Can exercise help avoid arthritis, or muscle wasting? Is distance running actually good for knees and hips? Can cycling help? What is the best way to start exercising from scratch? What difference does it make if you are young or old, male or female? Moreover, why is the ‘muscle factor’ so important?
We want to answer these questions, by using medical imaging (MRI) to scientifically test the effects, risks and benefits of exercise on joint health.
Marathon running is widely regarded as having benefits for cardiorespiratory and muscular health, but what about its impact on our joints? Many individuals avoid long distance running due to a perceived risk of joint damage to the spine, hips and knees.
We found that marathon running resulted in:
- No adverse effects on the lumbar spines of runners (even when early degenerative changes were present): How does running your first marathon affect your spine? — Exercise for Science
- Regression of pre-existing sacroiliac joint abnormalities post-marathon
- No significant pathological changes in the hips of runners: What effect does running your first marathon have on your hips? — Exercise for Science
- No significant long-term damage to the knees of runners: What happens to marathon runners’ knees in the long term? — Exercise for Science
- Sustained regression of pre-existing bone marrow oedema in the knees of runners: Can distance running be good for your knees? — Exercise for Science
These novel studies show that not only does marathon running pose a minimal threat to the joints; it may mitigate long-term joint deterioration and improve joint health.
Cycling is known to have cardiovascular benefits, but what about the implications for muscular health? We found that cycling can delay the onset of aging-related sarcopenia by the reducing fat-infiltration of muscles: How does cycling affect muscle mass? — Exercise for Science
To study how exercise affects different individuals, our studies are designed to represent individuals of different sex, age, BMI and with differing levels of regular activity. The gluteal muscles were found to be very similar volume in male and female cyclists, despite known fat composition differences: How do male and female cyclists’ muscles differ? — Exercise for Science
Fat infiltration of the gluteus maximus muscles was
found to be higher in individuals with:
- Low levels of physical activity
- Female sex
- Higher BMI
What do levels of muscle fat tell us about muscle health? — Exercise for Science
High levels of fat infiltration are found in the muscles of inactive individuals. We found that fat infiltration is a promising biomarker to indicate muscle, hip and general health. Fat infiltration in the hip abductors – key muscles for daily activities such as standing, walking and running – was found to well-represent muscular health: Can muscle fat levels predict future hip problems? — Exercise for Science
Fat infiltration can be quantified using an automated, 20-minute segmentation method, proven to work just as well as established manual methods: Can we speed up the measurement of fat in muscles? — Exercise for Science
See how intramuscular fat (IMF) can be seen on an MRI image of the gluteus maximus muscles:
A biological approach to treating Achilles tendinopathy using culture expanded autologous mesenchymal stem cells – A First in Man Study
Andy Goldberg (Senior Clinical Lecturer; Honorary Consultant Orthopaedic Surgeon), Roger Smith (Professor of Equine Orthopaedics), Caroline Doré (Head of Statistics)
UCL Institute of Orthopaedic & Musculoskeletal Science; Foot & Ankle, Royal National Orthopaedic Hospital; Royal Veterinary College; UCL Comprehensive Clinuical Trials Unit
More information: andy.
Tendon disorders compromise pain-free activity and often progress to chronic pain with a major impact on quality of life. More than 85,000 patients each year see their GP with Achilles Tendinopathy. The main current treatment is physiotherapy, although surgery is eventually considered in 25-45% of patients, an intervention that has unpredictable outcomes. Current treatment options that have relied on an inflammation-repair sequence have not proven to be of benefit and tendon healing following injury results in deposition of fibrous scar tissue that is functionally inferior to the original structure. There is a need for improved non-surgical treatments, which can promote regenerative processes to restore tendon structure and function. Treatment of naturally-occurring tendon over-strain injuries with culture-expanded autologous bone-marrow derived mesenchymal stem cells (MSCs) is already well established in a highly relevant equine model which has ageing and loading (exercise) similarities. Preclinical data from more than 1,800 racehorses suggest that MSCs can lead to improvement in pain-free function. We are translating the technology to humans and conducting a UK Stem Cell Foundation-funded ‘First-in-man’ study using to establish the safety of autologous culture expanded MSCs implanted in diseased human tendon and to correlate an objective outcome measure of tendon regeneration, Ultrasound Tissue Characterisation, with clinical outcome scores can be achieved. The outcome from this study will be used to design a larger randomised controlled clinical trial to demonstrate the efficacy and cost-effectiveness of the treatment.
Gordon Blunn (Professor of Biomedical Engineering), Melanie Coathup (Reader of Orthopaedic Implant Fixation and Bone Regeneration)
UCL Institute of Orthopaedic & Musculoskeletal Science
More information: g.
Segmental implants combined with a prosthetic joint are used after failure of a number of previous revisions or for treating patients with bone cancer to replace part of the diaphysis of the bone. For bone cancer patients, fixation is important as these patients are generally young and implants have to last. The aim of this project is to enhance the fixation of implants using a cell augmented prostheses. The team has shown improved bone regeneration in femoral defects when mesenchymal stem cells in fibrin glue were used (Lee, et al 2005). Radiographic and histological analysis demonstrated that spraying autologous mesenchymal stem cells in fibrin glue onto grooved HA-coated collars of segmental bone implants resulted in twice the level of bone adjacent to the collars and greater osteointegration in the treated group (Kalia, et al 2006, Coathup, et al 2013). A more recent study has shown that osteointegration of HA-coated collars reduced the formation of radiolucent lines and loosening around cemented intramedullary stems (Coathup, et al 2015). These studies demonstrated that a tissue-engineering approach to enhance bone integration of prostheses might be beneficial. We now aim to apply this technology to patients being treated at the RNOH. At the present time there is a requirement in patients with segmental revision implants to improve fixation but due to the risk of neoplastic autologous stem cells used for bone cancer patients we are restricting this project to treating patients requiring revision segmental prostheses.
Liza Osagie (PhD student), Timothy Briggs (Professor of Orthopaedic Surgery; Consultant Orthopaedic Surgeon), Gordon Blunn (Professor of Biomedical Engineering)
UCL Institute of Orthopaedic & Musculoskeletal Science; Bone Tumour Unit, Royal National Orthopaedic Hospital
More information: liza.
Exponential population ageing, increasing joint replacement surgery and rising osteoporosis all underpin the growing “musculoskeletal burden”. Concurrently, more patients are suffering osteoporotic fractures around implants (“periprosthetic fractures”), the surgical treatment of which leads to increased morbidity, mortality and socio-economic cost. Thus, at the Institute of Orthopaedics and Musculoskeletal Sciences, we are investigating how to improve periprosthetic fracture healing in the elderly via minimally invasive treatment. By 2021, 23% of the population will be over 65. Consequently, the 80,000 hip replacements performed annually-are forecast to increase by 200%, and the 70,000 annual hip fractures-to increase by over 300%¹'².Within this age group 1 in 3 women and 1 in 4 men will experience a fracture due to reduced bone quality (osteoporosis/osteopenia).
Patients with hip implants have up to an 11% lifetime peri-prosthetic fracture risk. The surgical management of these injuries is often complex and is associated with a 45% complication rate, 10% 30-day mortality and costs an up to estimated £24,000 per patient. Our aim is to develop a minimally invasive technique that accelerates and enhances bone formation that may translate to significantly impact fracture management; reducing hospital length of stay and returning patients to pre-morbid functionality quicker than current treatment options.
The team have previously demonstrated the efficacy of healing a fracture by filling the gap with bone marrow derived stem cells; this Rosetrees Trust and Gwen Fish Trust funded work goes one step further, aiming to heal fractures by percutaneously injecting stem cells into the fracture gap and combining this with systemic injections of parathyroid hormone. Ultimately, we aim to create a translatable technique that uses parathyroid hormone to increase the functionality of senile cells and subsequently enhance bone formation in both normal and osteoporotic animal models.
Tom Quick (Consultant Orthopaedic Surgeon), Ashok Singh (Specialist Registrar), Michael Fox (Consultant Orthopaedic Surgeon), Marco Sinisi (Consultant Orthopaedic Surgeon), Anthony Macquicllan (Consultant Orthopaedic Surgeon)
Peripheral Nerve Injury Unit, Royal National Orthopaedic Hospital
More information: t.
Brachial Plexus injuries are rare but severely debilitating as the plexus supplies motor and sensory functions to the upper limb. This not only results in physical disability and psychological distress but also has socioeconomic implications, as a significant proportion of patients are not able to make a return to their previous level of activity. Surgical intervention such as nerve repair and/or nerve transfer gives the best chance for regaining maximum functional use of the affected limb after brachial plexus injuries. Nerve transfer surgery to restore elbow flexion (that is one of the aims of any surgical planning in this group of patients) has been adopted across the world and the results have been very encouraging.
We have reported the distribution of the power restored to elbow flexion using continuous variable (publication submitted to BJJ). We have shown that 80% of patients undergoing nerve transfer, irrespective of their level of injury, gained an elbow flexion strength of MRC grade 4, which when compared quantitatively to the elbow flexion strength on contralateral side would range between one-eighth to two-thirds of normal power, and an average of one-third of normal. Also, when these values were plotted on a graph, we got a normal distribution and were able to obtain a Gaussian curve. We can thus confirm a predictable pattern for power distribution in this subgroup. Our study presents an example of how in a practical manner a continuous quantitative measurement for regained elbow strength can be carried out in clinics. Also the values obtained during our assessment are similar to those obtained under biomechanical laboratory conditions, supporting the feasibility of use of dynamometer as a measurement tool in clinics.
Our study empowers the clinician with a quantitative measurement of their surgical intervention, and holds the potential for playing a key role in future research for nerve injury recovery.
John Churchwell (Research Associate), Professor Allen Goodship (Professor of Orthopaedic Science), Richard Keen (Consultant Rheumatologist)
UCL Institute of Orthopaedic & Musculoskeletal Science; Rheumatology, Royal National Orthopaedic Hospital
More information: j.churchwell@ucl.ac.uk
Understanding and quantifying bone quality is of high importance in Britain’s aging society. Every year in the UK 300,000 patients receive treatment for fragility fractures as a result of osteoporosis and many patients are diagnosed with osteoarthritis. In addition, it is easy to confuse factures resulting from osteogenesis imperfecta in children with those from infant abuse.
Currently there is no definitive test for rapid non-invasive early stage diagnostic or screening for osteoarthritis or osteogenesis imperfecta. Also a key problem with DXA the current gold standard for osteoporosis diagnosis is the use of X-rays. Whilst radiography can be powerful for imaging some bone diseases and fractures, overexposure becomes dangerous and they do not provide any information on the organic part of bone, the collagen fibre matrix. The molecular level structure of collagen has a large effect on bone quality and strength. In fact only around 60-70% of bone strength can be related to bone mineral density – the parameter measured using DXA. It is therefore important that we take advantage of new methods that allow us to acquire information on the collagen component of bone in addition to bone mineral.
AT UCL IOMS in partnership with STFC and RNOH we are carrying out research using Raman spectroscopy. We have been developing Raman spectroscopy to understand bone quality in more detail. Spatially offset Raman spectroscopy (SORS) allows us to see through the skin and soft tissue and acquire spectral information back from the bone, a fingerprint of the bone chemistry for the individual patient. Recently our group have published journal articles that show differences can be detected with this technology between healthy bone and diseased, for osteoarthritis (Kerns, et al 2014), osteoporosis (Buckley, et al 2015) and osteogenesis imperfects. Most importantly our results have shown that is possible to discriminate between diseased and healthy bones non-invasively in vivo for a number of diseases. These results are very promising.
Our research also has the potential to yield new methods of diagnosis and early detection of bone disease. Offering the potential of saving those with undiagnosed osteoporosis from dangerous fragility fractures through cheap and reliable screening and patients with osteoarthritis from debilitating joint degradation by spotting the condition early ahead of irreversible debilitating joint destruction.
Oliver Chan (MD research student), Andy Goldberg (Senior Clinical Lecturer; Honorary Consultant Orthopaedic Surgeon), John Churchwell (Research Associate), Professor Allen Goodship (Professor of Orthopaedic Science)
UCL Institute of Orthopaedic & Musculoskeletal Science; Foot & Ankle, Royal National Orthopaedic Hospital
More information: oliver.chan@doctors.org.uk
Osteoarthritis (OA) of the ankle is a debilitating condition that results in pain and dysfunction due to the degeneration of cartilage, bone and soft tissues. More than 29,000 patients a year present to specialists with symptomatic ankle OA in the UK, a condition which causes pain, disability and affects quality of life as much as end stage heart failure.
Little is known about the interaction between cartilage and bone as an osteochondral unit and their role in the OA pathogenesis. Alteration in bone matrix chemistry is central to one theory. Raman spectroscopy is a non-invasive technique used to characterise and differentiate alterations in bone matrix chemistry (in simple terms the technique measures the anelastic energy changes in light scattered from materials including both mineral and organics phases). This contrasts to conventional imaging systems utilising ionising radiation that interrogate only the mineral phase of the matrix.
The use of Raman Spectroscopy in orthopaedics has been pioneered by researchers at UCL IOMS and RNOH, in particular to assess abnormal molecular changes observed in the matrix of Osteoarthritic knees (Kerns et al, 2014). Expanding on this experience and using funding from BOFAS, we will explore whether alterations in bone matrix chemistry are associated with an increased propensity to develop ankle osteoarthritis and whether the chemical differences are associated with altered material properties in subchondral bone.
Alister Hart (Professor of Orthopaedic Surgery; Consultant Orthopaedic Surgeon), Shiraz Sabah (Specialist Registra), Johan Henckel (Specialist Registra), John Skinner (Consultant Orthopaedic Surgeon)
UCL Institute of Orthopaedic & Musculoskeletal Science; Joint Reconstruction Unit, Royal National Orthopaedic Hospital
More information: a.
There is now a wealth of information available to patients on joint replacements. One of the biggest sources is the National Joint Registry (NJR) for England, Wales and Northern Ireland, who have collected data on more than 1.8 million operations making it the world’s largest joint registry. Data on failure rate of hip implants from the UK NJR was used to recall some types of metal on metal hips in 2010, 2011 and 2012. An earlier recall would have prevented patient suffering but it is unclear when such action should be taken in the future for other implants. We aim to improve this process of post-marketing surveillance.
In this Dunhill Medical Trust and Gwen Fish Trust funded project, we have linked the NJR database to a database of 1400 failed hip implants collected by The London Implant Retrieval Centre. The failed implants collected by the LIRC can provide indisputable data on component characteristics (e.g. manufacturer, size, reference number) and cause of failure.
Using the linked record, we were able to assess the quality of the NJR data. Although the NJR database contains the majority of the hip implants that should have been recorded, we have so far found two major issues: i) a sizable number of procedures, 17%, had the wrong outcome recorded (either as death, or unrevised) (Sabah, et al 2015); ii) missing data has meant that revisions could not be linked to their primary data entry in 60% of failures: this linkage is essential to enable the survival curves of implants to be accurately drawn in the NJR annual report (Sabah, et al accepted for publication).
Despite our findings, the NJR remains the best source of data we currently have to analyse how joint replacements perform. Across the NJR as a whole, missing data probably ‘averages itself out’ to give a good idea of how an implant is performing. However, for individual surgeons (or even hospitals), where the number of cases is much smaller, this missing data could affect how we interpret their performance.
We are currently analysing the linked record to investigate implant failure mechanisms by implant type. We plan to develop methodology for local centres to validate cause of failure on the NJR that will be piloted at RNOH and LIRC.