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Skeletal Alterations and Parathyroid Function

  • Elisabetta Romagnoli
  • Vincenzo Carnevale
Chapter

Abstract

Parathyroid hormone (PTH) action induces catabolic and anabolic skeletal effects. The continuous exposure of osteoblasts and osteocytes to PTH activates osteoclasts activity through the OPG-RANKL-RANK pathway. The enhanced bone formation mostly depends on the inhibition of sclerostin, an antagonist of the Wnt/β-catenin signalling.

Nowadays, the hallmark of primary hyperparathyroidism (PHPT), also in patients with minimal clinical manifestations, is the increased bone turnover rate, which translates in a preferential loss of cortical tissue with relative preservation of the trabecular bone. The current guidelines recommend areal bone mineral density (aBMD) assessment of the distal radius, lumbar spine, total hip and femoral neck, by dual-energy X-ray absorptiometry (DXA), every 1–2 years. Parathyroidectomy is indicated in postmenopausal women and men ≥50 years having a T-score ≤−2.5. DXA results do not fully explain the increased risk of fractures in PHPT, postmenopausal patients showing a higher vertebral fracture rate even with preserved BMD. High-resolution peripheral quantitative computed tomography (HR-pQCT) separately measures the true volumetric density (vBMD) of cortical and trabecular compartments, both decreased in PHPT. Trabecular bone score (TBS) indirectly estimates trabecular microarchitecture and correlates to μCT findings and to HR-pQCT-measured total, cortical, trabecular vBMD. Low TBS values are found also in patients with normal aBMD of the lumbar spine.

In hypoparathyroidism, the absent or inappropriately low serum PTH levels associate to BMD values above the average at the lumbar spine and femur, whereas TBS is unchanged. Long-term administration of rhPTH 1-84 stimulates bone remodelling and increases aBMD at the lumbar spine and femoral neck while decreases it at the distal radius. rhPTH 1-84 also promotes a transient increase in trabecular strength, whose effects on fracture risk are uncertain.

