Bone mineral density at different sites and 5 years mortality in end-stage renal disease patients: A cohort study

Abstract

Background

Bone disease with osteoporosis and renal osteodystrophy is common in end stage renal disease (ESRD) patients and associates with cardiovascular disease (CVD) and increased morbimortality. We investigated associations of low bone mineral density (BMD) at various bone sites with five year all-cause and CVD mortality in ESRD patients.

Methods

In a post hoc analysis of 426 ESRD patients (median age 56 years, 62% men) starting dialysis, BMD (whole-body dual-energy X-ray absorptiometry, DXA), body composition, nutritional status (subjective global assessment, SGA), handgrip strength (%HGS), Framingham CVD risk score (FRS) and biochemical biomarkers of nutrition and inflammation were assessed. We used the Fine and Gray competing risk regression analysis to assess survival analysis.

Results

In multivariate logistic regression analysis, %HGS and intact parathyroid hormone associated with low tertile of: BMD_total, BMD_head and BMD_pelvis, after adjusting for FRS, SGA, %HGS, s-albumin, hsCRP, lean body mass index and year of recruitment. Patients with high FRS had low BMD_head (p < 0.001). Low tertile of BMD_total (sHR, 1.53), BMD_head (sHR 1.54) and BMD_pelvis (sHR 1.60) associated with increased all-cause mortality whereas no such associations were found for the trabecular bone rich sites BMD arm, leg, trunk, rib or spine. Low tertile of BMD_total (sHR 1.94), BMD_head (sHR 1.68), BMD_leg (sHR 2.25) and BMD_pelvis (sHR 2.45) associated with increased CVD mortality whereas BMD at other sites did not associate with CVD mortality.

Conclusion

Low head and pelvis BMD, and low total BMD, as assessed by whole-body DXA, were independent predictors of increased risk of all-cause and CVD mortality. Cortical BMD appeared to have stronger association to survival in ESRD than trabecular BMD.

Introduction

Patients with chronic kidney disease (CKD) suffer from CKD-mineral and bone disorders (CKD-MBD) including osteoporosis and renal osteodystrophy that associate with generalized vascular calcification, coronary artery calcification (CAC) and cardiovascular disease (CVD). These common interlinked features contribute to severe and not seldom fatal complications leading to markedly increased mortality especially in patients with end stage renal disease (ESRD). Bone disease in CKD is a "mixture" of renal osteodystrophy characterized by low bone quality due to turnover, mineralization, volume defects caused by renal disease, and senile-menopausal osteoporosis. Thus, the mechanical properties of bones are compromised by low bone quality as well as by low bone mass in ESRD. Impaired bone status associates with aortic calcification and vascular stiffening [1], and a high CAC score in hemodialysis patients associate with CVD events [2], the major cause of mortality in these patients.

Central dual-energy X-ray absorptiometry (DXA) yielding measures of bone mineral density (BMD) is a well-established tool for diagnosis of osteoporosis. In addition, whole-body DXA analyzing body composition including bone mineral content (BMC) may also be used to assess BMD. While BMD assessed by central DXA or whole-body DXA reflect similar bone properties, these methods are not equivalent, and therefore for the diagnosis of osteoporosis, the interpretation of BMD values yielded by the two methods may differ [3,4]. Nevertheless, in ESRD patients, a low BMD - as assessed by central DXA, whole-body DXA, and also by digital image processing (DIP) - associates not only with increased risk of future fractures but also with arteriosclerosis and coronary and vascular calcification [[5], [6], [7]] as well as with low muscle strength, low lean body mass and poor nutritional status. In a previous study, low BMD by whole-body DXA was found to be associated with body composition, especially total fat mass, poor nutritional status and increased mortality risk in ESRD patients [8].

A meta-analysis based on prospective cohort studies in the general population demonstrated that lower BMD - at all investigated sites of BMD measurements – were associated with increased CVD-related and all-cause mortality [9]. In patients with ESRD, the bone-cardiovascular axis is perturbed due to the presence of CKD-MBD, vitamin D deficiency, secondary hyperparathyroidism, and numerous other metabolic and hormonal alterations [10,11] Bone status as assessed by BMD may therefore conceivably have an even greater impact on vascular calcification and cardiovascular events than in the general population. In ESRD patients, low total BMD by whole-body DXA associates with increased CVD-related and all-cause mortality [5,8], while there is much less information regarding the association between BMD at different bone sites and mortality. The aim of the present study was to evaluate the association of low BMD by whole-body DXA at various bone sites with all-cause and CVD mortality in ESRD patients.