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Expert Interview on Shoulder Arthrofibrosis

Updated: Jun 13, 2023

Dr Kayley Usher interviews Professor Neal Millar, an Academic Consultant Orthopaedic Surgeon specialising in shoulder surgery, on the topic of shoulder arthrofibrosis (Frozen Shoulder).

Professor Neal Millar is the first author of the research article 'Frozen Shoulder' which is published in the renowned journal Nature Reviews - Disease Primers. He describes the characterization of frozen shoulder and the transformation of fibroblasts into myofibroblasts with chronic inflammation. The abstract says 'management consists of physiotherapy, therapeutic modalities such as steroid injections, anti-inflammatory medications, hydrodilation and surgical interventions; however, their effectiveness remains unclear. Facilitating translational science should aid in development of novel therapies to improve outcomes among individuals with this debilitating condition.'

We've listed some highlights and important take-aways from the interview below.

"If you biopsy an ankle arthrofibrosis or knee arthrofibrosis and compare it to frozen shoulder, it's very, very, very similar diseases happening in the separate joints, there's no difference in the pathology."

I think the literature would say that it’s a self-limiting disease that people get better from. But actually, when you delve deep into it, I think about 40% of the patients never really make a full recovery.

Risk factors

"There's certain risk factors which are important. The most important is to ask your patient, are they diabetic? And ask if they have any thyroid problems because those two are strongly linked with an increased incidence of frozen shoulder. Particularly diabetes patients, they actually are more likely to have recurrent frozen shoulder."

"It's important to check for systemic metabolic issues.…hyperlipidemia (high cholesterol) and even hypoadrenalism. And there's some other risk factors, cardiac (heart), pulmonary (lung) disease, cerebrovascular (brain) disease, having a stroke, etcetera. And humoral fracture and there's also intrinsic factors in the shoulder, which can cause a frozen shoulder."

"You can have a rotator cuff tear that drives an inflammatory response in the capsule. That then means you get a secondary Frozen Shoulder, or even AC joint arthritis."

"So it's being able to understand those processes and the risk factors which can be can be quite important helping you and helping the patient understand maybe why this is happened."

Disruption in the homeostasis of the joint

"The mechanisms, most now point towards disruption in the homeostasis of the joint and the capsule is disrupted mainly from inflammation, neo angiogenesis. Neo angiogenesis is new blood vessel growth, and then some of the pain is thought to come from neo enervation or new nerves growing into inflammatory mix. I think all those 3 processes probably work in tandem in the fibrotic mechanisms and that inflammation, neo angiogenesis and neo enervation drive this painful restricted range of movement that then with certain treatments can improve."

"There is a lot of influx of immune cells, important immune cells such as T cells, dendritic cells, these things, drive chronicity, they talk to the resident cells, the fibroblasts within the shoulder capsule. And they really drive this persistent inflammatory response and they release small peptides called cytokines, which again just cause further inflammation and further damage to the capsule."

"And then come these new blood vessels and nerves and the nerves really are linked to a lot of the increased pain that patients see. It's all those cytokines, immune cells and things disrupt the resident important cell called the fibroblast and it all really affects the structure and that's why you get stiffness that's ultimately as a patient why you can't move your shoulder or it's irritable to move."

"The shoulder capsule is normally a few millimetres thick, it becomes thickened to, up to a centimetre in some cases, and you can imagine the process that's involved with that in matrix."

"In all diseases when you have inflammation, you get associated neuro-inflammation. In other words, the nervous system is irritated and starts and produces a range of factors. So I think the immune system is dysregulated, and with that dysregulation comes new nerve ingrowth. With that comes nerve mediators like substance P, which causes pain and all these mediators, histamine etcetera. So, nerves are very important, but I don't think they're the fundamental cause of the disease. I think they’re a result of the inflammatory process that's going on."

"So there's lots of factors that you cannot control, but certainly the ones that you can control are, if you have got any metabolic underlying disease, if you're better controlled in that respect, your risk of getting frozen shoulder does reduce."


"There's lots of different intensities of stretching and the patient's irritability (pain) level…the importance is the right treatment intensities for that patient. So it's understanding their pain limits and passive sort of stretching."

"The physiotherapy should really be patient orientated, so if your patient has very high pain levels, you're not going to do very much with them. Those weeks are to get their pain under control."

"I've moved away from using surgery as much because (now) I use as a surgery as a last resort. I like to use hydrodilation in my diabetic population because starting to operate on diabetics has a range of risk factors that come with it, infection etcetera."

"I think it’s rare, but yes, surgeries can certainly make things worse. They can get a pain response from that and they can become more stiff. It's not the norm…but you would have to counsel the patient. We can't always make everything better and there is a small risk of making it worse."

Responses to patient questions

"There's lots of potential therapies that we are looking at and working on and I think that's why it's really important that we continue to focus on the basic science of this disease and really understand what is causing it, because we may get to a point of using relax or calcitonin."

"A rotator cuff tear is very sore at the start, similar to frozen shoulder. The pain normally goes away reasonably quickly and with frozen shoulder the pain does not go away. If you're a good clinician and see these shoulders regularly, they're pretty easy to differentiate between a rotator cuff tear and frozen shoulder."

"One of the biggest problems sometimes is that corticosteroids can be administered by people who don't regularly do joint shoulder joint injections, which can be tricky. And so they maybe have had an injection, but they've had into the subacromial bursa, or they've had it somewhere else, and they don't see a benefit. Usually ultrasound guided injection is probably best."

"After a surgery you're in a sling for about 24 hours (post-op), we get you moving straight away, and then it's really a case of just seeing the physio immediately after this in the first few days, and really starting a strong stretching and range of movement protocol and that we ramp that up, in the first four to six weeks. We're really quite particular with that. I would say, overall from a capsular release, you're looking at about three month recovery period until you're getting good functionality back in your arm, and that sort of time frame is what to expect."

"You should do good general exercise … we know this in the musculoskeletal system through OA and through other joint diseases, you get the better general health. So good general health, but really nothing (no exercises) specific for the shoulder."

"And then the main exercise is obviously range of movement, their pain goes away on the whole. But yeah, if you don't engage in that process you can be left with a stiff, poor functioning shoulder."

"I don’t agree that surgery should be done aggressively and early because there's plenty of evidence to show physio and other things work. So why put the patient through, well, through a risky event."

"I think it's important that frozen shoulders is given more research, it has been under investigated, and it just affects so many people. I think that more research into this area, and in fibrosis in general, is useful. I think what you'll see over the next number of years is research into the immune system, certainly you know it has a massive role to play in this disease, and that therapies will be targeted towards that."


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