The effects of denosumab and alendronate on glucocorticoid-induced osteoporosis in patients with glomerular disease: A randomized, controlled trial

<div><p>Introduction</p><p>The clinical utility of denosumab for the treatment of glucocorticoid-induced osteoporosis (GIOP) has yet to be established. This study aimed to compare the effects of denosumab on bone mineral density (BMD) and bone turnover markers to those of alendronate in patients with GIOP.</p><p>Methods</p><p>A prospective, single-center study of 32 patients (18 men; median age, 66.0 years) with glomerular disease receiving prednisolone (PSL) who were diagnosed as having GIOP and had not received bisphosphonates before was conducted. Participants were randomized to either alendronate (35 mg orally once a week) or denosumab (60 mg subcutaneously once every 6 months), and all subjects received calcitriol. The primary endpoint was the percent change in lumbar spine (LS) BMD at 12 months of treatment.</p><p>Results</p><p>The demographic and clinical characteristics at baseline were not significantly different between the groups. Denosumab treatment markedly decreased serum levels of t-PINP, BAP, and TRACP-5b at 12 months compared to baseline (-57.4%, p<0.001; -30.9%, p<0.01; -57.7%, p<0.001, respectively). After 12 months of alendronate treatment, serum levels of t-PINP, BAP, and TRACP-5b were also significantly decreased compared to pretreatment (-38.9%, p<0.01; -16.3%, p<0.05; -43.5%, p<0.01, respectively). However, no significant differences in the changes of bone turnover markers were found between the two groups. As for the effects on BMD, denosumab treatment markedly increased LS BMD from 6 months compared to baseline, whereas no significant difference compared to pretreatment was found in the alendronate group during the study period. In the comparison of the two groups, a large increase of LS BMD was found in the denosumab treatment group compared to the alendronate treatment group at 12 months (p<0.05).</p><p>Conclusions</p><p>In patients with GIOP, denosumab treatment markedly suppressed bone turnover, which led to a significantly greater increase in LS BMD than with alendronate treatment. These results suggest that denosumab is a therapeutic option for the treatment of GIOP.</p></div

Effects of denosumab and alendronate on BMD.

<p>Percent changes (mean ± SEM) in bone mineral density from baseline to 12 months in the lumbar spine (A), femoral neck (B), and ultra-distal radius (C) in the denosumab and alendronate groups. *<i>P</i> compared with the alendronate group (by Wilcoxon’s rank sum test). ^#<i>P</i> compared with baseline (by Wilcoxon’s signed rank test).</p

Laboratory data and bone mineral density (BMD) at baseline.

<p>Laboratory data and bone mineral density (BMD) at baseline.</p

Patient disposition.

<p>Abbreviations: FAS, full analysis set.</p

Effects of denosumab and alendronate on bone turnover makers.

<p>Percent changes (means ± SEM) in bone turnover markers from baseline to 12 months in the denosumab and alendronate groups. *<i>P</i> compared with the alendronate group (by Wilcoxon’s rank sum test). ^#<i>P</i> compared with baseline (by Wilcoxon’s signed rank test). Abbreviations: TRACP-5b, tartrate-resistant acid phosphatase 5b; BAP, bone-specific alkaline phosphatase; t-PINP, total-type I collagen N-terminal propeptide.</p

Clinical characteristics at baseline.

<p>Clinical characteristics at baseline.</p

Baseline clinical characteristics.

<p>Baseline clinical characteristics.</p

Epidermal Growth Factor Receptor Inhibition with Erlotinib Partially Prevents Cisplatin-Induced Nephrotoxicity in Rats

<div><p>The effects of blocking the epidermal growth factor receptor (EGFR) in acute kidney injury (AKI) are controversial. Here we investigated the renoprotective effect of erlotinib, a selective tyrosine kinase inhibitor that can block EGFR activity, on cisplatin (CP)-induced AKI. Groups of animals were given either erlotinib or vehicle from one day before up to Day 3 following induction of CP- nephrotoxicity (CP-N). In addition, we analyzed the effects of erlotinib on signaling pathways involved in CP-N by using human renal proximal tubular cells (HK-2). Compared to controls, rats treated with erlotinib exhibited significant improvement of renal function and attenuation of tubulointerstitial injury, and reduced the number of apoptotic and proliferating cells. Erlotinib-treated rats had a significant reduction of renal cortical mRNA for profibrogenic genes. The Bax/Bcl-2 mRNA and protein ratios were significantly reduced by erlotinib treatment. <i>In vitro</i>, we observed that erlotinib significantly reduced the phosphorylation of MEK1 and Akt, processes that were induced by CP in HK-2. Taken together, these data indicate that erlotinib has renoprotective properties that are likely mediated through decreases in the apoptosis and proliferation of tubular cells, effects that reflect inhibition of downstream signaling pathways of EGFR. These results suggest that erlotinib may be useful for preventing AKI in patients receiving CP chemotherapy.</p></div

The prevalence of anti-PLA2R Abs evaluated by ELISA and CIIFA in MN patients.

<p>The prevalence of anti-PLA2R Abs evaluated by ELISA and CIIFA in MN patients.</p

Comparison of the prevalence of serum anti-PLA2R Abs with glomerular PLA2R Ag expression in IMN patients.

<p>Comparison of the prevalence of serum anti-PLA2R Abs with glomerular PLA2R Ag expression in IMN patients.</p