Bone Health Formula

SCIENTIFIC RESEARCH ON THE FOLLOWING INGREDIENTS:

Vitamin C

Effect of Vitamin C on Inflammation and Metabolic Markers in Hypertensive and/or Diabetic Obese Adults: A Randomized Controlled Trial ^*

Abstract

Background: Obesity is well associated as being an interfering factor in metabolic diseases such as hypertension and diabetes by increasing the secretion of proinflammatory markers from adipose tissue. Having healthy effects, vitamin C could work as an anti-inflammatory agent through its antioxidant capacity.

Registration: Registration number: FPSK_Mac [13]04.

Objective: The aim of the study reported here was to identify the effect of vitamin C on reducing the levels of inflammatory markers in hypertensive and/or diabetic obese adults.

Subjects and methods: Sixty-four obese patients, who were hypertensive and/or diabetic and had high levels of inflammatory markers, from primary health care centers in Gaza City, Palestine, were enrolled into one of two groups in an open-label, parallel, randomized controlled trial. A total of 33 patients were randomized into a control group and 31 patients were randomized into an experimental group. The experimental group was treated with 500 mg vitamin C twice a day.

Results: In the experimental group, vitamin C significantly reduced the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fasting blood glucose (FBG), and triglyceride (TG) after 8 weeks of treatment (overall: P<0.001); no changes appeared in total cholesterol (TC). In the control group, there were significant reductions in FBG and TG (P=0.001 and P=0.026, respectively), and no changes in hs-CRP, IL-6, or TC. On comparing the changes in the experimental group with those in the control group at the endpoint, vitamin C was found to have achieved clinical significance in treating effectiveness for reducing hs-CRP, IL-6, and FBG levels (P=0.01, P=0.001, and P<0.001, respectively), but no significant changes in TC or TG were found.

Conclusion: Vitamin C (500 mg twice daily) has potential effects in alleviating inflammatory status by reducing hs-CRP, IL-6, and FBG in hypertensive and/or diabetic obese patients.

Source: Mohammed S. Ellulu, Asmah Rahmat, Ismail Patimah, Huzwah Khaza’ai, and Yehia Abed. “Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial” Drug Design, Development and Therapy (2015): 9: 3405–3412.

The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments ^*

Abstract

Vitamin C is an important antioxidant and cofactor which is involved in the regulation of development, function and maintenance of several cell types in the body. Deficiencies in vitamin C can lead to conditions such as scurvy, which, among other ailments, causes gingivia, bone pain and impaired wound healing. This review examines the functional importance of vitamin C as it relates to the development and maintenance of bone tissues. Analysis of several epidemiological studies and genetic mouse models regarding the effect of vitamin C shows a positive effect on bone health. Overall, vitamin C exerts a positive effect on trabecular bone formation by influencing expression of bone matrix genes in osteoblasts. Recent studies on the molecular pathway for vitamin C actions that include direct effects of vitamin C on transcriptional regulation of target genes by influencing the activity of transcription factors and by epigenetic modification of key genes involved in skeletal development and maintenance are discussed. With an understanding of mechanisms involved in the uptake and metabolism of vitamin C and knowledge of precise molecular pathways for vitamin C actions in bone cells, it is possible that novel therapeutic strategies can be developed or existing therapies can be modified for the treatment of osteoporotic fractures.

Source: Patrick Aghajanian, Susan Hall, Montri D. Wongworawat, and Subburaman Mohan. “The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments” Journal of Bone and Mineral Research (2015): 30(11): 1945–1955.

Vitamin C ^*

Abstract:

Vitamin C is a powerful reducing agent that participates in several important hydroxylation reactions. Na+-coupled transporters help to facilitate entry of vitamin C into cells. Glial cells in the brain regenerate vitamin C from DHA. Vitamin C is needed for collagen, carnitine, catecholamine, and bile acid biosynthesis. Oxalate is a natural degradation product of vitamin C. Vitamin C uses Fe++ and Cu++ as cofactors, and it enhances intestinal Fe++ absorption. Vitamin C deficiency can result in “scurvy.” Although most mammals can synthesize vitamin C from glucose, it cannot be formed in primates, fish, flying mammals, songbirds, or the guinea pig. Vitamin C is a natural preservative added to pet food products.

Source: Larry R. Engelking. “Vitamin C” Textbook of Veterinary Physiological Chemistry (2015): pp. 254-259.

Decreasing Free Radicals Level on High Risk Person After Vitamin C and E Supplement Treatment ^*

Abstract

Has become a global issue that the increase in global warming mainly caused by high air pollution levels which are donated by motor vehicle emissions. As a rapidly developing country, Indonesia becomes vulnerable to health problems related to air pollution. Excessive freeradicals that is produced by air pollution can initiate stress oxidative. Already known that, stress oxidative trigger many health problems. Vitamin C and E is a non enzymatic antioxidant that can neutralize free radicals. This study aims to investigate the decreasing free radicals level by administering vitamin C and E. This research using pre and post experimental design study. There are 24 operators gasoline station Pertamina as samples, with an average age of 26 years. The samples were divided into 4 groups. Group 1 (control), group 2, were given vitamin C doses of 500mg / day, group 3 was given vitamin E doses of 250 IU / day and the group 4 was given a combination of vitamins C and E. The treatment was given for 30 days. Free radicals level is obtained from malonaldehyde (MDA) level by spectrophotometer. Before treatment the average of MDA level is 5.540 µm. After the treatment, MDA is significantly decreased become 3.992 µm (T-test, sig<0.05). This result can be used as a sign of side affect of air pollutant in the operator SPBU. As reminding to protect the employee with safety aid and supplement.

Source: M S Sitorus, D R Anggraini, Hidayat. “Decreasing Free Radicals Level on High Risk Person After Vitamin C and E Supplement Treatment” IOP Conference Series: Materials Science and Engineering (2016): Vol. 180.

Vitamin C Intake in Relation To Bone Mineral Density and Risk Of Hip Fracture and Osteoporosis: A Systematic Review and Meta-Analysis of Observational Studies ^*

Abstract

We aimed to systematically review available data on the association between vitamin C intake and bone mineral density (BMD), as well as risk of fractures and osteoporosis, and to summarise this information through a meta-analysis. Previous studies on vitamin C intake in relation to BMD and risk of fracture and osteoporosis were selected through searching PubMed, Scopus, ISI Web of Science and Google Scholar databases before February 2017, using MeSH and text words. To pool data, either a fixed-effects model or a random-effects model was used, and for assessing heterogeneity, Cochran's Q and I 2 tests were used. Subgroup analysis was applied to define possible sources of heterogeneity. Greater dietary vitamin C intake was positively associated with BMD at femoral neck (pooled r 0·18; 0·06, 0·30) and lumbar spine (pooled r 0·14; 95 % CI 0·06, 0·22); however, significant between-study heterogeneity was found at femoral neck: I 2=87·6 %, P heterogeneity<0·001. In addition, we found a non-significant association between dietary vitamin C intake and the risk of hip fracture (overall relative risk=0·74; 95 % CI 0·51, 1·08). Significant between-study heterogeneity was found (I 2=79·1 %, P heterogeneity<0·001), and subgroup analysis indicated that study design, sex and age were the main sources of heterogeneity. Greater dietary vitamin C intake was associated with a 33 % lower risk of osteoporosis (overall relative risk=0·67; 95 % CI 0·47, 0·94). Greater dietary vitamin C intake was associated with a lower risk of hip fracture and osteoporosis, as well as higher BMD, at femoral neck and lumbar spine.

Source: Hanieh Malmir, Sakineh Shab-Bidar, Kurosh Djafarian. “Vitamin C intake in relation to bone mineral density and risk of hip fracture and osteoporosis: a systematic review and meta-analysis of observational studies” The British Journal of Nutrition (2018): 119(8):847-858.

Vitamin C Reverses Bone Loss in an Osteopenic Rat Model of Osteoporosis ^*

Abstract

Fruits and vegetables are rich in vitamin C with antioxidant properties which are known to influence bone quality. This study evaluated whether vitamin C (1000 mg/L) added to drinking water reverses the bone loss in ovariectomized rats. Ninety-day-old female Sprague-Dawley rats were randomly assigned to either sham (n = 14) or ovariecotmized groups (n = 28). Sixty days after ovariectomy, the treatments were sham, ovariectomy (OVX), OVX + vitamin C (22 mg oral intake daily) for 60 days. Urine was collected for deoxypyridinoline (DPD) evaluation, rats were sacrificed, and antioxidant capacity, osteopontin, alkaline phosphatase (ALP), and bone specific tartrate resistant acid phosphatase (TRAP) were evaluated in the plasma. Right femur and 5^th lumbar were evaluated for bone density, strength, ash, Ca, and Mg concentrations. Antioxidant capacity, ALP activity, osteopontin decreased (p-value < 0.05), while TRAP and urinary DPD increased (p-value < 0.05) with ovariectomy. In contrast, vitamin C increased (p-value < 0.05) antioxidant capacity, ALP activity, osteopontin concentration and reduced (p-value < 0.05) TRAP and urinary DPD excretion, respectively. Ovariectomy reduced (p-value < 0.05) bone quality, bone ash, Ca and Mg concentrations. Vitamin C increased (p-value < 0.05) femoral density without affecting (p-value > 0.1) femoral strength, ash, or Ca, and Mg concentrations, while it increased (p-value < 0.05) the 5^th lumbar density, ash, and Ca and Mg concentrations. In conclusion, vitamin C increased bone quality and antioxidant capacity in ovariectomized rats.

Source: Farzad Deyhim, Kimberly Strong, Niaz Deyhim, Sarvenaz Vandyousefi, Alexis Stamatikos  and Bahram Faraji. “Vitamin C reverses bone loss in an osteopenic rat model of osteoporosis” International Journal for Vitamin and Nutrition Research (2018): 88, pp. 58-64.

Vitamin C Deficiency Accelerates Bone Loss Inducing an Increase in PPAR-Γ Expression in SMP30 Knockout Mice ^*

Abstract

Senescence marker protein (SMP) 30 knockout (KO) mice display symptoms of scurvy,including spontaneous bone fractures, and this was considered to be induced by a failure of collagen synthesis owing to vitamin C deficiency. However, low bone mineral density is also known to be associated with spontaneous bone fracture. Therefore, we investigated the effects of vitamin C deficiency on the balance between osteoblasts and osteoclasts in SMP30 KO mice as evidenced by histopathology. All mice were fed a vitamin C-free diet, and only one group (KV) mice were given water containing 1.5 g/l of vitamin C, whereas wild-type (WT) and KO mice were given normal drinking tap water without vitamin C for 16 weeks. After 16 weeks, all femur samples were removed for histopathological examination. The femurs of KO mice showed significantly reduced bone area and decreased number of osteoblasts compared with those of WT mice and KV mice. KO mice also exhibited the lowest level of alkaline phosphatase (ALP) expression in their femurs. However, KO mice showed the most elevated expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Moreover, KO mice had the strongest peroxisome proliferator-activated receptor (PPAR)-γ expression level in their osteoblasts and the highest number of TUNEL-positive bone marrow cells. Therefore, we concluded that vitamin C deficiency plays an important role in spontaneous bone fracture by inhibiting osteoblast differentiation and promoting transition of osteoblasts to adipocytes, and this could in turn be related to the increased PPAR-γ expression.

Source: Jin-Kyu Park, Eun-Mi Lee, Ah-Young Kim, Eun-Joo Lee, Chang-Woo Min, Kyung-Ku Kang, Myeong-Mi Lee, Kyu-Shik Jeong. “Vitamin C deficiency accelerates bone loss inducing an increase in PPAR-γ expression in SMP30 knockout mice” International Journal of Experimental Pathology (2012): 93(5):332-40.

Vitamin C and Bone Health: Evidence from Cell, Animal and Human Studies ^*

Abstract

Background: Vitamin C, traditionally associated with scurvy, is an important nutrient for maintaining bone health. It is essential in the production of collagen in bone matrix. It also scavenges free radicals detrimental to bone health.

Objective: This review aims to assess the current evidence of the bone-sparing effects of vitamin C derived from cell, animal and human studies.

Results: Cell studies showed that vitamin C was able to induce osteoblast and osteoclast formation. However, high-dose vitamin C might increase oxidative stress and subsequently lead to cell death. Vitamin C-deficient animals showed impaired bone health due to increased osteoclast formation and decreased bone formation. Vitamin C supplementation was able to prevent bone loss in several animal models of bone loss. Human studies generally showed a positive relationship between vitamin C and bone health, indicated by bone mineral density, fracture probability and bone turnover markers. Some studies suggested that the relationship between vitamin C and bone health could be U-shaped, more prominent in certain subgroups and different between dietary and supplemental form. However, most of the studies were observational, thus could not confirm causality. One clinical trial was performed, but it was not a randomized controlled trial, thus confounding factors could not be excluded.

Conclusion: vitamin C may exert beneficial effects on bone, but more rigorous studies and clinical trials should be performed to validate this claim.

Source:  Kok-Yong Chin, Soelaiman Ima-Nirwana. “Vitamin C and Bone Health: Evidence from Cell, Animal and Human Studies” Current Drug Targets (2018): Vol. 19, Issue 5.

Calcium

Calcium and Bone ^*

Abstract

Objective: Evaluate the role of calcium on bone health.

Methods: Review of literatures on calcium and bone development during childhood and bone health in adulthood and older age.

Results: Calcium intake influences skeletal calcium retention during growth and thus affects peak bone mass achieved in early adulthood. Increased calcium intake is associated with increased bone mineral accretion rate up to a threshold level in all ethnic groups. The minimum intake to achieve maximal retention is 1140 mg/day for white boys and 1300 mg/day for white girls. Calcium also plays a role in preventing bone loss and osteoporotic fractures in later life. Meta-analyses report that calcium supplementation reduce bone loss by 0.5-1.2% and the risk of fracture of all types by at least 10% in older people. Low calcium intake is a widespread problem across countries and age groups.

Conclusion: Adequate calcium intake throughout lifetime is important for bone health and the prevention of osteoporosis and related fractures.

Source: Kun Zhu, Richard L Prince. “Calcium and Bone” Clinical Biochemistry (2012): 45(12):936-42.

Calcium Intake and Bone Mineral Density: Systematic Review and Meta-Analysis ^*

Abstract

Objective To determine whether increasing calcium intake from dietary sources affects bone mineral density (BMD) and, if so, whether the effects are similar to those of calcium supplements.

Design Random effects meta-analysis of randomised controlled trials.

Data sources Ovid Medline, Embase, Pubmed, and references from relevant systematic reviews. Initial searches were undertaken in July 2013 and updated in September 2014.

Eligibility criteria for selecting studies Randomised controlled trials of dietary sources of calcium or calcium supplements (with or without vitamin D) in participants aged over 50 with BMD at the lumbar spine, total hip, femoral neck, total body, or forearm as an outcome.

Results We identified 59 eligible randomised controlled trials: 15 studied dietary sources of calcium (n=1533) and 51 studied calcium supplements (n=12 257). Increasing calcium intake from dietary sources increased BMD by 0.6-1.0% at the total hip and total body at one year and by 0.7-1.8% at these sites and the lumbar spine and femoral neck at two years. There was no effect on BMD in the forearm. Calcium supplements increased BMD by 0.7-1.8% at all five skeletal sites at one, two, and over two and a half years, but the size of the increase in BMD at later time points was similar to the increase at one year. Increases in BMD were similar in trials of dietary sources of calcium and calcium supplements (except at the forearm), in trials of calcium monotherapy versus co-administered calcium and vitamin D, in trials with calcium doses of ≥1000 versus <1000 mg/day and ≤500 versus >500 mg/day, and in trials where the baseline dietary calcium intake was <800 versus ≥800 mg/day.

Conclusions Increasing calcium intake from dietary sources or by taking calcium supplements produces small non-progressive increases in BMD, which are unlikely to lead to a clinically significant reduction in risk of fracture.

Source: Vicky Tai, William Leung, Andrew Grey, Ian R Reid, and Mark J Bolland. “Calcium intake and bone mineral density: systematic review and meta-analysis” British Medical Journal (2015): 351: h4183. 

A Natural, Calcium-Rich Marine Multi-mineral Complex Preserves Bone Structure, Composition and Strength in an Ovariectomised Rat Model of Osteoporosis ^*

Abstract

Calcium supplements are used as an aid in the prevention of osteopenia and osteoporosis and also for the treatment of patients when used along with medication. Many of these supplements are calcium carbonate based. This study compared a calcium-rich, marine multi-mineral complex (Aquamin) to calcium carbonate in an ovariectomised rat model of osteoporosis in order to assess Aquamin’s efficacy in preventing the onset of bone loss. Animals were randomly assigned to either non-ovariectomy control (Control), ovariectomy (OVX) plus calcium carbonate, ovariectomy plus Aquamin or ovariectomy plus Aquamin delay where Aquamin treatment started 8 weeks post OVX. At the end of the 20-week study, the trabecular architecture was measured using micro computed tomography, bone composition was assessed using Fourier transform infrared spectroscopy and the mechanical properties were assessed using nanoindentation and three-point bend testing. The study demonstrates that oral ingestion of Aquamin results in less deterioration of trabecular bone structure, mineral composition and tissue level biomechanical properties in the tibia of rats following ovariectomy than calcium carbonate. This study has shown that in an animal model of osteoporosis, Aquamin is superior to calcium carbonate at slowing down the onset of bone loss.

Source: Orlaith Brennan, Joseph Sweeney, Brian O’Meara, Amro Widaa, Franck Bonnier, Hugh J. Byrne, Denise M. O’Gorman & Fergal J. O’Brien. “ A Natural, Calcium-Rich Marine Multi-mineral Complex Preserves Bone Structure, Composition and Strength in an Ovariectomised Rat Model of Osteoporosis” Calcified Tissue International (2017): 101, pp. 445-455.

Calcium & Vitamin D

Vitamin D and Calcium Supplementation for Three Years in Postmenopausal Osteoporosis Significantly Alters Bone Mineral and Organic Matrix Quality ^*

Abstract

Prospective, controlled clinical trials in postmenopausal osteoporosis typically compare effects of an active drug with placebo in addition to vitamin D and calcium supplementation in both treatment arms. While clinical benefits are documented, the effect of this supplementation in the placebo arm and in clinical practice on bone material composition properties is unknown. The purpose of the present study was to evaluate these bone quality indices (specifically mineral/matrix, nanoporosity, glycosaminoglycan content, mineral maturity/crystallinity, and pyridinoline content) in patients that either received long-term vitamin D (400-1200IU) and calcium (1.0-1.5g) supplementation, or did not. We have analyzed by Raman microspectroscopy the bone forming trabecular surfaces of iliac crest in pre-treatment samples of a teriparatide study and the endpoint biopsies of the control arm obtained from the HORIZON trial. In general, the mineral/matrix ratio and the glycosaminoglycan (GAG) content was higher while nanoporosity, (a surrogate for tissue water content), the mineral maturity/crystallinity (MMC) and the pyridinoline (Pyd) content was lower in patients without long-term supplementation. Moreover, all indices were significantly dependent on tissue age. In conclusion, vitamin D and calcium supplementation is associated with altered mineral and organic matrix properties.

Source: E P Paschalis, S Gamsjaeger, N Hassler, A Fahrleitner-Pammer, H Dobnig, J J Stepan, I Pavo, E F Eriksen, K Klaushofer. “Vitamin D and calcium supplementation for three years in postmenopausal osteoporosis significantly alters bone mineral and organic matrix quality” Bone (2017): 95:41-46.

Vitamin D

The Effect of Vitamin D on Bone and Osteoporosis ^*

Abstract

The main effect of the active vitamin D metabolite 1,25(OH)2D is to stimulate the absorption of calcium from the gut. The consequences of vitamin D deficiency are secondary hyperparathyroidism and bone loss, leading to osteoporosis and fractures, mineralization defects, which may lead to osteomalacia in the long term, and muscle weakness, causing falls and fractures. Vitamin D status is related to bone mineral density and bone turnover. Vitamin D supplementation may decrease bone turnover and increase bone mineral density. Several randomized placebo-controlled trials with vitamin D and calcium showed a significant decrease in fracture incidence. However, very high doses of vitamin D once per year may have adverse effects. When patients with osteoporosis are treated with a bisphosphonate, they should receive a vitamin D and calcium supplement unless the patient is vitamin D replete. These subjects are discussed in detail in this review. Finally, the knowledge gaps and research agenda are discussed.

Source: Paul Lips, Natasja M van Schoor. “The effect of vitamin D on bone and osteoporosis” Best Practice & Research: Clinical Endocrinology & Metabolism (2011): 25(4):585-91.

The Role of Vitamin D in Maintaining Bone Health in Older People ^*

Abstract

This review summarises aspects of vitamin D metabolism, the consequences of vitamin D deficiency, and the impact of vitamin D supplementation on musculoskeletal health in older age. With age, changes in vitamin D exposure, cutaneous vitamin D synthesis and behavioural factors (including physical activity, diet and sun exposure) are compounded by changes in calcium and vitamin D pathophysiology with altered calcium absorption, decreased 25-OH vitamin D [25(OH)D] hydroxylation, lower renal fractional calcium reabsorption and a rise in parathyroid hormone. Hypovitaminosis D is common and associated with a risk of osteomalacia, particularly in older adults, where rates of vitamin D deficiency range from 10–66%, depending on the threshold of circulating 25(OH)D used, population studied and season. The relationship between vitamin D status and osteoporosis is less clear. While circulating 25(OH)D has a linear relationship with bone mineral density (BMD) in some epidemiological studies, this is not consistent across all racial groups. The results of randomized controlled trials of vitamin D supplementation on BMD are also inconsistent, and some studies may be less relevant to the older population, as, for example, half of participants in the most robust meta-analysis were aged under 60 years. The impact on BMD of treating vitamin D deficiency (and osteomalacia) is also rarely considered in such intervention studies. When considering osteoporosis, fracture risk is our main concern, but vitamin D therapy has no consistent fracture-prevention effect, except in studies where calcium is coprescribed (particularly in frail populations living in care homes). As a J-shaped effect on falls and fracture risk is becoming evident with vitamin D interventions, we should target those at greatest risk who may benefit from vitamin D supplementation to decrease falls and fractures, although the optimum dose is still unclear.

Source: Thomas R. Hill and  Terry J. Aspray. “The role of vitamin D in maintaining bone health in older people” Therapeutic Advances in Musculoskeletal Disease (2017): 9(4): 89–95. 

Latitude, Sun Exposure and Vitamin D Supplementation: Associations with Quality of Life and Disease Outcomes in a Large International Cohort of People with Multiple Sclerosis ^*

Abstract

Background: A growing evidence base implicates vitamin D, sun exposure and latitude in the aetiology of multiple sclerosis (MS), however there are less data on the associations of these variables with disease outcomes.

Methods: We undertook a cross-sectional survey of over 2000 people with MS recruited through internet platforms, seeking self-reported data on geographical location, intentional sun exposure for health, and supplementation with vitamin D, among other lifestyle variables. We also requested data on health-related quality of life (MSQOL-54), self-reported doctor-diagnosed relapse rate, and disability (Patient Determined Disease Steps). Bivariate and multivariate analyses were used for comparisons, including multiple linear regression modeling.

Results: Of 2301 participants, 82.3 % were female, median age was 45 years (IQR 38–53 years), with a median time since diagnosis of 6 years (IQR 3-12 years), the majority (61.6 %) having relapsing-remitting MS. Nearly two-thirds (64.6 %) lived in the Northern hemisphere, mostly in developed countries. Most (66.8 %) reported deliberate sun exposure to raise their vitamin D level, and the vast majority (81.8 %) took vitamin D supplements, mostly 2000–5000 IU a day on average. Unadjusted regression modeling incorporating deliberate sun exposure, latitude and vitamin D supplementation showed strong associations of sun exposure with HRQOL which disappeared when controlling for gender, age, disability, physical activity, and fish consumption. In contrast, associations between vitamin D supplementation and HRQOL were maintained adjusting for these variables, with a dose–response effect. Only latitude had significant adjusted associations with disability, with an increase of latitude by one degree (further from the equator) predicting increased odds of moderate disability (OR 1.02 (95 % CI 1.01–1.04)) or high disability (OR 1.03 (95 % CI 1.01–1.05)) compared to no/mild disability. Similarly, latitude was related to relapse rate, with increase in latitude of 1 degree associated with increased odds of having more relapses over the previous year (1.01 (1.00–1.02)).

Conclusions: We detected significant associations between latitude, deliberate sun exposure and vitamin D supplementation and health outcomes of this large group of people with MS. Vitamin D is likely to have a key role in these associations and its role in the health outcomes of people with MS urgently requires further study.

Source: George A. Jelinek, Claudia H. Marck, Tracey J. Weiland, Naresh Pereira, Dania M. van der Meer, and Emily J. Hadgkiss. “Latitude, sun exposure and vitamin D supplementation: associations with quality of life and disease outcomes in a large international cohort of people with multiple sclerosis” BMC Neurology (2015): 15: 132.

Magnesium

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

Abstract

Magnesium has been shown to increase bone mineral density when used in the treatment of osteoporosis, yet its mechanism of action is obscure. 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.

Source: Hasan Aydin, Oğuzhan Deyneli, Dilek Yavuz, Hülya Gözü, Nilgün Mutlu, Işik Kaygusuz, Sema Akalin. “Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women” Biological Trace Element Research (2010): 133(2):136-43.

Magnesium and Osteoporosis: Current State of Knowledge and Future Research Directions ^*

Abstract

A tight control of magnesium homeostasis seems to be crucial for bone health. On the basis of experimental and epidemiological studies, both low and high magnesium have harmful effects on the bones. Magnesium deficiency contributes to osteoporosis directly by acting on crystal formation and on bone cells and indirectly by impacting on the secretion and the activity of parathyroid hormone and by promoting low grade inflammation. Less is known about the mechanisms responsible for the mineralization defects observed when magnesium is elevated. Overall, controlling and maintaining magnesium homeostasis represents a helpful intervention to maintain bone integrity.

Source: Sara Castiglioni, Alessandra Cazzaniga, Walter Albisetti, and Jeanette A. M. Maier. “Magnesium and Osteoporosis: Current State of Knowledge and Future Research Directions” Nutrients (2013): 5(8): 3022–3033.

Dietary Magnesium May Be Protective for Aging of Bone and Skeletal Muscle in Middle and Younger Older Age Men and Women: Cross-Sectional Findings from the UK Biobank Cohort ^*

Abstract

Although fragility fractures, osteoporosis, sarcopenia, and frailty are becoming more prevalent in our aging society the treatment options are limited and preventative strategies are needed. Despite magnesium being integral to bone and muscle physiology, the relationship between dietary magnesium and skeletal muscle and bone health has not been investigated concurrently to date. We analysed cross-sectional associations between dietary magnesium and skeletal muscle mass (as fat free mass—FFM), grip strength, and bone density (BMD) in 156,575 men and women aged 39–72 years from the UK Biobank cohort. FFM was measured with bioelectrical impedance and was expressed as the percentage of body weight (FFM%) or as divided by body mass index (FFM_BMI). Adjusted mean grip strength, FFM%, FFM_BMI, and BMD were calculated according to quintiles of dietary magnesium, while correcting for covariates. Significant inter-quintile differences across intakes of magnesium existed in men and women, respectively, of 1.1% and 2.4% for grip strength, 3.0% and 3.6% for FFM%, 5.1% and 5.5% for FFM_BMI, and 2.9% and 0.9% for BMD. These associations are as great or greater than annual measured losses of these musculoskeletal outcomes, indicating potential clinical significance. Our study suggests that dietary magnesium may play a role in musculoskeletal health and has relevance for population prevention strategies for sarcopenia, osteoporosis, and fractures. 

Source: Ailsa A. Welch, Jane Skinner, and  Mary Hickson. “Dietary Magnesium May Be Protective for Aging of Bone and Skeletal Muscle in Middle and Younger Older Age Men and Women: Cross-Sectional Findings from the UK Biobank Cohort” Nutrients (2017): 9(11): 1189. 

Magnesium Intake, Bone Mineral Density, and Fractures: Results from The Women's Health Initiative Observational Study ^*

Abstract

Background: Magnesium is a necessary component of bone, but its relation to osteoporotic fractures is unclear.

Objective: We examined magnesium intake as a risk factor for osteoporotic fractures and altered bone mineral density (BMD).

Design: This prospective cohort study included 73,684 postmenopausal women enrolled in the Women's Health Initiative Observational Study. Total daily magnesium intake was estimated from baseline food-frequency questionnaires plus supplements. Hip fractures were confirmed by a medical record review; other fractures were identified by self-report. A baseline BMD analysis was performed in 4778 participants.

Results: Baseline hip BMD was 3% higher (P < 0.001), and whole-body BMD was 2% higher (P < 0.001), in women who consumed >422.5 compared with <206.5 mg Mg/d. However, the incidence and RR of hip and total fractures did not differ across quintiles of magnesium. In contrast, risk of lower-arm or wrist fractures increased with higher magnesium intake [multivariate-adjusted HRs of 1.15 (95% CI: 1.01, 1.32) and 1.23 (95% CI: 1.07, 1.42) for quintiles 4 and 5, respectively, compared with quintile 1; P-trend = 0.002]. In addition, women with the highest magnesium intakes were more physically active and at increased risk of falls [HR for quintile 4: 1.11 (95% CI: 1.06, 1.16); HR for quintile 5: 1.15 (95% CI: 1.10, 1.20); P-trend < 0.001].

Conclusions: Lower magnesium intake is associated with lower BMD of the hip and whole body, but this result does not translate into increased risk of fractures. A magnesium consumption slightly greater than the Recommended Dietary Allowance is associated with increased lower-arm and wrist fractures that are possibly related to more physical activity and falls.

Source: Tonya S Orchard, Joseph C Larson, Nora Alghothani, Sharon Bout-Tabaku, Jane A Cauley, Zhao Chen, Andrea Z LaCroix, Jean Wactawski-Wende, Rebecca D Jackson. “Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational Study” American Journal of Clinical Nutrition (2014): 99(4):926-33.

Vitamins K1 and K2

Vitamin K and Bone ^*

Summary

Vitamin K is mainly known as an agent involved in blood coagulation, maintaining the activity of coagulation factors in the liver. In addition, epidemiological studies suggested that a lack of vitamin K is associated with several diseases, including osteoporosis and vascular calcification. There are two main kinds of vitamin K: Phylloquinone (or PK) and Menaquinones (MKn), both act as co-enzyme of y-glutamyl carboxylase (GGCX) transforming under-carboxylated in carboxylated vitamin K dependent proteins, such as Bone Gla Protein (or Osteocalcin) and Matrix Gla Protein. Recently, Vitamin K was also identified as a ligand of the nuclear steroid and xenobiotic receptor (SXR) (in murine species Pregnane X Receptor: PXR), expressed in osteoblasts. The purpose of this literature review is to evaluate the protective role of Vitamin K in bone and vascular health.

Source: Maria Fusaro, Maria Cristina Mereu, Andrea Aghi, Giorgio Iervasi, and Maurizio Gallieni. “Vitamin K and Bone” Clinical Cases in Mineral and Bone Metabolism (2017): 14(2): 200–206.

Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human Health ^*

Abstract

Objective: To review the evidence for the use of vitamin K supplementation in clinical conditions such as osteoporosis, vascular calcification, arthritis, cancer, renal calculi, diabetes, and warfarin therapy.

Quality of Evidence: PubMed was searched for articles on vitamin K (K1 and K2) along with books and conference proceedings and health conditions listed above. Level I and II evidence supports the use of vitamins K1 and K2 in osteoporosis and Level II evidence supports vitamin K2 in prevention of coronary calcification and cardiovascular disease. Evidence is insufficient for use in diabetes, arthritis, renal calculi, and cancer.

Main Message: Vitamin K2 may be a useful adjunct for the treatment of osteoporosis, along with vitamin D and calcium, rivaling bisphosphonate therapy without toxicity. It may also significantly reduce morbidity and mortality in cardiovascular health by reducing vascular calcification. Vitamin K2 appears promising in the areas of diabetes, cancer, and osteoarthritis. Vitamin K use in warfarin therapy is safe and may improve INR control, although a dosage adjustment is required.

Conclusion: Vitamin K supplementation may be useful for a number of chronic conditions that are afflicting North Americans as the population ages. Supplementation may be required for bone and cardiovascular health.

Source: Gerry Kurt Schwalfenberg. “Vitamins K1 and K2: The Emerging Group of Vitamins Required for Human Health” Journal of Nutrition and Metabolism (2017): 2017: 6254836.

Vitamin K and the Prevention of Fractures: Systematic Review and Meta-Analysis of Randomized Controlled Trials ^*

Abstract

Background: Observational and some experimental data suggest that low intake of vitamin K may be associated with an increased risk of fracture.

Objective: To assess whether oral vitamin K (phytonadione and menaquinone) supplementation can reduce bone loss and prevent fractures.

Data sources: The search included the following electronic databases: MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), the Cochrane Library (issue 2, 2005), the ISI Web of Science (1945 to June 2005), the National Research Register (inception to the present), Current Controlled Trials, and the Medical Research Council Research Register.

Study selection: Randomized controlled trials that gave adult participants oral phytonadione and menaquinone supplements for longer than 6 months were included in this review.

Data extraction: Four authors extracted data on changes in bone density and type of fracture. All articles were double screened and double data extracted.

Data synthesis: Thirteen trials were identified with data on bone loss, and 7 reported fracture data. All studies but 1 showed an advantage of phytonadione and menaquinone in reducing bone loss. All 7 trials that reported fracture effects were Japanese and used menaquinone. Pooling the 7 trials with fracture data in a meta-analysis, we found an odds ratio (OR) favoring menaquinone of 0.40 (95% confidence interval [CI], 0.25-0.65) for vertebral fractures, an OR of 0.23 (95% CI, 0.12-0.47) for hip fractures, and an OR of 0.19 (95% CI, 0.11-0.35) for all nonvertebral fractures.

Conclusions: This systematic review suggests that supplementation with phytonadione and menaquinone-4 reduces bone loss. In the case of the latter, there is a strong effect on incident fractures among Japanese patients.

Source: Sarah Cockayne, Joy Adamson, Susan Lanham-New, Martin J Shearer, Simon Gilbody, David J Torgerson. “Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials” Archives of Internal Medicine (2006): 166(12):1256-61.

Zinc

Role of Nutritional Zinc in the Prevention of Osteoporosis ^*

Abstract

Zinc is known as an essential nutritional factor in the growth of the human and animals. Bone growth retardation is a common finding in various conditions associated with dietary zinc deficiency. Bone zinc content has been shown to decrease in aging, skeletal unloading, and postmenopausal conditions, suggesting its role in bone disorder. Zinc has been demonstrated to have a stimulatory effect on osteoblastic bone formation and mineralization; the metal directly activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational process of protein synthesis, in the cells, and it stimulates cellular protein synthesis. Zinc has been shown to stimulate gene expression of the transcription factors runt-related transcription factor 2 (Runx2) that is related to differentiation into osteoblastic cells. Moreover, zinc has been shown to inhibit osteoclastic bone resorption due to inhibiting osteoclast-like cell formation from bone marrow cells and stimulating apoptotic cell death of mature osteoclasts. Zinc has a suppressive effect on the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-induced osteoclastogenesis. Zinc transporter has been shown to express in osteoblastic and osteoclastic cells. Zinc protein is involved in transcription. The intake of dietary zinc causes an increase in bone mass. beta-Alanyl-L: -histidinato zinc (AHZ) is a zinc compound, in which zinc is chelated to beta-alanyl-L: -histidine. The stimulatory effect of AHZ on bone formation is more intensive than that of zinc sulfate. Zinc acexamate has also been shown to have a potent-anabolic effect on bone. The oral administration of AHZ or zinc acexamate has the restorative effect on bone loss under various pathophysiologic conditions including aging, skeletal unloading, aluminum bone toxicity, calcium- and vitamin D-deficiency, adjuvant arthritis, estrogen deficiency, diabetes, and fracture healing. Zinc compounds may be designed as new supplementation factor in the prevention and therapy of osteoporosis.

Source: Masayoshi Yamaguchi. “Role of nutritional zinc in the prevention of osteoporosis” Molecular and Cellular Biochemistry (2010): 338(1-2):241-54.

The Relationship Between Bone Health and Plasma Zinc, Copper Lead and Cadmium Concentration in Osteoporotic Women ^*

Abstract

Osteoporosis is a multi-factorial disease with dimension of genetic and nutritional considerations. The aim of this study was to present data from the association of plasma zinc, copper and toxic elements of lead and cadmium levels with bone mineral density in Iranian women. 135 women gave their information and enrolled. Fasting plasma was used for measurement of trace elements and heavy metals by Differential Pulse Anodic Stripping Voltammetry. Control group (n = 51) were normal in both lumbar spine (L₁-L₄) and femoral neck density (T-score ≥ −1), but just femoral neck T-score was considered as criterion in selection of patient group (n = 49, Tscore < −1). No differences were found in the nutritional status, number of diseases, drugs and functional activities between these groups. Plasma Zn, Cu, Pb, Cd levels were analyzed by, a method of voltammetry. Mean ± SD levels of copper and zinc was 1.168 ± 0.115, 1.097 ± 0.091 μg/ml in control group, 1.394 ± 0.133, 1.266 ± 0.11 μg/ml in total patient (TP) and 1.237 ± 0.182, 1.127 ± 0.176 μg/ml in Mild patients(−1 > T-score > −1.7), 1.463 ± 0.174, 1.327 ± 0.147 μg/ml in Severe patient group (T-score < −1.7); respectively. Mean ± SD plasma level of lead and cadmium was 168.42 ± 9.61 ng/l, 2.91 ± 0.18 ng/ml in control group, 176.13 ± 8.64 ng/l, 2.97 ± 0.21 ng/ml in TP, 176.43 ± 13.2 ng/l, 2.99 ± 0.1 ng/ml in mild patients, 221.44 ± 20 ng/l and 3.80 ± 0.70 ng/ml in severe patient group, respectively. In this study plasma zinc, copper, lead & cadmium concentrations were higher in the patients than in the control, though differences were not significant. However, differences were higher between the controls and patients with severe disease (T-score < −1.7). In addition adjusted T-score of femur with age and BMI showed negative significant correlation with plasma levels of zinc and lead in total participants (p < 0.05, r = −0.201, p = 0.044, r = −0.201). It seems that more extensive study with larger ample size might supply definite results about this association for copper and cadmium.

Source: Naficeh Sadeghi, Mohammad Reza Oveisi, Behrooz Jannat, Mannan Hajimahmoodi, Masoomeh Behzad,Abdolazim Behfar, Fatemeh Sadeghi, and  Sahereh Saadatmand. “The relationship between bone health and plasma zinc, copper lead and cadmium concentration in osteoporotic women” Journal of Environmental Health Science and Engineering (2014): 12: 125. 

Zinc Supplementation Improves Bone Density in Patients with Thalassemia: A Double-Blind, Randomized, Placebo-Controlled Trial ^*

Abstract

Background: Patients with thalassemia major (Thal) frequently have low plasma zinc, which has been associated with low bone mass.

Objective: The objective was to determine the effect of zinc supplementation on bone mass in patients with Thal.

Design: Forty-two subjects (21 females aged 10–30 y) with Thal and low bone mass were randomly assigned to receive 25 mg Zn/d or placebo. Bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed by using dual-energy X-ray absorptiometry, and fasting blood was collected for the measurement of plasma zinc at 0, 12, and 18 mo.

Results: Thirty-two subjects, 81% of whom were transfusion dependent, completed the study (mean ± SD: 17.1 ± 5.2 y). Plasma zinc was ≤70 μg/dL in 11 subjects at baseline and increased significantly with zinc supplementation (P = 0.014). Use of intention-to-treat analysis and linear models for longitudinal data, adjusted for baseline and pubertal stage, showed that the zinc group had significantly greater increases in whole-body BMC (adjusted mean ± SE: 63 ± 15 g; P = 0.02), and aBMD (0.023 ± 0.006 g/cm²; P = 0.04) than did the placebo group after 18 mo. Furthermore, adjusted spine and hip aBMD z scores each decreased by 0.3 SDs (both P = 0.04) in the placebo compared with the zinc group over the 18-mo study.

Conclusions: In young patients with Thal, zinc supplementation resulted in greater gains in total-body bone mass than did placebo. Zinc was well tolerated and is worthy of investigation in larger trials in Thal patients across a range of ages and disease severity. This trial was registered at clinicaltrials.gov as NCT00459732.

Source: Ellen B Fung, Janet L Kwiatkowski, James N Huang, Ginny Gildengorin, Janet C King, and Elliott P Vichinsky. “Zinc supplementation improves bone density in patients with thalassemia: a double-blind, randomized, placebo-controlled trial” American Journal of Clinical Nutrition (2013): 98(4): 960–971. 

Manganese & Copper

Effects on Bone Loss of Manganese Alone or with Copper Supplement in Ovariectomized Rats. A Morphometric and Densitomeric Study ^*

Abstract

Objective: The aim of this study was to examine the effect of manganese (Mn) alone and with the addition of copper (Cu) in the inhibition of osteopenia induced by ovariectomy (OVX) in rats. STUDY CONDITIONS: Four lots of 100-day-old female Wistar rats were divided into experimental groups of 15 each. One group received a diet supplemented with 40 mg/kg of Mn per kilogram of feed (OVX+Mn). The second group received the same diet as the first, but with an additional 15 mg/kg of copper (OVX+Mn+Cu). The third group of 15 OVX and the fourth group of 15 Sham-OVX received no supplements. At the conclusion of the 30-day experiment, the rats were slaughtered and their femurs and fifth lumbar vertebrae were dissected. Femoral and vertebral length were measured with caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone density (BMD) of the femur (F-BMC, mg and F-BMD, mg/cm(2)) and the fifth lumbar vertebra (V-BMC, mg and V-BMD, mg/cm(2)) were measured separately with dual energy X-ray absorptiometry.

Results: The F-BMD, mg/cm(2) was lower in the OVX than in the Sham-OVX group (P<0.0001) and in the other two groups receiving mineral supplements (P<0.005 in both). F-BMC, mg was significantly lower in the OVX group than in the other three (P<0.0001 in all cases). Calculations for V-BMC, mg and V-BMD, mg/cm(2) are similar to findings in the femur.

Conclusions: These data show that a Mn supplement is an effective inhibitor of loss of bone mass after OVX, both on the axial and the peripheral levels, although this effect is not enhanced with the addition of Cu.

Source: H Rico, N Gómez-Raso, M Revilla, E R Hernández, C Seco, E Páez, E Crespo. “Effects on bone loss of manganese alone or with copper supplement in ovariectomized rats. A morphometric and densitomeric study” European Joournal of Obstetrics & Gynecology and Reproductive Biology (2000): 90(1):97-101.

Effect of Manganese on Calcification of Bone ^*

Abstract

Young mice were maintained on a basal diet composed of meat, which is poor in both manganese and calcium. 2. The addition of small amounts (2·5–5·0mg./kg. of meat) of manganese improved weight gain and calcification of bone and decreased incorporation of injected radiocalcium into bone. 3. Prolonged treatment with larger amounts (10·0–25·0mg./kg. of meat) of manganese depressed growth, induced defective calcification of bone and increased incorporation of radiocalcium into bone.

Source: E. Tal and K. Guggenheim. “Effect of manganese on calcification of bone” Biochemical Journal (1965): 95(1): 94–97. 

Potassium

Dietary Potassium Intake is Beneficial to Bone Health in a Low Calcium Intake Population: The Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2011) ^*

Abstract

Dietary potassium may neutralize acid load and reduce calcium loss from the bone, leading to beneficial effect on bone mineral density. In this nationwide Korean population study, dietary potassium intake was associated with improved bone mineral density in older men and postmenopausal women.

Introduction: Nutrition is a major modifiable factor that affects bone health. The accompanying anion in dietary potassium may act as an alkaline source by neutralizing the acid load and reducing calcium loss from the bone. We aimed to evaluate the association between dietary potassium intake and bone mineral density (BMD) in the Korean population.

Methods: We analyzed a total of 3135 men aged >50 years and 4052 postmenopausal women from the Korean National Health and Nutrition Examination Survey (KNHANES). Lumbar spine, total hip, and femur neck BMD were measured using dual energy X-ray absorptiometry. The daily food intake was assessed using a food frequency questionnaire.

Results: When we divided the participants into tertiles based on the intake of potassium intake, the highest potassium intake tertile group showed a significantly higher total hip and femur neck BMD as compared to lower tertile groups (0.914 ± 0.004, 0.928 ± 0.003, 0.925 ± 0.004 mg/day across the tertiles, P = .014 for total hip; 0.736 ± 0.003, 0.748 ± 0.003, 0.750 ± 0.004 mg/day, P = .012 for femur neck). Postmenopausal women in the highest potassium intake tertile group showed significantly higher lumbar, total hip, and femur neck BMD as compared to those in lower potassium intake tertile groups (0.793 ± 0.004, 0.793 ± 0.003, 0.805 ± 0.004 mg/day across the tertiles, P = .029 for lumbar spine; 0.766 ± 0.003, 0.770 ± 0.002, 0.780 ± 0.003 mg/day, P = .002 for total hip; 0.615 ± 0.003, 0.619 ± 0.002, 0.628 ± 0.003 mg/day, P = .002 for femur neck).

Conclusions: Dietary potassium intake was positively associated with BMD in men aged >50 years and postmenopausal women, indicating the beneficial effects of dietary potassium intake on bone health.

Source: S H Kong, J H Kim, A R Hong, J H Lee, S W Kim, C S Shin. “Dietary potassium intake is beneficial to bone health in a low calcium intake population: the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2011)” Osteoporosis International (2017): 1577-1585.

The Effects of High Potassium Consumption on Bone Mineral Density in a Prospective Cohort Study of Elderly Postmenopausal Women ^*

Abstract

Few studies have investigated the long-term effects of potassium intake on BMD. In a cohort of 266 elderly women, we found that baseline potassium intake as reflected by 24-hour urine potassium excretion had positive association with BMD measured at 1 and/or 5 years later, suggesting a role of dietary potassium on osteoporosis prevention.

Introduction: High dietary potassium intake has been suggested to be beneficial for bone structure, but few studies have investigated the long-term effects of potassium intake on BMD in elderly women. We examined the relationship between potassium intake as reflected by 24-hour urine potassium excretion and bone density in a cohort of elderly women.

Methods: The study subjects were 266 elderly postmenopausal women aged 70-80 years. Twenty-four-hour urinary potassium excretion was determined at baseline. At one year hip DXA BMD was measured, at 5 years hip and total body DXA BMD and distal radius and tibia pQCT vBMD were measured. The effects of potassium were evaluated by ANCOVA according to the quartile of baseline urinary potassium excretion.

Results: After adjustment for confounding factors, subjects in the highest quartile of urinary potassium excretion had significantly higher total hip BMD at 1 (5%) and 5 years (6%), and significantly higher total body BMD (4%) and 4% distal tibia total (7%) and trabecular vBMD (11%) at 5 years than those in the lowest quartile.

Conclusions: Potassium intake shows positive association with bone density in elderly women, suggesting that increasing consumption of food rich in potassium may play a role in osteoporosis prevention.

Source: K Zhu, A Devine, R L Prince. “The effects of high potassium consumption on bone mineral density in a prospective cohort study of elderly postmenopausal women” Osteoporosis International (2009): 20(2):335-40.

The Association of Potassium Intake with Bone Mineral Density and the Prevalence of Osteoporosis Among Older Korean Adults ^*

Abstract

Background/objectives: Osteoporosis is characterized by low bone mass and results in vulnerability to fracture. Calcium and vitamin D are known to play an important role in bone health. Recently, potassium has been identified as another important factor in skeletal health. We examined the link between potassium intake and bone health among the Korean older adult population.

Subjects/methods: This retrospective, cross-sectional study included 8,732 men and postmenopausal women over 50 years old who completed the Korean National Health and Nutrition Survey (KNHANES) between 2008 and 2011. Potassium consumption was evaluated using a 24-hour recall method. Bone mineral density (BMD) was measured at three sites (total hip, femur neck, and lumbar spine) by dual-energy X-ray absorptiometry (DEXA). Multinomial logistic regression was used to examine the link between potassium intake and prevalence of osteoporosis and osteopenia, after controlling for potential confounding variables.

Results: The BMD of the total femur and Ward's triangle were significantly different according to the potassium intake among men (P = 0.031 and P = 0.010, respectively). Women in the top tertile for potassium intake showed higher BMD than those in the bottom tertile at all measurement sites (all P < 0.05). Daily potassium intake was significantly related to a decreased risk of osteoporosis at the lumbar spine in postmenopausal women (odds ratios: 0.68, 95% confidence interval: 0.48-0.96, P trend = 0.031). However, the dietary potassium level was not related to the risk of osteoporosis in men.

Conclusion: Current findings indicate that higher dietary potassium levels have a favorable effect on bone health and preventing osteoporosis in older Korean women.

Source: Jinwoo Ha, Seong-Ah Kim, Kyungjoon Lim, Sangah Shin. “The association of potassium intake with bone mineral density and the prevalence of osteoporosis among older Korean adults” Nutrition Research and Practice (2020): 14(1):55-61.

Bone Metabolism

The Role of the Osteocyte in Bone and Non-bone Disease ^*

Synopsis

When normal physiological functions go awry, disorders and disease occurs. This is universal, even for the osteocyte, a cell embedded within the mineralized matrix of bone. It was once thought that this cell was simply a place-holder in bone. However, within the last decade, the number of studies of osteocytes has dramatically increased leading to the discovery of novel functions of these cells. But with the discovery of novel physiological functions came the discoveries of how these cells can also be responsible for not only bone diseases and disorders, but also those of kidney, heart, and potentially muscle.

Source: Lynda F. Bonewald, PhD, Executive Director. “The Role of the Osteocyte in Bone and Non-bone Disease” Endocrinology and Metabolism Clinics of North America (2017):  46(1): 1–18.

Recent Progress in Osteocyte Research ^*

Abstract

The last decade has seen an exponential increase in our understanding of osteocytes function and biology. These cells, once considered inert by-standers trapped into the mineralized bone, has now risen to be key regulators of skeletal metabolism, mineral homeostasis, and hematopoiesis. As tools and techniques to study osteocytes improved and expanded, it has become evident that there is more to these cells than initially thought. Osteocytes are now recognized not only as the key responders to mechanical forces but also as orchestrators of bone remodeling and mineral homeostasis. These cells are the primary source of several important proteins, such as sclerostin and fibroblast growth factor 23, that are currently target as novel therapies for bone loss (as the case for antisclerostin antibodies) or phosphate disorders. Better understanding of the intricate cellular and molecular mechanisms that govern osteocyte biology will open new avenue of research and ultimately indentify novel therapeutics to treat bone and mineral disorders. This review summarizes novel findings and discusses future avenues of research.

Source: Paola Divieti Pajevic. “Recent Progress in Osteocyte Research” Endocrinology and Metabolism (2013): 28 (4): 255-261.

Osteocyte Signaling in Bone ^*

Abstract

Osteocytes, the cells residing within the bone matrix and comprising 90% to 95% of the all bone cells, have long been considered quiescent bystander cells compared to the osteoblasts and osteoclasts whose activities cause bone gain and loss, and whose dysfunction lead to growth defects and osteoporosis. However, recent studies show that osteocytes play a crucial, central role in regulating the dynamic nature of bone in all its diverse functions. Osteocytes are now known to be the principal sensors for mechanical loading of bone. They produce the soluble factors that regulate the onset of both bone formation and resorption. Osteocytes regulate local mineral deposition and chemistry at the bone matrix level, and they also function as endocrine cells producing factors that target distant organs such as the kidney to regulate phosphate transport. Osteocytes appear to be the major local orchestrator of many of bone’s functions.

Source: Mitchell B. Schaffler and Oran D. Kennedy. “Osteocyte Signaling in Bone” Current Osteoporosis Reports (2013): 10(2): 118–125.

The SWAN Song: Study of Women’s Health Across the Nation’s Recurring Themes ^*

Synopsis

There is a belief that reproductive health is a reflection of whole-body health. It then follows that abnormalities of reproductive milestones may be a manifestation of aberrant or unhealthy aging. In order to assess how menopause per se and the process of the menopause transition may affect future health risks and outcomes, the Study of Women’s Health Across the Nation was begun in 1994. SWAN, now in its 14^th follow-up year, has characterized the life experience of a multi-ethnic cohort of mid-life US women in an unprecedented level of detail. Several enduring themes have emerged from SWAN that have associated certain patterns of hormones and symptoms with metabolic status. Moreover, the nature of relationships between hormones, body size, ethnicity, metabolic status and cardiovascular disease symptoms risk vary as women traverse the menopause and ovarian hormone production eventually ceases. This review will describe these cross-cutting themes and their possible meaning for the health of the mid-life woman.

Source: Nanette Santoro, MD, E Stewart Taylor, and Kim Sutton-Tyrrell, PhD. “The SWAN Song: Study of Women’s Health Across the Nation’s Recurring Themes” Obstetrics and Gynecology Clinics of North America (2011):  38(3): 417–423.

Microelements for Bone Boost: The Last but Not the Least ^*

Summary

Osteoporosis is a major public health problem affects many millions of people around the world. It is a metabolic bone disease characterized by loss of bone mass and strength, resulting in increased risk of fractures. Several lifestyle factors are considered to be important determinants of it and nutrition can potentially have a positive impact on bone health, in the development and maintenance of bone mass and in the prevention of osteoporosis. There are potentially numerous nutrients and dietary components that can influence bone health, and these range from the macronutrients to micronutrients. In the last decade, epidemiological studies and clinical trials showed micronutrients can potentially have a positive impact on bone health, preventing bone loss and fractures, decreasing bone resorption and increasing bone formation. Consequently, optimizing micronutrients intake might represent an effective and low-cost preventive measure against osteoporosis.

Source: Giuseppe Della Pepa and Maria Luisa Brandi. “Microelements for bone boost: the last but not the least” Clinical Cases in Mineral and Bone Metabolism (2016): 13(3): 181–185.

 

References:

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300041/
2. https://dash.harvard.edu/bitstream/handle/1/11879695/3871031.pdf?sequence=1
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366431/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300041/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492638/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833003/
7. https://www.nytimes.com/2010/08/17/science/17qna.html?auth=login-google
8. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/vitamin-c
9. https://iopscience.iop.org/article/10.1088/1757-899X/180/1/012093/pdf
10. https://pubmed.ncbi.nlm.nih.gov/29644950/
11. https://econtent.hogrefe.com/doi/abs/10.1024/0300-9831/a000486?journalCode=vit&
12. https://pubmed.ncbi.nlm.nih.gov/22974214/#:~:text=Therefore%2C%20we%20concluded%20that%20vitamin,the%20increased%20PPAR%2D%CE%B3%20expression.
13. https://www.nutri-facts.org/en_US/news/u-s---nhanes.html
14. https://www.eurekaselect.com/134717/article
15. https://www.hopkinsmedicine.org/news/media/releases/calcium_supplements_may_damage_the_heart#:~:text=After%20analyzing%2010%20years%20of,a%20diet%20high%20in%20calcium%2D
16. https://www.mayoclinic.org/diseases-conditions/heart-attack/expert-answers/calcium-supplements/faq-20058352
17. https://www.ima-na.org/page/what_is_calcium_carb
18. https://www.eurekalert.org/pub_releases/2020-05/tnam-dci052720.php
19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185240/#:~:text=The%20Study%20of%20Women's%20Health%20Across%20the%20Nation%20(SWAN)%20is,factors%20for%20age%2Drelated%20diseases.
20. http://aquamin.com/science/bone-health-research/
21. Brennan, O., Sweeney, J., O’Meara, B. et al. Calcif Tissue Int (2017). https://doi.org/10.1007/s00223-017-0299-7
22. Slevin MM, Allsopp PJ, Magee PJ, et al. Supplementation with calcium and short -chain fructo-oligosaccharides affects markers of bone turnover but not bone mineral density in postmenopausal women. J Nutr. 2014;144(3):297-304.
23. O'Gorman DM, Tierney CM, Brennan O, O'Brien FJ. The marine-derived, multi-mineral formula, Aquamin, enhances mineralisation of osteoblast cells in vitro. Phytotherapy research 2012;26(3):375-80.
24. Quesada Gomez JM, Blanch Rubio J, Diaz Curiel M, et al. Calcium citrate and vitamin D in the treatment of osteoporosis. Clin Drug Investig. 2011;31(5):285-98.
25. Bikle DD. Vitamin D and bone. Curr Osteoporos Rep. 2012;10(2):151-9.
26. Schild A, Herter-Aeberli I, Fattinger K, et al. Oral Vitamin D Supplements Increase Serum 25-Hydroxyvitamin D in Postmenopausal Women and Reduce Bone Calcium Flux Measured by 41Ca Skeletal Labeling. J Nutr. 2015;145(10):2333-40.
27. https://pubmed.ncbi.nlm.nih.gov/27826025/
28. Weaver CM, Alexander DD, Boushey CJ, et al. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int. 2016;27(1):367-76.
29. https://www.scientificamerican.com/article/vitamin-d-deficiency-united-states/
30. https://www.kappabio.com/products/vitamin-k2/
31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494092/
32. https://wholefoodsmagazine.com/supplements/features-supplements/healthy-aging-4/
33. https://pubmed.ncbi.nlm.nih.gov/16801507/
34. https://www.medicalnewstoday.com/articles/316922#:~:text=Additionally%2C%20some%20previous%20studies%20have,and%20calcium%20homeostasis%20in%20bones.
35. https://pubmed.ncbi.nlm.nih.gov/19488681/
36. Matsuzaki H. Prevention of osteoporosis by foods and dietary supplements. Magnesium and bone metabolism. Clin Calcium. 2006;16(10):1655-60.
37. Yamaguchi M. Role of nutritional zinc in the prevention of osteoporosis. Mol Cell Biochem. 2010;338(1-2):241-54.
38. Yamaguchi M, Weitzmann MN. Zinc stimulates osteoblastogenesis and suppresses osteoclastogenesis by antagonizing NF-kappaB activation. Mol Cell Biochem. 2011;355(1-2):179-86.
39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318168/
40. https://pubmed.ncbi.nlm.nih.gov/28093633/#:~:text=Abstract,older%20men%20and%20postmenopausal%20women.
41. Strause L, Saltman P, Smith KT, et al. Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J Nutr. 1994;124(7):1060-4.