PTH prevents the adverse effects of focal radiation on bone architecture in young rats

Abhishek Chandra, Shenghui Lan, Ji Zhu, Tiao Lin, Xianrong Zhang, Valerie A. Siclari, Allison R. Altman, Keith A. Cengel, X. Sherry Liu, Ling Qin

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy.

Original languageEnglish (US)
Pages (from-to)449-457
Number of pages9
JournalBone
Volume55
Issue number2
DOIs
StatePublished - Aug 2013

Keywords

  • Osteoblasts
  • PTH
  • Radiation therapy
  • Trabecular bone
  • μCT

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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    Chandra, A., Lan, S., Zhu, J., Lin, T., Zhang, X., Siclari, V. A., Altman, A. R., Cengel, K. A., Liu, X. S., & Qin, L. (2013). PTH prevents the adverse effects of focal radiation on bone architecture in young rats. Bone, 55(2), 449-457. https://doi.org/10.1016/j.bone.2013.02.023