Ortho Bone™ Vegan


Helps develop and maintain healthy bones

  • Vegan forms of calcium and vitamin D
  • Provides active, effective forms of key bone-health nutrients
  • Improves bone growth & bone density while reducing bone loss
  • An unrivalled and comprehensive vegan bone formula exclusively available from AOR
Gluten Free

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Ortho Bone™ Vegan is an advanced bone health formula which provides nutrients that are fundamental for keeping bones strong, especially for those with osteoporosis, osteopenia or a history of bone fractures. Ortho Bone™ Vegan differs from AOR’s original Ortho Bone™ in that it is suitable for vegans, providing the most effective non-animal-based sources of calcium, vitamin D, and other bone-building nutrients.

Ortho Bone™ Vegan provides all of the vitamins and minerals known to benefit bone health, helping to reduce calcium loss and maintain bone mineral density. Calcium is the most abundant mineral found in bone, and calcium citrate-malate is the most absorbable vegan form of calcium. The special structure of calcium citrate-malate makes it six to nine times more easily dissolved in the stomach than plain calcium citrate and is absorbed 36% better; and calcium citrate is absorbed about 22% better than calcium carbonate. These statistics illustrate the superiority of calcium citrate-malate over both the citrate and carbonate forms.

While calcium is important, it is only part of the picture, and many other nutrients are needed to maintain strong, healthy bones. Ortho Bone™ Vegan also provides vitamins D and K for proper absorption and usage of calcium, vitamin C and silicon to support collagen production, magnesium which makes up a large part of the bone mineral matrix, boron to reduce magnesium loss, and trace minerals manganese, zinc and copper which are co-factors for enzymes involved in bone growth and repair. Lastly, vitamins B12 and folate are included to help reduce homocysteine, a metabolic by-product that is toxic to bone fibers.

AOR Advantage

AOR’s Ortho Bone™ Vegan is an advanced combination of important ingredients to support skeletal health. All key bone health nutrients are included in the formula in their most effective forms and in clinically-backed doses. Ortho Bone™ Vegan is an ideal formula for vegetarians, vegans, post-menopausal women, and those with osteopenia or a family history of osteoporosis.





Ortho Bone™ Vegan is a multi-vitamin and mineral supplement which contains ingredients that help in the development and maintenance of healthy bones. Calcium intake, when combined with sufficient vitamin D, a healthy diet, and regular exercise, may reduce the risk of developing osteoporosis. Ortho Bone™ Vegan also provides adequate folate which, along with other ingredients, helps to form red blood cells.


AOR™ guarantees that all ingredients have been declared on the label. Contains no wheat, gluten, peanuts, sesame seeds, sulphites, mustard, dairy, eggs or any animal by-product.

Adult Dosage

Take up to 10 capsules daily with meals, or as directed by a qualified health care practitioner. Take a few hours before or after taking other medications.


Consult a health care practitioner prior to use if you are taking blood thinners. Some people may experience diarrhea. This product contains corn and soy derived ingredient, do not consume if you have such allergies.

Main Applications
  • Vegeterian sources of calcium and vitamin D
  • Bone health
  • Osteopenia

The information and product descriptions appearing on this website are for information purposes only, and are not intended to provide or replace medical advice to individuals from a qualified health care professional. Consult with your physician if you have any health concerns, and before initiating any new diet, exercise, supplement, or other lifestyle changes.

Serving Size: 10 Capsules
Vitamin D3 (Cholecalciferol)
1000 IU (25 mcg)
120 mcg
60 mcg
60 mcg

Non-medicinal Ingredients: Tapioca dextrin, maltodextrin, citric acid, glycine, L-aspartic acid, rice and soy flour, magnesium trisilicate, silica, sucrose, acacia gum, corn starch, tricalcium phosphate, medium chain triglycerides.

Capsule: hypromellose.


