Skip to main content

Advertisement

SpringerLink
Log in

Biochemical bone turnover markers in hormonal disorders in adults: a narrative review

  • Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background

Hormonal disorders are often associated with abnormal levels of bone turnover markers (BTMs). N-terminal propeptide of type I procollagen (PINP) and serum C-terminal cross-linking telopeptide of type I collagen (CTX-I) are the reference markers of bone formation and bone resorption, respectively.

Methods

A comprehensive literature search within the MEDLINE and Web of Science databases was performed.

Results

Acromegaly is associated with higher BTM levels, which decrease during the remission after treatment. Adult-onset growth hormone deficiency is often associated with decreased BTM levels. Growth hormone replacement therapy stimulates bone turnover and increases BTM levels. Hypothyroidism is characterized by general slowing of bone metabolism which is reflected by lower BTM levels. The replacement thyroid hormone therapy increases the bone turnover rate and BTM levels increase. Patients with thyroid cancer receive a suppressive dose of thyroid hormones and may have slightly elevated BTM levels. Patients with overt hyperthyroidism had higher BTM levels and anti-thyroid therapy induces a rapid decrease in the BTM levels. Patients with overt primary hyperparathyroidism have higher BTM levels, whereas those with asymptomatic and normocalcemic hyperparathyroidism usually have normal BTM levels. Hypoparathyroidism is characterized by slightly decreased BTM levels. Cushing’s syndrome is characterized consistently by markedly decreased osteocalcin concentration, whereas data on other BTMs are discordant.

Conclusions

BTMs help us to better understand mechanisms of the impact of hormonal disorders and their treatment on bone metabolism. However, it is unknown whether BTMs may be used to monitor the effect of their treatments on bone in the clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

(Reproduced from Fairfield et al. [22] with permission from John Wiley and Sons)

Fig. 2

(Reproduced from Ueland et al. [28] with permission from ELSEVIER)

Fig. 3

(Reproduced from Meier et al. [77] with permission from Springer Verlag)

Fig. 4

(Reproduced from Acotto et al. [124] with permission from ELSEVIER)

Fig. 5

(Reproduced from Kaji et al. [157] with permission from Georg Thieme Verlag KG)

Fig. 6

(Reproduced from Rubin et al. [186] with permission from John Wiley & Sons)

Fig. 7

(Reproduced from Francucci et al. [211] with permission from John Wiley and Sons)

Similar content being viewed by others

References

  1. Halse J, Melsen F, Mosekilde L (1981) Iliac crest bone mass and remodelling in acromegaly. Acta Endocrinol (Copenh) 97:18–22

    CAS  Google Scholar 

  2. Dalle Carbonare L, Micheletti V, Cosaro E et al (2018) Bone histomorphometry in acromegaly patients with fragility vertebral fractures. Pituitary 21:56–64. https://doi.org/10.1007/s11102-017-0847-1

    Article  CAS  PubMed  Google Scholar 

  3. Tamada D, Kitamura T, Onodera T et al (2014) Rapid decline in bone turnover markers but not bone mineral density in acromegalic patients after transsphenoidal surgery. Endocr J 61:231–237

    PubMed  Google Scholar 

  4. 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 155:709–715

    CAS  PubMed  Google Scholar 

  5. White HD, Ahmad AM, Durham BH et al (2006) Effect of active acromegaly and its treatment on parathyroid circadian rhythmicity and parathyroid target-organ sensitivity. J Clin Endocrinol Metab 91:913–919

    CAS  PubMed  Google Scholar 

  6. Minisola S, Dionisi S, Pacitti MT et al (2002) Gender differences in serum markers of bone resorption in healthy subjects and patients with disorders affecting bone. Osteoporos Int 13:171–175

    CAS  PubMed  Google Scholar 

  7. Parkinson C, Kassem M, Heickendorff L, Flyvbjerg A, Trainer PJ (2003) Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal. J Clin Endocrinol Metab 88:5650–5655

    CAS  PubMed  Google Scholar 

  8. Constantin T, Tangpricha V, Shah R et al (2017) Calcium and bone turnover markers in acromegaly: a prospective, controlled study. J Clin Endocrinol Metab 102:2416–2424. https://doi.org/10.1210/jc.2016-3693

    Article  PubMed  Google Scholar 

  9. Kaji H, Sugimoto T, Nakaoka D et al (2001) Bone metabolism and body composition in Japanese patients with active acromegaly. Clin Endocrinol (Oxf) 55:175–181

    CAS  Google Scholar 

  10. 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 164:475–483. https://doi.org/10.1530/EJE-10-1005

    Article  CAS  PubMed  Google Scholar 

  11. Mazziotti G, Biagioli E, Maffezzoni F et al (2015) Bone turnover, bone mineral density, and fracture risk in acromegaly: a meta-analysis. J Clin Endocrinol Metab 100:384–394. https://doi.org/10.1210/jc.2014-2937

    Article  CAS  PubMed  Google Scholar 

  12. Godang K, Olarescu NC, Bollerslev J, Heck A (2016) Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study. Eur J Endocrinol 175:155–164. https://doi.org/10.1530/EJE-16-0340

    Article  CAS  PubMed  Google Scholar 

  13. 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 24:72–78

    PubMed  Google Scholar 

  14. Zhang Y, Liu M, Chen H et al (2020) Associations between circulating bone-derived hormones lipocalin 2, osteocalcin, and glucose metabolism in acromegaly. J Endcrinol Investig. https://doi.org/10.1007/s40618-020-01221-9

    Article  Google Scholar 

  15. Ueland T, Bollerslev J, Godang K, Müller F, Frøland SS, Aukrust P (2001) Increased serum osteoprotegerin in disorders characterized by persistent immune activation or glucocorticoid excess—possible role in bone homeostasis. Eur J Endocrinol 145:685–690

    CAS  PubMed  Google Scholar 

  16. Marazuela M, Astigarraga B, Tabuenca MJ, Estrada J, Marín F, Lucas T (1993) Serum bone Gla protein as a marker of bone turnover in acromegaly. Calcif Tissue Int 52:419–421. https://doi.org/10.1007/bf00571329

    Article  CAS  PubMed  Google Scholar 

  17. Piovesan A, Terzolo M, Reimondo G et al (1994) Biochemical markers of bone and collagen turnover in acromegaly or Cushing's syndrome. Horm Metab Res 26:234–237

    CAS  PubMed  Google Scholar 

  18. Kužma M, Vaňuga P, Ságová I et al (2019) Non-invasive DXA-derived bone structure assessment of acromegaly patients: a cross-sectional study. Eur J Endocrinol 180:201–211. https://doi.org/10.1530/EJE-18-0881

    Article  PubMed  Google Scholar 

  19. Ozer FF, Dagdelen S, Erbas T (2018) Relation of RANKL and OPG levels with bone resorption in patients with acromegaly and prolactinoma. Horm Metab Res 50:562–567. https://doi.org/10.1055/a-0630-1529

    Article  CAS  PubMed  Google Scholar 

  20. Kastelan D, Dusek T, Kraljevic I et al (2007) Bone properties in patients with acromegaly: quantitative ultrasound of the heel. J Clin Densitom 10:327–331. https://doi.org/10.1016/j.jocd.2007.03.103

    Article  PubMed  Google Scholar 

  21. Bolanowski M, Jedrzejuk D, Milewicz A, Arkowska A et al (2002) Quantitative ultrasound of the heel and some parameters of bone turnover in patients with acromegaly. Osteoporos Int 13:303–308. https://doi.org/10.1007/s001980200030

    Article  CAS  PubMed  Google Scholar 

  22. Fairfield WP, Sesmilo G, Katznelson L, Pulaski K et al (2002) Effects of a growth hormone receptor antagonist on bone markers in acromegaly. Clin Endocrinol (Oxf) 57:385–390

    CAS  Google Scholar 

  23. Legovini P, De Menis E, Breda F et al (1997) Long-term effects of octreotide on markers of bone metabolism in acromegaly: evidence of increased serum parathormone concentrations. J Endocrinol Investig 20:434–438. https://doi.org/10.1007/BF03347998

    Article  CAS  Google Scholar 

  24. Toogood AA, Adams JE, O'Neill PA, Shalet SM (1997) Elderly patients with adult-onset growth hormone deficiency are not osteopenic. J Clin Endocrinol Metab 82:1462–1466

