Skip to main content
SpringerLink
Log in

Vitamin D in hypoparathyroidism: insight into pathophysiology and perspectives in clinical practice

  • Mini Review
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by the absence or insufficient parathyroid hormone production resulting in chronic hypocalcemia. Complications of HypoPT include perturbation of several target organs. The conventional treatment consists of the administration of active vitamin D, namely calcitriol. Regarding vitamin D status, few data are available, mostly in HypoPT subjects supplemented with parent vitamin D. In addition, perturbation of vitamin D metabolism has been poorly investigated, as well as the contribution of altered vitamin D status on the clinical expression of the disease. The most recent consensus on the management of chronic HypoPT suggests the baseline evaluation of serum 25-hydroxy-vitamin D [25(OH)D] and supplementation with parent vitamin D with the aim to achieve and maintain serum 25(OH)D levels in the range of 30–50 ng/mL. The rationale for using supplementation with parent vitamin D (either ergocalciferol or cholecalciferol) in HypoPT would be to provide sufficient 25(OH)D substrate to the residual 1-α-hydroxylase activity, thus ensuring its conversion to active vitamin D in renal and extra-renal tissues. More data from experimental and clinical studies are needed for better assessing how these mechanisms may significantly influence metabolic control in HypoPT and eventually skeletal and extra-skeletal manifestation of the disease. Finally, future data will clarify how the currently available parent vitamin D compounds (ergocalciferol, cholecalciferol, calcifediol) would perform in addressing these specific issues.

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

Similar content being viewed by others

References

  1. S. Bjornsdottir, S. Ing, D.M. Mitchell, T. Sikjaer, L. Underbjerg, Z. Hassan-Smith, J. Sfeir, N.J. Gittoes, B.L. Clarke, Epidemiology and financial burden of adult chronic hypoparathyroidism. J. Bone Miner. Res. 37, 2602–2614 (2022). https://doi.org/10.1002/jbmr.4675

    Article  PubMed  Google Scholar 

  2. J.L. Pasieka, K. Wentworth, C.T. Yeo, S. Cremers, D. Dempster, S. Fukumoto, R. Goswami, P. Houillier, M.A. Levine, J.D. Pasternak, N.D. Perrier, A. Sitges-Serra, D.M. Shoback, Etiology and pathophysiology of hypoparathyroidism: a narrative review. J. Bone Miner. Res. 37, 2586–2601 (2022). https://doi.org/10.1002/jbmr.4714

    Article  PubMed  Google Scholar 

  3. L.H.X. Yao, M. Li, J. Li, M.M. Ahmed, C. Lin, M. Kandi, A. Sreekanta, N. Makhdami, D. Tamilselvan, D.S. Ali, K. Dandurand, K. Yang, J.P. Bilezikian, M.L. Brandi, B.L. Clarke, M. Mannstadt, L. Rejnmark, A.A. Khan, G. Guyatt, Complications, symptoms, presurgical predictors in patients with chronic hypoparathyroidism: a systematic review. J. Bone Min. Metab. 37, 2642–2653 (2022). https://doi.org/10.1002/jbmr.4673

    Article  CAS  Google Scholar 

  4. M.L. Brandi, J.P. Bilezikian, D. Shoback, R. Bouillon, B.L. Clarke, R.V. Thakker, A.A. Khan, J.T. Potts Jr., Management of hypoparathyroidism: summary statement and guidelines. J. Clin. Endocrinol. Metab. 101(6), 2273–2283 (2016). https://doi.org/10.1210/jc.2015-3907

    Article  CAS  PubMed  Google Scholar 

  5. J. Bollerslev, L. Rejnmark, C. Marcocci, D.M. Shoback, A. Sitges-Serra, W. van Biesen, O.M. Dekkers; European Society of Endocrinology, European Society of Endocrinology Clinical Guideline: treatment of chronic hypoparathyroidism in adults. Eur. J. Endocrinol. 173(2), G1–G20 (2015). https://doi.org/10.1530/EJE-15-0628

    Article  CAS  PubMed  Google Scholar 

  6. A.A. Khan, J.P. Bilezikian, M.L. Brandi, B.L. Clarke, N.J. Gittoes, J.L. Pasieka, L. Rejnmark, D.M. Shoback, J.T. Potts, G.H. Guyatt, M. Mannstadt, Evaluation and management of hypoparathyroidism summary statement and guidelines from the Second International Workshop. J. Bone Min. Metab. 37, 2568–2585 (2022). https://doi.org/10.1002/jbmr.4691

