Skeletal abnormalities in Hypoparathyroidism and in Primary Hyperparathyroidism

Abstract

Both hypoparathyroidism (HypoPT), as well as its pathological counterpart, primary hyperparathyroidism (PHPT), can lead to skeletal abnormalities. Chronic deficiency of PTH in patients with HypoPT is associated with a profound reduction in bone remodeling, with consequent increases in bone density, and abnormalities in microarchitecture and bone strength. It is still not clear whether there is an increase in fracture risk in HypoPT. While standard therapy with calcium supplements and active vitamin D does not restore bone homeostasis, treatment of HypoPT with PTH appears to correct some of those abnormalities. In PHPT, the continuous exposure to high levels of PTH causes an increase in bone remodeling, in which bone resorption prevails. In the symptomatic form of PHPT, patients can present with fragility fractures, and/or the classical radiological features of osteitis fibrosa cystica. However, even in mild PHPT, catabolic skeletal actions of PTH are evident through reduced BMD, deterioration of bone microarchitecture and increased risk of fragility fractures. Successful parathyroidectomy improves skeletal abnormalities. Medical treatment, such as bisphosphonates and denosumab, can also increase bone density in patients with PHPT who do not undergo surgery. This article reviews skeletal involvement in HypoPT and in PHPT, as assessed by bone remodeling, DXA, trabecular bone score, and quantitative computed tomography, as well as data on bone strength and fracture risk. The effects of PTH replacement on the skeleton in subjects with HypoPT, and the outcome of parathyroidectomy in patients with PHPT, are also reviewed here.

This is a preview of subscription content, access via your institution.

Data availability

not applicable.

References

  1. 1.

    Bilezikian JP. Hypoparathyroidism. J Clin Endocrinol Metab. 2020;105(6):1722–36. https://doi.org/10.1210/clinem/dgaa113.

    Article  Google Scholar 

  2. 2.

    Shoback DM, Bilezikian JP, Costa AG, Dempster D, Dralle H, Khan AA, et al. Presentation of Hypoparathyroidism: etiologies and clinical features. J Clin Endocrinol Metab. 2016;101(6):2300–12. https://doi.org/10.1210/jc.2015-3909.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Maeda SS, Moreira CA, VZC B, Bandeira F, MLF F, JLC B, et al. Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism. Arch Endocrinol Metab. 2018;62(1):106–24. https://doi.org/10.20945/2359-3997000000015.

    Article  PubMed  Google Scholar 

  4. 4.

    Catin-Cabral M, Clarke B. Epidemiology of hypoparathyroidism. In: John PB, Robert M, Michael AL, Claudio M, Shonni JS, John P, editors. The Parathyroids. 3rd ed. Elesevier Inc; 2015. p 707–717.

  5. 5.

    Mitchell DM, Regan S, Cooley MR, Lauter KB, Vrla MC, Becker CB, et al. Long-term follow-up of patients with hypoparathyroidism. J Clin Endocrinol Metab. 2012;97(12):4507–14. https://doi.org/10.1210/jc.2012-1808.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Tay YD, Tabacco G, Cusano NE, Williams J, Omeragic B, Majeed R, et al. Therapy of Hypoparathyroidism with rhPTH(1-84): a prospective, 8-year investigation of efficacy and safety. J Clin Endocrinol Metab. 2019;104(11):5601–10. https://doi.org/10.1210/jc.2019-00893.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Gafni RI, Collins MT. Hypoparathyroidism. N Engl J Med. 2019;380(18):1738–47. https://doi.org/10.1056/NEJMcp1800213.

    Article  PubMed  Google Scholar 

  8. 8.

    Cusano NE, Bilezikian JP. Signs and symptoms of Hypoparathyroidism. Endocrinol Metab Clin N Am. 2018;47(4):759–70. https://doi.org/10.1016/j.ecl.2018.07.001.

    Article  Google Scholar 

  9. 9.

    Langdahl BL, Mortensen L, Vesterby A, Eriksen EF, Charles P. Bone histomorphometry in hypoparathyroid patients treated with vitamin D. Bone. 1996;18(2):103–8. https://doi.org/10.1016/8756-3282(95)00443-2.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Rubin MR, Dempster DW, Zhou H, Shane E, Nickolas T, Sliney J Jr, et al. Dynamic and structural properties of the skeleton in hypoparathyroidism. J Bone Miner Res. 2008;23(12):2018–24. https://doi.org/10.1359/jbmr.080803.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Rubin MR, Dempster DW, Sliney J Jr, Zhou H, Nickolas TL, Stein EM, et al. PTH(1-84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism. J Bone Miner Res. 2011;26(11):2727–36. https://doi.org/10.1002/jbmr.452.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Silva BC, Rubin MR, Cusano NE, Bilezikian JP. Bone imaging in hypoparathyroidism. Osteoporos Int. 2017;28(2):463–71. https://doi.org/10.1007/s00198-016-3750-0.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Rejnmark L, Sikjaer T, Underbjerg L, Mosekilde L. PTH replacement therapy of hypoparathyroidism. Osteoporos Int. 2013;24(5):1529–36. https://doi.org/10.1007/s00198-012-2230-4.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Cusano NE, Rubin MR, Bilezikian JP. Parathyroid hormone therapy for hypoparathyroidism. Best Pract Res Clin Endocrinol Metab. 2015;29(1):47–55. https://doi.org/10.1016/j.beem.2014.09.001.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Bilezikian JP, Bandeira L, Khan A, Cusano NE. Hyperparathyroidism. Lancet. 2018;391(10116):168–78. https://doi.org/10.1016/S0140-6736(17)31430-7.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Bilezikian JP, Cusano NE, Khan AA, Liu JM, Marcocci C, Bandeira F. Primary hyperparathyroidism. Nat Rev Dis Primers. 2016;2:16033. https://doi.org/10.1038/nrdp.2016.33.

    Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Insogna KL. Primary hyperparathyroidism. N Engl J Med. 2018;379(11):1050–9. https://doi.org/10.1056/NEJMcp1714213.

    Article  PubMed  Google Scholar 

  18. 18.

    Cipriani C, Bilezikian JP. Three generational phenotypes of sporadic primary hyperparathyroidism: evolution defined by technology. Lancet Diabetes Endocrinol. 2019;7(10):745–7. https://doi.org/10.1016/S2213-8587(19)30188-3.

    Article  PubMed  Google Scholar 

  19. 19.

    Eastell R, Brandi ML, Costa AG, D'Amour P, Shoback DM, Thakker RV. Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the fourth international workshop. J Clin Endocrinol Metab. 2014;99(10):3570–9. https://doi.org/10.1210/jc.2014-1414.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Bandeira F, Cusano NE, Silva BC, Cassibba S, Almeida CB, Machado VC, et al. Bone disease in primary hyperparathyroidism. Arq Bras Endocrinol Metabol. 2014;58(5):553–61. https://doi.org/10.1590/0004-2730000003381.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Rubin MR, Bilezikian JP, McMahon DJ, Jacobs T, Shane E, Siris E, et al. The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J Clin Endocrinol Metab. 2008;93(9):3462–70. https://doi.org/10.1210/jc.2007-1215.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Hansen S, Beck Jensen JE, Rasmussen L, Hauge EM, Brixen K. Effects on bone geometry, density, and microarchitecture in the distal radius but not the tibia in women with primary hyperparathyroidism: a case-control study using HR-pQCT. J Bone Miner Res. 2010;25(9):1941–7. https://doi.org/10.1002/jbmr.98.

    Article  PubMed  Google Scholar 

  23. 23.

    Silva BC, Boutroy S, Zhang C, McMahon DJ, Zhou B, Wang J, et al. Trabecular bone score (TBS)--a novel method to evaluate bone microarchitectural texture in patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2013;98(5):1963–70. https://doi.org/10.1210/jc.2012-4255.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Stein EM, Silva BC, Boutroy S, Zhou B, Wang J, Udesky J, 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(5):1029–40. https://doi.org/10.1002/jbmr.1841.

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Vu TD, Wang XF, Wang Q, Cusano NE, Irani D, Silva BC, et al. New insights into the effects of primary hyperparathyroidism on the cortical and trabecular compartments of bone. Bone. 2013;55(1):57–63. https://doi.org/10.1016/j.bone.2013.03.009.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Vignali E, Viccica G, Diacinti D, Cetani F, Cianferotti L, Ambrogini E, et al. Morphometric vertebral fractures in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab. 2009;94(7):2306–12. https://doi.org/10.1210/jc.2008-2006.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    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(11):2504–10. https://doi.org/10.1002/jbmr.2273.

    Article  PubMed  Google Scholar 

  28. 28.

    Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L. The epidemiology of nonsurgical Hypoparathyroidism in Denmark: a Nationwide case finding study. J Bone Miner Res. 2015;30(9):1738–44. https://doi.org/10.1002/jbmr.2501.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Chawla H, Saha S, Kandasamy D, Sharma R, Sreenivas V, Goswami R. Vertebral fractures and Bone mineral density in patients with idiopathic Hypoparathyroidism on long-term follow-up. J Clin Endocrinol Metab. 2017;102(1):251–8. https://doi.org/10.1210/jc.2016-3292.

    Article  PubMed  Google Scholar 

  30. 30.

    Mendonca ML, Pereira FA, Nogueira-Barbosa MH, Monsignore LM, Teixeira SR, Watanabe PC, et al. Increased vertebral morphometric fracture in patients with postsurgical hypoparathyroidism despite normal bone mineral density. BMC Endocr Disord. 2013;13:1. https://doi.org/10.1186/1472-6823-13-1.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Abugassa S, Nordenstrom J, Eriksson S, Sjoden G. Bone mineral density in patients with chronic hypoparathyroidism. J Clin Endocrinol Metab. 1993;76(6):1617–21. https://doi.org/10.1210/jcem.76.6.8501170.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Chan FK, Tiu SC, Choi KL, Choi CH, Kong AP, Shek CC. Increased bone mineral density in patients with chronic hypoparathyroidism. J Clin Endocrinol Metab. 2003;88(7):3155–9. https://doi.org/10.1210/jc.2002-021388.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Chen Q, Kaji H, Iu MF, Nomura R, Sowa H, Yamauchi M, et al. Effects of an excess and a deficiency of endogenous parathyroid hormone on volumetric bone mineral density and bone geometry determined by peripheral quantitative computed tomography in female subjects. J Clin Endocrinol Metab. 2003;88(10):4655–8. https://doi.org/10.1210/jc.2003-030470.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Laway BA, Goswami R, Singh N, Gupta N, Seith A. Pattern of bone mineral density in patients with sporadic idiopathic hypoparathyroidism. Clin Endocrinol. 2006;64(4):405–9. https://doi.org/10.1111/j.1365-2265.2006.02479.x.

    CAS  Article  Google Scholar 

  35. 35.

    Sikjaer T, Rejnmark L, Rolighed L, Heickendorff L, Mosekilde L. The effect of adding PTH(1-84) to conventional treatment of hypoparathyroidism: a randomized, placebo-controlled study. J Bone Miner Res. 2011;26(10):2358–70. https://doi.org/10.1002/jbmr.470.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Takamura Y, Miyauchi A, Yabuta T, Kihara M, Ito Y, Miya A. Attenuation of postmenopausal bone loss in patients with transient hypoparathyroidism after total thyroidectomy. World J Surg. 2013;37(12):2860–5. https://doi.org/10.1007/s00268-013-2207-2.

