title: Parathyroid Hormone (1-34) Transiently Protects Against Radiation-Induced Bone Fragility.
abstract: Radiation therapy for soft tissue sarcoma or tumor metastases is frequently associated with damage to the underlying bone. Using a mouse model of limited field hindlimb irradiation, we assessed the ability of parathyroid hormone (1-34) fragment (PTH) delivery to prevent radiation-associated bone damage, including loss of mechanical strength, trabecular architecture, cortical bone volume, and mineral density. Female BALB/cJ mice received four consecutive doses of 5 Gy to a single hindlimb, accompanied by daily injections of either PTH or saline (vehicle) for 8 weeks, and were followed for 26 weeks. Treatment with PTH maintained the mechanical strength of irradiated femurs in axial compression for the first eight weeks of the study, and the apparent strength of irradiated femurs in PTH-treated mice was greater than that of naïve bones during this time. PTH similarly protected against radiation-accelerated resorption of trabecular bone and transient decrease in mid-diaphyseal cortical bone volume, although this benefit was maintained only for the duration of PTH delivery. Overall, PTH conferred protection against radiation-induced fragility and morphologic changes by increasing the quantity of bone, but only during the period of administration. Following cessation of PTH delivery, bone strength and trabecular volume fraction rapidly decreased. These data suggest that PTH does not negate the longer-term potential for osteoclastic bone resorption, and therefore, finite-duration treatment with PTH alone may not be sufficient to prevent late onset radiotherapy-induced bone fragility.
authors: Department of Orthopedic Surgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA. oestm@upstate.edu.
authors: Megan E
authors: ME
authors: Oest
authors: Department of Orthopedic Surgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA.
authors: Kenneth A
authors: KA
authors: Mann
authors: Department of Orthopedic Surgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA.
authors: Nicholas D
authors: ND
authors: Zimmerman
authors: Department of Orthopedic Surgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA.
authors: Timothy A
authors: TA
authors: Damron
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000528:radiation effects*; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D055114:X-Ray Microtomography
chemical_list: D010281:Parathyroid Hormone
keywords: Bone; Bone morphology; Bone strength; Fracture; Parathyroid hormone; Radiation