THE IMPACT OF DURATION OF MENOPAUSE ON BONE METABOLISM IN DETECTING AND PREVENTING OSTEOPOROTIC FRACTURES

ABSTRACT Background: Menopause accelerates bone loss after 10 years of cessation of the menstrual cycle causing osteoporosis. Hip fractures among postmenopausal women escalate morbidity and mortality in these women. Objective: The study was done to evaluate the effect of duration of menopause on BTMs so that it could detect post-menopausal osteoporosis at the earliest and predict the fracture risk Materials and Methods: The study was conducted in a tertiary hospital in Mangalore on 100 postmenopausal women. The duration of menopause was divided into quartiles. Evaluation and correlation of serum osteocalcin, urinary hydroxyproline, BMI, calcium, phosphorous and alkaline phosphatase was done on the duration of menopause. The subjects comprised 50 osteoporotic and 50 non-osteoporotic post-menopausal women. Continuous variables were represented as median and interquartile ranges. Comparison between two groups was done using the Mann Whitney U test. Comparison between more than two groups was done using the Kruskal Wallis test. The correlation was done using spearman’s correlation test. Statistical significance was considered at p<0.05. Results: Serum osteocalcin levels significantly declined and urinary hydroxyproline levels elevated between quartiles of duration of menopause in the entire study group and in osteoporotic women. (p<0.001). There was no significant difference in osteocalcin and hydroxyproline levels between the quartiles in the fracture group. 82% of the osteoporotic had >15 YSM. Conclusion: Osteocalcin levels plateaued after 8years of menopause and started decreasing after 15 YSM. Osteoporotic fractures were higher in more than 15 YSM and the osteocalcin level was 2.47 ng/ml in this quartile. There is no significant difference in osteocalcin levels in those with fractures, indicating no significance of screening for serum osteocalcin levels once the fractures have occurred. Hence concluding that the duration of menopause is the key indicator for osteoporosis and serum osteocalcin is a potent biomarker for detection of the risk of fracture. Monitoring of serum osteocalcin levels(<2.55ng/ml) after 8 years of menopause is very essential for early prophylactic treatment in order to prevent osteoporotic fractures and the burden associated with it. KEYWORDS: Duration of menopause, osteocalcin, quartiles, urinary hydroxyproline, osteoporotic fractures

A STUDY ON STATUS OF URINARY HYDROXYPROLINE IN POST MENOPAUSAL WOMEN

Introduction: WHO and the Stages of Reproductive Aging Workshop have defined menopausal transition as the time of an increase in follicle-stimulating hormone and either increased variability in menstrual cycle length, two skipped menstrual cycles with 60 days or more of amenorrhea, or both. It concludes with the final menstrual period. Post-menopause begins at that time, although it is not recognized until after 12 months of amenorrhea. During menopause, women face various physiological, psychological, and biochemical changes. Laboratory medicine has given a new background to overcome the clinicianÂÂs diagnostic dilemma. Hydroxyproline is mainly found in collagen and accounts for 13% of total amino acid content and derived from proline by post-translational hydroxylation. Hydroxyproline is derived from another amino acid such as proline. Direct urinary assay of hydroxyproline to measure bone resorption have clinical applications as part of screening programs to assess the risk of osteoporotic fractures. Method: A total of seventy patients with regular medical follow-up records, The Patients were pre and post-menopausal women (35 each) recruited for this study. Patient details like body mass index, education, smoking, alcohol intake, dietary habits, and family history were considered before selecting the patients. Analytical Methods: Urinary Hydroxyproline and Urinary creatinine was estimated by Modified Neumann et al and Spectrophotometric JaffeÂÂs reaction respectively. Result: The study population consisted of 70 participants of premenopausal (n=35) and postmenopausal women (n=35), mean age of 38.11 ± 4.3 and 54.40 ± 4.6 respectively. The bone mineralization marker urinary total hydroxyproline was quantified in pre and post-menopausal women, which is 80.3 ± 75mg/L and 136 ± 103mg/L respectively. The urinary creatinine level in pre and post-menopausal women was 53.7 ± 14.2mg/dL and 37.0 ± 27.3 respectively. The hydroxyproline: creatinine ratio (HCR) was 41% to 69% against the normal reference interval in pre and post-menopausal women. Conclusion: The obtained normative data for the premenopausal woman population would be a new reference range in Indian sub-population or otherwise general population normative reference range commonly being used as a reference interval in all kind of pathophysiological disorders. Hence, the derived parameter confirmed that HCR is the most prognostic significant diagnostic marker in pre and post-menopausal patients.

