medigraphic.com
ISSN 1817-5996 (Electronic)

2020, Number S1

<< Back Next >>

Rev Cub de Reu 2020; 22 (S1)

Osteosarcopenia: from muscle-bone unit aging to disease

Navarro DDA, Prado MC, Manzano OBR

Language: Spanish
References: 83
Page:
PDF size: 585.90 Kb.


ABSTRACT

Muscle and bone mass have the same embryological origin, development and function constituting the bone-muscle unit. However, the diseases associated with aging of this unit are considered independently. In recent years, the additive effect of sarcopenia and osteopenia / osteoporosis on the quality of life and health of the elderly has been revealed, and thus the concept of Osteosarcopenia emerged. In older adults, reporting a progressive decrease in muscle mass and strength. Along with the above, accidental falls at home (by fragility?) are among its main causes of death, suggesting that a group of these aging people may have undiagnosed Osteosarcopenia. To develop capacities for its prevention the objective of this narrative revision are update aspects related to the aging of muscle. Bone unit and diagnostic criteria and therapeutic options for Osteosarcopenia. Exhaustive review of complete articles, in English and Spanish, downloaded manually and published between 2010 and 2019, obtained from the Pubmed, Scielo Regional and Google Scholar databases. the fatty infiltration of the muscle-bone unit It is the most important event of aging, there is no uniformity in the diagnosis of sarcopenia and adequate protein intake, calcium and D vitamin and strength exercises are principal therapeutic options. There are no drugs with on both entities.


REFERENCES

  1. United Nations. Revision of World Population Prospects 2019. Department of Economic and Social Affairs Population Division World Population Prospects 2019. Highlights. New York: United Nations; 2019. [Acceso 25/01/2020]. Disponible en https://population.un.org/wpp/

  2. Del Pino Montes J. Osteoporosis: Concepto e importancia. Cuadro clínico. Rev Osteoporos Metab Miner. 2010 [Acceso 25/01/2020];2(Supl 4):S15-S20. Disponible en: http://revistadeosteoporosisymetabolismomineral.com/pdf/articulos/92010020400150020.pdf

  3. Fried LP, Tangen CM, Walston J, Newman AB, Hirschet C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A BiolSci Med Sci. 2001;56:M146-56.

  4. Hassan E, Duque G. Osteosarcopenia: A new geriatric Síndrome. AFP. 2017;46(11):849-53.

  5. Laurent R, Dubois V, Claessens F, Verschueren S, Vanderschueren D, Gielen E, et al. Muscle-bone interactions: from experimental models to the clinic? A critical update. Mol Cell Endocrinol. 2016;432:14-36. Doi: http://dx.doi.org/10.1016/j.mce.2015.10.017

  6. Reginster JY, Beaudart C, Buckinx F, Bruyere O. Osteoporosis and sarcopenia: two diseases or one? Curr Opin Clin Nutr Metab Care. 2016;19:31-6.

  7. Stefan D, Anker SD, Morley JE, von Haehling S. Welcome to the ICD-10 code for sarcopenia. J Cachexia, Sarcopenia and Muscle. 2016;7:512-4. Doi: http://dx.doi.org/10.1002/jcsm.12147=

  8. Reiss J, Iglseder B, Alzner R, Mayr-Pirker B, Pirich C, Kässmann H, et al. Sarcopenia and osteoporosis are interrelated in geriatric inpatients. Z Gerontol Geriat. 2019;52:688-93. Doi: https://doi.org/10.1007/s00391-019-01553-z

  9. Sepúlveda-Loyola W, Phu S, Bani Hassan E, Brennan-Olsen SL, Zanker J, Vogrin S, et al. The joint occurrence of Osteoporosis and Sarcopenia (Osteosarcopenia): Definitions and Characteristics. J Am Med Dir Assoc. 2020;21(2):220-5. Doi: http://dx.doi.org/10.1016/j.jamda.2019.09.005. Epub 2019 Oct 25.

