Pre and post test clinical trial to assess the efficacy of tila rasayana in osteoporosis

Osteoporosis is a disease of advancing age characterized by decrease in the bone density that leads to an increased risk of fracture. It is often nicknamed as silent disease due to absence of any marked symptoms unless produced with a fracture. It is a highly predominating health issue around the world, accounts for about 30% fractures occurring world-wide. Osteoporosis is not only a major cause of fracture, it also ranks high among disease that cause people to become bedridden with serious complications. These complications may be life threatening in elderly people. Because of the morbid consequences of osteoporosis, the prevention of this disease and its associated fractures is considered essential to the maintenance of health, quality of life and independence in elderly population. **NEED FOR THE STUDY:**Osteoporosis is a disease which affects the quality of life of people than causing fracture. The prevalence of Osteoporosis is high in India may be due to increased number of elderly population. Post-menopausal women are more prone to this condition due to impaired oestrogen function and reluctance and negligence for undergoing treatment. The medications presently available are either hormone supplements or need to be taken for a long time. Rasayana benefits man by imparting superior quality in Dhatus. It is meant to reduce the pace of ageing. Rasayana can be advised as Naimittika, where disease cure is its main aim along with Dhathu Poshana. Tila Rasayana is known to improve tooth health and general body health. Tila or sesame is palatable and can be consumed rather as a food than medicine. Tila may thereby increase the quality of life of individuals crippling with the morbidities of Osteoporosis. Tila Rasayana encountered in the study is said to be effective in controlling the associated symptoms of Danta Saata, Nakha Bheda etc. Hence this study is undertaken to find the efficacy of Tila Rasayana in the management of Osteoporosis. REVIEW OF LITERATURE The late phase of life is said to be dominant by Vata Dosha.This Vata Vruddhi deteriorates its Ashrayi Dhathu Asthiwhich may lead to Asthi Kshaya. The symptoms of Asthi Kshaya are Asthi Toda (pricking pain over bones), Shatana of Danta (falling teeth), Shatana of Kesa (hair fall), Shatana of Nakha (degeneration of nails). Dhatu Poshana can be achieved through wise administration of Rasayana. Tila Rasayana is explained under Naimittika Rasayana for the nourishment of body and strengthening of teeth. Danta is the Upadhatu of Asthi. Naimittika rasayana is administered after proper shodhana karma. Tila is one among the best Vatahara drug, it is Kesya and Dantya. Gandha Thaila indicated for Bhagna whose main ingredient is Tila. Tilakalka Udaka Gandusha is indicated for Dantaharsha (sensitive teeth) and Danatacala (loose teeth). Time for transformation of Ahara Rasa into Sukra Dhatu is one month.  Wanachewin O et.al (2012) identified that sesamin can stimulate osteoblast differentiation . The databases Pubmed, Scopus, Dhara, Ayush Research Portal and Google Scholar were thoroughly reviewed using Key words – Osteoporosis AND tila rasayana, Osteoporosis AND asthikshaya, tila rasayana AND asthi kshaya, Osteoporosis AND Sesamum indicum, Tila rasayana , Thila rasayana.Filter – Human. Finally one relevant with the most comprehensive data is obtained and included as main reference. Previous research studies reveal that many studies have been done to find out an effective management for osteoporosis. But rasayana studies with tila have not been done as mentioned in the context of rasayana chikitsa adhikara in ayurvedic literature. Previous research studies show that sesamin an active ingredient of Sesamum indicum can stimulate osteoblast differentiation through p38 and ERK ½ MAPK signalling pathways  AIM OF THE STUDY

To assess the effect of Tila Rasayana in Osteoporosis.

OBJECTIVES OF THE STUDY 1) To assess the effect of Tila Rasayana in Osteoporosis in relation to Bone mineral density. 2)To assess whether there is increase in quality of life of Osteoporosis patients after this treatment protocol. **MATERIALS AND METHOD:**Twenty patients of will be selected from OP and IP departments of Amrita School of Ayurveda, Vallikavu, Kerala Inclusion criteria: 1) Between age group of 35-65 years of both sexes. 2) Rasayana Arhas mentioned in classics 3) Virechana Arhas mentioned in classics 4) BMD t score of more than -2.5 using peripheral densitometry (pDXA scan of  heel bone) Exclusion Criteria: 1) Mentally unsound and illiterate 2) Pregnant and puerperal women. 3) Known case of bone T.B, bone neoplasm, bone fracture, uncontrolled cases of hypertension and diabetes mellitus, osteogenesis imperfecta and such other hereditary diseases, hyperthyroidism and hyperparathyroidism, Chronic Rheumatoid Arthritis, Menorrhagia. 4) Patients who are on treatment with corticosteroids.

Open labeled single-armed pre-experimental clinical research with an appropriate sample size conducted in Amrita School of Ayurveda. Patients are recruited by doing pDXA scan of heel bone with BMD t scoring. Those who satisfy the inclusion criteria will get admitted to the clinical trial. The selected 20 patients will be put under a single group. The patients will be receiving Pachana Deepana with Trikatu Churna 5g/tid for 3 days or till the attainment of Pakwa Mala Lakshana. This is followed by Sodhananga Snehapana with Murchitha Ghritha for 3-7 days or till the attainment of Samyak Snigdha Lakshana. Then Sarvanga Abhyanga Bashpa Sweda for the next three days will be done. On the third day of Sarvanga Abhyanga, Virechana will be done with Gandaravahasthadi Eranda Thaila -40ml with hot water. Till Sodhana the patient will be under IP care. Then Samsarjana Krama according to Sodhana Shuddi Prakara will be followed.  50 grams of Tila with water will be given in the early morning in an empty stomach for the next 30 days. **Assessment Criteria :**The assessment will be done on baseline prior to treatment initiation and after treatment completion.Subjective parameters nil. Objective parameters are BMD t score > - 2.5 with PDXA of the heel bone,  Quality of Life Assessment Questionnaire by International Osteoporosis Foundation, bone biomarker blood tests Serum Calcium and Total Alkaline Phosphatase

RESULTS: In parameters like Serum ALP and QOL tests were found to be statistically significant. And parameters like Serum Calcium, t score and bone mineral density were statistically insignificant before and after the trial. But Tila RasÄyana showed clinical significance by the reduction in pain, improvement in mobility etc. before and after the trial.

DISCUSSIONTila Rasayana is explained in classics for the strength of teeth and nourishment of the body. Sodhana purvaka Tila rasayana given for 1 month is sufficient to bring changes to Serum ALP which is an indicator for increased osteoblastic activity. Alkaline phosphatase activity is inevitable for the mineralization of bone and represents a useful biochemical marker of bone formation. And related medical researches are suggestive of activation of ALP by sesamin. The improvement in QOL suggests that due to Tila rasayana there is an increase in their pain reduction, activities of daily living, jobs around the house, mobility, leisure and social activities, general health perception and mental function. In the benefits obtained after rasÄyana especially kuti prÄvÄ“Å›ika, Ä€cÄrya Caraka says praṇati or social reverence, dÄ“ha bala or body strength which aid in improving quality of life. Thus improved QOL can be said due to the impact of rasÄyana karma of Tila. This is suggestive of providing a better life quality index which is very much essential for a disease like osteoporosis. But insignificant change in Serum Calcium and BMD and t score suggestive of not much change happened for bone formation and resorption process. So the bone resorption to bone formation process did not go hand in hand with the one month of scheduled Tila rasayana. DÄruṇa is the quality of vÄta by which it does Å›Åá¹£aṇa and brings kaá¹­hinata or hardness. This kaá¹­hinata can be compared to the density of asthi dhÄtu. DhÄtu vyÅ«hana is the karma of normal vÄta, by which sthÄyi dhÄtu will get nourished. This may result in an increase in Bone Mineral Density after Tila RasÄyana.  At the same time, there is an improvement in mean for Serum Calcium before and after the study. Sesamum indicum contains Calcium. By the rule vrÌ¥ddhi samÄnai sarvÄ“á¹£Äm, similar increases similar. Calcium in sesame increases Calcium in bones. The mean change in pain assessed by VAS. It is supported by the vatahara, vedanasthapana action of tila. This reduced pain can also be supported by the anti-inflammatory as well as antinociceptive action of sesame. The mean improvement in mobility by TUG test supports the sandhi dardyakara karma of tila. Body mass index needs to be not too less as it is a risk factor for osteoporosis. It is essential to maintain body mass index to normal level to keep bone mineral density stable. Tila is kaphakrÌ¥ t in nature which may result in brÌ¥ á¹haṇa. Hence the improvement in mean BMI is all suggestive of the clinical significance of Tila Rasayana. The treatment protocol adopted was helped in bringing srotosudhi and nourishing asthi dhatu. ÅšÅdhanÄá¹…ga snÄ“hapÄna helps in snÄ“hana and Å›Ådhana of dÅá¹£as. VirÄ“cana can bring vÄtÄnulÅmana and improvement in both dhÄtwagni and jaá¹­harÄgni. More than that purÄ«á¹£adhara kala and asthidhara kala is similar in nature. Hence virÄ“cana which clears purÄ«á¹£adhara kala may benefit in improving asthi dhÄtu. Sesamin is a major lignan compound found in Sesamin indicum. It has the capacity to trigger osteoblast differentiation by activation of the p38 (regeneration) and ERK MAPKinase (phosphorylation of MAP and cell division of osteoblast) signaling pathway and possibly indirectly modulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Hence sesame may be considered as a promising drug by the presence of various phytochemicals in Osteoporosis treatment. The sesame seed oil has a strong anti-oxidant activity due to the presence of lignans such as sesamin, sesamolin, and sesamol. The presence of sesamol, sesamolin, and gamma-tocopherol (Vitamin E) provides high oxidative stability to Sesamum indicum. Thus sesame helps in preventing the deleterious effects of oxidative stress produced on osteoblast and osteocyte and this may attribute rasÄyana guṇa to it.  Thus following asthi poshaka tila rasayana helps in breaking the dhatu kshayajanya vata pravruddha samprapti of osteoporosis.

CONCLUSION: The pre and post-test interventional study with Tila RasÄyana administered with pÅ«rva Å›Ådhana is statistically insignificant for improving t score, BMD and Serum Calcium. But found statistically significant for Serum ALP and Quality of Life assessment. It shows clinically significant outcomes in reducing pain, improving mobility and quality of life. Hence the null hypothesis is rejected and alternate hypothesis is accepted such that Tila RasÄyana is effective in managing Osteoporosis.