Preview

Obesity and metabolism

Advanced search

Joint involvement in patients with acromegaly: potential markers for early diagnosis

https://doi.org/10.14341/omet13133

Abstract

Acromegaly is a rare neuroendocrine disease caused by excessive production of growth hormone (GH), which acts as a trigger for cartilage tissue destruction leading to joint damage.

Patients with acromegaly, especially in the active stage, often complain of joint pain in various locations. Joint pain can be one of the first symptoms of the disease, the intensity of which worsens without proper treatment. Increased production of GH leads to configuration changes in the joints, which in turn trigger destructive processes typical of degenerative diseases such as osteoarthritis. Despite successful treatment of acromegaly, joint-related issues can persist and significantly worsen the quality of life for patients. In this regard, the search for potential markers of early joint involvement in acromegaly is relevant for use in predicting the severity of arthropathy progression and monitoring this cohort of patients.

This review provides a general overview of the effects of growth hormone on cartilage tissue, the characteristics of musculoskeletal pathology in patients with acromegaly and possible markers associated with early joint damage.

About the Authors

M. A. Perepelova
Endocrinology Research Centre
Russian Federation

Margarita A. Perepelova 

11 Dm. Ulyanova street, 117292 Moscow



A. S. Lutsenko
Endocrinology Research Centre
Russian Federation

Alexander S. Lutsenko, MD, PhD

Moscow



M. V. Utkina
Endocrinology Research Centre
Russian Federation

Marina V. Utkina, PhD in biology

Moscow



N. V. Tarbaeva
Endocrinology Research Centre
Russian Federation

Natalya V. Tarbaeva, MD, PhD

Moscow



E. G. Przhiyalkovskaya
Endocrinology Research Centre
Russian Federation

Elena G. Przhiyalkovskaya, MD, PhD

Moscow



References

1. Cangiano B, Giusti E, Premoli C, et al. Psychological complications in patients with acromegaly: relationships with sex, arthropathy, and quality of life. Endocrine. 2022;77(3):510-518. doi: https://doi.org/10.1007/s12020-022-03106-8

2. Giustina A, Barkan A, Beckers A, et al. A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update. J Clin Endocrinol Metab. 2020;105(4):e937-e946. doi: https://doi.org/10.1210/clinem/dgz096

3. Chanson P, Salenave S. Acromegaly. Orphanet J Rare Dis. 2008;3:17. doi: https://doi.org/10.1186/1750-1172-3-17

4. AlDallal S. Acromegaly: a challenging condition to diagnose. Int J Gen Med. 2018;11:337-343. doi: https://doi.org/10.2147/IJGM.S169611

5. Brue T, Rahabi H, Barry A, et al. Position statement on the diagnosis and management of acromegaly: The French National Diagnosis and Treatment Protocol (NDTP). Ann Endocrinol (Paris). 2023;84(6):697-710. doi: https://doi.org/10.1016/j.ando.2023.08.003

6. Claessen KM, Mazziotti G, Biermasz NR, Giustina A. Bone and Joint Disorders in Acromegaly. Neuroendocrinology. 2016;103(1):86-95. doi: https://doi.org/10.1159/000375450

7. Fedotova AS, Molitvoslovova NN, Alekseeva LI, et al. CONDITION OF THE MUSCULOSKELETAL SYSTEM IN PATIENTSWITH ACROMEGALY. Osteoporos Bone Dis. 2010;13(1):19-27. doi: https://doi.org/10.14341/osteo2010119-27

8. Claessen KMJA, Ramautar SR, Pereira AM, et al. Progression of acromegalic arthropathy despite long-term biochemical control: a prospective, radiological study. Eur J Endocrinol. 2012;167:235–244. doi: https://doi.org/10.1530/EJE-12-0147

9. Потешкин Ю., Пронин В.С., Мельниченко Г.А., и др. Влияние избытка гормона роста и ИФР-1 на костно-суставную систему при акромегалии // Актуальная эндокринология. — 2015. — №10.

