[Show abstract][Hide abstract] ABSTRACT: Cardiovascular disease, which is due in part to progressive vascular calcification, is the leading cause of death among patients with end stage kidney disease (ESKD) on dialysis. A role for vitamin K in the prevention of vascular calcification is plausible based on the presence of vitamin K dependent proteins in vascular tissue, including matrix gla protein (MGP). Evidence from animal models and observational studies support a role for vitamin K in the prevention of vascular calcification. A large-scale study is needed to investigate the effect of vitamin K supplementation on the progression of vascular calcification in patients with ESKD, a group at risk for sub-clinical vitamin K deficiency.
We plan a prospective, randomized, double-blind, multicenter controlled trial of incident ESKD patients on hemodialysis in centers within North America. Eligible subjects with a baseline coronary artery calcium score of greater than or equal to 30 Agatston Units, will be randomly assigned to either the treatment group (10 mg of phylloquinone three times per week) or to the control group (placebo administration three times per week). The primary endpoint is the progression of coronary artery calcification defined as a greater than 15% increase in CAC score over baseline after 12 months.
Vitamin K supplementation is a simple, safe and cost-effective nutritional strategy that can easily be integrated into patient care. If vitamin K reduces the progression of coronary artery calcification it may lead to decreased morbidity and mortality in men and women with ESKD.
[Show abstract][Hide abstract] ABSTRACT: The fact that bone disease and kidney disease co-exist is well known. Formally, this inter-relationship is called chronic kidney disease mineral bone disorder or CKD-MBD. Traditionally, it was thought that bone played a passive role in CKD-MBD - specifically that kidney disease caused disordered mineral metabolism which resulted in bone disease and ultimately fractures. More recently however our understanding of bone function in general and the role that bone plays in CKD-MBD in particular, has changed. This chapter will briefly review epidemiology of fractures in chronic kidney disease (CKD) and the roles that imaging and measuring markers of mineral metabolism can play in assessing fracture risk. We will then review more recent data consistent with the concept MBD occurs early in the course of CKD and, via the secretion of novel molecules and/or signalling pathways, the bone can influence other organ systems.
Reviews in Endocrine and Metabolic Disorders 07/2015; 16(2). DOI:10.1007/s11154-015-9314-3 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It remains uncertain whether kidney transplant recipients are a high-risk group for fracture.
We conducted a cohort study using Ontario, Canada health care databases to estimate the 3-, 5- and 10-year cumulative incidence of nonvertebral fracture (proximal humerus, forearm, hip) in adult kidney transplant recipients between 1994 and 2009, stratifying by sex and age (<50 versus ≥50 years) at transplant. We also assessed the 3-year cumulative incidence of all fracture locations (excluding skull, toes, and fingers) and falls, 10-year cumulative incidence of hip fracture alone, and nonvertebral fracture incidence in recipients compared to nontransplant reference groups matched on age, sex, and cohort entry year. We studied 4821 recipients (median age, 50 years).
Among the age and sex strata, female recipients aged 50 years or older had the highest 3-year cumulative incidence of nonvertebral fracture (3.1%; 95% confidence interval [95% CI], 2.1-4.4%). Recipients had a higher 3-year cumulative incidence of nonvertebral fracture (1.6%; 95% CI, 1.3-2.0%) compared to the general population with no previous nonvertebral fracture (0.5%; 95% CI, 0.4-0.6%; P < 0.0001) and nondialysis chronic kidney disease (1.1%; 95% CI, 0.9-1.2%; P = 0.03), but a lower fracture incidence than the general population with a previous nonvertebral fracture (2.3%; 95% CI, 1.9-2.8%; P = 0.007). The 10-year cumulative incidence of hip fracture in all recipients was 1.7% (≥3% defined as high risk in clinical guidelines).
Kidney transplant recipients may have a lower fracture risk than previously suggested in the literature. Results inform our understanding of fracture incidence after kidney transplantation and how it compares to nontransplant populations.
[Show abstract][Hide abstract] ABSTRACT: Fractures are more common and are associated with greater morbidity and morality in patients with kidney disease than in members of the general population. Thus, it is troubling that in chronic kidney disease (CKD) patients there has been a paradoxical increase in fracture rates over the past 20 years compared to the general population. Increased fracture incidence in CKD patients may be driven in part by the lack of screening for fracture risk. In the general population, dual energy X-ray absorptiometry (DXA) is the clinical standard to stratify fracture risk, and its use has contributed to decreases in fracture incidence. In contrast, in CKD, fracture risk screening with DXA has been uncommon due to its unclear efficacy in predicting fracture and its inability to predict type of renal osteodystrophy. Recently, several prospective studies conducted in patients across the spectrum of kidney disease have demonstrated that bone mineral density measured by DXA predicts future fracture risk and that clinically relevant information regarding fracture risk is provided by application of the World Health Organization cutoffs for osteopenia and osteoporosis to DXA measures. Furthermore, novel high-resolution imaging tools, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have been used to elucidate the effects of kidney disease on cortical and trabecular microarchitecture and bone strength and to identify potential targets for strategies that protect against fractures. This review will discuss the updated epidemiology of fractures in CKD, fracture risk screening by DXA, and the utility of state-of-the art imaging methods to uncover the effects of kidney disease on the skeleton.
Current Osteoporosis Reports 03/2015; 13(3). DOI:10.1007/s11914-015-0262-3
[Show abstract][Hide abstract] ABSTRACT: Men and women with chronic kidney disease (CKD) are at an increased risk of fracture, and this risk increases as kidney function deteriorates. Fractures are associated with morbidity, mortality, and economic costs. Despite this there is a paucity of data regarding how to evaluate risk for fractures in CKD and how to treat high-risk patients. Evidence suggests that bone mineral density (BMD) as assessed by dual energy x-ray absorptiometry (DXA) is associated with fractures and can also predict future fractures in predialysis (stages 1-3) CKD patients. In the absence of considerable abnormalities in markers of mineral metabolism, treatment with antiresorptive agents in men and women with early CKD at high fracture risk may be appropriate. Of note, recent data suggest that low BMD as measured by DXA can also predict fractures in patients with more advanced CKD (stages 4, 5, and 5D). However, treatment in patients with advanced CKD requires bone biopsy, the gold standard to assess bone turnover, prior to treatment. Further research, focusing on non-invasive methods to assess fracture risk and bone turnover, together with randomized controlled trials of treatments to reduce fractures in patients at all stages of CKD, are required. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of Internal Medicine 03/2015; 278(1). DOI:10.1111/joim.12361 · 6.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new definition and classification of chronic kidney disease-mineral and bone disorder (CKD-MBD) was proposed in 2005 and it was later followed by a guideline publication on this topic from Kidney Disease: Improving Global Outcomes (KDIGO) in 2009. This work recognized that CKD-MBD is a syndrome of bone abnormalities, laboratory abnormalities, and vascular calcification linked to fractures, cardiovascular disease, and mortality. Because of limited data at the time of the original guideline systematic review, many of the recommendations were cautiously vague. KDIGO convened a Controversies Conference in October 2013 to review the CKD-MBD literature published since the 2009 guideline. Specifically, the objective of this conference was to determine whether sufficient new data had emerged to support a reassessment of the CKD-MBD guideline and if so to determine the scope of these potential revisions. This report summarizes the results of these proceedings, highlighting important new studies conducted in the interval since the original KDIGO CKD-MBD guideline.Kidney International advance online publication, 4 February 2015; doi:10.1038/ki.2014.425.
Kidney International 02/2015; 87(3). DOI:10.1038/ki.2014.425 · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The utility of bone mineral density (BMD) testing in chronic kidney disease (CKD) is not known. We performed a meta-analysis of studies reporting on BMD and fracture in CKD. All but one study was cross-sectional. BMD was lower in those with CKD and fractures compared to those without fractures.
CKD is associated with an increased risk of fracture. The utility of dual energy X-ray absorptiometry (DXA) to assess fracture risk in CKD is unknown.
We performed an updated meta-analysis and systematic review of published studies that reported on the association between DXA and fracture (morphometric spine or clinical nonspine) in predialysis and dialysis CKD. We identified 2,894 potential publications, retrieved 292 for detailed review, and included 13. All but one study was cross-sectional and three reported on the ability of DXA to discriminate fracture status in predialysis CKD. Results were pooled using a random effects model and statistical heterogeneity was assessed using the I (2) statistic.
