Sophie A Jamal

Women's College Research Institute, Toronto, Ontario, Canada

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Publications (120)629.5 Total impact

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    ABSTRACT: 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. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 04/2015; DOI:10.1053/j.ajkd.2015.01.025 · 5.76 Impact Factor
  • Sarah L West, Pooja Patel, Sophie A. Jamal
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    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; DOI:10.1111/joim.12361 · 5.79 Impact Factor
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    ABSTRACT: 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. 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). 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). 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. Copyright © 2015 by the American Society of Nephrology.
    Clinical Journal of the American Society of Nephrology 02/2015; DOI:10.2215/CJN.06040614 · 5.25 Impact Factor
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    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; DOI:10.1038/ki.2014.425 · 8.52 Impact Factor
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    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
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    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
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    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; DOI:10.1002/jbmr.2406 · 6.59 Impact Factor
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    ABSTRACT: 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 Study (MrOS). 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, and incident and prevalent morphometric) for up to 9 years. We used cox proportional hazards models to analyze the association between serum sodium levels (<135mmol/L versus .135mmol/L) and risk of nonspine and hip fractures, with results presented as hazard ratios (HR) and 95% confidence intervals (CI). We examined the association between morphometric vertebral fractures and serum sodium using logistic regression models, presented as odds ratios (OR) 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 ≥ 135mmol/L, those with serum sodium <135mmol/L, had an increased risk hip fracture (HR=3.04; 95% CI: 1.37 to 6.75), prevalent (OR=2.46; 95% CI: 1.22 to 4.95) and incident (OR=3.53; 95% CI: 1.35 to 9.19) morphometric spine fractures but not nonspine fractures (OR=1.44; 95% CI: 0.85 to 2.44). Adjusting for bone mineral density did not change our findings. Our data demonstrate 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. © 2014 American Society for Bone and Mineral Research
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 10/2014; DOI:10.1002/jbmr.2383 · 6.59 Impact Factor
  • Sarah L West, Sophie A Jamal
    Seminars in Dialysis 06/2014; DOI:10.1111/sdi.12267 · 2.07 Impact Factor
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    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 · 8.52 Impact Factor
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    Maria Fusaro, Maurizio Gallieni, Sophie A Jamal
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    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 · 8.52 Impact Factor
  • Sarah L West, Charmaine E Lok, Sophie A Jamal
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    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; DOI:10.1007/s00774-013-0506-1 · 2.11 Impact Factor
  • S A Jamal, S L West, T L Nickolas
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    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
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    ABSTRACT: Bisphosphonates are widely used for the treatment of osteoporosis and are generally well tolerated. However, the United States Food and Drug Administration safety reports have highlighted the issue of renal safety in bisphosphonate-treated patients. All bisphosphonates carry labeled "warnings" or a contraindication for use in patients with severe renal impairment (creatinine clearance <30 or <35 mL/min). Data from pivotal trials and their extension studies of bisphosphonates approved for the management of osteoporosis were obtained via PubMed, and were reviewed with support from published articles available on PubMed. Renal safety analyses of pivotal trials of oral alendronate, risedronate and ibandronate for postmenopausal osteoporosis showed no short- or long-term effects on renal function. Transient post-infusion increases in serum creatinine have been reported in patients receiving intravenous ibandronate and zoledronic acid, however studies showed that treatment with these agents did not result in long-term renal function deterioration in clinical trial patients with osteoporosis. All bisphosphonate therapies have "warnings" for use in patients with severe renal impairment. Clinical trial results have shown that even in elderly, frail osteoporotic patients with renal impairment, intravenous bisphosphonate therapy administration in accordance with the prescribing information did not result in long-term renal function decline. Physicians should follow guidelines for bisphosphonate therapies administration at all times.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 10/2013; 28(10). DOI:10.1002/jbmr.2058 · 6.59 Impact Factor
