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Poor Bone Quality in Patients With Amyotrophic Lateral Sclerosis

Caplliure-Llopis, Jordi, Escrivá, Dolores, Benlloch, María, de la Rubia Ortí, José Enrique, Estrela, José María, Barrios, Carlos·2020·Frontiers in Neurology
DOI 10.3389/fneur.2020.599216PMC PMC7775537
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Abstract

Objective: Musculoskeletal functional deterioration in Amyotrophic lateral sclerosis (ALS) is associated with an increase in bone fractures. The purpose of this study was to evaluate the influence of sex, ALS type, on bone quality in patients with ALS compared to healthy controls. The impact on bone health of the clinical status and some metabolic parameters was also analyzed in ALS patients. Methods: A series of 33 voluntary patients with ALS, and 66 healthy individuals matched in sex and age underwent assessment of bone mass quality using quantitative ultrasound (QUS) of the calcaneus. Ultrasonic broadband attenuation (BUA), the speed of sound (SOS), stiffness index and T-score were measured. Bone mineral density (BMD) was estimated using standard equations. Apart from fat and muscle mass percentage determinations, clinical baseline measures in ALS patients included ALSFRS-R score, Barthel index for activities of daily living, pulmonary function measured using FVC, and muscular strength assessed by a modified MRC grading scale. Laboratory tests included serum calcium, 25-HO-cholecalciferol (Vitamin D), alkaline phosphatase (ALP), T4 and TSH. Results: All bone parameters evaluated were statistically significant lower in ALS patients than in healthy controls. ALS females showed significantly lower bone parameters than healthy females. According to the estimated BMD, there were 25 ALS patients (75.8%) and 36 (54.5%) healthy individuals showing an osteoporotic profile (BMD <0.700 g/cm 2). Only 16.7% of the ALS females had T-scores indicative of healthy bones. There was no correlation between any of the clinical parameters analyzed and the bone QUS measurements. Vitamin D and TSH levels positively correlated with all the bone parameters. Conclusions: This study confirms that ALS patients, particularly females, exhibited deteriorated bone health as compared to healthy individuals. These structural bone changes were independent of ALS subtype and clinical status. Bone health in ALS patients seems to be related to certain metabolic parameters such as Vitamin D and TSH levels.

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  • A cross-sectional study investigating clinical markers of bone health in participants with ALS found that participants with ALS had lower bone quality compared with healthy individuals and that bone quality was poor across age groups.

    “A cross-sectional study investigating clinical markers of bone health in participants with ALS found that participants with ALS had lower bone quality compared with healthy individuals and that bone quality was poor across age groups [71].”

    From Head Injury and Amyotrophic Lateral Sclerosis: Population-Based Study from the National ALS Registry (2025) · cites this paper as [71]

  • Patients with ALS have been shown to have a higher incidence of fractures, deteriorating bone health, and lower bone density.

    “Patients with ALS have been shown to have a higher incidence of fractures, deteriorating bone health, and lower bone density.”

    From Head Injury and Amyotrophic Lateral Sclerosis: Population-Based Study from the National ALS Registry (2025) · cites this paper as [71]

  • It is likely that skeletal function and health are impacted as the disease progresses, increasing the risk of fractures, and not that skull fractures increase the risk of ALS.

    “Therefore, it is likely that skeletal function and health are impacted as the disease progresses, increasing the risk of fractures, and not that skull fractures increase the risk of ALS [70,71,72,79].”

    From Head Injury and Amyotrophic Lateral Sclerosis: Population-Based Study from the National ALS Registry (2025) · cites this paper as [71]

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Research works printed but not linked: 45

