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Vertebral fractures, trabecular bone score and their determinants in chronic hypoparathyroidism

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Abstract

Purpose

Patients with hypoparathyroidism are at risk of vertebral fractures (VFs) despite high bone mineral density (BMD). We investigated this paradox by assessing trabecular bone score (TBS) and hip structural analysis (HSA) in non-surgical chronic hypoparathyroidism (cHypoPT) with and without VFs.

Methods

152 cHypoPT patients (age 40.2 ± 13.4 years, M: F = 81:71) with a median follow-up of 8 (2–13) years were assessed for BMD, VFs, TBS, and HSA and compared with 152 healthy controls. VFs at T7–L4 were assessed by Genant’s method. Average serum total calcium and phosphorus during follow-up were assessed.

Results

The lumbar spine and hip BMD were higher by 25.4 and 13.4% in cHypoPT than controls (P < 0.001). Paradoxically, VFs (30.9 vs.7.9%), including multiple (12.5 vs. 2.6%) were higher in cHypoPT (P < 0.001). Though overall average TBS (1.411 ± 0.091) was normal in cHypoPT, 25.4% of the females had subnormal TBS, more in post than pre-menopausal women (52.3 vs. 14%, P = 0.002) and as compared to males (6.1%, P = 0.001). TBS correlated with menopausal status and follow-up serum calcium–phosphorus product. For every gm/cm2 rise in BMD, TBS increase was only 0.227 in cHypoPT compared to 0.513 in controls. Frequency of VFs increased with declining TBS (P = 0.004). HSA was comparable between cHypoPT with and without VFs. 23.4% of cHypoPT with VFs had subnormal TBS.

Conclusion

31% of cHypoPT patients had VFs. TBS indicated degraded bone microarchitecture in 50% of the post-menopausal cHypoPT women. However, TBS has limitations to detect abnormal bone microarchitecture in cHypoPT as only one-fourth of patients with VFs showed low TBS.

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Data availability

All datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Cipriani C, Abraham A, Silva BC, Cusano NE, Rubin MR, McMahon DJ, Zhang C, Hans D, Silverberg SJ, Bilezikian JP (2017) Skeletal changes after restoration of the euparathyroid state in patients with hypoparathyroidism and primary hyperparathyroidism. Endocrine 55:591–598

    Article  CAS  PubMed  Google Scholar 

  2. Laway BA, Goswami R, Singh N, Gupta N, Seith A (2006) Pattern of bone mineral density in patients with sporadic idiopathic hypoparathyroidism. Clin Endocrinol (Oxford) 64:405–409

    CAS  Google Scholar 

  3. Chawla H, Saha S, Kandasamy D, Sharma R, Sreenivas V, Goswami R (2017) Vertebral fractures and bone mineral density in patients with idiopathic hypoparathyroidism on long-term follow-up. J Clin Endocrinol Metab 102:251–258

    PubMed  Google Scholar 

  4. Cipriani C, Minisola S, Bilezikian JP, Diacinti D, Colangelo L, Piazzolla V, Angelozzi M, Nieddu L, Pepe J, Diacinti D (2021) Vertebral fracture assessment in postmenopausal women with postsurgical hypoparathyroidism. J Clin Endocrinol Metab 106:1303–1311

    Article  PubMed  PubMed Central  Google Scholar 

  5. Yamamoto M, Yamauchi M, Sugimoto T (2019) Prevalent vertebral fracture is dominantly associated with spinal microstructural deterioration rather than bone mineral density in patients with type 2 diabetes mellitus. PLoS ONE 14(9):e0222571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Vinolas H, Grouthier V, Mehsen-Cetre N, Boisson A, Winzenrieth R, Schaeverbeke T, Mesguich C, Bordenave L, Tabarin A (2018) Assessment of vertebral microarchitecture in overt and mild Cushing’s syndrome using trabecular bone score. Clin Endocrinol (Oxf) 8:148–154