    CAS  PubMed  Google Scholar 

  25. Rosén T, Wilhelmsen L, Landin-Wilhelmsen K, Lappas G, Bengtsson BA (1997) Increased fracture frequency in adult patients with hypopituitarism and GH deficiency. Eur J Endocrinol 137:240–245

    PubMed  Google Scholar 

  26. Bravenboer N, Holzmann P, de Boer H, Blok GJ, Lips P (1996) Histomorphometric analysis of bone mass and bone metabolism in growth hormone deficient adult men. Bone 18:551–557

    CAS  PubMed  Google Scholar 

  27. Colao A, Di Somma C, Pivonello R et al (1999) Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab 84:1919–1924

    CAS  PubMed  Google Scholar 

  28. Ueland T, Odgren PR, Yndestad A et al (2003) Growth hormone substitution increases gene expression of members of the IGF family in cortical bone from women with adult onset growth hormone deficiency–relationship with bone turn-over. Bone 33:638–645

    CAS  PubMed  Google Scholar 

  29. Janssen YJ, Hamdy NA, Frölich M, Roelfsema F (1998) Skeletal effects of two years of treatment with low physiological doses of recombinant human growth hormone (GH) in patients with adult-onset GH deficiency. J Clin Endocrinol Metab 83:2143–2148

    CAS  PubMed  Google Scholar 

  30. Rota F, Savanelli MC, Tauchmanova L et al (2008) Bone density and turnover in young adult patients with growth hormone deficiency after 2-year growth hormone replacement according with gender. J Endocrinol Investig 31:94–102. https://doi.org/10.1007/BF03345574

    Article  CAS  Google Scholar 

  31. Longobardi S, Di Rella F, Pivonello R et al (1999) Effects of two years of growth hormone (GH) replacement therapy on bone metabolism and mineral density in childhood and adulthood onset GH deficient patients. J Endocrinol Investig 22:333–339. https://doi.org/10.1007/BF03343570

    Article  CAS  Google Scholar 

  32. Bravenboer N, Holzmann P, de Boer H et al (1997) The effect of growth hormone (GH) on histomorphometric indices of bone structure and bone turnover in GH-deficient men. J Clin Endocrinol Metab 82:1818–1822

    CAS  PubMed  Google Scholar 

  33. Brixen K, Hansen TB, Hauge E et al (2000) Growth hormone treatment in adults with adult-onset growth hormone deficiency increases iliac crest trabecular bone turnover: a 1-year, double-blind, randomized, placebo-controlled study. J Bone Miner Res 15:293–300

    CAS  PubMed  Google Scholar 

  34. Johannsson G, Rosén T, Bosaeus I, Sjöström L, Bengtsson BA (1996) Two years of growth hormone (GH) treatment increases bone mineral content and density in hypopituitary patients with adult-onset GH deficiency. J Clin Endocrinol Metab 81:2865–2873

    CAS  PubMed  Google Scholar 

  35. Sartorio A, Ortolani S, Galbiati E et al (2001) Effects of 12-month GH treatment on bone metabolism and bone mineral density in adults with adult-onset GH deficiency. J Endocrinol Investig 24:224–230

    CAS  Google Scholar 

  36. Sneppen SB, Hoeck HC, Kollerup G et al (2002) Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults—an 18-month randomised, placebo-controlled, double blinded trial. Eur J Endocrinol 146:187–195

    CAS  PubMed  Google Scholar 

  37. Ahmad AM, Thomas J, Clewes A et al (2003) Effects of growth hormone replacement on parathyroid hormone sensitivity and bone mineral metabolism. J Clin Endocrinol Metab 88:2860–2868

    CAS  PubMed  Google Scholar 

  38. Hansen TB, Brixen K, Vahl N et al (1996) Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study. J Clin Endocrinol Metab 81:3352–3359

    CAS  PubMed  Google Scholar 

  39. Fernholm R, Bramnert M, Hägg E et al (2000) Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease. J Clin Endocrinol Metab 85:4104–4112

    CAS  PubMed  Google Scholar 

  40. Finkenstedt G, Gasser RW, Höfle G, Watfah C, Fridrich L (1997) Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up. Eur J Endocrinol 136:282–289

    CAS  PubMed  Google Scholar 

  41. Välimäki MJ, Salmela PI, Salmi J et al (1999) Effects of 42 months of GH treatment on bone mineral density and bone turnover in GH-deficient adults. Eur J Endocrinol 140:545–554

    PubMed  Google Scholar 

  42. Kužma M, Kužmová Z, Zelinková Z et al (2014) Impact of the growth hormone replacement on bone status in growth hormone deficient adults. Growth Horm IGF Res 24:22–28. https://doi.org/10.1016/j.ghir.2013.12.001

    Article  CAS  PubMed  Google Scholar 

  43. Holmes SJ, Whitehouse RW, Swindell R et al (1995) Effect of growth hormone replacement on bone mass in adults with adult onset growth hormone deficiency. Clin Endocrinol (Oxf) 42:627–633

    CAS  Google Scholar 

  44. Kotzmann H, Riedl M, Bernecker P et al (1998) Effect of long-term growth-hormone substitution therapy on bone mineral density and parameters of bone metabolism in adult patients with growth hormone deficiency. Calcif Tissue Int 62:40–46

    CAS  PubMed  Google Scholar 

  45. Lanzi R, Losa M, Villa I et al (2003) GH replacement therapy increases plasma osteoprotegerin levels in GH-deficient adults. Eur J Endocrinol 148:185–191. https://doi.org/10.1530/eje.0.1480185

    Article  CAS  PubMed  Google Scholar 

  46. Bex M, Abs R, Maiter D, Beckers A, Lamberigts G, Bouillon R (2002) The effects of growth hormone replacement therapy on bone metabolism in adult-onset growth hormone deficiency: a 2-year open randomized controlled multicenter trial. J Bone Miner Res 17:1081–1094. https://doi.org/10.1359/jbmr.2002.17.6.1081

    Article  CAS  PubMed  Google Scholar 

  47. Bravenboer N, Holzmann PJ, ter Maaten JC et al (2005) Effect of long-term growth hormone treatment on bone mass and bone metabolism in growth hormone-deficient men. J Bone Miner Res 20:1778–1784

    CAS  PubMed  Google Scholar 

  48. Arwert LI, Roos JC, Lips P, Twisk JW, Manoliu RA, Drent ML (2005) Effects of 10 years of growth hormone (GH) replacement therapy in adult GH-deficient men. Clin Endocrinol (Oxf) 63:310–316

    CAS  Google Scholar 

  49. Appelman-Dijkstra NM, Claessen KM, Hamdy NA, Pereira AM, Biermasz NR (2014) Effects of up to 15 years of recombinant human GH (rhGH) replacement on bone metabolism in adults with growth hormone deficiency (GHD): the Leiden Cohort Study. Clin Endocrinol (Oxf) 81:727–735. https://doi.org/10.1111/cen.12493

    Article  CAS  Google Scholar 

  50. Appelman-Dijkstra NM, Rijndorp M et al (2016) Effects of discontinuation of growth hormone replacement in adult GH-deficient patients: a cohort study and a systematic review of the literature. Eur J Endocrinol 174:705–716. https://doi.org/10.1530/EJE-15-1086

    Article  CAS  PubMed  Google Scholar 

  51. White HD, Ahmad AM, Durham BH et al (2005) Growth hormone replacement is important for the restoration of parathyroid hormone sensitivity and improvement in bone metabolism in older adult growth hormone-deficient patients. J Clin Endocrinol Metab 90:3371–3380

    CAS  PubMed  Google Scholar 

  52. Abrahamsen B, Hangaard J, Horn HC et al (2002) Evaluation of the optimum dose of growth hormone (GH) for restoring bone mass in adult-onset GH deficiency: results from two 12-month randomized studies. Clin Endocrinol (Oxf) 57:273–281

    CAS  Google Scholar 

  53. Bassett JH, Williams GR (2016) Role of thyroid hormones in skeletal development and bone maintenance. Endocr Rev 37:135–187. https://doi.org/10.1210/er.2015-1106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Eriksen EF, Mosekilde L, Melsen F (1986) Kinetics of trabecular bone resorption and formation in hypothyroidism: evidence for a positive balance per remodeling cycle. Bone 7:101–108