  1. [1]Al-Chalabi A Hardiman O The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol. (2013) 9: 617– 28. 10.1038/nrneurol.2013.203 24126629 · DOI
  2. [2]Huisman MH de Jong SW van Doormaal PT Weinreich SS Schelhaas HJ van der Kooi AJ Population based epidemiology of amyotrophic lateral sclerosis using capture-recapture methodology. J Neurol Neurosurg Psychiatry. (2011) 82: 1165– 70. 10.1136/jnnp.2011.244939 21622937 · DOI
  3. [3]Forbes RB Colville S Swingler RJ The epidemiology of amyotrophic lateral sclerosis (ALS/MND) in people aged 80 or over. Age Ageing. (2004) 33: 131– 4. 10.1093/ageing/afh013 14960427 · DOI
  4. [4]Pradas J Puig T Rojas-García R Viguera ML Gich I Logroscino G Amyotrophic lateral sclerosis in Catalonia: a population based study. Amyotroph Lateral Scler Frontotemporal Degener. (2013) 14: 278– 83. 10.3109/21678421.2012.749915 23286747 · DOI
  5. [5]Andrews JA Meng L Kulke SF Rudnicki SA Wolff AA Bozik ME Association between decline in slow vital capacity and respiratory insufficiency, use of assisted ventilation, tracheostomy, ordeath in patients with amyotrophic lateral sclerosis. JAMA Neurol. (2018) 75: 58– 64. 10.1001/jamaneurol.2017.3339 29181534 PMC5833488 · DOI
  6. [6]Peters TL Weibull CE Fang F Sandler DP Lambert PC Ye W Kamel F Association of fractures with the incidence of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. (2017) 18: 419– 25. 10.1080/21678421.2017.1300287 28316249 PMC5527744 · DOI · Paper page
  7. [7]Brown RH Al-Chalabi A Amyotrophic Lateral Sclerosis. N Engl J Med. (2017) 377: 162– 72. 10.1056/NEJMra1603471 28700839 · DOI
  8. [8]Sato Y Honda Y Asoh T Kikuyama M Oizumi K Hypovitaminosis D and decreased bone mineral density in amyotrophic lateral sclerosis. Eur Neurol. (1997) 27: 225– 9. 10.1159/000117447 9208262 · DOI
  9. [10]Hamrick MW McNeil PL Patterson SL. Role of muscle-derived growth factors in bone formation. J Musculoskelet Neuronal Interact. (2010) 10: 64– 70. 20190381 PMC3753580
  10. [11]Zhou J Yi J Bonewald L. Muscle-bone crosstalk in amyotrophic lateral sclerosis. Curr Osteoporos Rep. (2015) 13: 274– 9. 10.1007/s11914-015-0281-0 26223903 · DOI · Paper page
  11. [12]Koh SH Baik W Noh MY Cho GW Kim HY Kim KS Kim SH. The functional deficiency of bone marrow mesenchymal stromal cells in ALS patients is proportional to disease progression rate. Exp Neurol. (2012) 233: 472– 80. 10.1016/j.expneurol.2011.11.021 22119626 · DOI
  12. [13]Cho GW Noh MY Kim HY Koh SH Kim KS Kim SH. Bone marrow-derived stromal cells from amyotrophic lateral sclerosis patients have diminished stem cell capacity. Stem Cells Dev. (2010) 19: 1035– 42. 10.1089/scd.2009.0453 20030561 · DOI
  13. [14]Neurology Research Group on Motor Neuron Diseases El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis, Amyotroph. Lateral Scler. Mot Neuron Disord. (2000) 1: 293– 9. 10.1080/146608200300079536 11464847 · DOI · Paper page
  14. [15]World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects JAMA. (2013) 310: 2191– 4. 10.1001/jama.2013.281053 24141714 · DOI · Paper page
  15. [16]Wang J Thornton JC Kolesnik S Pierson RN. Anthropometry in body composition. An overview. Ann NY Acad Sci. (2000) 904: 317– 26. 10.1111/j.1749-6632.2000.tb06474.x 10865763 · DOI
  16. [19]Chin KY Ima-Nirwana S. Calcaneal quantitative ultrasound as a determinant of bone health status: What properties of bone does itreflect? Int J Med Sci. (2013) 10: 1778– 83. 10.7150/ijms.6765 24273451 PMC3837236 · DOI