  10. Drey M, Sieber CC, Bertsch T, Bauer JM, Schmidmaier R. FIAT intervention group. Osteosarcopenia is more than sarcopenia and osteopenia alone. Aging Clin Exp Res. 2016;28(5):895-9. Doi: http://dx.doi.org/10.1007/s40520-015-0494-1

  11. Scot D, Cumming R. Does Combined Osteopenia/Osteoporosis and Sarcopenia Confer greater risk of falls and fracture than either condition alone in older men? The Concord Health and Ageing in Men Project. J Gerontol A Biol Sci Med Sci. 2019;74(6):827-34. Doi: http://dx.doi.org/10.1093/gerona/gly162.

  12. Kelly OJ, Gilman JC, Boschiero D, Ilich J. Osteosarcopenic Obesity: Current Knowledge, Revised Identification Criteria and Treatment Principles. Nutrients. 2019;11(4):747. Doi: http://dx.doi.org/10.3390/nu11040747

  13. García-González AI, Axtle-Serrano Z, López-Teros M, Szlejf C, Martínez-Ruiz A, Rosas-Carrasco O. Intervenciones clínicas en obesidad osteosarcopénica: alimentación, actividad física y psicológica Rev Med Inst Mex Seguro Soc. 2018;56(Supl 1):S82-93.

  14. Oficina Nacional de Estadística. Estudios y datos de la población cubana·2019. La Habana: Oficina Nacional de Estadística; 2020. [Acceso 25/01/2020]. Disponible en: http://www.onei.gob.cu/node/13818

  15. Morales Larramendi R, Román Montoya AC, Núñez Bourón AI, Lara Lafargue A, Marañón Cardonne M, Castillo Bonne J. Composición corporal: intervalos de lo normal en el estudio mediante bioimpedancia eléctrica de una población de referencia. MEDISAN. 2004 [Acceso 25/01/2020];8(4):22-34. Disponible en: http://bvs.sld.cu/revistas/san/vol8_4_04/san04404.htm

  16. Garcia AD, Piñera JA, García A, Bueno Capote C. Fuerza de agarre como predictor de discapacidad en adultos mayores activos. Rev Cubana Med Deporte & Cultura Física. 2018 [Acceso 25/01/2020];13(3). Disponible en: https://instituciones.sld.cu/imd/files/2019/02/Fuerza-de-agarre.pdf

  17. Fernández Patty B, Navarro Despaigne D. Sarcopenia y factores de riesgo asociados en mujeres mayores de 40 años del Policlínico Vedado. [Trabajo para optar por el Título de Especialista en 1er. Grado en Endocrinología]. La Habana: Instituto de Endocrinología, Facultad de Ciencias Médicas Comandante Manuel Fajardo, Universidad de Ciencias Médicas de La Habana; 2018.

  18. Dirección Nacional de Estadística. Anuario Estadístico de salud 2019. La Habana: Ministerio de Salud Pública; 2020. [Acceso 25/01/2020]. Disponible en: http://bvscuba.sld.cu/anuario-estadistico-de-cuba/

  19. Acosta Cedeño A, Acosta López L, Díaz Socorro C, Navarro Despaigne D, Cabrera Gámez M. Calidad ósea en adultos de edad mediana. Rev Cubana Endocrinol. 2015 [Acceso 25/01/2020];26(2):147-57. Disponible en: http://scielo.sld.cu/pdf/end/v26n2/end05215.pdf

  20. Navarro Despaigne DA, Acosta Cedeño A, Díaz Socorro C. Osteoporosis post menopausia. Experiencia de la Consulta de climaterio y osteoporosis. Instituto de Endocrinología 2007-2017. La Habana: Convención Internacional de Salud, Cuba Salud 2018; 2018. [Acceso 25/01/2020]. Disponible en: http://www.convencionsalud2018.sld.cu/index.php/connvencionsalud/2018/paper/viewFile/978/951)

  21. Sociedad Cubana de Endocrinología, Sociedad Cubana de Reumatología. Guía para el diagnóstico y tratamiento de la osteoporosis, 2018. Rev Cubana Endocrinol. 2019 [Acceso 25/01/2020];30(1). Disponible en: http://www.revendocrinologia.sld.cu/index.php/endocrinologia/article/view/105/117 Acceso 7/07/2020

  22. Cruz Jentoft AJ, Pierre Baeyens J, Bauer JM, Boirie Y, Cederholm T, Cooper C, et al. Report Sarcopenia: European consensus on definition and diagnosis. Age and Ageing Advance. 2010;39:412-23.