    CAS  PubMed  Google Scholar 

  55. Osterode W, Zettinig G, Pötzi C, Männer G (2002) Increased lead excretion in hypothyroid patients after levothyroxine medication. J Toxicol Environ Health A 65:649–654

    CAS  PubMed  Google Scholar 

  56. Persani L, Preziati D, Matthews CH, Sartorio A, Chatterjee VK, Beck-Peccoz P (1997) Serum levels of carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in the differential diagnosis of the syndromes of inappropriate secretion of TSH. Clin Endocrinol (Oxf) 47:207–214

    CAS  Google Scholar 

  57. Sabuncu T, Aksoy N, Arikan E, Ugur B, Tasan E, Hatemi H (2001) Early changes in parameters of bone and mineral metabolism during therapy for hyper- and hypothyroidism. Endocr Res 27:203–213

    CAS  PubMed  Google Scholar 

  58. Sekeroglu MR, Altun ZB, Algün E (2006) Serum cytokines and bone metabolism in patients with thyroid dysfunction. Adv Ther 23:475–480

    CAS  PubMed  Google Scholar 

  59. Lakatos P, Foldes J, Horvath C et al (1997) Serum interleukin-6 and bone metabolism in patients with thyroid function disorders. J Clin Endocrinol Metab 82:78–81

    CAS  PubMed  Google Scholar 

  60. Christy AL, D'Souza V, Babu RP et al (2014) Utility of C-terminal telopeptide in evaluating levothyroxine replacement therapy-induced bone loss. Biomark Insights 9:1–6. https://doi.org/10.4137/BMI.S13965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Miyakawa M, Tsushima T, Demura H (1996) Carboxy-terminal propeptide of type 1 procollagen (P1CP) and carboxy-terminal telopeptide of type 1 collagen (1CTP) as sensitive markers of bone metabolism in thyroid disease. Endocr J 43:701–708

    CAS  PubMed  Google Scholar 

  62. Mosekilde L, Melsen F (1978) Morphometric and dynamic studies of bone changes in hypothyroidism. Acta Pathol Microbiol Scand A 86:56–62

    CAS  PubMed  Google Scholar 

  63. Kojima N, Sakata S, Nakamura S et al (1992) Serum concentrations of osteocalcin in patients with hyperthyroidism, hypothyroidism and subacute thyroiditis. J Endocrinol Investig 15:491–496

    CAS  Google Scholar 

  64. Yoneda M, Takatsuki K, Yamauchi K et al (1988) Influence of thyroid function on serum bone Gla protein. Endocrinol Jpn 35:121–129

    CAS  PubMed  Google Scholar 

  65. Bergmann P, Dediste A, Demeester-Mirkine N, Deconinck I, Corvilain J (1989) Serum bone Gla protein (BGP) in primary hypothyroidism before and during treatment with thyroid hormones. Horm Metab Res 21:47–48

    CAS  PubMed  Google Scholar 

  66. Martinez ME, Herranz L, de Pedro C, Pallardo LF (1986) Osteocalcin levels in patients with hyper- and hypothyroidism. Horm Metab Res 18:212–214

    CAS  PubMed  Google Scholar 

  67. Boruah P, Baruah AJ, Hajong R et al (2016) A study to assess the validity of estimation of serum ostase level in hyperthyroid and hypothyroid cases. J Clin Diagn Res 10:BC08–BC11

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Kisakol G, Kaya A, Gonen S, Tunc R (2003) Bone and calcium metabolism in subclinical autoimmune hyperthyroidism and hypothyroidism. Endocr J 50:657–661

    CAS  PubMed  Google Scholar 

  69. Siru R, Alfonso H, Chubb SAP, Golledge J, Flicker L, Yeap BB (2018) Subclinical thyroid dysfunction and circulating thyroid hormones are not associated with bone turnover markers or incident hip fracture in older men. Clin Endocrinol (Oxf) 89:93–99. https://doi.org/10.1111/cen.13615

    Article  CAS  Google Scholar 

  70. Lee WY, Oh KW, Rhee EJ et al (2006) Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women. Arch Med Res 37:511–516. https://doi.org/10.1016/j.arcmed.2005.09.009

    Article  CAS  PubMed  Google Scholar 

  71. Coindre JM, David JP, Rivière L et al (1986) Bone loss in hypothyroidism with hormone replacement. A histomorphometric study. Arch Intern Med 146:48–53

    CAS  PubMed  Google Scholar 

  72. Langdahl BL, Loft AG, Eriksen EF, Mosekilde L, Charles P (1996) Bone mass, bone turnover and body composition in former hypothyroid patients receiving replacement therapy. Eur J Endocrinol 134:702–709. https://doi.org/10.1530/eje.0.1340702

    Article  CAS  PubMed  Google Scholar 

  73. Harvey RD, McHardy KC, Reid IW et al (1991) Measurement of bone collagen degradation in hyperthyroidism and during thyroxine replacement therapy using pyridinium cross-links as specific urinary markers. J Clin Endocrinol Metab 72:1189–1194

    CAS  PubMed  Google Scholar 

  74. Affinito P, Sorrentino C, Farace MJ et al (1996) Effects of thyroxine therapy on bone metabolism in postmenopausal women with hypothyroidism. Acta Obstet Gynecol Scand 75:843–848

    CAS  PubMed  Google Scholar 

  75. Guo CY, Weetman AP, Eastell R (1997) Longitudinal changes of bone mineral density and bone turnover in postmenopausal women on thyroxine. Clin Endocrinol (Oxf) 46:301–307

    CAS  Google Scholar 

  76. Gonzalez Rodriguez E, Stuber M, Del Giovane C et al (2020) Skeletal effects of levothyroxine for subclinical hypothyroidism in older adults: a TRUST randomized trial nested study. J Clin Endocrinol Metab 105:336–343. https://doi.org/10.1210/clinem/dgz058

    Article  Google Scholar 

  77. Meier C, Beat M, Guglielmetti M, Christ-Crain M, Staub JJ, Kraenzlin M (2004) Restoration of euthyroidism accelerates bone turnover in patients with subclinical hypothyroidism: a randomized controlled trial. Osteoporos Int 15:209–216

    PubMed  Google Scholar 

  78. Toivonen J, Tähtelä R, Laitinen K, Risteli J, Välimäki MJ (1998) Markers of bone turnover in patients with differentiated thyroid cancer with and following withdrawal of thyroxine suppressive therapy. Eur J Endocrinol 138:667–673

    CAS  PubMed  Google Scholar 

  79. Schneider R, Schneider M, Reiners C, Schneider P (2012) Effects of levothyroxine on bone mineral density, muscle force, and bone turnover markers: a cohort study. J Clin Endocrinol Metab 97:3926–3934. https://doi.org/10.1210/jc.2012-2570

    Article  CAS  PubMed  Google Scholar 

  80. Loviselli A, Mastinu R, Rizzolo E et al (1997) Circulating telopeptide type I is a peripheral marker of thyroid hormone action in hyperthyroidism and during levothyroxine suppressive therapy. Thyroid 7:561–566. https://doi.org/10.1089/thy.1997.7.561

    Article  CAS  PubMed  Google Scholar 

  81. Karner I, Hrgovic Z, Sijanovic S et al (2005) Bone mineral density changes and bone turnover in thyroid carcinoma patients treated with supraphysiologic doses of thyroxine. Eur J Med Res 10:480–488

    CAS  PubMed  Google Scholar 

  82. Tournis S, Antoniou JD, Liakou CG et al (2015) Volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in women with differentiated thyroid cancer under TSH suppression. Clin Endocrinol (Oxf) 82:197–204. https://doi.org/10.1111/cen.12560

    Article  Google Scholar 

  83. Marcocci C, Golia F, Vignali E, Pinchera A (1997) Skeletal integrity in men chronically treated with suppressive doses of L-thyroxine. J Bone Miner Res 12:72–77. https://doi.org/10.1359/jbmr.1997.12.1.72

    Article  CAS  PubMed  Google Scholar 

  84. Heijckmann AC, Huijberts MS, Geusens P, de Vries J, Menheere PP, Wolffenbuttel BH (2005) Hip bone mineral density, bone turnover and risk of fracture in patients on long-term suppressive L-thyroxine therapy for differentiated thyroid carcinoma. Eur J Endocrinol 153:23–29. https://doi.org/10.1530/eje.1.01933

