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Online Library: Osteoporosis

The following pages provide an overview of the most recent research and clinical studies about the health benefits of micronutrients in fighting osteoporosis. This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.

We encourage you to forward the link to this important online library on natural health ? one of the largest ones in the world ? to your friends. You may also print out the articles you find most important for your own health condition and share them with your doctor. Any responsibly acting health professional will be grateful to receive such science-based health education.

Boron

A Novel Carborane Analog, BE360, With a Carbon-Containing Polyhedral Boron-Cluster Is a New Selective Estrogen Receptor Modulator for Bone

Source: Biochemical and Biophysical Research Communications 2009; 380(2): 218-222

Author: Hirata M., Inada M., Matsumoto C., Takita M., Ogawa T., Endo Y., Miyaura C.

Affiliation: Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan

Abstract: Carboranes are a class of carbon-containing polyhedral boron-cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors. Estrogen deficiency results in marked bone loss due to increased osteoclastic bone resorption in females, but estrogen replacement therapy is not generally used for postmenopausal osteoporosis due to the risk of uterine cancer. We synthesized a novel carborane compound BE360 to clarify its anti-osteoporosis activity. BE360 showed a high binding affinity to estrogen receptors (ER), ERalpha and ERbeta. In ovariectomized (OVX) mice, femoral bone volume was markedly reduced and BE360 dose-dependently restored bone loss in OVX mice. However, BE360 did not exhibit any estrogenic activity in the uterus. BE360 also restored bone loss in orchidectomized mice without androgenic action in the sex organs. Therefore, BE360 is a novel selective estrogen receptor modulator (SERM) that may offer a new therapy option for osteoporosis.

Boron and Fish Oil Have Different Beneficial Effects on Strength and Trabecular Microarchitecture of Bone

Source: Journal of Trace Elements in Medicine and Biology 2009; 28(3): 195-203

Author: Nielsen, F.H., Stoecker, B.J.

Affiliation:

Abstract: Osteoporosis and associated fractures are major health problems in the United States. Fruits and vegetables intakes have been associated with better bone health. These foods are rich in two nutrients, boron and omega-3 fatty acids, that have been suggested to be beneficial for bone formation and maintenance. Thus, an experiment with rats was performed to confirm the beneficial effects these two nutrients and to determine whether dietary fatty acid composition would affect changes in bone microarchitecture and strength induced by boron deprivation, or vice versa. Male rats were fed diets containing fish oil (high in omega-3 fatty acids) or safflower oil (high in omega-6 fatty acids), and either deficient or adequate in boron from pre-conception to maturity. Boron deficiency resulted in microarchitectural changes in vertebra bone that reduces bone strength. In addition, boron decreased the breaking strength of a long bone (femur). Feeding fish oil instead of safflower oil did not affect bone microarchitecture as markedly as boron, but did increase vertebral and femur bone strength. The findings indicate that boron and omega-3 fatty acids found in fish oil have beneficial effects on bone through different mechanisms, and the combination of the two nutrients was most beneficial for bone microarchitecture and strength. The findings suggest that boron and omega-3 fatty acids are two factors in fruits and vegetables providing some of the beneficial effects these foods have on bone health.

Therapeutic Effect of Dietary Boron Supplement on Retinoic Acid-Induced Osteoporosis in Rats

Source: Nan Fang Yi Ke Da Xue Xue Bao 2006; 26(12): 1785-1788

Author: Xu P., Hu W.B., Guo X., Zhang Y.G., Li Y.F., Yao J.F., Cai Q.K.

Affiliation: Department of Orthopedics, Xi'an Red Cross Hospital, Xi'an 710054, China

Abstract: The objective of this study was to observe the therapeutic efficacy of dietary boron supplement on retinoic acid-induced osteoporosis in rats, so as to provide experimental evidence for clinical management of osteoporosis with boron. Thirty-two SD rats were randomized into normal control group (8 rats) and osteoporotic group (24 rats), and osteoporosis was induced in rats of the latter group by intragastric retinoic acid administration at the daily dose of 80 mg/kg for 15 consecutive days. The osteoporotic rats were subdivided into control group (8 rats) without treatment, boron treatment group (8 rats) and estradiol treatment group (8 rats). After 30 days of treatment, the serum contents of Ca, P, boron and the activities of alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (TRAP) in the rats were assayed, the bone mineral density (BMD) of the whole body, lumbar vertebrae and tibia were determined, and the morphological changes of the femurs were observed. The study concludes that the dietary boron supplement can increase the serum content of boron of osteoporotic rats to stimulate bone formation and inhibit bone resorption, producing therefore obvious therapeutical effect against osteoporosis.

Calcium

Nutrition and Bone Health. Calcium Intake and Bone Health

Source: Clinical Calcium 2009; 19(11): 1664-1669

Author: Uenishi K.

Affiliation: Kagawa Nutrition University, Japan.

Abstract: How much calcium is required for bone health, in terms of gaining and maintaining bone minerals?In the Guidelines on the management and treatment of osteoporosis (2006) , 800 mg of calcium intake per day is recommended, and Dietary Reference Intakes for Japanese (2010) , which is aimed at healthy people, shows that the recommended dietary allowance of calcium for adult women is 600 - 650 mg/day. These amounts are based on assumption when sufficient bone minerals were secured at their growth periods. Because there is a significant relationship between calcium intake and bone mass, more calcium intake should be recommended.

Nutrition and Bone: It Is More Than Calcium And Vitamin D

Source: Women's Health 2009; 5(6): 727-737

Author: Morgan S.L.

Affiliation: Department of Nutrition Sciences & Department of Medicine, The University of Alabama at Birmingham (UAB), The UAB Osteoporosis Prevention & Treatment Clinic and Bone Densitometry Service, 354 Learning Resources Center, 1714 9th Avenue South Birmingham, AL 35294-1270, USA

Abstract: Unlike pharmacological agents that are taken for proscribed periods of time, food and nutrient intakes have the possibility of affecting bone health over the entire lifespan. While deficiencies or excesses of individual nutrients have been shown to affect bone, it is likely that individual foods or dietary patterns have important effects related to skeletal health. While biochemical mechanisms exist to relate a deficiency of vitamin K to altered bone metabolism, clinical trials related to supplementation of this nutrient have been confusing. It is likely that these disparate results are related to the fact that interactions of nutrients have not been considered or the possibility that suboptimal nutrient status is a marker of poor nutritional status. Vitamin A excess has been postulated to be related to high fracture risk; however, it is likely that retinol is not the best marker for the proposed interaction. Altering whole food patterns, such as the Dietary Approaches to Stop Hypertension diet, have demonstrated beneficial effects on bone metabolism. Individuals who select some vegetarian patterns may need to consider supplementation with nutrients such as calcium and protein. Future studies should center on whole food and dietary patterns and their relationship to bone metabolism and fracture risk.

Evaluation of a Care Pathway in the Initiation of Calcium and Vitamin D Treatment of Patients After Hip Fracture

Source: Canadian Journal on Aging 2009;28(1): 21-26

Author: Crilly R.G., Speechley M., Overend T.J., Mackenzie R., Simon S., Cremer S.

Affiliation: Faculty of Medicine, University of Western Ontario, Ontario, Canada

Abstract: Hip fractures, fragility fractures, indicate an increased risk for further fragility fractures. Although the way to define osteoporosis, requiring antiresorptive therapy, is not clear, all patients who have had hip fractures should be prescribed calcium and vitamin D at a minimum. In a retrospective chart review, we have explored the effectiveness of incorporating a standing recommendation (but not a standing order) for calcium and vitamin D treatment in a hip fracture care pathway, comparing units where the pathway had been implemented with those where it had not yet been started. The pathway resulted in significantly more initiation of calcium and vitamin D compared to patients not on the pathway (72% vs. 13.5%, p < 0.01). However, a follow-up study after four years showed a marked decline in the frequency of the initiation of calcium and vitamin D, suggesting the need for ongoing encouragement for the intervention to continue to be successful.

Reducing Fracture Risk with Calcium and Vitamin D

Source: Clinical Endocrinology 2009 Sep 10. [Epub ahead of print]

Author: Lips P., Bouillon R., van Schoor N.M., Vanderschueren D., Verschueren S., Kuchuk N., Milisen K., Boonen S.

Affiliation: Department of Endocrinology and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands

Abstract: This article tries to define the types of patients, both at risk of osteoporosis and with established disease, who may benefit from calcium and vitamin D supplementation. The importance of adequate compliance in these individuals is also discussed. For primary disease prevention, supplementation should be targeted to those with dietary insufficiencies. Several serum 25-hydroxyvitamin D (25(OH)D) cut-offs have been proposed to define vitamin D insufficiency (as opposed to adequate vitamin D status), ranging from 30 to 100 nmol/l. Based on the relationship between serum 25(OH)D, bone mineral density, bone turnover, lower extremity function and falls, the study suggest that 50 nmol/l is the appropriate serum 25(OH)D threshold to define vitamin D insufficiency. Supplementation should therefore generally aim to increase 25(OH)D levels within the 50-75 nmol/l range. This level can be achieved with a dose of 800 IU/day vitamin D, the dose that was used in succesfull fracture prevention studies to date; a randomized clinical trial assessing whether higher vitamin D doses achieve a greater reduction of fracture incidence would be of considerable interest.

Calcium Intake in Elderly Patients with Hip Fractures

Source: Food & Nutrition Research 2008; 52: 10.3402/fnr.v52i0.1654

Author: Cho K., Cederholm T., Lökk J.

Affiliation: Geriatric Department, Institution of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.

Abstract: The objective of this study was to investigate daily calcium intake in patients with low energy hip fractures during four consecutive years. In total 120 patients (mean age 78+/-8.5 (SD) years) were included between 2002 and 2005. The patients answered a structured food frequency questionnaire (FFQ) and interviews on patients' daily calcium intake from food and supplements took place during a 6-month period before the fracture. Dual energy X-ray absorptiometry (DEXA) was performed in a subgroup of 15 patients. The mean daily calcium intake from food and supplementation was 970+/-500 mg. However, 38% of patients had an intake below the recommended 800 mg/day. There was no significant relationship between calcium intake and age, gender, bone mineral density, serum calcium or albumin, type of fracture or body mass index. The study concludes that hip fracture patients had a mean calcium intake above the recommended daily intake, as assessed by a FFQ. The intake appeared to decrease over the investigated years. The relationship between calcium intake and fracture susceptibility is complex.

Changes in Biochemical Indices of Bone Metabolism in Post-Menopausal Women Following a Dietary Intervention with Fortified Dairy Products

Source: Journal of Human Nutrition and Dietetics 2009; 22(2): 156-65

Author: Manios Y., Moschonis G., Panagiotakos D.B., Farajian P., Trovas G., Lyritis G.P.

Affiliation: Department of Nutrition and Dietetics, Harokopio University of Athens, Athens, Greece.

Abstract: The present study aimed to examine whether calcium supplementation alone could be as effective in achieving favorable changes on bone metabolism indices of Greek post-menopausal women as a holistic dietary approach combining consumption of dairy products fortified with calcium and vitamin D(3) and nutrition counseling sessions for five winter months. A sample of 101 post-menopausal women was randomized to a dairy intervention group (IG: n = 39), receiving approximately 1200 mg of calcium and 7.5 micrograms of vitamin D(3) per day via fortified dairy products and attending biweekly nutrition counseling sessions; a calcium-supplemented group (SG: n = 26) receiving a total of 1200 mg calcium per day; and a control group (CG: n = 36). This study shows that the application of a holistic intervention approach combining nutrition counseling and consumption of fortified dairy products for five winter months induced some more favorable changes in IGF-I and PTH levels compared to calcium supplementation alone. Intervention periods longer than 5 months might be required to achieve significant differences among groups for bone remodeling biomarkers as well.

Short-Term High Dietary Calcium Intake During Bed Rest Has No Effect on Markers of Bone Turnover in Healthy Men

Source: Nutrition 2009 September 16. [Epub ahead of print]

Author: Baecker N., Frings-Meuthen P., Smith S.M., Heer M.

Affiliation: Deutsches Zentrum fuer Luft und Raumfahrt, Institute of Aerospace Medicine, Linder Hoehe, Cologne, Germany.

Abstract: Immobilization and space flight are causes of disuse osteoporosis. Increasing calcium intake may counteract this disuse-induced bone loss. This study involved two bedrest experiments (crossover design: bedrest versus ambulatory control) in a metabolic ward, studying the effect of 1000mg/d of calcium intake (study A, length of intervention 14 d) compared with that of a high calcium intake of 2000mg/d (study B, 6 d) on markers of bone turnover. Both studies were randomized, controlled studies with the subjects staying under well-controlled environmental conditions (study A, 9 male subjects, age 23.6+/-3.0 y; study B, 8 male subjects, age 25.5+/-2.9 y). Blood was drawn to analyze serum calcium, parathyroid hormone, procollagen type I C-terminal propeptide, and bone alkaline phosphatase. Urine (24-h) was collected for analysis of calcium, C-terminal telopeptide of collagen type I, and N-terminal telopeptide of collagen type I. The study concludes that doubling calcium intake to 2000mg/d does not prevent increased bone resorption induced by bedrest.

