Publications by authors named "Nancy E Lane"

240 Publications

The Effect of Discontinuing Denosumab in Patients With Rheumatoid Arthritis Treated With Glucocorticoids.

Arthritis Rheumatol 2021 Sep 17. Epub 2021 Sep 17.

Metroplex Clinical Research Center, Dallas.

Objective: To evaluate changes in bone turnover and bone mineral density (BMD) in subjects with rheumatoid arthritis (RA) on glucocorticoid (GC) after discontinuing denosumab for 12 months.

Methods: Randomized, double-blind, placebo-controlled phase 2 study of subjects with RA. Subjects received placebo, or denosumab 60 or 180 mg every 6 months for 12 months and were followed for an additional 12 months after discontinuation, during which no bone loss prevention therapy was instituted. Changes from baseline in serum C-terminal telopeptide of type I collagen (CTX), procollagen type I N-terminal propeptide (P1NP), and lumbar spine (LS) and total hip (TH) BMD were evaluated.

Results: In this post-hoc analysis of subjects treated with GCs at study baseline (N = 82). CTX and P1NP decreased significantly from baseline in both denosumab groups. Following denosumab discontinuation, CTX returned to baseline and was not significantly different from placebo 6 and 12 months after discontinuation. Median percent changes from baseline P1NP with denosumab 60 mg were -0.16% and 15.3% at 6 and 12 months, respectively, after discontinuation (P = 0.062 and 0.017 vs placebo); corresponding changes with denosumab 180 mg were 9.0% and 75.8% (P = 0.018 and 0.002). Compared with placebo, LS and TH BMD increased in subjects receiving denosumab, and returned to baseline 12 months after discontinuation. No osteoporotic fractures were reported during the treatment or off-treatment periods.

Conclusion: In this analysis of short-term denosumab use in subjects with RA receiving GCs, denosumab discontinuation resulted in a gradual increase in bone turnover, which was associated with a return to baseline LS and TH BMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41981DOI Listing
September 2021

CT muscle density, D3Cr muscle mass and body fat associations with physical performance, mobility outcomes and mortality risk in older men.

J Gerontol A Biol Sci Med Sci 2021 Sep 16. Epub 2021 Sep 16.

California Pacific Medical Center Research Institute, San Francisco, CA.

Background: Muscle mass declines with age, while body adiposity increases. Sarcopenic obesity has been proposed to be particularly deleterious. However, previous methods for estimating muscle mass have been inadequate, and the relative contributions of total body fat vs. muscle fat to adverse outcomes have been unclear.

Methods: In a large cohort of older men (N= 1017), we measured muscle mass (D3 creatine dilution), muscle density (high resolution peripheral computed tomography in the diaphyseal tibia) as a proxy of muscle fat, and total body fat (dual energy x-ray absorptiometry). We examined their associations with physical performance (walking speed, grip strength, chair stand time), the risk of mobility outcomes (mobility limitations, mobility disability), and the risk of death over ~5 years.

Results: In combined models, lower muscle mass and muscle density were independently associated with worse physical performance and the risk of adverse outcomes, while total body fat was minimally related to physical performance and not related to mobility outcomes or mortality. For example, the relative risks for mortality per 1 standardized unit increase in muscle density, muscle mass, and total body fat were 0.84 (95% CI: 0.74, 0.70), 0.70 (0.57, 0.86), and 0.90 (0.64, 1.25), respectively.

Conclusions: Muscle mass and muscle density were associated with physical performance and adverse outcomes, and had independent, additive effects. There was little additional contribution of total body fat.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gerona/glab266DOI Listing
September 2021

Validation of a Semiautomatic Image Analysis Software for the Quantification of Musculoskeletal Tissues.

Calcif Tissue Int 2021 Sep 13. Epub 2021 Sep 13.

Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St. Albans, VIC, 3021, Australia.

Accurate quantification of bone, muscle, and their components is still an unmet need in the musculoskeletal field. Current methods to quantify tissue volumes in 3D images are expensive, labor-intensive, and time-consuming; thus, a reliable, valid, and quick application is highly needed. Tissue Compass is a standalone software for semiautomatic segmentation and automatic quantification of musculoskeletal organs. To validate the software, cross-sectional micro-CT scans images of rat femur (n = 19), and CT images of hip and abdomen (n = 100) from the Osteoporotic Fractures in Men (MrOS) Study were used to quantify bone, hematopoietic marrow (HBM), and marrow adipose tissue (MAT) using commercial manual software as a comparator. Also, abdominal CT scans (n = 100) were used to quantify psoas muscle volumes and intermuscular adipose tissue (IMAT) using the same software. We calculated Pearson's correlation coefficients, individual intra-class correlation coefficients (ICC), and Bland-Altman limits of agreement together with Bland-Altman plots to show the inter- and intra-observer agreement between Tissue Compass and commercially available software. In the animal study, the agreement between Tissue Compass and commercial software was r > 0.93 and ICC > 0.93 for rat femur measurements. Bland-Altman limits of agreement was - 720.89 (- 1.5e+04, 13,074.00) for MAT, 4421.11 (- 1.8e+04, 27,149.73) for HBM and - 6073.32 (- 2.9e+04, 16,388.37) for bone. The inter-observer agreement for QCT human study between two observers was r > 0.99 and ICC > 0.99. Bland-Altman limits of agreement was 0.01 (- 0.07, 0.10) for MAT in hip, 0.02 (- 0.08, 0.12) for HBM in hip, 0.05 (- 0.15, 0.25) for bone in hip, 0.02 (- 0.18, 0.22) for MAT in L1, 0.00 (- 0.16, 0.16) for HBM in L1, and 0.02 (- 0.23, 0.27) for bone in L1. The intra-observer agreement for QCT human study between the two applications was r > 0.997 and ICC > 0.99. Bland-Altman limits of agreement was 0.03 (- 0.13, 0.20) for MAT in hip, 0.05 (- 0.08, 0.18) for HBM in hip, 0.05 (- 0.24, 0.34) for bone in hip, - 0.02 (- 0.34, 0.31) for MAT in L1, - 0.14 (- 0.44, 0.17) for HBM in L1, - 0.29 (- 0.62, 0.05) for bone in L1, 0.03 (- 0.08, 0.15) for IMAT in psoas, and 0.02 (- 0.35, 0.38) for muscle in psoas. Compared to a conventional application, Tissue Compass demonstrated high accuracy and non-inferiority while also facilitating easier analyses. Tissue Compass could become the tool of choice to diagnose tissue loss/gain syndromes in the future by requiring a small number of CT sections to detect tissue volumes and fat infiltration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00223-021-00914-4DOI Listing
September 2021

Lower urinary tract symptoms are associated with musculoskeletal pain among older men: Preliminary evidence for central sensitization as a mechanism?

Neurourol Urodyn 2021 Aug 15. Epub 2021 Aug 15.

Division of Epidemiology Programs, Oregon Health & Science University-Portland State University School of Public Health, Portland, Oregon, USA.

