GRAPPA 2023: Major Projects, Key Advances, and Milestones.

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, members were updated on a number of ongoing activities during the key project update session. These activities included the Axial Involvement in Psoriatic Arthritis (AXIS) cohort, the Axial Psoriatic Arthritis Molecular and Clinical Characterization study, the Diagnostic Ultrasound Enthesitis Tool (DUET) study, the Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies in Psoriatic Arthritis (SAGE-PsA) study, the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES), the GRAPPA slide library, and the GRAPPA treatment recommendations.

Using Ultrasound to Improve Diagnostic Confidence and Management of Psoriatic Disease: Highlights From the GRAPPA 2023 Ultrasound Workshop.

The sensitivity of ultrasound (US) to detect, characterize, and monitor the relevant pathologies of psoriatic arthritis (PsA), including synovitis, enthesitis, tenosynovitis, and dactylitis, has made it an attractive tool for informing clinical decisions. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) US working group ran 2 sessions during the annual GRAPPA meeting held in July 2023 in Dublin, Ireland. During the first workshop, the group presented 2 topics, followed by a live demonstration and a group discussion. The 2 topics were (1) an overview of the Diagnostic Ultrasound Enthesitis Tool (DUET) enthesitis scoring methodology, and (2) small hand-held probes-will the promise deliver? The live demonstration that followed compared the performance of 2 hand-held US (HHUS) devices vs a console US machine in patients with PsA, and the interactive group discussion considered gaps in the literature and future research suggestions relating to HHUS and its application in psoriatic disease. During the second session, the US working group provided further updates regarding the GRAPPA US studies currently underway or recently completed.

Developing Ultrasound Measures for the Early Diagnosis of Psoriatic Arthritis.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound (US) steering committee provided an update at GRAPPA's 2022 annual meeting on activities to enable earlier diagnosis of psoriatic arthritis. An update of the Diagnostic Ultrasound Enthesitis Tool (DUET) study included preliminary reliability results for US enthesitis elementary lesions. Common scanning pitfalls were reviewed. New projects included widening the scope of US beyond large entheses and validating small point-of-care US probes to evaluate enthesitis.

Sex differences in the efficacy, safety and persistence of patients with psoriatic arthritis treated with tofacitinib: a post-hoc analysis of phase 3 trials and long-term extension.

BACKGROUND: Evaluate the impact of sex on tofacitinib efficacy, safety and persistence (time to discontinuation) in patients with psoriatic arthritis (PsA). METHODS: Data were pooled from two phase 3 randomised controlled trials. Patients were randomised to tofacitinib 5 mg or 10 mg two times per day, adalimumab 40 mg every 2 weeks or placebo. Efficacy outcomes to month 12 included American College of Rheumatology (ACR)20/50/70, minimal disease activity (MDA), Psoriasis Area Severity Index (PASI)75, change from baseline (∆) in Health Assessment Questionnaire-Disability Index (HAQ-DI) and ∆Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Safety was assessed to month 12 and persistence was assessed to month 42 of a long-term extension study. RESULTS: Overall, 816 patients were included (54.3% females). At baseline, higher tender joint counts, enthesitis scores and worse HAQ-DI and FACIT-F were reported in females versus males; presence of dactylitis and PASI were greater in males versus females. At month 3, tofacitinib efficacy generally exceeded placebo in both sexes. Overall, similar ACR20/50/70, PASI75, ∆HAQ-DI and ∆FACIT-F were observed for tofacitinib between sexes; females were less likely to achieve MDA. Similar proportions of males/females receiving tofacitinib (both doses) experienced treatment-emergent adverse events (AEs). Serious AEs occurred in 3.4%/6.6% and 4.0%/5.9% males/females with tofacitinib 5 mg and 10 mg two times per day. Persistence was generally similar between sexes. CONCLUSION: Tofacitinib efficacy exceeded placebo in both sexes and was comparable between sexes. Consistent with previous studies of PsA treatments, females were less likely to achieve MDA, likely due to baseline differences. Safety and time to discontinuation were generally similar between sexes. TRIAL REGISTRATION NUMBER: NCT01877668; NCT01882439; NCT01976364.

Hidden in plain sight: Is there a crucial role for enthesitis assessment in the treatment and monitoring of axial spondyloarthritis?

OBJECTIVE: To review the evidence surrounding the pathophysiology of enthesitis in axial spondyloarthritis (axSpA), its prevalence and contribution to the overall disease burden, and response to treatment at axial and peripheral sites. METHODS: Literature searches of the Cochrane Library, PubMed, and Embase / Medline using the terms "enthesitis", "enthesopathy", "spondyloarthritis", "axial spondyloarthritis", and "ankylosing spondylitis" were conducted. Publications mentioning enthesitis or enthesopathy in the context of pathophysiology, diagnosis, or treatment were included. RESULTS: Enthesitis is a common symptom of axSpA, occurring with high prevalence at axial and several peripheral sites. Inflammation at the site of enthesis is an early key manifestation of axSpA. Clinically evaluable enthesitis contributes significantly to the burden of disease, correlating with worse symptomatology and downstream structural damage. Despite its importance in driving axSpA disease processes, enthesitis is somewhat neglected in current approaches to disease assessment and management. Enthesitis is excluded from some commonly used disease activity measures, is not routinely assessed in clinical practice, and many methods of clinical assessment omit key accessible axial sites, such as the spinous processes. CONCLUSION: Enthesitis plays a central role in driving the pathophysiology of axSpA. There is a need for a renewed focus on the early detection, measurement and treatment of enthesitis.

The effects of an 8-week knitting program on osteoarthritis symptoms in elderly women: A pilot randomized controlled trial.

BACKGROUND: Exercise therapy is effective in reducing symptoms and disability associated with hand osteoarthritis (HOA) but often has low adherence. An intervention consisting in a meaningful occupation, such as knitting, may improve adherence to treatment. This pilot randomized controlled trial (RCT) studied the adherence and clinical effectiveness of a knitting program in older females suffering from HOA to evaluate the acceptability of this intervention and assess the feasibility of a larger-scale RCT. METHODS: Single-blind, two-arm pilot RCT with a parallel group design with 37 participants (18 control, 19 intervention). Control participants were given an educational pamphlet and assigned to a waiting list. The knitting program (8-week duration) had two components: bi-weekly 20-min group knitting sessions and daily 20-min home knitting session on the 5 remaining weekdays. Measures included knitting adherence (implementation outcomes) as well as stiffness, pain, functional status, hand physical activity level, patient's global impression of change, health-related quality of life, self-efficacy, and grip strength (clinical outcomes measured throughout the 8-week program and 4 weeks after the intervention). RESULTS: Our protocol is feasible and the intervention was acceptable and enjoyable for participants, who showed high adherence. No difference was observed between the two groups for any of the clinical outcome measures (all p > .05). CONCLUSION: Knitting is a safe and accessible activity for older women with HOA. However, our 8-week knitting program did not result in improvements in any of our outcome measures. Knitting for a longer period and/or with higher frequency may yield better outcomes.

The Role of Ultrasound in Research and Clinical Practice in Psoriatic Arthritis: Highlights From the GRAPPA Ultrasound Workshop.

Ultrasound (US) is a valuable imaging modality that can accurately identify relevant features of psoriatic arthritis (PsA), such as synovitis, tenosynovitis, and enthesitis. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Ultrasound Committee ran a workshop during the annual GRAPPA meeting that was held in July 2020. The group presented the following 3 topics: (1) the transition from psoriasis to PsA and the role of US; (2) the effect of biomechanical forces on the entheses in health and disease, and insight for PsA pathogenesis; and (3) differentiation of enthesitis from pain sensitization: use and limitations of clinical and sonographic evaluation of enthesitis. This article summarizes the key messages from this workshop.

The Role of Ultrasound in Research and Clinical Practice in Psoriatic Arthritis: Highlights From the GRAPPA Ultrasound Workshop.

