Bone metabolism disorders in endogenous Cushing syndrome
PDF

Keywords

Cushings disease
Cushing syndrome
cortisol
osteoporosis

How to Cite

Cylke -Falkowska, K., & Stelmachowska-Banaś, M. (2023). Bone metabolism disorders in endogenous Cushing syndrome. Wiedza Medyczna, 5(2), 15-20. https://doi.org/10.36553/wm.155

Abstract

Endogenous Cushing syndrome (CS) leading to an overproduction of cortisol is a major cause of secondary osteoporosis. Bone complications in CS, despite the fact that they not only reduce the quality of life, but also increase mortality, are still underdiagnosed. Hypercortisolemia results, among others,  in a reduced bone mineral density (BMD). However, an increased risk of fracture in CS may occur in bones with only a slight reduction or even normal BMD. The disease is usually insidious, prolonging the period of hypercortisolemia before diagnosis. Therefore, skeletal complications such as reduced BMD, osteoporosis and fractures are common in CS. Osteoporosis has a prevalence of 40-70%, osteopenia 80-85% and fractures 30-70% in patients with CS (1, 2). Fractures usually involve the lumbar and thoracic vertebrae, hips, ribs and pelvis as the trabecular bone is mainly affected. The most common pathogenesis of CS leading to bone lesions remains a topic of researches. Chronic hypercortisolemia leads not only to the reduction of BMD but also to changes in bone microarchitecture. Increased resorption and inhibited bone formation are the main mechanisms described in CS. Reversal of changes in bone mineral density after recovery from CS has been observed. Surgical treatment of pituitary or adrenal tumours should be the first line of treatment. However, vitamin D and calcium supplementation as well as treatment with antiresorptive drugs seems to be also essential. In this paper we presents a review of the current literature on bone complications in endogenous CS.  

https://doi.org/10.36553/wm.155
PDF

References

(1) Apaydin T, Yavuz DG. Assessment of non-traumatic vertebral fractures in Cushing's syndrome patients. J Endocrinol Invest 2021; 44(8):1767-73.

(2) Minetto M, Reimondo G, Osella G, Ventura M, Angeli A, Terzolo M. Bone loss is more severe in primary adrenal than in pituitary-dependent Cushing's syndrome. Osteoporos Int 2004; 15(11):855-61.

(3) Carney JA. The search for Harvey Cushing's patient, Minnie G, and the cause of her hypercortisolism. Am J Surg Pathol 1995; 19(1):100-8.

(4) Lindholm J, Juul S, Jorgensen JO, Astrup J, Bjerre P, Feldt-Rasmussen U, et al. Incidence and late prognosis of Cushing's syndrome: a population-based study. J Clin Endocrinol Metab 2001; 86(1):117-23.

(5) Agustsson TT, Baldvinsdottir T, Jonasson JG, Olafsdottir E, Steinthorsdottir V, Sigurdsson G, et al. The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur J Endocrinol 2015; 173(5):655-64.

(6) Bolland MJ, Holdaway IM, Berkeley JE, Lim S, Dransfield WJ, Conaglen JV, et al. Mortality and morbidity in Cushing's syndrome in New Zealand. Clin Endocrinol (Oxf) 2011; 75(4): 436-42.

(7) Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing's syndrome. Lancet 2006; 367(9522):1605-17.

(8) Etxabe J, Vazquez JA. Morbidity and mortality in Cushing's disease: an epidemiological approach. Clin Endocrinol (Oxf) 1994; 40(4):479-84.

(9) Lonser RR, Nieman L, Oldfield EH. Cushing's disease: pathobiology, diagnosis, and management. J Neurosurg 2017; 126(2):404-17.

(10) Nieman LK. Diagnosis of Cushing's Syndrome in the Modern Era. Endocrinol Metab Clin North Am 2018; 47(2):259-73.

(11) Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). 1932. Obes Res 1994; 2(5):486-508.

