Osteoporosis and Iron Overload
in [Arthritis]
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From: ironjustice on 3 Aug 2008 12:03 On Aug 3, 1:21 am, "Juhana Harju" <n...(a)mail.fi> wrote:I don't think that lactoferrin should be considered as an iron chelator _only_, because it has some other effects as well, e.g. it reduces bacterial growth. << The problem with your .. thinking .. is you fail to NOTICE the reason for its' .. antibacterial properties IS that very fact it DOES bind .. iron. Just like the tetracyclines .. "Iron chelation plays a prominent role in the tetracycline management of African trypanosomosis" Biokemistri Nigerian Society for Experimental Biology ISSN: 0795-8080 Vol. 16, No. 2, 2004, pp. 56-63 Bioline Code: bk04020 Full paper language: English Document available free of charge Biokemistri, Vol. 16, No. 2, 2004, pp. 56-63 Iron chelation excludes protein synthesis inhibition in the tetracycline management of African trypanosomosis Justine T. EKANEM, Titilayo O. JOHNSON, Iyabo S. ADENIRAN and Valeelat OKEOLA Abstract Ribonucleotide reductase, an iron requiring enzyme necessary in the production of deoxyribonucleotides required for replication in cell division and proliferation is induced during the S phase of the cell cycle. We have compared the trypanocidal properties of four antibiotics that show bactericidal activities by destabilizing ribosome-mRNA complex to inhibit protein synthesis. Tetracycline and oxytetracycline that have iron chelating properties extended the lifespan of trypanosome infected rats from 6 and 5 days of control to 15 and 12 days respectively while chloramphenicol and streptomycin that have no iron chelating properties could not extend the lifespan of infected rats. We confirm our earlier report that iron chelation plays a prominent role in the tetracycline management of African trypanosomosis. Keywords Tetracycline, iron chelation, T. brucei, growth inhibition © Copyright 2004 - Nigerian Society for Experimental Biology ---------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk . - Hide quoted text - - Show quoted text - > Therapeutic potential of iron chelators in diseases associated with > iron mismanagement. > Weinberg ED > J Pharm Pharmacol. 2006 May ; 58(5): 575-84 > A considerable array of diseases are now recognized to be associated > with misplacement of iron. Excessive deposits of the metal in > sensitive > tissue sites can result in formation of destructive hydroxyl radicals > as well as in stimulation of growth of neoplastic and microbial cell > invaders. To counteract potential iron damage, hosts employ the iron > chelators, transferrin and lactoferrin. These proteins have been > recently developed into pharmaceutical products. Additionally, a > variety of low molecular mass iron chelators are being used/tested to > treat whole body iron loading, and specific diseases for which the > metal is a known or suspected risk factor > ------------------------- > It is pretty straight forward. > First article finds .. lactoferrin .. an iron chelator .. allows > "phenomenal bone growth" > .. > THAT article was two years old .. > The article .. days old .. finds / recommends the .. iron > chelators .. > Because .. ? > "The results showed that this treatment / iron chelator mitigated the > loss of bone mass and the deterioration of bone micro-architecture." > Iron has been shown to lower bone density .. IRON .. specifically .. > Sooooo .. put the articles .. together .. and it seems the second > article / newest .. is CONFIRMED .. by the article two years .. old. > The REASON .. lactoferrin .. worked .. is iron chelation .. > "phenomenal bone growth" > Because .. ? Lactoferrin is .. an .. iron .. 'chelator' .. > Phlebotomy / venesection / bloodletting .. ALSO .. increases bone > mass .. leaves one with the thought .. "could it BE the iron .. ?" > ------------------ > "After phlebotomies bone mineral density of the lumbar spine > increased" > http://tinyurl.com/6bdw6m > Approximately 6 months after normalization of serum ferritin levels My view point is that both low and high iron levels can be detrimental to bone density. > ironjust...(a)aol.com wrote: > > On Jul 30, 12:13 am, "Juhana Harju" <n...