10. Chipman JJ, Attanasio AF, Birkett MA, et al. The safety profile of GH replacement therapy in adults. Clin Endocrinol (Oxf). 1997;46(4):473-481. doi: https://doi.org/10.1046/j.1365-2265.1997.1660984.x

11. Claessen KMJA, Canete AN, de Bruin PW, Pereira AM, et al. Acromegalic arthropathy in various stages of the disease: an MRI study. Eur J Endocrinol. 2017;176(6):779-790. doi: https://doi.org/10.1530/EJE-16-1073

12. Colao A, Cannavo S, Marzullo P, et al. Twelve months of treatment with octreotide-LAR reduces joint thickness in acromegaly. Eur J Endocrinol. 2003;148(1):31-38. doi: https://doi.org/10.1530/eje.0.1480031

13. Killinger Z, Payer J, Lazurova I, et al. Arthropathy in acromegaly. Rheum Dis Clin North Am. 2010;36(4):713-720. doi: https://doi.org/10.1016/j.rdc.2010.09.004

14. Barkan AL. Acromegalic arthropathy. Pituitary. 2001;4(4):263-4. doi: https://doi.org/10.1023/a:1020754615863

15. Tagliafico A, Resmini E, Ferone D, Martinoli C. Musculoskeletal complications of acromegaly: what radiologists should know about early manifestations. Radiol Med. 2011;116(5):781-92. doi: https://doi.org/10.1007/s11547-011-0671-z

16. Crisafulli S, Luxi N, Sultana J, et al. Global epidemiology of acromegaly: a systematic review and meta-analysis. Eur J Endocrinol. 2021;185(2):251-263. doi: https://doi.org/10.1530/EJE-21-0216

17. Dons RF, Rosselet P, Pastakia B, Doppman J, Gorden P. Arthropathy in acromegalic patients before and after treatment: a long-term follow-up study. Clin Endocrinol (Oxf). 1988;28(5):515-524. doi: https://doi.org/10.1111/j.1365-2265.1988.tb03686.x

18. Prencipe N, Scarati M, Manetta T, Berton AM, et al. Acromegaly and joint pain: is there something more? A cross-sectional study to evaluate rheumatic disorders in growth hormone secreting tumor patients. J Endocrinol Invest. 2020;43(11):1661-1667. doi: https://doi.org/10.1007/s40618-020-01268-8

19. Wassenaar MJE, Biermasz NR, van Duinen N, et al. High prevalence of arthropathy, according to the definitions of radiological and clinical osteoarthritis, in patients with long-term cure of acromegaly: a case–control study. Eur J Endocrinol. 2009;160(3):357-365. doi: https://doi.org/10.1530/EJE-08-0845

20. Killinger Z, Payer J, Lazúrová I, Imrich R, et al. Arthropathy in acromegaly. Rheum Dis Clin North Am. 2010;36(4):713-20. doi: https://doi.org/10.1016/j.rdc.2010.09.004

21. Romijn JA. Acromegalic arthropathy: current perspectives. Endocrine. 2013;43(2):245-6. doi: https://doi.org/10.1007/s12020-012-9781-1

22. Kropf LL, Madeira M, Neto LV, Roberto Gadelha M, de Farias MLF. Functional evaluation of the joints in acromegalic patients and associated factors. Clin Rheumatol. 2013;32(7):991-998. doi: https://doi.org/10.1007/s10067-013-2219-1

23. Паневин Т.С., Алексеева Л.И., Мельниченко Г.А. Ревматические проявления акромегалии // Остеопороз и остеопатии. — 2019. — Т. 22. — №2. — С. 14-22. doi: https://doi.org/10.14341/osteo11353

24. Morselli LL, Manetti L, Cosci C, et al. Bone and joint alterations in acromegaly. J Orthop Traumatol. 2006;7(4):169-175. doi: https://doi.org/10.1007/s10195-006-0143-8

25. Al‐Hadlaq M, Sroussi H. Acromegaly: Overview and associated temporomandibular joint disorders. Oral Dis. January 2024. doi: https://doi.org/10.1111/odi.14861

26. Bennett R. Growth hormone in musculoskeletal pain states. Curr Pain Headache Rep. 2005;9(5):331-338. doi: https://doi.org/10.1007/s11916-005-0009-4

27. Scarpa R, De Brasi D, Pivonello R, et al. Acromegalic axial arthropathy: a clinical case-control study. J Clin Endocrinol Metab. 2004;89(2):598-603. doi: https://doi.org/10.1210/jc.2003-031283

28. Bluestone R, Bywaters EG, Hartog M, Holt PJ, Hyde S. Acromegalic arthropathy. Ann Rheum Dis. 1971;30(3):243-258. doi: https://doi.org/10.1136/ard.30.3.243

29. Ribeiro de Moura C, Campos Lopes S, Monteiro AM. Determinants of skeletal fragility in acromegaly: a systematic review and meta-analysis. Pituitary. 2022;25(6):780-794. doi: https://doi.org/10.1007/s11102-022-01256-6

30. Heck A, Godang K, Lekva T, Markussen KN, et al. Endocortical Trabecularization in Acromegaly: The Cause for the Paradoxically Increased Vertebral Fracture Risk? JBMR Plus. 2023;7(10):e10787. doi: https://doi.org/10.1002/jbm4.10787