  23. Chan DCC, Lee WTK, Lo DHS, Leung JCS, Kwok AWL, Leung PC. Relationship between grip strength and bone mineral density in healthy Hong Kong adolescents. Osteopor Int. 2008;19:1485-95.

  24. Arazi H, Eghbali E. Osteosarcopenia and Physical Activity. Ann Sports Med Res. 2018;5(1):1130.

  25. Mastaglia S. Osteosarcopenia: un factor de riesgo para fracturas osteoporótica. Acta Bioquím Clín Latinoam. 2016;50(3):357-65.

  26. Paintin J, Cooper C, Dennison E. Osteosarcopenia. Br J Hosp Med (Lond). 2018;79(5):253-8. Doi: http://dx.doi.org/10.12968/hmed.2018.79.5.253

  27. Kaji H. Interaction between muscle and bone. J Bone Metab. 2014;21:29-40. Doi: http://dx.doi.org/10.11005/jbm.2014.21.1.29

  28. Kopiczko A. Bone mineral density in old age: the influence of age at menarche, menopause status and habitual past and present physical activity. Arch Med Sci. 2020;16(3):657-65. Doi: https://doi.org/10.5114/aoms.2019.81314

  29. Park HM. Current status of sarcopenia in Korea: A focus on Korean Geripausal women. Ann Geriatric Med Research. 2018;22(2):52-61. Doi: http://dx.doi.org/10.4235/agmr

  30. Pili FG, Dutto F, D´Amelio. Osteosarcopenia: A Geriatric Syndrome EC Orthopaedics. 2018;9(10):741-54.

  31. Maltais ML, Desroches J, Dionne IJ. Changes in muscle mass and strength after menopause. J Músculoskelet Neuronal Interact. 2009;9(4):186-97.

  32. Velez MP, Rosendaa IN, Alvarado B, Camara S, Belanger E, Pirkle C. Age at natural menopause and physical function in older women from Albania, Brazil, Colombia and Canada: A life-course perspective. Maturitas. 2019;122:22-30.

  33. Bonewald L. Use it or Lose it to Age: A Review of Bone and Muscle Communication. Bone. 2019;120:212-8. Doi: http://dx.doi.org/10.1016/j.bone.2018.11.002

  34. Dowling P, Zweyer M, Swandulla D, Ohlendieck K. Characterization of contractile proteins from skeletal muscle using Gel-Based Top-Down. Proteomics Proteomes. 2019;7(25). Doi: http://dx.doi.org/10.3390/proteomes7020025

  35. Pando-Robles RV, Lanz-Mendoza H. The significance of proteomics in public health. Salud Publica Mex. 2009;51(suppl 3):S386-S394.

  36. Vlachpoulos D, Ubago-Guisado E, Barker AR, Metcalf BS, Fatouros IG, Avloniti A, et al. Determinants of bone outcomes in adolescent athletes at baseline: The PRO-BONE study. Med Sci Sports Exerc. 2017;49:1389-96.

  37. Poggiogalle E, Cherry KE, Su J, Kim S, Myers L, Welsh DA, et al. Body Composition, IGF1 Status, and Physical Functionality in Nonagenarians: Implications for Osteosarcopenia. J Am Med Dir Assoc. 2019;20(1):70-5. Doi: http://dx.doi.org/10.1016/j.jamda.2018.07.007

  38. Armstrong VJ, Muzylak M, Sunters A, Zaman G, Saxon LK, Price JS, et al. Wnt/beta-catenin signaling is a component of osteoblastic bone cell early responses to load-bearing and requires estrogen receptor alpha. J of Biological Chemistry. 2007;282(28):20715-27. Doi: https://doi.org/10.1074/jbc.M703224200

  39. Raschke S, Eckel J. Adipo-Myokines: Two Sides of the Same Coin -Mediators of Inflammation and Mediators of Exercise. Review Article. Mediators of Inflammation. 2013;16. Doi: http://dx.doi.org/10.1155/2013/320724

  40. Forcina L, Miano C, Musaro A. The physiopathologic interplay between stem cells and tissue niche inmuscle regeneration and the role of IL-6 on muscle homeostasis and diseases. Cytokine Growth Factor Rev. 2018;41:1-9.

