Dennis M Black

University of California, San Francisco, San Francisco, California, United States

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Publications (283)2799.87 Total impact

  • Dennis M Black · Clifford J Rosen
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    ABSTRACT: Key Clinical Points Postmenopausal Osteoporosis Fractures and osteoporosis are common, particularly among older women, and hip fractures can be devastating. Treatment is generally recommended in postmenopausal women who have a bone mineral density T score of -2.5 or less, a history of spine or hip fracture, or a Fracture Risk Assessment Tool (FRAX) score indicating increased fracture risk. Bisphosphonates (generic) and denosumab reduce the risk of hip, nonvertebral, and vertebral fractures; bisphosphonates are commonly used as first-line treatment in women who do not have contraindications. Teriparatide reduces the risk of nonvertebral and vertebral fractures. Osteonecrosis of the jaw and atypical femur fractures have been reported with treatment but are rare. The benefit-to-risk ratio for osteoporosis treatment is strongly positive for most women with osteoporosis. Because benefits are retained after discontinuation of alendronate or zoledronic acid, drug holidays after 5 years of alendronate therapy or 3 years of zoledronic acid therapy may be considered for patients at lower risk for fracture.
    No preview · Article · Jan 2016 · New England Journal of Medicine
  • Steven R Cummings · Douglas P Kiel · Dennis M Black

    No preview · Article · Jan 2016 · JAMA Internal Medicine
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    ABSTRACT: 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 4.6 years 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 ≤ 17 pg/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.
    No preview · Article · Jan 2016 · Bone
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    ABSTRACT: Background: Prior to the initiation of menopausal hormone treatment (MHT), genetic variations in the innate immunity pathway were found to be associated with carotid artery intima-medial thickness (CIMT) and coronary arterial calcification (CAC) in women (n=606) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Whether MHT might affect these associations is unknown. Methods: The association of treatment outcomes with variation in the same 764 candidate genes was evaluated in same KEEPS participants four years after randomization to either oral conjugated equine estrogens (0.45 mg/day), transdermal 17β estradiol (50 µg/day), each with progesterone (200 mg/day) for 12 days each month, or placebo pills and patch. Results: Twenty SNPs within the innate immunity pathway most related with CIMT after 4 years were not among those associated with CIMT prior to MHT. In 403 women who completed the study in their assigned treatment group, SNPs within the innate immunity pathway were found to alter the treatment effect on 4-year change in CIMT (i.e. significant interaction between treatment and genetic variation in the innate immunity pathway; p<0.001). No SNPs by treatment effects were observed with changes of CAC >5 Agatston Units after 4 years. Conclusion: Results of this study suggest that hormonal status may interact with genetic variants to influence cardiovascular phenotypes, specifically, the pharmacogenomic effects within the innate immunity pathway for CIMT. Key words: atherosclerosis, candidate genes, estrogen, innate immunity, thrombosis.
    Preview · Article · Oct 2015 · Physiological Genomics
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    ABSTRACT: Objective: To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). Study design: Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction. Results: A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks. Conclusion: Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing. Trial registration: ClinicalTrials.gov: NCT01022580.
