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Bone Histomorphometry in Hypoparathyroidism

  • David W. DempsterEmail author
Chapter

Abstract

Analysis of the iliac crest bone biopsy by histomorphometric analysis and microcomputed tomography has shed new insight on the cellular and structural skeletal abnormalities in hypoparathyroidism. The disease is characterized by increased bone mass in both cancellous and cortical compartments with increased cortical and trabecular thickness. These changes are accompanied by reduced activation frequency of bone remodeling with a positive bone balance in each remodeling cycle. Treatment with PTH reverses some of these abnormalities, increasing remodeling activation frequency and reducing cortical bone mass by increasing porosity and decreasing trabecular thickness by stimulating intra-trabecular tunneling. Cancellous bone volume remains constant in adults but is further increased by treatment with PTH in adolescents. Mathematical modeling, based on real biopsy samples, suggests that, in addition to reduced remodeling activation frequency, the hypoparathyroid state leads to increased osteocyte mechanosensitivity, which results in a marked increase in bone formation early in the disease process.

Keywords

Hypoparathyroidism Bone Histomorphometry Microcomputed tomography Biopsy PTH 

Notes

Acknowledgment

I wish to acknowledge the seminal contributions of my colleagues and collaborators in the studies reviewed in this chapter, in particular Drs. John Bilezikian, Michaela Rubin, and Hua Zhou.

References

  1. 1.
    Langdahl BL, Mortensen L, Vesterby A, Eriksen EF, Charles P (1996) Bone histomorphometry in hypoparathyroid patients treated with vitamin D. Bone 18:103–108CrossRefPubMedGoogle Scholar
  2. 2.
    Rubin MR, Dempster DW, Zhou H, Shane E, Nickolas T, Sliney J Jr, Silverberg SJ, Bilezikian JP (2008) Dynamic and structural properties of the skeleton in hypoparathyroidism. J Bone Miner Res 23:2018–2024CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Rubin MR, Dempster DW, Kohler T, Stauber M, Zhou H, Shane E, Nickolas T, Stein E, Sliney J Jr, Silverberg SJ, Bilezikian JP, Müller R (2010) Three dimensional cancellous bone structure in hypoparathyroidism. Bone 46:190–195CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Cohen A, Dempster DW, Müller R, Guo XE, Nickolas TL, Liu XS, Zhang XH, Wirth AJ, van Lenthe GH, Kohler T, McMahon DJ, Zhou H, Rubin MR, Bilezikian JP, Lappe JM, Recker RR, Shane E (2010) Assessment of trabecular and cortical architecture and mechanical competence of bone by high-resolution peripheral computed tomography: comparison with transiliac bone biopsy. Osteoporos Int 21:263–273CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Rubin MR, Dempster DW, Sliney J Jr, Zhou H, Nickolas TL, Stein EM, Dworakowski E, Dellabadia M, Ives R, McMahon DJ, Zhang C, Silverberg SJ, Shane E, Cremers S, Bilezikian JP (2011) PTH(1–84) administration reverses abnormal bone-remodeling dynamics and structure in hypoparathyroidism. J Bone Miner Res 26(11):2727–2736CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Rubin MR, Manavalan JS, Dempster DW, Shah J, Cremers S, Kousteni S, Zhou H, McMahon DJ, Kode A, Sliney J, Shane E, Silverberg SJ, Bilezikian JP (2011) Parathyroid hormone stimulates circulating osteogenic cells in hypoparathyroidism. J Clin Endocrinol Metab 96(1):176–186CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    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 27:1811–1820CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Sikjaer T, Rejnmark L, Thomsen JS, Tietze A, Brüel A, Andersen G, Mosekilde L (2012) Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1–84): a randomized controlled study. J Bone Miner Res 27:781–788CrossRefPubMedGoogle Scholar
  9. 9.
    Theman TA, Collins MT, Dempster DW, Zhou H, Reynolds JC, Brahim JS, Roschger P, Klaushofer K, Winer KK (2009) PTH(1–34) replacement therapy in a child with hypoparathyroidism caused by a sporadic calcium receptor mutation. J Bone Miner Res 24:964–973CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Christen P, Ito K, Müller R, Rubin MR, Dempster DW, Bilezikian JP, van Rietbergen B (2012) Patient-specific bone modelling and remodelling simulation of hypoparathyroidism based on human iliac crest biopsies. J Biomech 45:2411–2416CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  1. 1.Department of Pathology and Cell BiologyCollege of Physicians and Surgeons of Columbia UniversityNew YorkUSA
  2. 2.Department of Regional Bone CenterHelen Hayes HospitalWest HaverstrawUSA

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