    Article  CAS  PubMed  Google Scholar 

  85. Ito M, Miyauchi A, Hisakado M et al (2017) (2017) Biochemical markers reflecting thyroid function in athyreotic patients on levothyroxine monotherapy. Thyroid 27:484–490. https://doi.org/10.1089/thy.2016.0426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Reverter JL, Colomé E, Holgado S et al (2010) Bone mineral density and bone fracture in male patients receiving long-term suppressive levothyroxine treatment for differentiated thyroid carcinoma. Endocrine 37:467–472. https://doi.org/10.1007/s12020-010-9339-z

    Article  CAS  PubMed  Google Scholar 

  87. Botella-Carretero JI, Alvarez-Blasco F, San Millán JL, Escobar-Morreale HF (2007) Thyroid hormone deficiency and postmenopausal status independently increase serum osteoprotegerin concentrations in women. Eur J Endocrinol 156:539–545

    CAS  PubMed  Google Scholar 

  88. Regalbuto C, Maiorana R, Alagona C et al (2007) Effects of either LT4 monotherapy or LT4/LT3 combined therapy in patients totally thyroidectomized for thyroid cancer. Thyroid 17:323–331. https://doi.org/10.1089/thy.2006.0084

    Article  CAS  PubMed  Google Scholar 

  89. Marcocci C, Golia F, Bruno-Bossio G, Vignali E, Pinchera A (1994) Carefully monitored levothyroxine suppressive therapy is not associated with bone loss in premenopausal women. J Clin Endocrinol Metab 78:818–823. https://doi.org/10.1210/jc.78.4.818

    Article  CAS  PubMed  Google Scholar 

  90. Mikosch P, Obermayer-Pietsch B, Jost R et al (2003) Bone metabolism in patients with differentiated thyroid carcinoma receiving suppressive levothyroxine treatment. Thyroid 13:347–356

    CAS  PubMed  Google Scholar 

  91. Kim CW, Hong S, Oh SH et al (2015) Change of bone mineral density and biochemical markers of bone turnover in patients on suppressive levothyroxine therapy for differentiated thyroid carcinoma. J Bone Metab 22:135–141. https://doi.org/10.11005/jbm.2015.22.3.135

    Article  PubMed  PubMed Central  Google Scholar 

  92. Iglesias SG, Dominguez MLM, Herrero EF et al (2019) Trabecular bone score and bone mineral density in patients with postsurgical hypoparathyroidism after total thyroidectomy for differentiated thyroid carcinoma. Surgery 165:814–819. https://doi.org/10.1016/j.surg.2018.10.034

    Article  PubMed  Google Scholar 

  93. Regalbuto C, Alagona C, Maiorana R et al (2006) Acute changes in clinical parameters and thyroid function peripheral markers following L-T4 withdrawal in patients totally thyroidectomized for thyroid cancer. J Endocrinol Investig 29:32–40

    CAS  Google Scholar 

  94. Eriksen EF (1986) Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease. Endocr Rev 7:379–408

    CAS  PubMed  Google Scholar 

  95. Eriksen EF, Mosekilde L, Melsen F (1985) Trabecular bone remodeling and bone balance in hyperthyroidism. Bone 6:421–428

    CAS  PubMed  Google Scholar 

  96. Amato G, Mazziotti G, Sorvillo F et al (2004) High serum osteoprotegerin levels in patients with hyperthyroidism: effect of medical treatment. Bone 35:785–791

    CAS  PubMed  Google Scholar 

  97. Akalin A, Colak O, Alatas O, Efe B (2002) Bone remodelling markers and serum cytokines in patients with hyperthyroidism. Clin Endocrinol (Oxf) 57:125–129

    CAS  Google Scholar 

  98. Akçay MN, Akçay G, BIlen H (2004) The effects of calcitonin on bone resorption in hyperthyroidism: a placebo-controlled clinical study. J Bone Miner Metab 22:90–93. https://doi.org/10.1007/s00774-003-0455-1

    Article  CAS  PubMed  Google Scholar 

  99. Al-Shoumer KA, Vasanthy BA, Al-Zaid MM (2006) Effects of treatment of hyperthyroidism on glucose homeostasis, insulin secretion, and markers of bone turnover. Endocr Pract 12:121–130

    PubMed  Google Scholar 

  100. Arbault P, Grimaux M, Pradet V, Preaudat C, Seguin P, Delmas PD (1995) Assessment of urinary pyridinoline excretion with a specific enzyme-linked immunosorbent assay in normal adults and in metabolic bone diseases. Bone 16:461–467

    CAS  PubMed  Google Scholar 

  101. Mhaibes SH, Ameen IA, Saleh ES, Taha KN, Kamil HS (2019) Impact of hyperthyroidism on biochemical markers of bone metabolism. J Clin Diagn Res 13:BC11–BC14. https://doi.org/10.7860/JCDR/2019/41445.13011

    Article  CAS  Google Scholar 

  102. De Menis E, Da Rin G, Roiter I, Legovini P, Foscolo G, Conte N (1992) Bone turnover in overt and subclinical hyperthyroidism due to autonomous thyroid adenoma. Horm Res 37:217–220

    PubMed  Google Scholar 

  103. El Hadidy HM, Ghonaim M, El Gawad SSh, El Atta MA (2011) Impact of severity, duration, and etiology of hyperthyroidism on bone turnover markers and bone mineral density in men. BMC Endocr Disord 11:15. https://doi.org/10.1186/1472-6823-11-15

    Article  CAS  PubMed Central  Google Scholar 

  104. Engler H, Oettli RE, Riesen WF (1999) Biochemical markers of bone turnover in patients with thyroid dysfunctions and in euthyroid controls: a cross-sectional study. Clin Chim Acta 289:159–172

    CAS  PubMed  Google Scholar 

  105. Garnero P, Vassy V, Bertholin A, Riou JP, Delmas PD (1994) Markers of bone turnover in hyperthyroidism and the effects of treatment. J Clin Endocrinol Metab 78:955–959

    CAS  PubMed  Google Scholar 

  106. Isaia GC, Roggia C, Gola D et al (2000) Bone turnover in hyperthyroidism before and after thyrostatic management. J Endocrinol Investig 23:727–731

    CAS  Google Scholar 

  107. Legovini P, De Menis E, Da Rin G et al (1994) Increased serum levels of carboxyterminal propeptide of type 1 collagen (PICP) in hyperthyroidism. Horm Metab Res 26:334–337. https://doi.org/10.1055/s-2007-1001698

    Article  CAS  PubMed  Google Scholar 

  108. Lee MS, Kim SY, Lee MC et al (1990) Negative correlation between the change in bone mineral density and serum osteocalcin in patients with hyperthyroidism. J Clin Endocrinol Metab 70:766–770

    CAS  PubMed  Google Scholar 

  109. Nagasaka S, Sugimoto H, Nakamura T et al (1997) Antithyroid therapy improves bony manifestations and bone metabolic markers in patients with Graves' thyrotoxicosis. Clin Endocrinol (Oxf) 47:215–221

    CAS  Google Scholar 

  110. Ohishi T, Kushida K, Takahashi M et al (1994) Urinary bone resorption markers in patients with metabolic bone disorders. Bone 15:15–20

    CAS  PubMed  Google Scholar 

  111. Psaltopoulou T, Ilias I, Toumanidis S et al (2007) Endogenous subclinical hyperthyroidism: metabolic and cardiac parameters. Eur J Intern Med 18:423–429. https://doi.org/10.1016/j.ejim.2006.12.010

    Article  CAS  PubMed  Google Scholar 

  112. Siddiqi A, Burrin JM, Noonan K et al (1997) A longitudinal study of markers of bone turnover in Graves' disease and their value in predicting bone mineral density. J Clin Endocrinol Metab 82:753–759

    CAS  PubMed  Google Scholar 

  113. Jódar E, Muñoz-Torres M, Escobar-Jiménez F et al (1997) Antiresorptive therapy in hyperthyroid patients: longitudinal changes in bone and mineral metabolism. J Clin Endocrinol Metab 82:1989–1994

    PubMed  Google Scholar 

  114. Wenisch C, Bankl HC, Schönthal E et al (1995) Serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen and laminin are elevated in Graves' disease but not in toxic nodular goiter. Clin Immunol Immunopathol 75:225–230

    CAS  PubMed  Google Scholar 

  115. Rosario PW (2008) Bone and heart abnormalities of subclinical hyperthyroidism in women below the age of 65 years. Arq Bras Endocrinol Metabol 52:1448–1451

    PubMed  Google Scholar 

  116. Tauchmanovà L, Nuzzo V, Del Puente A et al (2004) Reduced bone mass detected by bone quantitative ultrasonometry and DEXA in pre- and postmenopausal women with endogenous subclinical hyperthyroidism. Maturitas 48:299–306

    PubMed  Google Scholar 

  117. Ahn KH, Lee SH, Park HT et al (2010) Effect of adiponectin and sex steroid hormones on bone mineral density and bone formation markers in postmenopausal women with subclinical hyperthyroidism. J Obstet Gynaecol Res 36:370–376. https://doi.org/10.1111/j.1447-0756.2009.01132.x

    Article  PubMed  Google Scholar 

  118. Rosario PW, Carvalho M, Calsolari MR (2016) Symptoms of thyrotoxicosis, bone metabolism and occult atrial fibrillation in older women with mild endogenous subclinical hyperthyroidism. Clin Endocrinol (Oxf) 85:132–136. https://doi.org/10.1111/cen.12979

    Article  Google Scholar 

  119. Gürlek A, Gedik O (1999) Effect of endogenous subclinical hyperthyroidism on bone metabolism and bone mineral density in premenopausal women. Thyroid 9:539–543. https://doi.org/10.1089/thy.1999.9.539

    Article  PubMed  Google Scholar 

  120. Barsal G, Taneli F, Atay A, Hekimsoy Z, Erciyas F (2004) Serum osteocalcin levels in hyperthyroidism before and after antithyroid therapy. Tohoku J Exp Med 203:183–188

    CAS  PubMed  Google Scholar 

  121. Kumeda Y, Inaba M, Tahara H et al (2000) Persistent increase in bone turnover in Graves' patients with subclinical hyperthyroidism. J Clin Endocrinol Metab 85:4157–4161

    CAS  PubMed  Google Scholar 

  122. Olkawa M, Kushida K, Takahashi M et al (1999) Bone turnover and cortical bone mineral density in the distal radius in patients with hyperthyroidism being treated with antithyroid drugs for various periods of time. Clin Endocrinol (Oxf) 50:171–176

    CAS  Google Scholar 

  123. van de Ven AC, Erdtsieck RJ (2008) Changes of bone mineral density, quantitative ultrasound parameters and markers of bone turnover during treatment of hyperthyroidism. Neth J Med 66:428–432

    PubMed  Google Scholar 

  124. Acotto CG, Niepomniszcze H, Vega E, Mautalen CA (2004) Ultrasound parameters and markers of bone turnover in hyperthyroidism: a longitudinal study. J Clin Densitom 7:201–208

    PubMed  Google Scholar 

  125. Pantazi H, Papapetrou PD (2000) Changes in parameters of bone and mineral metabolism during therapy for hyperthyroidism. J Clin Endocrinol Metab 85:1099–1106

    CAS  PubMed  Google Scholar 

  126. Wilkinson H, Horsely E (1996) Changes in markers of bone collagen turnover in toxic and euthyroid states: a study of 22 patients. Ann Clin Biochem 33:454–455

    PubMed  Google Scholar 

  127. Schouten BJ, Prickett TC, Hunt PJ et al (2012) C-type natriuretic peptide forms in adult hyperthyroidism: correlation with thyroid hormones and markers of bone turnover. Clin Endocrinol (Oxf) 76:790–796. https://doi.org/10.1111/j.1365-2265.2011.04295.x

    Article  CAS  Google Scholar 

  128. Grieff M (2003) The hungry bone syndrome after medical treatment of thyrotoxicosis. Ann Intern Med 139:706–707

    PubMed  Google Scholar 

  129. Brockstedt H, Christiansen P, Mosekilde L, Melsen F (1995) Reconstruction of cortical bone remodeling in untreated primary hyperparathyroidism and following surgery. Bone 16:109–117

    CAS  PubMed  Google Scholar 

  130. Christiansen P, Steiniche T, Vesterby A, Mosekilde L, Hessov I, Melsen F (1992) Primary hyperparathyroidism: iliac crest trabecular bone volume, structure, remodeling, and balance evaluated by histomorphometric methods. Bone 13:41–49

    CAS  PubMed  Google Scholar 

  131. Eriksen EF, Mosekilde L, Melsen F (1986) Trabecular bone remodeling and balance in primary hyperparathyroidism. Bone 7:213–221

    CAS  PubMed  Google Scholar 

  132. Delmas PD, Demiaux B, Malaval L, Chapuy MC, Edouard C, Meunier PJ (1986) Serum bone gamma carboxyglutamic acid-containing protein in primary hyperparathyroidism and in malignant hypercalcemia. Comparison with bone histomorphometry. J Clin Investig 77:985–991

    CAS  PubMed  Google Scholar 

  133. van Doorn L, Lips P, Netelenbos JC, Hackeng WH (1993) Bone histomorphometry and serum concentrations of intact parathyroid hormone (PTH(1–84)) in patients with primary hyperparathyroidism. Bone Miner 23:233–242

    PubMed  Google Scholar 

  134. Christiansen P, Steiniche T, Brockstedt H, Mosekilde L, Hessov I, Melsen F (1993) Primary hyperparathyroidism: iliac crest cortical thickness, structure, and remodeling evaluated by histomorphometric methods. Bone 14:755–762

    CAS  PubMed  Google Scholar 

  135. Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ (2007) Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype. J Clin Endocrinol Metab 92:3001–3005

    CAS  PubMed  Google Scholar 

  136. Maruani G, Hertig A, Paillard M, Houillier P (2003) Normocalcemic primary hyperparathyroidism: evidence for a generalized target-tissue resistance to parathyroid hormone. J Clin Endocrinol Metab 88:4641–4648

    CAS  PubMed  Google Scholar 

  137. Bergenfelz A, Lindblom P, Lindergård B, Valdemarsson S, Westerdahl J (2003) Preoperative normal level of parathyroid hormone signifies an early and mild form of primary hyperparathyroidism. World J Surg 27:481–485

    PubMed  Google Scholar 

  138. Gómez-Ramírez J, Gómez-Valdazo A, Luengo P, Porrero B, Osorio I, Rivas S (2020) Comparative prospective study on the presentation of normocalcemic primary hyperparathyroidism. Is it more aggressive than the hypercalcemic form? Am J Surg 219:150–153. https://doi.org/10.1016/j.amjsurg.2019.10.032

    Article  PubMed  Google Scholar 

  139. Palermo A, Naciu AM, Tabacco G et al (2020) Clinical, biochemical and radiological profile of normocalcemic primary hyperparathyroidism. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgaa174

    Article  PubMed  PubMed Central  Google Scholar 

  140. Aresta C, Passeri E, Corbetta S (2019) Symptomatic hypercalcemia in patients with primary hyperparathyroidism is associated with severity of disease, polypharmacy, and comorbidity. Int J Endocrinol 2019:7617254. https://doi.org/10.1155/2019/7617254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Rubin MR, Lee KH, McMahon DJ, Silverberg SJ (2003) Raloxifene lowers serum calcium and markers of bone turnover in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab 88:1174–1178

    CAS  PubMed  Google Scholar 

  142. Silverberg SJ, Gartenberg F, Jacobs TP et al (1995) Longitudinal measurements of bone density and biochemical indices in untreated primary hyperparathyroidism. J Clin Endocrinol Metab 80:723–728

    CAS  PubMed  Google Scholar 

  143. Bandeira F, Griz LH, Bandeira C et al (2009) Prevalence of cortical osteoporosis in mild and severe primary hyperparathyroidism and its relationship with bone markers and vitamin D status. J Clin Densitom 12:195–199. https://doi.org/10.1016/j.jocd.2008.11.005

    Article  PubMed  Google Scholar 

  144. Adami S, Braga V, Squaranti R, Rossini M, Gatti D, Zamberlan N (1998) Bone measurements in asymptomatic primary hyperparathyroidism. Bone 22:565–570

    CAS  PubMed  Google Scholar 

  145. Palermo A, Jacques R, Gossiel F et al (2015) Normocalcaemic hypoparathyroidism: prevalence and effect on bone status in older women. The OPUS study. Clin Endocrinol (Oxf) 82:816–823. https://doi.org/10.1111/cen.12732

