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Horm Metab Res 2016; 48(09): 565-570
DOI: 10.1055/s-0042-112127
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Thyroid Function and its Implications in Oxidative Stress Influencing the Pathogenesis of Osteoporosis in Adults with Down Syndrome: A Cohort Study

E. R. Villani
1   Department of Geriatrics “Centro Medicina dell’Invecchiamento”, Catholic University of the Sacred Heart, Rome, Italy
,
G. Onder
1   Department of Geriatrics “Centro Medicina dell’Invecchiamento”, Catholic University of the Sacred Heart, Rome, Italy
,
A. Carfì
1   Department of Geriatrics “Centro Medicina dell’Invecchiamento”, Catholic University of the Sacred Heart, Rome, Italy
,
C. Di Segni
2   Division of Endocrinology, Department of Medical Sciences, Catholic University of the Sacred Heart, Rome, Italy
,
S. Raimondo
2   Division of Endocrinology, Department of Medical Sciences, Catholic University of the Sacred Heart, Rome, Italy
,
A. Silvestrini
3   Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy
,
E. Meucci
3   Institute of Biochemistry and Clinical Biochemistry, Catholic University of the Sacred Heart, Rome, Italy
,
A. Mancini
2   Division of Endocrinology, Department of Medical Sciences, Catholic University of the Sacred Heart, Rome, Italy
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Publikationsverlauf

received 12. März 2016

accepted 07. Juli 2016

Publikationsdatum:
24. August 2016 (online)

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Abstract

People with Down syndrome (DS) show lower bone mass density (BMD) and a higher prevalence of hypothyroidism compared to general population. Furthermore, DS is a well-known high oxidative stress (OS) condition because genes involved in OS map on chromosome 21. Thyroid function too is involved in OS. Since both thyroid function and OS lead to lower BMD and osteoporotic fractures, we have explored correlations among BMD, thyroid hormones, and parameters of OS in DS adults. A total of 105 DS patients (48 males; 21–71 years; mean BMI 28.88±7.12 kg/m2) were enrolled in a cohort study, 48 of them undergoing thyroid replacement therapy. We evaluated thyroid function, BMD, and total antioxidant capacity (TAC) in blood plasma. TAC was assayed by H2O2-metmyoglobin system, as source of radicals, and by the chromogenous ABTS, with a latency time (LAG) in the appearance of its cation ABTS+proportional to antioxidant concentration. BMD was evaluated with DEXA, using WHO criteria to classify osteoporosis. Low BMD was found in 83.78% of patients. TSH and LAG did not correlate with BMD. Nevertheless, LAG significantly correlates to Z-scores estimated at the lumbar spine (r2=0.558; p=0.03) in hypothyroid patients. Our data show that low TAC could be more associated with reduced BMD rather than TSH itself in DS patients and that the OS could have a role in the pathogenesis of osteoporosis regarding the hypothyroid subgroup.

Key words

bone mineral density - down syndrome - oxidative stress - thyroid function - total antioxidant capacity
 

  • References

  • 1 Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Anderson P, Mason CA, Collins JS, Kirby RS, Correa A. National Birth Defects Prevention Network. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A Clin Mol Teratol 2010; 88: 1008-1016
    CrossrefPubMedGoogle Scholar
  • 2 Lejeune J, Gautier M, Turpin R. Study of somatic chromosomes from 9 mongoloid children. C R Hebd Seances Acad Sci 1959; 248: 1721-1722
    PubMedGoogle Scholar
  • 3 Martin GM. Genetic syndromes in man with potential relevance to the pathobiology of aging. Birth Defects Orig Artic Ser 1978; 14: 5-39
    PubMedGoogle Scholar
  • 4 Nakamura E, Tanaka S. Biological ages of adult men and women with Down’s syndrome and its changes with aging. Mech Ageing Dev 1998; 105: 89-103
    CrossrefPubMedGoogle Scholar
  • 5 Thase ME. Longevity and mortality in Down’s syndrome. J Ment Defic Res 1982; 26: 177-192
    PubMedGoogle Scholar
  • 6 Karlsson B, Gustafsson J, Hedov G, Ivarsson SA, Annerén G. Thyroid dysfunction in Down’s syndrome: relation to age and thyroid autoimmunity. Arch Dis Child 1998; 79: 242-245
    CrossrefPubMedGoogle Scholar
  • 7 Colvin L, Jurenka SB, Van Allen MI. Down Syndrome. In: Hisami FM, Weissman SM, Martin G. (eds) Chromosomal Instability and Aging. New York: M. Dekker; 2003: 441-463
    CrossrefGoogle Scholar
  • 8 Selikowitz M. A five year longitudinal study of thyroid function in children with Down syndrome. Dev Med Child Neurol 1993; 35: 396-401
    PubMedGoogle Scholar
  • 9 Mancini A, Mariotti P, Conte G, Milardi D, Bianchi A, Fusco A, Fabrizi ML, Panichelli A, Littarru GP, De Marinis L. Hormonal and metabolical evaluation in Down syndrome: preliminary evidence for TSH dysregulation in hyperthyrotropinemic patients. Exp Clin Endocrinol Diabetes 2006; 114: 39-40
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 10 Doumoulin SC, Perret BP, Bennett AP, Caron PJ. Opposite effects of thyroid hormones on binding proteins for steroid hormones (sex hormones binding globulin and corticosteroid binding globulin) in humans. Eur J Endocrinol 1995; 132: 594-598
    CrossrefPubMedGoogle Scholar
  • 11 Mancini A, De Marinis L, Calabrò F, Fiumara C, Goglia A, Littarru GP. Physiopathological relevance of Coenzyme Q10 in thyroid disorders: CoQ10 concentrations in normal and diseased human thyroid tissue. In Folkers K, Littarru GP, Yamagami T. (eds.) Biomedical and Clinical Aspects of Coenzyme Q. Amsterdam: Elsevier Science Publisher; 1991: 441-448
    Google Scholar
  • 12 Mesri Alamdari N, Mahdavi R, Roshanravan N, Lotfi Yaghin N, Ostadrahimi AR, Faramarzi E. A Double-Blind, Placebo-Controlled Trial Related to the Effects of Melatonin on Oxidative Stress and Inflammatory Parameters of Obese Women. Horm Metab Res 2015; 47: 504-508
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 13 Parfentyeva E, Saha S, Hjellset VT, Kopprasch S, Schwarz PEH. Assessment of Small C-Fiber Status for Screening of Oxidative Stress in Patients at Risk of Diabetes. Horm Metab Res 2014; 46: 360-364
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 14 Zhang X, Yan SM, Zheng HL, Hu DH, Zhang YT, Guan QH, Ding QL. A Mechanism Underlying Hypertensive Occurrence in the Metabolic Syndrome: Cooperative Effect of Oxidative Stress and Calcium Accumulation in Vascular Smooth Muscle Cells. Horm Metab Res 2014; 46: 126-132
    Google Scholar
  • 15 Carmona YV, Coria MJ, Oliveros LB, Gimenez MS. Hypothyroidism and Oxidative Stress: Differential Effect on the Heart of Virgin and Pregnant Rats. Horm Metab Res 2014; 46: 14-20
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 16 Mancini A, Raimondo S, Di Segni C, Persano M, Gadotti G, Silvestrini A, Festa A, Tiano L, Pontecorvi A, Meucci E. Thyroid Hormones and Antioxidant Systems: Focus on Oxidative Stress in Cardiovascular and Pulmonary Diseases. Int J Mol Sci 2013; 14: 23893-23909
    CrossrefPubMedGoogle Scholar
  • 17 Lott IT. Antioxidants in Down syndrome. Biochim Biophys Acta 2011; 1822: 657-663
    PubMedGoogle Scholar
  • 18 Tiano L, Busciglio J. Mitochondrial dysfunction and Down syndrome: is there a role for CoQ10?. Biofactors 2011; 5: 386-392
    PubMedGoogle Scholar
  • 19 Coskun PE, Busciglio J. Oxidative stress and mitochondrial dysfunction in Down syndrome: relevance to aging and dementia. Curr Gerontol Geriatr Res 2012; 1: 49-56
