PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival

Abhishek Chandra, Tiao Lin, Mary Beth Tribble, Ji Zhu, Allison R. Altman, Wei Ju Tseng, Yejia Zhang, Sunday O. Akintoye, Keith Cengel, X. Sherry Liu, Ling Qin

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1-34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1-34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1-34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1-34. Furthermore, histological analyses revealed that PTH1-34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage.

Original languageEnglish (US)
Pages (from-to)33-40
Number of pages8
JournalBone
Volume67
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Osteocytes
Osteoblasts
Radiotherapy
Radiation
Bone and Bones
Parathyroid Hormone
Osteoradionecrosis
Anabolic Agents
Alendronate
X-Ray Microtomography
Metabolic Bone Diseases
Adiposity
Bone Resorption
Osteogenesis
Osteoporosis
Neoplasms
Bone Marrow
Apoptosis
Injections
Therapeutics

Keywords

  • Apoptosis
  • Image registration
  • Osteoblast
  • Parathyroid hormone
  • Radiotherapy
  • Trabecular bone

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival. / Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R.; Tseng, Wei Ju; Zhang, Yejia; Akintoye, Sunday O.; Cengel, Keith; Liu, X. Sherry; Qin, Ling.

In: Bone, Vol. 67, 01.01.2014, p. 33-40.

Research output: Contribution to journalArticle

Chandra, A, Lin, T, Tribble, MB, Zhu, J, Altman, AR, Tseng, WJ, Zhang, Y, Akintoye, SO, Cengel, K, Liu, XS & Qin, L 2014, 'PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival', Bone, vol. 67, pp. 33-40. https://doi.org/10.1016/j.bone.2014.06.030
Chandra, Abhishek ; Lin, Tiao ; Tribble, Mary Beth ; Zhu, Ji ; Altman, Allison R. ; Tseng, Wei Ju ; Zhang, Yejia ; Akintoye, Sunday O. ; Cengel, Keith ; Liu, X. Sherry ; Qin, Ling. / PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival. In: Bone. 2014 ; Vol. 67. pp. 33-40.
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abstract = "Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1-34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1-34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1-34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1-34. Furthermore, histological analyses revealed that PTH1-34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage.",
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AU - Chandra, Abhishek

AU - Lin, Tiao

AU - Tribble, Mary Beth

AU - Zhu, Ji

AU - Altman, Allison R.

AU - Tseng, Wei Ju

AU - Zhang, Yejia

AU - Akintoye, Sunday O.

AU - Cengel, Keith

AU - Liu, X. Sherry

AU - Qin, Ling

PY - 2014/1/1

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N2 - Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1-34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1-34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1-34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1-34. Furthermore, histological analyses revealed that PTH1-34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage.

AB - Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1-34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1-34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1-34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1-34. Furthermore, histological analyses revealed that PTH1-34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage.

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