    Full-text · Article · Oct 2015 · The Journal of pediatrics
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    ABSTRACT: To examine the degree of trauma in major osteoporotic fractures (MOF) in men vs. women, we used data from 15,698 adults aged ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study (5,994 men) and the Study of Osteoporotic Fractures (SOF) (9,704 women). Participants were contacted tri-annually to ascertain incident fractures, which were confirmed by radiographic reports and coded according to degree of self-reported trauma. Trauma was classified as low (fall from ≤ standing height; fall on stairs, steps or curb; minimal trauma other than fall [coughing, turning over]); moderate (collisions with objects during normal activity without associated fall); or high (fall from > standing height; severe trauma [motor vehicle accident, assault]). MOF included hip, clinical vertebral, wrist and humerus fractures. Mean fracture follow-up was 9.1 years in SOF and 8.7 years in MrOS. 14.6% of the MOF in men vs. 6.3% of the MOF in women were classified as high trauma (p < 0.001); men vs. women more often experienced fractures due to severe trauma as well as due to fall > standing height. High trauma fractures were more significantly common in men vs. women at the hip (p = 0.002) and wrist (p < 0.001), but not at the spine or humerus. Among participants with MOF, the odds ratio of a fracture related to high trauma fracture among men vs. women was 3.12 (95% CI 1.70-5.71) after adjustment for traditional risk factors. Findings were similar in analyses limited to participants with hip fractures (OR 3.34, 95% CI 1.04-10.67) and those with wrist fracture (OR 5.68, 95% CI 2.03-15.85). Among community-dwelling older adults, MOF are more likely to be related to high trauma in men than in women. These findings are not explained by sex differences in conventional risk factors and may reflect a greater propensity among men to engage in risky behavior. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jul 2015 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    A.H. Gee · G M Treece · C J Tonkin · D M Black · K E S Poole
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    ABSTRACT: Within each sex, there is an association between hip fracture risk and the size of the proximal femur, with larger femurs apparently more susceptible to fracture. Here, we investigate whether the thickness and density of the femoral cortex play a role in this association: might larger femurs harbour focal, cortical defects? To answer this question, we used cortical bone mapping to measure the distribution of cortical mass surface density (CMSD, mg/cm(2)) in cohorts of 308 males and 125 females. Principal component analysis of the various femoral surfaces led to a measure of size that is linearly independent from shape. After mapping the data onto a canonical femur surface, we used statistical parametric mapping to identify any regions where CMSD depends on size, allowing for other confounding covariates including shape. Our principal finding was a focal patch on the superior femoral neck, where CMSD is reduced by around 1% for each 1% increase in proximal-distal size (p<0.000005 in the males, p<0.001 in the females). This finding appears to be consistent with models of functional adaptation, and may help with the design of interventional strategies for reducing fracture risk. Copyright © 2015. Published by Elsevier Inc.
    Preview · Article · Jul 2015 · Bone
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    ABSTRACT: Data concerning the link between severity of abdominal aortic calcification (AAC) and fracture risk in postmenopausal women are discordant. This association may vary by skeletal site and duration of follow-up. Our aim was to assess the association between the AAC severity and fracture risk in older women over the short- and long-term. This is a case-cohort study nested in a large multicenter prospective cohort study. The association between AAC and fracture was assessed using Odds Ratios (OR) and 95% confidence intervals (95%CI) for vertebral fractures and using Hazard Risks (HR) and 95%CI for non-vertebral and hip fractures. AAC severity was evaluated from lateral spine radiographs using Kauppila's semiquantitative score. Severe AAC (AAC score 5+) was associated with higher risk of vertebral fracture during 4 years of follow-up, after adjustment for confounders (age, BMI, walking, smoking, hip bone mineral density, prevalent vertebral fracture, systolic blood pressure, hormone replacement therapy) (OR=2.31, 95%CI: 1.24-4.30, p<0.01). In a similar model, severe AAC was associated with an increased in the hip fracture risk (HR=2.88, 95%CI: 1.00-8.36, p=0.05). AAC was not associated with the risk of any non-vertebral fracture. AAC was not associated with the fracture risk after 15-years of follow-up. In elderly women, severe AAC is associated with higher short-term risk of vertebral and hip fractures, but not with the long-term risk of these fractures. There is no association between AAC and risk of non-vertebral-non-hip fracture in older women. Our findings lend further support to the hypothesis that AAC and skeletal fragility are related. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jun 2015 · Bone