    Article  Google Scholar 

  7. Calatayud M, Pérez-Olivares Martín L, Librizzi MS, Lora Pablos D, González Méndez V, Aramendi Ramos M, Martínez Diaz-Guerra G, Hawkins F (2021) Trabecular bone score and bone mineral density in patients with long-term controlled acromegaly. Clin Endocrinol (Oxford) 95:58–64

    Article  CAS  Google Scholar 

  8. Hans D, Goertzen AL, Krieg MA, Leslie WD (2011) Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: the Manitoba study. J Bone Miner Res 26:2762–2769

    Article  PubMed  Google Scholar 

  9. McCloskey EV, Odén A, Harvey NC, Leslie WD, Hans D, Johansson H, Barkmann R, Boutroy S, Brown J, Chapurlat R, Elders PJM, Fujita Y, Glüer CC, Goltzman D, Iki M, Karlsson M, Kindmark A, Kotowicz M, Kurumatani N, Kwok T, Lamy O, Leung J, Lippuner K, Ljunggren Ö, Lorentzon M, Mellström D, Merlijn T, Oei L, Ohlsson C, Pasco JA, Rivadeneira F, Rosengren B, Sornay-Rendu E, Szulc P, Tamaki J, Kanis JA (2016) A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX. J Bone Min Res 31:940–948

    Article  Google Scholar 

  10. Krohn K, Schwartz EN, Chung YS, Lewiecki EM (2019) Dual-energy X-ray absorptiometry monitoring with trabecular bone score: 2019 ISCD official position. J Clin Densitom 22:501–505

    Article  PubMed  Google Scholar 

  11. Sakane EN, Vieira MCC, Lazaretti-Castro M, Maeda SS (2019) Predictors of poor bone microarchitecture assessed by trabecular bone score in postsurgical hypoparathyroidism. J Clin Endocrinol Metab 104:5795–5803

    Article  PubMed  Google Scholar 

  12. Goswami R, Bhatia M, Goyal R, Kochupillai N (2002) Reversible peripheral neuropathy in idiopathic hypoparathyroidism. Acta Neurol Scand 105:128–131

    Article  CAS  PubMed  Google Scholar 

  13. Goswami R, Brown EM, Kochupillai N, Gupta N, Rani R, Kifor O, Chattopadhyay N et al (2004) Prevalence of calcium sensing receptor autoantibodies in patients with sporadic idiopathic hypoparathyroidism. Eur J Endocrinol 150:9–18

    Article  CAS  PubMed  Google Scholar 

  14. Goswami R, Sharma R, Sreenivas V, Gupta N, Ganapathy A, Das S (2012) Prevalence and progression of basal ganglia calcification and its pathogenic mechanism in patients with idiopathic hypoparathyroidism. Clin Endocrinol (Oxford) 77:200–206

    Article  CAS  Google Scholar 

  15. Saha S, Gantyala SP, Aggarwal S, Sreenivas V, Tandon R, Goswami R (2017) Long-term outcome of cataract surgery in patients with idiopathic hypoparathyroidism and its relationship with their calcemic status. J Bone Minel Metab 35:405–411

    Article  Google Scholar 

  16. Saha S, Kandasamy D, Sharma R, Bal C, Sreenivas V, Goswami R (2020) Nephrocalcinosis, renal dysfunction, and calculi in patients with primary hypoparathyroidism on long-term conventional therapy. J Clin Endocrinol Metab 105(4):dgz319

    Article  PubMed  Google Scholar 

  17. Goswami R, Ray D, Sharma R, Tomar N, Gupta R, Gupta N, Sreenivas V (2008) Presence of spondyloarthropathy and its clinical profile in patients with hypoparathyroidism. Clin Endocrinol (Oxford) 68:258–263

    CAS  Google Scholar 

  18. Tomar N, Bora H, Singh R, Gupta N, Kaur P, Chauhan SS, Sharma YD, Goswami R (2010) Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members. Eur J Endocrinol 162:407–421