31. Sorohan MC, Poiana C. Vertebral Fractures in Acromegaly: A Systematic Review. J Clin Med. 2022;12(1):164. doi: https://doi.org/10.3390/jcm12010164

32. Ikegawa S, Kurokawa T, Hizuka N, Hoshino Y, Ohnishi I, Shizume K. Increase of serum growth hormone-binding protein in patients with ossification of the posterior longitudinal ligament of the spine. Spine. 1993;18(13):1757–60. doi: https://doi.org/10.1097/00007632-199310000-00007

33. Goto K, Yamazaki M, Tagawa M, et al. Involvement of Insulin-Like Growth Factor I in Development of Ossification of the Posterior Longitudinal Ligament of the Spine. Calcif Tissue Int. 1998;62(2):158-165. doi: https://doi.org/10.1007/s002239900410

34. Kamakura D, Fukutake K, Nakamura K, Tsuge S, et al. Acromegaly presenting with myelopathy due to ossification of posterior longitudinal ligament: a case report. BMC Musculoskelet Disord. 2021;22(1):353. doi: https://doi.org/10.1186/s12891-021-04232-6

35. Pelsma ICM, Biermasz NR, van Furth WR, Pereira AM, et al. Progression of acromegalic arthropathy in long-term controlled acromegaly patients: 9 years of longitudinal follow-up. J Clin Endocrinol Metab. 2021;106(1):188-200. doi: https://doi.org/10.1210/clinem/dgaa747

36. Chiloiro S, Giampietro A, Gagliardi I, Bondanelli M, et al. Systemic comorbidities of acromegaly in real-life experience: which difference among young and elderly patients? Endocrine. 2023;80(1):142-151. doi: https://doi.org/10.1007/s12020-022-03261-y

37. Pelsma ICM, Kroon HM, van Trigt VR, et al. Clinical and radiographic assessment of peripheral joints in controlled acromegaly. Pituitary. 2022;25(4):622-635. doi: https://doi.org/10.1007/s11102-022-01233-z

38. Akkaya M, Pignataro A, Sandiford N, Gehrke T, Citak M. Clinical and functional outcome of total hip arthroplasty in patients with acromegaly: mean twelve year follow-up. Int Orthop. 2022;46(8):1741-1747. doi: https://doi.org/10.1007/s00264-022-05447-5

39. Pelsma ICM, Claessen KMJA, Slagboom PE, van Heemst D, et al. Variants of FOXO3 and RPA3 genes affecting IGF-1 levels alter the risk of development of primary osteoarthritis. Eur J Endocrinol. 2021;184(1):29-39. doi: https://doi.org/10.1530/EJE-20-0904

40. Mercado M, González B, Sandoval C, Esquenazi Y, et al. Clinical and biochemical impact of the d3 growth hormone receptor genotype in acromegaly. J Clin Endocrinol Metab. 2008;93(9):3411-5. doi: https://doi.org/10.1210/jc.2008-0391

41. Montefusco L, Filopanti M, Ronchi CL, Olgiati L, et al. d3-Growth hormone receptor polymorphism in acromegaly: effects on metabolic phenotype. Clin Endocrinol (Oxf). 2010;72(5):661-7. doi: https://doi.org/10.1111/j.1365-2265.2009.03703.x

42. Claessen KM, Kloppenburg M, Kroon HM, Bijsterbosch J, et al. Relationship between the functional exon 3 deleted growth hormone receptor polymorphism and symptomatic osteoarthritis in women. Ann Rheum Dis. 2014;73(2):433-6. doi: https://doi.org/10.1136/annrheumdis-2012-202713

43. Romijn JA. Acromegalic arthropathy: current perspectives. Endocrine. 2013;43(2):245-6. doi: https://doi.org/10.1007/s12020-012-9781-1

44. Fujita M, Nakano Y, Sakae H, Otsuka F. Dysphagia Induced by Acromegalic Arthropathy. Intern Med. 2021;60(7):1127-1128. doi: https://doi.org/10.2169/internalmedicine.5856-20

45. Karataş A, Artaş H, Uğur K, Koca SS. Sonoelastrographic finding of Achilles tendon in patients with ankylosing spondylitis and acromegaly. Eur J Rheumatol. 2022;9(3):122-125. doi: https://doi.org/10.5152/eujrheum.2022.21132

46. Fatti LM, Cangiano B, Vitale G, et al. Arthropathy in acromegaly: a questionnaire-based estimation of motor disability and its relation with quality of life and work productivity. Pituitary. 2019;22(5):552-560. doi: https://doi.org/10.1007/s11102-019-00966-8

47. Wechsler S. Facial Pain and Temporomandibular Joint Dysfunction Secondary to Acromegaly: Treatment With Manual Therapy, Neuromuscular Reeducation—A Case Report. Rehabil Oncol. 2020;38(3):127-133. doi: https://doi.org/10.1097/01.REO.0000000000000190

48. Lima TRL, Kasuki L, Gadelha M, Lopes AJ. Physical exercise improves functional capacity and quality of life in patients with acromegaly: a 12-week follow-up study. Endocrine. 2019;66(2):301-309. doi: https://doi.org/10.1007/s12020-019-02011-x

49. Bhosale AM, Richardson JB. Articular cartilage: structure, injuries and review of management. Br Med Bull. 2008;87(1):77-95. doi: https://doi.org/10.1093/bmb/ldn025

50. Ge Z, Li C, Heng BC, Cao G, Yang Z. Functional biomaterials for cartilage regeneration. J Biomed Mater Res Part A. 2012;100A(9):2526-2536. doi: https://doi.org/10.1002/jbm.a.34147

51. Guilak F, Nims RJ, Dicks A, Wu C-L, Meulenbelt I. Osteoarthritis as a disease of the cartilage pericellular matrix. Matrix Biol. 2018;71-72:40-50. doi: https://doi.org/10.1016/j.matbio.2018.05.008

52. Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK. Extracellular matrix structure. Adv Drug Deliv Rev. 2016;97:4-27. doi: https://doi.org/10.1016/j.addr.2015.11.001

53. Tush EV, Eliseeva TI, Khaletskaya V, et al. Extracellular matrix markers and methods for their study. Sovremennye Tehnologii v Medicine. 2019;11(2):133-147. doi: https://doi.org/10.17691/stm2019.11.2.20

54. Tyyni A, Karlsson J. Biological treatment of joint cartilage damage. Scand J Med Sci Sports. 2000;10(5):249-265. doi: https://doi.org/10.1034/j.1600-0838.2000.010005249.x

55. Крылов П.А. Рецепторный аппарат хондроцитов как объект управления в тканевой инженерии хрящевой ткани // Вестник ВолГУ. Серия 9: Исследования молодых ученых. — 2013. — №11

56. Kalson NS, Gikas PD, Briggs TWR. Current strategies for knee cartilage repair. Int J Clin Pract. 2010;64(10):1444-1452. doi: https://doi.org/10.1111/j.1742-1241.2010.02420.x

57. Smith MD. The normal synovium. Open Rheumatol J. 2011;5:100-106. doi: https://doi.org/10.2174/1874312901105010100

58. Tarner IH, Härle P, Müller-Ladner U, Gay RE, Gay S. The different stages of synovitis: Acute vs chronic, early vs late and non-erosive vs erosive. Best Pract Res Clin Rheumatol. 2005;19(1):19-35. doi: https://doi.org/10.1016/j.berh.2004.08.002

59. Mathiessen A, Conaghan PG. Synovitis in osteoarthritis: current understanding with therapeutic implications. Arthritis Res Ther. 2017;19(1):18. doi: https://doi.org/10.1186/s13075-017-1229-9

60. Hinegard D, Lorenzo P, Sanchet T. Matrix glycoprotein, proteoglycans, and cartilage. In Kelly’s Textbook of Rheumatology. Edited by: Reddy S, Harris Y.D., Sledge CB. 2001; 41-53

61. Żylińska B, Sobczyńska-Rak A, Lisiecka U, et al. Structure and Pathologies of Articular Cartilage. In Vivo. 2021;35(3):1355-1363. doi: https://doi.org/10.21873/invivo.12388

62. Okada Y. Proteinases and matrix destruction. In Kelly’s Textbook of Rheumatology. Edited by: Reddy S., Harris Ed Jr., Sledge CB. 2001:55-72

63. Garnero P, Gineyts E, Christgau S, Finck B, Delmas PD. Association of baseline levels of urinary glucosyl-galactosyl-pyridinoline and type II collagen C-telopeptide with progression of joint destruction in patients with early rheumatoid arthritis. Arthritis Rheum. 2002. doi: https://doi.org/10.1002/1529-0131(200201)46:1<21::AID-ART10061>3.0.CO;2-Q

64. Garnero P, Landewé R, Boers M, et al. Association of baseline levels of markers of bone and cartilage degradation with long‐term progression of joint damage in patients with early rheumatoid arthritis. Arthritis Rheum. 2002;46(11):2847-2856. doi: https://doi.org/10.1002/art.10616

65. Røtterud JH, Reinholt FP, Beckstrøm KJ, Risberg MA, Arøen A. Relationship between CTX-II and patient characteristics, patient-reported outcome, muscle strength, and rehabilitation in patients with a focal cartilage lesion of the knee: a prospective exploratory cohort study of 48 patients. BMC Musculoskelet Disord. 2014;15:99. doi: https://doi.org/10.1186/1471-2474-15-99

66. Shah SS. Editorial Commentary: Serum Cartilage Oligomeric Matrix Protein Appears to Be the Most Useful Biomarker for Tracking Early Osteoarthritis of the Knee in Anterior Cruciate Ligament Deficient Patients (But May Also Reflect Synovitis). Arthroscopy. 2022;38(3):879-880. doi: https://doi.org/10.1016/j.arthro.2021.08.015

67. Östlind E, Eek F, Stigmar K, Sant›Anna A, Ekvall Hansson E, Struglics A. Associations Between Physical Activity, Self-reported Joint Function, and Molecular Biomarkers in Working Age Individuals With Hip and/or Knee Osteoarthritis. Clin Med Insights Arthritis Musculoskelet Disord. 2022;15:11795441221081063. doi: https://doi.org/10.1177/11795441221081063

68. Bi X. Correlation of serum cartilage oligomeric matrix protein with knee osteoarthritis diagnosis: a meta-analysis. J Orthop Surg Res. 2018;13(1):262. doi: https://doi.org/10.1186/s13018-018-0959-y

69. Arellano RD, Aguilar LS, Argüello R, Hernadez F, et al. Cartilage Oligomeric Matrix Protein Levels in Synovial Fluid in Patients With Primary Knee Osteoarthritis And Healthy Controls: A Preliminary Comparative Analysis With Serum Cartilage Oligomeric Matrix Protein. Arch Rheumatol. 2017;32(3):189-196. doi: https://doi.org/10.5606/ArchRheumatol.2017.6220

70. Kumar S, Kumar H, Mittal A, Singh PP, et al. Correlation Between Synovial Fluid Levels of Matrix Metalloproteinase’s (MMP-1, MMP-3, and MMP-9) and TNF-α with the Severity of Osteoarthritis Knee in Rural Indian Population. Indian J Orthop. 2023;57(10):1659-1666. doi: https://doi.org/10.1007/s43465-023-00974-8

71. de Rooy DP, Zhernakova A, Tsonaka R, Willemze A, et al. A genetic variant in the region of MMP-9 is associated with serum levels and progression of joint damage in rheumatoid arthritis. Ann Rheum Dis. 2014;73(6):1163-9. doi: https://doi.org/10.1136/annrheumdis-2013-203375

72. Grillet B, Pereira RVS, Van Damme J, Abu El-Asrar A, et al. Matrix metalloproteinases in arthritis: towards precision medicine. Nat Rev Rheumatol. 2023;19(6):363-377. doi: https://doi.org/10.1038/s41584-023-00966-w

73. Pulik Ł, Łęgosz P, Motyl G. Matrix metalloproteinases in rheumatoid arthritis and osteoarthritis: a state of the art review. Reumatologia. 2023;61(3):191-201. doi: https://doi.org/10.5114/reum/168503

74. Chen J-J, Huang J-F, Du W-X, Tong P-J. Expression and significance of MMP3 in synovium of knee joint at different stage in osteoarthritis patients. Asian Pac J Trop Med. 2014;7(4):297-300. doi: https://doi.org/10.1016/S1995-7645(14)60042-0

75. Цориев Т.Т., Белая Ж.Е. Костно-суставные структурные нарушения при акромегалии // Проблемы ’ндокринологии. — 2018. — Т. 64. — №2. — С. 121-129. doi: https://doi.org/10.14341/probl9305


Supplementary files

1. Figure 1. Effects of GH and IGF-1 on bone and cartilage tissue.
Subject
Type Исследовательские инструменты
View (302KB)    
Indexing metadata ▾
2. Figure 2. Spinal lesions in a patient with acromegaly.
Subject
Type Исследовательские инструменты
View (176KB)    
Indexing metadata ▾
3. Figure 3. Algorithm for diagnosis of OA in patients with acromegaly.
Subject
Type Исследовательские инструменты
View (529KB)    
Indexing metadata ▾

Review

For citations:


Perepelova M.A., Lutsenko A.S., Utkina M.V., Tarbaeva N.V., Przhiyalkovskaya E.G. Joint involvement in patients with acromegaly: potential markers for early diagnosis. Obesity and metabolism. 2024;21(2):195-204. (In Russ.) https://doi.org/10.14341/omet13133

Views: 1575


ISSN 2071-8713 (Print)
ISSN 2306-5524 (Online)