Aims: Features of central sensitization (CS) are present in almost all chronic pain conditions, including painful urinary conditions and back pain. Recently CS was proposed as a mechanism of nonpainful lower urinary tract symptoms (LUTS). Using musculoskeletal pain as an indicator of CS, we investigated whether the prevalence of musculoskeletal pain is greater among community-dwelling men with moderate or severe LUTS compared to those with mild LUTS.

Methods: We conducted a cross-sectional study of 5966 men ≥65 years who attended the Osteoporotic Fractures in Men Study baseline visit. LUTS were assessed with the American Urological Association Symptom Index (AUA-SI) and categorized as none/mild (0-7), moderate (8-19), or severe (≥20). Self-reported back, neck, hip, or knee pain within the 12 months before baseline was categorized as any pain and multilocation pain. We tested our hypothesis using odds ratios (OR) and 95% confidence intervals (CI) estimated from multivariable logistic regression models.

Results: The adjusted odds of any pain were higher among men with moderate (OR 1.49, 95% CI: 1.29-1.72) and severe LUTS (OR 1.76, 95% CI: 1.28-2.40) compared to those with no/mild LUTS. The adjusted odds of pain at ≥ 2 locations were 69% higher among men with moderate (OR 1.69, 95% CI: 1.45-196) and more than double among men with severe LUTS (OR 2.24, 95% CI: 1.62-3.10) compared to men with no/mild LUTS.

Conclusions: Musculoskeletal pain, especially at multiple locations, is associated with greater LUTS severity among older men. CS may represent a novel shared mechanism of pain and LUTS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/nau.24767DOI Listing
August 2021

Opioid users show worse baseline knee osteoarthritis and faster progression of degenerative changes: a retrospective case-control study based on data from the Osteoarthritis Initiative (OAI).

Arthritis Res Ther 2021 05 22;23(1):146. Epub 2021 May 22.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, 185 Berry Street, Lobby 6, Suite 350, San Francisco, CA, 94107, USA.

Background: Opioids are frequently prescribed for pain control in knee osteoarthritis patients, despite recommendations by current guidelines. Previous studies have investigated the chondrotoxicity of different opioid subtypes. However, the impact opioids may have on progression of osteoarthritis in vivo remains unknown. The aim of this study was thus to describe the associations between opioid use and knee structural changes and clinical outcomes, over 4 years.

Methods: Participants with baseline opioid use (n=181) and who continued use for ≥1 year between baseline and 4-year follow-up (n=79) were included from the Osteoarthritis Initiative cohort and frequency matched with non-users (controls) (1:2). Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained, including a total summation score (WORMS total, range 0-96) and subscores for cartilage (0-36), menisci (0-24), and bone marrow abnormalities and subchondral cyst-like lesions (0-18, respectively). Knee Injury Osteoarthritis Outcomes score (KOOS) symptoms, quality of life (QOL), and pain were also obtained at baseline and follow-up (range 0-100; lower scores indicate worse outcomes). Using linear regression models, associations between baseline and longitudinal findings were investigated. As pain may modify observations, a sensitivity analysis was performed for longitudinal findings. All analyses were adjusted for sex, BMI, age, race, and Kellgren-Lawrence grade.

Results: Opioid users had greater structural degeneration at baseline (WORMS total: Coef. [95% CI], P; 7.1 [5.5, 8.8], <0.001) and a greater increase over 4 years (4.7 [2.9, 6.5], <0.001), compared to controls. Cartilage and meniscus scores increased greater in opioid users, compared to controls (P≤0.001), and findings withstood the adjustment for baseline pain (P≤0.002). All baseline KOOS scores were lower in opioid users compared to controls (P<0.001). QOL loss was greater, when adjusted for baseline KOOS pain (QOL -6.9 [-11.6, -2.1], 0.005).

Conclusions: Opioid users had worse baseline knee structural degeneration and faster progression. Opioid use was also associated with worse symptoms, pain, and QOL. Furthermore, QOL loss was greater in opioid users compared to controls, when adjusted for baseline KOOS pain, indicating that opioids may not be suited to prevent subjective disease progression in KOA patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-021-02524-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140460PMC
May 2021

Cross-Sectional and Prospective Associations of Rest-Activity Rhythms with Circulating Inflammatory Markers in Older Men.

J Gerontol A Biol Sci Med Sci 2021 Apr 5. Epub 2021 Apr 5.

Research Institute, California Pacific Medical Center, San Francisco, CA, USA.

Chronic increases in pro-inflammatory cytokines in older adults, known as inflammaging, is an important risk factor for morbidity and mortality in the aging population. It has been suggested that circadian disruption may play a role in chronic inflammation, but there has been limited study that investigated the overall profile of 24-hour rest-activity rhythms in relation to inflammation using longitudinal data. In the Outcomes of Sleep Disorders in Older Men Study, we applied the extended cosine model to derive multiple rest-activity rhythm characteristics using multi-day actigraphy, and examined their associations with six inflammatory markers (i.e., CRP, IL-6, TNF-α, TNF-α-sRII, IL-1 β, IFN-γ) measured from fasting blood. We assessed both the cross-sectional association between rest-activity rhythms and inflammatory markers measured at baseline, and the prospective association between baseline rest-activity rhythms and changes in in inflammatory markers over 3.5 years of follow up. We found that multiple rest-activity characteristics, including lower amplitude and relative amplitude, and decreased overall rhythmicity, were associated with higher levels of CRP, IL-6, TNF-α, and TNF-α-sRII, but not IL-1β and IFN-γ at baseline. Moreover, the lowest quartile of these three rest-activity characteristics was associated with an approximately two-fold increase in the odds of having elevated inflammation (i.e. having three or more markers in the highest quartile) at baseline. However, we found little evidence supporting a relationship between rest-activity rhythm characteristics and changes in inflammatory markers. Future studies should clarify the dynamic relationship between rest-activity rhythms and inflammation in different populations, and evaluate the effects of improving rest-activity profiles on inflammation and related disease outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gerona/glab095DOI Listing
April 2021

Weight Cycling and Knee Joint Degeneration in Individuals with Overweight or Obesity: Four-Year Magnetic Resonance Imaging Data from the Osteoarthritis Initiative.

Obesity (Silver Spring) 2021 05 1;29(5):909-918. Epub 2021 Apr 1.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.

Objective: The aim of this study was to investigate the associations between weight cycling and knee joint degeneration in individuals with overweight or obesity with different patterns of weight change over 4 years.

Methods: A total of 2,271 individuals from the Osteoarthritis Initiative database were assessed (case-control study). Linear regression models using annual BMI measurements over 4 years were used to classify participants as weight cyclers or noncyclers. 3-T magnetic resonance imaging was used to quantify knee cartilage transverse relaxation time (T2) and cartilage thickness annually over 4 years in all subjects. Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained for cartilage, meniscus, and bone-marrow abnormalities in 958 subjects at baseline and at the 4-year follow-up. The longitudinal differences in cartilage T2 and thickness between weight cyclers and noncyclers were assessed using general estimating equations, whereas the differences in WORMS outcomes were compared using general linear models.

