Pilot Study: Short Term Impact of Radiation Therapy on Bone Mineral Density and Bone Metabolism

Quirina C B S Thio; Olivier D R van Wulfften Palthe; Jos A M Bramer; Thomas F DeLaney; Miriam A Bredella; David W Dempster; Hua Zhou; Francis J Hornicek; Yen-Lin E Chen; Joseph H Schwab

doi:10.1007/s00223-023-01149-1

Pilot Study: Short Term Impact of Radiation Therapy on Bone Mineral Density and Bone Metabolism

Calcif Tissue Int. 2023 Dec;113(6):640-650. doi: 10.1007/s00223-023-01149-1. Epub 2023 Nov 1.

Authors

Quirina C B S Thio^{1

2

3}, Olivier D R van Wulfften Palthe^{4

5}, Jos A M Bramer⁴, Thomas F DeLaney⁶, Miriam A Bredella⁷, David W Dempster^{8

9}, Hua Zhou⁹, Francis J Hornicek¹⁰, Yen-Lin E Chen^#⁶, Joseph H Schwab^#⁵

Affiliations

¹ Department of Orthopedic Surgery, Academic University Medical Center, University of Amsterdam, Amsterdam, The Netherlands. [email protected].
² Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. [email protected].
³ Massachusetts General Hospital, Room 3.946, Yawkey Building, 55 Fruit Street, Boston, MA, 02114, USA. [email protected].
⁴ Department of Orthopedic Surgery, Academic University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
⁵ Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
⁹ Regional Bone Center, Helen Hayes Hospital, West Haverstraw, New York, USA.
¹⁰ Department of Orthopedic Surgery, UCLA Health, Los Angeles, CA, USA.

^# Contributed equally.

Abstract

Despite the risk of complications, high dose radiation therapy is increasingly utilized in the management of selected bone malignancies. In this study, we investigate the impact of moderate to high dose radiation (over 50 Gy) on bone metabolism and structure. Between 2015 and 2018, patients with a primary malignant bone tumor of the sacrum that were either treated with high dose definitive radiation only or a combination of moderate to high dose radiation and surgery were prospectively enrolled at a single institution. Quantitative CTs were performed before and after radiation to determine changes in volumetric bone mineral density (BMD) of the irradiated and non-irradiated spine. Bone histomorphometry was performed on biopsies of the irradiated sacrum and the non-irradiated iliac crest of surgical patients using a quadruple tetracycline labeling protocol. In total, 9 patients were enrolled. Two patients received radiation only (median dose 78.3 Gy) and 7 patients received a combination of preoperative radiation (median dose 50.4 Gy), followed by surgery. Volumetric BMD of the non-irradiated lumbar spine did not change significantly after radiation, while the BMD of the irradiated sacrum did (pre-radiation median: 108.0 mg/cm³ (IQR 91.8-167.1); post-radiation median: 75.3 mg/cm³ (IQR 57.1-110.2); p = 0.010). The cancellous bone of the non-irradiated iliac crest had a stable bone formation rate, while the irradiated sacrum showed a significant decrease in bone formation rate [pre-radiation median: 0.005 mm³/mm²/year (IQR 0.003-0.009), post-radiation median: 0.001 mm³/mm²/year (IQR 0.001-0.001); p = 0.043]. Similar effects were seen in the cancellous and endocortical envelopes. This pilot study shows a decrease of volumetric BMD and bone formation rate after high-dose radiation therapy. Further studies with larger cohorts and other endpoints are needed to get more insight into the effect of radiation on bone. Level of evidence: IV.

Keywords: Bone; Bone histomorphometry; Chondrosarcoma; Chordoma; Radiation therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Density*
Humans
Ilium
Lumbar Vertebrae
Pilot Projects
Sacrum* / surgery