BMD was statistically significantly lower at the femoral neck, lumbar spine, the 1/3 and ultradistal radius in subjects with fractures compared to those without regardless of dialysis status. For example, femoral neck BMD was 0.06 g/cm(2) lower in dialysis subjects and 0.102 g/cm(2) lower in predialysis subjects with fractures compared to those without. Lumbar spine BMD was 0.05 g/cm(2) lower in dialysis subjects and 0.108 g/cm(2) lower in predialysis subjects with fractures compared to those without. Our meta-analysis was limited to studies with small numbers of subjects and even smaller numbers of fractures. All of the studies were observational and only one was prospective. There was statistical heterogeneity at the lumbar spine, 1/3 and ultradistal radius.
Our findings suggest that BMD can discriminate fracture status in predialysis and dialysis CKD. Larger, prospective studies are needed.
Osteoporosis International 12/2014; 26(2). DOI:10.1007/s00198-014-2813-3 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathophysiology of atypical fractures is unknown. We compared characteristics of patients with atypical femoral fractures and hip fractures in typical locations of the femur. Patients with atypical fracture reported a longer duration of use of bisphosphonates, had higher body mass index, and higher total hip bone mineral density. Further studies are needed.
This study aims to describe the characteristics of patients with typical and atypical fractures of the femur assessed in a tertiary care osteoporosis center.
We abstracted clinical, laboratory, and radiographic data on subjects with a history of a low-impact fracture at the femur and/or hip (confirmed by review of radiograph and/or radiology report) from January 2008 to October 2011. Available radiographs were reviewed and fracture categorized as typical or atypical by a radiologist blinded to the original diagnosis.
Radiology reports were available for 72 subjects: 40 hip fractures in typical locations (typical fracture), 16 atypical femoral fracture (atypical fracture), and 16 were excluded. While both those with typical and atypical fractures reported taking bisphosphonates at the time of fracture, duration of use was longer with atypical fractures (104.2 ± 42.0 months) compared with typical (71.1 ± 62.8 months) (p = 0.04). Body mass index (BMI) was higher in patients with atypical fractures (26.2 ± 3.2 kg/m(2)) than in those with typical (23.1 ± 4.3 kg/m(2)) (p = 0.006). Total bone mineral density (BMD) was higher in patients with atypical fracture (0.795 ± 0.102) versus typical (0.686 ± 0.130) (p = 0.003) Previous history of cancer was reported by 7 of 16 patients with atypical and 7 of 40 patients with typical fracture (p = 0.04).
Compared to those with typical fractures, patients with atypical fracture report a longer duration of use of bisphosphonates, higher BMI, and higher total hip BMD. Future studies should examine if these differences contribute to the pathophysiology of atypical fractures.
Archives of Osteoporosis 12/2014; 9(1):171. DOI:10.1007/s11657-014-0171-6
[Show abstract][Hide abstract] ABSTRACT: Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA), and/or high resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women ≥ 18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low-trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4 and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures vs. those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm2 (95% Confidence Interval (CI): 0.73-0.80) and in those without fracture was 0.95 g/cm2 (95% CI: 0.92-0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture vs. those without. For example, volumetric BMD in those with incident fractures was 232 mgHA/cm3 (95% CI: 213-251) and in those without fracture was 317.6 mgHA/cm3 (95% CI: 306-329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD. This article is protected by copyright. All rights reserved
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 11/2014; 30(5). DOI:10.1002/jbmr.2406 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Knowing a person's fracture risk according to their kidney function, gender, and age may influence clinical management and decision-making. Using healthcare databases from Ontario, Canada, we conducted a cohort study of 679,114 adults of 40 years and over (mean age 62 years) stratified at cohort entry by estimated glomerular filtration rate ((eGFR) 60 and over, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73 m(2)), gender, and age (40-65 and over 65 years). The primary outcome was the 3-year cumulative incidence of fracture (proportion of adults who fractured (hip, forearm, pelvis, or proximal humerus) at least once within 3-years of follow-up). Additional analyses examined the fracture incidence per 1000 person-years, hip fracture alone, stratification by prior fracture, stratification by eGFR and proteinuria, and 3-year cumulative incidence of falls with hospitalization. The 3-year cumulative incidence of fracture significantly increased in a graded manner in adults with a lower eGFR for both genders and both age groups. The 3-year cumulative incidence of fracture in women over 65 years of age across the 5 eGFR groups were 4.3%, 5.8%, 6.5%, 7.8%, and 9.6%, respectively. Corresponding estimates for men over 65 years were 1.6%, 2.0%, 2.7%, 3.8%, and 5.0%, respectively. Similar graded relationships were found for falls with hospitalization and additional analyses. Thus, many adults with chronic kidney disease will fall and fracture. Results can be used for prognostication and guidance of sample size requirements for fracture prevention trials.Kidney International advance online publication, 15 January 2014; doi:10.1038/ki.2013.547.
Kidney International 01/2014; 86(4). DOI:10.1038/ki.2013.547 · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bone fractures in dialysis patients have been poorly studied in the past. Tentori et al. partially fill this gap, assessing the incidence of post-fracture morbidity and mortality in patients of the Dialysis Outcomes and Practice Patterns Study (DOPPS). A high frequency of fractures and increased adverse outcomes following a fracture were observed. The nephrology community should pay more attention to bone fractures in dialysis patients.
Kidney International 01/2014; 85(1):20-2. DOI:10.1038/ki.2013.302 · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We assessed the ability of the World Health Organization's fracture risk assessment tool (FRAX), bone mineral density (BMD), and age to discriminate fracture status in adults with pre-dialysis chronic kidney disease (CKD). In adults with CKD, FRAX was able to discriminate fracture status but performed no better than BMD alone.
Patients with CKD are at increased risk for fracture but the best method to assess fracture risk is not known.
We assessed the ability of the World Health Organization's FRAX, compared with BMD at the femoral neck (FN), and age to discriminate fracture status (prevalent clinical nonspine and/or morphometric vertebral) in men and women, 18 years and older with pre-dialysis CKD. Results are presented as area under receiver operator characteristic curves (AUC) with 95 % confidence intervals (CI).
We enrolled 353 subjects; mean age was 65 ± 14 years; weight was 79 ± 18 kg, and estimated glomerular filtration rate was 28 ml/min/1.73 m(2). About one third of the subjects had a prevalent clinical nonspine and/or morphometric vertebral fracture. FRAX was able to discriminate among those with prevalent clinical nonspine fractures (AUC, 0.72; 95 % CI, 0.65-0.78), morphometric vertebral fractures (AUC, 0.66; 95 % CI, 0.59-0.73), and any fracture (AUC, 0.71; 95 % CI, 0.65-0.77). The discriminative ability of BMD at the FN alone was similar to FRAX for morphometric vertebral and any fractures; FRAX performed better than BMD for prevalent clinical nonspine fractures (AUC for BMD alone, 0.66; 95 % CI, 0.60-0.73). Compared to FRAX, the AUC for age alone was lower for all fracture types.
Among men and women with CKD, FRAX is able to discriminate fracture status but performs no better than BMD alone.
Osteoporosis International 10/2013; 25(1). DOI:10.1007/s00198-013-2524-1 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fractures are common in men and women with chronic kidney disease (CKD) but the best tool to identify those at high risk is unknown. Increased circulating osteoprotegerin (OPG) is associated with fractures in postmenopausal women. We determined if serum OPG was associated with prevalent fractures (self-reported low-trauma fractures since 40 years of age and/or prevalent vertebral fractures identified by radiographs) in men (n = 97) and women (n = 67) with stage 3-5 CKD. Analyses were performed unadjusted and adjusted for stage of CKD. Results are expressed as mean ± standard deviation (SD), and as odds ratio (OR) per SD increase in OPG with 95 % confidence intervals (CI). The mean age was 62.7 ± 16.3 years, and mean weight was 78.9 ± 18.7 kg. Compared to those without fractures, those with fractures (n = 55) were older (p < 0.01). Serum OPG increased as kidney function decreased, and OPG was higher in those with fractures compared to those without (9.42 ± 4.08 vs 8.06 ± 3.11 pmol/L, p = 0.02). After adjusting for stage of CKD, increased OPG was associated with an increased fracture risk (OR 1.13, 95 % CI 1.02-1.25); however, OPG did not discriminate fracture status well (area under the receiver operating characteristic curve 0.61, 95 % CI 0.52-0.70). OPG is associated with fractures in men and women with stage 3-5 CKD; however, the ability of OPG to discriminate fracture status is poor and cannot be used in isolation to assess fracture risk. Further studies should examine the ability of OPG in combination with other risk factors to better discriminate fracture status in men and women with CKD.
Journal of Bone and Mineral Metabolism 10/2013; 32(4). DOI:10.1007/s00774-013-0506-1 · 2.46 Impact Factor