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1.
Nutrients ; 16(9)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38732575

ABSTRACT

Osteosarcopenia, the concurrent presence of sarcopenia and osteopenia/osteoporosis, poses a significant health risk to older adults, yet its impact on clinical outcomes is not fully understood. The aim of this prospective, longitudinal multicentre study was to examine the impact of osteosarcopenia on 3-year mortality and unplanned hospitalizations among 572 older hospitalized patients (mean age 75.1 ± 10.8 years, 78% female). Sarcopenia and low bone mineral density (BMD) were evaluated using Dual Energy X-ray Absorptiometry and the European Working Group on Sarcopenia in Older People (EWGSOP2) and WHO criteria, respectively. Among participants, 76% had low BMD, 9% were sarcopenic, and 8% had osteosarcopenia. Individuals with osteosarcopenia experienced a significantly higher rate of mortality (46%, p < 001) and unplanned hospitalization (86%, p < 001) compared to those without this condition. Moreover, "healthy" subjects-those without sarcopenia or low BMD-showed markedly lower 3-year mortality (9%, p < 001) and less unplanned hospitalization (53%, p < 001). The presence of osteosarcopenia (p = 0.009) increased the 3-year mortality risk by 30% over sarcopenia alone and by 8% over low BMD alone, underscoring the severe health implications of concurrent muscle and bone deterioration. This study highlights the substantial impact of osteosarcopenia on mortality among older adults, emphasizing the need for targeted diagnostic and therapeutic strategies.


Subject(s)
Bone Density , Bone Diseases, Metabolic , Hospitalization , Osteoporosis , Sarcopenia , Humans , Sarcopenia/mortality , Sarcopenia/complications , Sarcopenia/epidemiology , Female , Aged , Male , Hospitalization/statistics & numerical data , Aged, 80 and over , Prospective Studies , Osteoporosis/mortality , Osteoporosis/complications , Bone Diseases, Metabolic/mortality , Longitudinal Studies , Absorptiometry, Photon , Risk Factors
2.
Breast Cancer Res Treat ; 180(3): 675-685, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32124136

ABSTRACT

PURPOSE: The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2-3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. METHODS: We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan-Meier methods and Cox proportional hazards models were used for analyses. RESULTS: Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45-1.49), osteoporosis HR 1.10 (95% CI 0.26-4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40-1.42), osteoporosis HR 1.86 (95% CI 0.43-8.01)]. Moreover, bisphosphonate use did not impact DRFS. CONCLUSION: No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Bone Diseases, Metabolic/mortality , Breast Neoplasms/drug therapy , Diphosphonates/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Osteoporosis/mortality , Antineoplastic Agents, Hormonal/adverse effects , Bone Diseases, Metabolic/chemically induced , Bone Diseases, Metabolic/drug therapy , Bone Diseases, Metabolic/pathology , Breast Neoplasms/pathology , Carcinoma, Lobular/drug therapy , Carcinoma, Lobular/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Recurrence, Local/pathology , Osteoporosis/chemically induced , Osteoporosis/drug therapy , Osteoporosis/pathology , Prognosis , Survival Rate , Tamoxifen/adverse effects
3.
J Clin Endocrinol Metab ; 104(8): 3514-3520, 2019 08 01.
Article in English | MEDLINE | ID: mdl-30951170

ABSTRACT

CONTEXT: Although bone mineral density (BMD) is strongly associated with fracture and postfracture mortality, the burden of fractures attributable to low BMD has not been investigated. OBJECTIVES: We sought to estimate the population attributable fraction of fractures and fracture-related mortality that can be attributed to low BMD. DESIGN AND SETTING: This study is a part of an ongoing population-based prospective cohort study, the Dubbo Osteoporosis Epidemiology study. In total, 3700 participants aged ≥50 years participated in the study. Low-trauma fracture was ascertained by X-ray reports, and mortality was ascertained from the Birth, Death and Marriage Registry. RESULTS: Overall, 21% of women and 11% of men had osteoporotic BMD. In univariable analysis, 21% and 16% of total fractures in women and men, respectively, were attributable to osteoporosis. Osteoporosis combined with advancing age (>70 years) accounted for 34% and 35% of fractures in women and men, respectively. However, these two factors accounted for ∼60% of hip fractures. About 99% and 66% of postfracture mortality in women and men, respectively, were attributable to advancing age, osteoporosis, and fracture; however, most of the attributable proportion was accounted for by advancing age. CONCLUSIONS: A substantial health care burden of fracture is on people aged <70 years or nonosteoporosis, suggesting that treatment of people with osteoporosis is unlikely to reduce a large number of fractures in the general population.


