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Skeletal changes after restoration of the euparathyroid state in patients with hypoparathyroidism and primary hyperparathyroidism

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Abstract

Restoration of the euparathyroid state is associated with improvement of bone dynamics both in hypoparathyroidism and primary hyperparathyroidism. To date, no study has directly compared these two groups following correction of parathyroid hormone excess or deficiency. The study was designed to investigate changes in bone mineral density and trabecular bone score with restoration of the euparathyroid state by parathyroidectomy in primary hyperparathyroidism or recombinant parathyroid hormone [rhPTH(1-84)] replacement in hypoparathyroidism. This was a 2-year prospective intervention study in which we evaluated areal bone mineral density by DXA and trabecular bone score in 52 hypoparathyroid patients on rhPTH(1-84) replacement and 27 patients with primary hyperparathyroidism who underwent parathyroidectomy. We evaluated changes in areal bone mineral density by DXA and trabecular bone score at baseline, 6, 12, 18, and 24 months. After parathyroidectomy, areal bone mineral density increased from baseline at the lumbar spine and total hip at 6 months and at the femoral neck at 12 months, while there were no changes at the distal 1/3 radius. Treatment with rhPTH(1-84) was associated with significant increases in lumbar spine and decreases in distal 1/3 radius areal bone mineral density by 18 months in hypoparathyroid patients. At this time point, hypoparathyroid subjects demonstrated a significant increase in trabecular bone score from baseline, while there were no significant changes in trabecular bone score following parathyroidectomy. Bone mineral density increases both with administration of parathyroid hormone in a state of parathyroid hormone deficiency or removal of parathyroid hormone in a state of parathyroid hormone excess. However, only hypoparathyroid patients on rhPTH(1-84) appeared to have improvements in micro-architectural pattern as assessed by trabecular bone score.

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References

  1. B.C. Silva, A.G. Costa, N.E. Cusano, S. Kousteni, J.P. Bilezikian, Catabolic and anabolic actions of parathyroid hormone on the skeleton. J. Endocrinol. Invest. 34, 801–810 (2011)

    CAS  PubMed  PubMed Central  Google Scholar 

  2. S.J. Silverberg, E. Shane, L. de la Cruz, D.W. Dempster, F. Feldman, D. Seldin, T.P. Jacobs, E.S. Siris, M. Cafferty, M.V. Parisien, R. Lindsay, T.L. Clemens, J.P. Bilezikian, Skeletal disease in primary hyperparathyroidism. J. Bone Miner. Res. 4, 283–291 (1989)

    Article  CAS  PubMed  Google Scholar 

  3. D.W. Dempster, R. Muller, H. Zhou, T. Kohler, E. Shane, M. Parisien, S.J. Silverberg, J.P. Bilezikian, Preserved three-dimensional cancellous bone structure in mild primary hyperparathyroidism. Bone 41, 19–24 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. B.L. Langdahl, L. Mortensen, A. Vesterby, E.F. Eriksen, P. Charles, Bone histomorphometry in hypoparathyroid patients treated with vitamin D. Bone. 18, 103–108 (1996)

    Article  CAS  PubMed  Google Scholar 

  5. 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, 2018–2024 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. N.E. Cusano, K.K. Nishiyama, C. Zhang, M.R. Rubin, S. Boutroy, D.J. McMahon, X.E. Guo, J.P. Bilezikian, Non-invasive assessment of skeletal microstructure and estimated bone strength in hypoparathyroidism. J. Bone Miner. Res. (2015). doi:10.1002/jbmr.2609

  7. J.P. Bilezikian, A. Khan, J.T. Potts Jr., M.L. Brandi, B.L. Clarke, D. Shoback, H. Jüppner, P. D’Amour, J. Fox, L. Rejnmark, L. Mosekilde, M.R. Rubin, D. Dempster, R. Gafni, M.T. Collins, J. Sliney, J. Sanders, Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research. J. Bone Miner. Res. 26, 2317–2337 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. S. Khosla, L.J. Melton 3rd, R.A. Wermers, C.S. Crowson, W. O’Fallon, B. Riggs, Primary hyperparathyroidism and the risk of fracture: a population-based study. J. Bone Miner. Res. 14, 1700–1707 (1999)

    Article  CAS  PubMed  Google Scholar 

  9. E. Vignali, G. Viccica, D. Diacinti, F. Cetani, L. Cianferotti, E. Ambrogini et al., Morphometric vertebral fractures in postmenopausal women with primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 94, 2306–2312 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. P. Vestergaard, L. Mosekilde, Fractures in patients with primary hyperparathyroidism: nationwide follow-up study of 1201 patients. World J. Surg. 27, 343–349 (2003)