    Article  Google Scholar 

  7. M.C. Chapuy, P. Preziosi, M. Maamer, S. Arnaud, P. Galan, S. Hercberg, P.J. Meunier, Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos. Int. 7(5), 439–443 (1997)

    Article  CAS  PubMed  Google Scholar 

  8. F. Ferrone, J. Pepe, V.C. Danese, V. Fassino, V. Cecchetti, F. De Lucia, F. Biamonte, L. Colangelo, G. Ferrazza, E. Panzini, A. Scillitani, L. Nieddu, F. Blocki, S.D. Rao, S. Minisola, C. Cipriani, The relative influence of serum ionized calcium and 25-hydroxyvitamin D in regulating PTH secretion in healthy subjects. Bone 125, 200–206 (2019). https://doi.org/10.1016/j.bone.2019.05.029

    Article  CAS  PubMed  Google Scholar 

  9. R.F. Chun, B.E. Peercy, E.S. Orwoll, C.M. Nielson, J.S. Adams, M. Hewison, Vitamin D and DBP: the free hormone hypothesis revisited. J. Steroid Biochem. Mol. Biol. 144PA, 132–137 (2014). https://doi.org/10.1016/j.jsbmb.2013.09.012

    Article  CAS  Google Scholar 

  10. N. Latic, R.G. Erben, Interaction of vitamin D with peptide hormones with emphasis on parathyroid hormone, FGF23, and the renin-angiotensin-aldosterone system. Nutrients 14, 5186 (2022). https://doi.org/10.3390/nu14235186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. C. Cipriani, E. Romagnoli, A. Scillitani, I. Chiodini, R. Clerico, V. Carnevale, M.L. Mascia, C. Battista, R. Viti, M. Pileri, C. Eller-Vainicher, S. Minisola, Effect of a single oral dose of 600,000 IU of cholecalciferol on serum calciotropic hormones in young subjects with vitamin D deficiency: a prospective intervention study. J. Clin. Endocrinol. Metab. 95(10), 4771–4777 (2010). https://doi.org/10.1210/jc.2010-0502

    Article  CAS  PubMed  Google Scholar 

  12. M. Rossini, D. Gatti, O. Viapiana, E. Fracassi, L. Idolazzi, S. Zanoni, S. Adami, Short-term effects on bone turnover markers of a single high dose of oral vitamin D(3). J. Clin. Endocrinol. Metab. 97(4), E622–E626 (2012). https://doi.org/10.1210/jc.2011-2448

    Article  CAS  PubMed  Google Scholar 

  13. L. Cianferotti, C. Cricelli, J.A. Kanis, R. Nuti, J.Y. Reginster, J.D. Ringe, R. Rizzoli, M.L. Brandi,, The clinical use of vitamin D metabolites and their potential developments: a position statement from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the International Osteoporosis Foundation (IOF). Endocrine 50(1), 12–26 (2015). https://doi.org/10.1007/s12020-015-0606-x

    Article  CAS  PubMed  Google Scholar 

  14. R. Bouillon, C. Marcocci, G. Carmeliet, D. Bikle, J.H. White, B. Dawson-Hughes, P. Lips, C.F. Munns, M. Lazaretti-Castro, A. Giustina, J.P. Bilezikian, Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocr. Rev. 40, 1109–1151 (2019). https://doi.org/10.1210/er.2018-00126

    Article  PubMed  Google Scholar 

  15. M.F. Holick, L. Mazzei, S. Garcia Menéndez, V.M. Martín Giménez, F. Al Anouti, W. Manucha, Genomic or non-genomic? A question about the pleiotropic roles of vitamin D in inflammatory-based diseases. Nutrients 15, 767 (2023). https://doi.org/10.3390/nu15030767

