Long-Term Effect of Denosumab on Bone Disease in Patients with CKD.

BACKGROUND: The effect of long-term denosumab therapy and of denosumab discontinuation on the cortical bone of the hip regions in dialysis patients has not been studied. METHODS: This retrospective study investigated the cortical and trabecular compartments and estimated strength indices of the hip region, obtained using 3D-SHAPER software, after a maximum of 5 years of denosumab therapy in 124 dialysis patients. A Wilcoxon signed-rank test was used to identify the differences in each parameter before and after denosumab initiation. Similarly, we investigated the changes in these parameters after denosumab discontinuation in 11 dialysis patients. RESULTS: Integral and trabecular volumetric bone mineral densities (BMD) were significantly lower at the start of denosumab therapy than those in 1 year before denosumab initiation. After starting denosumab, areal BMD (median change +7.7% [interquartile range (IQR), +4.6 to +10.6]), cortical volumetric BMD (median change +3.4% [IQR, +1.0 to +4.7]), cortical surface BMD (median change +7.1% [IQR, +3.4 to +9.4]), and cortical thickness (median change +3.2% [IQR, +1.8 to +4.9]) showed a significantly higher trend for 3.5 years, which then stabilized at a higher value compared with baseline. A similar trend in the trabecular volumetric BMD (median change +9.8% [IQR, +3.8 to +15.7]) was observed over 2.5 years, with a higher value maintained thereafter. The whole area of the hip region improved after denosumab therapy. Similar trajectories were also found in the estimated strength indices. Conversely, at 1 year after denosumab discontinuation, these 3D parameters and estimated strength indices tended to largely worsen. The lateral aspect of the greater trochanter was the most pronounced location showing volumetric BMD loss. CONCLUSIONS: The BMD of both cortical and trabecular components in the hip region was significantly higher after starting denosumab therapy. However, these measurements exhibited a trend of declining substantially after the discontinuation of denosumab.

Bone density of the femoral neck in patients on maintenance dialysis.

BACKGROUND: Our institution recently started using the femoral neck (FN), as well as the non-shunted distal radius (Rd), to measure bone mineral density (BMD) in patients with chronic kidney disease. We examined the utility and characteristics of this measurement in patients on maintenance dialysis. METHODS: We selected 293 patients on chronic dialysis. We measured Rd and FN BMD using dual-energy X-ray absorptiometry, and we reviewed blood test findings, which included hemoglobin, albumin, blood urea nitrogen, creatinine, adjusted calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone. We conducted a multiple linear regression analysis that was stratified according to sex, age, body weight, height, and dialysis vintage. The Rd and FN BMD values were the dependent variables, and the blood test findings were the independent variables. We compared the areas under the curve (AUCs) of Rd and FN BMD using receiver operating characteristic curve analysis to differentiate between patients with and without fractures. RESULTS: FN BMD was significantly lower than Rd BMD. The general risk factors for osteoporosis, such as low body weight, older age, muscle mass loss, and malnutrition, influenced FN BMD. FN and Rd BMD were not correlated with calcium, phosphorous, or intact parathyroid hormone, whereas a significant, negative correlation with alkaline phosphatase was detected. Both men and women with a history of fragility fractures had significantly lower Rd and FN BMDs than patients without such a history. However, there was no significant difference between the AUCs of FN and Rd BMD for fractures in both men and women. CONCLUSIONS: FN BMD was significantly lower than Rd BMD. Additionally, FN BMD was not inferior to Rd BMD for assessing the risk of fracture in patients on maintenance dialysis.

Treatment of hyperphosphatemia with bixalomer in Japanese patients on long-term hemodialysis with gastrointestinal symptoms.

Bixalomer (Bix) is an amine-functional polymer, non-calcium-containing phosphate (P) binder, and has been clinically available in Japan recently. Bix is expected to cause fewer gastrointestinal (GI) side-effects as compared with sevelamer hydrochloride (SH), because of less expansion of Bix in the GI tract. In this prospective observational study, we evaluated changes in GI symptoms by the Gastrointestinal Symptom Rating Scale (GSRS) score in long-term hemodialysis (HD) outpatients with SH-associated GI symptoms who switched to Bix from SH. A total of 114 patients (age 63.7±10.8 year (mean±SD), female 65.5%, HD vintage 11.2±8.6 years, diabetes mellitus 27.4%) were enrolled. The GSRS score was checked at 0 and 12 weeks after the start of Bix. Bix was started at the initial dose of 750 mg/day, and then was titrated. Serum albumin, P and corrected calcium levels did not significantly change during Bix treatment. However, serum low-density lipoprotein-cholesterol and bicarbonate levels significantly increased during Bix treatment (P<0.001). In GSRS scores, total and domain-specific scores, including constipation, diarrhea, reflux and abdominal pain were significantly reduced at 0, 4, 12 and 24 weeks as compared with those at 0 weeks (P<0.05). This study shows that Bix was well tolerated and managed hyperphosphatemia effectively after switching from SH in Japanese patients on long-term HD. In addition, Bix might be less often associated with GI symptoms as compared with SH.