  41. Lee JH, Jun HS. Role of Myokines in Regulating Skeletal Muscle Mass and Function. Front Physiol. 2019;10(42). Doi: https://doi.org/10.3389/fphys.201900042

  42. Battafarano G, Rossi M, Marampon F, Minisola S, del Fattore A. Bone Control of Muscle Function. Int J Mol Sci. 2020;21(1178). Doi: http://dx.doi.org/10.3390/ijms21041178

  43. Dallas S, Prideaux M, Bonewald F. The Osteocyte: An Endocrine Cell and More. Endocrine Reviews. 2013;34(5):658-90. Doi: http://dx.doi.org/10.1210/er.2012-1026

  44. Graf C, Ferrari N. Metabolic Health -The Role of Adipo-Myokines. Int J Mol Sci. 2019;20:6159. Doi: http://dx.doi.org/10.3390/ijms20246159

  45. Hirschfeld HP, Kinsella R, Duque G. Osteosarcopenia: where bone, muscle and fat collide. Osteoporos Int. 2017. Doi: https://doi.org/10.1007/s00198-017-4151-8

  46. Wang X, You T, Yang R, Lyles MF, Demons J, Gong D, et al. Muscle strength is associated with adipose tissue gene expression of inflammatory adipokines in postmenopausal women. Age Ageing. 2010;39(5):656-9. Doi: http://dx.doi.org/10.1093/ageing/afq024

  47. Adamovich Y, Rousso-Noori L, Zwighaft Z, Neufeld-Cohen A, Golik M, Kraut-Cohen Y, et al. Circadian clocks and feeding time regulate the oscillations and levels of hepatic triglycerides. Metab. 2014;19(2):319-30. Doi: http://dx.doi.org/10.1016/j.cmet.2013.12.016

  48. Girgis CM, Mokbel N, Digirolamo DJ. Therapies for musculoskeletal disease: Can we treat two birds with one stone? Curr Osteoporos Rep. 2014;12:142-53. Doi: http://dx.doi.org/10.1007/s11914-014-0204-5

  49. Park Y, Pereira R, Erickson Ch, Tracy BS, Chounghun Kang CH, Van Pelt RE. Time since menopause and skeletal muscle estrogen receptors PGC-1a, and AMPK. Menopause. 2017;24(7):815-23. Doi: http://dx.doi.org/10.1097/GME.0000000000000829

  50. Kazemi M, Jarrett B, Parry S, Thalacker-Mercer A, Hoeger KM, Spandorfer SD, et al. SAT-23 osteosarcopenia in reproductive-aged women with Polycystic Ovary Syndrome: A Multicenter Case-Control Study. J Clin Endocrinol Metabol. 2020;105(9):e3400-e3414. Doi: http://doi.org/10.1210/clinem/dgaa046

  51. Horstman AM, Lichar Dillon E, Urban R, Sheffield-Moore M. The Role of androgens and estrogens on healthy aging and longevity. J Gerontol A Biol Sci Med Sci. 2012 Nov;67(11):1140-52. Doi: http://dx.doi.org/10.1093/gerona/gls068

  52. Erice A, Román L, Ulloa V, Peláez J, Juncal V, Álvarez R. Afecciones ginecológicas. En Álvarez Sintes R, Hernández Cabrera G, Baster Moreno JC, García Núñez R, eds. Medicina General Integral. Vol IV, Cap 105. La Habana: Editorial Ciencias Médicas; 2014. p. 1401-04.

  53. Pollanen E, Sipila S, Alen M, Ronkainen PHA, Ankarberg-Lindgren C, Puolakka J, et al. Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre- and postmenopausal women. Aging Cell. 2011;10:650-60. Doi: http://dx.doi.org/10.1111/j.1474-9726.2011.00701

  54. Sung-Woo K, Kim R. The association between hormone therapy and sarcopenia in postmenopausal women: The Korea National Health and Nutrition Examination Survey, 2008-2011. Menopause. 2020;27(5):506-11. Doi: http://dx.doi.org/10.1097/GME.0000000000001509

  55. Yuki A, Otsuka R, Kozakai R, Kitamura I, Okura T, Ando F, et al. Relationship between Low Free Testosterone Levels and Loss of Muscle Mass. Scientific Reports. 2013;3:1818. Doi: http://dx.doi.org/10.1038/srep018182013

