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3.4. Cortical bone distribution
There were no differences between groups for average endocortical, midcortical or pericortical vBMD of either the proximal tibia or radius (Table 3). There were also no differences between PCa and healthy controls for any cortical bone distribution outcomes.
To assess the effect of ADT duration on the results, men in the ADT group treated for < 12 months (N = 35, median [IQR] duration = 5.3 [4.1–8.2] months) were compared to those treated for > 12 months (N = 35, median [IQR] duration = 23.4 [15.3–59.4] months). Participant characteristics other than ADT duration and time since PCa diagnosis were equivalent between men treated for less than and > 12 months. There were no differences in any bone outcomes according to duration of ADT use, with the exception that men treated for < 12 months had 2.4% and 2.2% lower midcortical and pericortical vBMD of the proximal tibia, respectively compared to those treated for > 12 months. There were no significant correlations between ADT duration
and any bone outcomes, other than a weak negative correlation (r = −0.26, P < 0.05) with pericortical vBMD of the proximal tibia.
The main finding from this JQ-1 study was that ADT treatment in men with PCa was associated with lower pQCT-derived total and trabecular vBMD and compressive bone strength at distal skeletal sites as well as lower DXA-derived lumbar spine, and to a lesser extent hip aBMD compared to PCa and healthy controls. In contrast, there were no dif-ferences in cortical bone density, structure or bending strength between groups, which suggests that treatment with ADT may predominantly affect trabecular bone sites.
To our knowledge, there are few studies that have quantified the effects of ADT on other determinants of whole bone strength and fracture risk beyond aBMD. Prospective studies assessing the distal tibia and radius using HR-pQCT have reported a marked loss in cortical and trabecular vBMD (1.5% to 11.3% per annum) and cortical area (11.5% to 12.5% per annum) over the first 12-months of ADT , and an accelerated decline in cortical area, thickness and vBMD in ADT treated
compared to non-ADT treated men . In part support of these find-ings, we found that ADT-treated men had significantly lower com-pressive bone strength (BSI) at distal sites, which is likely due to lower total and/or trabecular vBMD compared to controls, particularly at the distal radius. However, the current study adds to this previous study by comparing ADT-treated men to control groups and by assessing prox-imal cortical bone sites of the tibia and radius. A key finding from our study was that there was no consistent evidence that cortical bone structural outcomes and bone strength (polar moment of inertia) were impaired at any site in our cohort of ADT treated men compared to controls. This suggests that ADT may predominantly affect trabecular bone, particularly at non weight-bearing sites.
Trabecular bone is suggested to be more responsive to rapid bone loss, as occurs with hypogonadism induced by ADT, than cortical bone due to a greater surface area for bone resorption or remodelling making trabecular bone more metabolically active [14,43]. In part support of this notion, hypogonadal men have been shown to have impaired QCT-derived trabecular density of the lumbar spine [44,45] and trabecular microarchitecture of the tibia assessed by micro-MRI . Further-more, these outcomes have been shown to improve with testosterone replacement therapy [44,47,48], supporting the importance of andro-gens in maintaining trabecular bone. Testosterone therapy for 12-months in hypogonadal older men has been shown to increase QCT-assessed vBMD and estimated bone strength at both the spine and hip, with greater increases observed in the spine compared to the hip . Lumbar spine aBMD was also shown to increase to a greater extent than total hip and femoral neck aBMD with testosterone therapy compared to placebo . Evidence from mice studies suggest that the mechan-isms responsible for trabecular and cortical bone loss differ following acute sex steroid deficiency , potentially explaining why lower trabecular vBMD was not accompanied by lower cortical vBMD in the current study. The differences in trabecular bone in the ADT-treated men in our study may also be related to the relatively short duration of ADT use in our men. Weak negative associations between ADT duration and trabecular bone indices of the distal radius assessed by HR-MRI have been reported previously . Overall, 50% of the men in the ADT group were treated for < 12-months, and thus it is possible that longer term treatment may lead to observable changes in cortical bone outcomes. While the comparison between men treated for < 12 months and > 12 months showed negligible differences in most bone outcomes, the analysis may have been limited by the modest sample size.