ANALYSIS OF MANIFESTATIONS IN MENOPAUSE AND HERBAL MANAGEMENT OF POSTMENOPAUSAL BONE LOSS

Abstract

The present investigation was undertaken to fulfill two aims. First, to investigate the menopausal experience of women residing in Uttarakhand state which has evaded attention so far and second to explore a new medicinal herb for preventing postmenopausal bone loss for which available therapies are limited by several side effects generated. Interview based cross-sectional survey to reveal age at menopause, frequency and severity of symptoms and associated factors was conducted among healthy women (n= 129, 35-60 years) in Haridwar district of Uttarakhand. The study included only premenopause, early postmenopause and late postmenopause women. The recalled mean age was 45.02 ± 4.35 years and age computed by probit analysis was 46.82 years. Socio-demographic factors like socio economic status and lifestyles significantly affect the onset of menopause. The Greene Climacteric Scale was used to assess the frequency and severity of the menopausal symptoms. Muscle and joint pain was the most prevalent and severe symptom in the whole population as well in the sample of postmenopausal women. This study is the first of its kind from the aforementioned state and an effort to fill the abandoned gap. In an independent project, both acute and chronic treatment studies were conducted to investigate the potential of Tinospora cordifolia (TC), an herbal medicine to prevent bone loss in ovariectomized rat model. For the study done acutely, female Sprague Dawley rats (n=7) were either sham operated (sham ovx) or ovariectomized (ovx) and treated with vehicle (benzyl benzoate: castor oil; 1:4), E2 (lug/day) or TC stem extract (10, 50, 100 mg/kg b.wt.) subcutaneouslyfor 4 weeks. At necropsy, Bone Mineral Density (BMD) measured by pQCT in the metaphysis of tibia was lower in ovx than ovx+E2 or sham ovx group. TC administration to ovx rats at the dose level 10 mg/kg b.wt. provided bone sparing effects by improving BMD. This could be explained by a trend towards decreased bone resorption since a significant positive shift was observed in the serum markers for bone turnover. Administration of TC also induced normalization of the increased levels of lipoproteins. Uterus and mammary gland showed no signs of proliferation after acute treatment with TC extract. Chronic studies were performed with TC (10 mg/kg b.wt.) and E2 (1 ug/d/animal) for over 3 months. Sham ovx or ovx rats were subcutaneously treated with respective test substances. Administration of TC extract and E2 for 12 weeks prevented the ovariectomy induced bone loss in rats. Histology and scanning electron microscopy studies on decalcified bone samples revealed that TC prevented estrogen deficiency induced decrease in trabecular thickness and restored the increase in trabecular separation. Efficacy of TC extract was further ascertained by analyzing the changes occurring in the stability of bone matrix using thermal analysis. Representative curves so obtained from thermogravimetry, differential thermal analysis and differential thermo gravimetry record weight changes and associated endothenuic and exothermic heat effects in bone as a function of temperature (50 to 1500°C). Results showed greater bone mass loss; particularly in the organic phase of matrix in ovx controls (69.4%) compared to TC treated animals (56.13%). Additionally, TC extract improved the energy absorption pattern of tibiae which in turn improve the integrity, structure and hence compactness of bone. In search for active phytochemicals that may be responsible for the antiosteoporotic action of TC, 20- fj hydroxyecdysone (Ecd) was identified as the possible candidate. To test the bone sparing effect of Ecd, ovx rats were orally treated over 3 months with 18 mg, 57 mg and 121 mg Ecd/day/animal. E2 served as the positive control. BMD of the metaphysis of tibia was determined before and after the treatment. Results revealed that BMD was reduced by more than 50% in the control but not in E2 animals. In the Ecd animals, BMD was dose dependently higher than in the control. Ovariectomy induced elevation in serum bone turnover markers was also modulated by E2 and Ecd. While cross-laps were lowered in Ecd and E2, osteocalcin was normalized only by E2. Ecd administration also lack uterotrophic effects. The findings derived u from bone mineral density and biochemical parameters indicate that the antiosteoporotic effect may be attributed at least in part to the presence of Ecd in the extract. TC has been extensively used as an anti-inflammatory, immunomodulatory, antiarthritic and anti-diabetic agent in the ayurvedic preparations. Present study is the first attempt to evaluate its anti-osteoporotic potential. Findings assessed show that TC can prevent ovariectomy induced bone loss without influences on reproductive organs. If these findings can be approved in human they may provide a useful alternative to HRT for the treatment of postmenopausal osteoporosis.