  56. Daly RM. Exercise and nutritional approaches to prevent frail bones, falls and fractures: an update. Climacteric. 2017;20:119-24. Doi: http://dx.doi.org/10.1080/13697137.2017.1286890

  57. Bruyere O, Cavalier E, Reginster JI. Vitamin D and osteosarcopenia: an update from epidemiological studies. Curr Opin Clin Nutr Metab Care. 2017;20:498-503. Doi: http://dx.doi.org/10.1097/MCO.0000000000000411

  58. Kirki B, Al Saedi A, Duquel G. Osteosarcopenia: A case of geroscience. Aging Medicine. 2019;2:147-56. Doi: http://dx.doi.org/10.1002/agm2.12080

  59. Cedeño Veloz B, Lopez-Doriga P, Duque G. Osteosarcopenia: una revisión narrativa. Rev Esp Geriatr Gerontol. 2019;54(2):103-08. Doi: https://doi.org/10.1016/j.regg.2018.09.010

  60. Park S, Na W, Sohn CH. Relationship between osteosarcopenic obesity and dietary inflammatory index in postmenopausal Korean women: 2009 to 2011 Korea National Health and Nutrition Examination Surveys. J Clin Biochem Nutr. 2018;63(3):211-16. Doi: http://dx.doi.org/10.3164/jcbn.18-10

  61. Fahimfar N, Zahedi Tajrishi F, Shafiee G, Tanha K, Heshmat R. Prevalence of Osteosarcopenia and Its Association with Cardiovascular Risk Factors in Iranian Older People: Bushehr Elderly Health (BEH) Program. Calcif Tissue Int. 2020;106(4):364-70. Doi: https://doi.org/10.1007/s00223-019-00646-6 Epub 2019 Dec 17

  62. Yoo JI, Kim H, Ha YC, Kwon H, Koo K. Osteosarcopenia in patients with hip fracture is related with high mortality. J Korean Med Sci. 2018;33:e27. Doi: https://doi.org/10.3346/lkms.2018.33.e27

  63. Huo R, Suriyaarachchi P, Gomez F, Curcio C, Boersman D, Muir S. Phenotype of osteosarcopenia in older individuals with a history of falling. J Am Med Dir Assoc. 2015;16(4):290-95.

  64. Intriago M, Maldonado G, Guerrero R, Messina OD, Rios C. Bone mass loss and Sarcopenia in Ecuadorian patients. J Aging Res. 2020;107. Doi: https://doi.org/10.1155/2020/1072675

  65. Wang YJ, Wang Y, Zhan JK, Tang ZY, He JY, Tan P, et al. Sarco-Osteoporosis: Prevalence and Association with Frailty in Chinese Community-Dwelling Older Adults. Int J Endocrinol. 2015;20:482940. Doi: http://dx.doi.org/10.1155/2015/482940

  66. Pasco J, Mohebbi M, Holloway K, Brennan-Olsen Sh, Hyde NK, Kotowicz MA. Musculoskeletal decline and mortality: prospective data from the Geelong Osteoporosis Study. J Cachexia Sarcopenia Muscle. 2017;8(3):482-9. Doi: http://dx.doi.org/10.1002/jcsm.12177

  67. Gomez Curcio CL, Brennan-Olsen S, Boersma D, Phu S, Vogrin S, Suriyaarachchi P, et al. Effects of the falls and fractures clinic as an integrated multidisciplinary model of care in Australia: a pre-post study. BMJ Open. 2019;9(7):e027013. Doi: http://dx.doi.org/10.1136/bmjopen-2018-027013

  68. Okamura H, Ishikawa K, Kudo Y, Matsuoka A, Maruyama H, Emori H, et al. Risk factors predicting osteosarcopenia in postmenopausal women with osteoporosis. A retrospective study. Plos One. 2015;15(9):e0237454. Doi: http://dx.doi.org/10.1371/journal.pone.0237454

  69. Kirk B, Zanker J, Duque G. Osteosarcopenia: epidemiology, diagnosis, and treatment-facts and numbers. J Cachexia, Sarcopenia and Muscle. 2020;11:609-18. Doi: http://dx.doi.org/10.1002/jcsm.12567

