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Long‐term loss of osteoclasts and unopposed cortical mineral apposition following limited field irradiation
Author(s) -
Oest Megan E.,
Franken Veerle,
Kuchera Timothy,
Strauss Judy,
Damron Timothy A.
Publication year - 2015
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22761
Subject(s) - osteoclast , apposition , resorption , bone resorption , cortical bone , bone remodeling , radiation therapy , medicine , pathology , chemistry , receptor
Late‐onset fragility fractures are a common complication following radiotherapy for metastatic disease and soft tissue sarcomas. Using a murine hindlimb focal irradiation model (RTx), we quantified time‐dependent changes in osteoclasts and mineral apposition rate (MAR). Mice received either a single, unilateral 5 Gy exposure or four fractionated doses (4 × 5 Gy). Osteoclast numbers and MAR were evaluated histologically at 1, 2, 4, 8, 12, and 26 weeks post‐RTx. Radiation induced an early, transient increase in osteoclasts followed by long‐term depletion. Increased osteoclast numbers correlated temporally with trabecular resorption; the resorbed trabeculae were not later restored. Radiotherapy did not attenuate MAR at any time point. A transient, early increase in MAR was noted in both RTx groups, however, the 4 × 5 Gy group exhibited an unexpected spike in MAR eight weeks. Persistent depletion of osteoclasts permitted anabolic activity to continue unopposed, resulting in cortical thickening. These biological responses likely contribute to post‐radiotherapy bone fragility via microdamage accumulation and matrix embrittlement in the absence of osteoclastic remodeling, and trabecular resorption‐induced decrease in bone strength. The temporal distribution of osteoclast numbers suggests that anti‐resorptive therapies may be of clinical benefit only if started prior to radiotherapy and continued through the following period of increased osteoclastic remodeling. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???–???, 2015.