    PubMedGoogle Scholar
  • 20 Duquet N. Osteoporosis: treatment and pharmaceutical care. J Pharm Belg 2014; 2: 14-24
    PubMedGoogle Scholar
  • 21 Ko YJ, Kim JY, Lee J, Song HJ, Kim JY, Choi NK, Park BJ. Levothyroxine dose and fracture risk according to the osteoporosis status in elderly women. J Prev Med Public Health 2014; 47: 36-46
    CrossrefPubMedGoogle Scholar
  • 22 Amashukeli M, Giorgadze E, Tsagareli M, Nozadze N, Jeiranashvili N. The impact of thyroid diseases on bone metabolism and fracture risk. Georgian Med News 2010; 184–185: 34-39
    PubMedGoogle Scholar
  • 23 Saeidnia S, Abdollahi M. Toxicological and pharmacological concerns on oxidative stress and related diseases. Toxicol Appl Pharamacol 2013; 15: 442-455
    PubMedGoogle Scholar
  • 24 Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res 1994; 9: 1137-1141
    PubMedGoogle Scholar
  • 25 Rice-Evans C, Miller NJ. Total antioxidant status in plasma and bodyfluids. Meth Enzymol 1994; 234: 279-293
    PubMedGoogle Scholar
  • 26 Meucci E, Milardi D, Mordente A, Martorana GE, Giacchi E, De Marinis L, Mancini A. Total antioxidant capacity in patients with varicoceles. Fertil Steril 2003; 79: 1577-1583
    CrossrefPubMedGoogle Scholar
  • 27 Baptista F, Varela A, Sardinha LB. Bone mineral mass in males and females withand without Down syndrome. Osteoporos Int 2005; 16: 380-388
    CrossrefPubMedGoogle Scholar
  • 28 Tyler CV, Snyder CW, Zyzanski S. Screening for osteoporosis in community-dwelling adults with mental retardation. Ment Retard 2000; 38: 316-321
    CrossrefPubMedGoogle Scholar
  • 29 Ejskjaer K, Uldbjerg N, Goldstein H. Menstrual profile and early menopause in women with Down syndrome aged 26-40 years. J Intellect Dev Disabil 2006; 31: 166-171
    CrossrefPubMedGoogle Scholar
  • 30 Lucendo AJ, García-Manzanares A. Bone mineral density in adult coeliac disease: an updated review. Rev Esp Enferm Dig 2013; 105: 154-162
    CrossrefPubMedGoogle Scholar
  • 31 Jaffe JS, Timell AM, Elolia R, Thatcher SS. Risk factors for low bone mineral density in individuals residing in a facility for the people with intellectual disability. J Intellect Disabil Res 2005; 49: 457-462
    CrossrefPubMedGoogle Scholar
  • 32 Angelopoulou N, Souftas V, Sakadamis A, Mandroukas K. Bone mineral density in adults with Down’s syndrome. Eur Radiol 1999; 9: 648-651
    CrossrefPubMedGoogle Scholar
  • 33 Van Allen MI, Fung J, Jurenka SB. Health care concerns and guidelines for adults with Down syndrome. Am J Med Genet 1999; 89: 100-110
    CrossrefPubMedGoogle Scholar
  • 34 Matute-Llorente A, González-AgüeroA Gómez-CabelloA Vicente-Rodríguez G, Casajús JA. Decreased levels of physical activity in adolescents with Down syndrome are related with low bone mineral density: a cross-sectional study. BMC Endocr Disord 2013; 13: 22-28
    CrossrefPubMedGoogle Scholar
  • 35 McKelvey KD, Fowler TW, Akel NS, Kelsay JA, Gaddy D, Wenger GR, Suva LJ. Low bone turnover and low bone density in acohort of adults with Down syndrome. Osteoporos Int 2013; 24: 1333-1338
    CrossrefPubMedGoogle Scholar
  • 36 Blazek JD, Gaddy A, Meyer R, Roper RJ, Li J. Disruption of bone development and homeostasis by trisomy in Ts65Dn Down syndrome mice. Bone 2011; 48: 275-280
    CrossrefPubMedGoogle Scholar
  • 37 Kaçmaz M, Atmaca M, Arslan A, Demir H, Özbay MF. Oxidative stress in patients with thyroidectomy and thyroparathyroidectomy under replacement therapy. Endocrine 2015; 48: 227-232
    CrossrefPubMedGoogle Scholar
  • 38 Mancini A, Festa R, Di Donna V, Leone E, Littarru GP, Silvestrini A, Meucci E, Pontecorvi A. Hormones and antioxidant systems: role of pituitary and pituitary-dependent axes. J Endocrinol Invest 2010; 33: 422-433
    CrossrefPubMedGoogle Scholar
  • 39 Mancini A, Raimondo S, Di Segni C. Non-Thyroidal illness: physiopathology and clinical implications. In: Potlukova E. (ed.). Current topics in hypothyroidism with focus on development. Rijeka: InTech; 2013: 183-202
    CrossrefGoogle Scholar
  • 40 Mancini A, Raimondo S, Di Segni C, Persano M, Di Geronimo E, Silvestrini A, Pontecorvi A, Meucci E, Tamburrelli FC. Comparison of plasma antioxidant levels in middle-aged and old male with idiopathic osteoporosis: preliminary data. Eur Rev Med Pharmacol Sci 2013; 18: 2013-2019
    PubMedGoogle Scholar