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Acromegaly and the long-term fracture risk of the vertebra and hip: a national cohort study

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Abstract

Summary

In this national cohort study, the patients with acromegaly had significantly higher risks of clinical vertebral (HR 2.09 [1.58–2.78]) and hip (HR 2.52 [1.61–3.95]) fractures than the controls. The increased fracture risk in patients with acromegaly was time-dependent and was observed even during the early period of follow-up.

Purpose

Acromegaly is characterized by the overproduction of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), both play important roles in regulating bone metabolism. We investigated the risk of vertebral and hip fractures in patients with acromegaly compared to age- and sex-matched controls.

Methods

This nationwide population-based cohort study included 1,777 patients with acromegaly aged 40 years or older in 2006–2016 and 8,885 age- and sex-matched controls. A Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) [95% confidence interval].

Results

The mean age was 54.3 years and 58.9% were female. For approximately 8.5 years of follow-up, the patients with acromegaly had significantly higher risks of clinical vertebral (HR 2.09 [1.58–2.78]) and hip (HR 2.52 [1.61–3.95]) fractures than the controls in the multivariate analyses. There were significant differences in the risks of clinical vertebral (P < 0.0001) and hip (P < 0.0001) fractures between the patients with acromegaly and the controls in the Kaplan–Meier survival analysis. The multivariable-adjusted HRs for clinical vertebral fractures comparing the patients with acromegaly with controls during and excluding the first 7 years of observation were 1.69 [1.15–2.49] and 2.70 [1.75–4.17], respectively. The HRs for hip fractures during and excluding the first 7 years of observation were 2.29 [1.25–4.18] and 3.36 [1.63–6.92], respectively.

Conclusions

The patients with acromegaly had a higher risk of hip fractures as well as clinical vertebral fractures than the controls. The increased fracture risk in patients with acromegaly was time-dependent and was observed even during the early period of follow-up.

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References

  1. Eller-Vainicher C, Falchetti A, Gennari L, Cairoli E, Bertoldo F, Vescini F, Scillitani A, Chiodini I (2019) DIAGNOSIS OF ENDOCRINE DISEASE: evaluation of bone fragility in endocrine disorders. Eur J Endocrinol. https://doi.org/10.1530/EJE-18-0991

    Article  PubMed  Google Scholar 

  2. Giustina A (2020) Acromegaly and vertebral fractures: facts and questions. Trends Endocrinol Metab 31(4):274–275. https://doi.org/10.1016/j.tem.2020.01.011

    Article  CAS  PubMed  Google Scholar 

  3. Carrone F, Ariano S, Piccini S, Milani D, Mirani M, Balzarini L, Lania AG, Mazziotti G (2021) Update on vertebral fractures in pituitary diseases: from research to clinical practice. Hormones (Athens) 20(3):423–437. https://doi.org/10.1007/s42000-021-00275-5

    Article  PubMed  Google Scholar 

  4. Hong S, Kim KS, Han K, Park CY (2022) Acromegaly and cardiovascular outcomes: a cohort study. Eur Heart J 43(15):1491–1499. https://doi.org/10.1093/eurheartj/ehab822

    Article  PubMed  Google Scholar 

  5. Mazziotti G, Biagioli E, Maffezzoni F, Spinello M, Serra V, Maroldi R, Floriani I, Giustina A (2015) Bone turnover, bone mineral density, and fracture risk in acromegaly: a meta-analysis. J Clin Endocrinol Metab 100(2):384–394. https://doi.org/10.1210/jc.2014-2937

    Article  CAS  PubMed  Google Scholar 

  6. Fleseriu M, Biller BMK, Freda PU et al (2021) A Pituitary Society update to acromegaly management guidelines. Pituitary 24(1):1–13. https://doi.org/10.1007/s11102-020-01091-7

    Article  PubMed  Google Scholar 

  7. Giustina A, Barkan A, Beckers A et al (2020) A consensus on the diagnosis and treatment of acromegaly comorbidities: an update. J Clin Endocrinol Metab 105(4). https://doi.org/10.1210/clinem/dgz096

  8. Mazziotti G, Lania AGA, Canalis E (2019) MANAGEMENT OF ENDOCRINE DISEASE: Bone disorders associated with acromegaly: mechanisms and treatment. Eur J Endocrinol 181(2):R45–R56. https://doi.org/10.1530/EJE-19-0184

    Article  CAS  PubMed  Google Scholar 

  9. Anthony JR, Ioachimescu AG (2014) Acromegaly and bone disease. Curr Opin Endocrinol Diabetes Obes 21(6):476–482. https://doi.org/10.1097/MED.0000000000000109

    Article  CAS  PubMed  Google Scholar 

  10. Tran O, Silverman S, Xu X, Bonafede M, Fox K, McDermott M, Gandra S (2021) Long-term direct and indirect economic burden associated with osteoporotic fracture in US postmenopausal women. Osteoporos Int 32(6):1195–1205. https://doi.org/10.1007/s00198-020-05769-3

