Predictors of Fracture Risk and Bone Mineral Density in Men with Prostate Cancer on Androgen Deprivation Therapy

Decrease of bone mineral density (BMD) and fracture risk is increased in men with prostate cancer receiving androgen deprivation therapy (ADT). We looked at possible predictors of decreased BMD and increased fracture risk in men with prostate cancer; most of whom were on ADT. In a retrospective study, we analyzed serum, BMD, and clinical risk factors used in the Fracture Risk Assessment (FRAX) tool and others in 78 men with prostate cancer with reported height loss. The subjects were divided in two groups: 22 men with and 56 without vertebral fractures. 17 of the 22 men with vertebral fractures on spine X-rays did not know they had a vertebral fracture. Of those 17 men, 9 had not previously qualified for treatment based on preradiograph FRAX score calculated with BMD, and 6 based on FRAX calculated without BMD. Performing spine films increased the predictive ability of FRAX for vertebral fracture. Vertebral fracture was better predicted by FRAX for other osteoporotic fractures than FRAX for hip fractures. The inclusion of BMD in FRAX calculations did not affect the predictive ability of FRAX. The PSA level showed a positive correlation with lumbar spine BMD and accounted for about 9% of spine BMD

The RADAR Study: Week 48 Safety and Efficacy of RAltegravir Combined with Boosted DARunavir Compared to Tenofovir/Emtricitabine Combined with Boosted Darunavir in Antiretroviral-Naive Patients. Impact on Bone Health

<div><p>Background</p><p>NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression.</p><p>Methods</p><p>In the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL) (n = 42) or tenofovir/emtricitabine (TDF/FTC) (n = 43), each with ritonavir-boosted darunavir (DRV/r). Virologic efficacy was assessed at weeks 24 and 48. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) scan at baseline and week 48, and bone turnover markers (BTM) assessed at weeks 0, 16 and 48.</p><p>Results</p><p>Using an intention-to-treat analysis, 62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL<48 copies/mL) at week 48 (p = 0.045; chi-square test). The proportions of patients achieving VL<200 copies/mL were similar: 72.5% and 86.0% (p = 0.175). Premature treatment discontinuation was the main cause for failure. No treatment-emergent resistance was observed. Changes from baseline in RAL vs. TDF/FTC for CD4⁺ (+199 vs. +216 cells/µL, p = 0.63), total cholesterol/HDL (−0.25 vs. −0.71 mg/dL (p = 0.270), and eGFR (−4.4 vs. −7.9 ml/min, p = 0.44) were comparable between groups. Changes in subtotal BMD to week 48 were: +9.2 with RAL vs. −7 g/cm² with TDF/FTC (p = 0.002). Mean CTX changes were +0.04 vs. +0.24 ng/mL (p = 0.001), and mean P1NP changes were +3.59 vs. +30.09 ng/mL (p = 0.023). BTM changes at week 16 predicted change in BMD by week 48 (R = −0.394, p = 0.003 for CTX; and R = −0.477, p<0.001 for P1NP).</p><p>Conclusion</p><p>The NRTI-sparing regimen RAL+DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC+DRV/r, but was better with regard to markers of bone health.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00677300?term=RADAR&rank=5" target="_blank">NCT 00677300</a></p></div

Proportion of subjects with plasma HIV-1 RNA<48 copies/mL and <200 copies/mL using the Intention-to-Treat Analysis (top) and the On-Treatment-Analysis (bottom, with number of patients indicated).

<p>Proportion of subjects with plasma HIV-1 RNA<48 copies/mL and <200 copies/mL using the Intention-to-Treat Analysis (top) and the On-Treatment-Analysis (bottom, with number of patients indicated).</p

Changes in bone turnover markers from baseline to week 48 (number of patients indicated).

<p>Top: Serum Terminal Telopeptide (CTX). †p<0.01 for TDF/FTC vs. RAL groups at specific time point *p<0.01 for TDF/FTC group versus baseline. Bottom: Serum Procollagen type 1 N-terminal propeptide (P1NP, bottom). ‡p<0.05 for TDF/FTC vs. RAL groups at specific time point *p<0.01 for TDF/FTC group versus baseline.</p

Correlation between early changes in bone turnover markers (week 16 vs. week 0) and change in BMD by week 48.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106221#pone-0106221-g004" target="_blank">Figure 4A:</a> Correlation for serum P1NP. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106221#pone-0106221-g004" target="_blank">Figure 4B:</a> Correlation for serum CTX.</p

Demographics and Baseline Characteristics.

<p>Demographics and Baseline Characteristics.</p

CONSORT Flow Diagram.

<p>CONSORT Flow Diagram.</p

Lipid parameters and Renal Function: Baseline values and changes at week 48.

<p>Lipid parameters and Renal Function: Baseline values and changes at week 48.</p