  16. M.R. Rubin, D.W. Dempster, H. Zhou, E. Shane, T. Nickolas, J. Sliney Jr., S.J. Silverberg, J.P. Bilezikian, Dynamic and structural properties of the skeleton in hypoparathyroidism. J. Bone Miner. Res. 23(12), 2018–2024 (2008). https://doi.org/10.1359/jbmr.080803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. M.R. Rubin, D.W. Dempster, J. Sliney Jr, H. Zhou, T.L. Nickolas, E.M. Stein, E. Dworakowski, M. Dellabadia, R. Ives, D.J. McMahon, C. Zhang, S.J. Silverberg, E. Shane, S. Cremers, J.P. Bilezikian, PTH(1-84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism. J. Bone Miner. Res. 26(11), 2727–2736 (2011). https://doi.org/10.1002/jbmr.452

    Article  CAS  PubMed  Google Scholar 

  18. M.L. Mendonca, F.A. Pereira, M.H. Nogueira-Barbosa, L.M. Monsignore, S.R. Teixeira, P.C. Watanabe, L.M. Maciel, F.J. de Paula, Increased vertebral morphometric fracture in patients with postsurgical hypoparathyroidism despite normal bone mineral density. BMC Endocr. Disord. 13, 1 (2013). https://doi.org/10.1186/1472-6823-13-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. A. Santonati, A. Palermo, E. Maddaloni, D. Bosco, A. Spada, F. Grimaldi, B. Raggiunti, R. Volpe, S. Manfrini, F. Vescini; the Hypoparathyroidism AME Group, PTH(1–34) for surgical hypoparathyroidism: a prospective, open-label investigation of efficacy and quality of life. J. Clin. Endocrinol. Metab. 100, 3590–3597 (2015). https://doi.org/10.1210/jc.2015-1855

    Article  CAS  PubMed  Google Scholar 

  20. N.E. Cusano, K.K. Nishiyama, C. Zhang, M.R. Rubin, S. Boutroy, D.J. McMahon, X.E. Guo, J.P. Bilezikian, Noninvasive assessment of skeletal microstructure and estimated bone strength in hypoparathyroidism. J. Bone Miner. Res. 31(2), 308–316 (2016). https://doi.org/10.1002/jbmr.2609

    Article  PubMed  Google Scholar 

  21. B.L. Clarke, T.J. Vokes, J.P. Bilezikian, D.M. Shoback, H. Lagast, M. Mannstadt, Effects of parathyroid hormone rhPTH(1–84) on phosphate homeostasis and vitamin D metabolism in hypoparathyroidism: REPLACE phase 3 study. Endocrine 55, 273–282 (2017). https://doi.org/10.1007/s12020-016-1141-0

  22. H. Chawla, S. Saha, D. Kandasamy, R. Sharma, V. Sreenivas, R. Goswami, Vertebral fractures and bone mineral density in patients with idiopathic hypoparathyroidism on long-term follow-up. J. Clin. Endocrinol. Metab. 102(1), 251–258 (2017). https://doi.org/10.1210/jc.2016-3292

    Article  PubMed  Google Scholar 

  23. G. Marcucci, L. Cianferotti, S. Parri, P. Altieri, E. Arvat, S. Benvenga, C. Betterle, M. Bondanelli, M. Boscaro, V. Camozzi, G.M. Centaro, F. Cetani, I. Chiodini, A. Ciampolillo, A. Colao, S. Corbetta, M.L. De Feo, E. Degli Uberti, A. Faggiano, R. Fornari, A.L. Gaspari, F. Giorgino, V. Giuliani, M. Iacobone, N. Innaro, O. Lamacchia, A. Lenzi, G. Mantovani, C. Marcocci, L. Masi, S. Migliaccio, S. Palmieri, R. Pasquali, G. Perigli, V. Piccini, E. Romagnoli, R.M. Ruggeri, F. Rulli, M.T. Samà, G. Tomaino, F. Trimarchi, M.C. Zatelli, M.L. Brandi, HypoparaNet: a database of chronic hypoparathyroidism based on expert medical-surgical Centers in Italy. Calcif. Tissue Int. 103, 151–163 (2018). https://doi.org/10.1007/s00223-018-0411-7

    Article  CAS  PubMed  Google Scholar 

  24. A.V.E. Meola, A. Matrone, F. Cetani, C. Marcocci, Efficacy and safety of long-term management of patients with chronic post-surgical hypoparathyroidism. J. Endocrinol. Invest. 41, 1221–1226 (2018). https://doi.org/10.1007/s40618-018-0857-5

    Article  CAS  PubMed  Google Scholar 

  25. G. Marcucci, G. Beccuti, G. Carosi, F. Cetani, L. Cianferotti, A.M. Colao, C. Di Somma, M. Duradoni, A. Elefante, L. Ghizzoni, M. Giusti, A.G. Lania, E. Lavezzi, B. Madeo, G. Mantovani, C. Marcocci, L. Masi, S. Parri, F. Pigliaru, A. Santonati, A. Spada, L. Vera, M.L. Brandi, Multicenter retro‑prospective observational study on chronic hypoparathyroidism and rhPTH (1–84) treatment. J. Endocrinol. Invest. 45, 1653–1662 (2022). https://doi.org/10.1007/s40618-022-01800-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. L. Mazoni, A. Matrone, M. Apicella, F. Saponaro, S. Borsari, E. Pardi, B. Cosci, I. Biagioni, P. Rossi, F. Pacciardi, A. Scionti, R. Elisei, C. Marcocci, F. Cetani, Renal complications and quality of life in postsurgical hypoparathyroidism: a case–control study. J. Endocrinol. Invest. 45, 573–582 (2022). https://doi.org/10.1007/s40618-021-01686-2

    Article  CAS  PubMed  Google Scholar 

  27. A.M. Naciu, G. Tabacco, J.P. Bilezikian, A. Santonati, D. Bosco, G.G. Incognito, G. Gaspa, S. Manfrini, A. Falchetti, P. Trimboli, G. Mazziotti, N. Napoli, G. Sanson, R. Cesareo, F. Vescini, P. Palermo, Calcium citrate versus calcium carbonate in the management of chronic hypoparathyroidism: a randomized, double-blind, crossover clinical trial. J. Bone Miner. Res. 37, 1251–1259 (2022). https://doi.org/10.1002/jbmr.4564

    Article  CAS  PubMed  Google Scholar 

  28. F. Saponaro, G. Alfi, F. Cetani, A. Matrone, L. Mazoni, M. Apicella, E. Pardi, S. Borsari, M. Laurino, E. Lai, A. Gemignani, C. Marcocci, Serum calcium levels are associated with cognitive function in hypoparathyroidism: a neuropsychological and biochemical study in an Italian cohort of patients with chronic post-surgical hypoparathyroidism. J. Endocrinol. Invest. 45, 1909–1918 (2022). https://doi.org/10.1007/s40618-022-01822-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. A. Zhukov, A. Povaliaeva, Z. Abilov, E. Kovaleva, L. Usoltseva, A. Eremkina, V. Ioutsi, L. Dzeranova, E. Pigarova, L. Rozhinskaya, N. Mokrysheva, Parameters of vitamin D metabolism in patients with hypoparathyroidism. Metabolites 12, 1–9 (2022). https://doi.org/10.3390/metabo12121279

    Article  CAS  Google Scholar 

  30. S. Agarwal, D.J. McMahon, J. Chen, A. Brossfield, J. Fernando, J.P. Bilezikian, N.E. Cusano, M.R. Rubin, The clinical and skeletal effects of long-term therapy of hypoparathyroidism with rhPTH(1-84). J. Bone Miner. Res. (2023). https://doi.org/10.1002/jbmr.4780

  31. A.A. Khan, M.R. Rubin, P. Schwarz, T. Vokes, D.M. Shoback, C. Gagnon, A. Palermo, C. Marcocci, B.L. Clarke, L.G. Abbott, L.C. Hofbauer, L. Kohlmeier, S. Pihl, X. An, W.F. Eng, A.R. Smith, J. Ukena, C.T. Sibley, A.D. Shu, L. Rejnmark, Efficacy and safety of parathyroid hrmone replacement with TransCon PTH in hypoparathyroidism: 26-week results from the phase 3 PaTHway Trial. J. Bone Miner. Res. 38, 14–25 (2023). https://doi.org/10.1002/jbmr.4726

    Article  CAS  PubMed  Google Scholar 

  32. F. Holtz, Die Behandlung der postoperativen Tetanie. Arch. f. klin. Chir. (Proc.) 177, 32 (1933)

  33. E.A. Streeten, Y. Mohtasebi, M. Konig, L. Davidoff, K. Ryan, Hypoparathyroidism: less severe hypocalcemia with treatment with vitamin D2 compared with calcitriol. J. Clin. Endocrinol. Metab. 102, 1505–1510 (2017). https://doi.org/10.1210/jc.2016-3712