  17. [20]Trimpou P Bosaeus I Bengtsson BA Landin-Wilhelmsen K. High correlation between quantitative ultrasound and DXA during 7 years of follow-up. Eur J Radiol. (2010) 73: 360– 4. 10.1016/j.ejrad.2008.11.024 19135327 · DOI
  18. [21]Xu Y Guo B Gong J Xu H Bai Z. The correlation between calcaneus stiffness index calculated by QUS and total body BMD assessed by DXA in Chinese children and adolescents. J Bone Mineral Metab. (2014) 32: 159– 66. 10.1007/s00774-013-0474-5 23695447 · DOI
  19. [22]Damilakis J Perisinakis K Gourtsoyiannis N. Imaging ultrasonometry of the calcaneus: Optimumt-score thresholds for the identification of osteoporotic subjects. Calcified Tissue Int. (2001) 68: 219– 24. 10.1007/s002230020014 11353948 · DOI
  20. [23]Frost ML Blake GM Fogelman I. Can the WHO criteria for diagnosing osteoporosis be applied to calcaneal quantitative ultrasound? Osteoporosis Int. (2000) 11: 321– 30. 10.1007/s001980070121 10928222 · DOI
  21. [24]Fang F Kwee LC Allen KD Umbach DM Ye W Watson M. Association between blood lead and the risk of amyotrophic lateral sclerosis. Am J Epidemiol. (2010) 171: 1126– 33. 10.1093/aje/kwq063 20406759 PMC2877471 · DOI · Paper page
  22. [25]Karam C Barrett MJ Imperato T MacGowan DJ Scelsa S Vitamin D deficiency and its supplementation in patients with amyotrophic lateral sclerosis. J Clin Neurosci. (2013) 20: 1550– 3. 10.1016/j.jocn.2013.01.011 23815870 · DOI · Paper page
  23. [26]Camu W Tremblier B Plassot C Alphandery S Salsac C Pageot N. Vitamin D confers protection to motoneurons and is a prognostic factor of amyotrophic lateral sclerosis. Neurobiol Aging. (2014) 35: 1198– 205. 10.1016/j.neurobiolaging.2013.11.005 24378089 · DOI · Paper page
  24. [27]Cruz DC Nelson LM McGuire V Longstreth WT Jr. Physical trauma and family history of neurodegenerative diseases in amyotrophic lateral sclerosis: a population-based case-control study. Neuroepidemiology. (1999) 18: 101– 10. 10.1159/000069413 10023133 · DOI
  25. [29]Seals RM Hansen J Gredal O Weisskopf MG. Physical trauma and amyotrophic lateral sclerosis: a population-based study using Danish national registries. Am J Epidemiol. (2015) 183: 294– 301. 10.1093/aje/kwv169 26825926 PMC4753279 · DOI · Paper page
  26. [30]Roos PM. Osteoporosis in neurodegeneration. J Trace Elem Med Biol. (2014) 28: 418– 21. 10.1016/j.jtemb.2014.08.010 25220531 · DOI
  27. [31]Zhu K Yi J Xiao Y Lai Y Song P Zheng W. Impaired bone homeostasis in amyotrophic lateral sclerosis mice with muscle atrophy. J Biol Chem. (2015) 290: 8081– 94. 10.1074/jbc.M114.603985 25648889 PMC4375466 · DOI
  28. [32]Ko FC Li J Brooks DJ Rutkove SB Bouxsein ML. Structural and functional properties of bone are compromised in amyotrophic lateral sclerosis mice. Amyotroph Lateral Scler Frontotemporal Degener. (2018) 19: 457– 62. 10.1080/21678421.2018.1452946 29569488 PMC6141014 · DOI
  29. [33]Hamrick M. JMNI special issue: basic science and mechanisms of muscle-bone interactions. J Musculoskelet Neuronal Interact. (2010) 10: 1– 2. 20190374
  30. [34]Kaji H Interaction between muscle and bone. J Bone Metab. (2014) 21: 29– 40. 10.11005/jbm.2014.21.1.29 24707465 PMC3970293 · DOI
  31. [35]Lang TF. The bone-muscle relationship in men and women. J Osteoporos. (2011) 2011: 702– 35. 10.4061/2011/702735 22007336 PMC3189615 · DOI
  32. [36]Lebrasseur NK Achenbach SJ Melton LJ Amin S Khosla S. Skeletal muscle mass is associated with bone geometry and microstructure and serum insulin like growth factor binding protein-2 levels in adult women and men. J Bone Miner Res. (2012) 27: 2159– 69. 10.1002/jbmr.1666 22623219 PMC3645866 · DOI