Results: No significant differences in the rate of change of cartilage thickness or T2 were found between weight cyclers and noncyclers. However, increases in maximum cartilage WORMS (P = 0.0025) and bone-marrow abnormalities (P = 0.04) were significantly greater in weight cyclers than in noncyclers.

Conclusions: Although participants' intent for weight cycling in this study was unknown, weight cyclers had significantly greater increases in cartilage and bone-marrow abnormalities over 4 years than noncyclers, independent of weight gain and loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/oby.23129DOI Listing
May 2021

Targeting Nerve Growth Factor for Pain Management in Osteoarthritis-Clinical Efficacy and Safety.

Rheum Dis Clin North Am 2021 05 12;47(2):181-195. Epub 2021 Mar 12.

Division of Rheumatology, Department of Internal Medicine, UC Davis Health, 4625 Second Avenue, Sacramento, CA 95917, USA.

Nerve growth factor (NGF) is a neurotrophin that mediates pain sensitization in pathologic states, including osteoarthritis. In clinical trials, antibodies to NGF reduce pain and improve physical function due to osteoarthritis of the knee or hip and have a long duration of action. Rapidly progressive osteoarthritis is a dose-dependent adverse event with these agents, and additional joint safety signals, such as subchondral insufficiency fractures and increased rates of total joint replacement, are reported. The effects on pain and potential mechanisms behind these joint events both are of considerable importance in the consideration of future use of anti-NGF therapies for osteoarthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rdc.2020.12.003DOI Listing
May 2021

Bone Strength/Bone Mass Discrepancy in Glucocorticoid-Treated Adult Mice.

JBMR Plus 2021 Mar 21;5(3):e10443. Epub 2020 Dec 21.

Center for Musculoskeletal Health University of California at Davis Medical Center Sacramento CA USA.

Glucocorticoids increase bone fragility in patients in a manner that is underestimated by bone mass measurement. This study aimed to determine if the adult mouse could model this bone strength/bone mass discrepancy. Forty-two 13-week-old BALB/cJ mice were randomized into vehicle and glucocorticoid groups, implanted with vehicle or 6-methylprednisolone pellets, and necropsied after 60 and 120 days. Bone strength and bone mass/microarchitecture were assessed at the right central femur (CF; cortical-bone-rich) and sixth lumbar vertebral body (LVB6; trabecular-bone-rich). Bound water (BW) of the whole right femur was analyzed by proton-nuclear magnetic resonance (H-NMR) relaxometry. Data were analyzed by two-factor ANOVA with time (day 60 and day 120) and treatment (vehicle and glucocorticoid) as main effects for all data. Significant interactions were further analyzed with a Tukey's post hoc test. Most bone strength measures in the CF were lower in the glucocorticoid group, regardless of the duration of treatment, with no time × treatment interaction. However, bone mass measures in the CF showed a significant time × treatment interaction ( = 0.0001). Bone strength measures in LVB6 showed a time × treatment interaction ( < 0.02) such that LVB6 strength was lower after 120 days of glucocorticoids compared with 120 days of vehicle treatment. Whole-femur-BW was lower with both glucocorticoid treatment ( = 0.0001) and time ( < 0.02), with a significant time × treatment interaction ( = 0.005). Glucocorticoid treatment of male BALB/cJ mice resulted in the lowering of bone strength in both cortical and trabecular bone that either appeared earlier or was greater than the treatment-related changes in bone mass/microarchitecture. The adult mouse may be a good model for investigating the bone strength/mass discrepancy observed in glucocorticoid-treated patients. © 2020 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/jbm4.10443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990143PMC
March 2021

Molecular pharming to support human life on the moon, mars, and beyond.

Crit Rev Biotechnol 2021 Sep 9;41(6):849-864. Epub 2021 Mar 9.

Center for the Utilization of Biological Engineering in Space (CUBES), Berkeley, CA, USA.

Space missions have always assumed that the risk of spacecraft malfunction far outweighs the risk of human system failure. This assumption breaks down for longer duration exploration missions and exposes vulnerabilities in space medical systems. Space agencies can no longer reduce the majority of the human health and performance risks through crew members selection process and emergency re-supply or evacuation. No mature medical solutions exist to address this risk. With recent advances in biotechnology, there is promise for lessening this risk by augmenting a space pharmacy with a biologically-based space foundry for the on-demand manufacturing of high-value medical products. Here we review the challenges and opportunities of molecular pharming, the production of pharmaceuticals in plants, as the basis of a space medical foundry to close the risk gap in current space medical systems. Plants have long been considered to be an important life support object in space and can now also be viewed as programmable factories in space. Advances in molecular pharming-based space foundries will have widespread applications in promoting simple and accessible pharmaceutical manufacturing on Earth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07388551.2021.1888070DOI Listing
September 2021

Joint-adjacent Adipose Tissue by MRI is Associated With Prevalence and Progression of Knee Degenerative Changes: Data from the Osteoarthritis Initiative.

J Magn Reson Imaging 2021 07 28;54(1):155-165. Epub 2021 Feb 28.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.

Background: Adipose tissue has recently gained interest as an independent imaging biomarker for osteoarthritis.

Purpose: To explore 1) cross-sectional associations between local subcutaneous fat (SCF) thickness at the knee and the extent of degenerative changes in overweight and obese individuals and 2) associations between local fat distribution and progression of osteoarthritis over 4 years.

Study Type: Retrospective cohort study.

Population: 338 obese and overweight participants from the Osteoarthritis Initiative cohort without radiographic evidence of osteoarthritis.

Field Strength: 3T: 3D-FLASH-WE; 3D-DESS-WE; T1w-SE; MSME.

Assessment: Baseline SCF thickness was measured in standardized locations medial, lateral and anterior to the knee and the average joint-adjacent SCF (ajSCF) was calculated. Right thigh SCF cross-sectional area was assessed. Quantitative cartilage T relaxation times and semi-quantitative whole organ MRI scores (WORMS) were obtained at baseline and 4-year follow-up. WORMS was calculated as sum of cartilage, bone marrow edema, subchondral cyst, and meniscal scores.

Statistical Tests: Associations of SCF measures with baseline, and 4-year change in T and WORMS were analyzed using regression models. SCF measurements were standardized using the equation . Analyses were adjusted for age, sex, physical activity, and BMI.

Results: Cross-sectionally, significant associations between lateral SCF, lateral compartment WORMS and T were found ( , [95% CI]: 0.53, [0.12-0.95], P < 0.05; ΔT : 0.50, [0.02-0.98], P < 0.05). Moreover, greater lateral SCF was associated with faster progression of lateral WORMS gradings (OR = 1.50, [1.05-2.15], P < 0.05). No significant positive associations were found for thigh SCF and WORMS (P = 0.44) or T measurements (medial: P = 0.15, lateral: 0.39, patellar: P = 0.75).

Data Conclusion: Joint-adjacent SCF thickness was associated with imaging parameters of knee osteoarthritis, both cross-sectionally and longitudinally, while thigh SCF was not, suggesting a spatial association of SCF and knee osteoarthritis. Based on these findings, joint-adjacent SCF may play a role in the development and progression of knee osteoarthritis.