    Article  PubMed  PubMed Central  Google Scholar 

  34. F. Albright, H.W. Sulkowitch, E. Bloomberg, A comparison of the effects of vitamin d, dihydro-tachysterol (a.t. 10), and parathyroid extract on the disordered metabolism of rickets. J. Clin. Invest. 18, 165–169 (1939). https://doi.org/10.1172/JCI101019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. D.M. Mitchell, S. Regan, M.R. Cooley, K.B. Lauter, M.C. Vrla, C.B. Becker, S.A. Burnett-Bowie, M. Mannstadt, Long-term follow-up of patients with hypoparathyroidism. J. Clin. Endocrinol. Metab. 97(12), 4507–4514 (2012). https://doi.org/10.1210/jc.2012-1808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. A.A. Khan, G. Guyatt, D.S. Ali, J.P. Bilezikian, M.T. Collins, K. Dandurand, M. Mannstadt, D. Murphy, I. M’Hiri, M.R. Rubin, R. Sanders, M. Shrayyef, H. Siggelkow, G. Tabacco, Y.K.D. Tay, S. Van Uum, T. Vokes, K.K. Winer, L. Yao, L. Rejnmark, Management of hypoparathyroidism. J. Bone Miner. Res. 37, 2663–2677 (2022). https://doi.org/10.1002/jbmr.4716

    Article  CAS  PubMed  Google Scholar 

  37. R.F.Y. Miura, S. Yumita, H.E. Sohn, K. Mizunashi, K. Yoshinaga, 25-Hydroxyvitamin D3 loading test in primary hyperparathyroidism, hypoparathyroidism and pseudohypoparathyroidism. Endocrinol. Jpn 34, 97–104 (1987). https://doi.org/10.1507/endocrj1954.34.97

    Article  CAS  PubMed  Google Scholar 

  38. B.L. Clarke, Hypoparathyroidism: update of guidelines from the 2022 International Task Force. Arch. Endocrinol. Metab. 66, 604–610 (2022). https://doi.org/10.20945/2359-3997000000549

    Article  PubMed  PubMed Central  Google Scholar 

  39. Y. Lou, I. Laaksi, A. Syvala, M. Blauer, T.L.J. Tammela, T. Ylikomi, P. Tuohimaa, 25-hydroxyvitamin D3 is an active hormone in human primary prostatic stromal cells. FASEB J. 18, 332–334 (2004)

    Article  CAS  PubMed  Google Scholar 

  40. Y.R. Lou, F. Molnár, M. Peräkylä, S. Qiao, A.V. Kalueff, R. St-Arnaud, C. Carlberg, P. Tuohimaa, 25-Hydroxyvitamin D-3 is an agonistic vitamin D receptor ligand. J. Steroid Biochem. Mol. Biol. 118, 162–170 (2010). https://doi.org/10.1016/j.jsbmb.2009.11.011

    Article  CAS  PubMed  Google Scholar 

  41. Y.R. Lou, T.C. Toh, Y.H. Tee, H. Yu, 25‐Hydroxyvitamin D3 induces osteogenic differentiation of human mesenchymal stem cells. Sci. Rep. 7, 42816 (2017). https://doi.org/10.1038/srep42816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. M.Y.K. Nishikawa, M. Takamatsu, K. Abe, K. Okamoto, K. Horibe, H. Mano, K. Nakagawa, N. Tsugawa, Y. Hirota, T. Horie, E. Hinoi, T. Okano, S. Ikushiro, T. Sakaki, Generation of novel genetically modified rats to reveal the molecular mechanisms of vitamin D actions. Sci. Rep. 10(1), 5677 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy

    Cristiana Cipriani

  2. Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale GB Morgagni 50, Florence, 50134, Italy

    Luisella Cianferotti

Authors
  1. Cristiana Cipriani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luisella Cianferotti
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to the ideation, literature search, drafting and final revision of the manuscript.

Corresponding author

Correspondence to Cristiana Cipriani.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cipriani, C., Cianferotti, L. Vitamin D in hypoparathyroidism: insight into pathophysiology and perspectives in clinical practice. Endocrine 81, 216–222 (2023). https://doi.org/10.1007/s12020-023-03354-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-023-03354-2

Keywords

Search

Navigation