South Yorkshire & North Derbyshire Musculoskeletal Biobank

About the biobank

The aim of the biobank is to make use of these clinical and tissue resources to address research questions relevant to musculoskeletal disease. The biobank holds tissue samples obtained from donors and completed, ethically approved projects with appropriate consent for biobank storage and use for future research projects. 

Samples are stored in the Sheffield Biorepository, which is an HTA-licensed facility.  The biobank operates under the guidance of a steering committee to assure compliance with current best ethical practices. 

All applications for use of tissue through the SYNDMB are submitted in collaboration with a member of the Academic Unit of Bone Metabolism and reviewed by the SYNDMB Steering Committee, which includes representatives from the Biorepository, STH Research Office, Lay members of the public and clinicians from the Metabolic Bone Centre and Orthopaedics.

Recent project applications

Validating microRNA biomarkers to optimise prediction and treatment of ageing and osteoarthritis, osteoporosis

Our research focuses on the effects of ageing on our musculoskeletal tissues (bone, muscle, cartilage and tendon) and vice versa (for example, do diseases of our musculoskeletal tissues, such as osteoarthritis, influence the rate at which we age?)  The role of our genes in ageing and musculoskeletal disease is of increasing interest and recently has involved new knowledge about how our genes’ abilities to produce specific proteins are switched on and off.

One of the ways in which genes are ‘switched off’ is by inhibition of the message, carried by a molecule called ribonucleic acid (RNA), from the gene to the part of the cell that produces the particular protein.  This inhibition is carried out by small RNA molecules (called microRNAs; miRNA) which bind to the RNA and stop the protein from being produced, potentially contributing to the development of disease.  Many miRNAs can be detected in blood samples and measurement of these might be useful in predicting or understanding diseases; if useful, such factors are called biomarkers. 

This application for samples will allow us to study these promising biomarkers by looking at their levels in subsets of older women from within the MRC Hip study.  This study, started in 1996, followed over 5200 women aged 75 and older in Sheffield for up to 5 years, during which some women sustained a broken hip (hip fracture) while most remained free of hip fracture. Likewise, some women died during follow-up whereas other lived longer than the duration of the study.

In these serum samples, we will examine whether microRNAs can detect women at increased risk of either of these outcomes (hip fracture or death). Such information could, for example, lead to the potential use of miRNA to improve the targeting of treatment to those older women at the highest risk of hip fracture.

sRNA Transcriptome Analysis to Identify Differentially Expressed miRNA in Blood Serum Between Individuals with Osteolysis and Healthy Controls: An exploratory analysis

Osteolysis of the hip is a condition where the bone around a joint replacement implant breaks down causing the replacement to become loose and causing pain. The only treatment for this problem is to take out the loose implant and replace it with another one. This is a highly undesirable outcome as it is associated with more pain, poorer walking ability and higher cost than the initial total hip replacement.

Small but powerful chemicals exist within our cells known as micro-RNAs that can change the way in which our cells behave. The levels of different micro-RNAs have been shown to be different between healthy individuals and those with a disease. Some basic research has already been performed on specific micro-RNAs in osteolysis. However, we can now test for all micro-RNAs using a single test. This may allow us to identify a broad, previously unseen range of micro-RNA differences between individuals with and without osteolysis.

The results of this research could give us a better idea of how to look for better diagnosis and treatment methods for osteolysis in the future

Evaluation of the Xtreme CT device for the assessment of bone: Further biochemical assessment 2

We want to better understand how people get weaker bones as they get older. We suspect that it could be caused by chemicals in the blood that controls the way bone is constantly broken down and replaced.

The plan of this study is to measure these chemicals in the blood of healthy men and women between the ages of 16 and 75 and test whether their levels might explain the levels of chemicals that reflect the changes in the bone as we get older. We are making use of blood samples that are stored in the Biobank. We have already a lot of information on these subjects.

Identification of control group for evaluation of miRNAs and bone quality in type 2 diabetes

Type 2 diabetes is a disorder in which the insulin produced by the pancreas does not function properly or the pancreas is not able to produce enough insulin. As a result, the amount of glucose (also known as sugar) in the blood remains high. Due to type 2 diabetes, bones in these patients become weak and are prone to fractures. The reasons why this happens are not well understood. We believe that understanding bone quality may be helpful to understand why patients with type 2 diabetes are more prone to fractures, also known as diabetic bone disease.

In our blood, there are several factors or molecules that help in normal body functioning. These factors are also important for good bone health. The levels of these factors or molecules are different between healthy people and those with disorders. Hence, we aim to develop suitable biomarkers from these factors or molecules for diabetic bone disease. 

Our project collaborator, Dr Morten Frost (Southern Denmark University, Odense, Denmark) has recruited 200 patients with type 2 diabetes. Blood samples as well as bone scans from these patients are available. Unfortunately, no healthy control population is available. Hence, we aim to identify healthy controls from the following studies based here in Sheffield: STH14463, SHT16353 and STH15688 (details below).

We plan to work with experienced teams to measure these factors or molecules in patients with type 2 diabetes and healthy controls. We will also look for associations between these factors or molecules and measurements from bone scans using appropriate tools. This large number of measurements will help us develop these factors or molecules as biomarkers to better understand disorders related to bone quality in patients with type 2 diabetes.

Are differentially expressed proteins identified at joint cartilage level that associate with osteoarthritis detectable in serum? A discovery analysis

Osteoarthritis is one of the most common chronic long-term conditions of the modern age and affects an estimated 1 in 20 of the world’s population. Osteoarthritis is currently a disease without any cure. We treat the patient with advice and painkillers until the disease gets to a stage where surgery can be used to remove and replace the damaged joint.

While we are working towards new treatments that may one day avoid the need for surgery, we also need to advance our knowledge of how the disease develops and how we might detect the disease earlier in its course. By identifying the disease in its early stages, we may be able to develop treatments that could slow its progression.

The purpose of the study proposed here is to see whether some of the chemicals we find in the joints of patients who have arthritis might also be found in their blood. This is an exploratory study (a first look to see if this is possible) and would not lead directly to a new blood test for arthritis, but rather guide us in the right direction.

We plan to compare blood samples from ~300 patients with known osteoarthritis of the knee with ~300 from patients of broadly similar age and sex from the background population to see if blood protein profiles indicate an osteoarthritis “signature”. If we find such a difference, we would plan to re-run the analysis in further independent patient populations.   

Are advanced glycation end products (AGEs) biomarkers of long-term low bone remodelling?

Most of the risk of fractures is estimated by bone density but other features like bone quality also play a role. Sugars can spontaneously link to proteins and form advanced glycation end products (AGEs). Therefore, AGEs are harmful compounds that are formed when protein or fat combine with sugar. This reaction leads to the browning of proteins and can modify their properties. The collagen in the ageing skeleton is affected by the formation of AGEs, making the bones brittle. 

We believe that AGEs can give us information on bone quality; how bone is renewing itself. Low renewal would allow more sugars to bind to collagen and increase AGEs. Some conditions are associated with increased AGEs and also increased risk of fractures. For example, diabetes is associated with higher sugars, higher AGEs and higher risk of both atypical femur fractures and osteoporotic fractures

We want to investigate if AGEs can give us information about bone quality and long-term bone renewal. We will measure AGEs in people who received bone-building treatment and antiresorptives. We suspect that bone-building treatment will reduce AGEs while antiresorptives will increase them. This might help us to personalise the therapy in the future; identifying people with poor bone quality and chronic low bone renewal at higher risk of atypical femur fractures.

Preclinical development of mesenchymal stem cell-based regenerative therapy for the treatment of human Osteoarthritis

Osteoarthritis is one of the most common causes of chronic disability in the UK and worldwide, affecting approximately 13% of the population. The key problem with arthritis is damage to the cartilage that covers the joint and makes it work smoothly. Unfortunately, although we can do a joint replacement to treat the symptoms of arthritis, to date we have no cure for the cartilage disease itself. The overall aim of the research proposed here is to explore whether we can help arthritic joints to “heal” by using cartilage cell injections to help the patients' own cartilage to regenerate.

What we are proposing here is very early-stage experiments to see if we can take fat cells from donor patients undergoing joint replacements and reprogramme them to turn into cartilage cells. We will then grow the cells in the lab to see if we can make them behave like cartilage cells and also test whether they would be safe to transplant into other patients in future studies. This early stage “in-vitro” or lab work, has been funded by the Medical Research Council, who are interested to help us see if this might in future be an alternative treatment to joint replacement for the 9 million people in the UK who suffer from arthritis.