Sex hormones, sex hormone binding globulin, and vertebral fractures in older men.

The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men.

Fracture Incidence in Adult Kidney Transplant Recipients.

BACKGROUND: It remains uncertain whether kidney transplant recipients are a high-risk group for fracture. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Bone kidney interactions.

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.

Inhibiting the progression of arterial calcification with vitamin K in HemoDialysis patients (iPACK-HD) trial: rationale and study design for a randomized trial of vitamin K in patients with end stage kidney disease.

BACKGROUND: 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. METHODS/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: NCT 01528800.

CONTEXTE: La maladie cardiovasculaire, qui est partiellement attribuable à la calcification vasculaire progressive, est la cause principale de décès chez les patients atteints d'insuffisance rénale terminale (IRT) en hémodialyse. La vitamine K pourrait jouer un rôle dans la prévention de la calcification vasculaire, en raison de la présence de protéines dépendantes à la vitamine K dans les tissus vasculaires, dont l'ostéocalcine. Le modèle animal, de même que des études d'observation, témoignent du rôle de la vitamine K dans la prévention de la calcification vasculaire. Une étude réalisée à grande échelle serait nécessaire afin d'étudier l'effet de la supplémentation de vitamine K sur la progression de la calcification vasculaire chez les patients atteints d'IRT, un groupe à risque pour les carences infracliniques en vitamine K. MÉTHODE/TYPE D'ÉTUDE: Nous prévoyons effectuer un essai clinique aléatoire, à double insu et multicentrique auprès de patients atteints d'IRT, traités en hémodialyse hospitalière en Amérique du Nord. On affectera au hasard les sujets admissibles qui présentent dans l'artère coronaire un taux de calcium supérieur ou égal à 30 unités d'Agatston, soit au groupe auquel on administre un traitement (10 mg de phylloquinone trois fois par semaine), soit au groupe témoin (administration du placebo trois fois par semaine). Le critère d'évaluation principal est la progression de la calcification de l'artère coronaire, définie comme une augmentation supérieure à 15% (résultat CAC) par rapport au point de référence, au bout de douze mois. DISCUSSION: La supplémentation de vitamine K est une stratégie nutritionnelle à la fois simple, sécuritaire et rentable, qui peut être aisément intégrée aux soins aux patients. S'il s'avère que la vitamine K réduit la progression de la calcification de l'artère coronaire, il pourrait y avoir une diminution de la morbidité et de la mortalité chez les hommes et les femmes atteints d'IRT.

Fractures in chronic kidney disease: pursuing the best screening and management.

PURPOSE OF REVIEW: Osteoporotic fractures are common and cause increased sickness and death. Men and women with chronic kidney disease (CKD) are at particularly high risk of osteoporotic fractures. Currently, however, there are no guidelines concerning noninvasive methods to assess fracture risk in CKD. Further, approved treatments to prevent fractures in otherwise healthy men and women are only recommended for use with caution in those with CKD. This review focuses on the recent data that support the use of noninvasive methods to assess fracture risk in CKD and highlights new therapies that could be used in fracture prevention in CKD. RECENT FINDINGS: Data from prospective studies demonstrate that low bone mineral density predicts fracture in CKD patients. Post-hoc analyses demonstrate that agents approved for the treatment of postmenopausal osteoporosis (bisphosphonates, denosumab and teriparatide) when given to those with CKD are well tolerated and potentially efficacious with respect to fracture risk reduction. SUMMARY: To date, patients, and nephrologists taking care of them, have largely ignored fracture risk assessment and treatment in CKD. This should change given recent data. Further studies are needed, specifically bone histomorphometric studies, which will increase our understanding of CKD-mineral bone disease (MBD) pathophysiology, and randomized clinical trials of therapy in patients with CKD.

Teriparatide and bone turnover and formation in a hemodialysis patient with low-turnover bone disease: a case report.

Teriparatide, a recombinant form of parathyroid hormone, is an anabolic agent approved for use in women and men with osteoporosis. However, it is not well studied in people with chronic kidney disease (CKD). We report on a patient with stage 5 CKD treated with dialysis who presented to our clinic with multiple fractures, including bilateral nondisplaced pelvic fractures resulting in chronic pain and interfering with the patient's ability to work. Bone histomorphometry demonstrated low-turnover bone disease, and he was treated with 20µg of teriparatide (subcutaneous injection) every morning for 24 months. Within 6 months of initiating therapy, the patient's pain resolved and he was able to resume work. Serum calcium and phosphate levels remained within reference ranges throughout his treatment, and he sustained no further fractures. During 24 months of treatment, bone mineral density was maintained at the lumbar spine, and there was an increase of 4% at the femoral neck and total hip. A second transiliac bone biopsy demonstrated improvements in static and dynamic parameters of bone formation. In our patient, 24-month treatment with teriparatide was safe and effective; however, larger studies are needed to determine the efficacy of teriparatide in the dialysis-dependent CKD population.

Can we compare serum sclerostin results obtained with different assays in hemodialysis patients?

PURPOSE: Sclerostin, secreted by osteocytes, plays a key role in antagonizing bone formation. Recent studies, which seldom include chronic kidney disease (CKD) patients, have reported on the association of sclerostin and mortality, with contradictory results. The assay-linked variability may contribute to these discrepant results. METHODS: We have compared sclerostin results obtained with two assays (TECO and Biomedica) in a cohort of 91 CKD patients undergoing hemodialysis. RESULTS: We found a strong correlation (r = 0.870, p < 0.0001) between the serum sclerostin concentrations measured by the two assays. Bland-Altman plot shows that, although there was a partial agreement between the assays, differences found for individual values (-0.27 ± 0.54; ranging from -1.3 to 0.8 ng/ml) were quite unpredictable. By using TECO, there was a significant relationship between serum sclerostin, and calcitonin (r = 0.224), IL-6 (r = 0.251) and FGF23 (r = 0.331) levels while no correlation was found with PTH or total alkaline phosphatase. Regarding Biomedica, there was a significant correlation with calcitonin (r = 0.260), and ß2 microglobulin (r = 0.210), but no correlation with PTH or total alkaline phosphatase. Overall, 25.3% among the patients had different classifications as to normal or high values, according to the manufacturer. CONCLUSION: Sclerostin levels should be interpreted with caution, as they can vary widely according to the assay used. Further studies are clearly needed before considering sclerostin as a true marker of mortality. Moreover, we do not know at present which serum sclerostin levels should be regarded as either normal or potentially dangerous in patients with CKD.

Bone imaging and fracture risk assessment in kidney disease.

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.

Vascular calcification in patients with nondialysis CKD over 3 years.

BACKGROUND AND OBJECTIVES: Vascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3-5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models. RESULTS: VC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to 2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were independently related to AS≥3. After a median follow-up of 35 months (interquartile range=17-36), there were 70 deaths (10%). After multivariate adjustment for age, smoking, diabetes, comorbidity, renal function, and level of phosphorous, AS≥3 but not KS>6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event-free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC did not predict renal progression. CONCLUSIONS: VC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful index to identify patients with CKD at high risk of death and morbidity as previously reported in patients on dialysis.

Revisiting KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder: a commentary from a Kidney Disease: Improving Global Outcomes controversies conference.

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.

Comparison of fracture risk prediction among individuals with reduced and normal kidney function.

BACKGROUND AND OBJECTIVES: The Fracture Risk Assessment Tool (FRAX) is widely used to predict the 10-year probability of fracture; however, the clinical utility of FRAX in CKD is unknown. This study assessed the predictive ability of FRAX in individuals with reduced kidney function compared with individuals with normal kidney function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The discrimination and calibration (defined as the agreement between observed and predicted values) of FRAX were examined using data from the Canadian Multicentre Osteoporosis Study (CaMos). This study included individuals aged ≥40 years with an eGFR value at year 10 of CaMos (defined as baseline). The cohort was stratified by kidney function at baseline (eGFR<60 ml/min per 1.73 m(2) [72.2% stage 3a, 23.8% stage 3b, and 4.0% stage 4/5] versus ≥60 ml/min per 1.73 m(2)) and followed individuals for a mean of 4.8 years for an incident major osteoporotic fracture (clinical spine, hip, forearm/wrist, or humerus). RESULTS: There were 320 individuals with an eGFR<60 ml/min per 1.73 m(2) and 1787 with an eGFR≥60 ml/min per 1.73 m(2). The mean age was 67±10 years and 71% were women. The 5-year observed major osteoporotic fracture risk was 5.3% (95% confidence interval [95% CI], 3.3% to 8.6%) in individuals with an eGFR<60 ml/min per 1.73 m(2), which was comparable to the FRAX-predicted fracture risk (6.4% with bone mineral density; 8.2% without bone mineral density). A statistically significant difference was not observed in the area under the curve values for FRAX in individuals with an eGFR<60 ml/min per 1.73 m(2) versus ≥60 ml/min per 1.73 m(2) (0.69 [95% CI, 0.54 to 0.83] versus 0.76 [95% CI, 0.70 to 0.82]; P=0.38). CONCLUSIONS: This study showed that FRAX was able to predict major osteoporotic fractures in individuals with reduced kidney function; further study is needed before FRAX should be routinely used in individuals with reduced kidney function.

Bone mineral density predicts fractures in chronic kidney disease.

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 versus 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 to 0.80) and in those without fracture was 0.95 g/cm2 (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm3 (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm3 (95% CI, 306 to 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.

Hyponatremia and Fractures: Findings From the MrOS Study.

Hyponatremia may be a risk factor for fracture. To determine the relationship between hyponatremia and fracture we conducted cross-sectional and longitudinal analyses using data from the Osteoporotic Fractures in Men (MrOS) study. The MrOS study enrolled 5122 community dwelling men aged ≥65 years from six centers across the United States. We excluded men taking bisphosphonates, those with unknown medication history, those without serum sodium measures, or those with out of range assays for serum sodium. Serum sodium was measured at study entry. Subjects were followed for fractures (nonspine [including hip], hip, incident morphometric, and prevalent morphometric) for up to 9 years. We used Cox proportional hazards models to analyze the association between serum sodium levels (<135 mmol/L versus ≥135 mmol/L) and risk of nonspine and hip fractures, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). We examined the association between morphometric vertebral fractures and serum sodium using logistic regression models, presented as odds ratios (ORs) and 95% CI. Hyponatremia was observed in 64 men (1.2% of the cohort). After adjusting for age, BMI, study center, and other covariates, we found that, compared to men with serum sodium ≥135 mmol/L, those with serum sodium <135 mmol/L, had an increased risk of hip fracture (HR = 3.04; 95% CI, 1.37 to 6.75), prevalent morphometric spine fracture (OR = 2.46; 95% CI, 1.22 to 4.95), and incident morphometric spine fracture (OR = 3.53; 95% CI, 1.35 to 9.19), but not nonspine fracture (OR = 1.44; 95% CI, 0.85 to 2.44). Adjusting for bone mineral density (BMD) did not change our findings. Our data show that hyponatremia is associated with up to a doubling in the risk of hip and morphometric spine fractures, independent of BMD. Further studies, to determine how hyponatremia causes fractures and if correction of hyponatremia decreases fractures, are needed.

The clinical characteristics of patients with hip fractures in typical locations and atypical femoral fractures.

UNLABELLED: 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. INTRODUCTION: This study aims to describe the characteristics of patients with typical and atypical fractures of the femur assessed in a tertiary care osteoporosis center. METHODS: 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. RESULTS: 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/m2) than in those with typical (23.1±4.3 kg/m2) (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). CONCLUSIONS: 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.

Fractures in chronic kidney disease: neglected, common, and associated with sickness and death.

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.

The three-year incidence of fracture in chronic kidney disease.

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.

Heterogeneity in skeletal load adaptation points to a role for modeling in the pathogenesis of osteoporotic fracture.

Genetic, environmental, or hormonal factors may cause heterogeneity in skeletal load response. Individuals with reduced sensitivity to load should require higher strains to generate an adaptive response, consequently have weaker bones and fracture more frequently. The purpose of our study was to determine if stresses (proportional to strains) at the femoral neck under equivalent loads were higher in women with a history of fractures compared with women without fractures. We studied postmenopausal women participating in the Canadian Multicentre Osteoporosis Study who had available hip structure analysis data from dual-energy X-ray absorptiometry scans (n = 2168). Women were categorized into 2 groups based on their number of self-reported fractures. We computed stress (megapascals) at the inferomedial margin of the femoral neck in a one-legged stance mode using a 2-dimensional engineering beam analysis. We used linear regression (SAS 9.3) to determine associations between stress, geometry parameters, and number of fractures. Postmenopausal women with 1 or more fractures had higher stress (2.6%), lower narrow neck bone mineral density (4.2%), cross-sectional area (3.9%), and section modulus (9.6%) than postmenopausal women without fractures (all p < 0.05). These findings provide evidence of heterogeneity in load response and suggest an important role for modeling in the pathogenesis of osteoporotic fracture.

Osteoprotegerin and fractures in men and women with chronic kidney disease.

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 3­5 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 1.02­1.25); however, OPG did not discriminate fracture status well (area under the receiver operating characteristic curve 0.61, 95 % CI 0.52­0.70). OPG is associated with fractures in men and women with stage 3­5 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.