(12) Tauchmanova L, Pivonello R, Di Somma C, Rossi R, De Martino MC, Camera L, et al. Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status. J Clin Endocrinol Metab 2006; 91(5):1779-84.

(13) Trementino L, Appolloni G, Ceccoli L, Marcelli G, Concettoni C, Boscaro M, et al. Bone complications in patients with Cushing's syndrome: looking for clinical, biochemical, and genetic determinants. Osteoporos Int 2014; 25(3):913-21.

(14) Calvo MS, Eyre DR, Gundberg CM. Molecular basis and clinical application of biological markers of bone turnover. Endocr Rev 1996; 17(4):333-68.

(15) Mancini T, Doga M, Mazziotti G, Giustina A. Cushing's syndrome and bone. Pituitary 2004; 7(4):249-52.

(16) Toth M, Grossman A. Glucocorticoid-induced osteoporosis: lessons from Cushing's syndrome. Clin Endocrinol (Oxf) 2013; 79(1):1-11.

(17) Kaltsas G, Makras P. Skeletal diseases in Cushing's syndrome: osteoporosis versus arthropathy. Neuroendocrinology 2010; 92 Suppl 1:60-4.

(18) Ueland T, Bollerslev J, Godang K, Muller F, Froland SS, Aukrust P. Increased serum osteoprotegerin in disorders characterized by persistent immune activation or glucocorticoid excess--possible role in bone homeostasis. Eur J Endocrinol 2001; 145(6):685-90.

(19) Kristo C, Ueland T, Godang K, Aukrust P, Bollerslev J. Biochemical markers for cardiovascular risk following treatment in endogenous Cushing's syndrome. J Endocrinol Invest 2008; 31(5):400-5.

(20) Camozzi V, Sanguin F, Albigier N, Scaroni C, Mantero F, Zaninotto M, et al. Persistent increase of osteoprotegerin levels after cortisol normalization in patients with Cushing's syndrome. Eur J Endocrinol 2010; 162(1):85-90.

(21) Canalis E, Giustina A. Glucocorticoid-induced osteoporosis: summary of a workshop. J Clin Endocrinol Metab 2001; 86(12):5681-5.

(22) Weinstein RS. Clinical practice. Glucocorticoid-induced bone disease. N Engl J Med 2011; 365(1):62-70.

(23) Laan RF, van Riel PL, van de Putte LB, van Erning LJ, van't Hof MA, Lemmens JA. Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study. Ann Intern Med 1993; 119(10):963-8.

(24) Wang Y, Zhao R, Gu Z, Dong C, Guo G, Li L. Effects of glucocorticoids on osteoporosis in rheumatoid arthritis: a systematic review and meta-analysis. Osteoporos Int 2020; 31(8):1401-9.

(25) Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. J Bone Miner Res 2000; 15(6):993-1000.

(26) Balasubramanian A, Wade SW, Adler RA, Saag K, Pannacciulli N, Curtis JR. Glucocorticoid Exposure and Fracture Risk in a Cohort of US Patients With Selected Conditions. J Bone Miner Res 2018; 33(10):1881-8.

(27) dos Santos CV, Vieira Neto L, Madeira M, Alves Coelho MC, de Mendonca LM, Paranhos-Neto Fde P, et al. Bone density and microarchitecture in endogenous hypercortisolism. Clin Endocrinol (Oxf) 2015; 83(4):468-74.

(28) Valassi E, Santos A, Yaneva M, Toth M, Strasburger CJ, Chanson P, et al. The European Registry on Cushing's syndrome: 2-year experience. Baseline demographic and clinical characteristics. Eur J Endocrinol 2011; 165(3):383-92.

(29) Lekamwasam S, Adachi JD, Agnusdei D, Bilezikian J, Boonen S, Borgstrom F, et al. A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. Osteoporos Int 2012; 23(9):2257-76.