    Article  PubMed  PubMed Central  Google Scholar 

  11. Uygur MM, Yazici DD, Bugdayci O, Yavuz DG (2021) Prevalence of vertebral fractures and serum sclerostin levels in acromegaly. Endocrine 73(3):667–673. https://doi.org/10.1007/s12020-021-02751-9

    Article  CAS  PubMed  Google Scholar 

  12. Frara S, Melin Uygur M, di Filippo L, Doga M, Losa M, Santoro S, Mortini P, Giustina A (2022) High prevalence of vertebral fractures associated with preoperative GH levels in patients with recent diagnosis of acromegaly. J Clin Endocrinol Metab 107(7):e2843–e2850. https://doi.org/10.1210/clinem/dgac183

    Article  PubMed  Google Scholar 

  13. Mazziotti G, Bianchi A, Porcelli T, Mormando M, Maffezzoni F, Cristiano A, Giampietro A, De Marinis L, Giustina A (2013) Vertebral fractures in patients with acromegaly: a 3-year prospective study. J Clin Endocrinol Metab 98(8):3402–3410. https://doi.org/10.1210/jc.2013-1460

    Article  CAS  PubMed  Google Scholar 

  14. Wassenaar MJ, Biermasz NR, Hamdy NA et al (2011) High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly. Eur J Endocrinol 164(4):475–483. https://doi.org/10.1530/EJE-10-1005

    Article  CAS  PubMed  Google Scholar 

  15. Mazziotti G, Bianchi A, Bonadonna S, Cimino V, Patelli I, Fusco A, Pontecorvi A, De Marinis L, Giustina A (2008) Prevalence of vertebral fractures in men with acromegaly. J Clin Endocrinol Metab 93(12):4649–4655. https://doi.org/10.1210/jc.2008-0791

    Article  CAS  PubMed  Google Scholar 

  16. Ha J, Jeong C, Han KD, Lim Y, Kim MK, Kwon HS, Song KH, Kang MI, Baek KH (2021) Comparison of fracture risk between type 1 and type 2 diabetes: a comprehensive real-world data. Osteoporos Int 32(12):2543–2553. https://doi.org/10.1007/s00198-021-06032-z

    Article  CAS  PubMed  Google Scholar 

  17. Bolanowski M, Halupczok J, Jawiarczyk-Przybylowska A (2015) Pituitary disorders and osteoporosis. Int J Endocrinol 2015(206853. https://doi.org/10.1155/2015/206853

  18. Petrossians P, Daly AF, Natchev E et al (2017) Acromegaly at diagnosis in 3173 patients from the Liege Acromegaly Survey (LAS) database. Endocr Relat Cancer 24(10):505–518. https://doi.org/10.1530/ERC-17-0253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kwon H, Jung JH, Han KD, Park YG, Cho JH, Lee DY, Han JM, Park SE, Rhee EJ, Lee WY (2018) Prevalence and annual incidence of thyroid disease in Korea from 2006 to 2015: a nationwide population-based cohort study. Endocrinol Metab (Seoul) 33(2):260–267. https://doi.org/10.3803/EnM.2018.33.2.260

    Article  CAS  PubMed  Google Scholar 

  20. Wang SM, Han KD, Kim NY, Um YH, Kang DW, Na HR, Lee CU, Lim HK (2020) Association of alcohol intake and fracture risk in elderly varied by affected bones: A nationwide longitudinal study. Psychiatry Investig 17(10):1013–1020. https://doi.org/10.30773/pi.2020.0143

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ueland T, Fougner SL, Godang K, Schreiner T, Bollerslev J (2006) Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients. Eur J Endocrinol 155(5):709–715. https://doi.org/10.1530/eje.1.02285

    Article  CAS  PubMed  Google Scholar 

  22. Bolanowski M, Daroszewski J, Medraś M, Zadrozna-Sliwka B (2006) Bone mineral density and turnover in patients with acromegaly in relation to sex, disease activity, and gonadal function. J Bone Miner Metab 24(1):72–78. https://doi.org/10.1007/s00774-005-0649-9

    Article  PubMed  Google Scholar 

  23. Piskinpasa ME, Piskinpasa H (2022) Bone biochemical markers in acromegaly: An association with disease activity and gonadal status. North Clin Istanb 9(1):74–81. https://doi.org/10.14744/nci.2020.35467

    Article  PubMed  PubMed Central  Google Scholar 

  24. Madeira M, Neto LV, de Paula Paranhos Neto F, Barbosa Lima IC, Carvalho de Mendonca LM, Gadelha MR, Fleiuss de Farias ML (2013) Acromegaly has a negative influence on trabecular bone, but not on cortical bone, as assessed by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab 98(4):1734–1741. https://doi.org/10.1210/jc.2012-4073

    Article  CAS  PubMed  Google Scholar 

  25. Ott SM (2018) Cortical or trabecular bone: What’s the difference? Am J Nephrol 47(6):373–375. https://doi.org/10.1159/000489672

    Article  PubMed  Google Scholar 

  26. Godang K, Lekva T, Normann KR, Olarescu NC, Øystese KAB, Kolnes A, Ueland T, Bollerslev J, Heck A (2019) Hip structure analyses in acromegaly: decrease of cortical bone thickness after treatment: a longitudinal cohort study. JBMR Plus 3(12):e10240. https://doi.org/10.1002/jbm4.10240

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mazziotti G, Lania AG, Canalis E (2022) Skeletal disorders associated with the growth hormone-insulin-like growth factor 1 axis. Nat Rev Endocrinol 18(6):353–365. https://doi.org/10.1038/s41574-022-00649-8

    Article  CAS  PubMed  Google Scholar 

  28. Liu Z, Solesio ME, Schaffler MB, Frikha-Benayed D, Rosen CJ, Werner H, Kopchick JJ, Pavlov EV, Abramov AY, Yakar S (2019) Mitochondrial function is compromised in cortical bone osteocytes of long-lived growth hormone receptor null mice. J Bone Miner Res 34(1):106–122. https://doi.org/10.1002/jbmr.3573

    Article  CAS  PubMed  Google Scholar 

  29. Dalle Carbonare L, Micheletti V, Cosaro E, Valenti MT, Mottes M, Francia G, Davì MV (2018) Bone histomorphometry in acromegaly patients with fragility vertebral fractures. Pituitary 21(1):56–64. https://doi.org/10.1007/s11102-017-0847-1

    Article  CAS  PubMed  Google Scholar 

  30. Malgo F, Hamdy NAT, Rabelink TJ, Kroon HM, Claessen K, Pereira AM, Biermasz NR, Appelman-Dijkstra NM (2017) Bone material strength index as measured by impact microindentation is altered in patients with acromegaly. Eur J Endocrinol 176(3):339–347. https://doi.org/10.1530/eje-16-0808

    Article  CAS  PubMed  Google Scholar 

  31. Cellini M, Biamonte E, Mazza M et al (2021) Vertebral fractures associated with spinal sagittal imbalance and quality of life in acromegaly: a radiographic study with EOS 2D/3D technology. Neuroendocrinology 111(8):775–785. https://doi.org/10.1159/000511811

    Article  CAS  PubMed  Google Scholar 

  32. Vestergaard P, Mosekilde L (2004) Fracture risk is decreased in acromegaly–a potential beneficial effect of growth hormone. Osteoporos Int 15(2):155–159. https://doi.org/10.1007/s00198-003-1531-z

    Article  CAS  PubMed  Google Scholar 

  33. Valassi E, Crespo I, Malouf J, Llauger J, Aulinas A, Marin AM, Biagetti B, Webb SM (2016) Reduction of trabecular and cortical volumetric bone mineral density at the proximal femur in patients with acromegaly. Eur J Endocrinol 174(2):107–114. https://doi.org/10.1530/EJE-15-0931

    Article  CAS  PubMed  Google Scholar 

  34. Appelman-Dijkstra NM, Biermasz NR (2017) Understanding and predicting fracture risk in acromegaly. Endocrine 55(3):662–663. https://doi.org/10.1007/s12020-017-1238-0

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  36. Sorohan MC, Poiana C (2022) Vertebral fractures in acromegaly: a systematic review. J Clin Med 12(1). https://doi.org/10.3390/jcm12010164

  37. Chiloiro S, Giampietro A, Frara S et al (2020) Effects of Pegvisomant and Pasireotide LAR on vertebral fractures in acromegaly resistant to first-generation SRLs. J Clin Endocrinol Metab 105(3). https://doi.org/10.1210/clinem/dgz054

  38. Vitali E, Palagano E, Schiavone ML, Mantovani G, Sobacchi C, Mazziotti G, Lania A (2022) Direct effects of octreotide on osteoblast cell proliferation and function. J Endocrinol Invest 45(5):1045–1057. https://doi.org/10.1007/s40618-022-01740-7

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-Ro, Jongno-Gu, Seoul, 03181, Republic of Korea

    Hyemi Kwon, Sun Joon Moon, Se Eun Park, Eun-Jung Rhee & Won-Young Lee

  2. Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea

    Kyung-Do Han & Bong-Sung Kim

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Hyemi Kwon, Kyung-Do Han, Bong-Sung Kim, Sun Joon Moon, Se Eun Park, Eun-Jung Rhee, and Won-Young Lee declare that they have no conflict of interest.

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Hyemi Kwon, Kyung-Do Han, Bong-Sung Kim, Sun Joon Moon, Se Eun Park, Eun-Jung Rhee, and Won-Young Lee declare that they have nothing to declare.

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Hyemi Kwon and Kyung-Do Han contributed equally (co-first authors).

Eun-Jung Rhee and Won-Young Lee contributed equally (co-corresponding authors).

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Kwon, H., Han, KD., Kim, BS. et al. Acromegaly and the long-term fracture risk of the vertebra and hip: a national cohort study. Osteoporos Int 34, 1591–1600 (2023). https://doi.org/10.1007/s00198-023-06800-z

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