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    ABSTRACT: Menopausal hormone therapy (MHT) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women, and whether MHT affects mood in younger women. The ancillary Cognitive and Affective Study (KEEPS-Cog) of the Kronos Early Estrogen Prevention Study (KEEPS) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women. KEEPS, a randomized, double-blinded, placebo-controlled clinical trial, was conducted at nine US academic centers. Of the 727 women enrolled in KEEPS, 693 (95.3%) participated in the ancillary KEEPS-Cog, with 220 women randomized to receive 4 y of 0.45 mg/d oral conjugated equine estrogens (o-CEE) plus 200 mg/d micronized progesterone (m-P) for the first 12 d of each month, 211 women randomized to receive 50 μg/d transdermal estradiol (t-E2) plus 200 mg/d m-P for the first 12 d of each month, and 262 women randomized to receive placebo pills and patches. Primary outcomes included the Modified Mini-Mental State examination; four cognitive factors: verbal learning/memory, auditory attention/working memory, visual attention/executive function, and speeded language/mental flexibility; and a mood measure, the Profile of Mood States (POMS). MHT effects were analyzed using linear mixed-effects (LME) models, which make full use of all available data from each participant, including those with missing data. Data from those with and without full data were compared to assess for potential biases resulting from missing observations. For statistically significant results, we calculated effect sizes (ESs) to evaluate the magnitude of changes. On average, participants were 52.6 y old, and 1.4 y past their last menstrual period. By month 48, 169 (24.4%) and 158 (22.8%) of the 693 women who consented for ancillary KEEPS-Cog were lost to follow-up for cognitive assessment (3MS and cognitive factors) and mood evaluations (POMS), respectively. However, because LME models make full use all available data, including data from women with missing data, 95.5% of participants were included in the final analysis (n = 662 in cognitive analyses, and n = 661 in mood analyses). To be included in analyses, women must have provided baseline data, and data from at least one post-baseline visit. The mean length of follow-up was 2.85 y (standard deviation [SD] = 0.49) for cognitive outcomes and 2.76 (SD = 0.57) for mood outcomes. No treatment-related benefits were found on cognitive outcomes. For mood, model estimates indicated that women treated with o-CEE showed improvements in depression and anxiety symptoms over the 48 mo of treatment, compared to women on placebo. The model estimate for the depression subscale was -5.36 × 10-2 (95% CI, -8.27 × 10-2 to -2.44 × 10-2; ES = 0.49, p < 0.001) and for the anxiety subscale was -3.01 × 10-2 (95% CI, -5.09 × 10-2 to -9.34 × 10-3; ES = 0.26, p < 0.001). Mood outcomes for women randomized to t-E2 were similar to those for women on placebo. Importantly, the KEEPS-Cog results cannot be extrapolated to treatment longer than 4 y. The KEEPS-Cog findings suggest that for recently postmenopausal women, MHT did not alter cognition as hypothesized. However, beneficial mood effects with small to medium ESs were noted with 4 y of o-CEE, but not with 4 y of t-E2. The generalizability of these findings is limited to recently postmenopausal women with low cardiovascular risk profiles. ClinicalTrials.gov NCT00154180 and NCT00623311.
    Full-text · Article · Jun 2015 · PLoS Medicine
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    ABSTRACT: Hip fracture risk is known to be related to material properties of the proximal femur, but fracture prediction studies adding richer quantitative computed tomography (QCT) measures to dual energy X-ray (DXA)-based methods have shown limited improvement. Fracture types have distinct relationships to predictors, but few studies have sub-divided fracture into types, since this necessitates regional measurements and more fracture cases. This work makes use of cortical bone mapping (CBM) to accurately assess, with no prior anatomical presumptions, the distribution of properties related to fracture type. CBM uses QCT data to measure the cortical and trabecular properties, accurate even for thin cortices below the imaging resolution. The osteoporotic fractures in men (MrOS) study is a predictive case-cohort study of men over 65: we analyse 99 fracture cases (44 trochanteric and 55 femoral neck) compared to a cohort of 308, randomly selected from 5,994. To our knowledge, this is the largest QCT-based predictive hip fracture study to date, and the first to incorporate CBM analysis into fracture prediction. We demonstrate that both cortical mass surface density, and endocortical trabecular BMD, show significant difference in fracture cases vs. cohort, in regions appropriate to fracture type. We incorporate these regions into predictive models using Cox proportional hazards regression to estimate hazard ratios, and logistic regression to estimate area under the receiver operating characteristic curve (AUC). Adding CBM to DXA-based BMD leads to a small but significant (p < 0.005) improvement in model prediction for any fracture, with AUC increasing from 0.78 to 0.79, assessed using leave-one-out cross-validation. For specific fracture types, the improvement is more significant (p < 0.0001), with AUC increasing from 0.71 to 0.77 (trochanteric fractures) and 0.76 to 0.82 (femoral neck fractures). In contrast, adding DXA-based BMD to a CBM-based predictive model does not result in any significant improvement. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Preview · Article · May 2015 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly−Pivotal Fracture Trial (HORIZON−PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n = 95) and Z6P3 (n = 95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was −0.54% in Z9 vs. −1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: −0.37%, 1.93%; p = 0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. © 2015 American Society for Bone and Mineral Research.