(30) Vestergaard P, Lindholm J, Jorgensen JO, Hagen C, Hoeck HC, Laurberg P, et al. Increased risk of osteoporotic fractures in patients with Cushing's syndrome. Eur J Endocrinol 2002; 146(1):51-6.

(31) Ohmori N, Nomura K, Ohmori K, Kato Y, Itoh T, Takano K. Osteoporosis is more prevalent in adrenal than in pituitary Cushing's syndrome. Endocr J 2003; 50(1):1-7.

(32) Belaya ZE, Hans D, Rozhinskaya LY, Dragunova NV, Sasonova NI, Solodovnikov AG, et al. The risk factors for fractures and trabecular bone-score value in patients with endogenous Cushing's syndrome. Arch Osteoporos 2015; 10:44.

(33) Faggiano A, Pivonello R, Filippella M, Di Somma C, Orio F Jr, Lombard G, et al. Spine abnormalities and damage in patients cured from Cushing's disease. Pituitary 2001; 4(3):153-61.

(34) Chiodini I, Torlontano M, Carnevale V, Trischitta V, Scillitani A. Skeletal involvement in adult patients with endogenous hypercortisolism. J Endocrinol Invest 2008; 31(3):267-76.

(35) Arnaldi G, Mancini T, Tirabassi G, Trementino L, Boscaro M. Advances in the epidemiology, pathogenesis, and management of Cushing's syndrome complications. J Endocrinol Invest 2012; 35(4):434-48.

(36) Futo L, Toke J, Patocs A, Szappanos A, Varga I, Glaz E, et al. Skeletal differences in bone mineral area and content before and after cure of endogenous Cushing's syndrome. Osteoporos Int 2008; 19(7):941-9.

(37) Godang K, Ueland T, Bollerslev J. Decreased bone area, bone mineral content, formative markers, and increased bone resorptive markers in endogenous Cushing's syndrome. Eur J Endocrinol 1999; 141(2):126-31.

(38) Rahaman SH, Jyotsna VP, Kandasamy D, Shreenivas V, Gupta N, Tandon N. Bone Health in Patients with Cushing's Syndrome. Indian J Endocrinol Metab 2018; 22(6):766-9.

(39) Pecori Giraldi F, Moro M, Cavagnini F, Study Group on the Hypothalamo-Pituitary-Adrenal Axis of the Italian Society of E. Gender- -related differences in the presentation and course of Cushing's disease. J Clin Endocrinol Metab 2003; 88(4):1554-8.

(40) Shibli-Rahhal A, Van Beek M, Schlechte JA. Cushing's syndrome. Clin Dermatol 2006; 24(4):260-5.

(41) Karavitaki N, Ioannidis G, Giannakopoulos F, Mavrokefalos P, Thalassinos N. Evaluation of bone mineral density of the peripheral skeleton in pre- and postmenopausal women with newly diagnosed endogenous Cushing's syndrome. Clin Endocrinol (Oxf) 2004; 60(2):264-70.

(42) Di Somma C, Pivonello R, Loche S, Faggiano A, Marzullo P, Di Sarno A, et al. Severe impairment of bone mass and turnover in Cushing's disease: comparison between childhood-onset and adulthood-onset disease. Clin Endocrinol (Oxf) 2002; 56(2):153-8.

(43) Kristo C, Jemtland R, Ueland T, Godang K, Bollerslev J. Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing's syndrome: a prospective, long-term study. Eur J Endocrinol 2006; 154(1):109-18.

(44) Hermus AR, Smals AG, Swinkels LM, Huysmans DA, Pieters GF, Sweep CF, et al. Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome. J Clin Endocrinol Metab 1995; 80(10):2859-65.

(45) Tauchmanova L, Pivonello R, De Martino MC, Rusciano A, De Leo M, Ruosi C, et al. Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism. Eur J Endocrinol 2007; 157(3):359-66.

(46) Barahona MJ, Sucunza N, Resmini E, Fernandez-Real JM, Ricart W, Moreno-Navarrete JM, et al. Deleterious effects of glucocorticoid replacement on bone in women after long-term remission of Cushing's syndrome. J Bone Miner Res 2009; 24(11):1841-6.

(47) Chiodini I, Carnevale V, Torlontano M, Fusilli S, Guglielmi G, Pileri M, et al. Alterations of bone turnover and bone mass at different skeletal sites due to pure glucocorticoid excess: study in eumenorrheic patients with Cushing's syndrome. J Clin Endocrinol Metab 1998; 83(6):1863-7.

(48) Belaya ZE, Rozhinskaya LY, Melnichenko GA, Solodovnikov AG, Dragunova NV, Iljin AV, et al. Serum extracellular secreted antagonists of the canonical Wnt/beta-catenin signaling pathway in patients with Cushing's syndrome. Osteoporos Int 2013; 24(8):2191-9.

(49) Klazen CA, Lohle PN, de Vries J, Jansen FH, Tielbeek AV, Blonk MC, et al. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial. Lancet 2010; 376(9746): 1085-92.

(50) Clark W, Bird P, Gonski P, Diamond TH, Smerdely P, McNeil HP, et al. Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 2016; 388(10052):1408-16.

(51) Al-Nakshabandi NA. Percutaneous vertebroplasty complications. Ann Saudi Med 2011; 31(3):294-7.

(52) Cheng J, Ju S, Zhang Z. Osteoporotic vertebral compression fractures caused by Cushing's syndrome in young women: case report and literature review. BMC Musculoskelet Disord 2023; 24(1):167.

(53) Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, et al. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev 2011; (7):CD000333.

(54) Scillitani A, Mazziotti G, Di Somma C, Moretti S, Stigliano A, Pivonello R, et al. Treatment of skeletal impairment in patients with endogenous hypercortisolism: when and how? Osteoporos Int 2014; 25(2):441-6.

(55) Di Somma C, Colao A, Pivonello R, Klain M, Faggiano A, Tripodi FS, et al. Effectiveness of chronic treatment with alendronate in the osteoporosis of Cushing's disease. Clin Endocrinol (Oxf) 1998; 48(5):655-62.

(56) Ding L, Hu J, Wang D, Liu Q, Mo Y, Tan X, et al. Efficacy and Safety of First- and Second-Line Drugs to Prevent Glucocorticoid-Induced Fractures. J Clin Endocrinol Metab 2020; 105(1).

(57) Laurent MR, Goemaere S, Verroken C, Bergmann P, Body JJ, Bruyere O, et al. Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club. Front Endocrinol (Lausanne) 2022; 13:908727.

(58) Pocock NA, Eisman JA, Dunstan CR, Evans RA, Thomas DH, Huq NL. Recovery from steroid-induced osteoporosis. Ann Intern Med 1987; 107(3):319-23.

(59) Manning PJ, Evans MC, Reid IR. Normal bone mineral density following cure of Cushing's syndrome. Clin Endocrinol (Oxf) 1992; 36(3):229-34.

(60) Leong GM, Abad V, Charmandari E, Reynolds JC, Hill S, Chrousos GP, et al. Effects of child- and adolescent-onset endogenous Cushing syndrome on bone mass, body composition, and growth: a 7-year prospective study into young adulthood. J Bone Miner Res 2007; 22(1):110-8.

(61) Lodish MB, Hsiao HP, Serbis A, Sinaii N, Rothenbuhler A, Keil MF, et al. Effects of Cushing disease on bone mineral density in a pediatric population. J Pediatr 2010; 156(6):1001-5.

(62) Kawamata A, Iihara M, Okamoto T, Obara T. Bone mineral density before and after surgical cure of Cushing's syndrome due to adrenocortical adenoma: prospective study. World J Surg 2008; 32(5):890-6.

Creative Commons License

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

Metrics



Downloads

Download data is not yet available.