Level Of Evidence: 4 TECHNICAL EFFICACY: Stage 5.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.27574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211379PMC
July 2021

Gut microbiome pattern reflects healthy ageing and predicts survival in humans.

Nat Metab 2021 02 18;3(2):274-286. Epub 2021 Feb 18.

Institute for Systems Biology, Seattle, WA, USA.

The gut microbiome has important effects on human health, yet its importance in human ageing remains unclear. In the present study, we demonstrate that, starting in mid-to-late adulthood, gut microbiomes become increasingly unique to individuals with age. We leverage three independent cohorts comprising over 9,000 individuals and find that compositional uniqueness is strongly associated with microbially produced amino acid derivatives circulating in the bloodstream. In older age (over ~80 years), healthy individuals show continued microbial drift towards a unique compositional state, whereas this drift is absent in less healthy individuals. The identified microbiome pattern of healthy ageing is characterized by a depletion of core genera found across most humans, primarily Bacteroides. Retaining a high Bacteroides dominance into older age, or having a low gut microbiome uniqueness measure, predicts decreased survival in a 4-year follow-up. Our analysis identifies increasing compositional uniqueness of the gut microbiome as a component of healthy ageing, which is characterized by distinct microbial metabolic outputs in the blood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42255-021-00348-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169080PMC
February 2021

Secondary analysis of change in physical function after exercise intervention in older adults with hyperkyphosis and low physical function.

BMC Geriatr 2021 02 22;21(1):133. Epub 2021 Feb 22.

Center for Musculoskeletal Health, University of California at Davis School of Medicine, 4625 2nd Ave, Suite 200, Davis, CA, 95817, USA.

Background: Hyperkyphosis is common in older adults and associated with low physical function and reduced health related quality of life (HrQol). Improved kyphosis has been previously established in kyphosis-targeted interventions in randomized controlled trials in older adults with hyperkyphosis; however, evidence for improved physical function is conflicting. Few studies have investigated change in physical function after a targeted kyphosis intervention in older adults with low physical function. The primary aim in this descriptive study was to explore change in physical function after a progressive high-intensity 3-month targeted kyphosis exercise and posture training intervention in older adults with low physical function and hyperkyphosis. Secondary aims were to explore change in HrQol, spinal strength and spinal curvature, and adherence and safety of the intervention.

Methods: In this secondary analysis of the Specialized Center of Research (SCOR) Kyphosis randomized trial, 101 community dwelling older men and women with hyperkyphosis who completed the intervention were divided into a low function group (LFG) and high function group (HFG). Baseline characteristics were compared between LFG and HFG. Physical function, HrQol, spinal strength and spinal curvature (kyphosis and lordosis) pre/post intervention change scores were explored within and between groups. Adherence and adverse events were examined in the LFG and HFG.

Results: Twenty-six (26%) older adults were LFG, mean Short Phyiscal Performance Battery (SPPB) 9.62 (SD = 1.17) points. At baseline, the LFG was older than HFG (p = 0.005), experienced more pain, (p = 0.060), had worse physical function and HrQol (p ≤ 0.001), and comparable kyphosis (p = 0.640). SPPB changed 0.62 (95% CI: - 0.20 to 1.44) points in the LFG and - 0.04 (95%CI: - 0.28 to 0.19) points in the HFG, p = 0.020. Gait speed changed 0.04 (95% CI: - 0.02 to 0.10) m/s in the LFG. Kyphosis improved equally in both groups. Adherence to the intervention was 83% in the LFG and 79% in the HFG. There were no adverse events in either group.

Conclusions: Older adults with low physical function and hyperkyphosis may improve physical function after a kyphosis targeted intervention. Older adults with low physical function may safely participate in targeted high-intensity kyphosis exercise and posture training. This observation needs to be confirmed in larger adequately powered studies.

Trial Registration: Clinicaltrials.gov identifier: NCT01766674 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12877-021-02062-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901174PMC
February 2021

Height Loss in Old Age and Fracture Risk Among Men in Late Life: A Prospective Cohort Study.

J Bone Miner Res 2021 06 19;36(6):1069-1076. Epub 2021 Mar 19.

Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

To assess the association of height loss in old age with subsequent risk of hip and any clinical fracture in men late in life while accounting for the competing risk of mortality, we used data from 3491 community-dwelling men (mean age 79.2 years). Height loss between baseline and follow-up (mean 7.0 years between examinations) was categorized as <1 cm (referent group), ≥1 to <2 cm, ≥2 to <3 cm, and ≥3 cm. Men were contacted every 4 months after the follow-up examination to ask about fractures (confirmed by radiographic reports) and ascertain vital status (deaths verified by death certificates). Competing risk methods were used to estimate absolute probabilities of fracture outcomes by height loss category and calculate adjusted risks of fracture outcomes by height loss. During an average of 7.8 years, 158 (4.5%) men experienced a hip fracture and 1414 (40.5%) died before experiencing this event. The absolute 10-year probability of fracture events accounting for the competing risk of death increased with greater height loss. For example, the hip fracture probability was 2.7% (95% confidence interval [CI] 1.9-3.8%) among men with height loss <1 cm increasing to 11.6% (95% CI 8.0-16.0%) among men with height loss ≥3 cm. After adjustment for demographics, fall history, multimorbidity, baseline height, weight change, and femoral neck bone mineral density and considering competing mortality risk, men with height loss ≥3 cm versus <1 cm had a nearly twofold (subdistribution hazard ratio [HR] = 1.94, 95% CI 1.06-3.55) higher risk of hip fracture and a 1.4-fold (subdistribution HR = 1.42, 95% CI 1.05-1.91) increased risk of any clinical fracture. Height loss ≥3 cm in men during old age was associated with higher subsequent risk of clinical fractures, especially hip fractures, even after accounting for the competing risk of death and traditional skeletal and non-skeletal risk factors. © 2021 American Society for Bone and Mineral Research (ASBMR).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.4278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255268PMC
June 2021

Characterization of individuals with osteoarthritis in the United States and their use of prescription and over-the-counter supplements.

Maturitas 2021 Mar 5;145:24-30. Epub 2020 Dec 5.

Pfizer Consumer Healthcare, Lautrupvang 8, 275, Ballerup, Denmark. Electronic address:

Purpose: Osteoarthritis (OA) is a frequently occurring, chronic condition; however, few studies describe the clinical characteristics of individuals with OA and the treatments they use to manage their symptoms. We conducted a study to characterize the OA population in the US and describe the nonsurgical management used by this population based on consumer research data collected through an online survey.

Methods: Data from the 2017 US National Health and Wellness Survey (NHWS) for adults aged ≥35 years were used to evaluate the relationship between OA and certain study participant characteristics and to identify the most commonly used treatment options. NHWS data were collected through a survey of individuals drawn from the internet panel maintained by Lightspeed Research (Bridgewater, New Jersey) and its panel partners. Weighted estimates were generated using data from the 2016 Current Population Survey (Annual Demographics File) of the US Census Bureau. Comparisons between the general and OA populations were made based on body mass index (BMI), exercise frequency, and comorbid diagnoses of hypertension or diabetes. Among the OA population, the use of dietary supplements, prescription or over-the-counter (OTC) treatments with chondroitin with or without glucosamine (Ch ± Gl), prescription treatment by time since OA diagnosis, and utilization of a physical therapist were also recorded.

Results: The prevalence of OA in the overall population was 17.6 % and was higher for individuals with a BMI ≥ 25 (21.9 %), patients diagnosed with hypertension or diabetes (36.2 %), and those who did not exercise regularly (19.0 %). Adults without OA were more likely to exercise regularly (12 days per month or more) than adults diagnosed with OA. Ch ± Gl (6.0 %) was the most commonly used OTC dietary supplement in the OA population, followed by omega-3 fatty acids (2.8 %), vitamin D (1.9 %), calcium (1.1 %), and multivitamins (0.7 %). Individuals using Ch ± Gl were more likely to use OTC only products (75.4 % vs 37.3 %) or prescription medications, namely non-steroidal anti-inflammatory drugs (NSAIDs) and/or opioids, and OTC products (24.6 % vs 13.0 %) compared with individuals not using Ch ± Gl, while individuals not using Ch ± Gl were more likely to be untreated (30.3 % vs 0) or to use prescription medications only (19.4 % vs 0). Nearly 32 % of individuals with OA reported using prescription treatments, and the likelihood of using a prescription treatment increased with number of years since OA diagnosis (<3 years: 27.5 %; ≥21 years: 32.5 %). The pharmaceutical products used by this population primarily consisted of nonsteroidal anti-inflammatory drugs, acetaminophen and opioids. Approximately 13 % of patients with OA had visited a physical therapist in the past 6 months.

Conclusions: The prevalence of OA was higher in those with a high BMI, and comorbid diabetes or hypertension. Individuals with OA using Ch ± Gl primarily reported use of OTC products only or used them in combination with prescription products. The likelihood of using prescription products increased with the length of OA history. These data provide valuable new information about demographics, clinical characteristics, and commonly used prescription and OTC treatments and dietary supplements in the OA population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.maturitas.2020.12.001DOI Listing
March 2021

Higher Fatigue Prospectively Increases the Risk of Falls in Older Men.

Innov Aging 2021 27;5(1):igaa061. Epub 2020 Nov 27.

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania, US.

Background And Objectives: Fatigue is a common complaint and shares many risk factors with falls, yet the independent contribution of fatigue on fall risk is unclear. This study's primary aim was to assess the association between fatigue and prospective fall risk in 5642 men aged 64-100 enrolled in the Osteoporotic Fractures in Men Study (MrOS). The secondary aim was to examine the association between fatigue and recurrent fall risk.

Research Design And Methods: Fatigue was measured at baseline using the Medical Outcomes Study (short form) single-item question "During the past four weeks, how much of the time did you feel energetic?" Responses were then classified: higher fatigue = "none," "a little," or "some" of the time and lower fatigue = "a good bit," "most," or "all" of the time. We assessed falls using triannual questionnaires. Fall risk was examined prospectively over 3 years; recurrent falling was defined as at least 2 falls within the first year. Generalized estimating equations and multinomial logistic regression modeled prospective and recurrent fall risk as a function of baseline fatigue status, adjusted for demographics, medications, physical activity, and gait speed.

Results: Men with higher (26%) versus lower baseline fatigue were older (75.1 ± 6.2 vs 73.2 ± 5.7 years), 24% less active, and had worse physical function (gait speed = 1.09 ± 0.24 vs 1.24 ± 0.21 m/s), all < .0001. Within 1 year, 25.4% ( = 1409) had fallen at least once, of which 47.4% ( = 668) were recurrent fallers. Men with higher versus lower fatigue had 25% increased fall risk (relative risk = 1.25, 95% CI: 1.14-1.36) over 3 years follow-up, but had 50% increased odds of recurrent falling (odds ratio = 1.50, 95% CI: 1.22-1.85) within the first year.

Discussion And Implications: Fatigue is an important risk factor of falling independent of established risk factors. Reductions in fatigue (ie, increased energy) may lessen the burden of falls in older men and provide a novel avenue for fall risk intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/geroni/igaa061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788315PMC
November 2020

The influence of adult hip shape genetic variants on adolescent hip shape: Findings from a population-based DXA study.

Bone 2021 02 4;143:115792. Epub 2020 Dec 4.

Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Objective: Hip shape is a well-recognized risk factor for hip osteoarthritis (OA) and hip fracture. We aimed to investigate whether the genetic variants known to be associated with adult hip shape were also associated with adolescent hip shape.

Methods: Hip DXA scans, obtained in offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) at two time points (mean ages 13.8 and 17.8 years), were used to quantify hip morphology using a 53-point Statistical Shape Model (SSM). Principal component analysis was used to generate hip shape modes (HSMs). Genetic variants which had previously shown genome-wide significant association with specific HSMs in adults were tested for association with the same HSMs in adolescents (at each timepoint separately) using SNPTEST v2.

Results: Complete genotypic and phenotypic data were available for 3550 and 3175 individuals at 14 and 18 years, respectively. The strongest evidence for association with adolescent hip shape was for a variant located near SOX9 (rs2158915) with consistent effects across both time points for HSM1 (age 14: beta -0.05, p = 9.9 × 10; age 18: -0.05, p = 3.3 × 10) and HSM5 (age 14: beta -0.07, p = 1.6 × 10; age 18: -0.1, p = 2.7 × 10). There was also strong evidence of association between rs10743612 (near PTHLH) and HSM1 (age 14: 0.05, p = 1.1 × 10; age 18: 0.04, p = 0.003) and between rs6537291 (near HHIP) and HSM2 (age 14: -0.06, p = 0.001; age 18: -0.07, p = 0.001) across both time points. The genes with the strongest associations with hip shape in adolescents, (SOX9, PTHLH and HHIP) are known to be involved in endochondral bone formation. HSM1 indicates narrower aspect ratio of the upper femur, whereas both HSM2 and HSM5 reflect variation in the femoral head size and femoral neck width, features previously found to be related to the risk of OA in later life. The SOX9 locus has previously been found to associate with increased risk of hip fracture.

Conclusion: In conclusion, variants implicated in endochondral bone formation appear to consistently influence hip shape between adolescence and adulthood, including those aspects related to risk of hip OA and/or fracture in later life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2020.115792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809624PMC
February 2021

The evolution of nerve growth factor inhibition in clinical medicine.

Nat Rev Rheumatol 2021 01 20;17(1):34-46. Epub 2020 Nov 20.

Center for Musculoskeletal Health, University of California Davis School of Medicine, Sacramento, CA, USA.