References

  1. 1.
    Goltzman D. Physiologic actions of PTH (I). PTH action on the skeleton. In: Bilezikian JP, Marcus R, Levine MA, Marcocci C, Silverberg SJ, Potts Jr JT, editors. The parathyroids: basic and clinical concepts. 3rd ed. London: Academic Press-Elsevier; 2015. p. 139–52.CrossRefGoogle Scholar
  2. 2.
    Divieti Pajevic P, Wein MN, Kronenberg HM. Parathyroid hormone actions on bone and kidney. In: Brandi ML, Brown EM, editors. Hypoparathyroidism. Milan: Springer-Verlag; 2015. p. 99–109.Google Scholar
  3. 3.
    Silva BC, Bilezikian JP. Parathyroid hormone: anabolic and catabolic actions on the skeleton. Curr Opin Pharmacol. 2015;22:41–50.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Silva BC, Kousteni S. Cellular actions of PTH. Osteoblasts, osteoclasts, and osteocytes. In: Bilezikian JP, Marcus R, Levine MA, Marcocci C, Silverberg SJ, Potts Jr JT, editors. The parathyroids: basic and clinical concepts. 3rd ed. London: Academic Press-Elsevier; 2015. p. 127–37.CrossRefGoogle Scholar
  5. 5.
    Silva BC, Bilezikian JP. Anabolic and catabolic pathways of parathyroid hormone on the skeleton. In: Bilezikian JP, Marcus R, Levine MA, Marcocci C, Silverberg SJ, Potts Jr JT, editors. The parathyroids: basic and clinical concepts. 3rd ed. London: Academic Press-Elsevier; 2015. p. 233–44.CrossRefGoogle Scholar
  6. 6.
    Dempster DW, Silverberg SJ, Shane E, Bilezikian JP. Bone histomorphometry and bone quality in primary hyperparathyroidism. In: Bilezikian JP, Marcus R, Levine MA, Marcocci C, Silverberg SJ, Potts Jr JT, editors. The parathyroids: basic and clinical concepts. 3rd ed. London: Academic Press-Elsevier; 2015. p. 429–45.CrossRefGoogle Scholar
  7. 7.
    Scillitani A, Dicembrino F, Chiodini I, et al. Global skeletal uptake of 99mTc-methylene diphosphonate (GSU) in patients affected by endocrine diseases: comparison with biochemical markers of bone turnover. Osteoporos Int. 2002;13:829–34.CrossRefPubMedGoogle Scholar
  8. 8.
    Carnevale V, Pacitti MT, Pileri M, et al. Short-term effects of surgery in post-menopausal patients with primary hyperparathyroidism and normal bone turnover. J Endocrinol Invest. 2001;24:575–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Silva BC, Cusano NE, Hans D, Lewiecki EM, Bilezikian JP. Skeletal imaging in primary hyperparathyroidism. In: Bilezikian JP, Marcus R, Levine MA, Marcocci C, Silverberg SJ, Potts Jr JT, editors. The parathyroids: basic and clinical concepts. 3rd ed. London: Academic Press-Elsevier; 2015. p. 447–54.CrossRefGoogle Scholar
  10. 10.
    Bilezikian JP, Brandi ML, Eastell R, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99:3561–9.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Castellano E, Attanasio R, Cesario F, Tassone F, Borretta G. Forearm DXA increases the rate of patients with asymptomatic primary hyperparathyroidism meeting surgical criteria. J Clin Endocrinol Metab. 2016;101:2728–32.CrossRefPubMedGoogle Scholar
  12. 12.
    Silverberg SJ. Primary hyperparathyroidism. In: Rosen CJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. 8th ed. New York: John Wiley & Sons; 2013. p. 543–52.CrossRefGoogle Scholar
  13. 13.
    Silverberg SJ, Shane E, Jacobs TP, Siris E, Bilezikian JP. A 10-year prospective study of primary hyperparathyroidism with or without surgery. N Engl J Med. 1999;341:1249–55.CrossRefPubMedGoogle Scholar
  14. 14.
    Rubin MR, Bilezikian JP, McMahon DJ, et al. The natural history of primary hyperparathyroidism with or without surgery after 15 years. J Clin Endocrinol Metab. 2008;93:346–3470.CrossRefGoogle Scholar
  15. 15.
    De Geronimo S, Romagnoli E, Diacinti D, D’Erasmo E, Minisola S. The risk of fractures in postmenopausal women with primary hyperparathyroidism. Eur J Endocrinol. 2006;155:415–20.CrossRefPubMedGoogle Scholar
  16. 16.
    Stein EM, Silva BC, Boutroy S, et al. Primary hyperparathyroidism is associated with abnormal cortical and trabecular microstructure and reduced bone stiffness in postmenopausal women. J Bone Miner Res. 2013;28:1029–40.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Silva BC, Boutroy S, Zhang C, et al. Trabecular bone score (TBS)—a novel method to evaluate bone microarchitecture texture in patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2013;98:1963–70.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Romagnoli E, Cipriani C, Nofroni I, et al. “Trabecular bone score” (TBS): an indirect measure of bone microarchitecture in postmenopausal patients with primary hyperparathyroidism. Bone. 2013;53:154–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Eller-Vainicher C, Filopanti M, Palmieri S, et al. Bone quality, as measured by trabecular bone score, in patients with primary hyperparathyroidism. Eur J Endocrinol. 2013;169:155–62.CrossRefPubMedGoogle Scholar
  20. 20.
    Bilezikian JP, Khan A, Potts JT Jr, et al. Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J Bone Miner Res. 2011;26:2317–37.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Dempster DW. Bone histomorphometry in hypoparathyroidism. In: Brandi ML, Brown EM, editors. Hypoparathyroidism. Milan: Springer-Verlag; 2015. p. 287–96.Google Scholar
  22. 22.
    Shoback DM, Bilezikian JP, Costa AG, et al. Presentation of hypoparathyroidism: etiologies and clinical features. J Clin Endocrinol Metab. 2016;101:2300–12.CrossRefPubMedGoogle Scholar
  23. 23.
    Cusano NE, Nishiyama KK, Zhang C, et al. Noninvasive assessment of skeletal microstructure and estimated bone strength in hypoparathyroidism. J Bone Miner Res. 2016;31:308–16.CrossRefPubMedGoogle Scholar
  24. 24.
    Mendonca ML, Pereira FA, Nogueira-Barbosa MH, et al. Increased vertebral morphometric fracture in patients with postsurgical hypoparathyroidism despite normal bone mineral density. BMC Endocr Disord. 2013;13:1–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L. Postsurgical hypoparathyroidism—risk of fractures, psychiatric diseases, cancer, cataract, and infections. J Bone Miner Res. 2014;29:2504–10.CrossRefPubMedGoogle Scholar
  26. 26.
    Rubin MR, Cusano NE, Fan WW, et al. Therapy of hypoparathyroidism with PTH(1-84): a prospective six year investigation of efficacy and safety. J Clin Endocrinol Metab. 2016;101:2742–50.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Rubin MR, Dempster DW, Sliney J Jr, et al. PTH(1-84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism. J Bone Miner Res. 2011;26:2727–36.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Rubin MR, Zwahlen A, Dempster DW, et al. Effects of parathyroid hormone administration on bone strength in hypoparathyroidism. J Bone Miner Res. 2016;31:1–7.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Experimental MedicineUniversity of Rome “Sapienza”RomeItaly
  2. 2.Unit of Internal Medicine“Casa Sollievo della Sofferenza” HospitalSan Giovanni RotondoItaly

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