097-2

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