    Article  CAS  Google Scholar 

  146. Lundstam K, Heck A, Godang K et al (2017) Effect of surgery versus observation: skeletal 5-year outcomes in a randomized trial of patients with primary HPT (the SIPH study). J Bone Miner Res 32:1907–1914. https://doi.org/10.1002/jbmr.3177

    Article  PubMed  Google Scholar 

  147. Garnero P, Gineyts E, Riou JP, Delmas PD (1994) Assessment of bone resorption with a new marker of collagen degradation in patients with metabolic bone disease. J Clin Endocrinol Metab 79:780–785

    CAS  PubMed  Google Scholar 

  148. Minisola S, Pacitti MT, Rosso R et al (1997) The measurement of urinary amino-terminal telopeptides of type I collagen to monitor bone resorption in patients with primary hyperparathyroidism. J Endocrinol Investig 20:559–565

    CAS  Google Scholar 

  149. De la Piedra C, Díaz Martín MA, Díaz Diego EM et al (1994) Serum concentrations of carboxyterminal cross-linked telopeptide of type I collagen (ICTP), serum tartrate resistant acid phosphatase, and serum levels of intact parathyroid hormone in parathyroid hyperfunction. Scand J Clin Lab Investig 54:11–15

    Google Scholar 

  150. Miguel GA, Carranza FH, Rodríguez JCR et al (2019) Trabecular bone score, bone mineral density and bone markers in patients with primary hyperparathyroidism 2 years after parathyroidectomy. Horm Metab Res 51:186–190. https://doi.org/10.1055/a-0850-8679

    Article  CAS  PubMed  Google Scholar 

  151. Rajeev P, Movseysan A, Baharani A (2017) Changes in bone turnover markers in primary hyperparathyroidism and response to surgery. Ann R Coll Surg Engl 99:559–562. https://doi.org/10.1308/rcsann.2017.0092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Guo CY, Holland PA, Jackson BF et al (2000) Immediate changes in biochemical markers of bone turnover and circulating interleukin-6 after parathyroidectomy for primary hyperparathyroidism. Eur J Endocrinol 142:451–459

    CAS  PubMed  Google Scholar 

  153. Guo CY, Thomas WE, al-Dehaimi AW, Assiri AM, Eastell R (1996) Longitudinal changes in bone mineral density and bone turnover in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab 81:3487–3491

    CAS  PubMed  Google Scholar 

  154. Minisola S, Pacitti MT, Romagnoli E et al (1999) Clinical validation of a new immunoradiometric assay for intact human osteocalcin. Calcif Tissue Int 64:365–369

    CAS  PubMed  Google Scholar 

  155. Alonso S, Ferrero E, Donat M et al (2012) The usefulness of high pre-operative levels of serum type I collagen bone markers for the prediction of changes in bone mineral density after parathyroidectomy. J Endocrinol Investig 35:640–644. https://doi.org/10.3275/7923

    Article  CAS  Google Scholar 

  156. Duda RJ Jr, O'Brien JF, Katzmann JA, Peterson JM, Mann KG, Riggs BL (1988) Concurrent assays of circulating bone Gla-protein and bone alkaline phosphatase: effects of sex, age, and metabolic bone disease. J Clin Endocrinol Metab 66:951–957

    CAS  PubMed  Google Scholar 

  157. Kaji H, Nomura R, Yamauchi M, Chihara K, Sugimoto T (2006) The usefulness of bone metabolic indices for the prediction of changes in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism. Horm Metab Res 38:411–416

    CAS  PubMed  Google Scholar 

  158. Woitge HW, Pecherstorfer M, Li Y et al (1999) Novel serum markers of bone resorption: clinical assessment and comparison with established urinary indices. J Bone Miner Res 14:792–801

    CAS  PubMed  Google Scholar 

  159. Scarnecchia L, Minisola S, Pacitti MT et al (1991) Clinical usefulness of serum tartrate-resistant acid phosphatase activity determination to evaluate bone turnover. Scand J Clin Lab Investig 51:517–524

    CAS  Google Scholar 

  160. Yoneda M, Takatsuki K, Yamauchi K et al (1988) Effect of parathyroid function on serum bone Gla protein. Endocrinol Jpn 35:39–45

    CAS  PubMed  Google Scholar 

  161. Christiansen P, Steiniche T, Brixen K et al (1997) Primary hyperparathyroidism: biochemical markers and bone mineral density at multiple skeletal sites in Danish patients. Bone 21:93–99

    CAS  PubMed  Google Scholar 

  162. Faggiano A, Di Somma C, Ramundo V et al (2011) Cinacalcet hydrochloride in combination with alendronate normalizes hypercalcemia and improves bone mineral density in patients with primary hyperparathyroidism. Endocrine 39:283–287. https://doi.org/10.1007/s12020-011-9459-0

    Article  CAS  PubMed  Google Scholar 

  163. Uebelhart D, Gineyts E, Chapuy MC, Delmas PD (1990) Urinary excretion of pyridinium crosslinks: a new marker of bone resorption in metabolic bone disease. Bone Miner 8:87–96

    CAS  PubMed  Google Scholar 

  164. Christiansen P, Steiniche T, Mosekilde L, Hessov I, Melsen F (1990) Primary hyperparathyroidism: changes in trabecular bone remodeling following surgical treatment-evaluated by histomorphometric methods. Bone 11:75–79

    CAS  PubMed  Google Scholar 

  165. Steiniche T, Christiansen P, Vesterby A et al (2000) Primary hyperparathyroidism: bone structure, balance, and remodeling before and 3 years after surgical treatment. Bone 26:535–543

    CAS  PubMed  Google Scholar 

  166. Tanaka Y, Funahashi H, Imai T, Tominaga Y, Takagi H (1997) Parathyroid function and bone metabolic markers in primary and secondary hyperparathyroidism. Semin Surg Oncol 13:125–133

    CAS  PubMed  Google Scholar 

  167. Abe Y, Ejima E, Fujiyama K et al (2000) Parathyroidectomy for primary hyperparathyroidism induces positive uncoupling and increases bone mineral density in cancellous bones. Clin Endocrinol (Oxf) 52:203–209

    CAS  Google Scholar 

  168. Carnevale V, Pacitti MT, Pileri M et al (2001) Short-term effects of surgery in post-menopausal patients with primary hyperparathyroidism and normal bone turnover. J Endocrinol Investig 24:575–579

    CAS  Google Scholar 

  169. Christiansen P, Steiniche T, Brixen K et al (1999) Primary hyperparathyroidism: short-term changes in bone remodeling and bone mineral density following parathyroidectomy. Bone 25:237–244

    CAS  PubMed  Google Scholar 

  170. Valdemarsson S, Lindergård B, Tibblin S, Bergenfelz A (1998) Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease. J Intern Med 243:115–122

    CAS  PubMed  Google Scholar 

  171. Tamura Y, Araki A, Chiba Y, Mori S, Hosoi T, Horiuchi T (2007) Remarkable increase in lumbar spine bone mineral density and amelioration in biochemical markers of bone turnover after parathyroidectomy in elderly patients with primary hyperparathyroidism: a 5-year follow-up study. J Bone Miner Metab 25:226–231. https://doi.org/10.1007/s00774-007-0754-z

    Article  PubMed  Google Scholar 

  172. Almqvist EG, Becker C, Bondeson AG, Bondeson L, Svensson J (2004) Early parathyroidectomy increases bone mineral density in patients with mild primary hyperparathyroidism: a prospective and randomized study. Surgery 136:1281–1288. https://doi.org/10.1016/j.surg.2004.06.059

    Article  PubMed  Google Scholar 

  173. Stilgren LS, Hegedüs LM, Beck-Nielsen H, Abrahamsen B (2003) Osteoprotegerin levels in primary hyperparathyroidism: effect of parathyroidectomy and association with bone metabolism. Calcif Tissue Int 73:210–216. https://doi.org/10.1007/s00223-002-2100-8

    Article  CAS  PubMed  Google Scholar 

  174. Garton M, Martin J, Stewart A et al (1995) Changes in bone mass and metabolism after surgery for primary hyperparathyroidism. Clin Endocrinol (Oxf) 42:493–500

    CAS  Google Scholar 

  175. Ohe MN, Bonanséa TCP, Santos RO et al (2019) Prediction of bone mass changes after successful parathyroidectomy using biochemical markers of bone metabolism in primary hyperparathyroidism: is it clinically useful? Arch Endocrinol Metab 63:394–401. https://doi.org/10.20945/2359-3997000000154