Determinant Factors of Osteoporosis Patients' Reported Therapeutic Adherence to Calcium and/or Vitamin D Supplements: a Cross-Sectional, Observational Study of Postmenopausal Women

Source: Drugs & Aging 2009; 26(10): 861-9

Author: Sanfelix-Genoves J., Gil-Guillen V.F., Orozco-Beltran D., Giner-Ruiz V., Pertusa-Martínez S., Reig-Moya B., Carratala C.

Affiliation: Nazaret's Health Centre, Department 5 CV, Valencia, Spain.

Abstract: The objective of the study was to analyze adherence to calcium and/or vitamin D treatment and to identify related predictors of non-adherence in a sample of postmenopausal women treated for osteoporosis in primary care. A cross-sectional, observational study was conducted in a sample of 630 postmenopausal women receiving pharmaceutical treatment for osteoporosis with vitamin D and/or calcium. Sociodemographic, general and osteoporosis-related data were collected. Patient's perceptions of the adverse effects of treatment, their knowledge of osteoporosis (Batalla test), their attitude towards treatment (Morisky-Green test) and their self-reported therapeutic adherence (Haynes-Sackett test) were assessed. The study concludes that only one in two postmenopausal women with osteoporosis who took calcium and/or vitamin D have good self-reported therapeutic adherence to this treatment. Determinant factors of adherence to calcium and/or vitamin D treatment were patient's attitude to the treatment, tolerability problems with the treatment and number of concurrent treatments.

EGCG (Epigallocatechin Gallate)

Epigallocatechin-3-Gallate Suppresses Osteoclast Differentiation and Ameliorates Experimental Arthritis in Mice

Source: Arthritis and Rheumatism 2008; 58(7): 2012-8

Author: Morinobu A., Biao W., Tanaka S., Horiuchi M., Jun L., Tsuji G., Sakai Y., Kurosaka M., Kumagai S.

Affiliation: Evidence-Based Laboratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Abstract: The objective of this study was to verify the effects of green tea cathechin-epigallocatechin-3-gallate (EGCG)- on differentiation of bone cells ?osteoclasts- and on experimental arthritis in mice. Human osteoclasts were differentiated from peripheral blood monocytes. The effects of EGCG were examined by tartrate-resistant acid phosphatase (TRAP) staining, bone resorption assay, Western blotting, and quantitative real-time polymerase chain reaction. Arthritis was induced in mice by injecting a cocktail of monoclonal antibodies against collagen. EGCG (20 microgram/gm body weight) was administered intraperitoneally every day from day 0 through the end of the experiments (day 15). The effects of EGCG were determined by assessments of joint swelling, histologic changes, and TRAP staining on day 15. The study concludes that EGCG suppressed osteoclast differentiation and ameliorated experimental arthritis in mice over the short term. It remains to be established whether EGCG is useful for the prevention and treatment of osteoporosis and rheumatoid arthritis.

Fish Oil (Omega-3-Fatty Acids)

An Increase in Dietary n-3 Fatty Acids Decreases a Marker of Bone Resorption in Humans

Source: Nutr Journal 2007; 6: 2

Author: Griel A.E., Kris-Etherton P.M., Hilpert K.F., Zhao G., West S.G., Corwin R.L.

Affiliation: Department of Nutritional Sciences, 126 S Henderson Bldg, The Pennsylvania State University, University Park, PA 16802, USA.

Abstract: This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA on bone turnover, assessed by serum concentrations of N-telopeptides (NTx) and bone-specific alkaline phosphatase (BSAP). Subjects (n = 23) consumed each diet for 6 weeks in a randomized, 3-period crossover design: 1) Average American Diet (AAD); 34% total fat, 13% saturated fatty acids (SFA), 13% monounsaturated fatty acids (MUFA), 9% polyunsaturated fatty acids (PUFA) (7.7% LA, 0.8% ALA)]), 2) Linoleic Acid Diet (LA; [37% total fat, 9% SFA, 12% MUFA, 16% PUFA (12.6% LA, 3.6% ALA)]), and 3) alpha-Linolenic Acid Diet (ALA; [38% total fat, 8% SFA, 12% MUFA, 17% PUFA (10.5% LA, 6.5% ALA)]). Walnuts and flaxseed oil were the predominant sources of ALA. Concentrations of NTx were positively correlated with the pro-inflammatory cytokine TNFalpha for all three diets. The results indicate that plant sources of dietary n-3 PUFA may have a protective effect on bone metabolism via a decrease in bone resorption in the presence of consistent levels of bone formation.

A Systematic Review of the Impact of n-3 Fatty Acids in Bone Health and Osteoporosis

Source: Medical Science Monitor 2008; 14(3): RA37-44

Author: Salari P., Rezaie A., Larijani B., Abdollahi M.

Affiliation: Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Abstract: Over the past several years evidence has been growing on the effects of dietary fatty acids on bone health. The objective of this paper was to provide a review of the current knowledge of dietary fatty acids and osteoporosis. Medline/Index Medicus and EMBASE/Excerpta Medica were searched for relevant papers regarding the effects of n-3 fatty acids on osteoporosis between 1963 and 2007 using the key words: osteoporosis, bone health, n-3 fatty acids, and PUFA. Bone mineral density and bone markers have been used in several animal studies to evaluate the beneficial effect of n-3 fatty acids on bone health and the prevention of osteoporosis. Generally, animal studies support the beneficial effects of n-3 fatty acids on bone health and osteoporosis; however, the dissimilar lipid metabolism in human and animals, the various study designs, and controversies over the human study outcomes make it difficult to draw a definite conclusion. The authors believe that conclusive findings in humans are still lacking in this area and it needs to be further investigated.

Effects of -3 Fatty Acids on Autoimmunity and Osteoporosis

Source: Frontiers in Bioscience 2008; 13: 4015-20

Author: Fernandes G., Bhattacharya A., Rahman M., Zaman K., Banu J.

Affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229-7868, USA.

Abstract: Decreased consumption of n-3 fatty acids (FA) and diets rich in animal proteins, saturated fats and n-6 vegetable oils are associated with a higher incidence of cardiovascular disease (CVD), certain malignancies and autoimmune disorders such as rheumatoid arthritis and Systemic Lupus Erythematosus (SLE), and renal disease. Recent studies show that reduced calorie intake and supplementation of diet with n-3 FA delays the onset of autoimmune renal disease, primarily, due to increased antioxidant enzyme activities, decreased NF-kappaB activation and decreased IL-1, IL-6 and TNF-alpha mRNA expression in the kidney tissue. Studies in rodents show that addition of n-3 FA and soy protein to diet affords protection against bone loss induced by ovariectomy in mice due to NF-kappaB expression and decreased activation of osteoclasts. Together, the available evidence show that increased daily intake of dietary n-3 FA decreases the severity of autoimmune disorders, lessens the chance of developing CVD, and protects against bone loss during post-menopause.

Green Tea

Protective Effect of Green Tea Polyphenols on Bone Loss in Middle-Aged Female Rats

Source: Osteoporos International 2008; 19(7): 979-90

Author: Shen C.L., Wang P., Guerrieri J., Yeh J.K., Wang J.S.

Affiliation: Department of Pathology, Texas Tech University Health Sciences Center, BB 198, 3601 4th street, Lubbock, TX, 79430-9097, USA.

Abstract: Recent studies suggested that green tea polyphenols (GTP) are promising agents for preventing bone loss in women. However, the mechanism related to the possible protective role of GTP in bone loss is not well understood. This study evaluated bioavailability, mechanisms, bone mass, and safety of GTP in preventing bone loss in middle-aged rats without (sham, SH) and with ovariectomy (OVX). The results show that there was no difference in femur bone mineral density between baseline and the SH+0.5% GTP group. Ovariectomy resulted in lower values for liver glutathione peroxidase activity, serum estradiol, and bone mineral density. GTP supplementation resulted in increased urinary epigallocatechin and epicatechin concentrations, liver glutathione peroxidase activity and femur bone mineral density, decreased urinary 8-hydroxy-2'-deoxyguanosine and urinary calcium levels, but no effect on serum estradiol and blood chemistry levels. The study concludes that a bone-protective role of GTP may contribute to an increase of antioxidant capacity and/or a decrease of oxidative stress damage.

Green Tea Polyphenols Mitigate Deterioration of Bone Microarchitecture in Middle-Aged Female Rats

Source: Bone 2009; 44(4): 684-90

Author: Shen C.L., Yeh J.K., Stoecker B.J., Chyu M.C., Wang J.S.

Affiliation: BB 198, 3601 4th Street, Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.

Abstract: The previous study demonstrated that green tea polyphenols (GTP) benefit bone health in middle-aged female rats without (sham, SH) and with ovariectomy (OVX), because of GTP's antioxidant capacity. The current study further evaluates whether GTP can restore bone micro-structure in both gonad-intact and gonadal-hormone-deficient middle-aged female rats. A 16-week study was performed based on a 2 (SH vs. OVX)x3 (no GTP, 0.1% GTP, and 0.5% GTP in drinking water) factorial design using 14-month-old female rats (n=10/group). An additional 10 rats were euthanized at the beginning of study to provide baseline parameters. Analysis using dual-energy X-ray absorptiometry, histomorphometry, and micro-computed tomography showed that GTP supplementation resulted in (a) increased trabecular volume, thickness, number, and bone formation of proximal tibia, periosteal bone formation rate of tibia shaft, and cortical thickness and area of femur, and (b) decreased trabecular separation and bone erosion of proximal tibia, and endocortical bone eroded surface of tibia shaft. The study concluds that drinking water supplemented with GTP mitigated deterioration of bone microarchitecture in both intact and ovariectomized middle-aged female rats by suppressing bone erosion, enhancing bone formation, and modulating endocortical and cancellous bone compartments, resulting in a larger net bone volume.

Green Tea and Bone Metabolism

Source: Nutrition Research 2009; 29(7): 437-56

Author: Shen C.L., Yeh J.K., Cao J.J., Wang J.S.

Affiliation: Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX 79430-9097, USA.

Abstract: Ingestion of green tea and green tea bioactive compounds may be beneficial in mitigating bone loss of this population and decreasing their risk of osteoporotic fractures. This review describes the effect of green tea or its bioactive components on bone health, with an emphasis on (i) the prevalence and etiology of osteoporosis; (ii) the role of oxidative stress and antioxidants in osteoporosis; (iii) green tea composition and bioavailability; (iv) the effects of green tea and its active components on osteogenesis (bone density), osteoblastogenesis (formation of bone building cells), and osteoclastogenesis (formation of bone resorbing cells )from human epidemiological, animal, as well as cell culture studies; (v) possible mechanisms explaining the osteoprotective effects of green tea bioactive compounds; (vi) other bioactive components in tea that benefit bone health; and (vii) a summary and future direction of green tea and bone health research and the translational aspects. In general, tea and its bioactive components might decrease the risk of fracture by improving bone mineral density and supporting osteoblastic activities while suppressing osteoclastic activities.

Green Tea Polyphenols and Tai Chi for Bone Health: Designing a Placebo-Controlled Randomized Trial

Source: BMC Musculoskelet Disorders 2009; 10: 110

Author: Shen C.L., Chyu M.C., Yeh J.K., Felton C.K., Xu K.T., Pence B.C., Wang J.S.

Affiliation: Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.

Abstract: Tea consumption may be beneficial to osteoporosis due to its antioxidant capability. This study was designed to test an intervention including green tea polyphenols (GTP) and TC exercise for feasibility, and to quantitatively assess their individual and interactive effects on postmenopausal women with osteopenia. One hundred and forty postmenopausal women with osteopenia (defined as bone mineral density T-score at the spine and/or hip between 1 to 2.5 SD below the reference database) were randomly assigned to 4 treatment arms: (1) placebo group receiving 500 mg medicinal starch daily, (2) GTP group receiving 500 mg of GTP per day, (3) placebo+TC group receiving both placebo treatment and TC training (60-minute group exercise, 3 times per week), and (4) GTP+TC group receiving both GTP and TC training for 24 weeks. The outcome measures were bone formation biomarker (serum bone alkaline phosphatase), bone resorption biomarker (serum tartrate resistant acid phosphatase), and oxidative DNA damage biomarker (urinary 8-hydroxy-2'-deoxyguanosine). All outcome measures were determined at baseline, 4, 12, and 24 weeks. This study presents the rationale, design, and methodology of a placebo-controlled randomized trial to investigate a new complementary and alternative medicine strategy featuring a dietary supplement and a mind-body exercise for alleviating bone loss in osteopenic postmenopausal women.

Lysine

L-Arginine and L-Lysine Stimulation on Cultured Human Osteoblasts

Source: Biomedicine & Pharmacotherapy 2002; 56(10): 492-7

Author: Torricelli P., Fini M., Giavaresi G., Giardino R., Gnudi S., Nicolini A., Carpi A.

Affiliation: Experimental Surgery Department, Research Institute Codivilla-Putti, Rizzoli Orthopedic Institute, Servizio di Chirurgia Sperimentale, via di Barbiano 1/10, 40136 Bologna, Italy.

Abstract: Essential amino acids, such as L-Arginine (Arg) and L-Lysine (Lys), are involved in bone metabolism and growth. This study evaluated the effect of L-Arg and L-Lys on cultured human osteoblasts. Primary human osteoblast cultures were divided into four groups: the Arg Group received 0.625 mg/ml per day of Arg, the Lys Group 0.587 mg/ml per day of Lys, the Arg-Lys Group received both amino acids, whereas the Control Group was sham-treated. Lys administration over the same time interval mainly affected cell proliferation, as evidenced by the MTT test and immunostaining for PDGF. The same positive effects evidenced by the single administrations of the two amino acids resulted from their simultaneous administration. However, synergism could be demonstrated only for the decrease in the level of IL-6. Arg and Lys show a positive effect on human osteoblasts, which is related partly to the production of those factors required for matrix synthesis, and partly to the direct or mediated activation of cell proliferation.

Human Osteopenic Bone-Derived Osteoblasts: Essential Amino Acids Treatment Effects

Source: Artificial Cells, Blood Substitutes, and Immobilization Biotechnology 2003; 31(1): 35-46

Author: Torricelli P., Fini M., Giavaresi G., Giardino R.

Affiliation: Experimental Surgery Department, Research Institute Codivilla-Putti, Rizzoli Orthopedic Institute, Bologna, Italy.

Abstract: After analyzing the effect of two essential amino acids, L-arginine (Arg) and L-lysine (Lys), in previous in vitro and in vivo studies, the present authors investigated the administration of Arg and Lys in osteoblasts derived from human osteopenic bone. After isolation, osteoblasts were cultured in DMEM supplemented with either Arg (0.625 mg/ml/day, Arg Group) or Lys (0.587 mg/ml/day, Lys Group), or both of them (Arg-Lys Group), whereas the Control Group was sham-treated. Results were compared with those obtained from human healthy bone to verify the effect of the amino acids on osteoblasts derived from pathological tissue. In addition, a comparison was also made with the results obtained from rat osteopenic bone to assess reliability of the in vitro model. The current results support previous findings and indicate that Arg and Lys stimulation has a positive effect on osteoblast proliferation, activation and differentiation. Therefore, administration of these amino acids may be useful in clinical treatment and prevention of osteoporosis.

Reductions in Degree of Mineralization and Enzymatic Collagen Cross-Links and Increases in Glycation-Induced Pentosidine in the Femoral Neck Cortex in Cases of Femoral Neck Fracture

Source: Osteoporos International 2006; 17(7): 986-95

Author: Saito M., Fujii K., Soshi S., Tanaka T.

Affiliation: Department of Orthopaedic Surgery, Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.

Abstract: The aim of our study was to understand the distinctive posttranslational modifications of collagen in areas with different degrees of mineralization with and without hip fracture. Sixteen female cases of intracapsular hip fracture (78+/-6 years) and 16 age- and gender-matched postmortem controls (76+/-6 years) were included in this study. A sample of each femoral neck cortex was fractionated into low (1.7 to 2.0 g/ml) and high (>2.0 g/ml) density portions. The contents of enzymatic cross-links (dihydroxylysinonorleucine, hydroxylysinonorleucine, lysinonorleucine, pyridinoline, and deoxypyridinoline) and nonenzymatic cross-links (pentosidine) and the extent of lysine (Lys) hydroxylation were determined in each fraction. The results show that pentosidine content of low-mineralized bone was significantly higher in fracture cases than in controls (p<0.0001). The extent of Lys hydroxylation was significantly higher in fracture cases than in controls (p<0.001). The higher hydroxylation of Lys in collagen from fracture cases relative to controls was associated with significantly higher values of hydroxylysine-derived cross-link such that the enzymatic cross-link patterns correlated with the extent of Lys hydroxylation in the collagen molecules. These results suggest that reductions in the degree of mineralization and enzymatic cross-links and excessive formation of pentosidine may play an important role in explaining poor bone quality in osteoporosis.

Biochemical Markers of Bone Turnover. New Aspect. Bone Collagen Metabolism: New Biological Markers for Estimation of Bone Quality

Source: Clinical Calcium 2009; 19(8): 1110-7

Author: Saito M.

Affiliation: Department of Orthopaedic Surgery, Jikei University of Medicine. Japan

Abstract: Collagen cross-links play important roles in the expression of bone strength and the proper biological function of bone. The cross-links of collagen can be roughly divided into two types : lysyl oxidase mediated cross-links (enzymatic immature and mature cross-links) and advanced glycation end-products (AGEs ; nonenzymatic cross-links, pentosidine) . Recently, the study showed that reduction in enzymatic cross-links and excessive formation of nonenzymatic cross-links, pentosidine in bone could be important for explaining the variation of fracture susceptibility in osteoporosis (Osteoporos. Int. 17 (7) : 986-995, 2006) and diabetes (Osteoporos. Int. 17 (10) : 1514-1523, 2006) . In this review, the author summarizes the recent literatures regarding bone quality markers.

Magnesium

Reduction of Dietary Magnesium by Only 50% in the Rat Disrupts Bone and Mineral Metabolism

Source: Osteoporosis International 2006; 17(7): 1022-32

Author: Rude R.K., Gruber H.E., Norton H.J., Wei L.Y., Frausto A., Kilburn J.

Affiliation: University of Southern California and the Orthopaedic Hospital, 1975 Zonal Ave., GNH 6602, Los Angeles, CA 90089-9317, USA.

Abstract: The objective of this study was to determine the effect of a moderate reduction of dietary magnesium [50% of nutrient requirement (50% NR)] on bone and mineral metabolism in the rat, and to explore possible mechanisms for the resultant reduced bone mass. Female rats were 6 weeks of age at the start of study. Serum magnesium (Mg), calcium (Ca), parathyroid hormone (PTH), 1,25(OH)(2)-vitamin D, alkaline phosphatase, osteocalcin, and pyridinoline were measured during the study at 3- and 6-month time points in control (dietary Mg of 100% NR) and Mg-deficient animals (dietary Mg at 50% NR). Femurs and tibias were also collected for mineral content analyses, micro-computerized tomography, histomorphometry, and immunohistochemical localization of substance P, TNFalpha, and IL-1beta at 3 and 6 months. The study data demonstrate that Mg intake of 50% NR in the rat causes a reduced bone mineral content and reduced volume of the distal femur. These changes may be related to altered PTH and 1,25(OH)(2)-vitamin D formation or action as well as to an increase release of substance P and the inflammatory cytokines TNFalpha and IL-1beta.

Magnesium Intake From Food and Supplements Is Associated With Bone Mineral Density in Healthy Older White Subjects

Source: Journal of the American Geriatrics Society 2005; 53(11): 1875-80

Author: Ryder K.M., Shorr R.I., Bush A.J., Kritchevsky S.B., Harris T., Stone K, Cauley J., Tylavsky F.A.

Affiliation: Department of Medicine, Health Science Center, University of Tennessee, Memphis, Tennessee 38105, USA.

Abstract: The objective of this study was to determine whether magnesium intake from supplemental and dietary sources is associated with bone mineral density (BMD) in older men and women. Two thousand thirty-eight older black and white men and women aged 70 to 79 at baseline enrolled in the Health, Aging and Body Composition Study. Dietary intake of magnesium was assessed using a semiquantitative food frequency questionnaire, and supplement data were collected based on a medication inventory. BMD of the whole body was obtained using a fan-beam densitometer. Additional covariates included age, body mass index (BMI), smoking status, alcohol use, physical activity, estrogen use, and supplemental calcium (Ca) and vitamin D use. The study concludes that greater magnesium intake was significantly related to higher BMD in white women and men. The lack of association observed in black women and men may be related to differences in Ca regulation or in nutrient reporting.

Prevention of Osteoporosis by Foods and Dietary Supplements. Magnesium and Bone Metabolism

Source: Clinical Calcium 2006; 16(10): 1655-60

Author: Matsuzaki H.

Affiliation: Junior College of Tokyo University of Agriculture, Department of Nutrition. Japan.

Abstract: About half the total magnesium (Mg) of the body is existed in bone. Bone is one of the main Mg pools in the body. Epidemiologic studies have demonstrated a positive correlation between Mg intake and bone mineral density. It is also reported that Mg deficiency induced a decrease in osteoblasts number, an increase in osteoclasts number and a decrease in bone strength in rats. In contrast, dietary Mg supplementation improved bone formation, bone resorption and bone strength in ovariectomized rats. Mg deficiency is known as a risk factor for osteoporosis, since Mg is essential mineral for normal bone growth. However, the detail of effects of Mg on bone metabolism remains unclear. Further studies should be developed to clarify the details.

Changes of Total Content of Serum magnesium in Elderly Chinese Women with Osteoporosis

Source: Biological Trace Element Research 2006; 110(3): 223-31

Author: Wang S., Lin S., Zhou Y.

Affiliation: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, PR China.

Abstract: The aim of this study was to explore whether the serum levels of magnesium (Mg) and calcium (Ca) differ between osteoporotic and nonosteoporotic elderly Chinese women. Using WHO classification criteria based on bone mineral density (BMD), general healthy Chinese women older than 65 yr were classified as osteoporosis (OP), osteopenia, and normal group according to the T-score of the femur neck. Then their physical characteristics, serum levels of magnesium (sMg), calcium (sCa), and other biochemical measurements were analyzed. Altogether, 324 subjects were included in the final analysis with 77 in OP, 137 in osteopenia, 110 in normal group. The study concludes that high content of sMg and potentially low content of sCa could be a feature of the serum profile of elderly Chinese women with OP, the clinical significance of which needs further elucidation. Supplementation of Mg for elderly Chinese women with OP did not appear to be necessary.

Magnesium, Zinc and Copper Status in Osteoporotic, Osteopenic and Normal Post-menopausal Women

Source: The Journal of International Medical Research 2007; 35(5): 692-5

Author: Mutlu M., Argun M., Kilic E., Saraymen R., Yazar S.

Affiliation: Department of Orthopaedics, Medical Faculty, Erciyes University, Kayseri, Turkey.

Abstract: Serum concentrations of magnesium, zinc and copper were measured in postmenopausal women with osteoporosis (n = 40), osteopenia (n = 40) or normal bone mineral density (n = 40) as classified on the basis of the T-score of the femur neck and dual energy X-ray absorptiometry results. Mean concentrations of magnesium and zinc were significantly lower in osteoporotic women than in both osteopenic women and normal women. In addition, magnesium and zinc concentrations in osteopenic women were significantly lower than in normal women. There were no statistically significant differences observed between the osteopenic, osteoporotic and control groups with respect to copper levels. The clinical significance of these changes needs further elucidation, but trace element supplementation, especially with magnesium and zinc and perhaps copper, may have beneficial effects on bone density.

A Case of Magnesium Deficiency Associated with Insufficient Parathyroid Hormone Action and Severe Osteoporosis

Source: Endocrine Journal 2007; 54(6): 935-40

Author: Kanazawa I., Yamamoto M., Yamaguchi T., Yamauchi M., Yano S., Sugimoto T.

Affiliation: Department of Internal Medicine 1, Shimane University Faculty of Medicine, Shimane, Japan.

Abstract: This study reports a case of an 82-year-old woman with a giant adenomatous goiter and severe osteoporosis with multiple vertebral fractures, whose clinical course indicated that her osteoporosis was probably due to Mg deficiency. Laboratory data showed the existence of hypomagnesemia, hypocalcemia, hypokalemia, vitamin D deficiency, and slightly elevated intact PTH. Intravenous administration of Mg not only improved these electrolyte abnormalities but also increased serum levels of intact PTH, bone formation markers, 1,25-dihydroxyvitamin D, as well as bone resorption markers in the urine, and lowered urinary phosphate reabsorption. Mg deficiency in this case seemed to cause impaired secretion of PTH from the parathyroid and the refractoriness of bone and kidney to the hormone, which led to the suppression of both bone remodeling and renal vitamin D production. These processes were probably linked to her severe osteoporosis, which was reversed by Mg supplementation.

Magnesium, Zinc, Copper, Manganese, and Selenium Levels in Postmenopausal Women with Osteoporosis. Can Magnesium Play a Key Role in Osteoporosis?

Source: Annals of the Academy of Medicine, Singapore 2008; 37(7): 564-7

Author: Odabasi E., Turan M., Aydin A., Akay C., Kutlu M.

Affiliation: Gulhane School of Medicine, Department of Medical Ecology and Hydroclimatology, Ankara, Turkey.