    Article  PubMed  Google Scholar 

  37. 37.

    Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N, et al. Trabecular bone score: a noninvasive analytical method based upon the DXA image. J Bone Miner Res. 2014;29(3):518–30. https://doi.org/10.1002/jbmr.2176.

    Article  PubMed  Google Scholar 

  38. 38.

    McCloskey EV, Oden A, Harvey NC, Leslie WD, Hans D, Johansson H, et al. A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX. J Bone Miner Res. 2015;31:940–8. https://doi.org/10.1002/jbmr.2734.

    Article  PubMed  Google Scholar 

  39. 39.

    Silva BC, Broy SB, Boutroy S, Schousboe JT, Shepherd JA, Leslie WD. Fracture risk prediction by non-BMD DXA measures: the 2015 ISCD official positions part 2: trabecular Bone score. J Clin Densitom. 2015;18(3):309–30. https://doi.org/10.1016/j.jocd.2015.06.008.

    Article  PubMed  Google Scholar 

  40. 40.

    Cipriani C, Abraham A, Silva BC, Cusano NE, Rubin MR, McMahon DJ, et al. Skeletal changes after restoration of the euparathyroid state in patients with hypoparathyroidism and primary hyperparathyroidism. Endocrine. 2017;55(2):591–8. https://doi.org/10.1007/s12020-016-1101-8.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Cusano NE, Nishiyama KK, Zhang C, Rubin MR, Boutroy S, McMahon DJ, et al. Noninvasive assessment of skeletal microstructure and estimated Bone strength in Hypoparathyroidism. J Bone Miner Res. 2016;31(2):308–16. https://doi.org/10.1002/jbmr.2609.

    Article  PubMed  Google Scholar 

  42. 42.

    Cusano NE, Rubin MR, Williams JM, Agarwal S, Tabacco G, Tay D, et al. Changes in skeletal microstructure through four continuous years of rhPTH(1-84) therapy in Hypoparathyroidism. J Bone Miner Res. 2020;35:1274–81. https://doi.org/10.1002/jbmr.4005.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Starr JR, Tabacco G, Majeed R, Omeragic B, Bandeira L, Rubin MR. PTH and bone material strength in hypoparathyroidism as measured by impact microindentation. Osteoporos Int. 2020;31(2):327–33. https://doi.org/10.1007/s00198-019-05177-2.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Bilezikian JP, Brandi ML, Cusano NE, Mannstadt M, Rejnmark L, Rizzoli R, et al. Management of Hypoparathyroidism: present and future. J Clin Endocrinol Metab. 2016;101(6):2313–24. https://doi.org/10.1210/jc.2015-3910.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Brandi ML, Bilezikian JP, Shoback D, Bouillon R, Clarke BL, Thakker RV, et al. Management of Hypoparathyroidism: summary statement and guidelines. J Clin Endocrinol Metab. 2016;101(6):2273–83. https://doi.org/10.1210/jc.2015-3907.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    Mannstadt M, Clarke BL, Vokes T, Brandi ML, Ranganath L, Fraser WD, et al. Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol. 2013;1(4):275–83. https://doi.org/10.1016/S2213-8587(13)70106-2.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Lakatos P, Bajnok L, Lagast H, Valkusz Z. An open-label extension study of parathyroid hormone Rhpth(1-84) in adults with Hypoparathyroidism. Endocr Pract. 2016;22(5):523–32. https://doi.org/10.4158/EP15936.OR.

    Article  PubMed  Google Scholar 

  48. 48.

    Mannstadt M, Clarke BL, Bilezikian JP, Bone H, Denham D, Levine MA, et al. Safety and efficacy of 5 years of treatment with recombinant human parathyroid hormone in adults with Hypoparathyroidism. J Clin Endocrinol Metab. 2019;104(11):5136–47. https://doi.org/10.1210/jc.2019-01010.

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Clarke BL, Vokes TJ, Bilezikian JP, Shoback DM, Lagast H, Mannstadt M. Effects of parathyroid hormone rhPTH(1-84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study. Endocrine. 2017;55(1):273–82. https://doi.org/10.1007/s12020-016-1141-0.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Rubin MR, Sliney J Jr, McMahon DJ, Silverberg SJ, Bilezikian JP. Therapy of hypoparathyroidism with intact parathyroid hormone. Osteoporos Int. 2010;21(11):1927–34. https://doi.org/10.1007/s00198-009-1149-x.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Cusano NE, Rubin MR, McMahon DJ, Zhang C, Ives R, Tulley A, et al. Therapy of hypoparathyroidism with PTH(1-84): a prospective four-year investigation of efficacy and safety. J Clin Endocrinol Metab. 2013;98(1):137–44. https://doi.org/10.1210/jc.2012-2984.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Rubin MR, Cusano NE, Fan WW, Delgado Y, Zhang C, Costa AG, et al. Therapy of Hypoparathyroidism with PTH(1-84): a prospective six year investigation of efficacy and safety. J Clin Endocrinol Metab. 2016;101(7):2742–50. https://doi.org/10.1210/jc.2015-4135.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Rubin MR, Zhou H, Cusano NE, Majeed R, Omeragic B, Gomez M, et al. The effects of long-term administration of rhPTH(1-84) in Hypoparathyroidism by Bone Histomorphometry. J Bone Miner Res. 2018;33(11):1931–9. https://doi.org/10.1002/jbmr.3543.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Sikjaer T, Rejnmark L, Thomsen JS, Tietze A, Bruel A, Andersen G, et al. Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1-84): a randomized controlled study. J Bone Miner Res. 2012;27(4):781–8. https://doi.org/10.1002/jbmr.1493.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Tabacco G, Tay YD, Cusano NE, Williams J, Omeragic B, Majeed R, et al. Quality of life in Hypoparathyroidism improves with rhPTH(1-84) throughout 8 years of therapy. J Clin Endocrinol Metab. 2019;104(7):2748–56. https://doi.org/10.1210/jc.2018-02430.