    Article  CAS  PubMed  Google Scholar 

  19. Tomar N, Gupta N, Goswami R (2013) Calcium-sensing receptor autoantibodies and idiopathic hypoparathyroidism. J Clin Endocrinol Metab 98:3884–3891

    Article  CAS  PubMed  Google Scholar 

  20. Shoback D (2008) Clinical practice hypoparathyroidism. New England J Med 359:391–403

    Article  CAS  Google Scholar 

  21. Gafni RI, Collins MT (2019) Hypoparathyroidism. N Engl J Med 380:1738–1747

    Article  PubMed  Google Scholar 

  22. Saha S, Goswami R (2019) Auditing the efficacy and safety of alfacalcidol and calcium therapy in idiopathic hypoparathyroidism. J Clin Endocrinol Metab 104:1325–1335

    Article  PubMed  Google Scholar 

  23. Zeytinoglu M, Jain RK, Vokes TJ (2017) Vertebral fracture assessment: enhancing the diagnosis, prevention, and treatment of osteoporosis. Bone 104:54–65

    Article  PubMed  Google Scholar 

  24. Broy SB, Cauley JA, Lewiecki ME, Schousboe JT, Shepherd JA, Leslie WD (2015) Fracture risk prediction by non-BMD DXA measures: the 2015 ISCD official positions part 1: hip geometry. J Clin Densitom 18:287–308

    Article  PubMed  Google Scholar 

  25. Hong AR, Lee JH, Kim JH, Kim SW, Shin CS (2019) Effect of endogenous parathyroid hormone on bone geometry and skeletal microarchitecture. Calcif Tissue Int 104:382–389

    Article  CAS  PubMed  Google Scholar 

  26. Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148

    Article  CAS  PubMed  Google Scholar 

  27. Malgo F, Hamdy NAT, Ticheler CHJM, Smit F, Kroon HM, Rabelink TJ, Dekkers OM, Appelman-Dijkstra NM (2017) Value and potential limitations of vertebral fracture assessment (VFA) compared to conventional spine radiography: experience from a fracture liaison service (FLS) and a meta-analysis. Osteoporos Int 28:2955–2965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Modi S, Tripathi M, Saha S, Goswami R (2014) Seizures in patients with idiopathic hypoparathyroidism: effect of antiepileptic drug withdrawal on recurrence of seizures and serum calcium control. Eur J Endocrinol 170:777–783

    Article  CAS  PubMed  Google Scholar 

  29. Saha S, Madan K, Jain D, Goswami R (2019) Pulmonary alveolar proteinosis (PAP) in idiopathic hypoparathyroidism. BMJ Case Rep. 12(11):e231053. https://doi.org/10.1136/bcr-2019-231053

    Article  PubMed  PubMed Central  Google Scholar 

  30. Seeman E, Wahner HW, Offord KP, Kumar R, Johnson WJ, Riggs BL (1982) Differential effects of endocrine dysfunction on the axial and the appendicular skeleton. J Clin Investig 69:1302–1309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rubin MR, Zhou H, Cusano NE, Majeed R, Omeragic B, Gomez M, Nickolas TL, Dempster DW, Bilezikian JP (2018) The effects of long-term administration of rhPTH(1–84) in hypoparathyroidism by bone histomorphometry. J Bone Miner Res 33:1931–1939

    Article  CAS  PubMed  Google Scholar 

  32. Gafni RI, Brahim JS, Andreopoulou P, Bhattacharyya N, Kelly MH, Brillante BA, Reynolds JC, Zhou H, Dempster DW, Collins MT (2012) Daily parathyroid hormone 1–34 replacement therapy for hypoparathyroidism induces marked changes in bone turnover and structure. J Bone Miner Res 27:1811–1820

    Article  CAS  PubMed  Google Scholar 

  33. Mendonça ML, Pereira FA, Nogueira-Barbosa MH, Monsignore LM, Teixeira SR, Watanabe PC, Maciel LM, de Paula FJ (2013) Increased vertebral morphometric fracture in patients with postsurgical hypoparathyroidism despite normal bone mineral density. BMC Endocr Disord 13:1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Formenti AM, Tecilazich F, Giubbini R, Giustina A (2019) Risk of vertebral fractures in hypoparathyroidism. Rev Endocr Metab Disord 20:295–302

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  36. Iglesias SG, Dominguez MLM, Herrero EF, Martinez-Pueyo JI, Arroba CM, Diaz-Guerra GM, Hawkins Carranza F (2019) Trabecular bone score and bone mineral density in patients with postsurgical hypoparathyroidism after total thyroidectomy for differentiated thyroid carcinoma. Surgery 165:814–819

    Article  PubMed  Google Scholar 

  37. Cipriani C, Pepe J, Silva BC, Rubin MR, Cusano NE, McMahon DJ, Nieddu L, Angelozzi M, Biamonte F, Diacinti D, Hans D, Minisola S, Bilezikian JP (2018) Comparative effect of rhPTH(1–84) on bone mineral density and trabecular bone score in hypoparathyroidism and postmenopausal osteoporosis. J Bone Miner Res 33:2132–2139

    Article  CAS  PubMed  Google Scholar 

  38. Hong AR, Kim JH, Kim SW, Kim SY, Shin CS (2016) Trabecular bone score as a skeletal fragility index in acromegaly patients. Osteoporos Int 27:1123–1129

    Article  CAS  PubMed  Google Scholar 

  39. Florez H, Hernández-Rodríguez J, Carrasco JL, Prieto-González S, Muxi A, Filella X, Ruiz-Gaspà S, Gómez-Puerta JA, Cid M, Espinosa G, Monegal A, Guañabens N, Peris P (2020) Vertebral fracture risk in glucocorticoid-induced osteoporosis: the role of hypogonadism and corticosteroid boluses. RMD Open 6(2):e001355

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gao Y, Wang O, Guan W, Wu X, Mao J, Wang X, Yu W, Nie M (2021) Bone mineral density and trabecular bone score in patients with 21-hydroxylase deficiency after glucocorticoid treatment. Clin Endocrinol (Oxford) 94:765–773

    Article  CAS  Google Scholar 

  41. Szulc P (2020) Biochemical bone turnover markers in hormonal disorders in adults: a narrative review. J Endocrinol Invest 43(10):1409–1427

    Article  CAS  PubMed  Google Scholar 

  42. Park HS, Seo DH, Rhee Y, Lim SK (2017) Site-specific difference of bone geometry indices in hypoparathyroid patients. Endocrinol Metab (Seoul) 32:68–76

    Article  CAS  Google Scholar 

  43. Clarke B (2008) Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 3:S131–S139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hamdy N, Decallonne B, Evenepoel P, Gruson D, van Vlokhoven-Verhaegh L (2021) Burden of illness in patients with chronic hypoparathyroidism not adequately controlled with conventional therapy: a Belgium and the Netherlands survey. J Endocrinol Invest 44(7):1437–1446

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The help of Mr. Arun Chandran in measuring biochemical parameters and Mr. Sushil in DXA is acknowledged. The help of Mr. Ram Sumer and Mr. Rambabu in assisting patients is acknowledged.

Funding

This research did not receive any specific grant from a funding agency in the public commercial.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, 110029, India

    S. Saha, V. Mannar & R. Goswami

  2. Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, 110029, India

    D. Kandasamy

  3. Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, 110029, India

    V. Sreenivas

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  1. S. Saha
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  2. V. Mannar
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Correspondence to R. Goswami.

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All studies were performed according to the declaration of Helsinki, and approved by the Institute Ethics Committee of All India Institute of Medical Sciences, New Delhi, India.

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Saha, S., Mannar, V., Kandasamy, D. et al. Vertebral fractures, trabecular bone score and their determinants in chronic hypoparathyroidism. J Endocrinol Invest 45, 1777–1786 (2022). https://doi.org/10.1007/s40618-022-01818-2

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  • DOI: https://doi.org/10.1007/s40618-022-01818-2

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