Publications by authors named "Robert R McLean"

60 Publications

Higher Hand Grip Strength Is Associated With Greater Radius Bone Size and Strength in Older Men and Women: The Framingham Osteoporosis Study.

JBMR Plus 2021 May 30;5(5):e10485. Epub 2021 Mar 30.

Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife Boston Massachusetts USA.

Mechanical loading by muscles elicits anabolic responses from bone, thus age-related declines in muscle strength may contribute to bone fragility in older adults. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to determine the association between grip strength and distal radius bone density, size, morphology, and microarchitecture, as well as bone strength estimated by micro-finite element analysis (μFEA), among older men and women. Participants included 508 men and 651 women participating in the Framingham Offspring Study with grip strength measured in 2011-2014 and HR-pQCT scanning in 2012-2015. Separately for men and women, analysis of covariance was used to compare HR-pQCT measures among grip strength quartiles and to test for linear trends, adjusting for age, height, weight, smoking, and physical activity. Mean age was 70 years (range, 50-95 years), and men had higher mean grip strength than the women (37 kg vs. 21 kg). Bone strength estimated by μFEA-calculated failure load was higher with greater grip strength in both men ( < 0.01) and women ( = 0.04). Higher grip strength was associated with larger cross-sectional area in both men and women ( < 0.01), with differences in area of 6% and 11% between the lowest to highest grip strength quartiles in men and women, respectively. Cortical thickness was positively associated with grip strength among men only ( = 0.03). Grip strength was not associated with volumetric BMD (vBMD) in men. Conversely, there was a trend for lower total vBMD with higher grip strength among women ( = 0.02), though pairwise comparisons did not reveal any statistically significant differences in total vBMD among grip strength quartiles. Bone microarchitecture (cortical porosity, trabecular thickness, trabecular number) was not associated with grip strength in either men or women. Our findings suggest that the positive association between hand grip strength and distal radius bone strength may be driven primarily by bone size. © 2021 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbm4.10485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101610PMC
May 2021

Genetic variants modify the associations of concentrations of methylmalonic acid, vitamin B-12, vitamin B-6, and folate with bone mineral density.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

Background: Elevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine β-synthase (CBS).

Objectives: We investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength.

Methods: We measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and <210 nmol/L; pyridoxal-5'-phosphate; vitamin B-12 continuously and ≥258 pmol/L; and folate. The outcomes of interest included areal and volumetric BMD, measured by DXA and quantitative computed tomography (QCT), respectively. We evaluated associations between the bone measures and interactions of single nucleotide polymorphism with a B vitamin or biomarker in Framingham participants (n = 4310 for DXA and n = 3127 for QCT). For analysis of DXA, we validated the association results in the B-PROOF cohort (n = 1072). Bonferroni-corrected locus-wide significant thresholds were defined to account for multiple testing.

Results: The interactions between rs2274976 and vitamin B-12 and rs34671784 and MMA <210 nmol/L were associated with lumbar spine BMD, and the interaction between rs6586281 and vitamin B-12 ≥258 pmol/L was associated with femoral neck BMD. For QCT-derived traits, 62 interactions between genetic variants and B vitamins and biomarkers were identified.

Conclusions: Some genetic variants in the 1-carbon methylation pathway modify the association of B vitamin and biomarker concentrations with bone density and strength.  These interactions require further replication and functional validation for a mechanistic understanding of the role of the 1-carbon metabolism pathway on BMD and risks of fracture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqab093DOI Listing
May 2021

Comparison of Men and Women With Axial Spondyloarthritis in the US-Based Corrona Psoriatic Arthritis/Spondyloarthritis Registry.

J Rheumatol 2021 Apr 15. Epub 2021 Apr 15.

From the Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, WA, USA; Corrona, LLC, Waltham, MA, USA; Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; Division of Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Funding: This study was sponsored by Corrona, LLC. Corrona, LLC, has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Crescendo, Eli Lilly and Company, Genentech, Gilead, GSK, Janssen, Merck, Momenta Pharmaceuticals, Novartis, Ortho Dermatologics, Pfizer Inc, Regeneron, Roche, Sun, and UCB. The design and conduct of the study were a collaborative effort between Corrona, LLC, and Novartis, and financial support for the study was provided by Novartis. Novartis participated in the interpretation of data and review and approval of the manuscript. Conflicts of interest: P.J. Mease has received research grants from AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Sun, and UCB; and consulting and/or speakers bureau fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Galapagos, Genentech, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, Sun, and UCB. R.R. McLean and B. Dube are employees of Corrona, LLC. E. M. Liu, S. Rebello, and M. Glynn were employees of Corrona, LLC, at the time of this analysis. Yi and Y. Park are employees of Novartis Pharmaceuticals Corporation. A. Ogdie has received consulting fees from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Corrona, Janssen, Lilly, Novartis, and Pfizer, and has received grant support from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, Pfizer (University of Pennsylvania), Amgen (FORWARD Databank), and Novartis (FORWARD Databank). Address correspondence to: Philip J. Mease, MD, Seattle Rheumatology Associates, 601 Broadway, Suite 600, Seattle, WA 98122; phone: (206) 386-2000; fax: (206) 386-2083; email:

Objective: To compare patient characteristics and disease burden between men and women with axial spondyloarthritis (axSpA) in the US-based Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry.

Methods: Patients aged ≥18 years with axSpA enrolled in the Corrona PsA/SpA Registry between March 2013 and November 2018 who were not concurrently diagnosed with PsA were included. Patient demographics, clinical characteristics, disease activity, patient-reported symptoms, work productivity, and treatment history at enrollment were compared between men and women using tests or Wilcoxon rank-sum tests for continuous variables and χ or Fisher's exact tests for categorical variables.

Results: Of 498 patients with axSpA and available sex information, 307 (61.6%) were men and 191 (38.4%) were women. Compared with men, women had higher disease activity as measured by Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and physician global assessment, and had higher tender/swollen joint counts and enthesitis scores (all ≤0.01). Women also had worse patient-reported symptoms (pain, fatigue, HAQ-S, and EQ-VAS; all <0.05), greater work and activity impairment, and were less likely to work full time than men. Prior csDMARD and prednisone use was more common in women than in men (both <0.05). Additionally, women were more likely to have diagnoses of depression and fibromyalgia (both <0.01).

Conclusion: In this US registry of patients with axSpA, women had higher overall disease burden and more peripheral manifestations than men. Improved awareness of sex differences in the presentation of axSpA may aid physicians in earlier identification and improved disease management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.201549DOI Listing
April 2021

Drug survival of ixekizumab, TNF inhibitors, and other IL-17 inhibitors in real-world patients with psoriasis: The Corrona Psoriasis Registry.