    Article  PubMed  Google Scholar 

  176. Chow CC, Chan WB, Li JK et al (2003) Oral alendronate increases bone mineral density in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab 88:581–587

    CAS  PubMed  Google Scholar 

  177. Orr-Walker BJ, Evans MC, Clearwater JM, Horne A, Grey AB, Reid IR (2000) Effects of hormone replacement therapy on bone mineral density in postmenopausal women with primary hyperparathyroidism: four-year follow-up and comparison with healthy postmenopausal women. Arch Intern Med 160:2161–2166

    CAS  PubMed  Google Scholar 

  178. Rossini M, Viapiana O, Kalpakcioglu B et al (2011) Long-term effects of neridronate and its discontinuation in patients with primary hyperparathyroidism. Calcif Tissue Int 89:21–28. https://doi.org/10.1007/s00223-011-9489-x

    Article  CAS  PubMed  Google Scholar 

  179. Khan AA, Bilezikian JP, Kung AW et al (2004) (2004) Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial. J Clin Endocrinol Metab 89:3319–3325. https://doi.org/10.1210/jc.2003-030908

    Article  CAS  PubMed  Google Scholar 

  180. Cesareo R, Di Stasio E, Vescini F et al (2015) Effects of alendronate and vitamin D in patients with normocalcemic primary hyperparathyroidism. Osteoporos Int 26:1295–1302. https://doi.org/10.1007/s00198-014-3000-2

    Article  CAS  PubMed  Google Scholar 

  181. Peacock M, Bilezikian JP, Klassen PS, Guo MD, Turner SA, Shoback D (2005) Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism. J Clin Endocrinol Metab 90:135–141

    CAS  PubMed  Google Scholar 

  182. Silverberg SJ, Rubin MR, Faiman C et al (2007) Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma. J Clin Endocrinol Metab 92:3803–3808

    CAS  PubMed  Google Scholar 

  183. Peacock M, Bilezikian JP, Bolognese MA et al (2011) Cinacalcet HCl reduces hypercalcemia in primary hyperparathyroidism across a wide spectrum of disease severity. J Clin Endocrinol Metab 96:E9–18. https://doi.org/10.1210/jc.2010-1221

    Article  CAS  PubMed  Google Scholar 

  184. Cetani F, Saponaro F, Banti C et al (2012) Cinacalcet efficacy in patients with moderately severe primary hyperparathyroidism according to the European Medicine Agency prescription labeling. J Endocrinol Investig 35:655–660. https://doi.org/10.3275/7970

    Article  CAS  Google Scholar 

  185. Marcocci C, Chanson P, Shoback D et al (2019) Cinacalcet reduces serum calcium concentrations in patients with intractable primary hyperparathyroidism. J Clin Endocrinol Metab 94:2766–2772. https://doi.org/10.1210/jc.2008-2640

    Article  CAS  Google Scholar 

  186. Rubin MR, Dempster DW, Sliney J Jr et al (2011) PTH(1–84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism. J Bone Miner Res 26:2727–2736. https://doi.org/10.1002/jbmr.452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Yoneda M, Takatsuki K, Yamauchi K et al (1988) Tomita A. Effect of parathyroid function on serum bone Gla protein. Endocrinol Jpn 35:39–45

    CAS  PubMed  Google Scholar 

  188. Mizunashi K, Furukawa Y, Miura R, Yumita S, Sohn HE, Yoshinaga K (1988) Effects of active vitamin D3 and parathyroid hormone on the serum osteocalcin in idiopathic hypoparathyroidism and pseudohypoparathyroidism. J Clin Investig 82:861–865

    CAS  PubMed  Google Scholar 

  189. Rubin MR, Dempster DW, Zhou H et al (2008) Dynamic and structural properties of the skeleton in hypoparathyroidism. J Bone Miner Res 23:2018–2024. https://doi.org/10.1359/jbmr.080803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Langdahl BL, Mortensen L, Vesterby A, Eriksen EF, Charles P (1996) Bone histomorphometry in hypoparathyroid patients treated with vitamin D. Bone 18:103–108

    CAS  PubMed  Google Scholar 

  191. Rubin MR, Zhou H, Cusano NE et al (2018) The effects of long-term administration of rhPTH(1–84) in hypoparathyroidism by bone histomorphometry. J Bone Miner Res 33:1931–1939. https://doi.org/10.1002/jbmr.3543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Sikjaer T, Rejnmark L, Rolighed L, Heickendorff L, Mosekilde L (2011) Hypoparathyroid Study Group. The effect of adding PTH(1–84) to conventional treatment of hypoparathyroidism: a randomized, placebo-controlled study. J Bone Miner Res 26:2358–2370. https://doi.org/10.1002/jbmr.470

    Article  CAS  PubMed  Google Scholar 

  193. Mannstadt M, Clarke BL, Bilezikian JP et al (2019) Safety and efficacy of 5 years of treatment with recombinant human parathyroid hormone in adults with hypoparathyroidism. J Clin Endocrinol Metab 104:5136–5147. https://doi.org/10.1210/jc.2019-01010

    Article  PubMed  PubMed Central  Google Scholar 

  194. Cusano NE, Rubin MR, McMahon DJ et al (2013) Therapy of hypoparathyroidism with PTH(1–84): a prospective four-year investigation of efficacy and safety. J Clin Endocrinol Metab 98:137–144. https://doi.org/10.1210/jc.2012-2984

    Article  CAS  PubMed  Google Scholar 

  195. Rubin MR, Cusano NE, Fan WW et al (2016) Therapy of Hypoparathyroidism With PTH(1–84): A Prospective Six Year Investigation of Efficacy and Safety. J Clin Endocrinol Metab 101:2742–2750. https://doi.org/10.1210/jc.2015-4135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Winer KK, Ko CW, Reynolds JC et al (2003) Long-term treatment of hypoparathyroidism: a randomized controlled study comparing parathyroid hormone-(1–34) versus calcitriol and calcium. J Clin Endocrinol Metab 88:4214–4220

    CAS  PubMed  Google Scholar 

  197. Winer KK, Zhang B, Shrader JA et al (2012) Synthetic human parathyroid hormone 1–34 replacement therapy: a randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism. J Clin Endocrinol Metab 97:391–399. https://doi.org/10.1210/jc.2011-1908

    Article  CAS  PubMed  Google Scholar 

  198. Gafni RI, Guthrie LC, Kelly MH et al (2015) Transient increased calcium and calcitriol requirements after discontinuation of human synthetic parathyroid hormone 1–34 (hPTH 1–34) replacement therapy in hypoparathyroidism. J Bone Miner Res 30:2112–2118. https://doi.org/10.1002/jbmr.2555

    Article  CAS  PubMed  Google Scholar 

  199. Winer KK, Yanovski JA, Cutler GB Jr (1996) Synthetic human parathyroid hormone 1–34 vs calcitriol and calcium in the treatment of hypoparathyroidism. JAMA 276:631–636

    CAS  PubMed  Google Scholar 

  200. CORRIGENDUM FOR 10.1210/jc.2011-1908 (2015) J Clin Endocrinol Metab 100:2800. https://doi.org/10.1210/jc.2015-2347

  201. Law WM Jr, Heath H 3rd (1984) Increased renal responses to exogenous parathyroid hormone in postsurgical hypoparathyroidism. J Clin Endocrinol Metab 59:394–397

    PubMed  Google Scholar 

  202. Szappanos A, Toke J, Lippai D et al (2010) Bone turnover in patients with endogenous Cushing's syndrome before and after successful treatment. Osteoporos Int 21:637–645. https://doi.org/10.1007/s00198-009-0978-y

    Article  CAS  PubMed  Google Scholar 

  203. Trementino L, Appolloni G, Ceccoli L et al (2014) Bone complications in patients with Cushing's syndrome: looking for clinical, biochemical, and genetic determinants. Osteoporos Int 25:913–921. https://doi.org/10.1007/s00198-013-2520-5

    Article  CAS  PubMed  Google Scholar 

  204. Guo W, Li F, Zhu C et al (2018) Effect of hypercortisolism on bone mineral density and bone metabolism: a potential protective effect of adrenocorticotropic hormone in patients with Cushing's disease. J Int Med Res 46:492–503. https://doi.org/10.1177/0300060517725660