Nerve growth factor (NGF) is a neurotrophin that activates nociceptive neurons to transmit pain signals from the peripheral to the central nervous system and that exerts its effects on neurons by signalling through tyrosine kinase receptors. Antibodies that inhibit the function of NGF and small molecule inhibitors of NGF receptors have been developed and tested in clinical studies to evaluate the efficacy of NGF inhibition as a form of analgesia in chronic pain states including osteoarthritis and chronic low back pain. Clinical studies in individuals with painful knee and hip osteoarthritis have revealed that NGF inhibitors substantially reduce joint pain and improve function compared with NSAIDs for a duration of up to 8 weeks. However, the higher tested doses of NGF inhibitors also increased the risk of rapidly progressive osteoarthritis in a small percentage of those treated. This Review recaps the biology of NGF and the studies that have been performed to evaluate the efficacy of NGF inhibition for chronic musculoskeletal pain states. The adverse events associated with NGF inhibition and the current state of knowledge about the mechanisms involved in rapidly progressive osteoarthritis are also discussed and future studies proposed to improve understanding of this rare but serious adverse event.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41584-020-00528-4DOI Listing
January 2021

A new anabolic compound, LLP2A-Ale, reserves periodontal bone loss in mice through augmentation of bone formation.

BMC Pharmacol Toxicol 2020 11 13;21(1):76. Epub 2020 Nov 13.

Department of Internal Medicine, University of California, Davis Medical Center, 4625 2nd Avenue, Sacramento, CA, 95817, USA.

Background: Currently, there are no effective medications to reverse periodontal disease (PD)-induced bone loss. The objective of this study was to test a new anabolic compound, LLP2A-Ale, or with the combination treatment of mesenchymal stromal cell (MSC), in the treatment of bone loss secondary to PD.

Methods: PD was induced in mice by placing a ligature around the second right molar. At one week after disease induction, the mice were treated with placebo, LLP2A-Ale, MSCs, or combination of LLP2A-Ale + MSCs, and euthanized at week 4.

Results: We found that PD induced alveolar bone loss that was associated with reduced bone formation. LLP2A-Ale alone or in combination with MSCs sustained alveolar bone formation and reversed alveolar bone loss. Additionally, PD alone caused systemic inflammation and increased the circulating levels of G-CSF, IP-10, MIP-1a, and MIP2, which were suppressed by LLP2A-Ale +/- MSCs. LLP2A-Ale +/- MSCs increased bone formation at the peripheral skeletal site (distal femur), which was otherwise suppressed by PD.

Conclusion: Our findings indicated that LLP2A-Ale treatment rescued alveolar bone loss caused by PD, primarily by increasing bone formation. LLP2A-Ale also attenuated the circulating levels of a series of inflammatory cytokines and reversed the PD-induced suppression of systemic bone formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40360-020-00454-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664094PMC
November 2020

Co-existing patterns of MRI lesions were differentially associated with knee pain at rest and on joint loading: a within-person knee-matched case-controls study.

BMC Musculoskelet Disord 2020 Oct 6;21(1):650. Epub 2020 Oct 6.

Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.

Background: To assess the association of co-existing MRI lesions with knee pain at rest or on joint loading.

Methods: We included participants from Osteoarthritis Initiative whose pain score, measured by WOMAC sub-scales, differed by ≥1 point at rest (in bed at night, sitting/lying down) or on joint loading (walking, stairs) between two knees. Cartilage morphology, bone marrow lesions, meniscus extrusion, meniscus morphology, Hoffa's synovitis and synovitis-effusion were assessed using the compartment-specific MRI Osteoarthritis Knee Score. We performed latent class analyses to identify subgroups of co-existing MRI lesions and fitted a conditional logistic regression model to examine their associations with knee pain.

Results: Among 130 eligible participants, we identified five subgroups of knees according to patterns of co-existing MRI lesions: I. minimal lesions; II. mild lesions; III. moderate morphological lesions; IV. moderate multiple reactive lesions; and V. severe lesions. Compared with subgroup I, the odds ratios (ORs) and 95% confidence intervals (CI) of greater pain in bed at night were 1.6 (0.3, 7.2), 2.2 (0.5, 9.5), 6.2 (1.3, 29.6) and 11.2 (2.1, 59.2) for subgroups II-V, respectively. A similar association was observed between aforementioned subgroups and pain with sitting/lying down. The ORs (95% CI) of greater pain with walking were 1.0 (reference), 1.7 (0.5, 6.1), 0.7 (0.2, 2.3), 5.0 (1.4, 18.6) and 7.9 (2.0, 31.5) for subgroup I-V, respectively. The corresponding analysis for pain on stairs showed similar results.

Conclusions: Distinct patterns of co-existing MRI lesions have different implications for the pathogenesis of osteoarthritic knee pain occurring with/without joint loading.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12891-020-03686-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541235PMC
October 2020

Cross-sectional and Prospective Associations of Rest-Activity Rhythms With Metabolic Markers and Type 2 Diabetes in Older Men.

Diabetes Care 2020 11 4;43(11):2702-2712. Epub 2020 Sep 4.

Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA.

Objective: Disruption of rest-activity rhythms is cross-sectionally associated with metabolic disorders, including type 2 diabetes, yet it remains unclear whether it predicts impaired glucose metabolism and homeostasis. The aim of this study is to examine the cross-sectional and prospective associations between rest-activity rhythm characteristics and glycemic measures in a cohort of older men.

Research Design And Methods: Baseline rest-activity rhythms were derived from actigraphy with use of extended cosine model analysis. With subjects fasting, glucose, insulin, and HOMA of insulin resistance (HOMA-IR) were measured from blood at baseline and after ∼3.5 years. Type 2 diabetes was defined based on self-report, medication use, and fasting glucose.

Results: In the cross-sectional analysis ( = 2,450), lower 24-h amplitude-to-mesor ratio (i.e., mean activity-adjusted rhythm amplitude) and reduced overall rhythmicity were associated with higher fasting insulin and HOMA-IR (all < 0.0001), indicating increased insulin resistance. The odds of baseline type 2 diabetes were significantly higher among those in the lowest quartile of amplitude (Q1) (odds ratio [OR] 1.63 [95% CI 1.14, 2.30]) and late acrophase group (OR 1.46 [95% CI 1.04, 2.04]). In the prospective analysis ( = 861), multiple rest-activity characteristics predicted a two- to threefold increase in type 2 diabetes risk, including a lower amplitude (OR 3.81 [95% CI 1.45, 10.00]) and amplitude-to-mesor ratio (OR 2.79 [95% CI 1.10, 7.07]), reduced overall rhythmicity (OR 3.49 [95% CI 1.34, 9.10]), and a late acrophase (OR 2.44 [1.09, 5.47]).

Conclusions: Rest-activity rhythm characteristics are associated with impaired glycemic metabolism and homeostasis and higher risk of incident type 2 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/dc20-0557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576417PMC
November 2020

Long-Term Efficacy of Treatment Effects After a Kyphosis Exercise and Posture Training Intervention in Older Community-Dwelling Adults: A Cohort Study.

J Geriatr Phys Ther 2021 Jul-Sep 01;44(3):127-138

Department of Medicine, University of California, Davis.

Background And Purpose: Treatments that prevent worsening kyphosis are important due to the progressive nature of kyphosis with aging. We assessed long-term efficacy of treatment effects after a short-term kyphosis exercise and posture training intervention in a cohort study among older adults with hyperkyphosis, and investigated whether long-term treatment effects differ among males and females.

Methods: In the original kyphosis intervention, 112 older adults enrolled in a waitlist design randomized controlled trial. One hundred three participants, mean age 70.0 (5.7) years and kyphosis 52.0° (7.4°), completed a twice weekly, 3-month, group exercise and posture training intervention, and were eligible to enroll in the follow-up study. We compared (1) change in outcomes pre-/postintervention to change postintervention over the follow-up period, (2) change in outcomes pre-/postintervention and postintervention to follow-up, stratified by sex, and (3) long-term change postintervention to follow-up in males and females. Primary outcome was change in kyphometer-measured thoracic kyphosis. Secondary outcomes were change in lumbar lordosis, objective measures of physical function, self-reported measures of physical activity, and health-related quality of life (HRQoL).

Results And Discussion: Forty-three participants, 42% of the eligible cohort, returned for follow-up, a mean 3.0 (0.7) years after completing the original intervention. Participants (27 females and 16 males) were 73.8 (6.1) years old, with mean kyphosis 48.9° (11.9°) at follow-up. Kyphosis declined -1.5° (95% confidence interval [CI]: -3.9° to 1.0°) postintervention to follow-up and this was no different than change pre-/postintervention, P = .173. Lordosis improved 8.9° (95% CI: 6.2° to 11.6°), more than change pre-/postintervention, P < .001. Gait speed measure of physical function increased 0.08 (95% CI: 0.02 to 0.14) m/s, Physical Activity Scale for the Elderly (PASE) measure of physical activity increased 4 (95% CI: -16 to 24) points, and Patient-Reported Outcomes Measurement Information System (PROMIS) mental health T-score measure of HRQoL increased 1.1 (95% CI: -1.0 to 3.1) points, but these improvements were not significantly more than change pre-/postintervention, P > .050. Other measures of physical function (modified Physical Performance Test [PPT], Timed Up and Go, and 6-minute walk) and HRQoL (Scoliosis Research Society [SRS-30] self-image and PROMIS physical function and physical health) declined at follow-up, significantly more than change pre/postintervention, P ≤ .050. Comparing change in outcomes pre-/postintervention and postintervention to follow-up, stratified by sex, both males and females increased lordosis, and decreased modified PPT and 6-minute walk measures of physical function, P < .050. Males and females differed in long-term change postintervention to follow-up. Time loaded standing and PASE improved in females compared with males, P = .008 and P = .092, respectively, and PROMIS mental health, physical health, and physical function declined in females compared with males, P = .073, P = .025, and P = .005, respectively.

Conclusions: In our follow-up study, a mean of 3.0 (0.07) years after a 3-month kyphosis exercise and posture training intervention, kyphosis maintained and did not progress as expected with age. There was long-term improvement in lordosis. Compared with treatment effects from the short-term intervention, gait speed maintained equally well in males and females, while trunk endurance improved in females. Further investigation of long-term benefits of a short-term kyphosis exercise and posture training intervention is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1519/JPT.0000000000000262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876164PMC
August 2021

Determining a Threshold of Medial Meniscal Extrusion for Prediction of Knee Pain and Cartilage Damage Progression Over 4 Years: Data From the Osteoarthritis Initiative.

AJR Am J Roentgenol 2021 05 29;216(5):1318-1328. Epub 2020 Jul 29.

Department of Radiology and Biomedical Imaging, Musculoskeletal Quantitative Imaging Research Group, University of California San Francisco, 185 Berry St, Ste 350, San Francisco, CA 94107.

The extent of medial meniscal extrusion (MME) that is associated with structural and symptomatic progression of knee osteoarthritis has not been defined yet. The purpose of our study was to investigate MRI-based thresholds of MME that are associated with structural progression of knee degenerative disease and symptoms over a period of 4 years. We studied 328 knees of 235 participants that were randomly selected from the Osteoarthritis Initiative cohort. MME was quantified on coronal sections of intermediate-weighted MRI sequences obtained at 3 T. Knee pain and cartilage abnormalities were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale and the cartilage whole-organ MRI score (WORMS). General estimating equations with logistic regression models were used to correlate baseline MME and changes in pain (WOMAC) and cartilage damage (WORMS). ROC analyses were performed to determine the area under the ROC curve (AUROC). Individual thresholds were determined by maximizing the product of sensitivity and specificity. The AUROC for predicting progression of knee pain, medial compartment cartilage damage, and medial tibial cartilage damage were 0.71, 0.70, and 0.72, respectively, and the individual thresholds for MME were 2.5, 2.7, and 2.8 mm. A single threshold of 2.5 mm was determined by maximizing the mean of the product of sensitivity and specificity of the three outcome variables (knee pain progression, medial compartmental cartilage damage progression, and medial tibial cartilage damage progression). MME was associated with knee pain and cartilage damage progression over 4 years. A single threshold of 2.5 mm was found to be the most useful threshold for predicting knee pain, medial compartment cartilage damage progression, and tibial cartilage damage progression over 4 years. This threshold could be used to standardize the diagnostic criterion of extrusion and to better characterize the risk for subsequent structural and symptomatic progression of knee osteoarthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.20.23864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183109PMC
May 2021

Obese and overweight individuals have greater knee synovial inflammation and associated structural and cartilage compositional degeneration: data from the osteoarthritis initiative.

Skeletal Radiol 2021 Jan 23;50(1):217-229. Epub 2020 Jul 23.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94158, USA.

Objective: This work aims to study (i) the relationship between body mass index (BMI) and knee synovial inflammation using non-contrast-enhanced MRI and (ii) the association of synovial inflammation versus degenerative abnormalities and pain.

Materials And Methods: Subjects with risk for and mild to moderate radiographic osteoarthritis were selected from the Osteoarthritis Initiative. Subjects were grouped into three BMI categories with 87 subjects per group: normal weight (BMI, 20-24.9 kg/m), overweight (BMI, 25-29.9 kg/m), and obese (BMI, ≥ 30 kg/m), frequency matched for age, sex, race, Kellgren-Lawrence grade, and history of knee surgery and injury. Semi-quantitative synovial inflammation imaging biomarkers were obtained including effusion-synovitis, size and intensity of infrapatellar fat pad signal abnormality, and synovial proliferation score. Cartilage composition was measured using T relaxation time and structural abnormalities using the whole-organ magnetic resonance imaging score (WORMS). The Western Ontario and McMasters (WOMAC) Osteoarthritis Index was used for pain assessment. Intra- and inter-reader reproducibility was assessed by kappa values.

Results: Overweight and obese groups had higher prevalence and severity of all synovial inflammatory markers (p ≤ 0.03). Positive associations were found between synovial inflammation imaging biomarkers and average T values, WORMS maximum scores and total WOMAC pain scores (p < 0.05). Intra- and inter-reader kappa values for imaging biomarkers were high (0.76-1.00 and 0.60-0.94, respectively).

Conclusion: Being overweight or obese was significantly associated with a greater prevalence and severity of synovial inflammation imaging biomarkers. Substantial reproducibility and high correlation with knee structural, cartilage compositional degeneration, and WOMAC pain scores validate the synovial inflammation biomarkers used in this study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00256-020-03550-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677197PMC
January 2021

INHIBITION OF WINGLESS-RELATED INTEGRATION SITE (WNT) SIGNALLING MAY TREAT OSTEOARTHRITIS OF THE KNEE.

Authors:
Nancy E Lane

Trans Am Clin Climatol Assoc 2020 ;131:55-64

SACRAMENTO, CALIFORNIA.

Osteoarthritis (OA) of the knee is the leading cause of disability in individuals over 60 years of age. Currently, treatments have been limited to analgesic and anti-inflammatory medications that reduce pain and improve function for short periods of time, until a joint replacement is required. Recently, inhibition of the Wnt/beta-catenin signaling pathway with lorecivivint (LOR; SMO496) was found to prevent the deterioration of the cartilage in preclinical models of posttraumatic OA. LOR appears to reduce both STAT signaling and Wnt signaling in the chondrocyte, allowing for both a reduction in pain and the production of enzymes associated with cartilage destruction. LOR has been tested in both Phase I and Phase 2 trials, and a dose of 0.07ug/kg administered through intra-articular injection reduced pain and preserved the articular joint space as assessed by radiograph. Therefore, reduction in Wnt signaling in the knee joint may reduce signs and symptoms and alter the course of osteoarthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358486PMC
March 2021

High susceptibility to collagen-induced arthritis in mice with progesterone receptors selectively inhibited in osteoprogenitor cells.

Arthritis Res Ther 2020 07 2;22(1):165. Epub 2020 Jul 2.

Department of Internal Medicine, University of California, Davis Medical Center, 4625 2nd Avenue, Sacramento, CA, 95817, USA.

Background: Progesterone receptor (PR) affects immunomodulation, and lack of PR in osteoprogenitor cells primarily affects pathways associated with immunomodulation, especially in males. In this study, we selectively deleted PR from osteoprogenitor cells using Prx1-Cre to evaluate the tissue-specific effects of PR on the pathegenesis of inflammatary arthritis (IA).

Methods: Collagen-induced arthritis (CIA) was used as an IA animal model. Both male and female PR mice and their wild-type (WT) littermates were immunized with collagen II (CII) emulsified complete Freund's adjuvant (CFA). Joint erosion, inflammation, and cartilage damage were assessed using a semiquantitative histologic scoring system. Bone volume and erosions in knee and ankle joints were quantitated using microCT and histology.

Results: Bone erosions developed in both paw joints in 37.5% and 41.7% of the WT and PR female mice and in 45.4 and 83.3% of the WT and PR male mice, respectively. Also, both joint damage and subchondral bone erosions were significantly more severe in male PRcKO-CIA mice than in male WT-CIA mice. Female PR mice also developed higher bone loss in the knee joints than the KO-normal or WT-CIA females although with less severity compared to the male mice.

Conclusions: The presence of PR in osteoprogenitor cells decreased the development of collagen-induced arthritis and might help to explain the sex differences observed in human inflammatory arthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-020-02242-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331177PMC
July 2020

Natural history of new horizontal meniscal tears in individuals at risk for and with mild to moderate osteoarthritis: data from osteoarthritis initiative.

Eur Radiol 2020 Nov 22;30(11):5971-5980. Epub 2020 Jun 22.

Department of Radiology and Biomedical Imaging, University of California San Francisco, 185 Berry Street, Lobby 6, Suite 350, San Francisco, CA, 94107, USA.

Objectives: To study the natural history of new horizontal meniscal tears and their association with progression of cartilage degeneration in individuals at risk for or with mild to moderate knee osteoarthritis over 4 years.

Methods: Individuals who developed a new meniscal tear in the right knee over 2 years were selected from the Osteoarthritis Initiative 3T MRI studies. Knee structural changes were analyzed at the time of tear appearance (baseline), and after 4 years using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Meniscal tears were classified as either horizontal tears or non-horizontal tears. Individuals without a meniscal tear were 1:3 frequency matched according to BMI, gender, race, and age and served as the control group. Linear regression analysis was used to compare cross-sectional and longitudinal changes in cartilage WORMS scores.

Results: Forty-one subjects developed horizontal tears, including one indiviudal who developed a tear in both menisci, and 34 developed non-horizonal tears. We found that (29/41 (70.7%)) of horizontal and (20/34 (58.8%)) of non-horizonatal tears were stable during follow-up (p = 0.281). Although knees with an incident tear had higher than controls WORMS MAX total knee scores at baseline (coef. = 0.47, p = 0.044, 95% CI = 0.01 to 0.93), there were no significant differences between the horizontal subgroup and knees without tears in overall cartilage scores at baseline and in progression over 4 years of follow-up.

Conclusions: New horizontal meniscal tears tended to be stable over 4 years and presented no significant differences in progression of cartilage degeneration when compared with knees without tears.

Key Points: • Most of horizonal meniscal tears were stable over 4 years. • There were no statistically significant differences in overall progression of cartilage degenerative changes between knees with horizonal meniscal tears and control knees without tears • Horizontal tears most often occurred at the posterior horn of the medial meniscus and at the body of the lateral meniscus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-020-06960-0DOI Listing
November 2020

Meniscal Root Tears and Extrusion Are Significantly Associated with the Development of Accelerated Knee Osteoarthritis: Data from the Osteoarthritis Initiative.

Cartilage 2020 Jun 21:1947603520934525. Epub 2020 Jun 21.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

Objective: To identify joint structural risk factors, measured using quantitative compositional and semiquantitative magnetic resonance imaging (MRI) scoring, associated with the development of accelerated knee osteoarthritis (AKOA) compared with a more normal rate of knee osteoarthritis (OA) development.

Design: From the Osteoarthritis Initiative we selected knees with no radiographic OA (Kellgren-Lawrence grade [KL] 0/1) that developed advanced-stage OA (KL 3/4; AKOA) within a 4-year timeframe and a comparison group with a more normal rate of OA development (KL 0/1 to KL 2 in 4 years). MRIs at the beginning of the 4-year timeframe were assessed for cartilage T2 values and structural abnormalities using a modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations of MRI findings with AKOA versus normal OA were assessed using multivariable logistic regression models.

Results: A total of 106 AKOA and 168 subjects with normal OA development were included. Mean cartilage T2 values were not significantly associated with AKOA (odds ratio [OR] 1.06; 95% confidence interval [CI] 0.82-1.36). Risk factors for AKOA development included higher meniscus maximum scores (OR 1.37; 95% CI 1.11-1.68), presence of meniscal extrusion (OR 6.30; 95% CI 2.57-15.49), presence of root tears (OR 4.64; 95% CI 1.61-13.34), and higher medial tibia cartilage lesion scores (OR 1.96; 95% CI 1.19-3.24).

Conclusions: We identified meniscal damage, especially meniscal extrusion and meniscal root tears as risk factors for AKOA development. These findings contribute to identifying subjects at risk of AKOA at an early stage when preventative measures targeting modifiable risk factors such as meniscal repair surgery could still be effective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1947603520934525DOI Listing
June 2020
-->