Dermatol Ther 2021 03 15;34(2):e14808. Epub 2021 Feb 15.

Eastern Virginia Medical School, Norfolk, Virginia, USA.

To compare drug survival of ixekizumab to other IL-17 inhibitors (IL-17i) and TNF inhibitors (TNFi) among patients with psoriasis (PsO) in a real-world setting. Participants included adult PsO patients enrolled in the Corrona Psoriasis Registry who initiated ixekizumab, TNFi, or other IL-17i between 16 March 2016 to 10 August 2019 and completed ≥1 follow-up visit. Multivariable adjusted hazard ratios (HR) were calculated to estimate the risk for drug discontinuation in the ixekizumab group relative to the other drugs. Among the 1604 drug initiations, 552 initiated ixekizumab, 450 initiated TNFi, and 602 initiated other IL-17i. Mean age was 51 years, 49% were women, and 52% were obese (BMI > 30). Ixekizumab patients had a higher proportion of patients with PASI >12 at drug initiation (24%) than TNFi (15%) and other IL-17i (19%). Over a median of 11 months of follow-up, 723/1604 (45%) drug discontinuations occurred. Persistence of ixekizumab, TNFi, and other IL-17i at 24-months were 68%, 33%, and 46%, among biologic-naïve patients (n = 543), and 46%, 23%, and 36%, for biologic-experienced patients (n = 1061), respectively. Ixekizumab patients had a 64% lower risk of discontinuation vs TNFi (HR = 0.36; 95% CI 0.27-0.47) and a 31% lower risk vs other IL-17i (HR = 0.69, 95% CI 0.55-0.87) after adjustment for biologic experience and other covariates. HRs were similar when limited to patients with moderate-to-severe PsO (BSA > 3, PASI > 3, and IGA > 1, n = 1076) at initiation. In our study of real-world patients with PsO, initiators of ixekizumab had more prolonged drug survival than both initiators of TNFi and other IL-17i up to 2 years of follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dth.14808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047872PMC
March 2021

Characteristics of Patients with Psoriasis Treated with Apremilast in the Corrona Psoriasis Registry.

Dermatol Ther (Heidelb) 2021 Feb 21;11(1):253-263. Epub 2021 Jan 21.

Yale University, New Haven, CT, USA.

Introduction: Data on the characteristics of apremilast patients in real-world settings are limited. We assessed the demographics and disease characteristics of apremilast-treated patients in the Corrona Psoriasis Registry overall and by treatment history.

Methods: The Corrona Psoriasis Registry is a large, independent, prospective, observational registry of adult patients (age ≥ 18 years) who initiate an eligible systemic medication for treatment of psoriasis at or after enrollment (incident users) or within 12 months before enrollment (prevalent users). The current analyses included psoriasis patients enrolled in the Corrona Psoriasis Registry between April 1, 2015, and January 7, 2018. Patients were adults (age ≥ 18 years) with psoriasis who were enrolled between April 1, 2015, and January 7, 2018 and initiated apremilast at the time of registry enrollment or a subsequent visit (incident users) or within the 12 months prior to registry enrollment (prevalent users). Patient characteristics were evaluated descriptively at the index date, defined as the enrollment date for prevalent users and the visit when apremilast was initiated for incident users.

Results: Among 660 patients who initiated apremilast at registry enrollment or a visit thereafter, psoriatic arthritis, hypertension, and hyperlipidemia were common. There were more systemic-experienced (61.4%) versus systemic-naive (38.6%) patients; 43.8% had prior biologic exposure. Most patients were not receiving concomitant systemic treatment (70.2%); 27.4% were receiving concomitant biologic therapy. Most patients had mild or moderate disease (psoriasis-involved body surface area ≤ 10% [76.0%], Investigator Global Assessment ≤ 3 [88.3%], Psoriasis Area and Severity Index ≤ 10 [84.5%]). Dermatologist-reported psoriatic arthritis was present in 47.0% of patients; 33.9% of patients had a Psoriasis Epidemiology Screening Tool score  of ≥ 3, suggestive of psoriatic arthritis. Systemic-experienced apremilast patients had higher rates of obesity and comorbidities and experienced a greater impact on quality of life (mean Dermatology Life Quality Index, 7.3 vs. 6.5) versus systemic-naive patients.

Conclusion: In this real-world observational study of apremilast users in the Corrona Psoriasis Registry, most patients had less-severe disease and higher rates of prior exposure to biologic treatments compared with patients with moderate-to-severe psoriasis enrolled in phase 3 clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13555-020-00479-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858993PMC
February 2021

Disease response and patient-reported outcomes among initiators of ixekizumab.

J Dermatolog Treat 2020 Dec 2:1-9. Epub 2020 Dec 2.

Eli Lilly and Company, Indianapolis, IN, USA.

Objectives: There is limited real-world evidence on using ixekizumab in psoriasis patients. Therefore, we characterized patients with psoriasis initiating ixekizumab and report 6-month changes in disease and patient-reported outcomes.

Methods: Adult patients with psoriasis who initiated ixekizumab and completed a 6-month follow-up visit were enrolled from the Corrona Psoriasis Registry. Disease characteristics and outcomes were assessed at ixekizumab initiation. Outcomes included the mean 6-month change in Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator Global Assessment (IGA), and IGA*BSA.

Results: From baseline to follow-up in all patients ( = 136), means decreased for IGA*BSA (-45.5) and BSA (-12.4), and a higher % achieved an absolute PASI ≤ 5 (84.6%), BSA 0-3 (72.1%), and IGA 0/1 (50.7%). Within stratified groups, means decreased for PASI <12 for IGA*BSA (-21.1) and BSA (-6.3); PASI≥12 for IGA*BSA (-94.8) and BSA (-24.6); weight <100 kg for IGA*BSA (-45.1) and BSA (-12.4); weight ≥100 kg for IGA*BSA (-46.2) and BSA (-12.3); concomitant PsA for IGA*BSA (-56.0) and BSA (-15.3); and in no concomitant PsA for IGA*BSA (-36.9) and BSA (-10.0).

Conclusions: We provide real-world evidence on the benefits of ixekizumab for treating psoriasis, regardless of baseline disease severity, weight, or concomitant PsA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09546634.2020.1853023DOI Listing
December 2020

Association of Nail Psoriasis With Disease Activity Measures and Impact in Psoriatic Arthritis: Data From the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.

J Rheumatol 2020 Oct 15. Epub 2020 Oct 15.

This study was sponsored by Corrona, LLC. Corrona, LLC, has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Crescendo, Eli Lilly and Company, Genentech, Gilead, GSK, Janssen, Merck, Momenta Pharmaceuticals, Novartis, Ortho Dermatologics, Pfizer Inc., Regeneron, Roche, Sun, and UCB. The design and conduct of the study were a collaborative effort between Corrona, LLC, and Novartis, and financial support for the study was provided by Novartis. Novartis participated in the interpretation of data and review and approval of the manuscript. 1P.J. Mease, MD, Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, Washington; 2M. Liu, PhD, S. Rebello, MPH, R.R. McLean, DSc, MPH, B. Dube, MPH, M. Glynn, MS, CPH, Corrona, LLC, Waltham, Massachusetts; 3P. Hur, PharmD, MBA, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey; 4A. Ogdie, MD, MCSE, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. PJM has received research grants from Celgene, Novartis, AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Pfizer, and UCB; consulting fees from Celgene, Corrona, Novartis, AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Gilead, Janssen, Lilly, Merck, Pfizer, Sun, and UCB; and speakers bureau fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Pfizer, and UCB. ML, SR, RRM, BD, and MG are employees of Corrona, LLC. PH is an employee of Novartis Pharmaceuticals Corporation. AO has received consulting fees from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Lilly, Novartis, and Pfizer, and has received grant support from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, Pfizer, and Novartis. Address correspondence to Dr. P. Mease, Seattle Rheumatology Associates, 601 Broadway, Suite 600, Seattle, WA 98122, USA. Email: Full Release Article. For details see Reprints and Permissions at jrheum.org. Accepted for publication Oct 6, 2020.

Objective: To examine the association of nail psoriasis with disease activity, quality of life, and work productivity in patients with psoriatic arthritis (PsA).

Methods: All patients with PsA who enrolled in the Corrona PsA/Spondyloarthritis Registry between March 2013 and October 2018 and had data on physician-reported nail psoriasis were included and stratified by presence vs absence of nail psoriasis at enrollment. Patient demographics, disease activity, quality of life (QOL), and work productivity at enrollment were compared between patients with vs without nail psoriasis using tests or Wilcoxon rank-sum tests for continuous variables and chi-square or Fisher exact tests for categorical variables.

Results: Of the 2841 patients with PsA included, 1152 (40.5%) had nail psoriasis and 1689 (59.5%) did not. Higher proportions of patients with nail psoriasis were male (51.9% vs 44.1%) and disabled from working (12.3% vs 7.8%) compared with patients without nail psoriasis (all < 0.05). Patients with nail psoriasis had higher disease activity than those without nail psoriasis, including higher tender and swollen joint counts, worse Disease Activity Index for Psoriatic Arthritis and Psoriatic Arthritis Disease Activity Score values, and increased likelihood of having enthesitis and dactylitis (all < 0.05). Patients with nail psoriasis had worse pain, fatigue, and work and activity impairment than those without nail psoriasis (all < 0.05).

Conclusion: Patients with PsA who have nail psoriasis had worse disease activity, QOL, and work productivity than those without nail involvement, emphasizing the importance of identification and management of nail disease in patients with PsA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.190923DOI Listing
October 2020

Effect of Multidomain Disease Presentations on Patients With Psoriatic Arthritis in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.

J Rheumatol 2021 May 1;48(5):698-706. Epub 2020 Oct 1.

P.J. Mease, MD, MACR, Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, Washington, USA.

Objective: To compare disease characteristics, quality of life (QOL), and work productivity of patients with psoriatic arthritis (PsA) who had multidomain vs single-domain presentations.

Methods: Adults with PsA enrolled in the Corrona PsA/Spondyloarthritis Registry (March 2013-August 2018) were included. Six PsA disease domains were evaluated: enthesitis, dactylitis, peripheral arthritis (PA), nail psoriasis, axial disease, and skin disease. Patients were classified as having multidomain (≥ 2 domains) or single-domain disease presentations; biologic initiators were characterized separately. Linear regression models evaluated the association of multidomain presentations with disease characteristics, QOL, and work productivity vs single-domain presentations.

Results: Of 2617 patients with PsA, 1698 (64.9%) had multidomain presentations, 617 (23.6%) had single-domain presentations, and 302 (11.5%) had no active disease features. Of 354 biologic initiators, 289 (81.6%) had multidomain presentations, 45 (12.7%) had single-domain presentations, and 20 (5.6%) had no active disease features. Overall, the most common single-domain and multidomain presentations, respectively, were skin disease (12.7%) and PA + skin disease (11.7%). Multidomain presenters were more likely to have fibromyalgia, depression, anxiety, and prior biologic use than single-domain presenters. Multidomain presentations were associated with significantly worse patient and physician global assessments of disease activity, pain, and fatigue; Health Assessment Questionnaire-Disability Index and EuroQol 5-dimension scores; and work productivity at enrollment.

Conclusion: In this US real-world cohort, most patients had multidomain disease presentations, which was associated with worse disease activity, QOL, and work productivity measures. This study highlights the heterogeneity of PsA and the importance of assessing all PsA domains for optimizing disease management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.200371DOI Listing
May 2021

Characterization of Patients With Axial Spondyloarthritis by Enthesitis Presence: Data from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.

ACR Open Rheumatol 2020 Jul 6;2(7):449-456. Epub 2020 Jul 6.

University of Pennsylvania, Philadelphia, Pennsylvania.

Objective: To compare the characteristics of patients with axial spondyloarthritis (axSpA) who had enthesitis versus those without enthesitis.

Methods: This study included adult patients with axSpA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry (March 2013 to August 2018). Enthesitis was assessed at enrollment via the Spondyloarthritis Research Consortium of Canada Enthesitis Index. Characteristics were compared between patients with and without enthesitis using t tests or Wilcoxon rank-sum tests for continuous variables and χ or Fisher exact tests for categorical variables.

Results: Of 477 patients with axSpA, 121 (25.4%) had enthesitis (mean, 3.9 sites) at enrollment. Higher proportions of patients with enthesitis were female and had nonradiographic axSpA than those without enthesitis (both P < 0.05). Additionally, higher proportions of patients with enthesitis had prior biologic (38.8% vs 27.2%) and conventional synthetic disease-modifying antirheumatic drug (csDMARD; 24.8% vs 13.3%) use and were currently receiving a combination of biologics and csDMARDs (28.6% vs 18.1%) than those without enthesitis. Patients with enthesitis had worse disease activity (tender and swollen joint counts, physician global assessment, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondylitis Functional Index), spinal mobility, and quality of life (pain, fatigue, Health Assessment Questionnaire, and EuroQol visual analog scale scores); greater work impairment; and had a history of depression and fibromyalgia than those without enthesitis (all P < 0.05).

Conclusion: In this US-based real-world study, enthesitis in patients with axSpA was associated with worse disease activity and quality of life than those with no enthesitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr2.11154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368134PMC
July 2020

Characterization of real-world patients with psoriasis and without a history of depression: The Corrona Psoriasis Registry.