    Article  CAS  PubMed  Google Scholar 

  205. Tauchmanovà L, Pivonello R, Di Somma C et al (2006) Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status. J Clin Endocrinol Metab 91:1779–1784

    PubMed  Google Scholar 

  206. Dobnig H, Stepan V, Leb G, Wolf G, Buchfelder M, Krejs GJ (1996) Recovery from severe osteoporosis following cure from ectopic ACTH syndrome caused by an appendix carcinoid. J Intern Med 239:365–369

    CAS  PubMed  Google Scholar 

  207. Borelli A, Leite MO, Correa PH et al (1992) Bone histomorphometry in Cushing's syndrome. J Endocrinol Investig 15:783–787

    CAS  Google Scholar 

  208. Riggs BL, Jowsey J, Kelly PJ (1996) Quantitative microradiographic study of bone remodeling in Cushing's syndrome. Metabolism 15:773–780

    Google Scholar 

  209. Meunier PJ, Dempster DW, Edouard C, Chapuy MC, Arlot M, Charhon S (1984) Bone histomorphometry in corticosteroid-induced osteoporosis and Cushing's syndrome. Adv Exp Med Biol 171:191–200

    CAS  PubMed  Google Scholar 

  210. Sartorio A, Conti A, Ferrero S, Giambona S, Re T, Passini E, Ambrosi B (1998) Evaluation of markers of bone and collagen turnover in patients with active and preclinical Cushing's syndrome and in patients with adrenal incidentaloma. Eur J Endocrinol 138:146–152

    CAS  PubMed  Google Scholar 

  211. Godang K, Ueland T, Bollerslev J (1999) Decreased bone area, bone mineral content, formative markers, and increased bone resorptive markers in endogenous Cushing's syndrome. Eur J Endocrinol 141:126–131

    CAS  PubMed  Google Scholar 

  212. Athimulam S, Delivanis D, Thomas M et al (2020) The impact of mild autonomous cortisol secretion on bone turnover markers. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgaa120

    Article  PubMed  Google Scholar 

  213. Kristo C, Jemtland R, Ueland T, Godang K, Bollerslev J (2006) 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 154:109–118

    CAS  PubMed  Google Scholar 

  214. Scillitani A, Dicembrino F, Chiodini I et al (2002) Global skeletal uptake of 99mTc-methylene diphosphonate (GSU) in patients affected by endocrine diseases: comparison with biochemical markers of bone turnover. Osteoporos Int 13:829–834

    CAS  PubMed  Google Scholar 

  215. Chiodini I, Carnevale V, Torlontano M et al (1998) 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 83:1863–1867

    CAS  PubMed  Google Scholar 

  216. Osella G, Terzolo M, Reimondo G et al (1997) Serum markers of bone and collagen turnover in patients with Cushing's syndrome and in subjects with adrenal incidentalomas. J Clin Endocrinol Metab 82:3303–3307

    CAS  PubMed  Google Scholar 

  217. Camozzi V, Sanguin F, Albigier N et al (2010) Persistent increase of osteoprotegerin levels after cortisol normalization in patients with Cushing's syndrome. Eur J Endocrinol 162:85–90. https://doi.org/10.1530/EJE-09-0800

    Article  CAS  PubMed  Google Scholar 

  218. Di Somma C, Pivonello R, Loche S et al (2002) Severe impairment of bone mass and turnover in Cushing's disease: comparison between childhood-onset and adulthood-onset disease. Clin Endocrinol (Oxf) 56:153–158. https://doi.org/10.1046/j.0300-0664.2001.01454.doc.x

    Article  Google Scholar 

  219. Belaya ZE, Iljin AV, Melnichenko GA et al (2016) Diagnostic performance of osteocalcin measurements in patients with endogenous Cushing's syndrome. Bonekey Rep 5:815. https://doi.org/10.1038/bonekey.2016.42

    Article  PubMed  PubMed Central  Google Scholar 

  220. Cortet B, Cortet C, Blanckaert F et al (2001) Quantitative ultrasound of bone and markers of bone turnover in Cushing's syndrome. Osteoporos Int 12:117–123

    CAS  PubMed  Google Scholar 

  221. Francucci CM, Pantanetti P, Garrapa GG, Massi F, Arnaldi G, Mantero F (2002) Bone metabolism and mass in women with Cushing's syndrome and adrenal incidentaloma. Clin Endocrinol (Oxf) 57:587–593

    CAS  Google Scholar 

  222. Ebeling PR, Peterson JM, Riggs BL (1992) Utility of type I procollagen propeptide assays for assessing abnormalities in metabolic bone diseases. J Bone Miner Res 7:1243–1250

    CAS  PubMed  Google Scholar 

  223. Di Somma C, Pivonello R, Loche S et al (2003) Effect of 2 years of cortisol normalization on the impaired bone mass and turnover in adolescent and adult patients with Cushing's disease: a prospective study. Clin Endocrinol (Oxf) 58:302–308

    Google Scholar 

  224. Sartorio A, Conti A, Ferrario S, Passini E, Re T, Ambrosi B (1996) Serum bone Gla protein and carboxyterminal cross-linked telopeptide of type I collagen in patients with Cushing's syndrome. Postgrad Med J 72:419–422

    CAS  PubMed  PubMed Central  Google Scholar 

  225. Belaya ZE, Rozhinskaya LY, Melnichenko GA et al (2013) Serum extracellular secreted antagonists of the canonical Wnt/β-catenin signaling pathway in patients with Cushing's syndrome. Osteoporos Int 24:2191–2199. https://doi.org/10.1007/s00198-013-2268-y

    Article  CAS  PubMed  Google Scholar 

  226. van Lierop AH, van der Eerden AW, Hamdy NA, Hermus AR, den Heijer M, Papapoulos SE (2012) Circulating sclerostin levels are decreased in patients with endogenous hypercortisolism and increase after treatment. J Clin Endocrinol Metab 97:E1953–E1957. https://doi.org/10.1210/jc.2012-2218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Hermus AR, Smals AG, Swinkels LM et al (1995) Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome. J Clin Endocrinol Metab 80:2859–2865

    CAS  PubMed  Google Scholar 

  228. Kawamata A, Iihara M, Okamoto T, Obara T (2008) Bone mineral density before and after surgical cure of Cushing's syndrome due to adrenocortical adenoma: prospective study. World J Surg 32:890–896. https://doi.org/10.1007/s00268-007-9394-7

    Article  PubMed  Google Scholar 

  229. Ambrosi B, Peverelli S, Passini E et al (1995) Abnormalities of endocrine function in patients with clinically "silent" adrenal masses. Eur J Endocrinol 132:422–428. https://doi.org/10.1530/eje.0.1320422

    Article  CAS  PubMed  Google Scholar 

  230. Torlontano M, Chiodini I, Pileri M et al (1999) Altered bone mass and turnover in female patients with adrenal incidentaloma: the effect of subclinical hypercortisolism. J Clin Endocrinol Metab 84:2381–2385

    CAS  PubMed  Google Scholar 

  231. Chiodini I, Tauchmanovà L, Torlontano M et al (2002) Bone involvement in eugonadal male patients with adrenal incidentaloma and subclinical hypercortisolism. J Clin Endocrinol Metab 87:5491–5494

    CAS  PubMed  Google Scholar 

  232. Eastell R, Pigott T, Gossiel F, Naylor KE, Walsh JS, Peel NFA (2018) Bone turnover markers: are they clinically useful? Eur J Endocrinol 178:R19–R31. https://doi.org/10.1530/EJE-17-0585

    Article  CAS  PubMed  Google Scholar 

  233. Szulc P, Naylor K, Hoyle NR, Eastell R, Leary ET (2017) Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability. Osteoporos Int 28:2541–2556. https://doi.org/10.1007/s00198-017-4082-4

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM UMR 1033, University of Lyon, Hôpital Edouard Herriot, Pavillon F, Place d’Arsonval, 69437, Lyon, France

    P. Szulc

Authors
  1. P. Szulc
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Szulc.

Ethics declarations

Conflict of interest

I have no potential conflict of interest concerning this paper.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Szulc, P. Biochemical bone turnover markers in hormonal disorders in adults: a narrative review. J Endocrinol Invest 43, 1409–1427 (2020). https://doi.org/10.1007/s40618-020-01269-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-020-01269-7

Keywords

Search

Navigation