    No preview · Article · May 2015 · Journal of Bone and Mineral Research
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    ABSTRACT: Roux-en-Y gastric bypass (RYGB) surgery has negative effects on bone, mediated in part by effects on nutrient absorption. Not only can RYGB result in vitamin D malabsorption, but also the bypassed duodenum and proximal jejunum are the predominant sites of active, transcellular, 1,25(OH)2D-mediated calcium (Ca) uptake. However, Ca absorption occurs throughout the intestine, and those who undergo RYGB might maintain sufficient Ca absorption, particularly if vitamin D status and Ca intake are robust. We determined the effects of RYGB on intestinal fractional Ca absorption (FCA) while maintaining ample 25OHD levels (goal ≥30 ng/mL) and Ca intake (1200 mg daily) in a prospective cohort of 33 obese adults (BMI 44.7 ± 7.4 kg/m2). FCA was measured pre-operatively and 6 months post-operatively with a dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and BMD by DXA and QCT. Mean 6-month weight loss was 32.5 ± 8.4 kg (25.8% ± 5.2% of pre-operative weight). FCA decreased from 32.7% ± 14.0% pre-operatively to 6.9% ± 3.8% post-operatively (p < 0.0001), despite median (interquartile range) 25OHD levels of 41.0 (33.1-48.5) and 36.5 (28.8-40.4) ng/mL, respectively. Consistent with the FCA decline, 24-hour urinary Ca decreased, PTH increased, and 1,25(OH)2D increased (p≤0.02). Bone turnover markers increased markedly, areal BMD decreased at the proximal femur, and volumetric BMD decreased at the spine (p < 0.001). Those with lower post-operative FCA had greater increases in serum CTx (ρ = -0.43, p = 0.01). Declines in FCA and BMD were not correlated over the 6 months. In conclusion, FCA decreased dramatically after RYGB, even with most 25OHD levels ≥30 ng/mL and with recommended Ca intake. RYGB patients may need high Ca intakes to prevent perturbations in Ca homeostasis, although the approach to Ca supplementation needs further study. Decline in FCA could contribute to the decline in BMD after RYGB, and strategies to avoid long-term skeletal consequences should be investigated. This article is protected by copyright. All rights reserved
    No preview · Article · Jan 2015 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean±SD decline 19.1±6.1kg or 36.5±10.9%, p<0.001). Areal bone mineral density (BMD) decreased by 5.2±3.5% and 4.1±2.6% at the femoral neck and total hip, respectively, and volumetric BMD decreased at the spine by 7.4±2.8% (p<0.001 for all). Effects of RYGB on marrow fat differed by diabetes status (adjusted p=0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% CI -10.0 to +11.7%, p=0.84). In contrast, marrow fat decreased in diabetic women (-7.5%, 95% CI -15.2 to +0.1%, p=0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r=-0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jan 2015 · Bone

  • No preview · Article · Dec 2014 · Bone
  • Lang Yang · Lisa Palermo · Dennis M Black · Richard Eastell
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    ABSTRACT: A bone fractures only when loaded beyond its strength. The purpose of this study was to determine the association of femoral strength, as estimated by finite element (FE) analysis of DXA scans, with incident hip fracture in comparison to hip BMD, FRAX® and hip structure analysis (HSA) variables. This prospective case-cohort study included a random sample of 1941 women and 668 incident hip fracture cases (295 in the random sample) during a mean ± SD follow-up of 12.8 ± 5.7 yrs from the Study of Osteoporotic Fractures (n = 7860 community-dwelling women ≥67 yr of age). We analyzed the baseline DXA scans (Holgoic 1000) of the hip using a validated plane-stress, linear-elastic finite element (FE) model of the proximal femur and estimated the femoral strength during a simulated sideways fall. Cox regression accounting for the case-cohort design assessed the association of estimated femoral strength with hip fracture. The age-BMI-adjusted hazard ratio (HR) per SD decrease for estimated strength (2.21, 95% CI 1.95-2.50) was greater than that for TH BMD (1.86, 95% CI 1.67-2.08; p < 0.05), FN BMD (2.04, 95% CI 1.79-2.32; p > 0.05), FRAX® scores (range 1.32-1.68; p < 0.0005) and many HSA variables (range 1.13-2.43; p < 0.005), and the association was still significant (p < 0.05) after further adjustment for hip BMD or FRAX® scores. The association of estimated strength with incident hip fracture was strong (Harrell's C index 0.770), significantly better than TH BMD (0.759, p < 0.05) and FRAX® scores (0.711-0.743, p < 0.0001) but not FN BMD (0.762, p > 0.05) Similar findings were obtained for intra- and extra-capsular fractures. In conclusion, the estimated femoral strength from FE analysis of DXA scans is an independent predictor and performs at least as well as FN BMD in predicting incident hip fracture in postmenopausal women. © 2014 American Society for Bone and Mineral Research.
