**4. Agents for intra-articular injection**

Agents for intra-articular injection include HA and corticosteroids like triamcinolone, betamethasone, and methylprednisolone. Intra-articular injection of corticosteroids showed a greater beneficial effect. Furthermore, during follow-up periods of 3 and 6 months, intra-articular injection of HA showed a better therapeutic effect. Intra-articular injection of a combination of HA and corticosteroids showed a moderate beneficial effect on the pathological process of OA. However, for long-term pain control, intra-articular injection of HA did not show a significant improvement [26].

Use of nonpharmacological modalities (e.g. exercise) as a first-line management for knee OA is little to be compared with pharmacological modalities and usually associated with higher rates of surgical interventions. The results indicate that nonpharmacological agents such as exercise and weight reduction are effective in management of knee OA with minimal adverse side effects. Therefore, exercise and weight reduction should be advised as part of the treatment in most patients owing to their minimal side effects and cost effectiveness, as well as associated health benefits. It is important to specify resources and invest in supporting general practitioners and other primary health care providers to provide lifestyle interventions as a tool in managing knee OA [27].

Irrespective of a large body of evidence concerning the benefits of their use, opiates are used to manage pain associated with Knee OA. No studies fulfilled the inclusion criteria as the follow-up periods of these studies concerning safety were less than 6 months. A recent systematic review of chronic pain management found that there is insufficient evidence to support the effectiveness of long-term opioid therapy [28]. Opioids provide effective analgesia; however, benefits are usually encountered by frequent side effects such as nausea (30%), dizziness (20%), vomiting (13%), constipation (23%), and somnolence (18%) as well as the risk of addiction increases on chronic opioid use. The evidence on the safety and effectiveness of long-term opioid therapy for Knee OA cannot be evaluated. This is a concern and a limitation of the available evidence related to management of Knee OA. In the USA, there has been a significant increase in opioid prescriptions for patients suffering from knee OA, and opioids were prescribed to 15.9% of patients with knee OA [29].

*Recent Advances in Bone Tumours and Osteoarthritis*
