Osteosarcopenia: pathogenesis, diagnosis and therapeutic approaches

Cover Page
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract


Osteosarcopenia was identified as a separate syndrome in 2009, and is defined as a combination of sarcopenia and osteopenia/osteoporosis. Osteosarcopenia develops mainly in old age, leads to a decrease in quality of life, an increased risk of falls and low-traumatic fractures. Patients with osteosarcopenia have worse indicators of physical functions, compared with people suffering from only one of the components of the syndrome. An important role in the osteosarcopenia prevention is played by the lifestyle of patients, Adherence to diet with the consumption of adequate amount of protein, physical activity and preventive prescription of calcium and vitamin D are important for osteosarcopenia prevention. The article summarizes data on the prevalence, pathogenesis and risk factors of osteosarcopenia, provides diagnostic criteria for the disease and discusses therapeutic approaches.


Full Text

Restricted Access

About the authors

Tatiana A. Grebennikova

The National Medical Research Center for Endocrinology

Author for correspondence.
Email: Grebennikova@hotmail.com
ORCID iD: 0000-0003-1413-1549
SPIN-code: 4380-5447

Russian Federation, 11 Dm. Ulyanova str., 117036, Moscow

MD, PhD

Timur T Tsoriev

The National Medical Research Center for Endocrinology

Email: timur.tsoriev@gmail.com
ORCID iD: 0000-0001-9074-2291
SPIN-code: 7234-2499

Russian Federation, Moscow

MD

Juliya R Vorobeva

The National Medical Research Center for Endocrinology

Email: ju.vorobeva.ru@gmail.com
ORCID iD: 0000-0003-2884-1349

Russian Federation, Moscow

Resident

Zhanna E Belaya

The National Medical Research Center for Endocrinology

Email: jannabelaya@gmail.com
ORCID iD: 0000-0002-6674-6441
SPIN-code: 4746-7173

Russian Federation, Moscow

MD, PhD

References

  1. Rosenberg I. Summary comments. Am J Clin Nutr. 1989;50(5):1231–1233. doi: 10.1093/ajcn/50.5.1231.
  2. Cruz-Jentoft A, Baeyens J, Bauer J, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on sarcopenia in older people. Age Ageing. 2010;39(4):412–423. doi: 10.1093/ageing/afq034.
  3. Cruz-Jentoft A, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(4):601–601. doi: 10.1093/ageing/afz046.
  4. Мельниченко Г.А., Белая Ж.Е., Рожинская Л.Я., и др. Федеральные клинические рекомендации по диагностике, лечению и профилактике остеопороза // Проблемы эндокринологии. — 2017. — Т. 63. — № 6. — С. 392–426. [Mel’nichenko GA, Belaya ZhE, Rozhinskaya LYa, et al. Russian federal clinical guidelines on the diagnostics, treatment, and prevention of osteoporosis. Problems of Endocrinology. 2017;63(6):392–426. (In Russ.)]
  5. Binkley N, Buehring B. Beyond FRAX®: it’s time to consider “Sarco-Osteopenia”. J Clin Dent. 2009;12(4):413–416. doi: 10.1016/j.jocd.2009.06.004.
  6. Huo Y, Suriyaarachchi P, Gomez F, et al. Phenotype of osteosarcopenia in older individuals with a history of falling. J Am Med Dir Assoc. 2015;16(4):290–295. doi: 10.1016/j.jamda.2014.10.018.
  7. Cheung AM, Papaioannou A, Morin S, et al. Postmenopausal osteoporosis. New England Journal of Medicine. 2016;374(21):2095–2097. doi: 10.1056/nejmc1602599.
  8. Wright N, Looker A, Saag K, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone. 2014;29(11):2520–2526. Miner Res doi: 10.1002/jbmr.2269.
  9. Лесняк О.М. Аудит состояния проблемы остеопороза в странах Восточной Европы и Центральной Азии // Остеопороз и остеопатии. — 2011. — Т. 14. — № 2. — C. 3–6. doi: 10.14341/osteo201123-6. [Lesnyak O. Audit sostoyaniya problemy osteoporoza v stranakh vostochnoy evropy i tsentral’noy azii. Osteoporosis and Bone Diseases. 2011;14(2):3–6. doi: 10.14341/osteo201123-6. (In Russ.)]
  10. Lauretani F, Russo C, Bandinelli S, et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. J Appl Physiol. 2003;95(5):1851–1860. doi: 10.1152/japplphysiol.00246.2003.
  11. Cruz-Jentoft A, Landi F, Schneider S, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43(6):748–759. doi: 10.1093/ageing/afu115.
  12. Di Monaco M, Vallero F, Di Monaco R, et al. Prevalence of sarcopenia and its association with osteoporosis in 313 older women following a hip fracture. Arch Gerontol Geriatr. 2011;52(1):71–74. doi: 10.1016/j.archger.2010.02.002.
  13. Fatima M, Brennan-Olsen S, Duque G. Therapeutic approaches to osteosarcopenia: insights for the clinician. Ther Adv Musculoskelet Dis. 2019;11:1759720X1986700. doi: 10.1177/1759720x19867009.
  14. Laurent M, Dubois V, Claessens F, et al. Muscle-bone interactions: from experimental models to the clinic? A critical update. Mol Cell Endocrinol. 2016;432:14–36. doi: 10.1016/j.mce.2015.10.017.
  15. Ucer S, Iyer S, Kim H, et al. The effects of aging and sex steroid deficiency on the murine skeleton are independent and mechanistically distinct. J Bone Miner Res. 2016;32(3):560–574. doi: 10.1002/jbmr.3014.
  16. Dubois V, Simitsidellis I, Laurent M, et al. Enobosarm (GTx-024) modulates adult skeletal muscle mass independently of the androgen receptor in the satellite cell lineage. Endocrinology. 2015;156(12):4522–4533. doi: 10.1210/en.2015-1479.
  17. Гребенникова Т.А., Белая Ж.Е., Никитин А.Г., и др. Экспрессия микро-РНК, регулирующих костное ремоделирование, в плазме крови у пациентов с акромегалией // Ожирение и метаболизм. — 2017. — Т. 14. — № 3. — С. 32–37. doi: 10.14341/omet2017332-37. [Grebennikova T, Belaya Z, Nikitin A, et al. Expression of microRNA related to bone remodeling regulation in plasma in patients with acromegaly. Obesity and metabolism. 2017;14(3):32–37. doi: 10.14341/omet2017332-37. (In Russ.)]
  18. Никитин А.Г., Белая Ж.Е., Бровкина О.И., и др. Эпигенетическая регуляция в костной ткани // Остеопороз и остеопатии. — 2016. — Т. 19. — № 1. — С. 15–16. [Nikitin AG, Belaya ZhE, Brovkina OI, et al. Epigenetic regulation in bone tissue. Osteoporosis and Bone Diseases. 2016;19(1):15–16. (In Russ.)]
  19. Цориев Т.Т., Белая Ж.Е., Рожинская Л.Я., и др. Содержание миокинов в сыворотке крови у пациентов с эндогенным гиперкортицизмом и акромегалией: одномоментное исследование «случай–контроль» // Вестник Российской академии медицинских наук. — 2016. — Т. 71. — № 3. doi: 10.15690/vramn659. [Tsoriev TT, Belaya ZE, Rozhinskaya LY, et al. Serum myokines levels in patients with endogenous cushing syndrome and acromegaly: cross-sectional case-control study. Annals of the Russian Academy of Medical Sciences. 2016;71(3). doi: 10.15690/vramn659. (In Russ.)]
  20. Daly R. Exercise and nutritional approaches to prevent frail bones, falls and fractures: an update. Climacteric. 2017;20(2):119–124. doi: 10.1080/13697137.2017.1286890.
  21. Mera P, Laue K, Ferron M, et al. Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise. Cell Metab. 2016;23(6):1078–1092. doi: 10.1016/j.cmet.2016.05.004.
  22. Colnot C, Zhang X, Knothe Tate ML. Current insights on the regenerative potential of the periosteum: molecular, cellular, and endogenous engineering approaches. J Orthop Res. 2012;30:1869–1878. doi: 10.1002/jor.22181.
  23. Evans SF, Parent JB, Lasko CE, et al. Periosteum, bone‘s “smart” bounding membrane, exhibits direction-dependent permeability. J Bone Miner Res. 2013;28:608–617. doi: 10.1002/jbmr.1777.
  24. Henrotin Y. Muscle: a source of progenitor cells for bone fracture healing. BMC Med. 2011;9:136. doi: 10.1186/1741-7015-9-136.
  25. Compston J, Cooper A, Cooper C, et al. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos. 2017;12(1). doi: 10.1007/s11657-017-0324-5.
  26. Kanis J, Melton L, Christiansen C, et al. The diagnosis of osteoporosis. J Bone Miner Res. 2009;9(8):1137–1141. doi: 10.1002/jbmr.5650090802.
  27. Ishii S, Tanaka T, Shibasaki K, et al. Development of a simple screening test for sarcopenia in older adults. Geriatr Gerontol Int. 2014;14:93–101. doi: 10.1111/ggi.12197.
  28. Shen G, Li Y, Zhao G, et al. Cigarette smoking and risk of hip fracture in women: a meta-analysis of prospective cohort studies. Injury. 2015;46(7):1333–1340. doi: 10.1016/j.injury.2015.04.008.
  29. Hirschfeld H, Kinsella R, Duque G. Osteosarcopenia: where bone, muscle, and fat collide. Osteoporos Int. 2017;28(10):2781–2790. doi: 10.1007/s00198-017-4151-8.
  30. Cuenca-Sánchez M, Navas-Carrillo D, Orenes-Piñero E. Controversies surrounding high-protein diet intake: satiating effect and kidney and bone health. Adv Nutr. 2015;6(3):260–266. doi: 10.3945/an.114.007716.
  31. Cramer J, Cruz-Jentoft A, Landi F, 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. 2016;17(11):1044–1055. doi: 10.1016/j.jamda.2016.08.009.
  32. Пигарова Е.А., Рожинская Л.Я., Белая Ж.Е., и др. Клинические рекомендации Российской ассоциации эндокринологов по диагностике, лечению и профилактике дефицита витамина D у взрослых // Проблемы эндокринологии. — 2016. — Т. 62. — № 4. — С. 60–84. doi: 10.14341/probl201662460-84. [Pigarova E, Rozhinskaya L, Belaya J, et al. Russian Association of Endocrinologists recommendations for diagnosis, treatment and prevention of vitamin D deficiency in adults. Problems of Endocrinology. 2016;62(4):60–84. doi: 10.14341/probl201662460-84. (In Russ.)]
  33. Rizzoli R, Stevenson J, Bauer J, et al. Erratum to “The role of dietary protein and vitamin D in maintaining musculoskeletal health in postmenopausal women: a consensus statement from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)”. Maturitas. 2015;80(3):337. doi: 10.1016/j.maturitas.2014.11.005.
  34. Kanis J, Cooper C, Rizzoli R, et al. Correction to: European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2019. doi: 10.1007/s00198-019-05184-3.
  35. Deutz N, Bauer J, Barazzoni R, et al. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clin Nutr. 2014;33(6):929–936. doi: 10.1016/j.clnu.2014.04.007.
  36. Kearns A, Khosla S, Kostenuik P. Receptor activator of nuclear factor κB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2007;29(2):155–192. doi: 10.1210/er.2007-0014.
  37. Белая Ж.Е., Рожинская Л.Я. Новые направления в терапии остеопороза — применение моноклональных человеческих антител к RANKL (деносумаб) // Остеопороз и остеопатии. — 2011. — № 2. — С. 1. [Belaya ZhE, Rozhinskaya LYa. Novye napravlenija v terapii osteoporoza — primenenie monoklonal’nyh chelovecheskih antitel k RANKL (denosumab). Osteoporosis and Bone Diseases. 2011;2:1. (In Russ.)]
  38. Cummings S, Martin J, McClung M, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. Obstet Gynecol Surv. 2009;64(12):805–807. doi: 10.1097/01.ogx.0000363236.41902.96.
  39. Dong H, Huang H, Yun X, et al. bilirubin increases insulin sensitivity in leptin-receptor deficient and diet-induced obese mice through suppression of ER stress and chronic inflammation. Endocrinology. 2014;155(3):818–828. doi: 10.1210/en.2013-1667.
  40. Bonnet N, Bourgoin L, Biver E, et al. RANKL inhibition improves muscle strength and insulin sensitivity and restores bone mass. J Clin Invest. 2019;129(8):3214–3223. doi: 10.1172/jci125915.
  41. Lefkowitz S, Lefkowitz D, Kethley J. Treatment of facioscapulohumeral muscular dystrophy with Denosumab. Am J Case Rep. 2012;13:66–68. doi: 10.12659/ajcr.882771.
  42. Tracz M, Sideras K, Boloña E, et al. Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials. J Clin Endocrinol Metab. 2006;91(6):2011–2016. doi: 10.1210/jc.2006-0036.
  43. LeBlanc E, Nielson C, Marshall L, et al. The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men. J Clin Endocrinol Metab. 2009;94(9):3337–3346. doi: 10.1210/jc.2009-0206.
  44. Wolfe R, Ferrando A, Sheffield-Moore M, et al. Testosterone and muscle protein metabolism. Mayo Clin Proc. 2000;75(1):S55–S60. doi: 10.1016/s0025-6196(19)30644-5.
  45. Haren M, Siddiqui A, Armbrecht H, et al. Testosterone modulates gene expression pathways regulating nutrient accumulation, glucose metabolism and protein turnover in mouse skeletal muscle. International Journal of Andrology. 2011;34(1):55–68. doi: 10.1111/j.1365-2605.2010.01061.x.
  46. Bhasin S, Woodhouse L, Casaburi R, et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab. 2005;90(2):678–688. doi: 10.1210/jc.2004-1184.
  47. Wittert G, Chapman I, Haren M, et al. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci. 2003;58(7):M618–M625. doi: 10.1093/gerona/58.7.m618.
  48. Morley J, Perry H. Androgens and women at the menopause and beyond. J Gerontol A Biol Sci Med Sci. 2003;58(5):M409–M416. doi: 10.1093/gerona/58.5.m409.
  49. Snyder P, Kopperdahl D, Stephens-Shields A, et al. Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone. JAMA Intern Med. 2017;177(4):471. doi: 10.1001/jamainternmed.2016.9539.
  50. Bhasin S, Ellenberg S, Storer T, et al. Effect of testosterone replacement on measures of mobility in older men with mobility limitation and low testosterone concentrations: secondary analyses of the Testosterone Trials. Lancet Diabetes Endocrinol. 2018;6(11):879–890. doi: 10.1016/s2213-8587(18)30171-2.
  51. Mohler M, Bohl C, Jones A, et al. Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit. J Med Chem. 2009;52(12):3597–3617. doi: 10.1021/jm900280m.
  52. Bhasin S, Jasuja R. Selective androgen receptor modulators as function promoting therapies. Curr Opin Clin Nutr Metab Care. 2009;12(3):232–240. doi: 10.1097/mco.0b013e32832a3d79.
  53. Sharma S, Arneja A, McLean L, et al. Anabolic steroids in COPD: a review and preliminary results of a randomized trial. Chron Respir Dis. 2008;5(3):169–176. doi: 10.1177/1479972308092350.
  54. Frisoli A, Chaves P, Pinheiro M, et al. The effect of nandrolone decanoate on bone mineral density, muscle mass, and hemoglobin levels in elderly women with osteoporosis: a double-blind, randomized, placebo-controlled clinical trial. J Gerontol A Biol Sci Med Sci. 2005;60(5):648–653. doi: 10.1093/gerona/60.5.648.
  55. Macdonald J, Marcora S, Jibani M, et al. Nandrolone decanoate as anabolic therapy in chronic kidney disease: a randomized phase II dose-finding study. Nephron Clinical Practice. 2007;106(3):c125–c135. doi: 10.1159/000103000.
  56. Papanicolaou D, Ather S, Zhu H, et al. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia. J Nutr Health Aging. 2013;17(6):533–543. doi: 10.1007/s12603-013-0335-x.
  57. Morley J. Pharmacologic options for the treatment of sarcopenia. Calcif Tissue Int. 2015;98(4):319–333. doi: 10.1007/s00223-015-0022-5.
  58. Basaria S, Collins L, Dillon E, et al. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontol A Biol Sci Med Sci. 2010;68(1):87–95. doi: 10.1093/gerona/gls078.
  59. Dalton J, Barnette K, Bohl C, et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J Cachexia Sarcopenia Muscle. 2011;2(3):153–161. doi: 10.1007/s13539-011-0034-6.
  60. Dobs A, Boccia R, Croot C, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013;14(4):335–345. doi: 10.1016/s1470-2045(13)70055-x.
  61. Rudman D, Feller A, Nagraj H, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990;323(1):1–6. doi: 10.1056/nejm199007053230101.
  62. Barake M, Arabi A, Nakhoul N, et al. Effects of growth hormone therapy on bone density and fracture risk in age-related osteoporosis in the absence of growth hormone deficiency: a systematic review and meta-analysis. Endocrine. 2017;59(1):39–49. doi: 10.1007/s12020-017-1440-0.
  63. Kim MJ, Morley JE. The hormonal fountains of youth: myth or reality? J Endocrinol Invest. 2005;28(11):5–14.
  64. Liu H, Bravata D, Olkin I, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med. 2007;146(2):104. doi: 10.7326/0003-4819-146-2-200701160-00005.
  65. Elkina Y, von Haehling S, Anker S, et al. The role of myostatin in muscle wasting: an overview. J Cachexia Sarcopenia Muscle. 2011;2(3):143–151. doi: 10.1007/s13539-011-0035-5.
  66. Camporez J, Petersen M, Abudukadier A, et al. Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice. Proc Natl Acad Sci U S A. 2016;113(8):2212–2217. doi: 10.1073/pnas.1525795113.
  67. Becker C, Lord S, Studenski S, et al. Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial. Lancet Diabetes Endocrinol. 2015;3(12):948–957. doi: 10.1016/s2213-8587(15)00298-3.
  68. Tang L, Gao X, Yang X, et al. Combination of weight-bearing training and Anti-MSTN polyclonal antibody improve bone quality in rats. Int J Sport Nutr Exerc Metab. 2016;26(6):516–524. doi: 10.1123/ijsnem.2015-0337.
  69. Attie K, Borgstein N, Yang Y, et al. A single ascending-dose study of muscle regulator ace-031 in healthy volunteers. Muscle Nerve. 2012;47(3):416–423. doi: 10.1002/mus.23539.
  70. Scullen T, Santo L, Vallet S, et al. Lenalidomide in combination with an activin A-neutralizing antibody: preclinical rationale for a novel anti-myeloma strategy. Leukemia. 2013;27(8):1715–1721. doi: 10.1038/leu.2013.50.
  71. Glasser C, Gartner M, Wilson D, Miller B, Sherman M, Attie K. Locally acting ACE-083 increases muscle volume in healthy volunteers. Muscle Nerve. 2018;57(6):921–926. doi: 10.1002/mus.26113.
  72. Amato A, Sivakumar K, Goyal N, et al. Treatment of sporadic inclusion body myositis with bimagrumab. Neurology. 2014;83(24):2239–2246. doi: 10.1212/wnl.0000000000001070.
  73. Garcia J, Boccia R, Graham C, et al. Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials. Lancet Oncol. 2015;16(1):108–116. doi: 10.1016/s1470-2045(14)71154-4.
  74. White H, Petrie C, Landschulz W, et al. Effects of an oral growth hormone secretagogue in older adults. J Clin Endocrinol Metab. 2009;94(4):1198–1206. doi: 10.1210/jc.2008-0632.

Supplementary files

There are no supplementary files to display.

Statistics

Views

Abstract - 84

PDF (Russian) - 1

Cited-By


PlumX

Dimensions



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies