NIHRDataInsights/HRCSData huggingface dataset:
Title: A randomised, double-blind, placebo controlled trial of vitamin D supplements for pregnant women with low levels of vitamin D in early pregnancy (MAVIDOS)
Funder: Arthritis Research UK

Abstract: Women will have their vitamin D status assessed when they attend for nuchal fold scanning in the twelfth week of pregnancy. Women with circulating 25(OH)-vitamin D levels between 25-100 nmol/l will be randomised in a double blind design to receive an oral vitamin D supplement (800 or 1200 iu/day, dose to be confirmed following a pilot study that will assess therapeutic response to 2 doses) or placebo at 14 weeks gestation. Questionnaire data obtained will include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. Women will be seen again at 19 weeks pregnancy and also at 34 weeks pregnancy. Blood samples will be taken at 14 and 34 weeks pregnancy to measure 25(OH)-vitamin D, PTH and bone biochemistry. Maternal anthropometry will be measured at each time point. Following delivery, the baby will undergo DXA within the first 10 days after birth.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: MUSCULOSKELETAL
Title: Regulation of bone metabolism by cannabinoid receptors: mechanisms of action and implications for the treatment of bone disease
Funder: Arthritis Research UK

Abstract: We and others have recently shown that cannabinoid receptors play an important role in regulating bone mass and bone turnover in mice. The mechanisms by which cannabinoid receptor signaling affects the skeleton are poorly understood however, and the clinical relevance of these observations remain to be explored. Here we propose to investigate the signaling pathways that cannabinoid receptors use to regulate bone cell activity; to determine the effects that absence of both cannabinoid receptors have on the skeleton and to determine whether the type 1 cannabinoid receptor regulates bone mass by a neuronal or bone cell specific mechanism. We will also study the effects of CB ligands on human bone function and evaluate the effects of exogenous cannabinoids on bone turnover and bone mass in humans. The information gained will enhance understanding of the basis mechanisms that control bone mass and turnover and will also underpin the development of new strategies for the treatment of bone disease based on pharmacological modulation of CB receptors.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Senior Lecturer in Physiotherapy
Funder: Arthritis Research UK

Abstract: Back pain is costly to patients, the health service and society; therefore treatments must be effective and maximise health gain. Within physiotherapy, research has mainly focused on interventions and paid little attention to communication between patients and therapists. Furthermore, little is known about how communication influences clinical decision-making (ie. the development of knowledge upon which diagnosis and treatment are based). This research programme evaluates the verbal and non-verbal communication occurring between physiotherapists and patients with back pain in an out-patient setting. The content of the communication and its influence on clinical decision-making is considered, and whether these can be changed to improve outcome. The expected outcomes include: determining patients' expectations and understanding of diagnosis; measurement of verbal and non-verbal communication; shared decision-making; empathy; enablement; and satisfaction. In addition, the feasability of a future, multi-centred trial will be determined. In summary, this research aims to enhance shared decision-making and improve patients' experiences.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: MUSCULOSKELETAL
Title: A pragmatic randomised clinical trial of the effectiveness and cost effectiveness of targeted population screening for low bone mineral density in the prevention of neck of femur fractures (SCOOP Trial)
Funder: Arthritis Research UK

Abstract: The proposed randomised controlled trial aims to evaluate the effectiveness and cost-effectiveness of a community based screening program for osteoporosis in women aged 70 to 85. Those women randomised to the screening arm of the trial will provide information on clinical risk factors followed by bone mineral density (BMD) measurements where this information would be deemed useful. Based upon this information, a 10-year absolute risk for fracture will be calculated. This information will be given to study subjects’ GPs with an indication of whether this risk exceeds a pre-determined treatment threshold or not. Those women in the control arm will be treated ‘as usual’. The primary effiacy outcome, to be ascertained from hospital records will be fracture at any site. The follow up period will be 5 years and a sample size of 11 500 women will be sufficient to provided 90% power to detect a 18% relative reduction in fractures.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: MUSCULOSKELETAL
Title: Preventing SQSTM1 mediated Paget's disease by genetic testing and prophylactic bisphosphonate therapy
Funder: Arthritis Research UK

Abstract: Paget’s disease of bone (PDB) is a common rheumatic disease characterised by focal increases in bone turnover which impairs the mechanical integrity of bone. This in turn leads to bone expansion, deformity, pain, deafness, fracture and osteoarthritis. Mutations in the SQSTM1 gene are an important cause of PDB and recent evidence suggests that early during the evolution of the disease, affected individuals develop a generalised increase in bone turnover, before they develop focal lesions. In this study we will perform a prospective study to confirm whether or not this is the case and conduct a randomised controlled intervention study to determine if prophylactic treatment with bisphosphonate therapy can prevent this increase in bone turnover and potentially alter the natural history of the disease.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: Cell Therapy for Osteoarthritis
Funder: Arthritis Research UK

Abstract: The RJAH Orthopaedic Hospital Oswestry has pioneered autologous cell therapy in the UK to repair cartilage defects. This treatment is indicated for patients with local cartilage damage and gives them better function and less pain in the mid to long term. Healing cartilage defects by cell therapy could delay progression to osteoarthritis associated with cartilage lesions. Moreover, evidence suggests that cell therapy could treat patients who have osteoarthritis with osteophytes and bone defects. However, our understanding of biological processes and determinants for clinical outcome does not currently suffice to assess the potential for cell therapy to address osteoarthritis. The key goals of this research programme are to study the biology of repair, determine predictive factors for successful cell therapy and determine if cell therapy can (i) delay osteoarthritis and (ii) treat patients with extensive cartilage and bony defects characteristic of osteoarthritis


Research activity codes: 5.1 PHARMACEUTICALS;6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: Developing new treatment approaches for osteoarthritis
Funder: Arthritis Research UK

Abstract: Osteoarthritis (OA) is the most common form of arthritis and remains one of the few chronic diseases of ageing for which there is little effective treatment. Knee osteoarthritis affects 12% of persons age 60 and causes pain and often disability in those affected. We propose in this programme two related goals: firstly, to test the efficacy of potential treatments for knee OA in a series of trials and, secondly, in our approach to evaluating these treatments, to introduce a new model that facilitates the general development of treatments for OA. We suggest that different subgroups of OA patients will respond to targeted treatment. For each subgroup, we will conduct a trial with targeted treatment for their problem. One common theme of these trials is that patients will be followed after treatment to see if both their pain gets better and structural abnormalities seen on the knee MRI scan improve.


Research activity codes: 6.3 MEDICAL DEVICES;6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: Educational interventions to improve general practitioner management of shoulder pain
Funder: Arthritis Research UK

Abstract: Osteoarthritis has strong genetic and environmental determinants. Paucity of effective models means that OA aetiology and repair remain elusive. We have rederived mice predisposed to spontaneous OA (Str/ort) and developed a non-surgical model allowing us to hypothesise: that applied loading of joints accelerates progression of OA. This will be examined in normal mice and in Str/ort mice which are genetically prone to OA. OA grading, biochemical cartilage changes and locomotor analyses will: i) determine whether biomechanical changes predict OA degeneration, ii) establish whether severity of load-induced injury determines risk of OA-like degeneration or repair and, iii) define whether loading accelerates OA in genetically susceptible mice with restricted repair. Our studies will help clarify the relative contribution of genetic and mechanical factors to the aetiology of OA. These studies will also aim to provide a robust non-surgical model for the evaluation of OA therapies.


Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: MUSCULOSKELETAL
Title: Arthritis Research UK Pain Centre
Funder: Arthritis Research UK

Abstract: We aim to bring together clinical and non-clinical scientists who will identify and investigate the effectiveness and mechanisms of action of novel and existing treatments for arthritis pain. We will increase our knowledge of how many different factors in the joint and nervous system contribute to arthritis pain.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Mechanical factors involved in the aetiology of knee arthritis
Funder: Arthritis Research UK

Abstract: We have recently demonstrated that in the medial compartment the initial lesion occurs when the knee is flexed at 10°, whereas in the lateral compartment it occurs at 40° flexion. The aim of this study is to investigate the mechanical factors involved in the aetiology of arthritis and in particular to identify any abnormal mechanical parameters that occur in the cartilage of the medial compartment at 10° flexion and in the lateral compartment at 40°.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Extracellular nucelotides and P2 receptors: a key local regulatory system in bone
Funder: Arthritis Research UK

Abstract: There is mounting evidence that extracellular nucleotides, signalling through P2 receptors, play significant local regulatory roles in bone, modulating both osteoblast and osteoclast function. Nucleotides may also exert non-receptor mediated actions in bone via the ATP hydrolysis product, pyrophosphate. The programme of work in this fellowship will: 1) identify the P2Y and P2X receptors important in the regulation of bone formation and mineralisation; 2) clarify the role of the E-NPP enzymes which generate pyrophosphate from ATP; 3) define the major P2 receptors involved in the regulation of osteoclast formation and activity; 4) investigate the effects of purinergic signalling on osteocyte and chondrocyte function; 5) examine the interactions between extracellular nucleotides and other local regulators of bone cell function. This ‘early stage' basic research will shed light on a fundamental signalling system for skeletal cells and could identify new drug targets.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MUSCULOSKELETAL
Title: Maintained physical activity and physiotherapy in the management of distal arm pain
Funder: Arthritis Research UK

Abstract: Distal arm pain - pain in the elbow, forearm, wrist or hand - comprises a number of specific and non-specific conditions. It is common in people of working age and results in considerable lost work time, demand for health care and disability._x000D_ _x000D_ The best approach to management is unclear and, in addition to physiotherapy, patients are often advised to avoid presumed harmful activities. While this may be sensible where there is clear disease of local tissues, an analogy can be drawn with non-specific low back pain which for many years was managed by bed rest, until trials demonstrated an improved prognosis if patients were advised to remain mobile. It seems plausible that distal arm pain might also benefit from such a plan of care._x000D_ _x000D_ We propose a trial to test the hypothesis that patients with distal arm pain who are advised to maintain usual activities while waiting to receive physiotherapy will experience improvements in function compared to those advised to rest the arm. All participants will be offered physiotherapy (as per usual care) at six weeks. A pragmatic opportunity therefore also exists to determine the value of early physiotherapy in comparison with treatment that is delayed until the normal time.


Research activity codes: 6.7 PHYSICAL
Health categories: MUSCULOSKELETAL
Title: Understanding Joint Stem Cell Niches to Prevent Osteoarthritis
Funder: Arthritis Research UK

Abstract: Osteoarthritis (OA) is a very common condition and its incidence is predicted to increase as the ageing population grows, placing a significant financial burden on the NHS. Prevention and treatment of OA are therefore healthcare and socioeconomic priorities.Currently, the therapy of OA is only symptomatic. The development of disease modifying OA drugs is hindered by the poor knowledge of OA pathogenesis. The investigation of the cellular and molecular mechanisms underlying cartilage regeneration is of paramount importance to develop novel measures for prevention and treatment of OA. We recently reported that joint surface injury heals in young adult DBA/1 mice. This model of cartilage regeneration in DBA/1 mice offers a unique opportunity to investigate the cellular mechanisms leading to cartilage regeneration. This study is designed to test the hypothesis that mesenchymal/stromal stem cells from synovium and bone marrow contribute to the repair cartilage tissue. We will perform in vivo double nucleoside labelling experiments in young adult DBA/1 mice carrying genetically marked synovium and bone marrow stroma to (i) localize the native stem cells within the joint and (ii) investigate their proliferation, migration and differentiation into the repair cartilage tissue by prospectively monitoring their fate, coupling cell-tracking techniques with marker analysis.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MUSCULOSKELETAL
Title: Experiencing Multidisciplinary treatment of Benign joint hypermobility syndrome In Childhood (EMBIC)
Funder: Arthritis Research UK

Abstract: Benign Joint Hypermobility occurs in up to 30% of children, underlying many musculokeletal symptoms, with broad impacts on patients' lives . Physical treatment approaches are currently central to its management. However, with no publications on recommended treatment regimes, approaches used differ widely. We are conducting a NIHR-funded RCT of a structured multidisciplinary education and treatment programme for newly-diagnosed children, focusing on pain reduction and physical function outcomes._x000D_ _x000D_ Any management strategy for BJH should consider wider perspectives, including individuals' attitudes to pain, tolerance of treatment and their enthusiasm for the therapy as influences on its success._x000D_ _x000D_ This study will add a qualitative dimension to the RCT evidence, interviewing children with BJH, parents and health professionals on their understandings and experiences of participating in either treatment as usual (TAU) or the intervention (multidisciplinary treatment programme ) to examine :_x000D_ _x000D_ · Engagement in and acceptability of treatment regimes_x000D_ _x000D_ · Experienced changes in wellbeing_x000D_ _x000D_ · Parents' and health professionals contribution to treatment outcomes _x000D_ _x000D_ We expect findings from this work to help improve:_x000D_ _x000D_ · the acceptability and feasibility of treatment, including a new, evidence-based childhood treatment programme for BJH_x000D_ _x000D_ · communication between users, families and health professionals_x000D_ _x000D_ · childrens' attendance and concordance with treatment


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: MUSCULOSKELETAL
Title: The role of Plekhm1 in vesicular trafficking in osteoclasts
Funder: Arthritis Research UK

Abstract: The activity of bone-resorbing osteoclasts is dependent on polarised trafficking of vesicles towards theunique ruffled border membrane using poorly understood pathways. We recently found that mutations in Plekhm1 cause the bone disease osteopetrosis by disturbing osteoclast activity, implicating Plekhm1 in osteoclast function. We hypothesize that Plekhm1 is involved in endosomal trafficking to the ruffled border, since it is recruited to these vesicles by Rab7, a known regulator on late endosomal trafficking, and because osteoclasts from the patient with the Plekhm1 mutation lack ruffled borders. The aims of this project are to determine: (i) the importance of Plekhm1 for osteoclast function, by analyzing the bone phenotype and osteoclasts derived from Plekhm1-/- mice; (ii) the nature of the disease-causing Plekhm1 mutations, by transfecting osteoclasts from Plekhm1-/- mice with the mutant forms of Plekhm1; (iii) the subcellular localisation of Plekhm1 in resorbing osteoclasts, either by immunostaining or by transfecting osteoclasts with tagged forms of Plekhm1; and (iv) the precise role of Plekhm1 in vesicular trafficking in osteoclasts, using live cell imaging. This project will begin to unravel essential elements in the unique endosomal vesicular trafficking pathways in osteoclasts and may unveil novel therapeutic targets to inhibit osteoclastic resorption.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MUSCULOSKELETAL
Title: Effect of bisphosphonate therapy on healing and clinical outcome of wrist fractures: randomised controlled trial
Funder: Arthritis Research UK

Abstract: Bisphosphonates are widely used in the treatment of patients with osteoporosis to prevent fragility fractures. Bisphosphonates have potent inhibitory effects on bone remodelling and because of this there is a concern that bisphosphonate therapy might impair fracture healing since restoration of the original shape and strength of a bone following fracture depends on remodelling of callus by osteoclasts. Adverse effects of bisphosphonates on fracture healing have not been observed in preclinical studies, but the effect of bisphosphonate therapy on healing of fractures in man has been little studied. Here we will investigate the effects of early treatment with the bisphosphonate alendronic acid on healing and clinical outcome of wrist fractures in postmenopausal women within the context of a randomised placebo-controlled controlled trial. The study will provide new information on the effects of bisphosphonate therapy on healing of one of the most common osteoporotic fractures and will have important implications in deciding upon the optimal timing of bisphosphonate therapy following the occurrence of an osteoporotic fracture.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: The function of microRNAs in cartilage metabolism and osteoarthritis
Funder: Arthritis Research UK

Abstract: In recent years, microRNAs have come to the fore as major regulators of gene expression. MiR-140 is highly expressed in cartilage and the miR-140 null mouse has an osteoarthritis phenotype, however, the molecular mechanisms by which it functions remain opaque. We have discovered that miR-455, which resides within an intron of the cartilage collagen gene Col27a1, is regulated during chondrogenesis similarly to miR-140, functions to regulate Smad signaling and is altered in expression in human OA cartilage compared to normal. Our hypothesis is that these (and other) microRNAs are key regulators of cartilage homeostasis with their dysregulation leading to osteoarthritis._x000D_ _x000D_ This application will establish a pipeline in which to examine in detail the function and molecular mechanisms of microRNA action in cartilage and OA, with an initial focus on miR-455 and miR-140. We will examine expression in a mouse model of OA, identify microRNA targets in primary human articular chondrocytes and establish in vitro and in vivo models to probe microRNA function. We will also identify novel microRNAs expressed in human articular cartilage. The long term goal is to understand the networks of microRNAs and their targets that regulate cartilage homeostasis in health and mediate its destruction in disease.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Arthritis Research UK Tissue Engineering Centre
Funder: Arthritis Research UK

Abstract: A Centre is proposed, with leading academic UK orthopaedic clinicians working with ‘tissue engineering' scientists to apply their knowledge to revolutionise techniques already in the clinic (schematic overview in attached figure 1). The Centre of Excellence will focus on innovative tissue engineering (TE) developments linked directly to patient deliverables in order to prevent or treat osteoarthritis (OA). The Centre will form a partnership led by Newcastle University in collaboration with Aberdeen, Oswestry/Keele and York Universities - all leading clinically focused UK centres for orthopaedic treatments. We will increase effectiveness and longevity and decrease costs of current TE approaches. Our objectives are to:_x000D_ _x000D_ 1. Optimize and reduce the cost of cell therapy for joint surface repair, simplifying delivery anddeveloping an ‘off-the-peg' source of cells._x000D_ _x000D_ 2. Optimize microfracture-based therapies, and particularly improve structural outcome anddurability._x000D_ _x000D_ 3. Seek novel injectable preparations which will be easy to use in the clinic._x000D_ _x000D_ 4. Extend this approach in other relevant tissues: tendon, meniscus and intervertebral disc._x000D_ _x000D_ 5. Facilitate cell therapy delivery to all suitable patients (without requirement to be near a specialist centre)._x000D_ _x000D_ Our mission is: to combine emerging TE technologies with minimally invasive surgical solutions in order to treat OA.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES;5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL