Top

Published in:

01-02-2014 | Opinion Paper

Treatment of skeletal impairment in patients with endogenous hypercortisolism: when and how?

Authors: A. Scillitani, G. Mazziotti, C. Di Somma, S. Moretti, A. Stigliano, R. Pivonello, A. Giustina, A. Colao, On behalf of ABC Group

Published in: Osteoporosis International | Issue 2/2014

Abstract

Guidelines for the management of osteoporosis induced by endogenous hypercortisolism are not available. Both the American College of Rheumatology and the International Osteoporosis Foundation recommend to modulate the treatment of exogenous glucocorticoid-induced osteoporosis (GIO) based on the individual fracture risk profile (calculated by FRAX) and dose of glucocorticoid used, but it is difficult to translate corticosteroid dosages to different degrees of endogenous hypercortisolism, and there are no data on validation of FRAX stratification method in patients with endogenous hypercortisolism. Consequently, it is unclear whether such recommendations may be adapted to patients with endogenous hypercortisolism. Moreover, patients with exogenous GIO take glucocorticoids since suffering a disease that commonly affects bone. On the other hand, the correction of coexistent risk factors, which may contribute to increase the fracture risk in patients exposed to glucocorticoid excess, and the removal of the cause of endogenous hypercortisolism, may lead to the recovery of bone health. Although the correction of hypercortisolism and of possible coexistent risk factors is necessary to favor the normalization of bone turnover with recovery of bone mass; in some patients, the fracture risk could not be normalized and specific anti-osteoporotic drugs should be given. Who, when, and how the patient with endogenous hypercortisolism should be treated with bone-active therapy is discussed.

Mazziotti G, Canalis E, Giustina A (2010) Drug-induced osteoporosis: mechanisms and clinical implications. Am J Med 123:877–884PubMedCrossRef

Mancini T, Doga M, Mazziotti G, Giustina A (2004) Cushing’s syndrome and bone. Pituitary 7:249–252PubMedCrossRef

Pivonello R, De Martino MC, De Leo M, Lombardi G, Colao A (2008) Cushing’s syndrome. Endocrinol Metab Clin North Am 37:135–249PubMedCrossRef

Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A (2006) Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab 17:144–149PubMedCrossRef

O’Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145:1835–1841PubMedCrossRef

Lane NE, Yao W, Balooch M, Nalla RK, Balooch G, Habelitz S, Kinney JH, Bonewald LF (2006) Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. J Bone Miner Res 21:466–476PubMedCentralPubMedCrossRef

Van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C (2003) Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 48:3224–3229PubMedCrossRef

Tauchmanovà L, Pivonello R, Di Somma C, Rossi R, De Martino MC, Camera L, Klain M, Salvatore M, Lombardi G, Colao A (2006) Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status. J Clin Endocrinol Metab 91:1779–1784PubMedCrossRef

Chiodini I, Morelli V, Masserini B, Salcuni AS, Eller-Vainicher C, Viti R, Coletti F, Guglielmi G, Battista C, Carnevale V, Iorio L, Beck-Peccoz P, Arosio M, Ambrosi B, Scillitani A (2009) Bone mineral density, prevalence of vertebral fractures, and bone quality in patients with adrenal incidentalomas with and without subclinical hypercortisolism: an Italian multicenter study. J Clin Endocrinol Metab 94:3207–3214PubMedCrossRef

10.

Angeli A, Guglielmi G, Dovio A, Capelli G, de Feo D, Giannini S, Giorgino R, Moro L, Giustina A (2006) High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone 39:253–259PubMedCrossRef

11.

Nevitt MC, Ettinger B, Black DM, Stone K, Jamal SA, Ensrud K, Segal M, Genant HK, Cummings SR (1998) The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med 128:793–800PubMedCrossRef

12.

Jalava T, Sarna S, Pylkkänen L, Mawer B, Kanis JA, Selby P, Davies M, Adams J, Francis RM, Robinson J, McCloskey E (2003) Association between vertebral fracture and increased mortality in osteoporotic patients. J Bone Miner Res 18:1254–1260PubMedCrossRef

13.

Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM (2008) The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 93:1526–1540PubMedCrossRef

14.

Randazzo ME, Grossrubatscher E, Dalino Ciaramella P, Vanzulli A, Loli P (2012) Spontaneous recovery of bone mass after cure of endogenous hypercortisolism. Pituitary 15:193–201PubMedCrossRef

15.

Pivonello R, De Martino MC, De Leo M, Tauchmanovà L, Faggiano A, Lombardi G, Colao A (2007) Cushing’s syndrome: aftermath of the cure. Arq Bras Endocrinol Metabol 51:1381–1391PubMedCrossRef

16.

Mancini T, Porcelli T, Giustina A (2010) Treatment of Cushing disease: overview and recent findings. Ther Clin Risk Manag 6:505–516PubMedCentralPubMed

17.

Morelli V, Eller-Vainicher C, Salcuni AS, Coletti F, Iorio L, Muscogiuri G, Della Casa S, Arosio M, Ambrosi B, Beck-Peccoz P, Chiodini I (2011) Risk of new vertebral fractures in patients with adrenal incidentaloma with and without subclinical hypercortisolism: a multicenter longitudinal study. J Bone Miner Res 26:1816–1821PubMedCrossRef

18.

Faggiano A, Pivonello R, Filippella M, Di Somma C, Orio F Jr, Lombard G, Colao A (2001) Spine abnormalities and damage in patients cured from Cushing’s disease. Pituitary 4:153–161PubMedCrossRef

19.

Grossman JM, Gordon R, Ranganath VK, Deal C, Caplan L, Chen W, Curtis JR, Furst DE, McMahon M, Patkar NM, Volkmann E, Saag KG (2010) American college of rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 62:1515–1526CrossRef

20.

Lekamwasam S, Adachi JD, Agnusdei D, Bilezikian J, Boonen S, Borgström F, Cooper C, Diez Perez A, Eastell R, Hofbauer LC, Kanis JA, Langdahl BL, Lesnyak O, Lorenc R, McCloskey E, Messina OD, Napoli N, Obermayer-Pietsch B, Ralston SH, Sambrook PN, Silverman S, Sosa M, Stepan J, Suppan G, Wahl DA, Compston JE (2012) Joint IOF-ECTS GIO guidelines working group. A framework for the development of guidelines for the management of glucocorticoid-induced osteoporosis. Osteoporos Int 23:2257–2276PubMedCrossRef

21.

Füto L, Toke J, Patócs A, Szappanos A, Varga I, Gláz E, Tulassay Z, Rácz K, Tóth M (2008) Skeletal differences in bone mineral area and content before and after cure of endogenous Cushing’s syndrome. Osteoporos Int 19:941–949PubMedCrossRef

22.

Vestergaard P, Lindholm J, Jørgensen JO, Hagen C, Hoeck HC, Laurberg P, Rejnmark L, Brixen K, Kristensen LØ, Feldt-Rasmussen U, Mosekilde L (2002) Increased risk of osteoporotic fractures in patients with Cushing’s syndrome. Eur J Endocrinol 146:51–56PubMedCrossRef

23.

Kung AW, Chan TM, Lau CS, Wong RW, Yeung SS (1999) Osteopenia in young hypogonadal women with systemic lupus erythematosus receiving chronic steroid therapy: a randomized controlled trial comparing calcitriol and hormonal replacement therapy. Rheumatology (Oxford) 38:1239–1244CrossRef

24.

Tauchmanovà L, Pivonello R, De Martino MC, Rusciano A, De Leo M, Ruosi C, Mainolfi C, Lombardi G, Salvatore M, Colao A (2007) Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism. Eur J Endocrinol 157:359–366PubMedCrossRef

25.

Weinstein RS, Jia D, Powers CC, Stewart SA, Jilka RL, Parfitt AM, Manolagas SC (2004) The skeletal effects of glucocorticoid excess override those of orchidectomy in mice. Endocrinology 145:1980–1987PubMedCrossRef

26.

Giustina A, Mazziotti G, Canalis E (2008) Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29:535–559PubMedCrossRef

27.

Tauchmanova L, Di Somma C, Rusciano A, Lombardi G, Colao A (2007) The role for growth hormone in linking arthritis, osteoporosis, and body composition. J Endocrinol Invest 30(6 Suppl):35–41PubMed

28.

Mazziotti G, Porcelli T, Bianchi A, Cimino V, Patelli I, Mejia C, Fusco A, Giampietro A, De Marinis L, Giustina A (2010) Glucocorticoid replacement therapy and vertebral fractures in hypopituitary adult males with GH deficiency. Eur J Endocrinol 163:15–20PubMedCrossRef

29.

Magiakou MA, Mastorakos G, Gomez MT, Rose SR, Chrousos GP (1994) Suppressed spontaneous and stimulated growth hormone secretion in patients with Cushing’s disease before and after surgical cure. J Clin Endocrinol Metab 78:131–137PubMed

30.

Hughes NR, Lissett CA, Shalet SM (1999) Growth hormone status following treatment for Cushing’s syndrome. Clin Endocrinol (Oxf) 51:61–66CrossRef

31.

Pecori Giraldi F, Andrioli M, De Marinis L, Bianchi A, Giampietro A, De Martin M, Sacco E, Scacchi M, Pontecorvi A, Cavagnini F (2007) Significant GH deficiency after long-term cure by surgery in adult patients with Cushing’s disease. Eur J Endocrinol 156:233–239PubMedCrossRef

32.

Giustina A, Bussi AR, Jacobello C, Wehrenberg WB (1995) Effects of recombinant human growth hormone (GH) on bone and intermediary metabolism in patients receiving chronic glucocorticoid treatment with suppressed endogenous GH response to GH-releasing hormone. J Clin Endocrinol Metab 80:122–129PubMed

33.

Lebrethon MC, Grossman AB, Afshar F, Plowman PN, Besser GM, Savage MO (2000) Linear growth and final height after treatment for Cushing’s disease in childhood. J Clin Endocrinol Metab 85:3262–3265PubMed

34.

Bismuth E, Chevenne D, Czernichow P, Simon D (2010) Moderate deterioration in glucose tolerance during high-dose growth hormone therapy in glucocorticoid-treated patients with juvenile idiopathic arthritis. Horm Res Paediatr 73:465–472PubMedCrossRef

35.

Mazziotti G, Gazzaruso C, Giustina A (2011) Diabetes in Cushing syndrome: basic and clinical aspects. Trends Endocrinol Metab 22:499–506PubMedCrossRef

36.

Di Somma C, Colao A, Pivonello R, Klain M, Faggiano A, Tripodi FS, Merola B, Salvatore M, Lombardi G (1998) Effectiveness of chronic treatment with alendronate in the osteoporosis of Cushing’s disease. Clin Endocrinol (Oxf) 48:655–662CrossRef

37.

Tauchmanova L, Guerra E, Pivonello R, De Martino MC, De Leo M, Caggiano F, Lombardi G, Colao A (2009) Weekly clodronate treatment prevents bone loss and vertebral fractures in women with subclinical Cushing’s syndrome. J Endocrinol Invest 32:390–394PubMed

38.

Chiodini I, Torlontano M, Carnevale V, Trischitta V, Scillitani A (2008) Skeletal involvement in adult patients with endogenous hypercortisolism. J Endocrinol Invest 31:267–276PubMed

39.

Hansen KE, Wilson HA, Zapalowski C, Fink HA, Minisola S, Adler RA (2011) Uncertainties in the prevention and treatment of glucocorticoid-induced osteoporosis. J Bone Miner Res 26:1989–1996PubMedCrossRef

40.

McClung MR (2006) Inhibition of RANKL as a treatment for osteoporosis: preclinical and early clinical studies. Curr Osteoporos Rep 4:28–33PubMedCrossRef

41.

Dore RK, Cohen SB, Lane NE, Palmer W, Shergy W, Zhou L, Wang H, Tsuji W, Newmark R, Denosumab RA Study Group (2010) Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates. Ann Rheum Dis 69:872–875PubMedCrossRef

42.

Colao A, Tauchmanovà L, Pivonello R, Vuolo L, De Leo M, Rota F, Guerra E, Vitale P, Contaldi P, Lombardi G, Di Somma C (2009) Teriparatide treatment in osteoporosis of patients with Cushing’s Syndrome. ENEA Workshop Novel insights in the management of Cushing’s Syndrome, Napoli 4-6 Dicembre

43.

Lasco A, Catalano A, Morabito N, Gaudio A, Basile G, Trifiletti A, Atteritano M (2011) Adrenal effects of teriparatide in the treatment of severe postmenopausal osteoporosis. Osteoporos Int 22:299–303PubMedCrossRef

44.

Sun P, Cai DH, Li QN, Chen H, Deng WM, He L, Yang L (2010) Effects of alendronate and strontium ranelate on cancellous and cortical bone mass in glucocorticoid-treated adult rats. Calcif Tissue Int 86:495–501PubMedCrossRef

45.

Szappanos A, Toke J, Lippai D, Patócs A, Igaz P, Szücs N, Füto L, Gláz E, Rácz K, Tóth M (2010) Bone turnover in patients with endogenous Cushing’s syndrome before and after successful treatment. Osteoporos Int 21:637–645PubMedCrossRef

Title: Treatment of skeletal impairment in patients with endogenous hypercortisolism: when and how?
Authors: A. Scillitani
G. Mazziotti
C. Di Somma
S. Moretti
A. Stigliano
R. Pivonello
A. Giustina
A. Colao
On behalf of ABC Group
Publication date: 01-02-2014
Publisher: Springer London
Published in: Osteoporosis International / Issue 2/2014
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-013-2588-y

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Treatment of skeletal impairment in patients with endogenous hypercortisolism: when and how?

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2014

Frailty and osteoporosis in older women—a prospective study

Acute hypophosphatasemia

Changes in thigh muscle volume predict bone mineral density response to lifestyle therapy in frail, obese older adults

Age–period–cohort effects in the incidence of hip fractures: political and economic events are coincident with changes in risk

Development of the osteoporosis assessment questionnaire—physical function (OPAQ-PF): an osteoporosis-targeted, patient-reported outcomes (PRO) measure of physical function

Impact of nutrition on muscle mass, strength, and performance in older adults: response to Scott and Jones