Response to Letter to the Editor From Sumi et al: "Lower Bone Turnover and Skeletal PTH Responsiveness in Japanese Compared to European Patients Receiving Hemodialysis"

peer reviewe

Lower Bone Turnover and Skeletal PTH Responsiveness in Japanese Compared to European Patients on Hemodialysis.

peer reviewed("[en] CONTEXT: Parathyroid hormone (PTH) treatment targets for patients receiving hemodialysis (HD) are lower in Japan than in Europe. Whether this translates to lower bone turnover is unknown and could depend on skeletal PTH responsiveness. OBJECTIVE: This study investigates whether skeletal PTH responsiveness is better preserved in Japanese vs European patients receiving HD. METHODS: This is a post hoc analysis of data from 2 prospective cohort studies, using a case-control design. Patients receiving chronic intermittent HD therapy were eligible for inclusion. Participating Belgian and Japanese patients (n = 374) were matched 1:1 by age (59 ± 12 years), sex (66% male), diabetes (34%), and dialysis duration (39 months [22-63 months]). PTH, bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were measured centrally in Liège, Belgium. RESULTS: Japanese patients had lower levels of iPTH (207 vs 268 pg/mL; P < .001), BALP (15.3 vs 24.5 μg/L; P < .001), and TRAP5b (3.35 vs 5.79 U/L; P < .001). Linear regression analyses revealed lower levels of bone turnover markers for any given level of PTH in Japanese vs Belgian patients, indicating lower skeletal PTH responsiveness. Consistently, bone turnover markers were significantly lower in Japanese vs Belgian patients when stratifying or matching according to PTH levels. Male sex, obesity, and hyperphosphatemia were the main determinants of the bone turnover marker/PTH ratios. CONCLUSION: Japanese patients receiving HD have lower bone turnover than their European counterparts, even at similar PTH levels. The rationale for the current regional differences in PTH treatment targets remains obscure and deserves further attention.","[en] ",""

Bone turnover markers are associated with bone density, but not with fracture in end stage kidney disease: a cross-sectional study

Abstract Background Fracture risk is increased in chronic kidney disease (CKD), but assessment of bone fragility remains controversial in these patients. This study investigated the associations between bone turnover markers, bone mineral density (BMD), and prevalent fragility fracture in a cohort of kidney transplantation candidates. Methods Volumetric BMD of spine and hip was measured by quantitative computed tomography. Parathyroid hormone (PTH), bone-specific alkaline phosphatase, procollagen type-1 N-terminal propeptide, tartrate resistant alkaline phosphatase, and C- and N-terminal telopeptides of type 1 collagen were analyzed from fasting morning blood samples. Fragility fractures included prevalent vertebral fractures and previous low-trauma clinical fractures. Results The fracture prevalence was 18% in 157 adult kidney transplant candidates. Fractured patients had reduced BMD and Z-score at both spine and hip. Levels of bone turnover markers were significantly higher in patients on maintenance dialysis than in pre-dialysis patients; but did not differ between patients with and without fracture. There were strong, positive correlations between PTH and all bone turnover markers. PTH was negatively associated with Z-score at lumbar spine and total hip; in contrast, bone turnover markers were only negatively associated with total hip Z-score. Conclusions Bone turnover markers were negatively associated with bone density, but not associated with prevalent fracture in kidney transplantation candidates. The role of bone turnover markers in assessing bone fragility in CKD will require further investigation. Trial registration This study was registered at ClinicalTrials.gov with identifier NCT01344434

Bioavailable Testosterone Is Positively Associated With Bone Mineral Density in Male Kidney Transplantation Candidates

Introduction: Low levels of sex hormones are common in patients with chronic kidney disease (CKD) and may be a contributing factor to bone fragility. We investigated associations between levels of sex hormones and bone mineral density (BMD) in adult kidney transplantation candidates. Methods: Volumetric BMD of spine and hip were measured by computed tomography. Parathyroid hormone (PTH), testosterone (T), estradiol (E), and sex hormone–binding globulin were measured from fasting morning blood samples. Bioavailable (Bio) T and E were calculated based on constants for protein binding. Results: A total of 146 patients (102 men and 44 women) were included in the analyses. The median age was 54 years (range, 32−72 years); 32% were diabetic; and 36% received maintenance dialysis therapy. In men, Bio T was positively associated with BMD at the lumbar spine (β = 5.02, P = 0.002), total hip (β = 6.35, P = 0.001), and femoral neck (β = 13.9, P = 0.002), independently of age, body mass index, dialysis, diabetes type 1 and 2, parathyroid hormone, and steroid exposure. Bio E was positively associated with BMD at the lumbar spine (β = 0.23, P = 0.03) and femoral neck (β = 0.61, P = 0.04) using the same fully adjusted model. In postmenopausal women, Bio T was positively correlated with lumbar spine BMD (r = 0.46, P = 0.02). Conclusion: High endogenous levels of sex hormones are associated with greater BMD in male kidney transplantation candidates. Disturbances in the gonadal axis may contribute to skeletal fragility in men with late-stage CKD. Keywords: bone density, chronic kidney disease, gonadal sex steroids, hypogonadism, osteoporosi

Osteoprotegerin and mortality in hemodialysis patients with cardiovascular disease

Abstract. Background: Patients treated with hemodialysis (HD) have an increased mortality, mainly caused by cardiovascular disease (CVD). Osteoprotegerin (OPG) is a glycoprotein involved in the regulation of the vascular calcification process. Previous studies have demonstrated that OPG is a prognostic marker of mortality. The aim of this study was to investigate if OPG was a prognostic marker of all-cause mortality in high-risk patients with end-stage renal disease and CVD. Methods: We prospectively followed 206 HD patients with CVD. OPG was measured at baseline and the patients were followed for 2 years or until reaching the primary endpoint, i.e., all-cause mortality. Results: All-cause mortality during follow-up was 44% (90/206). High OPG was associated with increased mortality, using the first tertile as reference, with an unadjusted HR of 1.70 (CI 1.00 -2.88) for the second tertile and HR of 1.63 (CI 0.96 -2.78) for the third tertile. In a multivariate Cox-regression analysis age, CRP and OPG in both the second and third tertile were significantly associated with increased mortality. In the unadjusted survival analysis, a test for trend of OPG yielded a p-value of 0.08; in the adjusted analyses, the p-value for trend was 0.03. Conclusions: In a high-risk population of hemodialysis patients with previously documented cardiovascular disease, a high level of OPG was an independent risk marker of all-cause mortality