  70. Shintia Viana da Costa S, Ceolim MF, Liberalesso Neri A. Problemas de sueño y soporte social: estudio multicéntrico sobre Fragilidad en Ancianos Brasileños. Rev Latino Am Enfermagem. 2011 [Acceso 09/07/2020];19(4):[08 patallas]. Disponible en: http://www.eerp.usp.br/rlae

  71. Guerri S, Mercatelli D, Aparisi Gómez MP, Napoli A, Battista G, Guglielmi G, et al. A Quantitative imaging techniques for the assessment of osteoporosis and sarcopenia. Quant Imaging Med Surg. 2018;8(1):60-85. Doi: http://dx.doi.org/10.21037/qims.2018.01.05

  72. Saeki Ch, Takano K, Oikawa T, Aoki Y, Kanai T, Takakura K, et al. Comparative assessment of sarcopenia using the JSH, AWGS, and EWGSOP2 criteria and the relationship between sarcopenia, osteoporosis, and osteosarcopenia in patients with liver cirrhosis. BMC Músculoskelet Disord. 2019;20:615. Doi: http://dx.doi.org/10.1186/s12891-019-2983-4

  73. Rangel Peniche DB, Alemán Mateo H, Aguilera Barreiro MA, Ruiz Valenzuela RE, Ramírez-Torres M, Urquidez-Romero R. Differences in body composition in older people from two Regions of Mexico: Implications for diagnoses of Sarcopenia and Sarcopenic Obesity. Biomed Res Int. 2018;7538625. Doi: http://dx.doi.org/10.1155/2018/7538625

  74. Tegola L, Mattera M, Cornacchia S, Cheng X, Guglielmi G. Diagnostic imaging of two related chronic diseases: Sarcopenia and Osteoporosis. J Frailty Sarcopenia Falls. 2018;3(3):138-47. Doi: http://dx.doi.org/10.22540/JFSF-03-138

  75. Fatima M, Brennan-Olsen S, Duque G. Therapeutic approaches to osteosarcopenia: insights for the clinician. Ther Adv Musculoskel Dis. 2019;11:1-15. Doi: http://dx.doi.org/10.1177/1759720X19867009

  76. González Morales I, Torres Amengual M, Martinez Fernandez CA, Luque Vara T. La dieta mediterránea en distintos grupos de edad. European J Health Research. 2016;2(2):73-81.

  77. Hansen M. Female hormones: do they influence muscle and tendon protein metabolism? Conference on "Nutrition and exercise for health and performance". Symposium 2: Maintenance of muscle mass for healthy ageing. Proceedings of the Nutrition Society. 2018;77:32-41. Doi: http://dx.doi.org/10.1017/S0029665117001951

  78. Ram Hong A, Sang Wan K. Effects of Resistance Exercise on Bone Health Endocrinol Metab (Seoul). 2018;33(4):435-44. Doi: http://dx.doi.org/10.3803/EnM.2018.33.4.435

  79. Kemmler W, Haberle L, von Stengel S. Effects of exercise on fracture reduction in older adults: a systematic review and meta-analysis. Osteoporos Int. 2013;24:1937-50. Doi: http://dx.doi.org/10.1007/s00198-012-2248-7

  80. Conzade R, Phu S, Vogrin S, Bani Hassan E, Sepúlveda-Loyola W, Thorand B, et al. Changes in Nutritional Status and Musculoskeletal Health in a Geriatric Post-Fall. Care Plan Setting Nutrients. 2019;11(7):1551. Doi: http://dx.doi.org/10.3390/nu11071551

  81. Yoo J, Ha Y. Review of Epidemiology, diagnosis and treatment of osteosarcopenia in Korea. J Bone Metab. 2018 Feb;25(1):1-7. Doi: http://dx.doi.org/10.11005/jbm.2018.25.1.1

  82. Compston J, Cooper A, Cooper C, Gittoes N, Gregson C, Harvey N, et al. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. 2017;12:43. Doi: http://dx.doi.org/10.1007/s11657-017-0324-5

  83. Skinner J, Otzel D, Bowser A, Nargi D, Agarwal S, Peterson M, et al. Muscular responses to testosterone replacement vary by administration route: A systematic review and meta-analysis. J Cachexia, Sarcopenia and Muscle. 2018;9:465-81. Doi: http://dx.doi.org/10.1002/jcsm.12291




2020     |     www.medigraphic.com