J Am Acad Dermatol 2021 May 27;84(5):1444-1447. Epub 2020 Jun 27.

Department of Dermatology, Yale University, New Haven, Connecticut; Central Connecticut Dermatology, Cromwell, Connecticut. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2020.06.994DOI Listing
May 2021

Chronic Musculoskeletal Pain and Foot Reaction Time in Older Adults.

J Pain 2021 01 26;22(1):76-85. Epub 2020 Jun 26.

Department of Exercise and Health Sciences, College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, Massachusetts.

This cross-sectional study examines the association between chronic musculoskeletal pain and foot reaction time (RT) among older community-living adults. Participants were 307 adults aged 71 years and older in the MOBILIZE Boston Study II. Pain severity, interference, and location were measured by the Brief Pain Inventory and a joint pain questionnaire. With participants seated, simple foot reaction time was measured as self-selected foot response time to an intermittent light, and choice foot reaction time was measured as response time to the light on the corresponding side of the sensored gait mat. We performed multivariable linear regression to determine associations of pain and foot RT, adjusted for sociodemographic and health characteristics, and serially adjusted for cognitive function (MMSE or Trail Making A). Pain severity and interference were associated with slower simple foot reaction time (P < .05). Pain severity and knee pain were associated with slower choice foot reaction time (P < .05). Adjustment for cognitive measures had little impact on the pain-RT relationship. This significant relationship was only observed among participants with less education. These results support the idea that chronic pain may lead to slower foot RT, thus could represent a fall hazard in older adults. Neuromotor mechanisms underlying the pain-fall relationship warrant further investigation. PERSPECTIVE: This study provides insights on the mechanisms underlying the pain-fall relationship. Chronic pain may contribute to slower foot RT thus increase fall risk in older adults. This may help inform interventions such as stepping training to reduce fall risk in older adults living with chronic pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpain.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762729PMC
January 2021

Disease Characteristics, Quality of Life, and Work Productivity by Enthesitis Site: Real-world Data From the US Corrona Psoriatic Arthritis/Spondyloarthritis Registry.

J Rheumatol 2020 Jun 1. Epub 2020 Jun 1.

This study was sponsored by Corrona, LLC. Corrona, LLC, has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Crescendo, Eli Lilly and Company, Genentech, Gilead, GSK, Janssen, Merck, Momenta Pharmaceuticals, Novartis, Ortho Dermatologics, Pfizer Inc., Regeneron, Roche, Sun, and UCB. The design and conduct of the study were a collaborative effort between Corrona, LLC, and Novartis, and financial support for the study was provided by Novartis. Novartis participated in the interpretation of data and review and approval of the manuscript. P.J. Mease, MD, MACR, Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, Washington; M. Liu, PhD, S. Rebello, MPH, W. Hua, MS, R.R. McLean, DSc, MPH, Corrona, LLC, Waltham, Massachusetts; P. Hur, PharmD, MBA, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey; A. Ogdie, MD, MCSE, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA. PJM has received research grants from Celgene, Novartis, AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Pfizer, and UCB; consulting fees from Celgene, Corrona, Novartis, AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Gilead, Janssen, Eli Lilly, Merck, Pfizer, Sun, and UCB; and speakers bureau fees from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen, Pfizer, and UCB. M. Liu, S. Rebello, WH, and RRM are employees of Corrona, LLC. PH is an employee of Novartis Pharmaceuticals Corporation. AO has received consulting fees from Amgen, AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Novartis, and Pfizer, and has received grant support from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Psoriasis Foundation, Rheumatology Research Foundation, Pfizer, and Novartis. Address correspondence to Dr. P. Mease, Seattle Rheumatology Associates, 601 Broadway, Suite 600, Seattle, WA 98122, USA. Email: Full Release Article. For details see Reprints and Permissions at jrheum.org. Accepted for publication May 14, 2020.

Objective: To assess the effect of clinical enthesitis by body site in patients with psoriatic arthritis (PsA).

Methods: Adults with PsA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry (March 2013-March 2018) were included. Enthesitis at enrollment was assessed by the Spondyloarthritis Research Consortium of Canada Enthesitis Index and classified by affected sites (upper, lower, or both). Disease activity (e.g., Clinical Disease Activity Index, Clinical Disease Activity Index for PsA), patient-reported outcomes (PRO; e.g., patient-reported pain and fatigue), and work productivity were compared between those with and without enthesitis using or Wilcoxon rank-sum tests for continuous variables and chi‑square or Fisher exact tests for categorical variables. The association of enthesitis with disease activity and PRO measures versus no enthesitis was modeled using multivariable-adjusted linear or logistic regression.

Results: Of 2003 patients with PsA, 391 (19.5%) had enthesitis: 80 (20.5%) in upper sites only; 137 (35.0%) in lower sites only; and 174 (44.5%) in both. Regardless of location, disease activity and PRO were worse in patients with versus without enthesitis. In adjusted models, the presence of enthesitis at any site was significantly associated with worse disease activity versus no enthesitis. Enthesitis in lower or both upper and lower sites was associated with higher pain and fatigue scores and greater work impairment versus no enthesitis.

Conclusion: Patients with clinical enthesitis had worse disease activity regardless of enthesitis location versus those without enthesitis, and patients with enthesitis in lower or both upper and lower sites had worse pain, fatigue, and work impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.191117DOI Listing
June 2020

Chronic Pain Characteristics and Gait in Older Adults: The MOBILIZE Boston Study II.

Arch Phys Med Rehabil 2020 03 18;101(3):418-425. Epub 2019 Oct 18.

College of Nursing and Health Sciences, University of Massachusetts Boston, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address:

Objective: To investigate a proposed cognitively-mediated pathway whereby pain contributes to gait impairments by acting as a distractor in community-living older adults.

Design: A cross-sectional study of a population-based cohort of older adults.

Setting: Urban and suburban communities in a large metropolitan area.

Participants: Community-living participants (N=302) 70 years and older recruited from a previous population-based cohort.

Interventions: Not applicable.

Main Outcome Measures: Gait parameters including gait speed, stride length, double support and swing characteristics, and variability were assessed under single- and dual-task conditions involving cognitive challenges (eg, counting backward). A joint pain questionnaire assessed pain distribution in the back and major joints. We examined pain-gait relationships using multivariable linear regression and bootstrapping mediation procedures.

Results: Forty-three percent of participants had pain in 2 or more musculoskeletal sites. Pain distribution was related to slower gait speed and other gait characteristics for all gait conditions. Associations persisted after adjustment for age, sex, education, body mass index, medication, and vision. Decrements in gait measures related to pain were comparable with decrements in gait related to dual-task conditions. There were no differences in dual-task cost among the pain distribution groups. Adjusted for confounders, pain-gait relationships appear mediated by selective attention.

Conclusions: These findings suggest that chronic pain contributes to decrements in gait, including slower gait speed, and that it operates through a cognitively-mediated pathway. Further research is needed to understand the mechanisms via pain alters mobility and to develop interventions to improve mobility among older adults with chronic pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apmr.2019.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050337PMC
March 2020

Predictors of Imminent Risk of Nonvertebral Fracture in Older, High-Risk Women: The Framingham Osteoporosis Study.

JBMR Plus 2019 Jun 18;3(6):e10129. Epub 2019 Jan 18.

Institute for Aging Research Hebrew SeniorLife Department of Medicine Beth Israel Deaconess Medical Center, and Harvard Medical School Boston MA USA.

Osteoporosis treatment decisions are often based solely on BMD or on 10-year fracture risk; little is known about factors increasing imminent fracture risk. Understanding factors contributing to imminent risk of fracture is potentially useful for personalizing therapy, especially among those at high risk. Our aim was to identify predictors of nonvertebral fracture for 1- and 2-year periods in women at high risk for fracture. The Framingham Osteoporosis Study cohort included 1470 women (contributing 2778 observations), aged ≥65 years with BMD hip -score ≤ -1.0, or history of fragility fracture (irrespective of -score). Nonvertebral fractures were ascertained prospectively over 1 year and 2 years following a baseline BMD scan. Potential risk factors included age, anthropometric variables, comorbidities/medical history, cognitive function, medications, history of fracture, self-rated health, falls in the past year, smoking, physical performance, hip BMD -score, Activities of Daily Living (ADL) score, and caffeine and alcohol intakes. Predictive factors with value ≤ 0.10 in bivariate Cox proportional hazards regression models were subsequently considered in multivariable models. Mean baseline age was 75 years (SD 6.0). During 1-year follow-up, 89 nonvertebral fractures occurred; during 2-year follow-up, 176 fractures occurred. Of the variables considered in the bivariate models, significant predictors of nonvertebral fractures included age, history of fracture, self-rated health, falls in the prior year, BMD -score, ADL, renal disease, dementia, and current use of nitrates, beta-blockers, calcium channel blockers, or antidepressants. In multivariable models, significant independent risk factors were history of fracture, self-rated health, hip BMD -score, and use of nitrates. Significant 1-year results were attenuated at the 2-year follow-up. In addition to the traditional factors of BMD and fracture history, self-rated health and use of nitrates were independently associated with imminent risk of fracture in older, high-risk women. These specific risk factors thus may be useful in identifying which women to target for therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbm4.10129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636767PMC
June 2019

Serial sodium values and adverse outcomes in heart failure with preserved ejection fraction.

Int J Cardiol 2019 09 22;290:119-124. Epub 2019 Mar 22.

Massachusetts Veterans Epidemiology and Research Information Center (MAVERIC), Veterans Affairs Boston Healthcare System, Boston, MA, United States of America; Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America. Electronic address:

Objective: The purpose of our study is to examine whether serial measurements of serum sodium values after diagnosis identify a higher-risk subset of patients with heart failure with preserved ejection fraction.

Methods: We identified 50,932 subjects with HFpEF with 759,577 recorded sNa measurements (mean age 72 ± 11 years) using a validated algorithm in the VA national database from 2002 to 2012. We examined the association of repeated measures of sNa with mortality using a multivariable Cox proportional hazards model.

Results: After a median follow-up of 2.9 years (IQR: 1.2-5.4), 19,011 deaths occurred. After adjusting for age, sex, race, BMI, glomerular filtration rate, potassium, coronary artery disease, hypertension, hyperlipidemia, atrial fibrillation, pulmonary disease, diabetes, anemia, and medications, we found J-shaped associations of serum sodium with mortality. HRs for all-cause mortality were 2.48 (95% CI: 2.38-2.60) for the sNA 115.00-133.99 category; and 1.40 (95% CI: 1.35-1.46) for the sNA 143.00-175.00 category compared to the 137.01-140.99 category (ref). We used generalized estimating equation-based negative binomial regression to compute the incidence density ratios (IDR) to examine days hospitalized for heart failure and for all causes. There were a total of 1,275,614 days of all-cause hospitalization and 104,006 days of heart-failure hospitalization. The IDRs for the lowest sNA group were 2.03 (95% CI: 1.90-2.18) for all-cause hospitalization and 1.73 (95% CI: 1.39-2.16) for heart-failure hospitalization.

Conclusions: Our findings suggest that monitoring of serum sodium values during longitudinal follow-up can identify HFpEF patients at risk of adverse outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2019.03.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077233PMC
September 2019

Relationship between intra-operative vein graft treatment with DuraGraft® or saline and clinical outcomes after coronary artery bypass grafting.

Expert Rev Cardiovasc Ther 2018 Dec 14;16(12):963-970. Epub 2018 Oct 14.

f Division of Aging , Brigham and Women's Hospital , Boston , MA , USA.

Background: Saphenous vein grafts (SVGs) remain the most often used conduits for coronary bypass grafting (CABG). Progressive intimal hyperplasia contributes to vein-graft disease and vein-graft failure (VGF). We compared the impact of intraoperative preservation of SVGs in a storage solution (DuraGraft®) versus heparinized saline on VGF-related outcomes after CABG.

Methods: From 1996 to 2004, 2436 patients underwent isolated CABG with ≥ 1 SVG. SVGs were consecutively treated with DuraGraft in 1036 patients (2001-2004) and heparinized saline in 1400 patients (1996-1999). Short- (< 30 days) and long-term (≥ 1000 days) outcomes were assessed using repeat revascularization (primary end point), and major adverse cardiac events (MACE) consisting of the composite of death, nonfatal myocardial infarction, or repeat revascularization.

Results: Mean follow-up in the DuraGraft group was 8.5 ± 4.2 years and 9.9 ± 5.6 years in controls. Short-term event rates were low and generally did not differ between groups. DuraGraft was associated with a 45% lower occurrence of nonfatal myocardial infarction after 1000 days (hazard ratio 0.55, 95% CI 0.41-0.74; P < 0.0001). There was 35% and 19% lower long-term risk for revascularization (HR 0.65, 95% CI 0.44-0.97; P = 0.037) and MACE (HR 0.81, 95% CI 0.70-0.94; P = 0.0051), respectively, after DuraGraft. Mortality was comparable between both groups at 1, 5, and 10 years. There was no statistically significant association between DuraGraft exposure and time to death starting at 30 or 1000 days (HR 0.91, 95% CI 0.76-1.09; P = 0.29).

Conclusion: In this study, intraoperative treatment of SVGs with DuraGraft was associated with a lower risk of long-term adverse events suggesting that efficient intraoperative SVG treatment may reduce VGF-related complications post-CABG. These data warrant randomized clinical trials to validate these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14779072.2018.1532289DOI Listing
December 2018

Development and validation of a heart failure with preserved ejection fraction cohort using electronic medical records.

BMC Cardiovasc Disord 2018 06 28;18(1):128. Epub 2018 Jun 28.

Massachusetts Veterans Epidemiology and Research Information Center (MAVERIC), Veterans Affairs Boston Healthcare System, Boston, MA, USA.

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) comprises nearly half of prevalent HF, yet is challenging to curate in a large database of electronic medical records (EMR) since it requires both accurate HF diagnosis and left ventricular ejection fraction (EF) values to be consistently ≥50%.

Methods: We used the national Veterans Affairs EMR to curate a cohort of HFpEF patients from 2002 to 2014. EF values were extracted from clinical documents utilizing natural language processing and an iterative approach was used to refine the algorithm for verification of clinical HFpEF. The final algorithm utilized the following inclusion criteria: any International Classification of Diseases-9 (ICD-9) code of HF (428.xx); all recorded EF ≥50%; and either B-type natriuretic peptide (BNP) or aminoterminal pro-BNP (NT-proBNP) values recorded OR diuretic use within one month of diagnosis of HF. Validation of the algorithm was performed by 3 independent reviewers doing manual chart review of 100 HFpEF cases and 100 controls.

Results: We established a HFpEF cohort of 80,248 patients (out of a total 1,155,376 patients with the ICD-9 diagnosis of HF). Mean age was 72 years; 96% were males and 12% were African-Americans. Validation analysis of the HFpEF algorithm had a sensitivity of 88%, specificity of 96%, positive predictive value of 96%, and a negative predictive value of 87% to identify HFpEF cases.

Conclusion: We developed a sensitive, highly specific algorithm for detecting HFpEF in a large national database. This approach may be applicable to other large EMR databases to identify HFpEF patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-018-0866-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022342PMC
June 2018

Prognostic Significance of Baseline Serum Sodium in Heart Failure With Preserved Ejection Fraction.

J Am Heart Assoc 2018 06 13;7(12). Epub 2018 Jun 13.

Massachusetts Veterans Epidemiology and Research Information Center (MAVERIC), Veterans Affairs Boston Healthcare System, Boston, MA

Background: The purpose of this study was to evaluate the relationship between serum sodium at the time of diagnosis and long term clinical outcomes in a large national cohort of patients with heart failure with preserved ejection fraction.

Methods And Results: We studied 25 440 patients with heart failure with preserved ejection fraction treated at Veterans Affairs medical centers across the United States between 2002 and 2012. Serum sodium at the time of heart failure diagnosis was analyzed as a continuous variable and in categories as follows: low (115.00-134.99 mmol/L), low-normal (135.00-137.99 mmol/L), referent group (138.00-140.99 mmol/L), high normal (141.00-143.99 mmol/L), and high (144.00-160.00 mmol/L). Multivariable Cox regression and negative binomial regression were performed to estimate hazard ratios (95% confidence interval [CI]) and incidence density ratios (95% CI) for the associations of serum sodium with mortality and hospitalizations (heart failure and all-cause), respectively. The average age of patients was 70.8 years, 96.2% were male, and 14% were black. Compared with the referent group, low, low-normal, and high sodium values were associated with 36% (95% CI, 28%-44%), 6% (95% CI, 1%-12%), and 9% (95% CI, 1%-17%) higher risk of all-cause mortality, respectively. Low and low-normal serum sodium were associated with 48% (95% CI, 10%-100%) and 38% (95% CI, 8%-77%) higher risk of number of days of heart failure hospitalizations per year, and with 44% (95% CI, 32%-56%) and 18% (95% CI, 10%-27%) higher risk of number of days of all-cause hospitalizations per year, respectively.

Conclusions: Both elevated and reduced serum sodium, including values currently considered within normal range, are associated with adverse outcomes in patients with heart failure with preserved ejection fraction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.117.007529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220546PMC
June 2018

Chronic Pain and Attention in Older Community-Dwelling Adults.

J Am Geriatr Soc 2018 07 6;66(7):1318-1324. Epub 2018 Jun 6.

New England Geriatric, Research, Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts.

Objectives: To examine the cross-sectional relationship between chronic pain and complex attention in a population of community-living older adults.

Design: Prospective cross-sectional cohort study.

Setting: Population-based Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston Study II.

Participants: Individuals aged 71 to 101 (N=354).

Measurements: Chronic pain was measured using the pain severity and interference subscales of the Brief Pain Inventory. Four subscales of the Test of Everyday Attention were used to measure domains of attention switching and selective, sustained, and divided attention.

Results: Before and after multivariable adjustment, pain severity was associated with poorer scores on measures of selective and sustained attention. Pain interference scores also were significantly inversely associated with selective attention.

Conclusion: Chronic pain is associated with poorer performance in selective and sustained attention in community-dwelling older adults. Further research is needed to determine whether effective pain management could lead to better attentional performance in older adults. Older adults who live with chronic pain, often undertreated, are potentially at risk of cognitive difficulties and related functional consequences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.15413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181226PMC
July 2018

Long-Term and Recent Weight Change Are Associated With Reduced Peripheral Bone Density, Deficits in Bone Microarchitecture, and Decreased Bone Strength: The Framingham Osteoporosis Study.

J Bone Miner Res 2018 10 15;33(10):1851-1858. Epub 2018 Jun 15.

Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

Weight loss in older adults is associated with increased bone loss and fracture. Little is known about the potential impact of weight loss on cortical and trabecular bone density, microarchitecture, and strength. In this study, participants were members of the Framingham Offspring Cohort (769 women, 595 men; mean age 70 ± 8 years), who underwent high-resolution peripheral quantitative computed tomography (HR-pQCT) scanning at the tibia and radius in 2012 to 2016. Weight measurements taken every 4 to 6 years were used to assess recent weight change over 6 years and long-term change over 40 years. General linear models, adjusting for age, sex, height, smoking, and diabetes, were used to evaluate the association between HR-pQCT indices and relative long-term and recent weight change. We found that long-term and recent weight loss were associated with lower cortical density and thickness, higher cortical porosity, and lower trabecular density and number. Associations were stronger for the tibia than radius. Failure load was lower in those individuals with long-term but not short-term weight loss. Deterioration in both cortical and trabecular indices, especially at the weight-bearing skeleton, characterizes bone fragility associated with long-term and recent weight loss in older adults. © 2018 American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.3472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368222PMC
October 2018

Meta-analysis of epigenome-wide association studies of cognitive abilities.

Mol Psychiatry 2018 11 8;23(11):2133-2144. Epub 2018 Jan 8.

Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Cognitive functions are important correlates of health outcomes across the life-course. Individual differences in cognitive functions are partly heritable. Epigenetic modifications, such as DNA methylation, are susceptible to both genetic and environmental factors and may provide insights into individual differences in cognitive functions. Epigenome-wide meta-analyses for blood-based DNA methylation levels at ~420,000 CpG sites were performed for seven measures of cognitive functioning using data from 11 cohorts. CpGs that passed a Bonferroni correction, adjusting for the number of CpGs and cognitive tests, were assessed for: longitudinal change; being under genetic control (methylation QTLs); and associations with brain health (structural MRI), brain methylation and Alzheimer's disease pathology. Across the seven measures of cognitive functioning (meta-analysis n range: 2557-6809), there were epigenome-wide significant (P < 1.7 × 10) associations for global cognitive function (cg21450381, P = 1.6 × 10), and phonemic verbal fluency (cg12507869, P = 2.5 × 10). The CpGs are located in an intergenic region on chromosome 12 and the INPP5A gene on chromosome 10, respectively. Both probes have moderate correlations (~0.4) with brain methylation in Brodmann area 20 (ventral temporal cortex). Neither probe showed evidence of longitudinal change in late-life or associations with white matter brain MRI measures in one cohort with these data. A methylation QTL analysis suggested that rs113565688 was a cis methylation QTL for cg12507869 (P = 5 × 10 and 4 × 10 in two lookup cohorts). We demonstrate a link between blood-based DNA methylation and measures of phonemic verbal fluency and global cognitive ability. Further research is warranted to understand the mechanisms linking genomic regulatory changes with cognitive function to health and disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-017-0008-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035894PMC
November 2018

Lower Lean Mass Measured by Dual-Energy X-ray Absorptiometry (DXA) is Not Associated with Increased Risk of Hip Fracture in Women: The Framingham Osteoporosis Study.

Calcif Tissue Int 2018 07 5;103(1):16-23. Epub 2018 Jan 5.

Institute for Aging Research, Hebrew SeniorLife, 1200 Centre Street, Boston, MA, 02131, USA.

Although muscle mass influences strength in older adults, it is unclear whether low lean mass measured by dual-energy X-ray absorptiometry (DXA) is an independent risk factor for hip fracture. Our objective was to determine the association between DXA lean mass and incident hip fracture risk among 1978 women aged 50 years and older participating in the Framingham Study Original and Offspring cohorts. Leg and total body lean mass (kg) were assessed from whole-body DXA scans collected in 1992-2001. Hip fracture follow-up extended from DXA assessment to the occurrence of fracture, death, drop-out, or end of follow-up in 2007. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) estimating the relative risk of hip fracture associated with a 1-kg increase in baseline lean mass. Mean age was 66 years (range 50-93). Over a median of 8 years of follow-up, 99 hip fractures occurred. In models adjusted for age, height, study cohort, and percent total body fat, neither leg (HR 1.11; 95% CI 0.94, 1.31) nor total body (HR 1.06; 95% CI 0.99, 1.13) lean mass were associated with hip fracture. After further adjustment for femoral neck bone mineral density, leg lean mass results were similar (HR 1.10; 95% CI 0.93, 1.30). In contrast, 1 kg greater total body lean mass was associated with 9% higher hip fracture risk (HR 1.09; 95% CI 1.02, 1.18). Our findings suggest that in women, lower lean mass measured by DXA is not associated with increased risk of hip fracture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00223-017-0384-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013345PMC
July 2018

Diabetes and Deficits in Cortical Bone Density, Microarchitecture, and Bone Size: Framingham HR-pQCT Study.

J Bone Miner Res 2018 01 20;33(1):54-62. Epub 2017 Sep 20.

Beth Israel Deaconess Medical Center, Center for Advanced Orthopedic Studies, Boston, MA, USA.

Older adults with type 2 diabetes (T2D) tend to have normal or greater areal bone mineral density (aBMD), as measured by DXA, than those who do not have diabetes (non-T2D). Yet risk of fracture is higher in T2D, including 40% to 50% increased hip fracture risk. We used HR-pQCT to investigate structural mechanisms underlying skeletal fragility in T2D. We compared cortical and trabecular bone microarchitecture, density, bone area, and strength in T2D and non-T2D. In secondary analyses we evaluated whether associations between T2D and bone measures differed according to prior fracture, sex, and obesity. Participants included 1069 members of the Framingham Study, who attended examinations in 2005 to 2008 and underwent HR-pQCT scanning in 2012 to 2015. Mean age was 64 ± 8 years (range, 40 to 87 years), and 12% (n = 129) had T2D. After adjustment for age, sex, weight, and height, T2D had lower cortical volumetric BMD (vBMD) (p < 0.01), higher cortical porosity (p = 0.02), and smaller cross-sectional area (p = 0.04) at the tibia, but not radius. Trabecular indices were similar or more favorable in T2D than non-T2D. Associations between T2D and bone measures did not differ according to sex or obesity status (all interaction p > 0.05); however, associations did differ in those with a prior fracture and those with no history of fracture. Specifically, cortical vBMD at the tibia and cortical thickness at the radius were lower in T2D than non-T2D, but only among those individuals with a prior fracture. Cortical porosity at the radius was higher in T2D than non-T2D, but only among those who did not have a prior fracture. Findings from this large, community-based study of older adults suggest that modest deterioration in cortical bone and reductions in bone area may characterize diabetic bone disease in older adults. Evaluation of these deficits as predictors of fracture in T2D is needed to develop prevention strategies in this rapidly increasing population of older adults. © 2017 American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.3240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771832PMC
January 2018

Visceral Adipose Tissue Is Associated With Bone Microarchitecture in the Framingham Osteoporosis Study.

J Bone Miner Res 2017 01 6;32(1):143-150. Epub 2016 Sep 6.

Institute for Aging Research, Hebrew SeniorLife, Boston, MA, USA.

Obesity has been traditionally considered to protect the skeleton against osteoporosis and fracture. Recently, body fat, specifically visceral adipose tissue (VAT), has been associated with lower bone mineral density (BMD) and increased risk for some types of fractures. We studied VAT and bone microarchitecture in 710 participants (58% women, age 61.3 ± 7.7 years) from the Framingham Offspring cohort to determine whether cortical and trabecular BMD and microarchitecture differ according to the amount of VAT. VAT was measured from CT imaging of the abdomen. Cortical and trabecular BMD and microarchitecture were measured at the distal tibia and radius using high-resolution peripheral quantitative computed tomography (HR-pQCT). We focused on 10 bone parameters: cortical BMD (Ct.BMD), cortical tissue mineral density (Ct.TMD), cortical porosity (Ct.Po), cortical thickness (Ct.Th), cortical bone area fraction (Ct.A/Tt.A), trabecular density (Tb.BMD), trabecular number (Tb.N), trabecular thickness (Tb.Th), total area (Tt.Ar), and failure load (FL) from micro-finite element analysis. We assessed the association between sex-specific quartiles of VAT and BMD, microarchitecture, and strength in all participants and stratified by sex. All analyses were adjusted for age, sex, and in women, menopausal status, then repeated adjusting for body mass index (BMI) or weight. At the radius and tibia, Ct.Th, Ct.A/Tt.A, Tb.BMD, Tb.N, and FL were positively associated with VAT (all p-trend <0.05), but no other associations were statistically significant except for higher levels of cortical porosity with higher VAT in the radius. Most of these associations were only observed in women, and were no longer significant when adjusting for BMI or weight. Higher amounts of VAT are associated with greater BMD and better microstructure of the peripheral skeleton despite some suggestions of significant deleterious changes in cortical measures in the non-weight bearing radius. Associations were no longer significant after adjustment for BMI or weight, suggesting that the effects of VAT may not have a substantial effect on the skeleton independent of BMI or weight. © 2016 American Society for Bone and Mineral Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.2931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316419PMC
January 2017

A Cinderella Tale: Can New Shoes Change the Life of a Person With Knee Osteoarthritis?

Ann Intern Med 2016 09 12;165(6):443-4. Epub 2016 Jul 12.

From Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts, and Arcadia University, Glenside, Pennsylvania.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7326/M16-1459DOI Listing
September 2016

Mid-adulthood cardiometabolic risk factor profiles of sarcopenic obesity.

Obesity (Silver Spring) 2016 Feb;24(2):526-34

National Heart, Lung, and Blood Institute's Framingham Heart Study and Population Sciences Branch, Framingham, Massachusetts, USA.

Objective: Midlife and contemporaneous cardiometabolic risk factors associated with sarcopenic obesity were examined.

Methods: Utilizing BMI and sex-specific 24-h urinary creatinine excretion, 1,019 participants from the Framingham cohorts were categorized as non-sarcopenia non-obese (NSNO), non-obese sarcopenia, non-sarcopenic obesity, and sarcopenic obesity. Cardiometabolic risk factors were quantified by standard laboratory assessment cross-sectionally and 10, 20, and 30 years before sarcopenic obesity assessment.

Results: NSNO, sarcopenia, obesity, and sarcopenic obesity accounted for 30.0%, 39.6%, 20.0%, and 10.4% of study participants, respectively. Cross-sectionally, participants with sarcopenic obesity had a higher proportion of hypertension, metabolic syndrome, and type 2 diabetes than those with NSNO or sarcopenia (all P < 0.03). Similar patterns were observed retrospectively at 10, 20, and 30 years. Compared with NSNO or sarcopenia, sarcopenic obesity was associated with a higher prevalence of type 2 diabetes at 10 years and hypertension and metabolic syndrome at all three time points before baseline (all P < 0.03). Individuals with sarcopenic obesity had more type 2 diabetes than those with obesity alone at baseline and 10 years prior (all P < 0.001).

Conclusions: Older adults with sarcopenic obesity had more adverse midlife cardiometabolic risks, particularly diabetes 10 years earlier, which suggests the importance of early identification of risk factors associated with sarcopenic obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/oby.21356DOI Listing
February 2016

Comparison of Handgrip and Leg Extension Strength in Predicting Slow Gait Speed in Older Adults.

J Am Geriatr Soc 2016 Jan;64(1):144-50

University of Connecticut Health Center, Farmington, Connecticut.

Objectives: To compare the relative predictive power of handgrip and leg extension strength in predicting slow walking.

Design: Report of correlative analysis from two epidemiological cohort studies.

Setting: Foundation of the National Institutes of Health Sarcopenia Project.

Participants: Men and women aged 67 to 93 (N=6,766).

Measurements: Leg strength, handgrip strength, and gait speed were measured. Strength cutpoints associated with slow gait speed were developed using classification and regression tree analyses and compared using ordinary least squares regression models.

Results: The cutpoints of lower extremity strength associated with slow gait speed were 154.6 N-m in men and 89.9 N-m in women for isometric leg extension strength and 94.5 N-m in men and 62.3 N-m in women for isokinetic leg extension strength. Weakness defined according to handgrip strength (odds ratios (OR)=1.99 to 4.33, c-statistics=0.53 to 0.67) or leg strength (ORs=2.52 to 5.77; c-statistics=0.61 to 0.66) was strongly related to odds of slow gait speed. Lower extremity strength contributed 1% to 16% of the variance and handgrip strength contributed 3% to 17% of the variance in the prediction of gait speed depending on sex and mode of strength assessment.

Conclusion: Muscle weakness of the leg extensors and forearm flexors is related to slow gait speed. Leg extension strength is only a slightly better predictor of slow gait speed. Thus, handgrip and leg extension strength appear to be suitable for screening for muscle weakness in older adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.13871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490244PMC
January 2016

Dietary Protein Intake Is Protective Against Loss of Grip Strength Among Older Adults in the Framingham Offspring Cohort.

J Gerontol A Biol Sci Med Sci 2016 Mar 2;71(3):356-61. Epub 2015 Nov 2.

Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Background: Age-related decline in muscle strength is an important public health issue for older adults. Dietary protein has been associated with maintenance of muscle mass, yet its relation to muscle strength remains unclear.

Methods: We determined the association of dietary protein (total, animal, and plant) intake, measured by food frequency questionnaire, with change in grip strength over 6 years in 1,746 men and women from the Framingham Offspring cohort.

Results: Mean age at baseline was 58.7 years (range: 29-85), and mean total, animal, and plant protein intakes were 79, 57, and 22 g/d, respectively. Adjusted baseline mean grip strength did not differ across quartiles of energy-adjusted total, animal or protein intake. Greater protein intake, regardless of source, was associated with less decrease in grip strength (all p for trend ≤.05): participants in the lowest quartiles lost 0.17% to 0.27% per year while those in the highest quartiles gained 0.52% to 0.60% per year. In analyses stratified by age, participants aged 60 years or older (n = 646) had similar linear trends on loss of grip strength for total and animal (all p for trend <.03) but not plant protein, while the trends in participants younger than 60 years (n = 896) were not statistically significant.

Conclusions: Higher dietary intakes of total and animal protein were protective against loss of grip strength in community-dwelling adults aged 60 years and older. Increasing intake of protein from these sources may help maintain muscle strength and support prevention of mobility impairment in older adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gerona/glv184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864162PMC
March 2016