Osteoarthritis affecting 50% of people above middle age is most prevalent disability and basis of degraded quality of life. Palliative non-steroidal anti-inflammatory therapy is marred by health hazards for aging people who require long term therapy amid presence of comorbidities. Joint replacement surgery is not a feasible option for all. Disease modifying drugs have therefore evolved over past some decades but their role is not adequately explored and hence no certain guidelines exist for their use in Osteoarthritis.

The study was a part of post graduate thesis and was completed in 2011. Â·  Present study prospectively examined the outcomes of use of four such therapies in comparison to NSAIDs in the orthopedic outpatients of SS Hospital at BHU, a tertiary care centre. Forty or more patients of osteoarthritis were studied for each treatment regimen employed in the centre as per sample size requirement of central limit theorem. 

The base of clinical evidence resulting from study in 217 patients constitutes modest endeavor for a rationale definition of particulars of disease and sufferer likely to benefit as well as the correct therapeutic practice of the available disease modifying drugs for osteoarthritis of knee. 

 Personal history, disease duration, radiological grading and clinical scoring of disability from knee osteoarthritis on KOOS scale were noted for patients with NSAIDs and the various therapeutic regimens. The doses prescribed were at the discretion of treating orthopaedician. Post treatment KOOS scores were then elucidated and outcomes in each group were computed.

Data were analyzed by Mann-Whitney U test for the overall KOOS scores as absolute changes and also as percentage change from the base line status. Examination of influences of person-specific traits, disease specific profile and drug treatment effects was performed by applying Moods-Median test statistic on rate of good (above median) and bad (below median) therapeutic outcomes in patients.Median values of outcomes pooled for 217 cases were found for above stated parameters at focus, and observation in each group was analyzed with reference to such common median. 

The standard NSAID treatment fared poorly with respect to many ad-on therapies, in overall improvements on KOOS scale and also in its components i.e. relief of pain, symptoms, joint stiffness and overall quality of life.Glucosamine sulfate-chondroitin sulfate combination  prescribed as per recommended doses showed no benefits over NSAIDs treatment in the three months study on any of the examined parameters. It was not deemed rational. Given the wide notion of GS-CS efficacy, long term studies may be necessary to define its utility in specific stage of the disease. Actual drug content of formulations must be ascertained. Oral Hyaluronic acid treatment was prescribed as 20% of recommended dose. Nevertheless, it significantly improved both functional and symptom profiles better than NSAID. Lubricant role was most suggesting and subject to successful achievement with the administered oral dose regimen, albeit although barely 1/5^th of the recommended dose. The hyaluronic acid treatment is apparently very rational for wide adoption. Cost reduction may be possible by using such lower dose.

·  S-adenosyl methionine administered at recommended maintenance dose of 400 mg daily, without initial loading dose over two weeks was another excellent means of improving clinical outcomes. Activity parameters and quality of life significantly improved over the compared NSAID treatment. Results point to research need for defining the role of S-adenosyl methionine deficiency in pathogenesis of osteoarthritis, given especially, its known role in common disorders of aging and obesity. It is rational to combine SAMe with NSAIDs particularly in overweight osteoarthritis patents. Presently the cost burden seems limiting.