A Preliminary estimation of baseline urinary hydroxyproline/creatinine levels in a study population of healthy Nigerians

Background: Hydroxyproline is one of the biochemical markers that can be measured objectively as an indicator of normal biological processes or pathological processes. It is usually raised in disease conditions that are associated with bone resorption. Aim: To determine the urinary hydroxyproline/creatinine levels in a study population of healthy Nigerians. Methods: This study recruited 22 consenting participants who served as control for another study at the University of Nigeria Teaching Hospital (UNTH) Ituku-Ozalla, Enugu. All participants were required to fast for at least 12 hours overnight and their early morning second void urine collected between 7am and 8am. The collected urine samples were stored frozen at -20oC until analysis. Colorimetric method of analysis of urinary hydroxyproline and creatinine were done using Biovisionhydroxyproline kit and Randoxcreatinine kit respectively. Bivariate analysis was conducted on the collated data using statistical package of social science (SPSS) version 19. The results were recorded as urinary hydroxyproline alone (μg/μL) and as urinary hydroxyproline/creatinine ratio. Results: The mean urinary hydroxyproline level of 0.020±0.013μg/μL and urinary hydroxyproline/ creatinine ratio of 0.016±0.006 were noted for healthy Nigerians. Conclusions: The urinary hydroxyproline levels in the study population of healthy Nigerians are within normal values reported in other healthy populations.

24 Hours Urinary Hydroxyproline - A Noninvasive, Cost-Effective and Early Biochemical Marker Which May be Used to Screen the Osteoporotic Lesion in Postmenopausal Women

Introduction: Osteoporosis results due increased rate of bone turnover. It has multifactorial etiology and most common in women after menopause. Objective: The current study was aimed to assess the rate of bone turnover towards detection of osteoporotic changes by measuring 24 hours urinary hydroxyproline which is an early as well as non- invasive biochemical bone marker. Methods: Urinary hydroxyproline was measured in 40 postmenopausal women and compared with similar number of premenopausal women as controls. Results: 24 hours urinary hydroxyproline levels were significantly higher (p<0.001) in postmenopausal women than premenopausal groups. This indicates a higher rate of bone turnover suggesting osteoporotic changes. 24 hour urinary hydroxyproline is also positively correlated (r= 0.934) with age. Conclusion: The present study suggests that measurement of 24 hours urinary hydroxyproline which is a cost-effective and non- invasive technique, may be used for screening and early detection of osteoporotic changes in women of postmenopausal age group.DOI: http://dx.doi.org/10.3126/ajms.v6i4.11853 Asian Journal of Medical Sciences Vol.6(4) 2015 21-24

Antioxidative role of selected herbs against ethanol induced liver injury in rats

The purpose of this study was to know the hepatotoxicity of ethanol in laboratory rats Rattus rattus and to observe the individual and combined phytotherapeutic role of five herbs viz. Arctium lappa, Curcuma longa, Piper longum, Plumbago zeylanica and Terminalia chebula through biochemical and histopathological parameters. Ethanol is commonly used as solvent, pharmaceutical, drugs and alcohol abuse. Lipidperoxidation, glutathione content, urinary hydroxyproline, collagen and histopathological studies showed hepatotoxicity of 1 ml/kg bodyweight dose of ethanol and protective role of 100 mg/kg body weight dose of herbs. Histopathological changes observed in the liver of rats after ethanol treatment showed hepatitis, collagenesis, fatty infiltration, sclerosis, perilobular necrosis, cytoplasmic degeneration, enlarged bile canaliculi, hydropic degeneration, focal necrosis, binucleated hepatocytes and nuclear degeneration. Mild cytoplasmic degeneration, necrosis, collagenesis and hepatocytes regenerations were observed in rats treated with same dose of ethanol and herbal combination.Ethanol treatment decreased the glutathione content, increased tissue malondialdehyde and collagen content, thus causing tissue injury and liver collagenesis. Urinary hydroxyproline level and biochemical parameters also showed the protective role of herbs against ethanol induced toxicity. Herbal combination i. e. 100ml/kg body weight from the mixture of five herbs given orally was found more effective than their individual role. Herbs and plants contain aromatic substances, secondary metabolites, alkaloids and polyphenols which act as antioxidant thus showing protective role.