Altered vertebral biomechanical properties in prostate cancer patients following androgen deprivation therapy

Abstract

Androgen deprivation therapy (ADT) for localised and metastatic prostate cancer (PCa) is known to improve survival in patients but has been associated with negative long-term impacts on the skeleton, including decreased bone mineral density (BMD) and increased fracture risk. Generally, dual-enery X-ray absorptiometry (DXA) measurements of areal BMD (aBMD) of vertebrae are used clinically to assess bone health. However, a prediction of vertebral bone strength requires information that aBMD cannot provide, such as geometry and volumetric BMD (vBMD). This study aims to investigate the effect of ADT on the densitometric (aBMD, trabecular vBMD, integral vBMD) and mechanical integrity (failure load and failure strength) of vertebrae, using a combination of DXA, quantitative computed tomography (QCT) and finite element (FE) modelling. For the FE analyses, 3D models were reconstructed from QCT images of 26 ADT treated patients, and their matched controls, collected as part of the ANTELOPE clinical trial. The ADT treated group experienced significantly decreased trabecular and integral vBMD (trabecular vBMD: -18 %, p < 0.001, integral vBMD: -11 %, p < 0.001) compared to control patients that showed no significant temporal changes (trabecular vBMD p = 0.037, integral vBMD p = 0.56). A similar trend was seen in the ADT treated group for the failure load and failure strength, where a decrease of 14 % was observed (p < 0.001). When comparing the proficiency in predicting the mechanical properties from densitometric properties, the integral vBMD performed best in the pooled data (r = 0.86-0.87, p < 0.001) closely followed by trabecular vBMD (r = 0.73-0.75, p < 0.001) with aBMD having a much weaker predictive ability (r = 0.19-0.21, p < 0.01). In conclusion, ADT significantly reduced both the densitometric properties and the mechanical strength of vertebrae. A stronger relationship between both trabecular vBMD and integral vBMD with the mechanical properties than the aBMD was observed, suggesting that such clinical measurements could improve predictions of fracture risk in prostate cancer patients treated with ADT.

Keywords: Androgen deprivation therapy (ADT); Prostate cancer; Vertebral biomechanics.