Ultrasound (US) is a valuable imaging modality that can accurately identify relevant features of psoriatic arthritis (PsA), such as synovitis, tenosynovitis, and enthesitis. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Ultrasound Committee ran a workshop during the annual GRAPPA meeting that was held in July 2020. The group presented the following 3 topics: (1) the transition from psoriasis to PsA and the role of US; (2) the effect of biomechanical forces on the entheses in health and disease, and insight for PsA pathogenesis; and (3) differentiation of enthesitis from pain sensitization: use and limitations of clinical and sonographic evaluation of enthesitis. This article summarizes the key messages from this workshop.

Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 × 10-5) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.

The impact of smoking on prevalence of psoriasis and psoriatic arthritis.

OBJECTIVES: In this systematic literature review and meta-analysis, we aimed to investigate the impact of cigarette smoking on the prevalence and incidence of psoriasis and psoriatic arthritis (PsA). METHOD: We performed a systematic literature review using the MEDLINE, EMBASE and Cochrane Central Register databases. The literature included publications from January 1980 to July 2019. The studies that provided clear information on the number of patients with ever smoking data were included in the meta-analysis. RESULTS: The systematic literature review identified 52 and 24 articles for the prevalence of smoking in psoriasis and PsA, respectively. Of these, 16 articles on psoriasis and three and four (general population and psoriasis, respectively) articles on PsA met the criteria and were included in the meta-analysis. The prevalence of ever smoking was increased in psoriasis compared with the general population (OR: 1.84; 95% CI: 1.4, 2.3). For PsA the prevalence of ever smoking was reduced in psoriasis patients (OR: 0.70; 95% CI: 0.60, 0.81), but not changed compared with the general population (OR: 1.10; 95% CI: 0.92, 1.32). CONCLUSION: This meta-analysis showed that ever smoking increases the risk of psoriasis in the general population, but may reduce the risk of PsA in psoriasis patients. The latter may be also due to the collider effect. Whether smoking cessation neutralizes the risk of developing psoriasis requires a well-defined smoking data collection for the past history and this is currently unavailable in the literature.

Evidence that systemic therapies for psoriasis may reduce psoriatic arthritis occurrence.

OBJECTIVES: Contemporary biologic therapies for psoriasis are independently licensed for psoriatic arthritis (PsA). Since skin disease generally predates PsA and PsA has a subclinical phase, we investigated the pattern of PsA evolution in psoriasis treated with biologic agents compared to other medications including oral therapy, topical agents or no treatments. METHODS: A retrospective chart review was performed in psoriasis patients with musculoskeletal symptoms referred for rheumatological assessment. Patients who had a final diagnosis of PsA were identified. The frequency and clinical features of PsA were compared for biologics versus the other strategies. RESULTS: Between 2015-18, 203 psoriasis patients were referred for musculoskeletal symptoms with 25 on biologics, 31 on non-biologic systemic therapies and 147 on topical/no therapies. A final diagnosis of PsA was similar in all groups (biologics: 36%; non-biologic systemic treatments: 35.4%; none/local treatments: 37.4%). Most patients had musculoskeletal symptoms before systemic therapy initiation but new onset PsA was evident in 12% (3/25) biologics treated patients, 9.6% (3/31) in non-biologic systemic therapy patients and was significantly higher in patients on topical/no therapy (55/147; 37.4%, p<0.001). Among patients with PsA, none of the patients on biologics exhibited dactylitis compared to 28.6% of other systemic treatments and 48.6% of none/local treatments (p=0.046). CONCLUSIONS: New symptoms and signs leading to PsA diagnosis appear to decrease with systemic treatments. The characteristic PsA dactylitis lesion was not evident in the biologic therapy group.

Impact of Having Family History of Psoriasis or Psoriatic Arthritis on Psoriatic Disease.

OBJECTIVE: Psoriatic arthritis (PsA) has a genetic background. Approximately 40% of patients with psoriasis or PsA have a family history of psoriasis or PsA, which may affect disease features. The aim of this study was to assess the effects of family history of psoriasis and PsA on disease phenotypes. METHODS: Data from 1,393 patients recruited in the longitudinal, multicenter Psoriatic Arthritis International Database were analyzed. The effects of family history of psoriasis and/or PsA on characteristics of psoriasis and PsA were investigated using logistic regression. RESULTS: A total of 444 patients (31.9%) had a family history of psoriasis and/or PsA. These patients were more frequently women, had earlier onset of psoriasis, more frequent nail disease, enthesitis, and deformities, and less frequently achieved minimal disease activity. Among 444 patients, 335 only had psoriasis in their family, 74 had PsA, and 35 patients were not certain about having PsA and psoriasis in their family, so they were excluded from further analysis. In the multivariate analysis, family history of psoriasis was associated with younger age at onset of psoriasis (odds ratio [OR] 0.976) and presence of enthesitis (OR 1.931), whereas family history of PsA was associated with lower risk of plaque psoriasis (OR 0.417) and higher risk of deformities (OR 2.557). Family history of PsA versus psoriasis showed increased risk of deformities (OR 2.143) and lower risk of plaque psoriasis (OR 0.324). CONCLUSION: Family history of psoriasis and PsA impacts skin phenotypes, musculoskeletal features, and disease severity. The link between family history of psoriasis/PsA and pustular/plaque phenotypes may point to a different genetic background and pathogenic mechanisms in these subsets.

Update on Outcome Measure Development in Large-vessel Vasculitis: Report from OMERACT 2018.

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group seeks to develop validated outcome measures for use in trials for large-vessel vasculitis (LVV). METHODS: An international Delphi exercise conducted among investigators identified items considered important to measure active disease. In parallel, qualitative research with patients was conducted, including interviews and focus groups. RESULTS: Next steps prioritized by the group for LVV include (1) defining disease states (remission, flare, and patient-acceptable symptom state) and (2) selection of patient-reported outcome tools. CONCLUSION: The ultimate goal is to develop an OMERACT-endorsed core set of outcome measures for use in clinical trials of LVV.

Psoriatic Arthritis Sonographic Enthesitis Instruments: A Systematic Review of the Literature.

OBJECTIVE: As part of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound working group, we performed a systematic review of the literature to assess the evidence and knowledge gaps in scoring instruments of enthesitis in psoriatic arthritis (PsA). METHODS: A systematic search of PubMed, EMBase, and Cochrane databases was performed. The search strategy was constructed to find original publications containing terms related to ultrasound, enthesitis, spondyloarthritis (SpA) or PsA. Data extraction focused on the properties of the sonographic enthesitis instruments used in each study following components of the Outcome Measures in Rheumatology (OMERACT) filter: feasibility, test-retest reliability, construct validity as related to clinical assessment of enthesitis, biomarkers of inflammation and imaging of enthesitis by other modalities, discriminative validity, and responsiveness to treatment. RESULTS: Fifty-one of 310 identified manuscripts were included. Only 1 scoring instrument of enthesitis was specifically developed and validated in patients with PsA. Only 18 (35%) of the studies involved patients with PsA, while the remaining studies focused on SpA. In PsA, construct validity was assessed using biomarkers and clinical examination in 1 (2%) and 11 (21.5%) of the studies, respectively, whereas no studies used imaging for the same purpose. Only 2 (4%) of the studies assessed discriminative validity in PsA. Responsiveness to treatment was assessed in 7 studies, none of which included patients with PsA. CONCLUSION: Although sonographic enthesitis scoring instruments have been developed for SpA, only a few have been validated in PsA. None of them passed the OMERACT filter in patients with PsA. Additional research is required before endorsing a specific instrument for the assessment of enthesitis in patients with PsA.

The Ottawa Panel guidelines on programmes involving therapeutic exercise for the management of hand osteoarthritis.