    Article  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Cipriani C, Pepe J, Silva BC, Rubin MR, Cusano NE, McMahon DJ, et al. Comparative effect of rhPTH(1-84) on Bone mineral density and trabecular Bone score in Hypoparathyroidism and postmenopausal osteoporosis. J Bone Miner Res. 2018;33(12):2132–9. https://doi.org/10.1002/jbmr.3554.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Rubin MR, Zwahlen A, Dempster DW, Zhou H, Cusano NE, Zhang C, et al. Effects of parathyroid hormone administration on Bone strength in Hypoparathyroidism. J Bone Miner Res. 2016;31(5):1082–8. https://doi.org/10.1002/jbmr.2777.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Fujiyama K, Kiriyama T, Ito M, Nakata K, Yamashita S, Yokoyama N, et al. Attenuation of postmenopausal high turnover bone loss in patients with hypoparathyroidism. J Clin Endocrinol Metab. 1995;80(7):2135–8. https://doi.org/10.1210/jcem.80.7.7608266.

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Silva BC, Cusano NE, Bilezikian JP. Primary hyperparathyroidism. Best Pract Res Clin Endocrinol Metab. 2018;101247:101247. https://doi.org/10.1016/j.beem.2018.09.013.

    CAS  Article  Google Scholar 

  60. 60.

    Eufrazino C, Veras A, Bandeira F. Epidemiology of primary hyperparathyroidism and its non-classical manifestations in the City of Recife. Brazil Clin Med Insights Endocrinol Diab. 2013;6:69–74. https://doi.org/10.4137/CMED.S13147.

    CAS  Article  Google Scholar 

  61. 61.

    Bandeira F, Griz L, Caldas G, Bandeira C, Freese E. From mild to severe primary hyperparathyroidism: the Brazilian experience. Arq Bras Endocrinol Metabol. 2006;50(4):657–63.

    Article  Google Scholar 

  62. 62.

    Yadav SK, Johri G, Bichoo RA, Jha CK, Kintu-Luwaga R, Mishra SK. Primary hyperparathyroidism in developing world: a systematic review on the changing clinical profile of the disease. Arch Endocrinol Metab. 2020;64(2):105–10. https://doi.org/10.20945/2359-3997000000211.

    Article  PubMed  Google Scholar 

  63. 63.

    Silva B, Kousteni S. Cellular actions of PTH: Osteoblasts, osteoclasts, and osteocytes. In: The Parathyroids. 3rd ed.: Elsevier Inc.; 2015. p. 127–137.

  64. 64.

    Misiorowski W, Czajka-Oraniec I, Kochman M, Zgliczynski W, Bilezikian JP. Osteitis fibrosa cystica-a forgotten radiological feature of primary hyperparathyroidism. Endocrine. 2017;58(2):380–5. https://doi.org/10.1007/s12020-017-1414-2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Guo CY, Thomas WE, al-Dehaimi AW, Assiri AM, Eastell R. Longitudinal changes in bone mineral density and bone turnover in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab. 1996;81(10):3487–91. https://doi.org/10.1210/jcem.81.10.8855790.

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    Silverberg SJ, Clarke BL, Peacock M, Bandeira F, Boutroy S, Cusano NE, et al. Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the fourth international workshop. J Clin Endocrinol Metab. 2014;99(10):3580–94. https://doi.org/10.1210/jc.2014-1415.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Costa AG, Bilezikian JP. Bone turnover markers in primary hyperparathyroidism. J Clin Densitom. 2013;16(1):22–7. https://doi.org/10.1016/j.jocd.2012.11.004.

    Article  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Lundstam K, Heck A, Godang K, Mollerup C, Baranowski M, Pernow Y, et al. 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. 2017;32(9):1907–14. https://doi.org/10.1002/jbmr.3177.

    Article  PubMed  Google Scholar 

  69. 69.

    Faggiano A, Di Somma C, Ramundo V, Severino R, Vuolo L, Coppola A, et al. Cinacalcet hydrochloride in combination with alendronate normalizes hypercalcemia and improves bone mineral density in patients with primary hyperparathyroidism. Endocrine. 2011;39(3):283–7. https://doi.org/10.1007/s12020-011-9459-0.

    CAS  Article  PubMed  Google Scholar 

  70. 70.

    Rajeev P, Movseysan A, Baharani A. Changes in bone turnover markers in primary hyperparathyroidism and response to surgery. Ann R Coll Surg Engl. 2017;99(7):559–62. https://doi.org/10.1308/rcsann.2017.0092.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Rossini M, Gatti D, Isaia G, Sartori L, Braga V, Adami S. Effects of oral alendronate in elderly patients with osteoporosis and mild primary hyperparathyroidism. J Bone Miner Res. 2001;16(1):113–9. https://doi.org/10.1359/jbmr.2001.16.1.113.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Alonso S, Ferrero E, Donat M, Martinez G, Vargas C, Hidalgo M, et al. 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. 2012;35(7):640–4. https://doi.org/10.3275/7923.

    CAS  Article  Google Scholar 

  73. 73.