  33. [37]Shackelford LC LeBlanc AD Driscoll TB Evans HJ Rianon NJ Smith SM. Resistance exercise as a countermeasure to disuse induced bone loss. J Appl Physiol. (2014) 97: 119– 29. 10.1152/japplphysiol.00741.2003 15220316 · DOI · Paper page
  34. [38]Hamrick MW McNeil PL Patterson SL Role of muscle-derived growth factors in bone formation. J Musculoskelet Neuronal Interact. (2010) 10: 64– 70. 20190381 PMC3753580
  35. [39]Kahn J Shwartz Y Blitz E Krief S Sharir A Breitel DA. Muscle contraction is necessary to maintain joint progenitor cell fate. Dev Cell. (2009) 16: 734– 43. 10.1016/j.devcel.2009.04.013 19460349 · DOI
  36. [40]Sharir A Stern T Rot C eShahar R Zelzer E. Muscle force regulates bone shaping for optimal load-bearing capacity during embryogenesis. Development. (2011) 138: 3247– 59. 10.1242/dev.063768 21750035 · DOI
  37. [41]Shwartz Y Farkas Z Stern T Aszódi A Zelzer E. Muscle contraction controls skeletal morphogenesis through regulation of chondrocyte convergent extension. Dev Biol. (2012) 370: 154– 63. 10.1016/j.ydbio.2012.07.026 22884393 · DOI
  38. [42]Li H Johnson NR Usas A Lu A Poddar M Wang Y Huard J. Sustained release of bone morphogenetic protein 2 via coacervate improves the osteogenic potential of muscle-derived stem cells. Stem Cells Transl Med. (2013) 2: 667– 77. 10.5966/sctm.2013-0027 23884640 PMC3754467 · DOI
  39. [43]Oishi T Uezumi A Kanaji A Yamamoto N Yamaguchi A Yamada H Tsuchida K. Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells. PLoS ONE. (2013) 8: 56641. 10.1371/journal.pone.0056641 23457598 PMC3572948 · DOI
  40. [44]Sun JS Wu SY Lin FH. The role of muscle-derived stem cells in bone tissue engineering. Biomaterials. (2005) 26: 3953– 60. 10.1016/j.biomaterials.2004.10.016 15626442 · DOI
  41. [45]Bikle DD Sakata T Halloran BP The impact of skeletal unloading on bone formation. Gravit Space Biol Bull. (2003) 16: 45– 54. 12959131
  42. [46]Robling AG Niziolek PJ Baldridge LA Condon KW Allen MR Alam I. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem. (2008) 283: 5866– 75. 10.1074/jbc.M705092200 18089564 · DOI · Paper page
  43. [47]Sato Y Honda Y Iwamoto J. Etidronate for fracture prevention in amyotrophic lateral sclerosis: a randomized controlled trial. Bone. (2006) 39: 1080– 6. 10.1016/j.bone.2017.10.008 16777503 · DOI
  44. [48]Grondin J Grimal Q Yamamoto K Matsukawa M Saied A Laugier P. Relative contributions of porosity and mineralized matrix properties to the bulk axial ultrasonic wave velocity in human cortical bone. Ultrasonics. (2012) 52: 467– 71. 10.1016/j.ultras.2011.11.008 22182403 · DOI
  45. [49]Khaw KT Reeve J Luben R Bingham S Welch A Wareham N. Prediction of total and hip fracture risk in menand women by quantitative ultrasound of the calcaneus: EPIC-Norfolk prospective population study. Lancet. (2004) 363: 197– 202. 10.1016/S0140-6736(03)15325-1 14738792 · DOI

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Authors
Caplliure-Llopis, J., Escrivá, D., Benlloch, M., de la Rubia Ortí, J. E., Estrela, J. M., & Barrios, C.
Venue
Frontiers in Neurology
Publisher
Frontiers Media SA
Published
2020-12-18
Volume
11
ISSN
1664-2295
DOI
10.3389/fneur.2020.599216
PMC
PMC7775537
Cited by
17
References
4
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
Universidad Católica de Valencia San Vicente Màrtir (2017-216-001)

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