​The management of young patients with knee osteoarthritis presents a unique set of considerations requiring a multidisciplinary, shared care approach. Discover the key role of the general practitioner – which includes analgesia, weight loss advice, and timely referral to specialists for more invasive interventions if necessary.


Osteoarthritis (OA) has a high global and economic burden and is estimated by the World Health Organization to become the fourth leading cause of disability. In Singapore, 10% of adults and 20% of elderly people suffer from knee OA.


Unique considerations

Although total knee replacement has often been used as the gold standard for long-term treatment of knee OA, younger patients (aged below 55 years) were found to be more dissatisfied with it compared to older patients at the time of the procedure.1

Young patients with knee OA are a challenging group to manage as they are often still active in sporting activities, and subsequent inevitable arthroplasty revision rates are higher. Quality of life and satisfaction of patients with revision implants are also much lower than those with primary total knee replacement.

Rising prevalence

The reason for an increasing number of young patients seeking medical consultation for knee OA is multifactorial:

  • There is an increased proportion of the population continuing to be physically active in sports well into their fifth, sixth and seventh decades with increasing life expectancy.

  • There is also an increase in obesity rates, which increases the risk of knee OA.

The patient also expects to return to their previous high level of activity post-injury or treatment. Hence, there is a need to find more options that can prolong time to arthroplasty and restore their physical activity level.


Knee OA is a result of mechanical factors, biological factors or a combination of both.

Primary OA is more common than secondary OA, which can be caused by a previous injury.

Biochemical workings

On a biochemical level, the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumour necrosis factor alpha (TNFα) are the main drivers of inflammation in OA by elevating chondrocyte production of matrix metalloproteinases (MMPs).2,3

These MMPs cause a breakdown of cartilage matrix, fuelling inflammation that drives a positive feedback loop – consisting of the promotion of tissue damage by inflammatory cytokines, causing further tissue damage and cytokine response. As a result, cartilage destruction and degeneration occur over time, causing advanced OA.

Pathophysiological response

A common pathophysiological response to a joint with OA is to repair the injury by improving the joint environment and improving the mechanical stresses in it.

If this environment is persistently abnormal, conservative treatment will not aid in the recovery of OA and the condition can worsen.


In view of the myriad of factors that contribute to OA, a multidisciplinary approach is needed to manage young patients with the condition.

The Osteoarthritis Research Society International (OARSI) recommends that the initial treatment of knee OA should be conservative, comprising the following:4

  • Physiotherapy

  • Education

  • Weight reduction

  • Viscosupplementation

  • Corticosteroid injections

  • Analgesia

  • Anti-inflammatory treatment


Referral to physiotherapy and analgesia

In the initial phase of management, general practitioners (GPs) can consider referring to the physiotherapist to initiate targeted lower limb exercises to relieve pain, maintain range of motion and build strength.

This should also be complemented with analgesia such as nonsteroidal anti-inflammatory drugs (NSAIDs) to aid with rehabilitation.

Advice for weight loss

For patients whose BMI is above 23, GPs can offer dietary and exercise advice for weight loss and consider referral to the dietitian and potentially psychologist as well, as weight loss can be a difficult journey.

A multidisciplinary approach is taken across all SingHealth institutions. At Sengkang General Hospital (SKH), there is a weight loss clinic, the SWITCH Centre, which is run by endocrinologists, bariatric surgeons, physiotherapists, dietitians and psychologists. Patients who are referred there will be given advice on medical and surgical means of losing weight while being supported by the allied health teams.

If the patient does not respond to these initial measures, intra-articular injections, such as hyaluronic acid, can be considered as an interim treatment.

Referral to sports medicine

Referral to sports medicine physicians can be considered for exercise prescription and more advanced intraarticular knee injections.


Exercise prescription

Specific exercises to strengthen the thigh, hip and calf muscles are important in reducing pain in patients with knee OA.

Aerobic exercises such as swimming, walking and cycling are also beneficial for weight loss, cardiovascular health and maintaining the patient's function.

Intraarticular knee injections

Intraarticular knee joint injections can also be considered for patients who still have persistent pain.

Typically, OARSI guidelines recommend either hyaluronic acid or steroids. However, orthobiologics are emerging as an alternative, and autologous protein solution (APS) is key among them.


What it is

APS is an autologous interleukin-1 receptor antagonist (IL-1Ra) blood-derived product that has been shown in a recent systematic review to have acceptable safety and efficacy for the treatment of mild to moderate knee OA.5 Today, nSTRIDE® (Biomet Biologics, Warsaw, IN, USA) is the only available APS for clinical use in knee OA patients.

APS is currently being used as one of the orthobiologics for the treatment of knee OA by targeting the pathways that involve IL-1β and TNFα.

The aim of APS is to improve pain and hamper the progression of OA, and it achieves this via an injection into the knee joint with minimal systematic complications.

In SKH, patients with Kellgren and Lawerence grades 1 to 3 are offered a single one-off intraarticular injection of APS, with a possible addition of hyaluronic acid.

How it works

As described in Kon et. al., blood extracted from the patient is passed through an APS kit which involves a two-stage process:

  1. The APS separator separates white blood cells and platelets (cellular components).

  2. The resultant solution is then concentrated in the next process involving an APS concentrator (consisting of polyacrylamide beads). These beads act as a dehydrating agent, resulting in a high concentration of cytokines in the APS solution which can be two to three times that of the cytokine concentration in normal blood plasma.

The anti-inflammatory cytokines in APS are antagonistic to IL-1β and TNFα, and consist of IL-1Ra and soluble receptors I and II against TNFα (sTNF-RI, and sTNF-RII).

Clinical safety

With regard to clinical safety, the literature shows no severe adverse effects, with only minor complications such as swelling, effusion, stiffness and arthralgia of the injected joint.


In knee OA, the most common compartment affected is the medial compartment. This results in a varus deformity which perpetuates the increasing load on the medial compartment.

Hence, there are some cases where patients fail to respond to all the above treatment options as the mechanical environment continues to be abnormal and OA still progresses.

Should conservative treatment fail, referral to an orthopaedic surgeon for surgical intervention should be carried out.

Realignment osteotomy

In patients with mechanical alignment issues of the lower limb, realignment osteotomies have been gaining traction recently as an effective means to correct the mechanical overload of the medial compartment causing OA symptoms6, with a high tibial osteotomy (HTO) as the most common procedure performed.

HTO is advantageous when performed on younger patients who present with earlier stages of OA, to offset the potential positive feedback loop of cartilage destruction that arises in later stages.

Osteotomies only delay the time for a joint replacement by allowing the patient to have earlier adequate symptomatic relief.

Other procedures

Besides osteotomies, other procedures that can be performed for young patients with OA can vary from arthroscopic debridement, to cartilage repair/resurfacing and unicompartmental arthroplasties.


The treatment of knee OA in young patients is challenging and involves a multidisciplinary approach.

Initial approaches consist of addressing mechanical factors by weight loss and strengthening, as well as addressing biochemical factors with NSAIDs. This can be done at a primary care level, with the aid of allied health input from dietitians, psychologists and physiotherapists.

Escalation to more invasive methods by sports medicine physicians and orthopaedic surgeons include intraarticular knee injections with APS to reduce the cytokine cascade, correction of the mechanical axis via osteotomies, cartilage repair surgeries and unicompartmental arthroplasties.

These aim to reduce pain and still allow these patients to maintain their previous high level of physical activity, in addition to delaying the time needed for total knee arthroplasty.


  1. Lange JK, Lee YY, Spiro SK, Haas SB. Satisfaction Rates and Quality of Life Changes Following Total Knee Arthroplasty in Age-Differentiated Cohorts. J Arthroplasty. 2018;33(5):1373-1378.

  2. Kon E, Engebretsen L, Verdonk P, Nehrer S, Filardo G. Autologous Protein Solution Injections for the Treatment of Knee Osteoarthritis: 3-Year Results. Am J Sports Med. 2020;48(11):2703-2710. 

  3. Khan M, Adili A, Winemaker M, Bhandari M. Management of osteoarthritis of the knee in younger patients. CMAJ. 2018;190(3):E72-E79. 

  4. Bannuru, R. R., Osani, M. C., Vaysbrot, E. E., Arden, N. K., Bennell, K., Bierma-Zeinstra, S. M. A., Kraus, V. B., Lohmander, L. S., Abbott, J. H., Bhandari, M., Blanco, F. J., Espinosa, R., Haugen, I. K., Lin, J., Mandl, L. A., Moilanen, E., Nakamura, N., Snyder-Mackler, L., Trojian, T., Underwood, M., … McAlindon, T. E. (2019). OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis and cartilage, 27(11), 1578–1589.

  5. Ajrawat, P., Dwyer, T., & Chahal, J. (2019). Autologous Interleukin 1 Receptor Antagonist Blood-Derived Products for Knee Osteoarthritis: A Systematic Review. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association, 35(7), 2211–2221.

  6. He, M., Zhong, X., Li, Z., Shen, K., & Zeng, W. (2021). Progress in the treatment of knee osteoarthritis with high tibial osteotomy: a systematic review. Systematic reviews, 10(1), 56.


Dr Krishmen Rasu is a sports medicine Resident Physician with a Masters in Sports Medicine from the University of Melbourne. He has a keen interest in intraarticular injections of the knee and runs the Orthopaedic and Sports Interventional Service (OASIS) in Sengkang General Hospital.


GPs can call the SingHealth Duke-NUS Sport & Exercise Medicine Centre for appointments at the following hotlines, or visit the website more information:
Singapore General Hospital: 6326 6060
Changi General Hospital: 6788 3003
Sengkang General Hospital: 6930 6000
KK Women’s and Children’s Hospital: 6692 2984