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    ABSTRACT: Organic nitrates uncouple bone turnover, improve bone mineral density, and improve trabecular and cortical components of bone. These changes in turnover, strength and geometry may translate into an important reduction in fractures. However, before proceeding with a large fracture trial, there is a need to identify the nitrate formulation that has both the greatest efficacy (with regards to bone turnover markers) and gives the fewest headaches. Ascertaining which nitrate formulation this may be is the purpose of the current study.Methods and design: This will be an open-label randomized, controlled trial conducted at Women's College Hospital comparing five formulations of nitrates for their effects on bone turnover markers and headache. We will recruit postmenopausal women age 50 years or older with no contraindications to nitroglycerin. Our trial will consist of a run-in phase and a treatment phase. We will enroll 420 women in the run-in phase, each to receive all of the 5 potential treatments in random order for 2 days, each with a 2-day washout period between treatments. Those who tolerate all formulations will enter the 12-week treatment phase and be randomly assigned to one of five groups: 0.3 mg sublingual nitroglycerin tablet, 0.6 mg of the sublingual tablet, a 20 mg tablet of isosorbide mononitrate, a 160 mg nitroglycerin transdermal patch (used for 8 h), and 15 mg of nitroglycerin ointment as used in a previous trial by our group. We will continue enrolment until we have randomized 210 women or 35 women per group. Concentrations of bone formation (bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide) and bone resorption (C-telopeptides of collagen crosslinks and N-terminal crosslinks of collagen) agents will be measured in samples taken at study entry (the start of the run in phase) and 12 weeks. Subjects will record the frequency and severity of headaches daily during the run-in phase and then monthly after that. We will use the 'multiple comparisons with the best' approach for data analyses, as this strategy allows practical considerations of ease of use and tolerability to guide selection of the preparation for future studies. Data from this protocol will be used to develop a randomized, controlled trial of nitrates to prevent osteoporotic fractures.Trial registration: ClinicalTrials.gov Identifier: NCT01387672. Controlled-Trials.com: ISRCTN08860742.
    Trials 09/2013; 14(1):284. DOI:10.1186/1745-6215-14-284 · 2.12 Impact Factor
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    ABSTRACT: Phosphate binders (calcium-based and calcium-free) are recommended to lower serum phosphate and prevent hyperphosphataemia in patients with chronic kidney disease, but their effects on mortality and cardiovascular outcomes are unknown. We aimed to update our meta-analysis on the effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease. We did a systematic review of articles published in any language after Aug 1, 2008, up until Oct 22, 2012, by searching Medline, Embase, International Pharmaceutical Abstracts, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature. We included all randomised and non-randomised trials that compared outcomes between patients with chronic kidney disease taking calcium-based phosphate binders with those taking non-calcium-based binders. Eligible studies, determined by consensus with predefined criteria, were reviewed, and data were extracted onto a standard form. We combined data from randomised trials to assess the primary outcome of all-cause mortality using the DerSimonian and Laird random effects model. Our search identified 847 reports, of which eight new studies (five randomised trials) met our inclusion criteria and were added to the ten (nine randomised trials) included in our previous meta-analysis. Analysis of the 11 randomised trials (4622 patients) that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders (risk ratio 0·78, 95% CI 0·61-0·98). Non-calcium-based phosphate binders are associated with a decreased risk of all-cause mortality compared with calcium-based phosphate binders in patients with chronic kidney disease. Further studies are needed to identify causes of mortality and to assess whether mortality differs by type of non-calcium-based phosphate binder. None.