(a)mail.fi> wrote:Association > > between iron overload and osteoporosis << > > > Age-associated Iron Accumulation in Bone: Implications for > > Postmenopausal Osteoporosis and a New Target for Prevention and > > Treatment by Chelation. > > Liu G, Men P, Kenner GH, Miller SC > > Biometals. 2006 May 11; > > > Iron accumulation in tissues is believed to be a characteristic of > > aged > > humans and a risk factor for some chronic diseases. However, it is > > not > > known whether age-associated iron accumulation is part of the > > pathogenesis of postmenopausal osteoporosis that affects > > approximately > > one out three women worldwide. Here, we confirmed that this > > accumulation of iron was associated with osteopenia in ovariectomized > > (OVX) rats (a model of peri- and postmenopausal osteoporosis due to > > estrogen deficiency). To further investigate whether the increased > > iron > > level plays a causal role in the onset of bone loss, we treated OVX > > rats with an orally active and bone targeted chelator that prevented > > iron accumulation in their skeletal tissues. The results showed that > > this treatment mitigated the loss of bone mass and the deterioration > > of > > bone micro-architecture. We also found that one possible mechanism of > > the protective action of iron chelation was to significantly reduce > > bone resorption. Thus, these findings provide a novel target and a > > potentially useful therapeutic strategy for the prevention and > > treatment of postmenopausal osteoporosis and perhaps other age- > > related > > diseases. > > > --------------------------------------------------- > > "phenomenal bone growth" > > > Lactoferrin discovered for osteoporosis treatment > > >www.chinaview.cn2004-11-25 14:44:25 > > > WELLINGTON, Nov. 25 (Xinhuanet) -- New Zealand researchers have > > discovered remarkable bone-building properties in the milk protein > > lactoferrin, which could lead to new treatments for osteoporosis. > > > Auckland's Osteoporosis Research Group has found that the milk > > protein, already produced commercially by New Zealand dairy giant > > Fonterra and the Tatua dairy company, not only inhibits bone > > breakdown > > but boosts bone growth four times faster than normal when injected > > directly into bone cells, New Zealand Press Association reported > > Thursday. > > > Research leader Jill Cornish unveiled the findings at the > > WorldDairy Summit in Melbourne Wednesday. > > > The injection of lactoferrin had resulted in such "phenomenal > > bone > > growth" and it could be applied directly to fractures to promote > > faster > > healing, Cornish said. > > > The research is part of the LactoPharma project - a joint venture > > between Fonterra and Auckland UniServices - set up to discover and > > commercialize new bioactive components in milk and colostrum. > > > There was still a lot of work to be done, Cornish said. But there > > was every reason to hope that these findings could result innew drugs > > and nutraceuticals for the prevention and cure of osteoporosis. > > > The dairy industry has touted the wider benefits of lactoferrin > > for > > about a decade. > > > "It's a goody molecule," Cornish said. "It is good for the immune > > system. It's anti-bacterial, anti-viral and anti-fungal. When white > > blood cells respond to infection, they spurt out lactoferrin > > naturally." > > > LactoPharma has already filed patent applications for lactoferrin > > as a bone-growth promoter. > > > It also plans to patent two new receptors that the team has > > uncovered on bone-forming cells. > > > Receptors and molecules like lactoferrin had a lock and key > > relationship, which together could activate the process that makes > > new > > bone, Cornish said. > > > Once Lacto Pharma has established the patents and put together > > aportfolio of intellectual property it will be in a position to > > commercially license the technology. > > > Fonterra will be well-positioned to develop it further but is > > likely to be most interested in developing lactoferrin as a > > nutraceutical to be consumed in dairy drinks and foods as a > > preventative to osteoporosis. > > > Osteoporosis is estimated to affect 200 million people worldwide, > > and costs New Zealand about 200 million NZ dollars (about 140 million > > US dollars) in health care and related costs. > > > So far there is only one osteoporosis drug on the market that can > > enhance the process of bone formation, Cornish said. > > > New Zealand dairy companies already commercially produce > > lactoferrin. It sells for 500 NZ dollars (about 350 US dollars) a > > kilogram in Japan and Korea. > > > About 10,000 tons of milk are used to produce one tonne of > > lactoferrin. Enditem > > > -------------- > > > "iron chelators, transferrin and lactoferrin counteract potential iron > > damage" > > That was an interesting posting, Tom. However, I don't think that > lactoferrin should be considered as an iron chelator _only_, because it has > some other effects as well, e.g. it reduces bacterial growth. > > > > > > > Therapeutic potential of iron chelators in diseases associated with > > iron mismanagement. > > Weinberg ED > > J Pharm Pharmacol. 2006 May ; 58(5): 575-84 > > > A considerable array of diseases are now recognized to be associated > > with misplacement of iron. Excessive deposits of the metal in > > sensitive > > tissue sites can result in formation of destructive hydroxyl radicals > > as well as in stimulation of growth of neoplastic and microbial cell > > invaders. To counteract potential iron damage, hosts employ the iron > > chelators, transferrin and lactoferrin. These proteins have been > > recently developed into pharmaceutical products. Additionally, a > > variety of low molecular mass iron chelators are being used/tested to > > treat whole body iron loading, and specific diseases for which the > > metal is a known or suspected risk factor > > > ------------------------- > > > It is pretty straight forward. > > > First article finds .. lactoferrin .. an iron chelator .. allows > > "phenomenal bone growth" > > .. > > > THAT article was two years old .. > > > The article .. days old .. finds / recommends the .. iron > > chelators .. > > > Because .. ? > > > "The results showed that this treatment / iron chelator mitigated the > > loss of bone mass and the deterioration of bone micro-architecture." > > > Iron has been shown to lower bone density .. IRON .. specifically .. > > > Sooooo .. put the articles .. together .. and it seems the second > > article / newest .. is CONFIRMED .. by the article two years .. old. > > > The REASON .. lactoferrin .. worked .. is iron chelation .. > > > "phenomenal bone growth" > > > Because .. ? Lactoferrin is .. an .. iron .. 'chelator' .. > > > Phlebotomy / venesection / bloodletting .. ALSO .. increases bone > > mass .. leaves one with the thought .. "could it BE the iron .. ?" > > > ------------------ > > > "After phlebotomies bone mineral density of the lumbar spine > > increased" > >http://tinyurl.com/6bdw6m > > > Approximately 6 months after normalization of serum ferritin levels > > My view point is that both low and high iron levels can be detrimental to > bone density. > > > was achieved by frequent phlebotomies, he became eugonadal and bone > > mineral density of the > > lumbar spine increased. > > Our observations suggest that osteoporosis might occur in the state of > > JH even at a young age, mainly due to the deprivation of sex steroids > > and the direct tissue toxicity of iron. > > > PMID: 15997423 > > > --------------------------------------------------------------------------- > > > "Bone density increased" > > > Effect of venesection on bone mineral density in an eugonadal woman > > with haemochromatosis. > > It should be noticed that haemochromatosis is a pathological condition. It > can not be concluded from this study that venesection would improve BMD in > healthy women. > > > > > J Gastroenterol Hepatol 1999 Feb;14(2):176-8 > > > Hibbert EJ, Fulcher GR, Coyle L, Gates F, Clifton-Bligh P, Stiel D > > > Department of Endocrinology, Royal North Shore Hospital, St Leonards, > > NSW, > > Australia. > > > BACKGROUND: > > A 41-year-old premenopausal woman with newly diagnosed > > haemochromatosis was found to have osteopenia on screening bone > > mineral densitometry. > > METHODS AND RESULTS: > > Liver biopsy showed grade 3 haemochromatosis with an hepatic iron > > index of 4. Investigation for secondary factors for osteopenia > > revealed no cause. > > The patient was clinically and biochemically eugonadal. Following > > venesection of 8 L blood (4 g iron) over 17 months and calcium > > supplementation, her bone density rose significantly. > > Neck of femur bone density increased by 6.0% over 13 months and lumbar > > vertebral bone density increased by 7.2%. There are no previous > > reports of response of b one density to venesection in eugonadal > > patients or in women with haemochromatosis. > > > PMID: 10029301, UI: 99151759 > > > ---------------------------------------------------------------- > > > Who loves ya. > > Tom > > > Jesus Was A Vegetarian! > >http://tinyurl.com/2r2nkh > > > Man Is A Herbivore! > >http://tinyurl.com/4rq595 > > > DEAD PEOPLE WALKING > >http://tinyurl.com/zk9fk > >> ironjustice wrote: > >>> Osteoporos Int. 2008 Jul 26. > >>> Association between iron overload and osteoporosis in patients with > >>> hereditary hemochromatosis. > > >> (1) J Nutr. 2003 Nov;133(11):3598-602. > >> Dietary iron is associated with bone mineral density in healthy > >> postmenopausal women. > >> Harris MM, Houtkooper LB, Stanford VA, Parkhill C, Weber JL, > >> Flint-Wagner H, Weiss L, Going SB, Lohman TG. > >> Department of Physiology, The University of Arizona, Tucson, AZ > >> 85721, USA. > > >> Healthy nonsmoking postmenopausal women (n = 242; ages 40-66 y) were > >> included in the Bone, Estrogen, and Strength Training (BEST) Study. > >> Bone mineral density (BMD) was measured at five sites (lumbar spine > >> L2-L4, trochanter, femur neck, Ward's triangle and total body) using > >> dual energy X-ray absorptiometry (DXA). Mean nutrient intakes were > >> assessed using > > ... > > read more »- Hide quoted text - > > - Show quoted text -- Hide quoted text - > > - Show quoted text -- Hide quoted text - > > - Show quoted text -
From: ironjustice on 8 Aug 2008 11:42
Osteoporos Int. 2008 Jul 26. Association between iron overload and osteoporosis in patients with hereditary hemochromatosis. Valenti L, Varenna M, Fracanzani AL, Rossi V, Fargion S, Sinigaglia L. Dipartimento di Medicina Interna, UO Medicina Interna IB, Padiglione Granelli, Universita degli Studi di Milano, Ospedale Policlinico Mangialli e Regina Elena Fondazione IRCCS, Via F Sforza 35, 20122, Milan, Italy. In 87 patients with hereditary hemochromatosis, osteoporosis was detected in 25%, and osteopenia in 41%. Bone mineral density was independently associated with BMI, ALP levels, hypogonadism/ menopause, and the amount of iron removed to reach depletion, but not with cirrhosis. Osteoporosis is influenced by iron overload in hemochromatosis. INTRODUCTION: To analyze prevalence, clinical characteristics and genetic background associated with osteoporosis in a retrospective study in Italian patients with hereditary hemochromatosis (HHC). METHODS: In 87 consecutive patients with HHC, bone mineral density was systematically evaluated by dual energy x-ray absorptiometry of the lumbar spine (n = 87) and femoral neck (n = 66). RESULTS: Osteoporosis was detected in 22 (25.3%), and osteopenia in 36 (41.4%) patients. Mean Z scores were -0.92 +/- 1.42 at lumbar spine and -0.35 +/- 1.41 at femoral neck. Lumbar spine T-score was independently associated with total ALP (p = 0.002), hypogonadism/menopause (p = 0.026), and iron overload (p = 0.033 for ferritin and p = 0.017 for iron removed). We observed a borderline significance for BMI (p = 0.069) and smoking status (p = 0.086). Lumbar spine osteoporosis was independently associated with lower BMI (OR 0.73, 95% CI 0.54-0.94), total ALP (OR 1.17, 95% CI 1-1.39 per 10 unit increase) and the amount of iron removed (OR 1.53, 95% CI 1-2.5 per 5 g increase). HFE genotypes did not differ between patients with and without osteoporosis. CONCLUSIONS: Osteoporosis is observed in a quarter of unselected patients with HHC, independently of the genetic background, and is associated with ALP, hypogonadism, body weight, and severity of iron overload. PMID: 18661088 ------------------------------ "iron overload contributed to the osteoporosis" Ascorbic acid deficiency, iron overload and alcohol abuse underlie the severe osteoporosis in black African patients with hip fractures--a bone histomorphometric study. Schnitzler CM, Schnaid E, MacPhail AP, Mesquita JM, Robson HJ Calcif Tissue Int. 2005 Feb ; 76(2): 79-89 Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order. Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/2r2nkh Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk |