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Tuesday, 8 December 2015

Most Common Diseases of elder: The Clinical Trials and Studies of Musculo-Skeletal disorders: Osteoporosis - The Miracle of Antioxidants

Musculoskeletal disorders (MSDs) are  medical condition mostly caused by work related occupations and working environment, affecting patients’ muscles, joints, tendons, ligaments and nerves and developing over time. According to a community sample of 73 females and 32 males aged 85 and over underwent a standardised examination at home, musculoskeletal pain was reported by 57% of those interviewed(1).

      Types of Musculo-Skeletal disorders in elder(2)

1. Osteoarthritis
2. Gout
3. Rheumatoid Arthritis
4. Polymalagia Arthritis
5. Cervical myleopathy and spinal canal stenosis
6. Osteoporosis
7. Low back pain
8. Fibromyalgia

                                Osteoporosis

Osteoporosis is defined as a condition of thinning of bone and bone tissues as a result of the loss of bone density over a long period of time. It is a widespread degenerative disease of skeletal joints and often associated with senescence in vertebrates due to excessive or abnormal mechanical loading of weight-bearing joints, arising from heavy long-term use or specific injuries(6).



                               The Prevention and Management 
The prevention and management of osteoporosis are always important due to the prevalent of the diseases in  in all populations and all ages(221), especially to elder, causing a significant physical, psychosocial, and financial consequences(220).

Antioxidants and Osteoporosis

Oxidative stress can induce impairment of bone mass and fragility fractures through its effects in causing apoptosis in osteoblasts, due to continuously generated of reactive oxygen species (ROS), such as H2O2-induced oxidative damage-implications(246) involved lipid peroxidation, protein damage, and DNA lesions of that exhibit the increased risk of osteoporosis(245)(248).
Antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, and catalase reduced the excessive production of free radicals in the organism, and the imbalance between the concentrations of these and the antioxidant defenses have found to attenuate the risk of osteoporosis (OP) in postmenopausal women, according to the study by the Adnan Menderes University School of Medicine(247). Further more, decrease antioxidant defenses due to aging may also may contribute to this process(250).
Dietary and endogenous antioxidants were consistently lower in patients with osteoporosis, according to University of Perugia, of that can lead to decrease antioxidant defenses and promoting pathogenesis of osteoporosis(249).

The Miracle of antioxidants
Antioxidants may have a direct and profound influence to the risk factor of osteoporosis(306), due to its effect in bone turn over. Oxidative stress (OS) continuous generating reactive oxygen species (ROS), such as H2O2-induced oxidative damage-implications has found to consist a correlation between bone mineral density (BMD) and OS in postmenopausal women, according to the jopint study lead by the Aligarh Muslim University(307).

1. Lycopene
Lycopene found abundantly in tomato, watermelon, grapefruit has significantly increased antioxidant capacity and decreased oxidative stress, through activation of bone resorption markers in reduced the risk of osteoporosis(308). On postmenopausal models, risk of osteoporosis increase by 10 fold due to reduce production of Sex hormones. Treatment with lycopene suppressed bone turnover to restore bone strength through down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with improved oxidative damage activities(309).
Recent study also suggested that lycopene inhibit bone resorption(310)(311), facilitates bone formation(311) and improved bone mineral density(311) and rat skeletal system in experimental conditions(310).

2. Omega 3 Fatty acid
Omega 3 Fatty acid found abundantly in deep sea fishes, and seeds such flax seed may contribute to the reduced and preventive risk of osteopororsis(312) through intervention of the decreased osteoclastogenesis and loss of bone mass(313). But according to the joint study by Université d'Auvergne, due to fatty acid function in trigger several different independent pathways (receptors, metabolites…), its effects on bone metabolism may require further integrated study(314).

3. Resveratrol
Resveratrol, an powerful antioxidant(315) found abundantly grapes, red and white wine, blueberries,cranberries may have a exclusive impact on bone metabolism due to its effect in reduced oxidative stress by direct interfering with the production of reactive oxygen species (ROS)(316). According to the joint study lead by Fudan University, resveratrol oligomer derivative, isopaucifloral F improved bone mineral density, bone volume/tissue volume, trabecular thickness, trabecular separation/spacing, through its estrogenic effect  may be a promising antioxidant for treatment on postmenopausal osteoporosis(317). Dietary resveratrol also significantly prevented bone loss in the osteoporotic mice, through its effects on reactive oxygen species (ROS), improved the antioxidant/prooxidant equilibrium and balancing the disequilibrium between bone formation and bone resorption(318)in iron load mice study.

4. Silibin 
 Silibin, a major active constituent of silymarin found abundantly in Milk thistle seeds may be beneficiary for patient with osteoporosis due to its effect in promoted bone-forming osteoblastogenesis and encumber osteoclastic bone resorption through accelerated cell proliferation and promoted matrix mineralization, Hallym University suggested(319). In other study, silibin through its osteogenic activity, improves time of bone healing in case of fracture  and bone strength with elevated BMD(320), by stimulating alkaline phosphatase (ALP) activity and calcium nodule formation(320). and promotes osteogenic differentiation of human bone marrow stromal cells(321) throguh bone morphogenetic protein signaling(321)

5. Lignans
Lignans,an phytoestrogen antioxidant found in flax, pumpkin, sunflower, poppy, sesame,etc,..may be a potential sources for ameliorating the post-menopausal osteoporosis as its effects on bone mineral density through significantly decrease in the levels of serum bone turnover markers osteocalcin(322) and alkaline phosphatas(323). According to the recent joint study lead by Jinan University, phytoestrogen ligans significantly promoted osteoblastic cell proliferation and increased osteoblastic
(UMR106)(325)(324) cell numbers of that can induce the bone minera ldensity protective effects(324).


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References
(1) Prevalence of rheumatic symptoms, rheumatoid arthritis, ankylosing spondylitis, and gout in Shanghai, China: a COPCORD study by Dai SM1, Han XH, Zhao DB, Shi YQ, Liu Y, Meng JM.(PubMed)
(2) Musculoskeletal Disorders in the Elderly by Ramon Gheno, Juan M. Cepparo, Cristina E. Rosca,1 and Anne Cotten(PMC)
(3) Osteoporosis(Life extension)
(5) Growth hormone and bone by Ohlsson C1, Bengtsson BA, Isaksson OG, Andreassen TT, Slootweg MC.(PubMed)
(6) GH and bone--experimental and clinical studies by Isaksson OG1, Ohlsson C, Bengtsson BA, Johannsson G.(PubMed)
(205) New advances in imaging osteoporosis and its complications by Griffith JF1, Genant HK.(PubMed)
(207) Severe osteoporosis: diagnosis of non-hip non-vertebral (NHNV) fractures by Giovanni D’Elia,1 Giuliana Roselli,1 Loredana Cavalli,2 Paolo Innocenti,1 and Maria Luisa Brandi2(PubMed)
(208) Whole bone geometry and bone quality in distal forearm fracture by Parkinson IH1, Fazzalari NL.(PubMed)
(209) Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density inosteoporosis by Shiraki M1, Shiraki Y, Aoki C, Miura M.(PubMed)
(210) Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase ofbone turnover in postmenopausal osteoporosis: a randomized prospective study by Shiraki M1, Itabashi A.(PubMed)
(211) Association of Body Weight and Body Mass Index with Bone Mineral Density in Women and Men from Kosovo by Rexhepi S1, Bahtiri E2, Rexhepi M1, Sahatciu-Meka V3, Rexhepi B1.(PubMed)
(212) Should we prescribe calcium or vitamin D supplements to treat or prevent osteoporosis? by Bolland MJ1, Grey A1, Reid IR1.(PubMed)
(306) Antioxidants and bone turnover in involutional osteoporosis by Maggio D1, Barabani M, Pierandrei M, Macchiarulo MC, Cecchetti R, Pedrazzoni M, Senin U, Cherubini A.(PubMed)
(307Correlation between bone mineral density and oxidative stress in postmenopausal women by Sharma T1, Islam N2, Ahmad J3, Akhtar N4, Beg M1.(PubMed)
(308) Supplementation with the antioxidant lycopene significantly decreases oxidative stress parameters and the bone resorption marker N-telopeptide of type I collagen in postmenopausal women by Mackinnon ES1, Rao AV, Josse RG, Rao LG.(PubMed)
(309) Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model by Ardawi MM1, Badawoud MH2, Hassan SM2, Rouzi AA3, Ardawi JM4, AlNosani NM5, Qari MH6, Mousa SA7.(PubMed)
(310) [Effects of lycopene on the skeletal system].[Article in Polish] by Sołtysiak P1, Folwarczna J1.(PubMed)
(311) Lycopene intake facilitates the increase of bone mineral density in growing female rats by Iimura Y1, Agata U, Takeda S, Kobayashi Y, Yoshida S, Ezawa I, Omi N.(PubMed)
(312) The impact of omega-3 fatty acids on osteoporosis by Maggio M1, Artoni A, Lauretani F, Borghi L, Nouvenne A, Valenti G, Ceda GP.(PubMed)
(313) Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice by Sun D1, Krishnan A, Zaman K, Lawrence R, Bhattacharya A, Fernandes G.(PubMed)
(314) Pros and cons of fatty acids in bone biology by Wauquier F1, Léotoing L1, Philippe C1, Spilmont M1, Coxam V1, Wittrant Y2.(PubMed)
(315) Resveratrol improves oxidative stress and prevents the progression of periodontitis via the activation of the Sirt1/AMPK and the Nrf2/antioxidant defense pathways in a rat periodontitis model by Tamaki N1, Cristina Orihuela-Campos R2, Inagaki Y3, Fukui M2, Nagata T3, Ito HO2.(PubMed)
(316) Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis.
Bhattarai G1, Poudel SB1, Kook SH2, Lee JC3.(PubMed)
(317) Synthesis, estrogenic activity, and anti-osteoporosis effects in ovariectomized rats of resveratrol oligomer derivatives by Hao XD1, Chang J1, Qin BY2, Zhong C1, Chu ZB1, Huang J3, Zhou WJ4, Sun X5.(PubMed)
(318) Effects of dietary resveratrol on excess-iron-induced bone loss via antioxidative character by Zhao L1, Wang Y2, Wang Z1, Xu Z3, Zhang Q4, Yin M5.(PubMed)
(319) Osteoblastogenesis and osteoprotection enhanced by flavonolignan silibinin in osteoblasts and osteoclasts by Kim JL1, Kang SW, Kang MK, Gong JH, Lee ES, Han SJ, Kang YH(PubMed)
(320) Osteogenic activity of silymarin through enhancement of alkaline phosphatase and osteocalcin in osteoblasts and tibia-fractured mice by Kim JL1, Park SH, Jeong D, Nam JS, Kang YH.(PubMed)
(321) Silibinin promotes osteoblast differentiation of human bone marrow stromal cells via bone morphogenetic protein signaling by Ying X1, Sun L, Chen X, Xu H, Guo X, Chen H, Hong J, Cheng S, Peng L.(PubMed)
(322) Ameliorative effects of Schizandra chinensis on osteoporosis via activation of estrogen receptor (ER)-α/-β by Kim MH1, Choi YY, Han JM, Lee HS, Hong SB, Lee SG, Yang WM.(PubMed)
(323) Antiosteoporotic activity of Saururus chinensis extract in ovariectomized ratsby Sung MJ1, Davaatseren M, Hur HJ, Kim HJ, Ryu SY, Choi YH, Cha MR, Kwon DY.(PubMed)
(324) New lignans from the bioactive fraction of Sambucus williamsii Hance and proliferation activities on osteoblastic-like UMR106 cells byXiao HH1, Dai Y2, Wong MS3, Yao XS4.(PubMed)
(325) Lignans from the stems of Sambucus williamsii and their effects on osteoblastic UMR106 cells.by Yang XJ1, Wong MS, Wang NL, Chan SC, Yao XS.(PubMed)