Monday, 7 December 2015

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

Kyle J. Norton (Scholar)

Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

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 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 Antioxidant Minerals
1. Selenium
 Selenium, one of the powerful antioxidant in promotion of optimal antioxidative status and greatest immune defense, many studies suggested(273)(274). It also plays an essential role metabolic processes, immune function, thyroid hormone metabolism, male infertility, neoplasms and cardiovascular disease in other research(276).
The rabbits study by the Ankara University, showed that combination of  selenium with vitamin E and vitamin C induced more significant effect than combinations of vitamins to prevent structural alterations in these model bones(275).
Unfortunately, subchronic exposure to selenium(278)(277) and diazinon(277) may be a possible risk factor for osteoporosis, according to the animal study by Georg-August University and Constantine the Philosopher University, respectively. Contrasted to the above studies, in postmenopausal women, Dr, Pedrera-Zamorano JD and the research team at the University of Extremadura, insisted that elevated selenium intake may negatively affects bone mass of women over the age of 51 but only if calcium intake is also less than 800 mg / day(279).

2. Magnesium
Magnesium plays an important role in bone regeneration if it is used together with calcium in form of mesoporous magnesium–calcium silicate (m-MCS)(280) as it improved the cell-positive responses, including the attachment, proliferation and differentiation of MC3T3-E1 cells(281).
Magnesium intake, necessary for bone health, according to the study of 73,684 postmenopausal women exhibited improvement of bone mineral density (BMD) in the hip and whole but did not automatically transforming to lower the risk fractures(282)(283), Patient with osteoporosis is found to have lower levels of magnesium of that effect the function of bone formation, decrease production of sex hormone and other nutrients deficiency, such as calcium, of which is important for bone health(284).

3. Calcium
Calcium found mostly in the skeleton of human body is considered as one of the most important trace mineral with direct interaction with osteoporosis. Deficiency of calcium in most case, depending to the levels of vitamin D(285) is found to associate to risk factor of osteoporosis(286). The dietary sources of calcium are dairy products (milk, yoghurts and cheese) fish (sardines with bones), few vegetables and fruits. supplement may be necessary if dietary sources are scarce or not well tolerated(287)
Dr. Meunier P.said" It is now possible to partly stop bone loss in elderly people and it is never too late to prevent hip fractures with calcium and vitamin D supplements"(288).
Because of the important of levels of vitamin D in related to skeleton health, screening the 25(OH)D, baseline 25(OH)D levels may reduce risk for mortality and falls in older population(289). Other researchers suggested that the screening of serum of vitamin D is important due to its function in influence to digestive absorption of calcium(290)
Daily doses of 400-800 IU of vitamin D, given alone or in combination with calcium, are able to reverse vitamin D insufficiency, to prevent bone loss and to improve bone density in the elderly, according to University of Siena(287).

In need, sold in bottle, found in every corners of the foods store, needless to say for their promotion on the counters on pharmaceutical and drug locations, synthetic mineral calcium, magnesium and vitamin D3 combination are exposed by vitamin giants as a osteoporosis reduced supplement of that induced many buyers from the older population.

Beside calcium (Ca), fluoride, magnesium several trace elements, minerals copper (Cu), manganese (Mn) and zinc (Zn), are essential in bone metabolism as cofactors for certain enzymes(271). In take of calcium supplementation with and without the addition of zinc, manganese (5.0 mg/d) and copper significantly prevent bone loss on spine in postmenopausal women, according to a 2 years, double-blind, placebo-controlled trial(272).

The important of minerals copper, manganese, zinc and fluoride in related to risk factors of osteoporosis?
4. Copper(Cu)
Intake of copper supplement is recommended to post menopausal women due to its direct effects with other minerals, such as magnesium, zinc and calcium in reduced risk of mineral deficiency causes of low bone density(291)(292). According to Dr. Zheng J and the research team at the Sun Yat-sen University, low serum levels of copper Cu are found to associate to increase risk of osteoporosis and suggested that a well-designed studies with adequate control for confounding factors are necessary for future investigations(293).

5. Manganese(Mn)
Levels of serum of manganese may have a direct impart in influence risk factor of osteoporosis in postmenopausal women(294), probably due to Mg transport mechanisms into the cell(294).
According to the Shandong Agricultural University, deficiency of manganese Mn can decrease trabecular thickness, trabecular number and trabecular bone area of that induce risk of osteoporosis in chicken study(296).

6. Zinc(Zn)
Trace mineral zinc is best known for its function as nutritional factor in the growth of human body. The levels of zinc decreased slowly in the conjunction of aging progression(298).
  Zinc, as an essential trace element, or genistein, is found to increase bone mass through stimulating the formation of osteoblastic bone and inhibiting osteoclastic bone resorption, according to Dr. Yamaguchi M at the University of Georgia(299).
Some researchers suggested that the increased the inflammatory response and worsens bone biomechanics by immunity may induce osteoporosis in animal with even a marginal zinc deficiency(300). And zinc deficiency can exaggerate the bone loss risk(293), especially with patient with diabetes(301).

7. Fluoride
Sodium fluoride, according to some researchers may be the most potent agent for treatment of spinal bone mass deficiency(302). In a randomized placebo-controlled trial of 65 postmenopausal osteoporosis, slow-release sodium fluoride (SR-NaF) or fluoride treatment, virtually eliminated new spinal fractures, vertebral fracture rate in comparison with placebo(303).
The University of Texas Southwestern Medical Center researchers insisted that used in conjunction with calcium citrate, slow-release sodium fluoride administered for about 2.5 years, improved vertebral fractures, increased spinal bone mass without decreasing the radial shaft bone density(304), especially in menopausal women(305).

Arthritis Is Curable
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By addressing the Underlying Causes through Clinical Trials and Studies

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(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)
(4) Hormone and bone by Francisco Bandeira1, Marise Lazaretti-Castro2, John P. Bilezikian3
(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)
(221) Osteoporosis prevention, diagnosis, and therapy by [No authors listed](PubMed)
(245) Protein Phosphatase 2A Mediates Oxidative Stress Induced Apoptosis in Osteoblasts by Huang CX1, Lv B1, Wang Y1.(PubMed)
(246) Hydrogen sulfide protects MC3T3-E1 osteoblastic cells against H2O2-induced oxidative damage-implications for the treatment of osteoporosis by Xu ZS1, Wang XY, Xiao DM, Hu LF, Lu M, Wu ZY, Bian JS.(PubMed)
(247) Antioxidant status in patients with osteoporosis: a controlled study by Sendur OF1, Turan Y, Tastaban E, Serter M.(PubMed)
(248) Role of antioxidant systems, lipid peroxidation, and nitric oxide in postmenopausal osteoporosis by Ozgocmen S1, Kaya H, Fadillioglu E, Aydogan R, Yilmaz Z.(PubMed)
(249) Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study by Maggio D1, Barabani M, Pierandrei M, Polidori MC, Catani M, Mecocci P, Senin U, Pacifici R, Cherubini A.(PubMed)
(250) Alterations of antioxidant enzymes and oxidative stress markers in aging by Kasapoglu M1, Ozben T.(PubMed)
(222) Eating Guidelines to Prevent Osteoporosis - It's Never Too Late! by dietitian of Canada
(273) Influence of the forms and levels of dietary selenium on antioxidant status and oxidative stress-related parameters in rainbow trout (Oncorhynchus mykiss) fry by Fontagné-Dicharry S1, Godin S2, Liu H1, Antony Jesu Prabhu P1, Bouyssière B2, Bueno M2, Tacon P3, Médale F1, Kaushik SJ1.(PubMed)
(274) The immune system is limited by oxidative stress: Dietary selenium promotes optimal antioxidative status and greatest immune defense in pacu Piaractus mesopotamicus by Biller-Takahashi JD1, Takahashi LS2, Mingatto FE3, Urbinati EC4.(PubMed)
(275) Selenium combined with vitamin E and vitamin C restores structural alterations of bones in heparin-inducedosteoporosis by Turan B1, Can B, Delilbasi E(PubMed)
(276) Dietary products consumption in relation to serum 25-hydroxyvitamin D and selenium level in Saudi children and adults by Al-Daghri NM1, Al-Attas O1, Yakout S1, Aljohani N2, Al-Fawaz H3, Alokail MS1.(PubMed)
(277) Simultaneous subchronic exposure to selenium and diazinon as possible risk factor for osteoporosis in adult male rats by Martiniaková M, Boboňová I, Omelka R, Grosskopf B1, Chovancová H, Spanková J, Toman R.(PubMed)
(278) Structural changes in femoral bone tissue of rats after subchronic peroral exposure to selenium by Martiniaková M1, Boboňová I, Omelka R, Grosskopf B, Stawarz R, Toman R.(PubMed)
(279) The protective effect of calcium on bone mass in postmenopausal women with high selenium intake by Pedrera-Zamorano JD1, Calderon-García JF, Roncero-Martin R, Mañas-Nuñez P, Moran JM, Lavado-Garcia JM.(PubMed)
(280) In vitro degradability, bioactivity and primary cell responses to bone cements containing mesoporousmagnesium-calcium silicate and calcium sulfate for bone regeneration by Ding Y1, Tang S1, Yu B2, Yan Y3, Li H3, Wei J4, Su J5.(PubMed)
(281) In vitro degradability, bioactivity and primary cell responses to bone cements containing mesoporous magnesium–calcium silicate and calcium sulfate for bone regeneratio by Yueting Ding, Songchao Tang, Baoqing Yu, Yonggang Yan, Hong Li, Jie Wei, Jiacan Su(The Royral Society)
(282) Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational Study by Orchard TS1, Larson JC, Alghothani N, Bout-Tabaku S, Cauley JA, Chen Z, LaCroix AZ, Wactawski-Wende J, Jackson RD.(PubMed)
(283) Bone. Maximizing bone health--magnesium, BMD and fractures by Nieves JW1.(PubMed)
(284) [Nutrition and bone health. Magnesium and bone].[Article in Japanese] by Ishimi Y1.(PubMed)
(285) The standardized creation of a lumbar spine vertebral compression fracture in a sheep osteoporosis model induced by ovariectomy, corticosteroid therapy and calcium/phosphorus/vitamin D-deficient diet by Eschler A1, Röpenack P2, Herlyn PK2, Roesner J3, Pille K2, Büsing K4, Vollmar B5, Mittlmeier T2, Gradl G6.(PubMed)
(286) Low vitamin D, and bone mineral density with depressive symptoms burden in menopausal and postmenopausalwomen by Bener A1, Saleh NM2.(PubMed)
(287) Calcium and vitamin D nutrition and bone disease of the elderly by Gennari C1.(PubMed)
(288) Prevention of hip fractures by correcting calcium and vitamin D insufficiencies in elderly people. by Meunier P1.(PubMed)
(289) Screening for Vitamin D Deficiency: Systematic Review for the U.S. Preventive Services Task Force Recommendation [Internet] by LeBlanc E, Chou R, Zakher B, Daeges M, Pappas M.(PubMed)
(290) Vitamin D and intestinal calcium absorption by Christakos S1, Dhawan P, Porta A, Mady LJ, Seth T.(PubMed)
(291) Copper, magnesium, zinc and calcium status in osteopenic and osteoporotic post-menopausal women by Mahdavi-Roshan M1, Ebrahimi M2, Ebrahimi A3.(PubMed)
(292) Magnesium, zinc and copper status in osteoporotic, osteopenic and normal post-menopausal women by Mutlu M1, Argun M, Kilic E, Saraymen R, Yazar S.(PubMed)
(293) Low serum levels of zinc, copper, and iron as risk factors for osteoporosis: a meta-analysis by Zheng J1, Mao X, Ling J, He Q, Quan J.(PubMed)
(294) Magnesium, zinc, copper, manganese, and selenium levels in postmenopausal women with osteoporosis. Can magnesium play a key role in osteoporosis? by Odabasi E1, Turan M, Aydin A, Akay C, Kutlu M.(PubMed)
(295) Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies by Samsel A1, Seneff S2.(PubMed)
(296) Effects of manganese deficiency on the microstructure of proximal tibia and OPG/RANKL gene expression in chicks by Liu R1, Jin C, Wang Z, Wang Z, Wang J, Wang L.(PubMed)
(297) Higher Dietary Acidity is Associated with Lower Bone Mineral Density in Postmenopausal Iranian Women, Independent of Dietary Calcium Intake by Shariati-Bafghi SE1, Nosrat-Mirshekarlou E, Karamati M, Rashidkhani B.(PubMed)
(298) Role of nutritional zinc in the prevention of osteoporosis by Yamaguchi M1.(PubMed)
(299) Nutritional factors and bone homeostasis: synergistic effect with zinc and genistein in osteogenesis by Yamaguchi M1(PubMed)
(300) Implications of compromised zinc status on bone loss associated with chronic inflammation in C57BL/6 mice by Chongwatpol P1, Rendina-Ruedy E1, Stoecker BJ1, Clarke SL1, Lucas EA1, Smith BJ1.(PubMed)
(301) Zinc deficiency exaggerates diabetic osteoporosis by Fushimi H1, Inoue T, Yamada Y, Horie 
(302) Sodium fluoride therapy of postmenopausal osteoporosis. by Kleerekoper M1, Mendlovic DB.(PubMed)
(303) Comparison of nonrandomized trials with slow-release sodium fluoride with a randomized placebo-controlled trial in postmenopausal osteoporosis by Pak CY1, Adams-Huet B, Sakhaee K, Bell NH, Licata A, Johnston C, Rubin B, Bonnick S, Piziak V, Graham H, Ballard J, Berger R, Fears W, Breslau N, Rubin C.(PubMed)
(304) Slow-release sodium fluoride in the management of postmenopausal osteoporosis. A randomized controlled trial by Pak CY1, Sakhaee K, Piziak V, Peterson RD, Breslau NA, Boyd P, Poindexter JR, Herzog J, Heard-Sakhaee A, Haynes S, Adams-Huet B, Reisch JS.(PubMed)
(305) Treatment of postmenopausal osteoporosis with slow-release sodium fluoride. Final report of a randomized controlled trial by Pak CY1, Sakhaee K, Adams-Huet B, Piziak V, Peterson RD, Poindexter JR.(PubMed)

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