    No preview · Article · Dec 2014 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
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    ABSTRACT: We describe the methods and reliability of radiographic vertebral fracture assessment in MrOS, a cohort of community dwelling men aged ≥ 65 yrs. Lateral spine radiographs were obtained at Visit 1 (2000-2) and 4.6 years later (Visit 2). Using a workflow tool (SpineAnalyzerTM, Optasia Medical), a physician reader completed semi-quantitative (SQ) scoring. Prior to SQ scoring, technicians performed “triage” to reduce physician reader workload, whereby clearly normal spine images were eliminated from SQ scoring with all levels assumed to be SQ = 0 (no fracture, “triage negative”); spine images with any possible fracture or abnormality were passed to the physician reader as “triage positive” images. Using a quality assurance sample of images (n = 20 participants; 8 with baseline only and 12 with baseline and follow-up images) read multiple times, we calculated intra-reader kappa statistics and percent agreement for SQ scores. A subset of 494 participants’ images were read regardless of triage classification to calculate the specificity and sensitivity of triage. Technically adequate images were available for 5958 of 5994 participants at Visit 1, and 4399 of 4423 participants at Visit 2. Triage identified 3215 (53.9%) participants with radiographs that required further evaluation by the physician reader. For prevalent fractures at Visit 1 (SQ ≥ 1), intra-reader kappa statistics ranged from 0.79-0.92; percent agreement ranged from 96.9%-98.9%; sensitivity of the triage was 96.8% and specificity of triage was 46.3%. In conclusion, SQ scoring had excellent intra-rater reliability in our study. The triage process reduces expert reader workload without hindering the ability to identify vertebral fractures.
    No preview · Article · Oct 2014 · Bone

  • No preview · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Background/aims The pathogenesis of BPD is multifactorial. In preterm infants ≤28 wk GA requiring ventilation at 7–14 days, >60% have surfactant dysfunction. Survival without BPD in these infants is <25%. Inhaled nitric oxide (iNO) may improve outcome in some infants (Schreiber, NEJM 2003, Ballard NEJM, 2006). Methods Preterm infants ≤28 wk GA requiring mechanical ventilation at 7–14 days were enrolled in a RCT at 25 US centres. All infants received iNO and were randomised to receive surfactant (Infasurf) or sham instillation behind a screen every 1–2 days; maximum of 5 doses. Infants were evaluated by physiologic oxygen/flow reduction at 36 and 40 wk. Pulmonary outcome to 18 months is being collected. Results Between January 2010 and September 2013, 511 of the planned 524 infants were enrolled. There was no difference between groups in mean BW (701 ± 164 grams), GA (25.2 ± 1.2 wk), percentage under 26 wk (70.6%), race, gender, severity of disease at enrollment or co-morbidities of prematurity. Survival without BPD was not different between treated vs. controls at 36 wk (31.3% vs.31.7%; relative benefit 0.98 (0.75, 1.28 p = 0.89) or 40 wk (58.7% vs. 54.1%; relative benefit 1.08 (0.92, 1.27 p = 0.33). Overall survival without BPD at 36wk in African Americans was better than whites (37.2% vs. 25.4%p = 0.008). Conclusions Late treatment with surfactant in ventilated preterm infants did not improve survival without BPD at 36 or 40 weeks PMA. Overall better outcome in African-American infants may be due to a racial response to iNO. Pulmonary and neurodevelopmental assessment are on-going.
    Full-text · Article · Oct 2014 · Archives of Disease in Childhood
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    ABSTRACT: Context: Data are needed to guide therapeutic decisions about stopping bisphosphonates after an initial treatment period. Objective: To define significant predictors of fracture and quantify fracture incidence in risk factor-defined subgroups of women who discontinue zoledronic acid (ZOL) after 3 years of treatment. To determine if continuing ZOL reduces fracture risk in subgroups. Design: 3 year extension of HORIZON. Setting: Multicenter trial. Participants: 1233 women who previously received 3 ZOL treatments during Core trial. Intervention: Randomization to 3 additional annual ZOL (Z6, n=616) or placebo infusions (Z3P3, n=617). Main Outcomes: Risk of Morphometric vertebral fractures (MorphVertFx) and clinical nonvertebral fractures (NVF). Results: Incidence of MorphVertFx in Z3P3 was predicted by: Femoral Neck (FN) T-score ≤-2.5 [OR 3.3(1.4, 8.0), p=0.008], Total Hip (TH) T-score ≤-2.5 [OR 4.0(1.8, 9.0), p=0.0007], and incident MorphVertFx during Core [OR 4.75(1.4, 16.8), p<0.015]. Incidence of NVF was predicted by TH T-score [for 1 decline, HR 1.7(1.2, 2.6), p=0.008], incident NVF during Core [HR 2.5(1.2, 5.3), p=0.014], and prevalent vertebral fracture [HR 3.0(1.4, 6.3), p=0.005]. For MorphVertFx, there were no significant treatment subgroup interactions; absolute fracture reductions with continued ZOL were greatest in high-risk subgroups. For NVF, there were no significant treatment reductions overall or in subgroups and no significant interactions. Conclusions: After 3 years of ZOL, in women who have a TH T-score above -2.5, no recent incident fracture and no more than one risk factor (almost 55% of the population), risk for subsequent fracture is low if treatment is discontinued (for MorphVertFx average risk 3.2%, range 2.8-3.8% for subgroups, and for NVF average risk 5.8%, range 1.1-8.8% for subgroups). In these patients, discontinuation for up to 3 years is reasonable.
    No preview · Article · Sep 2014 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: In men, the association between poor physical performance and likelihood of incident vertebral fractures is unknown.Using data from the MrOS study (N=5958), we describe the association between baseline physical performance [walking speed, grip strength, leg power, repeat chair stands, narrow walk (dynamic balance)] and incidence of radiographic and clinical vertebral fractures. At baseline and follow-up an average of 4.6 years later, radiographic vertebral fractures were assessed using semi-quantitative (SQ) scoring on lateral thoracic and lumbar radiographs. Logistic regression modeled the association between physical performance and incident radiographic vertebral fractures (change in SQ grade≥ from baseline to follow-up). Every four months after baseline, participants self-reported fractures; clinical vertebral fractures were confirmed by centralized radiologist review of the baseline study radiograph and community acquired spine images. Proportional hazards regression modeled the association between physical performance with incident clinical vertebral fractures. Multivariate models were adjusted for age, BMD (by DXA), clinical center, race, smoking, height, weight, history of falls, activity level and co-morbid medical conditions; physical performance was analyzed as quartiles.Of 4332 men with baseline and repeat radiographs, 192 (4.4%) had an incident radiographic vertebral fracture. With the exception of walking speed, poorer performance on repeat chair stands, leg power, narrow walk and grip strength were each associated in a graded manner with an increased risk of incident radiographic vertebral fracture (p for trend across quartiles <0.001). In addition, men with performance in the worst quartile on three or more exams had an increased risk of radiographic fracture (OR: 1.81, 9% CI: 1.33, 2.45) compared to men with better performance on all exams. Clinical vertebral fracture (N=149 of 5,813, 2.6%) was not consistently associated with physical performance.We conclude that poorer physical performance is associated with an increased risk of incident radiographic (but not clinical) vertebral fracture in older men. © 2014 American Society for Bone and Mineral Research
    Full-text · Article · Sep 2014 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research

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39k Citations
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Institutions

  • 1984-2015
    • University of California, San Francisco
      • • Department of Epidemiology and Biostatistics
      • • Division of General Internal Medicine
      • • Division of Prevention Science
      • • Department of Medicine
      San Francisco, California, United States
  • 2013
    • University of San Francisco
      San Francisco, California, United States
  • 2007-2011
    • California Pacific Medical Center Research Institute
      • Research Institute
      San Francisco, California, United States
    • The Chinese University of Hong Kong
      Hong Kong, Hong Kong
  • 2009
    • University of Leuven
      Louvain, Flemish, Belgium
  • 1995-2009
    • University of Pittsburgh
      • • Department of Epidemiology
      • • Department of Orthopaedic Surgery
      • • Graduate School of Public Health
      Pittsburgh, Pennsylvania, United States
  • 2004
    • Columbia University
      New York, New York, United States
  • 2002
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2001
    • University of Toronto
      Toronto, Ontario, Canada
  • 2000
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
  • 1999
    • Kaiser Permanente
      Oakland, California, United States
  • 1997
    • Spokane VA Medical Center
      Spokane, Washington, United States
    • Children's Hospital & Research Center Oakland
      Oakland, California, United States
  • 1996
    • CSU Mentor
      • Department of Medicine
      Long Beach, California, United States
  • 1989
    • Potomac Institute for Policy Studies
      Arlington, Virginia, United States