    The Lancet 07/2013; 382(9900). DOI:10.1016/S0140-6736(13)60897-1 · 39.21 Impact Factor
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    ABSTRACT: Context: Calcium and vitamin D are recommended for bone health, but there are concerns about adverse risks. Some clinical studies suggest that calcium intake may be cardioprotective, whereas others report increased risk associated with calcium supplements. Both low and high serum levels of 25-hydroxyvitamin D have been associated with increased mortality. Objective: The purpose of this study was to determine the association between total calcium and vitamin D intake and mortality and heterogeneity by source of intake. Design: The Canadian Multicentre Osteoporosis Study cohort is a population-based longitudinal cohort with a 10-year follow-up (1995-2007). Setting: This study included randomly selected community-dwelling men and women. Participants: A total of 9033 participants with nonmissing calcium and vitamin D intake data and follow-up were studied. Exposure: Total calcium intake (dairy, nondairy food, and supplements) and total vitamin D intake (milk, yogurt, and supplements) were recorded. Outcome: The outcome variable was all-cause mortality. Results: There were 1160 deaths during the 10-year period. For women only, we found a possible benefit of higher total calcium intake, with a hazard ratio of 0.95 (95% confidence interval, 0.89-1.01) per 500-mg increase in daily calcium intake and no evidence of heterogeneity by source; use of calcium supplements was also associated with reduced mortality, with hazard ratio of 0.78 (95% confidence interval, 0.66-0.92) for users vs nonusers with statistically significant reductions remaining among those with doses up to 1000 mg/d. These associations were not modified by levels of concurrent vitamin D intake. No definitive associations were found among men. Conclusions: Calcium supplements, up to 1000 mg/d, and increased dietary intake of calcium may be associated with reduced risk of mortality in women. We found no evidence of mortality benefit or harm associated with vitamin D intake.
    The Journal of Clinical Endocrinology and Metabolism 07/2013; 98(7):3010-8. DOI:10.1210/jc.2013-1516 · 6.31 Impact Factor
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    ABSTRACT: Objective Recent data suggest that women with type 2 diabetes mellitus (T2DM) might be more susceptible to fractures due to an impaired adaptive response to mechanical load, despite reportedly higher bone mineral density (BMD). The purpose of this study was to use an engineering beam analysis to calculate and compare the load stresses on the femurs of healthy women and women with T2DM and compare these levels to conventional measures of femoral neck BMD.Materials/Methods We studied 3658 women who participated in the Canadian Multicentre Osteoporosis Study (CaMos), and who had available Hip Structure Analysis (HSA) data from baseline dual energy x-ray absorptiometry (DXA) scans. Women were categorized into two groups based on the presence or absence of self-reported T2DM. We computed stress in megapascals (MPa) at the infero-medial margin of the femoral neck in a one-legged stance using an engineering beam analysis incorporating dimensions and geometry from DXA scans using the HSA method. We used linear regression (SAS 9.3) to determine the association between T2DM status and stress. We also determined the association between T2DM status and femoral neck BMD.ResultsStresses were 4.5% higher in T2DM women than in non-diabetics (11.03 ± 0.18 vs. 10.56 ± 0.04 MPa; p = 0.0093). Femoral neck BMD was 4.2% greater in women with T2DM than in non-diabetics (0.74 ± 0.002 vs. 0.71 ± 0.01 g/cm2; p = 0.0008).Conclusions Despite higher femoral neck BMD, higher stress indicates weaker skeletal geometry for a given load, and suggests an impaired skeletal adaptive response to load may be present in women with T2DM.
    Metabolism: clinical and experimental 06/2013; DOI:10.1016/j.metabol.2013.05.004 · 3.61 Impact Factor

Publication Stats

3k Citations
629.50 Total Impact Points

Institutions

  • 2012–2015
    • Women's College Research Institute
      Toronto, Ontario, Canada
  • 2000–2015
    • University of Toronto
      • • Department of Medicine
      • • Saint Michael's Hospital
      • • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
  • 2008–2014
    • Women's College Hospital
      Toronto, Ontario, Canada
  • 2005–2008
    • St. Michael's Hospital
      Toronto, Ontario, Canada
  • 1998
    • University of California, San Francisco
      • Department of Epidemiology and Biostatistics
      San Francisco, CA, United States