Abstract: The aim of the study was to assess the plasma and red blood concentrations of some elements in postmenopausal women with osteoporosis. Seventy-seven postmenopausal women with osteoporosis aged 61 years (median interquartile range, 7.5; range, 46 to 74) and 61 age- and BMI-matched healthy postmenopausal women aged 60 years (median interquartile range, 8.0; range, 44 to 76) were included in the study. Element concentrations in plasma and red blood cells including magnesium (Mg), zinc, copper, manganese, and selenium were measured by atomic absorption spectrophotometry in both postmenopausal women with osteoporosis and healthy postmenopausal women. Only statistically significant difference between the osteoporotic (51.51 [15.40] microgram/mL) and healthy subjects (54.54 [15.42] microgram/mL) was observed in red blood cell (RBC) magnesium concentration (Z=-2.07, P=0.039). However, no significant difference was found between patient and control groups, both in plasma and in red blood concentrations, for zinc, copper, manganese, and selenium. The study concludes that Mg levels in red blood cells are significantly lower in postmenopausal women with osteoporosis. It is concluded that Mg transport mechanism(s) into the cell could be affected in patients with osteoporosis.

Short-Term Oral Magnesium Supplementation Suppresses Bone Turnover in Postmenopausal Osteoporotic Women

Source: Biological Trace Element Research 2009 June 2. [Epub ahead of print]

Author: Aydın H., Deyneli O., Yavuz D., Gozu H., Mutlu N., Kaygusuz I., Akalın S.

Affiliation: Department of Internal Medicine, Section of Endocrinology and Metabolism, Yeditepe University Hospital, Devlet Yolu Ankara Cad. No: 102, Kozyatagi, Istanbul, 34752, Turkey.

Abstract: In this study, the effects of daily oral magnesium supplementation on biochemical markers of bone turnover were investigated. Twenty postmenopausal women have been divided into two groups. Ten patients were given magnesium citrate (1,830 mg/day) orally for 30 days. Ten postmenopausal women of matching age, menopause duration, and BMI were recruited as the control group and followed without any medication. Fasting blood and first-void urine samples were collected on days 0, 1, 5, 10, 20, and 30, respectively. Total magnesium, calcium, phosphorus, iPTH and osteocalcin were determined in blood samples. Deoxypyridinoline levels adjusted for creatinine were measured in urine samples. Thirty consecutive days of oral magnesium supplementation caused significantly decrease in serum iPTH levels in the Mg-supplemented group (p < 0.05). Serum osteocalcin levels were significantly increased (p < 0.001) and urinary deoxypyridinoline levels were decreased (p < 0.001) in the Mg-supplemented group. This study has demonstrated that oral magnesium supplementation in postmenopausal osteoporotic women suppresses bone turnover.

Skeletal and Hormonal Effects of Magnesium Deficiency

Source: Journal of the American College of Nutrition 2009; 28(2): 131-41

Author: Rude R.K., Singer F.R., Gruber H.E.

Affiliation: USC Keck School of Medicine, Los Angeles, CA, USA.

Abstract: The objective of this paper is to review the evidence for Mg deficiency-induced osteoporosis and potential reasons why this occurs, including a cumulative review of work in our laboratories and well as a review of other published studies linking Mg deficiency to osteoporosis. Epidemiological studies have linked dietary Mg deficiency to osteoporosis. As diets deficient in Mg are also deficient in other nutrients that may affect bone, studies have been carried out with select dietary Mg depletion in animal models. Severe Mg deficiency in the rat (Mg at <0.0002% of total diet; normal = 0.05%) causes impaired bone growth, osteopenia and skeletal fragility. This degree of Mg deficiency probably does not commonly exist in the human population. In this study dietary Mg deprivation was induced in the rat at 10%, 25% and 50% of recommended nutrient requirement. We observed bone loss, decrease in osteoblasts, and an increase in osteoclasts by histomorphometry. Such reduced Mg intake levels are present in our population. The study also investigated potential mechanisms for bone loss in Mg deficiency. The data support the notion at dietary Mg intake at levels not uncommon in humans may perturb bone and mineral metabolism and be a risk factor for osteoporosis.

Nutrient Combinations

Influence of Nutrients Intake on Bone Turnover Markers

Source: Clinical Calcium 2005; 15(9): 1529-34

Author: Katsuyama H., Sunami S., Fukunaga M.

Affiliation: Department of Public Health, Kawasaki Medical School.

Abstract: Bone strength is determined by bone mineral density and bone quality. Bone quality can be assessed by only bone turnover markers. Nutrients that reduce bone resorption markers are calcium and isoflavone, nutrients that increase bone formation markers are vitamin C, vitamin D and vitamin K. These nutrients affect bone turnover and, as a result, improve bone density. These nutrients might contribute to prevent the incidence of osteoporosis when they are taken from adolescence.

Association of Hip Fracture Incidence and Intake of Calcium, Magnesium, Vitamin D, and Vitamin K

Source: European Journal of Epidemiology 2008; 23(3): 219-25

Author: Yaegashi Y., Onoda T., Tanno K., Kuribayashi T., Sakata K., Orimo H.

Affiliation: Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 020-8505, Japan.

Abstract: The aim of this study was to analyze the association between hip fracture incidence in 12 regional blocks within Japan and dietary intake of four key nutrients: calcium, magnesium, vitamin D, and vitamin K. Using data from the 2002 national survey on the incidence of hip fracture and the National Nutritional Survey of Japan, a standardized incidence ratio of hip fracture was calculated, and the association between the standardized incidence ratio and each nutritional intake was assessed for each region using Pearson's correlation coefficient and partial correlation analysis. RESULTS: There were significant correlations between the standardized incidence ratio by region and magnesium, vitamin D, and vitamin K in both men and women, and calcium in women. The strongest inverse correlations were found in vitamin K in both men and women (r = -0.844, P = 0.001, and r = -0.834, P = 0.001, respectively). After adjusting for calcium, magnesium, and vitamin D, the partial correlation between the standardized incidence ratio by regional block and vitamin K was strongest in both men and women (partial correlation coefficient, pcc = -0.673, P = 0.04; pcc = -0.575, P = 0.106, respectively).

Comparison Between Dietary Assessment Methods for Determining Associations Between Nutrient Intakes and Bone Mineral Density in Postmenopausal Women

Source: Journal of the American Dietetic Association 2009; 109(5): 899-904

Author: Farrell V.A., Harris M., Lohman T.G., Going S.B., Thomson C.A., Weber J.L., Houtkooper L.B.

Affiliation: Department of Nutritional Sciences, University of Arizona, Shantz 118, PO Box 210038, Tucson, AZ 85721, USA.

Abstract: The goal of this study was to compare the equivalency of nutrient intakes assessed by diet records and the Arizona Food Frequency Questionnaire and the associations of these nutrients with bone mineral density (BMD). This is a secondary analysis of cross-sectional data that was analyzed from six cohorts (fall 1995 to fall 1997) of postmenopausal women (n=244; 55.7+/-4.6 years) participating in a 12-month, block-randomized, clinical trial. One-year dietary intakes were assessed using 8 days of diet records and the Arizona Food Frequency Questionnaire. Participants' BMD was measured at the lumbar spine (L2-L4), femur trochanter, femur neck, Ward's triangle, and total body using dual-energy x-ray absorptiometry. Linear regression analyses (P< or =0.05) were adjusted for the effects of exercise, hormone therapy use, body weight at 1 year, years post menopause, and total energy intake. Significant correlations (r=0.30 to 0.70, P< or =0.05) between dietary assessment methods were found with all dietary intake variables. Iron and magnesium were consistently and significantly positively associated with BMD at all bone sites regardless of the dietary assessment method. Zinc, dietary calcium, phosphorous, potassium, total calcium, and fiber intakes were positively associated with BMD at three or more of the same bone sites regardless of the dietary assessment method.

Nutrient Intakes Related to Osteoporotic Fractures in Men and Women-the Brazilian Osteoporosis Study (BRAZOS)

Source: Nutrition Journal 2009; 8: 6

Author: Pinheiro M.M., Schuch N.J., Genaro P.S., Ciconelli R.M., Ferraz M.B., Martini L.A.

Affiliation: Rheumatology Division, Universidade Federal de Sao Paulo/EPM, Sao Paulo, Brazil.

Abstract: The aim of the present study was to evaluate bone health-related nutrients intake and its association with osteoporotic fractures in a representative sample of 2344 individuals aged 40 years or older in Brazil. In a transversal population-based study, a total of 2420 individuals over 40 years old were evaluated from March to April 2006. Participants were men and women from all socio-economic classes and education levels living around the Brazilian territory Individuals responded a questionnaire including self reported fractures as well a 24-hour food recall. Nutrient intakes were evaluated by Nutrition Data System for Research software (NDSR, University of Minnesota, 2007). Low trauma fracture was defined as that resulting of a fall from standing height or less. Fractures were reported by 13% of men and 15% of women. Women with fractures presented significantly higher calcium, phosphorus and magnesium intakes. However, in all regions and socio-economical levels mean intakes of bone related nutrients were below the recommended levels. It was demonstrated that for every 100 mg/phosphorus increase the risk of fractures by 9% (OR 1.09; IC95% 1.05-1.13, p < 0.001). The results demonstrated inadequacies in bone related nutrients in our population as well that an increase in phosphorus intake is related to bone fractures.

Nutrition and Bone Health. Present Knowledge and Practice

Source: Clinical Calcium 2009; 19(7): 1028-31

Author: Uenishi K.

Affiliation: Kagawa Nutrition University. Japan

Abstract: All the components which constitute our body are reconstructed from the nutrients taken in as the foods. Bone is also the same and various nutrients are involving for the formation and maintenance. Calcium, vitamin D, protein, vitamin K, magnesium, zinc, vitamin B groups, vitamin A, etc. are important for bone health. Moreover, the importance of fruit and vegetables is also suggested.

Proline

Leucine7 to Proline7 Polymorphism in Prepro-NPY Gene and Femoral Neck Bone Mineral Density in Postmenopausal Women

Source: Bone 2004; 35(3): 589-94

Author: Heikkinen A.M., Niskanen L.K., Salmi J.A., Koulu M., Pesonen U., Uusitupa M.I., Komulainen M.H., Tuppurainen M.T., Kröger H., Jurvelin J., Saarikoski S.

Affiliation: Department of Obstetrics and Gynecology, Kuopio University Hospital, FIN-70211 Kuopio, Finland.

Abstract: Neuropeptide Y (NPY) is a versatile neurotransmitter that has recently been shown to regulate bone metabolism in animal and in vitro studies. This study examined the influence of leucine7-to-proline7 (Leu7/Pro7) polymorphism of the NPY signal peptide gene on bone mineral density (BMD) before and after a 5-year hormone replacement therapy (HRT) in 316 early postmenopausal women participating in a randomized controlled trial nested in the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The participants were randomized into two treatment groups: the HRT group (n = 146) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate and calcium lactate, 500 mg/day (equal to 93 mg Ca2+) alone or in combination with vitamin D3, 100-300 IU/day. The non-HRT group (n = 170) received calcium lactate, 500 mg alone or in combination with vitamin D3, 100-300 IU/day. At baseline, there were no significant differences in the lumbar or femoral neck BMD between the subjects who had Leu7Pro7 polymorphism and the normal subjects. After 5 years, the BMD of the femoral neck remained unaltered and that of the lumbar spine increased by 1.7% in the HRT group, whereas both BMDs were decreased by 4-5% in the non-HRT group. After 5 years, the femoral neck BMD was significantly lower in those with the wild-type NPY polymorphism than in those with Leu7/Pro7 polymorphism (P = 0.040) in the non-HRT group. The study concludes that the Leu7/Pro7 polymorphism in NPY signal gene may favorably affect femoral neck BMD in postmenopausal women.

Proline-Rich Tyrosine Kinase 2 Regulates Osteoprogenitor Cells and Bone Formation, and Offers an Anabolic Treatment Approach for Osteoporosis

Source: Proceedings of the National Academy of Sciences of the United States of America 2007; 104(25): 10619-24

Author: Buckbinder L., Crawford D.T., Qi H., Ke H.Z., Olson L.M., Long K.R., Bonnette P.C., Baumann A.P., Hambor J.E., Grasser W.A. 3rd, Pan L.C., Owen T.A., Luzzio M.J., Hulford C.A., Gebhard D.F., Paralkar V.M., Simmons H.A., Kath J.C., Roberts W.G., Smock S.L., Guzman-Perez A., Brown T.A., Li M.

Affiliation: Pfizer Global Research and Development, Groton, CT 06340, USA

Abstract: Cumulative in vitro studies indicated that proline-rich tyrosine kinase 2 (PYK2) is a positive mediator of osteoclast function and activity. However, this study investigation of PYK2-/- mice did not reveal evidence supporting an essential function for PYK2 in osteoclasts either in vivo or in culture. We find that PYK2-/- mice have high bone mass resulting from an unexpected increase in bone formation. Consistent with the in vivo findings, mouse bone marrow cultures show that PYK2 deficiency enhances differentiation and activity of osteoprogenitor cells, as does expressing a PYK2-specific short hairpin RNA or dominantly interfering proteins in human mesenchymal stem cells. Furthermore, the daily administration of a small-molecule PYK2 inhibitor increases bone formation and protects against bone loss in ovariectomized rats, an established preclinical model of postmenopausal osteoporosis. In summary, the study finds that PYK2 regulates the differentiation of early osteoprogenitor cells across species and that inhibitors of the PYK2 have potential as a bone anabolic approach for the treatment of osteoporosis.

