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Title:	Factors associated with deterioration of bone health in Malaysian men and the use of tocotrienol to prevent osteoporosis in a testosterone-deficient rat model
Authors:	Chin Kok Yong (P62373)
Supervisor:	Ima Nirwana Soelaiman, Prof. Dr.
Keywords:	Deterioration of bone Osteoporosis Dissertations, Academic -- Malaysia
Issue Date:	29-Aug-2014
Description:	Kajian ini bertujuan untuk menentukan faktor-faktor yang mempengaruhi kesihatan tulang lelaki di Malaysia dan kesan tokotrienol terbitan anato dalam pencegahan osteoporosis dengan model osteoporosis haiwan yang bersesuaian. Untuk mencapai objectif pertama, suatu kajian keratan rentas telah dijalankan ke atas lelaki Cina dan Melayu berumur 20 tahun ke atas di kawasan Kuala Lumpur. Kesihatan tulang mereka ditentukan dengan teknik ultrabunyi kuantitatif dan nilai kelajuan ultrabunyi (SOS) kalkaneus diukur sebagai penentu kesihatan tulang mereka. Pengukuran antropometri dan analisis biokimia serum juga dilakukan ke atas subjek. Hasil kajian ini mendapati kesihatan tulang dan aras testosteron lelaki di Malaysia menurun beransur-ansur mengikut umur. Umur dan antropometri badan berhubung kait secara signifikan dengan nilai SOS dalam subjek. Aras testosteron (fraksi biotersedia dan bebas) dan globulin pengikat hormon seks dalam serum merupakan pengantara yang signifikan dalam hubungan umur dengan SOS. Kesimpulannya kemerosotan kesihatan tulang di kalangan lelaki di Malaysia akibat penuaan sememangnya berlaku. Penurunan bioketersediaan testosteron mengikut usia merupakan komponen penting dalam kemerosotan kesihatan tulang ini. Untuk mencegah osteoporosis akibat defisiensi testosteron ini, model osteoporosis tikus aruhan kekurangan testosteron yang mencirikan kemerosotan kesihatan tulang lelaki yang digambarkan dalam kajian terdahulu digunakan untuk menguji keberkesanan tokotrienol anato (AnTT) sebagai agen antiosteoporosis. Tikus terokidektomi menerima AnTT 60 mg/kg berat badan selama lapan minggu secara paksa oral dan keberkesanannya dibandingkan dengan tikus yang tidak menerima rawatan dan tikus yang menerima rawatan gantian testosteron (7 mg/kg berat badan setiap minggu, intraotot). Tikus sham dan asas disediakan sebagai kawalan. Indeks struktur pada tibia proksimal diuji dengan microtomografi sinaran-X, indeks struktur dan dinamik pada distal femur diuji dengan teknik histomorfometri, penanda pemodelan semula tulang diuji dalam serum dan ekspresi gen dalam femur distal diuji. Hasil kajian menunjukkan rawatan AnTT dapat mencegah perubahan degeneratif pada tulang trabekular akibat orkidektomi di femur distal. Bagaimanapun, keberkesanan AnTT adalah lebih rendah berbanding dengan rawatan testosteron. Kajian selanjutnya menunjukkan AnTT berciri anabolik dengan meningkatan permukaan berlabel ganda dua fluoresens dan ekspresi gen yang terlibat dalam pembentukan tulang. Kesimpulannya, AnTT berpotensi sebagai agen antiosteoporosis dalam pencegahan osteoporosis akibat kekurangan testosteron dalam lelaki kerana AnTT bersifat anabolik ke atas tulang. Dos dan jangka rawatan AnTT perlu diselaraskan untuk mencapai kesan optimumnya.,The present study aimed to determine the factors that were associated with deterioration of bone health in Malaysian men and the effects of tocotrienol in preventing osteoporosis using a suitable male rat model. A cross-sectional study on Chinese and Malay men aged 20 years and above residing in Kuala Lumpur was conducted to achieve the first objective. Their bone health was assessed using quantitative ultrasound technique and calcaneal speed of sound (SOS) was used as the indicator of bone health. Anthropometric measurement and serum biochemical evaluation were also performed. The results of this study showed that bone health and testosterone level of Malaysian men declined gradually with the increase in age. Age and body anthropometry were significantly associated with calcaneal SOS in the subjects. Testosterone (bioavailable and free fractions) and sex hormone binding globulin levels were significant partial mediators in the relationship between age and SOS. As a conclusion, age associated degeneration in bone health in Malaysian men does occur. The age related decline in the bioavailability of testosterone is an important component in explaining the degeneration of bone health in men. In order to find an agent that can prevent testosterone-deficient osteoporosis, an orchidectomized rat model of osteoporosis due to testosterone deficiency, which mimicked the degeneration of bone health in men found in the earlier study, was used to test the efficacy of tocotrienol derived from annatto beans (AnTT) as an antiosteoporotic agent. Orchidectomized rats were given 60 mg/kg body weight AnTT orally for eight weeks and its efficacy was compared against untreated and testosterone-treated rats (7 mg/kg body weight weekly, intramuscularly). Sham-operated and baseline rats were also prepared as controls. Structural indices of proximal tibia were tested with X-ray microtomography, structural and dynamic indices of distal femur were tested with histomorphometric technique, bone remodeling markers were tested in serum and gene expression in the distal femur was tested. The results indicated that AnTT treatment prevented degenerative changes of trabecular bone due to orchidectomy in the distal femur. However, its efficacy was lower compared to testosterone treatment. Further study showed that AnTT possessed anabolic effects on the bone, in which it increased double-labelled fluorescent surface and gene expression related to bone formation. As a conclusion, AnTT is a potential antiosteoporotic agent in preventing osteoporosis due to testosterone deficiency in men because it exerts anabolic effects on bone. The dose and treatment period of AnTT should be adjusted to achieve its optimal effects. Overall, this study shows that degeneration of bone health status happens in Malaysian men and it is mediated by an age-dependent decline of bioavaibility of testosterone. Tocotrienol may be a potential agent in preventing the decline of bone health in men.,PhD
Pages:	155
Publisher:	UKM, Kuala Lumpur
Appears in Collections:	Faculty of Medicine / Fakulti Perubatan

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