OBJECTIVE:: To identify programmes involving therapeutic exercise that are effective for the management of hand osteoarthritis and to provide stakeholders with updated, moderate to high-quality recommendations supporting exercises for hand osteoarthritis. METHODS:: A systematic search and adapted selection criteria included comparable trials with exercise programmes for managing hand osteoarthritis. Based on the evaluated evidence, a panel of experts reached consensus through a Delphi approach endorsing the recommendations. A hierarchical alphabetical grading system (A, B, C+, C, C-, D-, D, D+, E, F) was based on clinical importance (≥15%) and statistical significance ( P < 0.05). RESULTS:: Ten moderate- to high-quality studies were included. Eight studies with programmes involving therapeutic exercise (e.g. range of motion (ROM) + isotonic + isometric + functional exercise) seemed to be effective. Forty-six positive grade recommendations (i.e. A, B, C+) were obtained during short-term (<12 weeks) trials for pain, stiffness, physical function, grip strength, pinch strength, range of motion, global assessment, pressure pain threshold, fatigue and abductor pollicis longus moment and during long-term (>12 weeks) trials for physical function and pinch strength. CONCLUSION:: Despite that many programmes involving exercise with positive recommendations for clinical outcomes are available to healthcare professionals and hand osteoarthritis patients that aid in the management of hand osteoarthritis, there is a need for further research to isolate the specific effect of exercise components.

Options for Assessing Joints and Entheses in Psoriatic Arthritis by Ultrasonography and Magnetic Resonance Imaging: How to Move Forward.

Psoriatic arthritis (PsA) is a heterogeneous disease with various manifestations of musculoskeletal inflammation. Recent advances in imaging, including ultrasound (US) and magnetic resonance imaging (MRI), allow for the accurate evaluation of the extent of inflammation and damage in the peripheral joints, spine, and entheses. The development and validation of outcome measures are critical steps in creating standardized evaluations of musculoskeletal inflammation and damage in psoriatic patients. At the 2017 meeting of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA), recent work on outcome measures from the GRAPPA US and MRI working groups was summarized. The GRAPPA US group has been developing and validating a sonographic enthesitis scoring system in PsA. The GRAPPA MRI group focuses on the evaluation of whole-body MRI for the assessment of musculoskeletal inflammation in the joints and entheses in patients with PsA.

Dactylitis: A hallmark of psoriatic arthritis.

OBJECTIVE: Dactylitis-long considered a hallmark clinical feature of psoriatic arthritis (PsA)-occurs in 16-49% of patients with PsA. In this review, we discuss the pathology of dactylitis in PsA and clinical and imaging tools used to diagnose and monitor dactylitis. METHODS: PubMed literature searches were conducted using the terms psoriatic arthritis, dactylitis, pathology, imaging, ultrasound, magnetic resonance imaging, clinical, and indices. Articles were deemed relevant if they provided insight into the pathology, diagnosis, and/or monitoring of dactylitis in PsA, or if they discussed clinical or imaging indices used to assess dactylitis. RESULTS: Dactylitis in PsA often occurs asymmetrically, involves the feet more than the hands, and affects multiple digits simultaneously. Although dactylitis can be assessed clinically, imaging (radiography, ultrasound, magnetic resonance imaging, and bone scintigraphy) has provided key insights by documenting the various anatomic targets affected. Although inflammation can occur in most of the digital compartments, the nail has not been as well studied in dactylitic digits. Outcome measures for dactylitis range from dichotomous documentation to the Leeds dactylometer. Imaging outcome tools utilizing magnetic resonance imaging or ultrasound are under development. CONCLUSION: Dactylitis, which is associated with more erosive forms of PsA, is often the inaugural feature of PsA and may be the only feature for months to years. Early diagnosis and treatment of PsA favors better outcomes, possibly mitigating radiographic progression and destructive changes. Ultrasound and magnetic resonance imaging are useful tools that have not only shed light on the diverse tissues affected in dactylitis but can also be used to document ongoing inflammation. Ultrasound imaging dactylitis scores are being developed that will assist in diagnosing and documenting which compartments optimally respond to various treatment modalities.

Enthesitis: A hallmark of psoriatic arthritis.

OBJECTIVE: To describe the growing importance of enthesitis in patients with psoriatic arthritis (PsA) and discuss the advantages and disadvantages of clinical and imaging methods currently used to assess enthesitis. METHODS: PubMed literature searches were conducted using the terms psoriatic arthritis, entheses, enthesitis, pathology, imaging, ultrasound, magnetic resonance imaging, clinical, and indices. Articles were deemed relevant if they provided insight into the pathology, monitoring, and/or diagnosis of enthesitis in PsA, or if they discussed clinical or imaging indices used to assess enthesitis. RESULTS: Enthesitis is an early manifestation of PsA that is associated with increased disease activity and reduced quality of life. A variety of clinical indices exist to assess enthesitis in PsA; however, the Leeds Enthesitis Index and Maastricht Ankylosing Spondylitis Enthesitis Score index have been the most frequently used indices in recent clinical trials. Limitations of these indices include an inability to discern structural involvement, risk of missing subclinical enthesitis, and lack of sensitivity in detecting enthesitis, especially in patients with central sensitization and/or pain amplification. Such limitations have led to the emergent importance of imaging techniques in the assessment of enthesitis. Although there have been recent advances in magnetic resonance imaging, ultrasound (US) appears to be the preferred method for detecting enthesitis because it allows for accurate assessment of the soft-tissue components of entheses and also for new bone formation. Hypoechogenicity, increased thickness of tendon insertion, calcifications, enthesophytes, erosions, and Doppler activity have been identified as important US characteristics of enthesitis. CONCLUSION: Enthesitis is thought to be integrally involved in the pathogenesis of PsA and is associated with worse prognostic outcomes in patients with PsA. A validated US index with entheses that are less confounded by mechanical factors and obesity would be the most effective measure of enthesitis in PsA. As imaging techniques continue to advance, our understanding of enthesitis and its involvement in PsA will also improve.

The knitting community-based trial for older women with osteoarthritis of the hands: design and rationale of a randomized controlled trial.

BACKGROUND: The prevalence of hand osteoarthritis (HOA) has been reported to be higher amongst women over 50 years old (66%) compared to men of the same age (34%). Although exercise therapy has been shown effective in reducing symptoms and disability associated with HOA, adherence to treatment programs remains low. The primary objective of this RCT is to examine the effectiveness of a 12-week knitting program for morning stiffness (primary outcome) and pain relief (secondary outcome) 2 h post-wakening in females (aged 50 to 85 years old) with mild to moderate hand osteoarthritis (HOA). METHODS/DESIGN: A single-blind, two-arm randomized controlled trial (RCT) with a parallel group design will be used to reach this objective and compare results to a control group receiving an educational pamphlet on osteoarththritis (OA) designed by the Arthritis Society. The premise behind the knitting program is to use a meaningful occupation as the main component of an exercise program. The knitting program will include two components: 1) bi-weekly 20-min knitting sessions at a senior's club and 2) 20-min home daily knitting sessions for the five remaining weekdays. Participants assigned to the control group will be encouraged to read the educational pamphlet and continue with usual routine. Pain, morning stiffness, hand function, self-efficacy and quality of life will be measured at baseline, six weeks, 12 weeks (end of program) with standardized tools. We hypothesize that participants in the knitting program will have significant improvements in all clinical outcomes compared to the control group. A published case study as well as the preliminary results of a feasibility study as examined through a 6-week pre-post study (n = 5 women with HOA) involving 20-min daily knitting morning sessions led to this proposed randomized controlled trial research protocol. This article describes the intervention, the empirical evidence to support it. DISCUSSION: This knitting RCT has the potential to enhance our understanding of the daily HOA symptoms control and exercise adherence, refine functional exercise recommendations in this prevalent disease, and reduce the burden of disability in older women. TRIAL REGISTRATION: (ACTRN12617000843358) registered on 7/06/2017.