Subject(s)
Bone Diseases, Metabolic/mortality , Fractures, Bone/mortality , Aged , Aged, 80 and over , Aging , Bone Density , Bone Diseases, Metabolic/complications , Female , Fractures, Bone/etiology , Humans , Male , Middle Aged , Prospective Studies , Registries , Risk Factors
4.
Clin Nutr ; 38(6): 2770-2777, 2019 12.
Article in English | MEDLINE | ID: mdl-30595376

ABSTRACT

BACKGROUND & AIMS: Osteopenia is a condition in which bone mineral density (BMD) is lower than normal, and it is an important determinant of bone fragility. However, the utility of osteopenia in assessing the risks of surgery is unclear. This study investigated the impact of preoperative low BMD on the outcomes in patients undergoing resection of extrahepatic biliary cancers. METHODS: A retrospective analysis was performed with 181 patients who underwent resections of extrahepatic biliary cancers between 2005 and 2015. Their BMD was measured on preoperative computed tomography images. Overall survival (OS) and recurrence-free survival (RFS) rates were compared according to BMD (normal vs. low), and the prognostic factors after surgery were assessed. Propensity score matching was used to minimize the bias in patient background. RESULTS: Older age and female were strongly associated with low BMD. These factors were used to construct the propensity score model, which yielded a matched cohort of 52 legs in each group. The OS (21.2% vs. 53.9% at 5 years, p < .001) and RFS (21.8% vs. 64.6% at 5 years, p < .001) rates were significantly lower in patients with low BMD (osteopenia) than in those with normal BMD (non-osteopenia). Multivariable analyses showed that low BMD was an independent factor predictive of poor OS (hazard ratio [HR]: 2.343, 95% confidence interval [CI]: 1.362-4.129, p = .002) and poor RFS (HR: 3.648, 95% CI: 1.986-6.990, p=<.001). CONCLUSIONS: Preoperative low BMD is closely related to mortality and cancer recurrence after the resection of extrahepatic biliary cancers. BMD screening in patients with cancer should be further highlighted in the oncology field.


Subject(s)
Bile Duct Neoplasms , Bone Density/physiology , Bone Diseases, Metabolic , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/surgery , Bone Diseases, Metabolic/complications , Bone Diseases, Metabolic/diagnostic imaging , Bone Diseases, Metabolic/mortality , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Retrospective Studies , Sarcopenia/complications , Sarcopenia/mortality , Tomography, X-Ray Computed
5.
Osteoporos Int ; 29(11): 2447-2456, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30094609

ABSTRACT

Low bone mineral density (BMD) gives an increased risk of fractures, which can lead to premature death. Can BMD of the wrist predict mortality? BMD consistent with osteopenia and osteoporosis gave a significantly increased risk of death for both men and women in a general population in Tromsø, Norway. INTRODUCTION: To investigate if bone mineral density (BMD) levels of the distal forearm, consistent with osteopenia and osteoporosis, can predict mortality and if grip strength is an effect modifier. METHODS: The study population constituted 6565 participants aged 50-79 years at baseline in the Tromsø Study wave 4 conducted in 1994-1995. Forearm BMD measured by SXA was categorized as "normal," "osteopenia," or "osteoporosis" following WHO's definition. Cox regression with all-cause mortality as the outcome over 22 years of follow-up was performed for men and women separately, adjusting for health-related factors, as well as BMD by grip strength interaction. A secondary analysis with a 15-year follow-up also adjusted for hip fractures and osteoporotic fractures. RESULTS: During follow-up, 3176 of participants died (47%). Those categorized as osteoporotic had higher mortality hazard ratio (HR) compared to those with normal BMD; men HR = 1.37 (95% confidence interval (CI) 1.19, 1.58) and women HR = 1.32 (1.14, 1.53) were adjusted for age, body mass index, physical activity, smoking habits, education, health status, chronic diseases, and grip strength. Corresponding HRs for osteopenia were men HR = 1.13 (1.00, 1.27) and women HR = 1.17 (1.01, 1.35). Further adjustments for fractures did only marginally attenuate the results, and HRs were still significant. There was no grip strength by BMD interaction. CONCLUSION: Men and women with low distal forearm BMD values, consistent with osteoporosis or osteopenia, had an increased mortality compared to normal BMD participants. High grip strength did not modify this association, and the association remained after adjustment for a range of health-related factors.


Subject(s)
Bone Diseases, Metabolic/mortality , Forearm/physiopathology , Hand Strength/physiology , Absorptiometry, Photon/methods , Age Distribution , Aged , Bone Density/physiology , Bone Diseases, Metabolic/physiopathology , Female , Follow-Up Studies , Hip Fractures/mortality , Hip Fractures/physiopathology , Humans , Male , Middle Aged , Norway/epidemiology , Osteoporosis/mortality , Osteoporosis/physiopathology , Osteoporotic Fractures/mortality , Osteoporotic Fractures/physiopathology , Reference Values , Sex Distribution
6.
PLoS One ; 13(8): e0202417, 2018.
Article in English | MEDLINE | ID: mdl-30138402

ABSTRACT

International Guidelines for mineral bone disorders recommend that in Non Dialytic-Chronic Kidney Disease (ND-CKD) clinical decisions should be based on the trend of serum PTH changes over time rather than on a single value. However, the prognostic impact of these changes in ND-CKD patients remains unknown. We performed a multicenter cohort study in ND-CKD patients (stage 1-5) followed for 36 months in 24 Italian Nephrology Units. PTH changes (ΔPTH) were defined as the absolute differences between all available PTH measurements following the first control and basal value. Primary endpoint in this subanalysis was renal death (End-Stage Renal Disease (ESRD) or all-causes death before ESRD). Association between renal death and ΔPTH was assessed by time-dependent Cox model for repeated measurements. Out of the original cohort (N = 884), we selected 543 patients (66.3±15.4 ys, 58.4% males) with at least two serum PTH measurements. At baseline, eGFR was 36 (IQR: 22.4-56.8) mL/min/1.73m2 and serum PTH 46 (IQR: 28-81) pg/mL. ΔPTH was in median 0 (IQR:-18/18) pg/mL. Basal predictors of longitudinal PTH increments were higher serum phosphate, more advanced CKD stages and lower serum PTH. Fully adjusted Cox model with ΔPTH quartiles as discrete time-dependent covariate showed a significant risk of renal death in the highest quartile (HR: 1.91; 95%CI:1.08-3.38; P = 0.026). Considering ΔPTH, as continuous time-dependent variable, (HR:1.02; 95%C.I.: 1.01-1.04; P = 0.004), risk of renal death progressively rose as ΔPTH increased. An increment in serum PTH over time is associated with a worse prognosis in ND-CKD patients, independently from baseline or any absolute concentration of serum PTH and phosphate.


Subject(s)
Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/mortality , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/mortality , Parathyroid Hormone/blood , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Follow-Up Studies , Humans , Italy/epidemiology , Male , Middle Aged , Prospective Studies , Survival Rate , Tertiary Care Centers
7.
Blood Purif ; 45(1-3): 1-7, 2018.
Article in English | MEDLINE | ID: mdl-29161692

ABSTRACT

BACKGROUND/AIMS: We examined the association between markers of chronic kidney disease - mineral and bone disorder (CKD-MBD) and mortality in hemodialysis (HD) patients. METHODS: We retrospectively reviewed the association between markers of CKD-MBD and mortality in 1,126 HD patients from 2009 to 2013 with baseline (B), time-average (TA), and time-dependent (TD) Cox regression models. RESULTS: Hypercalcemia (10.9-11.9 mg/dL) indicated an increased risk of all-cause mortality (TA: hazard ratio [HR] 3.49; p = 0.01). Hypophosphatemia (2.0-2.5 mg/dL) was significantly associated with an increased risk of all-cause mortality (TA: HR 5.18; p = 0.01). Hypophosphatemia (<2.0 mg/dL) was significantly associated with an increased risk of cardiovascular mortality in all models. Intact parathyroid hormone levels <60 and >1,500 pg/mL indicated an increased risk of all-cause mortality (TA: HR 1.64; p = 0.02; TD: HR 2.26; p = 0.02). CONCLUSION: Extreme values of CKD-MBD markers are associated with mortality risk in HD patients. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=478972.