    Article  PubMed  Google Scholar 

  11. N. Yu, P.T. Donnan, R.W. Flynn, M.J. Murphy, D. Smith, A. Rudman, G.P. Leese, Increased mortality and morbidity in mild primary hyperparathyroid patients. The Parathyroid Epidemiology and Audit Research Study (PEARS). Clin. Endocrinol. (Oxf.) 73, 30–34 (2010)

    Google Scholar 

  12. J.P. Roux, J. Wegrzyn, S. Boutroy, M.L. Bouxsein, D. Hans, R. Chapurlat, The predictive value of trabecular bone score (TBS) on whole lumbar vertebrae mechanics: an ex vivo study. Osteoporos. Int. 24, 2455–2460 (2013)

    Article  CAS  PubMed  Google Scholar 

  13. C. Muschitz, R. Kocijan, J. Haschka, D. Pahr, A. Kaider, P. Pietschmann, D. Hans, G.K. Muschitz, A. Fahrleitner-Pammer, H. Resch, BS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures. Bone 79, 259–266 (2015)

    Article  PubMed  Google Scholar 

  14. S. Hansen, J.E. Beck Jensen, L. Rasmussen, E.M. Hauge, K. Brixen, 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. 25, 1941–1947 (2010)

    Article  PubMed  Google Scholar 

  15. B.C. Silva, S. Boutroy, C. Zhang, D.J. McMahon, B. Zhou, J. Wang, J. Udesky, S. Cremers, M. Sarquis, X.D. Guo, D. Hans, J.P. Bilezikian, Trabecular bone score (TBS)--a novel method to evaluate bone microarchitectural texture in patients with primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 98, 1963–1970 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. E.M. Stein, B.C. Silva, S. Boutroy, B. Zhou, J. Wang, J. Udesky, C. Zhang, D.J. McMahon, M. Romano, E. Dworakowski, A.G. Costa, N. Cusano, D. Irani, S. Cremers, E. Shane, X.E. Guo, J.P. Bilezikian, Primary hyperparathyroidism is associated with abnormal cortical and trabecular microstructure and reduced bone stiffness in postmenopausal women. J. Bone Miner. Res. 28, 1029–1040 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  17. S.J. Silverberg, E. Shane, T.P. Jacobs, E. Siris, J.P. Bilezikian, A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N. Engl. J. Med. 341, 1249–1255 (1999)

    Article  CAS  PubMed  Google Scholar 

  18. M.R. Rubin, J.P. Bilezikian, D.J. McMahon, T. Jacobs, E. Shane, E. Siris, J. Udesky, S.J. Silverberg, The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J. Clin. Endocrinol. Metab. 93, 3462–3470 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. S.J. Silverberg, F. Gartenberg, T.P. Jacobs, E. Shane, E. Siris, R.B. Staron, D.J. McMahon, J.P. Bilezikian, Increased bone mineral density after parathyroidectomy in primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 80, 729–734 (1995)

    CAS  PubMed  Google Scholar 

  20. C. Eller-Vainicher, M. Filopanti, S. Palmieri, F.M. Ulivieri, V. Morelli, V.V. Zhukouskaya, E. Cairoli, R. Pino, A. Naccarato, U. Verga, A. Scillitani, P. Beck-Peccoz, I. Chiodini, Bone quality, as measured by trabecular bone score, in patients with primary hyperparathyroidism. Eur. J. Endocrinol. 169, 155–162 (2013)

    Article  CAS  PubMed  Google Scholar 

  21. L. Underbjerg, T. Sikjaer, L. Mosekilde, L. Rejnmark, Postsurgical hypoparathyroidism--risk of fractures, psychiatric diseases, cancer, cataract, and infections. J. Clin. Endocrinol. Metab. 29, 2504–2510 (2014)

    Google Scholar 

  22. M.L. Mendonça, 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. (2013). doi: 10.1186/1472-6823-13-1

  23. 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, 2727–2736 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. N.E. Cusano, M.R. Rubin, D.J. McMahon, C. Zhang, R. Ives, A. Tulley, J. Sliney Jr, S.C. Cremers, J.P. Bilezikian, Therapy of hypoparathyroidism with PTH(1-84): a prospective four-year investigation of efficacy and safety. J. Clin. Endocrinol. Metab. 98, 137–144 (2013)

    Article  CAS  PubMed  Google Scholar 

  25. Y. Duan, V. De Luca, E. Seeman, Parathyroid hormone deficiency and excess: similar effects on trabecular bone but differing effects on cortical bone. J. Clin. Endocrinol. Metab. 84, 718–722 (1999)

    Article  CAS  PubMed  Google Scholar 

  26. Q. Chen, H. Kaji, M.F. Iu, R. Nomura, H. Sowa, M. Yamauchi, T. Tsukamoto, T. Sugimoto, K. Chihara, 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. 88, 4655–4658 (2003)

    Article  CAS  PubMed  Google Scholar 

  27. M.R. Rubin, J. Sliney Jr., D.J. McMahon, S.J. Silverberg, J.P. Bilezikian, Therapy of hypoparathyroidism with intact parathyroid hormone. Osteoporos. Int. 21, 1927–1934 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. N.E. Cusano, M.R. Rubin, D.J. McMahon, D. Irani, L. Anderson, E. Levy et al.. PTH(1-84) is associated with improved quality of life in hypoparathyroidism through 5 years of therapy. J. Clin. Endocrinol. Metab. 99, 3694–3699 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. J.P. Bilezikian, A.A. Khan, J.T. Potts Jr., Third International Workshop on the Management of Asymptomatic Primary H. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop. J. Clin. Endocrinol. Metab. 94, 335–339 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. N.C. Harvey, C.C. Glüer, N. Binkley, E.V. McCloskey, M.L. Brandi, C. Cooper, D. Kendler, O. Lamy, A. Laslop, B.M. Camargos, J.Y. Reginster, R. Rizzoli, J.A. Kanis, Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice. Bone 78, 216–224 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. P.D. Miller, P.D. Delmas, R. Lindsay, N.B. Watts, M. Luckey, J. Adachi, K. Saag, S.L. Greenspan, E. Seeman, S. Boonen, S. Meeves, T.F. Lang, J.P. Bilezikian, Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate. J. Clin. Endocrinol. Metab. 93, 3785–3793 (2008)

    Article  CAS  PubMed  Google Scholar 

  32. R.M. Neer, C.D. Arnaud, J.R. Zanchetta, R. Prince, G.A. Gaich, J.Y. Reginster, A.B. Hodsman, E.F. Eriksen, S. Ish-Shalom, H.K. Genant, O. Wang, B.H. Mitlak, Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. 344, 1434–41 (2001)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  34. R.P. Heaney, The basis for the post-parathyroidectomy increase in bone mass. J. Bone Miner. Res. 17(Suppl 2), N154–157 (2002)

    PubMed  Google Scholar 

  35. E. Romagnoli, C. Cipriani, I. Nofroni, C. Castro, M. Angelozzi, A. Scarpiello, J. Pepe, D. Diacinti, S. Piemonte, V. Carnevale, S. Minisola, Trabecular Bone Score (TBS): an indirect measure of bone micro-architecture in postmenopausal patients with primary hyperparathyroidism. Bone 53, 154–159 (2013)

    Article  PubMed  Google Scholar 

  36. C. Cipriani, B.C. Silva, N. Cusano, A. Costa, D. Irani, A. Abraham, D. McMahon, L.B. Anderson, E. Levy, M. Rubin, J.P. Bilezikian, Beneficial Effects of PTH(1-84) in Hypoparathyroidism as Determined by Trabecular Bone Score (TBS) 2014 ASBMR poste # SU0015 (2014)

  37. S. Hansen, E.M. Hauge, L. Rasmussen, J.E. Jensen, K. Brixen, 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. 27, 1150–1158 (2012)

    Article  PubMed  Google Scholar 

  38. L. Rolighed, L. Rejnmark, T. Sikjaer, L. Heickendorff, P. Vestergaard, L. Mosekilde, P. Christiansen, Vitamin D treatment in primary hyperparathyroidism: a randomized placebo controlled trial. J. Clin. Endocrinol. Metab. 99, 1072–1080 (2014)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We want to acknowledge support from National Institutes of Health DK069350, DK 32333, and DK074457.

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Authors and Affiliations

  1. Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, USA

    Cristiana Cipriani, Alice Abraham, Barbara C. Silva, Natalie E. Cusano, Mishaela R. Rubin, Donald J. McMahon, Chengchen Zhang, Shonni J. Silverberg & John P. Bilezikian

  2. Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Rome, Italy

    Cristiana Cipriani

  3. Medical School, Federal University of Minas Gerais, Belo Horizonte, Brazil

    Barbara C. Silva

  4. Center of Bone Diseases, Lausanne University Hospital, Lausanne, Switzerland

    Didier Hans

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  1. Cristiana Cipriani
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  2. Alice Abraham
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  3. Barbara C. Silva
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  4. Natalie E. Cusano
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  5. Mishaela R. Rubin
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  9. Shonni J. Silverberg
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  10. John P. Bilezikian
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Correspondence to John P. Bilezikian.

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DH is co-owner of the TBS patent and has corresponding ownership shares and interest in Medimaps group. All the other authors have nothing to disclose.

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Cristiana Cipriani and Alice Abraham are co-primary authors

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Cipriani, C., Abraham, A., Silva, B.C. et al. Skeletal changes after restoration of the euparathyroid state in patients with hypoparathyroidism and primary hyperparathyroidism. Endocrine 55, 591–598 (2017). https://doi.org/10.1007/s12020-016-1101-8

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