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Background: Pelvic radiotherapy causes symptomatic Radiotherapy Related Insufficiency Fractures (RRIFs) in around 20% of patients. Pathophysiology and predisposing factors for RRIFs are not well understood. Some studies have determined low BMD/osteoporosis to be a risk factor but only a few utilised DXA assessment of BMD at baseline prior to radiotherapy or at the time of RRIF development. Primary or secondary interventions to prevent/treat RRIFs have not been assessed. Methods: Retrospective analysis of patients (n=44; 42F; median age 65.5yrs [IQR 55, 73]) who underwent a DXA (Hologic) scan (Lumbar Spine (LS) (L1-4), Total Hip (TH), Femoral neck (FN) and Trabecular Bone Score (TBS)) following a diagnosis of pelvic RRIF between 2010–2019 at a tertiary referral cancer centre in the UK. Patient characteristics and treatment history were assessed. Osteoporosis (T-score &amp;lt;-2.5), osteopenia (T-score &amp;lt;-1 &amp;gt;-2.5) and normal BMD (T-score &amp;gt;-1) were defined as per WHO classification. Results: Cancer diagnoses; cervical (n=17), endometrial (n=9), vaginal (n=6), anal (n=6), other (n=6). Cancer treatments; chemotherapy (n=36), surgery (n=22), brachytherapy (n=26). Conventional risk factors for osteoporosis; previous fragility fracture (n=9, one on bisphosphonate prior to RRIF), smoking (n=7), glucocorticoid use (n=4), parental hip fracture (n=3), alcohol excess (n=3) and hypogonadism (n=2 and 8 on HRT). Median BMI = 25.4 [22.8, 28.5] kg/m2. Median interval between initiation of radiotherapy and RRIF was 9.8 [7.1, 19.3] months and between RRIF and DXA 3.5 [2, 8] months. At the time of the RRIF, 5 had normal BMD, 20 had osteopenia and 16 osteoporosis. Three patients were &amp;lt;40yrs at time of DXA (lowest Z-score -2 at LS in n=1). Median T-scores in LS, FN and TH were -1.8 [-2.8, -0.98], -1.65 [-2.4, -1.18] and -1.25 [-1.68, -0.5] respectively; N=24 had all Z-scores ≥-1. Median TBS T-score was -2.65 [-3.48, -2]. Median 10-yr hip fracture risk (FRAX HF) was 1.8% [0.7–4.1], major osteoporotic fracture risk (FRAX MO) was 8.9% [5.2- 13] (if RRIF included as FRAX risk factor: 2.9% [1–5] and 15% [8.7- 20] respectively). FRAX HF was ≥ 3% in n=14 and FRAX MO ≥ 20% in n=6 (accounting for RRIF: n= 20 and 12 respectively). Most patients therefore fell below the intervention threshold. Pelvic radiotherapy dose was negatively associated with LS BMD (p=0.0228). Body mass index was positively correlated with LS BMD (p=0.002). Discussion: Most patients did not have osteoporosis at the time of RRIF and overall had low fragility fracture risk as defined by FRAX. RRIFs can also occur with normal hip and spine BMD. Low BMD at the spine was however associated with higher pelvic radiotherapy dose. The mechanism of RRIFs is likely different to osteoporotic fragility fractures and whilst low BMD is a probable risk factor, further studies are required to fully understand their pathophysiology and how fracture risk should be best assessed in these patients.

Bone Mineral Density Assessment Following Radiotherapy Related Insufficiency Fractures (RRIFs) of the Pelvis