Subject(s)
Bone Density , Bone Diseases, Metabolic , Hypercalcemia , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic , Aged , Biomarkers/blood , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/genetics , Bone Diseases, Metabolic/mortality , Female , Humans , Hypercalcemia/blood , Hypercalcemia/etiology , Hypercalcemia/mortality , Male , Middle Aged , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/therapy , Retrospective Studies , Risk Factors
8.
J Cachexia Sarcopenia Muscle ; 8(3): 482-489, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28025860

ABSTRACT

BACKGROUND: We aimed to examine the relationship between musculoskeletal deterioration and all-cause mortality in a cohort of women studied prospectively over a decade. METHODS: A cohort of 750 women aged 50-94 years was followed for a decade after femoral neck bone mineral density (BMD) and appendicular lean mass (ALM) were measured using dual energy X-ray absorptiometry, in conjunction with comorbidities, health behaviour data, and other clinical measures. The outcome was all-cause mortality identified from the Australian National Deaths Index. Using Cox proportional hazards models and age as the time variable, mortality risks were estimated according to BMD groups (ideal-BMD, osteopenia, and osteoporosis) and ALM groups (T-scores > -1.0 high, -2.0 to -1.0 medium, <-2.0 low). RESULTS: During 6712 person years of follow-up, there were 190 deaths, the proportions increasing with diminishing BMD: 10.7% (23/215) ideal-BMD, 23.5% (89/378) osteopenia, 49.7% (78/157) osteoporosis; and with diminishing ALM: 17.0% (59/345) high, 26.2% (79/301) medium, 50.0% (52/104) low. In multivariable models adjusted for smoking, polypharmacy, and mobility, compared with those with ideal BMD, mortality risk was greater for those with osteopenia [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.11-2.81] and osteoporosis (HR 2.61, 95%CI 1.60-4.24). Similarly, compared with those with high ALM, adjusted mortality risk was greater for medium ALM (HR 1.36, 95%CI 0.97-1.91) and low ALM (HR 1.65, 95%CI 1.11-2.45). When BMD and ALM groups were tested together in the model, BMD remained a predictor of mortality (HR 1.74, 95%CI 1.09-2.78; HR 2.82, 95%CI 1.70-4.70; respectively), and low ALM had borderline significance (HR 1.52, 95%CI 1.00-2.31), which was further attenuated after adjusting for smoking, polypharmacy, and mobility. CONCLUSIONS: Poor musculoskeletal health increased the risk for mortality independent of age. This appears to be driven mainly by a decline in bone mass. Low lean mass independently exacerbated mortality risk, and this appeared to operate through poor health exposures.


Subject(s)
Musculoskeletal Diseases/mortality , Musculoskeletal Diseases/pathology , Absorptiometry, Photon , Aged , Aged, 80 and over , Australia/epidemiology , Body Composition , Bone Density , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/mortality , Bone Diseases, Metabolic/pathology , Female , Humans , Middle Aged , Musculoskeletal Diseases/epidemiology , Musculoskeletal Diseases/etiology , Osteoporosis/epidemiology , Osteoporosis/etiology , Osteoporosis/mortality , Osteoporosis/pathology , Proportional Hazards Models , Registries
9.
Transplantation ; 100(3): 497-505, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26356179

ABSTRACT

The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.


Subject(s)
Bone Diseases, Metabolic/etiology , Cardiovascular Diseases/etiology , Kidney Transplantation , Kidney/metabolism , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/surgery , Biomarkers/blood , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/diagnosis , Bone Diseases, Metabolic/mortality , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Graft Survival , Humans , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/mortality , Risk Factors , Signal Transduction , Treatment Outcome
12.
Clin J Am Soc Nephrol ; 8(12): 2132-40, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24052218

ABSTRACT

BACKGROUND AND OBJECTIVES: Parathyroid hormone, calcium, and phosphate have been independently associated with cardiovascular event risk. Because these parameters may be on the same causal pathway and have been proposed as quality measures, an integrated approach to estimating event risks is needed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prevalent dialysis patients were followed from August 31, 2005 to December 31, 2006. A two-stage modeling approach was used. First, the 16-month probabilities of death and composite end point of death or cardiovascular hospitalization were estimated and adjusted for potential confounders. Second, patients were categorized into 1 of 36 possible phenotypes using average parathyroid hormone, calcium, and phosphate values over a 4-month baseline period. Associations among phenotypes and outcomes were estimated and adjusted for the underlying event risk estimated from the first model stage. RESULTS: Of 26,221 patients, 98.5% of patients were in 22 groups with at least 100 patients and 20% of patients were in the reference group defined using guideline-based reference ranges for parathyroid hormone, calcium, and phosphate. Within the 22 most common phenotypes, 20% of patients were in groups with significantly (P<0.05) higher risk of death and 54% of patients were in groups with significantly higher risk of the composite end point relative to the in-target reference group. Increased risks ranged from 15% to 47% for death and from 8% to 55% for the composite. More than 40% of all patients were in the three largest groups with elevated composite end point risk (high parathyroid hormone, target calcium, and high phosphate; target high parathyroid hormone, target calcium, and high phosphate; and target high parathyroid hormone, target calcium, and target phosphate). CONCLUSION: After adjusting for baseline risk, phenotypes defined by categories of parathyroid hormone, calcium, and phosphate identify patients at higher risk of death and cardiovascular hospitalization. Identifying common high-risk phenotypes may inform clinical interventions and policies related to quality of care.


Subject(s)
Bone Diseases, Metabolic/etiology , Cardiovascular Diseases/etiology , Hospitalization , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/therapy , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/diagnosis , Bone Diseases, Metabolic/mortality , Calcium/blood , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Cause of Death , Child , Child, Preschool , Female , Hospital Mortality , Humans , Infant , Infant, Newborn , Male , Middle Aged , Parathyroid Hormone/blood , Phenotype , Phosphates/blood , Proportional Hazards Models , Renal Dialysis/mortality , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/mortality , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
13.
Arch Osteoporos ; 7: 209-18, 2012.
Article in English | MEDLINE | ID: mdl-23196864

ABSTRACT

UNLABELLED: This article describes the adaptation of a model assessing the incidence of osteoporotic fractures and prevalence of postmenopausal osteoporosis (PMO) in Germany. PURPOSE: The purpose of this paper is to estimate the epidemiological burden of PMO in Germany from 2010 to 2020. METHODS: For each year of the study, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures (1, 2 or ≥3) and deaths. Although the fracture site was not explicitly accounted for in the model structure, the site (hip, vertebral, non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected the site-specific risk of death and of subsequent fractures. Model inputs included population size and life tables from 1970 to 2020, incidence of fracture and BMD by age in the general population (mean and standard deviation). RESULTS: In 2010, the number of osteoporotic fractures was estimated at 349,560 in women aged 50 years or more, including 80,177 hip and 48,550 vertebral fractures. By 2020, the population is expected to grow by 13.1 %. As a result, the number of fractures is predicted to increase by 15.2 %. The improvement in life expectancy is predicted to lead to a relatively smaller increase in the number of deaths attributable to fractures (+12.8 %), but also to an increase in the prevalence of women with multiple prior fractures (+25.5 %). CONCLUSION: The PMO disease model, first developed for Sweden, was adapted to Germany. Due to the ageing of the population, the number of osteoporotic fractures is expected to increase markedly by +15.2 % by 2020.


Subject(s)
Hip Fractures/epidemiology , Osteoporosis, Postmenopausal/epidemiology , Spinal Fractures/epidemiology , Age Distribution , Aged , Aged, 80 and over , Bone Density , Bone Diseases, Metabolic/epidemiology , Bone Diseases, Metabolic/mortality , Cost of Illness , Female , Germany/epidemiology , Hip Fractures/mortality , Humans , Incidence , Middle Aged , Models, Statistical , Osteoporosis, Postmenopausal/mortality , Postmenopause , Prevalence , Risk Factors , Spinal Fractures/mortality
14.
Nephrol Dial Transplant ; 27(7): 2899-907, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22207323

ABSTRACT

BACKGROUND: Maintenance hemodialysis (MHD) patients with polycystic kidney disease (PKD) have better survival than non-PKD patients. Mineral and bone disorders (MBD) are associated with accelerated atherosclerosis and cardiovascular death in MHD patients. It is unknown whether the different MBD mortality association between MHD populations with and without PKD can explain the survival differential. METHODS: Survival models were examined to assess the association between different laboratory markers of MBD [such as serum phosphorous, parathyroid hormone (PTH), calcium and alkaline phosphatase] and mortality in a 6-year cohort of 60,089 non-PKD and 1501 PKD MHD patients. RESULTS: PKD and non-PKD patients were 57±13 and 62±15 years old and included 46 and 45% women and 14 and 32% Blacks, respectively. Whereas PKD individuals with PTH 150 to <300 pg/mL (reference) had the lowest risk for mortality, the death risk was higher in patients with PTH<150 [hazard ratio (HR): 2.16 (95% confidence interval 1.53-3.06)], 300 to <600 [HR: 1.30 (0.97-1.74)] and ≥600 pg/mL [HR: 1.46 (1.02-2.08)], respectively. Similar patterns were found in non-PKD patients. Fully adjusted death HRs of time-averaged serum phosphorous increments<3.5, 5.5 to <7.5 and ≥7.5 mg/dL (reference: 3.5 to <5.5 mg/dL) for PKD patients were 2.82 (1.50-5.29), 1.40 (1.12-1.75) and 2.25 (1.57-3.22). The associations of alkaline phosphatase and calcium with mortality were similar in PKD and non-PKD patients. CONCLUSION: Bone-mineral disorder markers exhibit similar mortality trends between PKD and non-PKD MHD patients, although some differences are observed in particular in low PTH and phosphorus ranges.


Subject(s)
Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/mortality , Minerals/metabolism , Polycystic Kidney Diseases/complications , Renal Dialysis/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Bone Diseases, Metabolic/metabolism , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Risk Factors , Survival Rate , Young Adult
16.
Curr Opin Nephrol Hypertens ; 20(4): 376-81, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21519253

ABSTRACT

PURPOSE OF REVIEW: Chronic kidney disease-mineral and bone disorder (CKD-MBD) encompasses a broad spectrum of abnormalities related to bone and cardiovascular health. Many reports related to therapeutic interventions specifically aimed at these disorders describe an effect only on surrogate outcomes. This review will focus on recent literature pertaining to interventions directed at CKD-MBDs that emphasize the clinical outcome of mortality. RECENT FINDINGS: Higher levels of serum phosphorus (including those within the normal range) and its regulatory hormone, fibroblast growth factor 23 (FGF-23), are associated with increased mortality in patients with all stages of CKD. Reports investigating specific interventions that affect dietary intake of phosphorus, as well as serum levels of phosphorus, FGF-23, calcium, and parathyroid hormone have recently been published which support the hypothesis that abnormal mineral metabolism is directly linked to increased mortality. Unfortunately, with the exception of altered dialysis prescription, no intervention has been subject to the scrutiny of placebo-controlled randomized clinical trials. SUMMARY: Observational evidence continues to accumulate relating specific therapeutic interventions to improved survival in patients with kidney disease including phosphate binders, calcimimetics, and altered dietary and dialysis prescription patterns. It is time for randomized clinical trials to definitively establish whether or not interventions directed at CKD-MBD effect improvement in hard clinical outcomes in patients with kidney disease.


Subject(s)
Bone Diseases, Metabolic/therapy , Bone Remodeling , Kidney Diseases/therapy , Animals , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/mortality , Bone Remodeling/drug effects , Calcimimetic Agents/therapeutic use , Chelating Agents/therapeutic use , Chronic Disease , Diet , Evidence-Based Medicine , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/blood , Humans , Kidney Diseases/blood , Kidney Diseases/complications , Kidney Diseases/mortality , Parathyroid Hormone/blood , Phosphorus/blood , Renal Dialysis , Treatment Outcome , Vitamin D/therapeutic use
17.
Nephrol Dial Transplant ; 26(6): 1948-55, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20466670

ABSTRACT

BACKGROUND: A number of US observational studies reported an increased mortality risk with higher intact parathyroid hormone (iPTH), calcium and/or phosphate. The existence of such a link in a European haemodialysis population was explored as part of the Analysing Data, Recognising Excellence and Optimising Outcomes (ARO) Chronic Kidney Disease (CKD) Research Initiative. METHODS: The association between the markers of mineral and bone disease and clinical outcomes was examined in 7970 patients treated in European Fresenius Medical Care facilities over a median of 21 months. Baseline and time-dependent (TD) Cox regression were performed using Kidney Disease Outcomes Quality Initiative (KDOQI) target ranges as reference categories, adjusting for demographics, medical history, dialysis parameters, inflammation, medications and laboratory parameters. Fractional polynomial (FP) models were also used. RESULTS: Hazard ratio (HR) estimates from baseline analysis for iPTH were U-shaped [>600 pg/mL, HR = 2.10, 95% confidence interval (CI) 1.62-2.73; <75 pg/mL, HR = 1.46, 95% CI 1.17-1.83]. TD analysis confirmed the results for iPTH. Baseline analysis showed that calcium >2.75 mmol/L increased risk of death (HR = 1.70, 95% CI 1.19-2.42). TD analysis showed that both low (HR = 1.19, 95% CI 1.04-1.37) and high calcium (HR = 1.74, 95% CI 1.30-2.34) increased risk of death. Baseline analysis for phosphate showed a U-shaped pattern (<1.13 mmol/L, HR = 1.18, 95% CI 1.01-1.37; >1.78 mmol/L, HR = 1.32, 95% CI 1.13-1.55). TD analysis confirmed the results for phosphate <1.13 mmol/L. HR estimates were higher in patients with diabetes versus those without diabetes for baseline analysis only (P-value = 0.014). FP analysis confirmed the results of baseline and TD analyses. CONCLUSION: Patients with iPTH, calcium and phosphate levels within the KDOQI target ranges have the lowest risk of mortality compared with those outside the target ranges.


Subject(s)
Calcium/blood , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/mortality , Minerals/metabolism , Parathyroid Hormone/blood , Phosphorus/blood , Renal Dialysis/mortality , Aged , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/mortality , Cohort Studies , Creatinine/blood , Europe , Female , Follow-Up Studies , Glomerular Filtration Rate , Humans , Male , Middle Aged , Survival Rate
18.
Nephron Clin Pract ; 118(2): c211-6, 2011.
Article in English | MEDLINE | ID: mdl-21178378

ABSTRACT

INTRODUCTION: A very low parathyroid hormone (PTH) level (VLPL) is associated with an increased risk of adynamic bone disease, vascular calcification, and mortality in haemodialysis (HD) patients. The aim of the study was to assess the frequency, the associated factors, and the prognosis of non-surgical VLPL in a cohort of prevalent HD patients. METHODS: In July 2005, a cross-sectional study was performed on the French ARNOS cohort in 1,348 prevalent HD patients from 24 dialysis centres in the Rhône-Alpes area. Patients with a baseline intact PTH level <50 pg/ml (VLPL, Group 1) and ≥ 50 pg/ml (Group 2) were compared and a 42-month survival analysis was performed. Patients with prevalent or incident parathyroidectomy were excluded. RESULTS: We studied 1,138 prevalent HD patients. As compared to patients of Group 2 (n = 1,019), patients with VLPL (Group 1, n = 119) had lower serum albumin levels (34.5 ± 5 vs. 36.4 ± 5 g/l, p < 0.0001), less protein intake (nPCR 0.99 ± 0.28 vs. 1.1 ± 0.28 g/kg/day, p = 0.01), higher calcaemia (2.30 ± 0.2 vs. 2.26 ± 0.2 mmol/l, p = 0.01) and were more frequently treated with calcium carbonate (67 vs. 54%, p < 0.001). Patients with VLPL had a higher mortality rate (HR: 1.4 (1.07-1.8), p = 0.006) after adjustment for age, gender, diabetes, and dialysis vintage. The odds ratios of mortality for patients with VLPL remained higher in all calcaemia and serum albumin quartiles. Only 3/119 patients in Group 1 did not receive any PTH-lowering therapies (i.e. calcium carbonate (67%), alfacalcidol (38%), cinacalcet (10.1%), and dialysate calcium ≥ 1.5 mmol/l (94%)). CONCLUSION: In this observational French cohort, VLPL was observed in 10% of prevalent HD patients and was associated with poor survival rates. An inadequate therapeutic strategy could be responsible for this observation. The real consequences of this iatrogenic adynamic bone disease remain hypothetical, but it may be related to the risk of developing vascular calcification. It is hypothesized that a more adequate strategy, using fewer PTH-lowering therapies in cases of VLPL, may help in improving the poor prognosis.


Subject(s)
Parathyroid Hormone/blood , Renal Dialysis/mortality , Aged , Aged, 80 and over , Biomarkers/blood , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/mortality , Cohort Studies , Cross-Sectional Studies , Female , France/epidemiology , Humans , Male , Middle Aged , Renal Dialysis/adverse effects , Survival Rate/trends
19.
Clin Calcium ; 20(7): 1078-87, 2010 Jul.
Article in Japanese | MEDLINE | ID: mdl-20585187

ABSTRACT

The final goal of CKD-MBD (chronic kidney disease, mineral and bone disorder) is to reduce the risk of death in uremic patients. To achieve this objective, it is of importance to manage laboratory abnormalities, bone abnormalities, and vascular calcification appropriately. Many observation studies suggested that the good control of serum phosphate, calcium, and PTH concentration would lead to the lower risk of death. Fracture and vascular calcification would increase the risk for mortality. In addition, some randomized clinical trials have shown that the use of CKD-MBD related drugs, e.g. vitamin D, phosphate binder, might lead to reductions in the risk of death.


Subject(s)
Bone Diseases, Metabolic/mortality , Kidney Diseases/mortality , Bone Diseases, Metabolic/drug therapy , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/metabolism , Calcinosis , Calcium/metabolism , Chronic Disease , Cinacalcet , Humans , Kidney Diseases/complications , Kidney Diseases/drug therapy , Kidney Diseases/metabolism , Naphthalenes/therapeutic use , Parathyroid Hormone/metabolism , Phosphorus/metabolism , Polyamines/therapeutic use , Prognosis , Risk , Sevelamer , Survival Rate , Vascular Diseases , Vitamin D/therapeutic use
20.
G Ital Nefrol ; 26 Suppl 49: S3-10, 2009.
Article in Italian | MEDLINE | ID: mdl-19941272

ABSTRACT

Evidence has been accumulating in recent years that chronic kidney disease (CKD) is a common disease associated with a high risk of morbidity and mortality. Cardiovascular complications are the leading cause of death in patients with CKD, and the risk of cardiovascular mortality is 10-30-fold higher in dialysis patients than in age-, gender- and race-matched controls. On the basis of this evidence it has been suggested that the cardiovascular risk profile of CKD patients is different from that of the general population, resulting from a complex and peculiar interaction of risk factors. In fact, traditional risk factors such as hypertension, aging, smoking, diabetes, and lipid disorders do not fully explain the high frequency of cardiovascular disease in CKD, so other factors must be involved in the high mortality rate in uremic patients. In this article we will provide an overview of the epidemiology of the cardiovascular risk factors in CKD. Among the non-traditional risk factors we have focused particularly on those related to mineral metabolism, which contribute the high rates of cardiovascular events observed in CKD.


Subject(s)
Bone Diseases, Metabolic/epidemiology , Cardiovascular Diseases/epidemiology , Kidney Failure, Chronic/epidemiology , Bone Diseases, Metabolic/complications , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/mortality , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Humans , Hypertension/epidemiology , Italy/epidemiology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/mortality , Renal Dialysis/adverse effects , Risk Factors
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