title: PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival.
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.
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Chandra
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Tiao
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Tribble
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Altman
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Wei-Ju
authors.initials: WJ
authors.lastname: Tseng
authors.affiliation: Philadelphia Veterans Affairs Medical Center, Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yejia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sunday O
authors.initials: SO
authors.lastname: Akintoye
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Cengel
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: X Sherry
authors.initials: XS
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: qinling@mail.med.upenn.edu.
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001847:Bone Diseases / Q000188:drug therapy* / Q000209:etiology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D010011:Osteocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D010281:Parathyroid Hormone / Q000627:therapeutic use*; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D013977:Tibia / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects
chemical_list: D010281:Parathyroid Hormone
keywords: Apoptosis; Image registration; Osteoblast; Parathyroid hormone; Radiotherapy; Trabecular bone