Ankle Osteoarthritis and Hyaluronic Acid

By December 22, 2023 No Comments

Ankle osteoarthritis is a chronic disease affecting 3.4 to 6.5% of the population. In all patients with osteoarthritis, it comprises approximately 2-4% of the cases.

Ankle osteoarthritis is much less common than knee or hip osteoarthritis. Although ankle osteoarthritis is not as common as other areas of osteoarthritis, it is equally as debilitating.


Age: OA can occur at any time in life but is common in the older population

Obesity: Obesity adds stress to the joint by the increased weight

Repeated Stress: High impact to the joint over a long period of time increases the risk

Genetics: Family history increases the risk

Malalignment: Deformities also increases risk of the development over time

Injuries: For ankle arthritis previous injury is the primary etiology

Unlike hip and knee osteoarthritis, ankle OA is classified as idiopathic in only 7-9% of the cases.!3% is classified as secondary to other causes such as rheumatoid arthritis or osteonecrosis. The primary etiology in 75-80% of the cases is previous trauma. Fractures are the most common etiology with 62% of the cases related to previous fractures of the malleolus, tibia, talus and other bones of the foot. 16% are cases related to ligamentous injuries especially the lateral collateral ligament. This ligament when affected by previous trauma is a common cause of ankle osteoarthritis so much so it has been termed, “ligamentary ankle osteoarthritis”.

Given the post traumatic etiology of ankle osteoarthritis, the patients tend to be younger than OA in other areas. Common age group is between 18-44 years of age. These patients also suffer a more rapid loss of function with progression to more advanced stages of the disease occurring 10-20 years after the initial insult.

Studies have shown initial degenerative changes secondary to ankle fractures develop within 12 months of the initial injury.


As with all types of degenerative arthritis, symptoms appear slowly and increase over time

A. Pain and stiffness: typically, worse in the AM or after prolonged sitting

B. Swelling: diffuse to the joint or one side

C. Decreased Range of Motion: loss of flexion and extension

D. Tenderness and Pain

E. Difficulty weight bearing and walking


X-rays show the loss of joint space. There are 28 bones in the ankle /foot with 30 joint spaces. There is usually decreased joint space with osteophytes and loose bodies. Erosions may be present.

CT or MRI is reserved for patients who need a surgical procedure.

Lab testing is done to r/o different types of arthritis that may need alternative treatments such as rheumatoid arthritis.


Non-drug treatments include physical therapy, weight loss, modification of activities bracing such as AFO braces. Topical creams such as capsaicin, camphor based or CBD


Pain meds including NSAIDS

Topical gels


Hyaluronic acid

Platelet Rich Plasma



Arthroscopic surgery done to remove loose bodies.

Arthrodesis: A procedure to fuse joints in the area to eliminate the motion in the joint

Arthroplasty: This procedure involved total replacement of the ankle, the damaged cartilage and bones are removed and replaced with metal or plastic parts

Side effects to surgical procedures include nonunion and broken hardware. Wound healing and infection as well as increase incidence of blood clots. Loss of motion after surgery causes other nearby joints to have increased incidence of arthritis.

Revision surgery to replace hardware has a much lower incidence for success.

Foot and ankle surgery is painful and recovery in most cases is months.

Tibiotalar Cartilage

Being a frequently injured joint, osteoarthritis of the ankle joint is less common than other weight bearing joints such as the hip and knee. This is due to the biomolecular peculiarities of ankle cartilages, as well as anatomical and biochemical differences.

Ankle cartilage receives the greatest force per unit of all hyaline cartilage in the human body. The ankle cartilage is subjected to at least three times greater force than the knee or hip.

Anatomically, the load distribution differs from other joints as the compressive forces are distributed over a greater surface area.

Ankle cartilage is much thinner than knee cartilage. It is stiffer and less permeable and has a greater capacity for self-repair than the knee or hip cartilage. Since it is stiffer and less permeable, it produces a greater water and proteoglycan content, and this helps protect against mechanical damage.

Chondrocytes in the ankle are biologically more active than other sites and respond quicker the anabolic factors influencing cartilage synthesis. Increased levels of osteogenic protein 1 and c propeptide of type 2 collagen stimulate cartilage rejuvenation and are much more active in the ankle joint.

Ankle cartilage is less sensitive to catabolic mediators which inhibit collagen synthesis. The concentration of metalloproteinases, which are responsible for protein degradation in other tissues are undetectable in the ankle joint.

Therefore, ankle cartilage is less prone to joint degeneration than the hip and knee but highly susceptible to lesions where asymmetric forces cause misalignment as in fractures and impact injuries. This explains the high correlation between OA of the ankle and a history of trauma.

Cartilage Damage Mechanism

Since it is well documented that trauma causes osteoarthritis of the ankle, what is the mechanism? The proposed mechanism involves an increase in oxidative stress following the release of mitochondria from chondrocytes that are subject to greater contact stress from reactive oxygen species causing cell damage, chondrocyte death and extracellular matrix degradation. Fibronectin fragments released from joint cartilage also promote matrix degradation and inhibition of molecular repair pathways. Chondrocytes attempt to repair damaged areas by activation of progenitor cells, but these cells can release chemokines and cytokines that may contribute to added inflammation which causes more cartilage loss.

Studies have proven apoptosis spread from fracture lines to apparently healthy areas in 48 hours following trauma. This suggests the intra-articular mediators of cell damage are release from the damaged chondrocytes and the negatively affect health chondrocytes and surrounding tissue.

Joint incongruence and instability following ankle trauma has been observed in studies to lead to a substantial increase in ankle osteoarthritis. Incongruence has been shown to increase joint stress and causes cell death and damage to cartilage. In open fractures where surgical repair has been attempted, a postoperative step off is the most important factor predicting post traumatic osteoarthritis.

In osteoarthritis of the ankle joint, tibiotalar joint alignment is asymmetrical in 70% of cases.

The resulting malalignment causes chronic inflammatory changes in the joint.

Proinflammatory Mediators in the Synovial Fluid

In a study done by Adams et al, the presence of proinflammatory mediators and promoters of extracellular matrix degradation in the synovial fluid obtained post operatively from patients undergoing osteosynthesis for ankle fracture demonstrated many substances that cause osteoarthritis. Interleukins IL-6 and IL-8, metalloproteinases and others were in high concentrations. These substances all contributed to osteoarthritis development. At 6 months, they were still present. This highlighted that joint lavage at the time of surgery may act as a prophylactic to the development of osteoarthritis in the future.

Since osteoarthritis of the ankle joint is a chronic condition, it would seem to this author that treatment protocols should be tailored to cause no harm to the joint space. Steroids can reduce inflammation over a short period of time. However, steroids when used multiple times for this chronic disease, will cause degradation of the cartilage and surrounding soft tissues. The bone itself may even be negatively affected by repeated steroid use. Steroids can also cause problems with blood sugars and other negative systemic effects.

High dose NSAIDS cause significant systemic side effects. They are a leading cause of gastrointestinal bleeding and kidney and liver problems. Studies have now proven, NSAIDs can degrade cartilage over prolonged use.

Hyaluronic acid, platelet rich plasma and biologics are all rational choices for the treatment of osteoarthritis of the ankle joint. Although, Medicare and other commercial insurance programs do not cover their use.

Hyaluronic acid is a natural component of synovial fluid. Hyaluronic acid injections called viscosupplementation, are gel like fluid injections which lubricate the joint and act as shock absorber for joint loads.

In multiple studies, after six months post hyaluronic acid injections, pain and physical function were measured.

A. People who received injections with hyaluronic acid rated their pain and physical function 24 points lower on a scale of 1-100.

B. No patients experienced a serious side effect.


Hyaluronic Acid and Other Conservative Options for Osteoarthritis of the Ankle

Cochrane Database 2015 Oct;2015(10):CD010643. PMID 26475434

Objectives: To assess the benefits and harms of any conservative treatment for ankle OA in adults in order to provide synthesis of the evidence as a base for treatment guidelines.

Conclusion: HA can be conditionally recommended if patients have an inadequate response to simple analgesics. It remains unclear which patients (age, grade of ankle OA) benefit the most from HA injections and which dosage schedule should be used.

Intra-Articular Hyaluronic Acid Compared to Exercise Therapy in Osteoarthritis of the Ankle. A Prospective Randomized Trial with Long-Term Follow Up

Clin Exp Rheumatol 2008 Mar-Apr;26(2):288-294

Objective: The goal of this study has been to determine whether hyaluronic acid or exercise therapy can improve functional parameters in patients with osteoarthritis of the ankle.

Conclusion: This prospective randomized trial confirmed that both HA injections and exercise therapy provide functional improvement.

The Effect of Three Weekly Intra-Articular Injections of Hyaluronate on Pain, Function, and Balance in Patients with unilateral Ankle Arthritis

Background: Ankle arthritis can cause substantial pain and functional limitation. Previous studies have indicated that five weekly intra-articular injections of hyaluronate were safe and effective in the treatment of ankle arthritis. The purpose of this study was to evaluate the effects and safety of three weekly injections of hyaluronate in patients with unilateral ankle arthritis.

Conclusion: This study suggests that three weekly injections of hyaluronate are well tolerated and can provide pain relief and improve function and balance in patients with unilateral ankle osteoarthritis.

Efficacy of Intra-Articular Hyaluronic Acid in Patients with Osteoarthritis of the Ankle: A Prospective Study

Osteoarthritis Cartilage 2006 Sep;14(9):867-874. PMID 16635582

Objective: To investigate the efficacy, safety and duration of treatment effectiveness of intra-articular hyaluronic acid in patients with ankle osteoarthritis

Conclusion: Five weekly intra-articular injections provide pain relief and functional improvements in patients with Kallgren-Lawrence grades I and II ankle OA. The clinical effect was rapid at 1 week and may last for 6 months or more.

Integrative Practice Solutions has been collaborating with medical professionals and office staff for over a decade. Our experience in the use of viscosupplementation for the treatment of osteoarthritic conditions is vast and all encompassing. From personal professional instruction of techniques performed under guidance, to proper coding and marketing, IPS has the knowledge and staff to incorporate this therapy into your existing practice and add additional patients seeking nonsurgical alternatives for the treatment of their arthritic disease.

Integrative Practice Solutions has given more than 230 clinics in the US, guidance in the treatments of osteoarthritis while adding to their profitability. IPS has answers to many other areas of regenerative medicine via their sister corporation, Juventix Regenerative Medical. IPS is always striving to continue to be in the forefront of the regenerative medical field ,while providing the means for our collaborators to augment patient care and maximize business yields.


Regenerative Regards,

Dr. Robert McGrath