    Costa AG, Cremers S, Rubin MR, McMahon DJ, Sliney J Jr, Lazaretti-Castro M, et al. Circulating sclerostin in disorders of parathyroid gland function. J Clin Endocrinol Metab. 2011;96(12):3804–10. https://doi.org/10.1210/jc.2011-0566.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Christiansen P, Steiniche T, Brixen K, Hessov I, Melsen F, Heickendorff L, et al. Primary hyperparathyroidism: short-term changes in bone remodeling and bone mineral density following parathyroidectomy. Bone. 1999;25(2):237–44. https://doi.org/10.1016/s8756-3282(99)00150-7.

    CAS  Article  PubMed  Google Scholar 

  75. 75.

    Dempster DW, Parisien M, Silverberg SJ, Liang XG, Schnitzer M, Shen V, et al. On the mechanism of cancellous bone preservation in postmenopausal women with mild primary hyperparathyroidism. J Clin Endocrinol Metab. 1999;84(5):1562–6. https://doi.org/10.1210/jcem.84.5.5652.

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Silverberg SJ, Shane E, de la Cruz L, Dempster DW, Feldman F, Seldin D, et al. Skeletal disease in primary hyperparathyroidism. J Bone Miner Res. 1989;4(3):283–91. https://doi.org/10.1002/jbmr.5650040302.

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Castellano E, Attanasio R, Gianotti L, 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(7):2728–32. https://doi.org/10.1210/jc.2016-1513.

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Eller-Vainicher C, Filopanti M, Palmieri S, Ulivieri FM, Morelli V, Zhukouskaya VV, et al. Bone quality, as measured by trabecular bone score, in patients with primary hyperparathyroidism. Eur J Endocrinol. 2013;169(2):155–62. https://doi.org/10.1530/EJE-13-0305.

    CAS  Article  PubMed  Google Scholar 

  79. 79.

    Romagnoli E, Cipriani C, Nofroni I, Castro C, Angelozzi M, Scarpiello A, et al. "trabecular Bone score" (TBS): an indirect measure of bone micro-architecture in postmenopausal patients with primary hyperparathyroidism. Bone. 2013;53(1):154–9. https://doi.org/10.1016/j.bone.2012.11.041.

    Article  PubMed  Google Scholar 

  80. 80.

    Leere JS, Kruse C, Robaczyk M, Karmisholt J, Vestergaard P. Associations between trabecular bone score and biochemistry in surgically vs conservatively treated outpatients with primary hyperparathyroidism: a retrospective cohort study. Bone Rep. 2018;9:101–9. https://doi.org/10.1016/j.bonr.2018.08.001.

    Article  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Tay YD, Cusano NE, Rubin MR, Williams J, Omeragic B, Bilezikian JP. Trabecular Bone score in obese and nonobese subjects with primary hyperparathyroidism before and after Parathyroidectomy. J Clin Endocrinol Metab. 2018;103(4):1512–21. https://doi.org/10.1210/jc.2017-02169.

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Munoz-Torres M, Manzanares Cordova R, Garcia-Martin A, Aviles-Perez MD, Nieto Serrano R, Andujar-Vera F, et al. Usefulness of trabecular Bone score (TBS) to identify Bone fragility in patients with primary hyperparathyroidism. J Clin Densitom. 2019;22(2):162–70. https://doi.org/10.1016/j.jocd.2018.06.005.

    Article  PubMed  Google Scholar 

  83. 83.

    Parisien M, Silverberg SJ, Shane E, de la Cruz L, Lindsay R, Bilezikian JP, et al. The histomorphometry of bone in primary hyperparathyroidism: preservation of cancellous bone structure. J Clin Endocrinol Metab. 1990;70(4):930–8. https://doi.org/10.1210/jcem-70-4-930.

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Dempster DW, Muller R, Zhou H, Kohler T, Shane E, Parisien M, et al. Preserved three-dimensional cancellous bone structure in mild primary hyperparathyroidism. Bone. 2007;41(1):19–24. https://doi.org/10.1016/j.bone.2007.03.020.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Khosla S, Melton LJ 3rd, Wermers RA, Crowson CS, O'Fallon W, Riggs B. Primary hyperparathyroidism and the risk of fracture: a population-based study. J Bone Miner Res. 1999;14(10):1700–7. https://doi.org/10.1359/jbmr.1999.14.10.1700.

    CAS  Article  PubMed  Google Scholar 

  86. 86.

    Vestergaard P, Mollerup CL, Frokjaer VG, Christiansen P, Blichert-Toft M, Mosekilde L. Cohort study of risk of fracture before and after surgery for primary hyperparathyroidism. BMJ. 2000;321(7261):598–602. https://doi.org/10.1136/bmj.321.7261.598.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Vestergaard P, Mosekilde L. Fractures in patients with primary hyperparathyroidism: nationwide follow-up study of 1201 patients. World J Surg. 2003;27(3):343–9. https://doi.org/10.1007/s00268-002-6589-9.

    Article  PubMed  Google Scholar 

  88. 88.

    Yu N, Donnan PT, Flynn RW, Murphy MJ, Smith D, Rudman A, et al. Increased mortality and morbidity in mild primary hyperparathyroid patients. The Parathyroid Epidemiology and Audit Research Study (PEARS). Clin Endocrinol (Oxf). 2010;73(1):30–4. https://doi.org/10.1111/j.1365-2265.2009.03766.x.

    Article  Google Scholar 

  89. 89.

    Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the fourth international workshop. J Clin Endocrinol Metab. 2014;99(10):3561–9. https://doi.org/10.1210/jc.2014-1413.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Kenny AM, MacGillivray DC, Pilbeam CC, Crombie HD, Raisz LG. Fracture incidence in postmenopausal women with primary hyperparathyroidism. Surgery. 1995;118(1):109–14. https://doi.org/10.1016/s0039-6060(05)80017-0.

    CAS  Article  PubMed  Google Scholar 

  91. 91.

    Melton LJ 3rd, Atkinson EJ, O'Fallon WM, Heath H 3rd. Risk of age-related fractures in patients with primary hyperparathyroidism. Arch Intern Med. 1992;152(11):2269–73.

    Article  Google Scholar 

  92. 92.

    Larsson K, Ljunghall S, Krusemo UB, Naessen T, Lindh E, Persson I. The risk of hip fractures in patients with primary hyperparathyroidism: a population-based cohort study with a follow-up of 19 years. J Intern Med. 1993;234(6):585–93. https://doi.org/10.1111/j.1365-2796.1993.tb01017.x.

    CAS  Article  PubMed  Google Scholar 

  93. 93.

    Wilson RJ, Rao S, Ellis B, Kleerekoper M, Parfitt AM. Mild asymptomatic primary hyperparathyroidism is not a risk factor for vertebral fractures. Ann Intern Med. 1988;109(12):959–62. https://doi.org/10.7326/0003-4819-109-12-959.

    CAS  Article  PubMed  Google Scholar 

  94. 94.

    Kaji H, Yamauchi M, Chihara K, Sugimoto T. The threshold of bone mineral density for vertebral fractures in female patients with primary hyperparathyroidism. Eur J Endocrinol. 2005;153(3):373–8. https://doi.org/10.1530/eje.1.01985.

    CAS  Article  PubMed  Google Scholar 

  95. 95.

    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(3):415–20. https://doi.org/10.1530/eje.1.02225.

    CAS  Article  PubMed  Google Scholar 

  96. 96.

    Ambrogini E, Cetani F, Cianferotti L, Vignali E, Banti C, Viccica G, et al. Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial. J Clin Endocrinol Metab. 2007;92(8):3114–21. https://doi.org/10.1210/jc.2007-0219.

    CAS  Article  PubMed  Google Scholar 

  97. 97.

    Bollerslev J, Jansson S, Mollerup CL, Nordenstrom J, Lundgren E, Torring O, et al. Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial. J Clin Endocrinol Metab. 2007;92(5):1687–92. https://doi.org/10.1210/jc.2006-1836.

    CAS  Article  PubMed  Google Scholar 

  98. 98.

    Rao DS, Phillips ER, Divine GW, Talpos GB. Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic primary hyperparathyroidism. J Clin Endocrinol Metab. 2004;89(11):5415–22. https://doi.org/10.1210/jc.2004-0028.

    CAS  Article  PubMed  Google Scholar 

  99. 99.

    Yeh MW, Zhou H, Adams AL, Ituarte PH, Li N, Liu IL, et al. The relationship of Parathyroidectomy and bisphosphonates with fracture risk in primary hyperparathyroidism: an observational study. Ann Intern Med. 2016;164(11):715–23. https://doi.org/10.7326/M15-1232.

    Article  PubMed  Google Scholar 

  100. 100.

    Nilsson IL, Norenstedt S, Zedenius J, Pernow Y, Branstrom R. Primary hyperparathyroidism, hypercalciuria, and bone recovery after parathyroidectomy. Surgery. 2017;162(2):429–36. https://doi.org/10.1016/j.surg.2017.02.017.

    Article  PubMed  Google Scholar 

  101. 101.

    Vestergaard P, Mosekilde L. Parathyroid surgery is associated with a decreased risk of hip and upper arm fractures in primary hyperparathyroidism: a controlled cohort study. J Intern Med. 2004;255(1):108–14.

    CAS  Article  Google Scholar 

  102. 102.

    Rolighed L, Rejnmark L, Sikjaer T, Heickendorff L, Vestergaard P, Mosekilde L, et al. Vitamin D treatment in primary hyperparathyroidism: a randomized placebo controlled trial. J Clin Endocrinol Metab. 2014;99(3):1072–80. https://doi.org/10.1210/jc.2013-3978.

    CAS  Article  PubMed  Google Scholar 

  103. 103.

    Miguel GA, Carranza FH, Rodriguez JCR, Ramos MA, Pablos DL, Herrero EF, et al. Trabecular Bone score, Bone mineral density and Bone markers in patients with primary hyperparathyroidism 2 years after Parathyroidectomy. Horm Metab Res. 2019;51(3):186–90. https://doi.org/10.1055/a-0850-8679.

    CAS  Article  PubMed  Google Scholar 

  104. 104.

    Cusano NE, Rubin MR, Silva BC, Tay YD, Williams JM, Agarwal S, et al. Skeletal microstructure and estimated Bone strength improve following Parathyroidectomy in primary hyperparathyroidism. J Clin Endocrinol Metab. 2018;103(1):196–205. https://doi.org/10.1210/jc.2017-01932.

    Article  PubMed  Google Scholar 

  105. 105.

    Hansen S, Hauge EM, Rasmussen L, Jensen JE, Brixen K. Parathyroidectomy improves bone geometry and microarchitecture in female patients with primary hyperparathyroidism: a one-year prospective controlled study using high-resolution peripheral quantitative computed tomography. J Bone Miner Res. 2012;27(5):1150–8. https://doi.org/10.1002/jbmr.1540.

    Article  PubMed  Google Scholar 

  106. 106.

    Battista C, Guarnieri V, Carnevale V, Baorda F, Pileri M, Garrubba M, et al. Vitamin D status in primary hyperparathyroidism: effect of genetic background. Endocrine. 2017;55(1):266–72. https://doi.org/10.1007/s12020-016-0974-x.

    CAS  Article  PubMed  Google Scholar 

  107. 107.

    Viccica G, Cetani F, Vignali E, Miccoli M, Marcocci C. Impact of vitamin D deficiency on the clinical and biochemical phenotype in women with sporadic primary hyperparathyroidism. Endocrine. 2017;55(1):256–65. https://doi.org/10.1007/s12020-016-0931-8.

    CAS  Article  PubMed  Google Scholar 

  108. 108.

    Wang X, Shapses SA, Al-Hraishawi H. Free and bioavailable 25-Hydroxyvitamin D levels in patients with primary hyperparathyroidism. Endocr Pract. 2017;23(1):66–71. https://doi.org/10.4158/EP161434.OR.

    Article  PubMed  Google Scholar 

  109. 109.

    Chow CC, Chan WB, Li JK, Chan NN, Chan MH, Ko GT, et al. Oral alendronate increases bone mineral density in postmenopausal women with primary hyperparathyroidism. J Clin Endocrinol Metab. 2003;88(2):581–7. https://doi.org/10.1210/jc.2002-020890.

    CAS  Article  PubMed  Google Scholar 

  110. 110.

    Khan AA, Bilezikian JP, Kung A, Dubois SJ, Standish TI, Syed ZA. Alendronate therapy in men with primary hyperparathyroidism. Endocr Pract. 2009;15(7):705–13. https://doi.org/10.4158/EP08178.ORR.

    Article  PubMed  PubMed Central  Google Scholar 

  111. 111.

    Khan AA, Bilezikian JP, Kung AW, Ahmed MM, Dubois SJ, Ho AY, et al. Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial. J Clin Endocrinol Metab. 2004;89(7):3319–25. https://doi.org/10.1210/jc.2003-030908.

    CAS  Article  PubMed  Google Scholar 

  112. 112.

    Parker CR, Blackwell PJ, Fairbairn KJ, Hosking DJ. Alendronate in the treatment of primary hyperparathyroid-related osteoporosis: a 2-year study. J Clin Endocrinol Metab. 2002;87(10):4482–9. https://doi.org/10.1210/jc.2001-010385.

    CAS  Article  PubMed  Google Scholar 

  113. 113.

    Tournis S, Fakidari E, Dontas I, Liakou C, Antoniou J, Galanos A, et al. Effect of parathyroidectomy versus risedronate on volumetric bone mineral density and bone geometry at the tibia in postmenopausal women with primary hyperparathyroidism. J Bone Miner Metab. 2014;32(2):151–8. https://doi.org/10.1007/s00774-013-0473-6.

    Article  PubMed  Google Scholar 

  114. 114.

    Eller-Vainicher C, Palmieri S, Cairoli E, Goggi G, Scillitani A, Arosio M, et al. Protective effect of Denosumab on Bone in older women with primary hyperparathyroidism. J Am Geriatr Soc. 2018;66(3):518–24. https://doi.org/10.1111/jgs.15250.

    Article  PubMed  Google Scholar 

  115. 115.

    Leere JS, Karmisholt J, Robaczyk M, Lykkeboe S, Handberg A, Steinkohl E, et al. Denosumab and cinacalcet for primary hyperparathyroidism (DENOCINA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2020;8(5):407–17. https://doi.org/10.1016/S2213-8587(20)30063-2.

    CAS  Article  PubMed  Google Scholar 

  116. 116.

    Miyaoka D, Imanishi Y, Kato E, Toi N, Nagata Y, Kurajoh M, et al. Effects of denosumab as compared with parathyroidectomy regarding calcium, renal, and bone involvement in osteoporotic patients with primary hyperparathyroidism. Endocrine. 2020;69:642–9. https://doi.org/10.1007/s12020-020-02401-6.

    CAS  Article  PubMed  Google Scholar 

  117. 117.

    Peacock M, Bilezikian JP, Klassen PS, Guo MD, Turner SA, Shoback D. Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2005;90(1):135–41. https://doi.org/10.1210/jc.2004-0842.

    CAS  Article  PubMed  Google Scholar 

  118. 118.

    Marcocci C, Bollerslev J, Khan AA, Shoback DM. Medical management of primary hyperparathyroidism: proceedings of the fourth international workshop on the Management of Asymptomatic Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2014;99(10):3607–18. https://doi.org/10.1210/jc.2014-1417.

    CAS  Article  PubMed  Google Scholar 

  119. 119.

    Cetani F, Saponaro F, Banti C, Cianferotti L, Vignali E, Chiavistelli S, et al. Cinacalcet efficacy in patients with moderately severe primary hyperparathyroidism according to the European medicine agency prescription labeling. J Endocrinol Investig. 2012;35(7):655–60. https://doi.org/10.3275/7970.

    CAS  Article  Google Scholar 

  120. 120.

    Luque-Fernandez I, Garcia-Martin A, Luque-Pazos A. Experience with cinacalcet in primary hyperparathyroidism: results after 1 year of treatment. Ther Adv Endocrinol Metab. 2013;4(3):77–81. https://doi.org/10.1177/2042018813482344.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  121. 121.

    Peacock M, Bolognese MA, Borofsky M, Scumpia S, Sterling LR, Cheng S, et al. Cinacalcet treatment of primary hyperparathyroidism: biochemical and bone densitometric outcomes in a five-year study. J Clin Endocrinol Metab. 2009;94(12):4860–7. https://doi.org/10.1210/jc.2009-1472.

    CAS  Article  PubMed  Google Scholar 

  122. 122.

    Keutgen XM, Buitrago D, Filicori F, Kundel A, Elemento O, Fahey TJ 3rd, et al. Calcimimetics versus parathyroidectomy for treatment of primary hyperparathyroidism: retrospective chart analysis of a prospective database. Ann Surg. 2012;255(5):981–5. https://doi.org/10.1097/SLA.0b013e31824c5252.

    Article  PubMed  Google Scholar 

  123. 123.

    Lowe H, McMahon DJ, Rubin MR, Bilezikian JP, Silverberg SJ. Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype. J Clin Endocrinol Metab. 2007;92(8):3001–5. https://doi.org/10.1210/jc.2006-2802.

    CAS  Article  PubMed  Google Scholar 

  124. 124.

    Marques TF, Vasconcelos R, Diniz E, Rego D, Griz L, Bandeira F. Normocalcemic primary hyperparathyroidism in clinical practice: an indolent condition or a silent threat? Arq Bras Endocrinol Metabol. 2011;55(5):314–7.

    Article  Google Scholar 

  125. 125.

    Tordjman KM, Greenman Y, Osher E, Shenkerman G, Stern N. Characterization of normocalcemic primary hyperparathyroidism. Am J Med. 2004;117(11):861–3. https://doi.org/10.1016/j.amjmed.2004.06.037.

    Article  PubMed  Google Scholar 

  126. 126.

    Sho S, Kuo EJ, Chen AC, Li N, Yeh MW, Livhits MJ. Biochemical and skeletal outcomes of Parathyroidectomy for Normocalcemic (incipient) primary hyperparathyroidism. Ann Surg Oncol. 2019;26(2):539–46. https://doi.org/10.1245/s10434-018-6998-0.

    Article  PubMed  Google Scholar 

  127. 127.

    Siprova H, Frysak Z, Soucek M. Primary hyperparathyroidism, with a focus on Management of the Normocalcemic Form: to treat or not to treat? Endocr Pract. 2016;22(3):294–301. https://doi.org/10.4158/EP15704.OR.

    Article  PubMed  Google Scholar 

  128. 128.

    Palermo A, Naciu AM, Tabacco G, Falcone S, Santonati A, Maggi D, et al. Clinical, Biochemical, and Radiological Profile of Normocalcemic Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2020;105(7). https://doi.org/10.1210/clinem/dgaa174.

  129. 129.

    Wade TJ, Yen TW, Amin AL, Wang TS. Surgical management of normocalcemic primary hyperparathyroidism. World J Surg. 2012;36(4):761–6. https://doi.org/10.1007/s00268-012-1438-y.

    Article  PubMed  Google Scholar 

  130. 130.

    Cakir I, Unluhizarci K, Tanriverdi F, Elbuken G, Karaca Z, Kelestimur F. Investigation of insulin resistance in patients with normocalcemic primary hyperparathyroidism. Endocrine. 2012;42(2):419–22. https://doi.org/10.1007/s12020-012-9627-x.

    CAS  Article  PubMed  Google Scholar 

  131. 131.

    Amaral LM, Queiroz DC, Marques TF, Mendes M, Bandeira F. Normocalcemic versus Hypercalcemic primary hyperparathyroidism: more stone than Bone? J Osteoporos. 2012;2012:128352–4. https://doi.org/10.1155/2012/128352.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  132. 132.

    Diaz-Soto G, de Luis RD, Jauregui OI, Briongo L, Romero E, Perez-Castrillon JL. Trabecular Bone score in patients with Normocalcemic hyperparathyroidism. Endocr Pract. 2016;22(6):703–7. https://doi.org/10.4158/EP151055.OR.

    Article  PubMed  Google Scholar 

  133. 133.

    Rejnmark L, Vestergaard P, Brot C, Mosekilde L. Increased fracture risk in normocalcemic postmenopausal women with high parathyroid hormone levels: a 16-year follow-up study. Calcif Tissue Int. 2011;88(3):238–45. https://doi.org/10.1007/s00223-010-9454-0.

    CAS  Article  PubMed  Google Scholar 

  134. 134.

    Koumakis E, Souberbielle J-C, Sarfati E, Meunier M, Maury E, Gallimard E, et al. Bone mineral density evolution after successful parathyroidectomy in patients with normocalcemic primary hyperparathyroidism. J Clin Endocrinol Metabol. 2013;98(8):3213–20.

    CAS  Article  Google Scholar 

  135. 135.

    Cesareo R, Di Stasio E, Vescini F, Campagna G, Cianni R, Pasqualini V, et al. Effects of alendronate and vitamin D in patients with normocalcemic primary hyperparathyroidism. Osteoporos Int. 2015;26(4):1295–302. https://doi.org/10.1007/s00198-014-3000-2.

    CAS  Article  PubMed  Google Scholar 

Download references

Funding

NIH DK32333.

Author information

Affiliations

Authors

Contributions

BCS and JPB have written, revised and approved the final version of this manuscript.

Corresponding author

Correspondence to John P. Bilezikian.

Ethics declarations

Conflict of interest

Barbara C. Silva declares that she has no conflict of interest.

John P. Bilezikian is a consultant for Takeda Pharmaceuticals, Amgen and Radius.

Ethics approval

not applicable.

Consent to participate

not applicable.

Consent for publication

not applicable.

Code availability

not applicable.

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

Verify currency and authenticity via CrossMark

Cite this article

Silva, B.C., Bilezikian, J.P. Skeletal abnormalities in Hypoparathyroidism and in Primary Hyperparathyroidism. Rev Endocr Metab Disord (2020). https://doi.org/10.1007/s11154-020-09614-0

Download citation

Keywords

  • Hypoparathyroidism
  • Primary hyperparathyroidism
  • Fracture risk
  • Osteoporosis
  • PTH(1–84)
  • Parathyroidectomy