Prolyl-Hydroxyproline Dipeptide in Non-Hydrolyzed Morning Urine and Its Value in Postmenopausal Osteoporosis

Source: Clinical Chemistry and Laboratory Medicine 2008; 46(10): 1391-7

Author: Husek P., Svagera Z., Vsiansky F., Franekova J., Simek P.

Affiliation: Institute of Clinical Biochemistry, Faculty Hospital Ostrava, Ostrava, Czech Republic.

Abstract: Owing to the high correlation between the level of prolyl-4-hydroxyproline dipeptide in non-hydrolyzed urine and that of 4-hydroxyproline in hydrolyzed urine, we examined whether the dipeptide might function as a valuable marker of bone turnover. Based on densitometric measurements, 68 postmenopausal women were divided into groups of non-osteopathic, osteopenic and osteoporotic subjects. The dipeptide and current urinary resorption markers were assayed in morning urine, the former using liquid chromatography, the others plus serum formation markers by means of immunoassay procedures. Together with the assay of basal levels, diet-related changes and healing effect of yearly alendronate therapy were assessed. The study concludes that ease of the dipeptide assay in non-hydrolyzed urine surpasses that of hydroxyproline, and the results present the compound as a real competition to other commonly assessed markers in osteopathies.

Soy

Evaluation of the Preventive Effect of Isoflavone Extract on Bone Loss in Ovariectomized Rats

Source: Bioscience, Biotechnology and Biochemistry 2004; 68(5): 1040-5

Author: Lee Y.B., Lee H.J., Kim K.S., Lee J.Y., Nam S.Y., Cheon S.H., Sohn H.S.

Affiliation: Central Research Institute, Dr Chung's Food Co, Ltd, Korea.

Abstract: To examine a potential role for soybean phytoestrogens in postmenopausal bone loss, twenty-four 12-week-old Sprague-Dawley rats were divided randomly into 4 groups and given controlled diets for 16 weeks. The treatment groups were as followed: sham operated, ovariectomized (OVX) control, OVX + isoflavone extract (6.25 g/kg), and OVX + 17beta-estradiol (4 mg/kg). The results show that supplementation with isoflavone prevented the losses of bone density and mineral content caused by ovariectomized (OVX) (p<0.01). Although both isoflavone and 17beta-estradiol exhibited similar bone-sparing ability on the OVX-induced bone loss, the effect of isoflavone was not the same as that of 17beta-estradiol on the serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), body weight increase, and uterine weight change. The study concluds that dietary supplementation with soybean isoflavone can prevent postmenopausal bone loss via a different mechanism of estrogen in OVX rats.

Soy Isoflavones Mitigate Long-Term Femoral and Lumbar Vertebral Bone Loss in Middle-Aged Ovariectomized Mice

Source: Journal of Medicinal Food 2009; 12(3): 536-41

Author: Kim D.W., Yoo K.Y., Lee Y.B., Lee K.H., Sohn H.S., Lee S.J., Cho K.H., Shin Y.K., Hwang I.K., Won M.H., Kim D.W.

Affiliation: Research Center, Natural F&P Corp., Hallym University, Chuncheon, Republic of Korea.

Abstract: This study evaluated the protective effects of soy isoflavones (SIF) against osteoporosis in middle-aged ovariectomized (OVX) mice. SIF (30 mg/kg or 60 mg/kg) or 17beta-estradiol (E(2)) was administered to OVX mice for 4 months after bilateral ovariectomy. The biochemical markers of bone turnover, e.g., alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) were observed in serum. The bone mineral density (BMD) in femurs and lumbar vertebrae were also observed. In addition, the study examined trabecular bone and interstitial cells in the femur using hematoxylin and eosin staining. The results suggest that 60 mg/kg SIF effectively mitigates ovariectomy-induced osteoporosis in middle-aged mice.

Gender-Specific Associations Between Soy and Risk of Hip Fracture in the Singapore Chinese Health Study

Source: American Journal of Epidemiology 2009; 170(7): 901-9

Author: Koh W.P., Wu A.H., Wang R., Ang L.W., Heng D., Yuan J.M., Yu M.C.

Affiliation: Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Abstract: Although there is some epidemiologic evidence that soy may reduce risk of osteoporotic fracture in women, it is not known whether this risk reduction also occurs for men. The authors examined gender-specific associations between soy intake and hip fracture risk in the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese living in Singapore. At recruitment between 1993 and 1998, each subject was administered a food frequency questionnaire and questions on medical history and lifestyle factors. As of December 31, 2006, 276 incident cases of hip fracture in men and 692 cases in women were identified via linkage with hospital discharge databases. For both genders, hip fracture risk was positively associated with cigarette smoking and was inversely associated with body mass index. There was a statistically significant association of tofu equivalents, soy protein, and isoflavones with hip fracture risk among women but not among men. Compared with women in the lowest quartile of intakes for tofu equivalents (<49.4 g/day), soy protein (<2.7 g/day), and isoflavones (<5.8 mg/1,000 kcal/day), those in the second-fourth quartiles exhibited 21%-36% reductions in risk (all P < 0.036). Risk levels were comparable across the second, third, and fourth quartiles of soy intake categories.

Soy Isoflavone Supplementation and Bone Mineral Density in Menopausal Women: a 2-y Multicenter Clinical Trial

Source: The American Journal of Clinical Nutrition 2009; 90(5): 1433-9

Author: Wong W.W., Lewis R.D., Steinberg F.M., Murray M.J., Cramer M.A., Amato P., Young R.L., Barnes S., Ellis K.J., Shypailo R.J., Fraley J.K., Konzelmann K.L., Fischer J.G., Smith E.O.

Affiliation: US Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract: This multi?center, randomized, double-blind, placebo-controlled 24-months trial was conducted to assess the effects of daily supplementation with 80 or 120 mg of soy hypocotyl aglycone isoflavones plus calcium and vitamin D on bone changes in 403 postmenopausal women. Study subjects were tested annually and changes in whole-body and regional bone mineral density (BMD), bone mineral content (BMC), and T scores were assessed. Changes in serum biochemical markers of bone metabolism were also assessed. The study concludes that daily supplementation with 120 mg soy hypocotyl isoflavones reduces whole-body bone loss but does not slow bone loss at common fracture sites in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.

Vitamin C

Musculoskeletal Manifestations of Scurvy

Source: Joint, Bone, Spine 2005; 72(2): 124-8

Author: Fain O.

Affiliation: Internal Medicine Department, Jean Verdier Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Paris-North University-School of Medicine, UPRES EA 3409, avenue de 14 Juillet, 93143 Bondy cedex, France.

Abstract: In 80% of cases, the manifestations of scurvy include musculoskeletal symptoms consisting of arthralgia, myalgia, hemarthrosis, and muscular hematomas. Vitamin C depletion is responsible for structural collagen alterations, defective osteoid matrix formation, and increased bone resorption. Imaging studies may show osteolysis, joint space loss, osteonecrosis, osteopenia, and/or periosteal proliferation. Trabecular and cortical osteoporosis is common. Children experience severe lower limb pain related to subperiosteal bleeding. Laboratory tests show nonspecific abnormalities including anemia and low levels of cholesterol and albumin. The finding of a serum ascorbic acid level lower than 2.5 mg/l confirms the diagnosis. Vitamin C supplementation ensures prompt resolution of the symptoms.

Spontaneous Fractures in the Mouse Mutant SFX are Caused by Deletion of the Gulonolactone Oxidase Gene, Causing Vitamin C Deficiency

Source: Journal of Bone and Mineral Research 2005; 20(9): 1597-610

Author: Mohan S., Kapoor A., Singgih A., Zhang Z., Taylor T., Yu H., Chadwick R.B., Chung Y.S., Donahue L.R., Rosen C., Crawford G.C., Wergedal J., Baylink D.J.

Affiliation: Molecular Genetics Division, Musculoskeletal Disease Center, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, California, USA. Subburaman.

Abstract: Using a mouse mutant that fractures spontaneously and dies at a very young age, this study identified that a deletion of the GULO gene, which is involved in the synthesis of vitamin C, is the cause of impaired osteoblast differentiation, reduced bone formation, and development of spontaneous fractures. Skeletal phenotype of the spontaneous fractures (sfx) phenotype was evaluated by DXA using PIXImus instrumentation and by dynamic histomorphometry. The sfx gene was identified using various molecular genetic approaches, including fine mapping and sequencing of candidate genes, whole genome microarray, and PCR amplification of candidate genes using cDNA and genomic DNA as templates. Gene expression of selected candidate genes was performed using real-time PCR analysis. Osteoblast differentiation was measured by bone marrow stromal cell nodule assay. The results show that the sfx is a mutation of the GULO gene, which leads to ascorbic acid deficiency, impaired osteoblast cell function, and fractures in affected mice. Based on these and other findings, the study suggests that ascorbic acid is essential for the maintenance of differentiated functions of osteoblasts and other cell types.

Ascorbic Acid Deficiency, Iron Overload and Alcohol Abuse Underlie the Severe Osteoporosis in Black African Patients with Hip Fractures - a Bone Histomorphometric Study

Source: Calcified Tissue International 2005; 76(2): 79-89

Author: Schnitzler C.M., Schnaid E., MacPhail A.P., Mesquita J.M., Robson H.J.

Affiliation: MRC Mineral Metabolism Research Unit, University of the Witwatersrand, Johannesburg, South Africa.

Abstract: 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%. 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. The study concludes 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.

Influence of Nutrients Intake [Including Vitamin C] on Bone Turnover Markers

Source: Clinical Calcium 2005; 15(9): 1529-34

Author: Katsuyama H., Sunami S., Fukunaga M.

Affiliation: Department of Public Health, Kawasaki Medical School.

Abstract: Bone strength is determined by bone mineral density and bone quality. Bone quality can be assessed by only bone turnover markers. Nutrients that reduce bone resorption markers are calcium and isoflavone, nutrients that increase bone formation markers are vitamin C, vitamin D and vitamin K. These nutrients affect bone turnover and, as a result, improve bone density. These nutrients might contribute to prevent the incidence of osteoporosis when they are taken from adolescence.

Antioxidant Vitamin Supplements and Markers of Bone Turnover in a Community Sample of Nonsmoking Women

Source: Journal of Women's Health 2006; 15(3): 295-300

Author: Pasco J.A., Henry M.J., Wilkinson L.K., Nicholson G.C., Schneider H.G., Kotowicz M.A.

Affiliation: The University of Melbourne, Department of Clinical and Biomedical Sciences, Barwon Health, Geelong, Victoria, Australia.

Abstract: Whereas several epidemiological studies suggest that low dietary intake of vitamins C and E is linked to increased hip fracture in smokers and antioxidants (dietary and endogenous) are reduced in elderly osteoporotic women, none has demonstrated an effect of supplemental antioxidants on bone turnover. This observational study of 533 randomly selected women investigated the associations among the use of antioxidant supplements, vitamins C and E, serum levels of biochemical markers of bone turnover (C-telopeptide [CTx] and bone-specific alkaline phosphatase [BSAP]), and whole body bone mineral density (BMD). Twenty-two women were identified as current users of supplemental vitamin C or E. Duration of antioxidant supplement use was negatively associated with age-adjusted and weight-adjusted serum CTx, such that mean CTx levels (natural log transformed) were 0.022 units lower for each year of exposure. No significant differences were detected for adjusted serum BSAP or whole body BMD. The results suggest that antioxidant vitamin E or C supplements may suppress bone resorption in nonsmoking postmenopausal women. Coupling of bone formation and resorption may explain the absence of an effect on bone formation markers, given evidence of enhanced effects of antioxidants on osteoblast differentiation; this warrants further investigation. This work adds to the growing body of evidence that antioxidants may play a role in preventing osteoporosis.

Vitamin C, Vitamin B12, Folate and the Risk of Osteoporotic Fractures. A Case-Control Study

Source: International Journal for Vitamin and Nutrition Research 2007; 77(6): 359-68

Author: Martínez-Ramírez M.J., Palma Perez S., Delgado-Martínez A.D., Martínez-Gonzalez M.A., De la Fuente Arrillaga C., Delgado-Rodríguez M.

Affiliation: Service of Endocrinology and Nutrition, Hospital of Jaen, & Division of Medicine, University of Jaen.

Abstract: Water-soluble vitamins influence the development of an adequate structure of bone This study analyzed whether serum vitamin C, vitamin B12, and erythrocyte folate, or dietary intake of vitamin C and folate, are related with osteoporotic fractures in the elderly. A hospital-based case-control study was carried out at the Hospital of Jaen (167 cases, 167 controls), Spain. Cases were defined as patients aged 65 or more years with a low-energy fracture. Controls were people without fracture, matched for age and sex with cases. Diet was assessed by a semi-quantitative food frequency questionnaire. Serum vitamin C was measured using high-performance liquid chromatography (HPLC). Folic acid and vitamin B12 were measured using procedures of competitive or immunometric immunoassay. Multivariable analyses were also fitted to adjust for confounding using analysis of covariance (for the comparison of adjusted means) and conditional logistic regression (for estimating adjusted odds ratios). A statistically significant difference between cases and controls for vitamin C blood levels was found, being higher for controls (p = 0.01). Analysis of the association between serum vitamin C and fracture risk showed a linear trend (p = 0.03) with a significantly reduced risk for the upper quartile (OR = 0.31; 95% CI 0.11-0.87). In conclusion, serum vitamin C levels were lower in cases with osteoporotic fractures than in controls.

Regional Transient Osteoporosis of the Foot and Vitamin C Deficiency

Source: Clinical Rheumatology 2007; 26(6): 976-8

Author: Rodriguez S., Paniagua O., Nugent K.M., Phy M.P.

Affiliation: Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 4th Street STOP 9410, Lubbock, TX 79430, USA.

Abstract: This study describes the clinical presentation and diagnostic tests of a patient with regional transient osteoporosis (RTO) of the foot. This patient presented with a 4-month history of left-foot pain, nonpitting edema, and brownish discolorations of both feet. He had a history of tobacco abuse, alcohol abuse, and malnutrition. Radiological studies revealed severe osteopenia in the feet, and a MRI revealed bone marrow edema. The bone biopsy was consistent with RTO. This patient also had vitamin C deficiency. This case suggests a link between vitamin C deficiency and RTO, a hypothesis supported by our review of relevant literature on osteoporosis and vitamin C.

High Vitamin C Intake Is Associated with Lower 4-Year Bone Loss in Elderly Men

Source: The Journal of Nutrition 2008; 138(10): 1931-8

Author: Sahni S., Hannan M.T., Gagnon D., Blumberg J., Cupples L.A., Kiel D.P., Tucker K.L.

Affiliation: Dietary Assessment and Epidemiology Research Program, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.

Abstract: Vitamin C is essential for collagen formation and normal bone development. This study evaluated associations of total, supplemental, and dietary vitamin C intake with bone mineral density (BMD) at the hip [femoral neck, trochanter], spine, and radial shaft and 4-y BMD change in elderly participants from the Framingham Osteoporosis Study. Energy-adjusted vitamin C intakes were estimated from the Willett FFQ in 1988-89. Mean BMD and 4-y BMD change was estimated, for men and women, by tertile/category of vitamin C intake, adjusting for covariates. In the study interaction with smoking, calcium, and vitamin E intake were also tested. Among 334 men and 540 women, the mean age was 75 y and mean vitamin D intake was 8.25 mug/d (women) and 8.05 mug/d (men). The results showed negative associations between total and supplemental vitamin C intake and trochanter-BMD among current male smokers (P-trend = 0.01). Among male nonsmokers, total vitamin C intake was positively associated with femoral neck BMD (P-trend = 0.04). Higher total vitamin C intake was associated with less femoral neck and trochanter-BMD loss in men with low calcium (all P-trend

Citrus Bioactive Compounds Improve Bone Quality and Plasma Antioxidant Activity in Orchidectomized Rats

Source: Phytomedicine 2009; 16(6-7): 513-20

Author: Mandadi K., Ramirez M., Jayaprakasha G.K., Faraji B., Lihono M., Deyhim F., Patil B.S.

Affiliation: Texas A&M University-Kingsville Citrus Center, Kingsville, TX 78596, USA.

Abstract: In the present study, effects of feeding citrus bioactive compounds and crude extract on bone quality in castrated (orchidectomized) rats were evaluated. Seventy 90-days-old male rats were randomly assigned to five groups for 60 days of feeding study. The treatment groups were SHAM-control, orchidectomy (ORX), ORX+crude extract, ORX+limonin, and ORX+naringin. At termination, animals were euthanized, blood was collected for the plasma antioxidant status. Bone resorption and bone formation markers in the blood and urine were evaluated. Bone quality in the femur and the 5th lumbar and the total calcium concentration in the bones and excreta were evaluated. The study concludes that potential benefit of the citrus crude extract and its bioactive compounds on bone quality appears to preserve bone calcium concentration and increase antioxidant status.

Feeding Orange Pulp Improved Bone Quality in a Rat Model of Male Osteoporosis

Source: Journal of Medicinal Food 2009; 12(2): 298-303

Author: Morrow R., Deyhim F., Patil B.S., Stoecker B.J.

Affiliation: Department of Nutritional Sciences, Oklahoma State University, Stillwater, Oklahoma 74078-6141, USA.

Abstract: Oxidative stress and inflammation have been linked to bone loss. This study evaluated the effects of feeding orange pulp (OP), a source of vitamin C and flavonoids, on bone quality in a rat model of male osteoporosis. One-year-old retired breeder rats (n = 43) were orchidectomized (ORX) or sham-operated (SHAM). The results show that ORX decreased (P < .05) antioxidant status, while OP as low as 2.5% maintained the antioxidant capacity of ORX rats comparable to that of the SHAM group. Cortical thickness at the tibial midshaft was significantly decreased by ORX and increased by OP, and urinary DPD was significantly increased by ORX and decreased by OP. In fourth lumbar trabecular cores, ORX rats had significantly reduced bone volume fraction, connectivity density, and trabecular number and increased trabecular separation. OP significantly increased bone volume fraction and trabecular number and decreased trabecular separation in ORX rats. Improvements due to OP in microarchitectural properties of vertebral bones and in cortical thickness of long bones were subtle but significant.

Protective Effect of Total and Supplemental Vitamin C Intake on the Risk of Hip Fracture - a 17-Year Follow-Up from the Framingham Osteoporosis Study

Source: Osteoporosis International 2009; 20(11): 1853-61

Author: Sahni S., Hannan M.T., Gagnon D., Blumberg J., Cupples L.A., Kiel D.P., Tucker K.L.

Affiliation: Dietary Assessment and Epidemiology Research Program, Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) and Friedman School of Nutrition Science and Policy (FSNSP), Tufts University, Boston, MA, USA.

Abstract: In the Framingham Study, subjects with higher total or supplemental vitamin C intake had fewer hip fractures and non-vertebral fractures as compared to subjects with lower intakes. Therefore, vitamin C may have a protective effect on bone health in older adults. This study evaluated associations of vitamin C intake (total, dietary, and supplemental) with incident hip fracture and non-vertebral osteoporotic fracture, over a 15- to 17-year follow-up. Three hundred and sixty-six men and 592 women (mean age 75 +/- 5 years) completed a food frequency questionnaire (FFQ) in 1988-1989 and were followed for non-vertebral fracture until 2003 and hip fracture until 2005. Tertiles of vitamin C intake were created from estimates obtained using the Willett FFQ, after adjusting for total energy (residual method). Hazard ratios were estimated using Cox-proportional hazards regression, adjusting for covariates. The results indicate that subjects in the highest tertile of total vitamin C intake had significantly fewer hip fractures (P trend = 0.04) and non-vertebral fractures (P trend = 0.05) compared to subjects in the lowest tertile of intake. Subjects in the highest category of supplemental vitamin C intake had significantly fewer hip fractures (P trend = 0.02) and non-vertebral fractures (P trend = 0.07) compared to non-supplement users. Dietary vitamin C intake was not associated with fracture risk (all P > 0.22). These results suggest a possible protective effect of vitamin C on bone health in older adults.

Supplementation of ascorbic acid and alpha-tocopherol is useful to preventing bone loss linked to oxidative stress in elderly.

Source: J Nutr Health Aging. 2010;14(6):467-72.

Author: Ruiz-Ramos M, Vargas LA, Fortoul Van der Goes TI, Cervantes-Sandoval A, Mendoza-Nunez VM.

Affiliation: Unidad de Investigación en Gerontología, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, México DF, México.

Abstract: This double-blind, controlled clinical assay was carried out in a sample of 90 elderly subjects divided into three age-paired random groups with 30 subjects in each group, to determine the effect of ascorbic acid and alpha-tocopherol on oxidative stress and bone mineral density (BMD) in elderly people. The conclusions suggest that that administration of 1,000 mg of ascorbic acid together with 400 IU of alpha-tocopherol could be useful in preventing or aiding in the treatment of age-related osteoporosis.

Vitamin D

Effectiveness and Safety of Vitamin D in Relation to Bone Health

Source: Evidence Report / Technology Assessment 2007; (158): 1-235

Author: Cranney A., Horsley T., O'Donnell S., Weiler H., Puil L., Ooi D., Atkinson S., Ward L., Moher D., Hanley D., Fang M., Yazdi F., Garritty C., Sampson M., Barrowman N., Tsertsvadze A., Mamaladze V.

Affiliation:

Abstract: The objective of this study was to review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children, women of reproductive age, postmenopausal women and elderly men; the effect of dietary intakes (foods fortified with vitamin D and/or vitamin D supplementation) and sun exposure on serum 25(OH)D; the effect of vitamin D on bone mineral density (BMD) and fracture or fall risk; and the identification of potential harms of vitamin D above current reference intakes. Data sources were: MEDLINE(R) (1966-June Week 3 2006); Embase (2002-2006 Week 25); CINAHL (1982-June Week 4, 2006); AMED (1985 to June 2006); Biological Abstracts (1990-February 2005); and the Cochrane Central Register of Controlled Trials (2nd Quarter 2006). The evidence for fracture reduction with vitamin D supplementation was inconsistent across 15 trials. The combined results of trials using vitamin D(3) (700 - 800 IU daily) with calcium (500 - 1,200 mg) was consistent with a benefit on fractures although in a subgroup analysis by setting, benefit was primarily in elderly institutionalized women (fair evidence from two trials). The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups.

Summary of Evidence-Based Review on Vitamin D Efficacy and Safety in Relation to Bone Health

Source: The American Journal of Clinical Nutrition 2008; 88(2): 513S-519S

Author: Cranney A, Weiler HA, O?Donnel S, Puil L

Affiliation: Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa Hospital, and The University of Ottawa Evidence-based Practice Center, Ottawa, Ontario, Canada.

Abstract: The objective of this evidence review was to synthesize the literature on the effectiveness and safety of nutritional and ultraviolet radiation sources of vitamin D with respect to bone health outcomes at all stages of life. The goals were to identify knowledge gaps for the research community and to highlight areas that required further research. This report provides an overview of the methods and a summary of the key findings. In addition, it discusses areas where the evidence is inconclusive, as well as methodologic issues that were encountered. The findings show inconsistent evidence of an association between serum 25-hydroxyvitamin D [25(OH)D] concentration and bone mineral content in infants and fair evidence of an association with bone mineral content or density in older children and older adults. The evidence of an association between serum 25(OH)D concentration and some clinical outcomes (fractures, performance measures) in postmenopausal women and older men was inconsistent, and the evidence of an association with falls was fair. The evidence for a benefit of vitamin D on falls and fractures varied. We found fair evidence that adults tolerated vitamin D at doses above current dietary reference intake levels, but we had no data on the association between long-term harms and higher doses of vitamin D.

Determinant Factors of Osteoporosis Patients' Reported Therapeutic Adherence to Calcium and/or Vitamin D Supplements: a Cross-Sectional, Observational Study of Postmenopausal Women

Source: Drugs & Aging 2009; 26(10): 861-9

Author: Sanfelix-Genovés J, Gil-Guillén VF, Orozco-Beltran D, Giner-Ruiz V, Pertusa-Martínez S, Reig-Moya B, Carratalá C.

Affiliation: Nazaret's Health Centre, Department 5 CV, Valencia, Spain.

Abstract: The objective of the study was to analyse adherence to calcium and/or vitamin D treatment and to identify related predictors of non-adherence in a sample of postmenopausal women treated for osteoporosis in primary care. A cross-sectional, observational study was conducted in a sample of postmenopausal women receiving pharmaceutical treatment for osteoporosis with vitamin D and/or calcium. Sociodemographic, general and osteoporosis-related data were collected. Patient's perceptions of the adverse effects of treatment, their knowledge of osteoporosis (Batalla test), their attitude towards treatment (Morisky-Green test) and their self-reported therapeutic adherence (Haynes-Sackett test) were assessed. The study concludes that only one in two postmenopausal women with osteoporosis who took calcium and/or vitamin D have good self-reported therapeutic adherence to this treatment. Determinant factors of adherence to calcium and/or vitamin D treatment were patient's attitude to the treatment, tolerability problems with the treatment and number of concurrent treatments.

Minimum Required Vitamin D Level for Optimal Increase in Bone Mineral Density with Alendronate Treatment in Osteoporotic Women

Source: Calcified Tissue International 2009; 85(5): 398-404

Author: Ishijima M., Sakamoto Y., Yamanaka M., Tokita A., Kitahara K., Kaneko H., Kurosawa H.

Affiliation: Department of Orthopaedics, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Abstract: Vitamin D insufficiency and deficiency are common in the elderly. Most previous studies using pharmaceutical treatments, such as alendronate have used vitamin D supplementation regardless of individual vitamin D status. However, the minimum required vitamin D levels for the efficacy of alendronate treatment of osteoporosis remain unclear. Fifty-two postmenopausal women, diagnosed with osteoporosis, were enrolled in this prospective study, in which they took 5 mg of alendronate daily for 6 months without any supplements. Associations between baseline factors and their changes during the treatment and the change in the lumbar spine bone mineral density (LS-BMD) were examined. The most appropriate cut-off level of 25-hydroxyvitamin D (25[OH]D) for the optimal increase in LS-BMD with alendronate was determined using the Akaike information criterion statistical criterion. Overall, alendronate treatment significantly increased LS-BMD by 4.7%. The basal serum 25(OH)D and change in urinary NTX were significantly associated with the increase in LS-BMD. The increase in LS-BMD between the two groups was not different when comparing those with baseline 25(OH)D above vs. below 30 ng/ml. However, 25(OH)D of 25 ng/ml was determined to be the minimum required vitamin D level for an adequate effect of alendronate. Vitamin D status may affect the increase in LS-BMD with alendronate treatment in individuals being treated for osteoporosis, and a 25(OH)D level >25 ng/ml appears to be required for an optimal LS-BMD response.

Evaluation of a Care Pathway in the Initiation of Calcium and Vitamin D Treatment of Patients after Hip Fracture

Source: Canadian Journal on Aging 2009; 28(1): 21-6

Author: Crilly R.G., Speechley M., Overend T.J., Mackenzie R., Simon S., Cremer S.

Affiliation: Faculty of Medicine, University of Western Ontario, Ontario, Canada.

Abstract: Hip fractures, fragility fractures, indicate an increased risk for further fragility fractures. Although the way to define osteoporosis, requiring antiresorptive therapy, is not clear, all patients who have had hip fractures should be prescribed calcium and vitamin D at a minimum. In a retrospective chart review, this study have explored the effectiveness of incorporating a standing recommendation (but not a standing order) for calcium and vitamin D treatment in a hip fracture care pathway, comparing units where the pathway had been implemented with those where it had not yet been started. The pathway resulted in significantly more initiation of calcium and vitamin D compared to patients not on the pathway (72% vs. 13.5%, p < 0.01). However, a follow-up study after four years showed a marked decline in the frequency of the initiation of calcium and vitamin D, suggesting the need for ongoing encouragement for the intervention to continue to be successful.

Vitamin D Status and Response to Treatment in Post-Menopausal Osteoporosis

Source: Osteoporos International 2009; 20(2): 239-44

Author: Adami S., Giannini S., Bianchi G., Sinigaglia L., Di Munno O., Fiore C.E., Minisola S., Rossini M.

Affiliation: Rheumatology Unit, Ospedale di Valeggio, Verona, Italy.

Abstract: Several drugs were registered for the treatment of osteoporosis on the basis of clinical trials in which vitamin D repletion was a pre-requisite inclusion criteria and vitamin D supplements were used as adjunctive therapy. However, in routine clinical practice these supplements are not consistently recommended. This study examined 1515 women with postmenopausal osteoporosis under treatment with anti-resorbing agents (alendronate, risedronate, raloxifene) for 13.1 months with an adherence > 75%. The patients were classified as vitamin D deficient (N = 514) or vitamin D repleted (N = 1001) according to risk factors (N = 1062) or the level of 25(OH) vitamin D [25(OH)D] above or below 50 nmol/l (N = 453). The results show that vitamin D deficient and vitamin D repleted subjects differed significantly for annualized spine and hip bone mineral density (BMD) changes adjusted for all available confounding factors (type of treatment, age, global calcium intake, baseline BMD values). The study concludes that optimal vitamin D repletion seems to be necessary to maximize the response to anti-resorbers in terms of both BMD changes and anti-fracture efficacy.

Vitamin D Supplementation May Reduce the Risk of Osteoporosis in Low Income Premenopausal Bangladeshi Women

Source: Br J Nutr. 2010;104(2):241-7.

Author: Islam MZ, Shamim AA, Viljakainen HT, Akhtaruzzaman M, Jehan AH, Khan HU, Al-Arif FA, Lamberg-Allardt C.

Affiliation: Calcium Research Unit, Division of Nutrition, Department of Applied Chemistry and Microbiology, PO Box 66, 00014 University of Helsinki, Finland.

Abstract: Due to little outdoor activity and low dietary intake of vitamin D (VD), Bangladeshi low-income women are at risk for osteoporosis at an early age. The present study assessed the effect of VD, Ca and multiple micronutrient supplementation on VD and bone status in Bangladeshi young female garment factory workers. This placebo-controlled 1-year intervention randomly assigned 200 apparently healthy subjects (aged 16-36 years) to four groups. Supplementation with VD-Ca should be recommended as a strategic option to reduce the risk of osteomalacia and osteoporosis in these subjects. MMN-Ca [multiple micronutrients + calcium] may have analogous positive health implications with additional non-skeletal benefits.

Vitamin E

Antioxidant Vitamin Supplements [Vitamin E and C] and Markers of Bone Turnover in a Community Sample of Nonsmoking Women

Source: Journal of Women's Health 2006; 15(3): 295-300

Author: Pasco J.A., Henry M.J., Wilkinson L.K., Nicholson G.C., Schneider H.G., Kotowicz M.A.

Affiliation: The University of Melbourne, Department of Clinical and Biomedical Sciences, Barwon Health, Geelong, Victoria, Australia

Abstract: Whereas several epidemiological studies suggest that low dietary intake of vitamins C and E is linked to increased hip fracture in smokers and antioxidants (dietary and endogenous) are reduced in elderly osteoporotic women, none has demonstrated an effect of supplemental antioxidants on bone turnover. In an observational study of 533 randomly selected women, this study investigated the associations among the use of antioxidant supplements, vitamins C and E, serum levels of biochemical markers of bone turnover (C-telopeptide [CTx] and bone-specific alkaline phosphatase [BSAP]), and whole body bone mineral density (BMD). The results suggest that antioxidant vitamin E or C supplements may suppress bone resorption in nonsmoking postmenopausal women. Coupling of bone formation and resorption may explain the absence of an effect on bone formation markers, given evidence of enhanced effects of antioxidants on osteoblast differentiation; this warrants further investigation. This work adds to the growing body of evidence that antioxidants may play a role in preventing osteoporosis.

The Role of Vitamin E in Reversing Bone Loss

Source: Aging Clinical and Experimental Research 2008; 20(6): 521-7

Author: Chai S.C., Wei C.I., Brummel-Smith K., Arjmandi B.H.

Affiliation: Department of Nutrition, Food and Exercise Sciences, College of Human Sciences, Florida State University, Tallahassee, FL 32306, USA.

Abstract: The present study was conducted to evaluate the extent to which higher doses of vitamin E than normal dose (75 IU per kg diet) can reverse bone loss in aged osteopenic orchidectomized male rats. Forty 12-month old male Sprague- Dawley rats were either sham-operated (Sham) or orchidectomized (Orx), and fed control diet for 120 days to establish bone loss. Thereafter, rats were assigned to their corresponding treatment groups (n= 10 per group): Sham and one Orx groups received 75 IU vitamin E and served as controls, and the other two Orx groups received either 250 or 500 IU vitamin E per kg diet for 90 days. Overall, the findings of the present study suggest that supplemental doses of vitamin E do not increase BMD values in male rat model of osteoporosis. However, human studies are needed to confirm the population findings indicating that individuals with higher vitamin E intake have higher bone mass.

Effect of Antioxidants [Vitamin E and C] Combined to Resistance Training on BMD in Elderly Women: a Pilot Study

Source: Osteoporosis International 2009; 20(7): 1253-8

Author: Chuin A., Labonte M., Tessier D., Khalil A., Bobeuf F., Doyon C.Y., Rieth N., Dionne I.J.

Affiliation: Research Centre on Aging, Sherbrooke Geriatric University Institute, Sherbrooke, QC, Canada.

Abstract: The purpose of this pilot study was to determine the effects of antioxidant supplements combined to resistance training on bone mineral density (BMD) in healthy elderly women. Thirty-four postmenopausal women (66.1 +/- 3.3 years) were randomized in four groups (placebo, n = 7; antioxidants, n = 8; exercise and placebo, n = 11; and exercise and antioxidants, n = 8). The 6-month intervention consisted in antioxidant supplements (600 mg vitamin E and 1,000 mg vitamin C daily) or resistance exercise (3x/week). Femoral neck and lumbar spine BMD (DXA) and dietary intakes (3-day food record) were measured before and after the intervention. For statistical assessments a repeated measure ANOVA and non-parametric Mann-Whitney U tests were used. The study concludes that antioxidant vitamins may offer some protection against bone loss in the same extent as resistance exercise although combining both does not seem to produce additional effects. Our results suggest to further investigate the impact of antioxidant supplements on the prevention of osteoporosis.

Vitamin E Exhibits Bone Anabolic Actions in Normal Male Rats

Source: Journal of Bone and Mineral Metabolism 2009 September 25. [Epub ahead of print]

Author: Shuid A.N., Mehat Z., Mohamed N., Muhammad N, Soelaiman I.N.

Affiliation: Department of Pharmacology, Faculty of Medicine UKM, Universiti Kebangsaan Malaysia, Jln Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia.

Abstract: Recently, vitamin E has been found to promote the bone structure of nicotine-treated rats well above their baseline values, thus suggesting that vitamin E may have some anabolic action. A bone anabolic agent acts by improving the bone structure leading to stronger bone. To assess the possible anabolic action vitamin E on bone, normal male rats were supplemented with alpha-tocopherol (ATF) or gamma-tocotrienol (GTT) at 60 mg/kg or vehicle [normal control (NC) group] for 4 months and their bone structure and biomechanical properties were measured. Histomorphometric analysis revealed that vitamin E-supplemented rats have better trabecular volume, thickness, number, and separation than rats receiving vehicle only. For the first time this study reports that GTT improves all the parameters of bone biomechanical strength, while ATF only improved some of the parameters compared to the NC group. Vitamin E supplementation, especially with the gamma isomer, improves bone structure, which contributed to stronger bone. Therefore, vitamin E has the potential to be used as an anabolic agent to treat osteoporosis or as bone supplements for young adults to prevent osteoporosis in later years.

Vitamin K

Vitamin K to Prevent Fractures in Older Women: Systematic Review and Economic Evaluation

Source: Health Technology Assessment 2009; 13(45): iii-xi, 1-134

Author: Stevenson M., Lloyd-Jones M., Papaioannou D.

Affiliation: University of Sheffield, School of Health and Related Research (ScHARR), UK.

Abstract: The aim of this study was to determine the clinical and cost-effectiveness of vitamin K in preventing osteoporotic fractures in postmenopausal women. Searches were conducted in May 2007 in MEDLINE, MEDLINE In-Process, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, BIOSIS, CINAHL, DARE, NHS EED and HTA databases, AMED, NRR, Science Citation Index and Current Controlled Trials. The MEDLINE search was updated in March 2009. Selected studies were assessed and subjected to data extraction and quality assessment using standard methods. Where appropriate, meta-analysis was carried out. A mathematical model was constructed to estimate the cost-effectiveness of vitamin K1. The study concludes that there is currently large uncertainty over whether vitamin K1 is more cost-effective than alendronate; further research is required. It is unlikely that the present prescribing policy (i.e. alendronate as first-line treatment) would be altered.

Effect of Low Dose Vitamin K2 (MK-4) Supplementation on Bio-Indices in Postmenopausal Japanese Women

Source: Journal of nutritional sciences and vitaminology 2009; 55(1): 15-21

Author: Koitaya N., Ezaki J., Nishimuta M., Yamauchi J., Hashizume E., Morishita K., Miyachi M., Sasaki S., Ishimi Y.

Affiliation: Nutritional Epidemiology Program, National Institute of Health and Nutrition, 1-23-1, Toyama, Shinjyuku-ku, Tokyo 162-8636, Japan.

Abstract: The aim of this study is to examine the effects of the supplementation of 1.5 mg/d menaquinone-4 (MK-4 for 4) on bone and lipid metabolism in healthy postmenopausal Japanese women. The study was performed as a randomized double blind placebo-controlled trial. The participants aged 53-65 y were randomly assigned to 2 groups and supplemented with 1.5 mg/d of MK-4 or a placebo for 4 wk (n=20 for each group). The most marked effects of MK-4 intake were observed on serum osteocalcin (OC) concentrations. The results suggest that supplementation with 1.5 mg/d MK-4 accelerated the degree of OC gamma-carboxylation. The concentrations of serum lipids and other indices were not different between the groups at either intervention period. Thus, the additional intake of MK-4 might be beneficial in the maintenance of bone health in postmenopausal Japanese women.

Vitamin K Treatment Reduces Undercarboxylated Osteocalcin but Does Not Alter Bone Turnover, Density, or Geometry in Healthy Postmenopausal North American Women

Source: Journal of bone and mineral research 2009; 24(6): 983-91

Author: Binkley N., Harke J., Krueger D., Engelke J, Vallarta-Ast N., Gemar D., Checovich M., Chappell R., Suttie J.

Affiliation: University of Wisconsin Osteoporosis Clinical Research Program, Madison, Wisconsin 53705, USA.

Abstract: Low vitamin K status is associated with low BMD and increased fracture risk. Additionally, a specific menaquinone, menatetrenone (MK4), may reduce fracture risk. However, whether vitamin K plays a role in the skeletal health of North American women remains unclear. Moreover, various K vitamers (e.g., phylloquinone and MK4) may have differing skeletal effects. The objective of this study was to evaluate the impact of phylloquinone or MK4 treatment on markers of skeletal turnover and BMD in nonosteoporotic, postmenopausal, North American women. In this double-blind, placebo-controlled study, 381 postmenopausal women received phylloquinone (1 mg daily), MK4 (45 mg daily), or placebo for 12 months. All participants received daily calcium and vitamin D(3) supplementation. The results show no effect of phylloquinone or MK4 on lumbar spine or proximal femur BMD or proximal femur geometric parameters. This study does not support a role for vitamin K supplementation in osteoporosis prevention among healthy, postmenopausal, North American women receiving calcium and vitamin D supplementation.

High-Dose Vitamin K Supplementation Reduces Fracture Incidence in Postmenopausal Women: a Review of the Literature

Source: Nutrition research 2009; 29(4): 221-8

Author: Iwamoto J., Sato Y., Takeda T., Matsumoto H.

Affiliation: Institute for Integrated Sports Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.

Abstract: The objective of the present review of the literature was to evaluate the effect of vitamin K supplementation on the skeleton of postmenopausal women. PubMed was used to search the reliable literature for RCTs by using the search terms "vitamin K(1) or vitamin K(2)," "bone," and "postmenopausal women" and the following inclusion criteria: approximately 50 or more subjects per group and study period of 2 years or longer. Seven RCTs met the inclusion criteria. The results of these RCTs showed that vitamin K(1) and vitamin K(2) supplementation reduced serum undercarboxylated osteocalcin levels regardless of dose but that it had inconsistent effects on serum total osteocalcin levels and no effect on bone resorption. Despite the lack of a significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K(1) and vitamin K(2) supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures. The review of the reliable literature confirmed the effect of vitamin K(1) and vitamin K(2) supplementation on the skeleton of postmenopausal women mediated by mechanisms other than bone mineral density and bone turnover.

Vitamin K1 Intake Is Associated with Higher Bone Mineral Density and Reduced Bone Resorption in Early Postmenopausal Scottish Women: No Evidence of Gene-Nutrient Interaction with Apolipoprotein E Polymorphisms

Source: The American journal of clinical nutrition 2008; 87(5): 1513-20

Author: Macdonald HM, McGuigan FE, Lanham-New SA, Fraser WD, Ralston SH, Reid DM

Affiliation: Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.

Abstract: The objective of this study was to investigate the relation between dietary vitamin K(1) intake, APOE polymorphisms, and markers of bone health. DESIGN: The bone mineral density (BMD) was measured at the lumbar spine (LS) and femoral neck (FN) in a cohort of Scottish women aged 49-54 y in 1990-1994 (baseline) and in 1997-2000 (visit 2). At visit 2, bone markers (urinary pyridinoline crosslinks and serum N-terminal propeptide of type 1 collagen) were measured, 3199 women completed a food-frequency questionnaire, and 2721 women were genotyped for APOE. The study concludes that vitamin K(1) intake was associated with markers of bone health, but no interaction was observed with APOE alleles on BMD or markers of bone turnover.

Concurrent Treatment of Osteoporosis Including Vitamin K

Source: Clinical calcium 2007; 17(11): 1731-7

Author: Kobayashi S., Shiraki M., Takaoka K.

Affiliation: Shinshu University School of Medicine, Department of Orthopaedic Surgery.

Abstract: The 2006 version of the guideline for prophylaxis and treatment of osteoporosis recommends vitamin K (VK) supplementation in the state of its deficiency. As VK(2) gained grade B in all aspects in the guideline, single use of the drug is limited. VK(2) may be used concurrently with other drugs in the treatment of osteoporosis. In this paper, the results of the concurrent use of two of vitamin D(3), VK(2), and EHDP are summarized, and the combined therapy including VK(2) is reviewed.

No Effect of Vitamin K1 Intake on Bone Mineral Density and Fracture Risk in Perimenopausal Women

Source: Osteoporosis international 2006; 17(8): 1122-32

Author: Rejnmark L., Vestergaard P., Charles P., Hermann A.P., Brot C., Eiken P., Mosekilde L.

Affiliation: Department of Endocrinology and Metabolism C, Aarhus Sygehus, Aarhus University Hospital, Tage-Hansens Gade 2, Aarhus C, 8000, Denmark.

Abstract: The aim of this study was to investigate the relationship between vitamin K(1) intake and bone mineral density (BMD) and fracture risk in a perimenopausal Danish population. The study was performed within the Danish Osteoporosis Prevention Study (DOPS), including a population-based cohort of 2,016 perimenopausal women. During the study approximately 50% of the women received hormone replacement therapy (HRT). Associations between vitamin K(1) intake and BMD were assessed at baseline and after 5-years of follow-up (cross-sectional design). Moreover, associations between vitamin K(1) intake and 5-year and 10-year changes in BMD were studied (follow-up design). Finally, fracture risk was assessed in relation to vitamin K(1) intake (nested case-control design).This study concludes that in a group of perimenopausal and early postmenopausal women, vitamin K(1) intake was not associated with effects on BMD or fracture risk.

Zinc

Zinc Increases the Effects of Essential Amino Acids-Whey Protein Supplements in Frail Elderly

Source: The Journal of Nutrition, Health & Aging 2009; 13(6): 491-7

Author: Rodondi A., Ammann P., Ghilardi-Beuret S., Rizzoli R.

Affiliation: Division of Bone Diseases, Department of Rehabilitation and Geriatrics, University Hospitals and Faculty of Medicine of Geneva, CH - 1211 Geneva 14, Switzerland.

Abstract: The objective of this study was to determine the influence of dietary zinc addition on IGF-I and bone turnover responses to essential amino acids-whey (EAA-W) protein supplements in frail elderly. A daily oral protein supplement was given to hospitalized patients for 4 weeks. On a randomized, double-blind basis, patients received either an additional 30 mg/day of zinc or control. Sixty-one hospitalized elderly aged 66.7 to 105.8, with a mini-nutritional assessment score between 17 and 24 were enrolled. Activities of daily living; dietary intakes; serum IGF-I, IGF-BP3, CrossLapsTM, osteocalcin and zinc were measured before and after 1, 2 and 4 weeks of protein supplementation. The study concludes that in the elderly, zinc supplementation accelerated the serum IGF-I response to EAA-W protein by 1 week and decreased a biochemical marker of bone resorption.

Differences in Zinc Status Between Patients with Osteoarthritis and Osteoporosis

Source: Journal of trace elements in medicine and biology 2009; 23(1): pp.1-8.

Author: Ovesen J., Moller-Madsen B., Nielsen P.T., Christensen P.H., Simonsen O., Hoeck H.C., Laursen M.B., Thomsen J.S.

Affiliation: Department of Orthopaedic Surgery, Randers Regional Hospital, DK-8900 Randers, Denmark.

Abstract: The aim of the study was to investigate and compare the zinc status and bone turnover, density, and biomechanical properties of osteoarthritic and osteoporotic patients. The study comprised 40 women who underwent hip replacement due to osteoarthritis or osteoporosis. Serum and urine zinc content, and bone resorption markers and serum bone formation markers were determined. The unaffected hip and the exarticulated affected femoral head underwent DEXA scanning. Bone biopsies were obtained from the femoral heads and the biomechanical properties were determined. The biopsies were ashed and the bone zinc content was ascertained. Osteoarthritic patients had significantly higher serum zinc concentrations and lower urine zinc concentrations than osteoporotic patients, whereas the bone zinc content did not differ. The zinc status was not found to be a predictor for the bone strength. In conclusion, the finding that the zinc status of osteoporotic patients is significantly different from that of osteoartritic patients is new and supports the view that osteoporosis and osteoarthritis rarely occur in the same individual.

Long-Term Marginal Zinc Supply is Not Detrimental to the Skeleton of Aged Female Rats

Source: The Journal of Nutrition 2009; 139(4): 703-9

Author: Erben R.G., Lausmann K., Roschger P., Schuler C., Skalicky M., Klaushofer K., Windisch W.

Affiliation: Institute of Physiology, Physiological Chemistry and Animal Nutrition, Ludwig Maximilians University, 80539 Munich, Germany.

Abstract: This experiment investigated the long-term effects of a marginal zinc (Zn) supply on bone metabolism in aged rats. Nine-mo-old female Fischer-344 rats were divided into 8 weight-matched groups of 8 rats each. All rats were adapted for 1 mo to restrictive feeding (7.5 g/d) of a purified diet containing 8 g/kg sodium phytate and 64 mg/kg Zn. Control rats were pair-fed throughout the experiment. During the 1-month depletion phase, controls received the Zn-replete diet with 64 mg/kg Zn, whereas Zn-deficient rats were fed the same diet with 2.2 mg/kg Zn. The depletion phase was followed by a 3-months marginal phase in which the rats fed the diet with 2.2 mg/kg Zn received an additional daily Zn supplement of 75 micrograms Zn/rat by gavage. In the following 2-mo repletion phase, a marginal group was switched to the Zn-replete diet, while the other groups were maintained on marginal Zn supply or on the Zn-replete diet. The data suggest that Zn does not play an essential role in bone metabolism in aged rats and cast doubt on the hypothesis that Zn deficiency is a risk factor for osteoporosis.

Effects of Zinc on the Mineralization of Bone Nodules from Human Osteoblast-Like Cells

Source: Biological Trace Elements Research 2007; 116(1): 61-71

Author: Cerovic A., Miletic I., Sobajic S., Blagojevic D., Radusinovic M., El-Sohemy A.

Affiliation: Department of Bromatology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.

Abstract: The objective of this study was to determine the effects of zinc on the differentiation of SaOS-2 human osteoblastlike cells and the formation of mineralized bone nodules. Cells were cultured for 8 d and then transferred to zinc-free medium and treated with varying concentrations (0-50 microM) of zinc. Alkaline phosphatase (ALP) activity was used as a measure of osteoblast differentiation, and bone nodules were detected by von Kossa staining. After 4, 6, and 8 d of treatment, zinc increased ALP activity at 1 and 10 microM, but decreased activity at 50 microM. After 9 d of treatment, zinc increased both the number and area of mineralized bone nodules at low concentrations (1 and 10 microM), but decreased both at higher concentrations (25 and 50 microM). These findings demonstrate that zinc has biphasic effects on the differentiation and mineralization of human osteoblast-like cells.

Effect of Controlled Zinc Release on Bone Mineral Density from Injectable Zn-Containing Beta-Tricalcium Phosphate Suspension in Zinc-Deficient Diseased Rats

Source: Journal of Biomedical Materials Research. Part A 2004; 69(3): 552-60

Author: Otsuka M., Ohshita Y., Marunaka S., Matsuda Y, Ito A., Ichinose N., Otsuka K., Higuchi W.I.

Affiliation: Kobe Pharmaceutical University, Department of Pharmaceutical Technology, Motoyama-Kitamachi 4-19-1, Higashi-Nada, Kobe 658-8558, Japan.

Abstract: The purpose of this study was to evaluate the efficacy of zinc (Zn)-containing beta-tricalcium phosphate (Zn-TCP) in correcting the bone mineral deficiency noted in osteoporosis using ovariectomized rat model. Four rats were used for each of the four experimental groups: D0, D10, D20, and N10. The rats in D0, D10, and D20 groups were ovariectomized, and fed a vitamin D-, Ca-, and Zn-deficient diet, and induced Zn-deficient osteoporoses for 9 weeks. In contrast, the N10 group was the normal rats fed normal healthy diet for 9 weeks. D0 group was injected with pure beta-TCP suspension, D10 and D20 groups were injected with suspensions containing 10 mg of 10 mol % (6.17 wt % Zn) and 20 mol % (12.05 wt % Zn) Zn-TCP, respectively, and the healthy group, N10 were injected with 10 mol %. Zn-TCP suspensions. Injections were administered intramuscularly in the left thigh once a week in all rats, and fed a vitamin D- and Zn-deficient diet for 9 weeks. The body weight of D10 and D20 groups significantly increased with time, that of the D0 group increased slightly, and that of the N10 group remained unchanged for the entire experimental period. The BMD of the lumbar vertebrae of the D10 and D20 groups (about 100 mg/cm(2)) was significantly higher than that of the D0 group but lower than that of the N10 group. The BMD of the left femur increased more than that of the right femur with the increase in the amount of Zn in the suspension. The results of this study suggest that the local effect on BMD was more pronounced than the effect on the whole body.