Core Bone-Building Nutrients

A superior nutritional supplement for bone health must be built on a foundation of ossein Microcrystalline Hydroxyapatite Complex (MCHC) as the calcium source, and fortified with well-established nutrient cofactors such as Magnesium, Zinc, Manganese, Copper, Vitamin C, and Vitamin D3 and Vitamin K2, whose revolutionary effects on bone health are now well-known. Ortho•Bone Vegan offers all the essential vitamins and minerals for good bone health in their superior vegan forms for optimal bone support. Ortho•Bone Vegan differs from Ortho•Bone in two ways: it contains calcium citrate-malate, the most bioavailable vegan calcium source instead of MCHC, and  plant-sourced vitamin D2 rather than vitamin D3 from sheep wool.

Maintaining bone health is a hot topic today, yet there remains confusion in the minds of many health-conscious people about the right dose and form of even the most well-known bone health nutrients, while the importance of other key nutrients in keeping the skeleton strong remains largely unknown. Here’s a review of the controversies and recent discoveries of important bone health nutrients and their various forms and doses.

 Take Enough Vitamins D & K2

Aside from improving calcium absorption, vitamin D is needed for proper muscle function, which may play a role in protecting against fractures by reducing falls. But you simply can’t rely on the sun to meet your requirements, especially in Northern climates. At least 800 IUs per day are recommended.

Similarly to Vitamin D,Vitamin K2 is essential to absorbing and properly utilizing the calcium you ingest. Vitamin K2 helps shunt the calcium from the bloodstream into the bones. In fact, taking a lot of calcium without adequate vitamins D & K can be dangerous.

Ortho•Bone Vegan contains vitamin D3, a vegetarian form of vitamin D, and vitamin K2 in the forms of MK-4 & MK-7, the most effective forms of K2.

Get the Right Kind of Calcium

Too many health-conscious people believe that conventional calcium supplements (or conventional calcium plus vitamin D) can put an end to bone loss. They can’t. As multiple studies have documented, conventional calcium supplements – such as calcium gluconate, calcium citrate, and calcium carbonate – slow, but do not halt or reverse, menopausal bone loss, whether taken alone or with vitamin D. You simply can’t force the bones to take in more calcium, and build more bone, by taking more and more calcium: the mineral itself can only provide the raw material needed to support your existing bone mass, or to allow other factors in your skeletal health program to build up new bone. But there is one seeming exception.

MCHC: The Best Form of Calcium

Ossein microcrystalline hydroxyapatite complex (MCHC) consistently halts, or even reverses, bone loss in controlled human trials. When put head-to-head against other calcium supplemental forms, MCHC consistently trumps conventional calcium supplements.

Calcium Citrate-Malate for Vegetarians

Unfortunately, of course, vegetarians cannot consume MCHC because it is an animal product (although premium MCHC supplements use free-range, pasture-fed livestock from countries like New Zealand or Australia as sources for the raw materials). For vegetarians, the best calcium source is calcium citrate-malate.

Calcium citrate-malate is not the same thing as calcium citrate, or as a simple admixture of calcium citrate and calcium malate. Calcium citrate-malate is prepared in such a way that a significant number of its calcium atoms are bound to both citrate and malate molecules at once. This unique form makes calcium citrate-malate six to nine times more easily dissolved in the stomach than plain calcium citrate. This superior solubility may be at least part of the reason for the fact that calcium citrate-malate is considerably better-absorbed than calcium citrate.

Bottom line: take your calcium in the form of MCHC if you are comfortable with animal products; choose calcium citrate-malate if you’re not.

When to Take Your Calcium

Several recent studies have suggested that when you take your calcium can make a big difference in terms of both the amount of calcium you’ll absorb, and the effects of that calcium on your bones. For starters, take your calcium with food, as doing so will increase absorption. It’s also important to spread your calcium supplements over the course of the day, which increases your total absorption of calcium and keeps parathyroid hormone (PTH) under control throughout the day. To get the best possible results, take the largest single dose of calcium later in the day, at dinner or with a late-night snack.


Magnesium is another mineral commonly associated with the maintenance of bone health, which is very easy to fathom when one considers that two-thirds of the body’s magnesium stores are located in our bone structure. Much of the magnesium within this bone structure is part of the bone’s crystal lattice (which can metaphorically be referred to as the “bone scaffolding”) where it binds together with the minerals phosphorus and calcium. Magnesium on its own has been shown to slow the rate of bone turnover, which is when the growth of new bone is outpaced by the degeneration of old. Magnesium shortages result in the reduced assimilation of vitamin D as well as the inhibition of parathyroid hormone, leading to low blood calcium levels.


Boron’s effect on bone appears to be mediated by its ability to reduce the urinary excretion of calcium and magnesium, and this ability is due to its actions in the kidney. As stated above, this calcium-preserving effect of boron becomes pronounced in circumstances in which dietary magnesium is low. Therefore, boron is in effect acting as a backup system for magnesium in order to preserve calcium in the blood and reduce urinary calcium loss.

Boron also appears to enhance vitamin D, and although there is likely a relationship between this and its calcium-preserving effect, an accurate description for the mechanism of action of boron’s vitamin D enhancement is unclear.

Zinc, Copper & Manganese

Several other minerals have also been identified as co-factors for enzymes involved in bone metabolism – notably zinc, copper, and manganese. The latter is essential for the proper function of the osteoblast cells that are responsible for building new bone. Manganese also increases the activity of the enzyme alkaline phosphatase and as well as growth factors such as estrogen and IGF-1 in a manner that is directly pertinent to these osteoblast cells. Copper is essential for producing an enzyme called lysyl oxidase which cross-links (strengthens) collagen. Zinc, in turn, is essential for the operation of copper, since unbalanced zinc intake can reduce copper absorption.

Silicon, Vitamin C, B12 & Folate

Additionally, recent research indicates that silicon stimulates the formation of type 1 collagen as well as playing an important role in the body’s glycosaminoglycan network, which utilizes compounds such as hyaluronic acid and chondroitin sulfate in the cartilage, bone, and skin. Even vitamin C, a substance not normally associated with bone health, has been identified as a “possibly important modifiable risk factor for osteoporosis and bone fracture.” Finally, methylating nutrients such as vitamin B12 and folic acid may also be important to bone health, perhaps due to their ability to counter the toxic effects of homocysteine on the protein fibers in bone.




News Flash: The amount of calcium consumed is not the same as the amount of calcium absorbed. Calcium citrate-malate is a more bioavailable calcium than simple calcium citrate, and its documented support for bone health is superior to that of any other vegetarian calcium source. In fact, one study demonstrated the absorption efficiency from a 250 milligram dose of calcium citrate malate to be 35%; from calcium carbonate, 27%; and from tricalcium phosphate, 25%. In comparison, the rate of calcium absorption from milk was found to be 29%. The scientific reasoning for the aforementioned calcium recommendations for high risk groups used traditional (dietary) calcium sources for calculating the required amounts.

Calcium citrate-malate is not the same as calcium citrate, or as a simple admixture of calcium citrate and calcium malate. Calcium citrate-malate is prepared in such a way that a significant number of its calcium atoms are bound to both citrate and malate molecules at once. This unique form makes calcium citrate-malate six to nine times more easily dissolved in the stomach than plain calcium citrate.

Calcium citrate-malate has been used successfully in many controlled trials to support bone mass and/or to lower fracture risk. Some of these trials have involved a direct face-off between calcium citrate-malate and other forms of calcium. Such trials demonstrate that, as might be expected from its greater bioavailability, calcium citrate-malate gives better protection to the bones than other vegetarian calcium sources – although its effects are still not as impressive as those of MCHC.

A review published in 2012 cited that the most prevalent factors associated with both osteoporosis and atherosclerosis were low calcium intake, deficiencies in vitamins D & K, and high sodium intake. Clinical trials show that calcium supplementation provides better results when combined with vitamin D at doses greater than 300 IU per day.

A double-blind, controlled clinical trial on post-menopausal women examined the effects of a plain dairy product versus a dairy product enriched with 800 mg of calcium, 10 mcg of vitamin D and 100 mcg of either vitamin K1 or K2. While total bone mass density increased for all the dairy groups, lumbar spine bone mineral density increased significantly only in the two groups receiving the treatments enriched with calcium and vitamins D & K.

Vitamin D: 800 IUs

Another nutrient essential to bone health is vitamin D. Vitamin D is the single most important factor in the absorption of calcium. Vitamin D3  is the plant form of vitamin D found in vegetables and yeast. Although humans are fully capable of endogenous vitamin D production, this is dependent upon adequate exposure to the UVB rays in sunlight, making a constant, steady intake of this vitamin difficult for high-risk demographics who are often confined indoors.

From what we now know, the old RDA of 400 IU will not protect you from vitamin D insufficiency except in the sunniest of climates. Even in sunny Spain, researchers have found that 80% of children have inadequate vitamin D levels in March and October. In fact, in one remarkable recent study, researchers at Creighton University were able to document that even North Americans who spend nearly all day in the sun during the summer (such as landscapers and agricultural workers) were still at a 58% risk of being too low in vitamin D to support optimal calcium metabolism by the end of the winter! Studies show that a 400 IU vitamin D supplement is just not enough to keep serum levels of the active vitamin above the cutoff for insufficiency, and the use of 400 IU supplements have not been shown to reduce fracture rates. Even 600 IU has little effect on BMD. Instead, controlled studies show that vitamin D, together with calcium, helps to reduce the risk of fracture at a dose of at least 800 IU per day and recent trials suggest much higher dosages are needed to maintain optimal blood levels.

Vitamin K2

Recent studies have suggested that vitamin K2 is better absorbed and persists longer in the plasma then vitamin K1. Studies have also shown that it also has greater benefits to the skeletal and vascular systems than vitamin K1. Vitamin K is important for bone health as it is able to regulate calcium through the amino acid gamma-carboxyglutamic acid (Gla), and in particular the protein osteocalcin, which helps maintain calcium in bone, but at the same time keeps it out of soft tissue.

The advantages of taking both MK-4 and MK-7

More recently, Vitamin K2 in the forms of MK-4 and MK-7 has emerged as bone-building superstars.  MK-4 is a specific form of vitamin K2 produced in the body from phylloquinone (vitamin K1) or even the bacterial menaquinones (which are also forms of vitamin K2). It is thought that other forms of vitamin K are converted to MK-4 in order to be absorbed by cells. Multiple clinical trials show that megadose MK-4 supplements reduce fracture rates in osteoporotic women as much as Fosamax®-type drugs by improving the quality of the bone itself, measured by bone mineral content and width. Another study found that MK-4 combined with 1500 mg of calcium carbonate significantly increased bone density in the lumbar spine and decreased the amount of undercarboxylated osteocalcin compared to just the 1500 mg of calcium alone.

In a recent study comparing MK-4 against MK-7, one of the first actually comparing the two head-to-head, it was found that when subjects took a single dose administration of 420 μg of MK-4 or MK-7, the MK-7 was well absorbed and reached maximal serum level at 6 h after intake and was detected up to 48 h after intake. MK-4 was not detectable in the serum of all subjects at any time point. It is not yet clear whether this is because MK-4 was metabolized very quickly (some nutrients actually benefit from a short half-life) or because it was not absorbed. Consecutive administration of MK-7 at 60 μg for 7 days demonstrated that MK-7 increased serum MK-7 levels significantly in all subjects and activated osteocalcin at this dose. Further research is warranted on the benefits of both forms of vitamin K2, as MK-4 has shown many beneficial effects in humans that have not yet been studied with MK-7 (for example, liver cancer), and there appears to be a cellular receptor specific to MK-4 in humans. Therefore, AOR has chosen to provide both MK-4 and MK-7 in Ortho•Bone to maximize the potential benefits of each.

Absorbable Magnesium 

Take a magnesium you can absorb. Magnesium citrate is absorbed at 29.64%, but much better absorption is available from other forms – especially fully-reacted magnesium aspartate, with a remarkable 41.7% bioavailability.

In a two-year, open, controlled trial, 71% of women receiving magnesium supplements experienced increased bone mineral density where as the women not receiving supplements suffered bone loss. The amount of magnesium in even the highest quality multi-vitamin/multi-mineral supplements is still well below levels which researchers believe are needed for prevention in high risk demographics.


Market Trends

You Need More Than Just Calcium!

Calcium supplements are among the highest sellers among elderly people, especially women. However, healthy bones require more than just calcium. Other minerals also contribute to healthy bone material, and vitamins D & K help with calcium absorption and usage. Massive dosing with calcium salts (like calcium citrate, the most common form) alone may certainly contribute to other health issues. Orthomolecular medicine requires that all of the nutrients be provided for optimal health at appropriate doses and in the right forms.

Don’t fall for the “Coral Calcium” Hype 

Some companies are making wild claims about the efficacy of calcium taken from coral reefs, not just for osteoporosis but for almost every ailment under the sun. These claims are simply bogus. There is nothing magical about “coral calcium:” it is actually almost entirely calcium carbonate, with a sprinkling of some trace minerals. Not one clinical trial has ever been performed to show that “coral calcium” is better absorbed or better utilized than other conventional calcium sources. Instead, astoundingly, the claims of high bioavailability for “coral calcium” are not based on controlled studies in humans, but on the stuff’s ability to dissolve in water; and as has been shown, such a silly test bears little relationship to the ability of a living body to absorb calcium.


Epstein O, Kato Y, Dick R, Sherlock S. “Vitamin D, hydroxyapatite, and calcium gluconate in treatment of cortical bone thinning in postmenopausal women with primary biliary cirrhosis.” Am J Clin Nutr 1982 Sep; 36(3): 426-30.

Heaney RP, Dowell MS, Barger-Lux MJ. “Absorption of calcium as the carbonate and citrate salts, with some observations on method.” Osteoporosis Int. 1999; 9:19-23.

Hirota T, Hirota K. “Osteoporosis and intake of vitamins” Clin Calcium. 2005 May;15(5):854-7.

Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S. Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells. J Mol Endocrinol. 2007 Oct;39(4):239-47.

Ilich JZ, Kerstetter JE. “Nutrition in bone health revisited: a story beyond calcium”. J Am Coll Nutr. 2000 Nov-Dec; 19(6):715-37.

Marie PJ, Ammann P, Boivin G, Rey C. “Mechanisms of action and therapeutic potential of strontium in bone”. Calcif Tissue Int. 2001 Sep; 69(3): 121-9.

Reffitt DM, Ogston N, Jugdaohsingh R, et al. “Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro”. Bone. 2003 Feb;32(2):127-35.

Sato T, Schurgers LJ, Uenishi K. Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J. 2012 Nov 12;11:93.

Zittermann A. “Effects of vitamin K on calcium and bone metabolism.” Curr Opin Clin Nutr Metab Care. 2001 Nov; 4(6): 483-7.



Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women.

Nutr J. 2012 Nov 12;11:93.

Sato T, Schurgers LJ, Uenishi K.

BACKGROUND: Vitamin K?contributes to bone and cardiovascular health. Therefore, two vitamin K? homologues, menaquinone-4 (MK-4) and menaquinone-7 (MK-7), have been used as nutrients by the food industry and as nutritional supplements to support bone and cardiovascular health. However, little is known about the bioavailability of nutritional MK-4. To investigate MK-4 and MK-7 bioavailability, nutritional doses were administered to healthy Japanese women.

FINDINGS: Single dose administration of MK-4 (420 μg; 945 nmol) or MK-7 (420 μg; 647 nmol) was given in the morning together with standardized breakfast. MK-7 was well absorbed and reached maximal serum level at 6 h after intake and was detected up to 48 h after intake. MK-4 was not detectable in the serum of all subjects at any time point. Consecutive administration of MK-4 (60 μg; 135 nmol) or MK-7 (60 μg; 92 nmol) for 7 days demonstrated that MK-4 supplementation did not increase serum MK-4 levels. However, consecutive administration of MK-7 increased serum MK-7 levels significantly in all subjects.

CONCLUSIONS: We conclude that MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels. MK-7, however significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues.


Essential Nutrients for Bone Health and a Review of their Availability in the Average North American Diet.

Open Orthop J. 2012;6:143-9.

Price CT, Langford JR, Liporace FA.

Osteoporosis and low bone mineral density affect millions of Americans. The majority of adults in North America have insufficient intake of vitamin D and calcium along with inadequate exercise. Physicians are aware that vitamin D, calcium and exercise are essential for maintenance of bone health. Physicians are less likely to be aware that dietary insufficiencies of magnesium, silicon, Vitamin K, and boron are also widely prevalent, and each of these essential nutrients is an important contributor to bone health. In addition, specific nutritional factors may improve calcium metabolism and bone formation. It is the authors’ opinion that nutritional supplements should attempt to provide ample, but not excessive, amounts of factors that are frequently insufficient in the typical American diet.In contrast to dietary insufficiencies, several nutrients that support bone health are readily available in the average American diet. These include zinc, manganese, and copper which may have adverse effects at higher levels of intake. Some multivitamins and bone support products provide additional quantities of nutrients that may be unnecessary or potentially harmful.The purpose of this paper is to identify specific nutritional components of bone health, the effects on bone, the level of availability in the average American diet, and the implications of supplementation for each nutritional component. A summary of recommended dietary supplementation is included.

The Relationship Among Hypertension, Antihypertensive Medications, and Osteoporosis: A Narrative Review.

Calcif Tissue Int. 2012 Nov 29.

Ili? K, Obradovi? N, Vujasinovi?-Stupar N.

Osteoporosis and hypertension are two frequent diseases among the aging population that share a similar etiopathology and often coexist. Moreover, treatment of hypertension affects bone mineral density and, therefore, can worsen osteoporosis. This narrative review considers the influence of the main etiologic factors that contribute to the development of hypertension and osteoporosis and examines the effect of the most often used antihypertensives on bones. A computerized literature search of relevant English publications regarding the etiology of hypertension and osteoporosis as well as the impact of antihypertensives on osteoporosis from 1996 to 2011 was completed in October 2011. The latest update in the search was performed from May to June 2012. The most relevant nongenetic factors in the etiology of osteoporosis and hypertension are low calcium intake, vitamin D and vitamin K deficiency, high consumption of sodium salt, and the effects of different forms of nitric oxide. Thiazide diuretics are the only antihypertensives that have a positive influence on bone mineral density. For other antihypertensive drugs, the data are conflicting, indicating that they may have a potentially negative or positive influence on bone mineral density and fracture risk reduction. Some studies did not find a correlation between the use of antihypertensives and bone mineral density. Due to the frequent coexistence of hypertension and osteoporosis, when selecting long-term antihypertensive therapy the potential effects of antihypertensive drugs on development, worsening, or improvement of osteoporosis should also be considered.


Changes in parameters of bone metabolism in postmenopausal women following a 12-month intervention period using dairy products enriched with calcium, vitamin D, and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K (2)): the Postmenopausal Health Study II.

Calcif Tissue Int. 2012 Apr;90(4):251-62.

Kanellakis S, Moschonis G, Tenta R, Schaafsma A, van den Heuvel EG, Papaioannou N, Lyritis G, Manios Y.

The objective of the present study was to examine the effect of dairy products enriched with calcium, vitamin D(3), and phylloquinone (vitamin K(1)) or menaquinone-7 (vitamin K(2)) on parameters of bone metabolism in postmenopausal women following a 12-month intervention. Postmenopausal women were divided into three intervention groups and a control group (CG). All three intervention groups attended biweekly sessions and received fortified dairy products providing daily 800 mg of calcium and 10 μg of vitamin D(3) (CaD). Furthermore, in two of the three intervention groups the dairy products were also enriched with vitamin K, providing daily 100 μg of either phylloquinone (CaDK1) or menaquinone-7 (CaDK2). The increase observed for serum 25(OH)D levels in all intervention groups and the increase observed for serum IGF-I levels in the CaDK2 group differed significantly compared to the changes observed in CG (P = 0.010 and P = 0.028, respectively). Furthermore, both the CaDK1 and CaDK2 groups had a significantly lower mean serum undercarboxylated osteocalcin to osteocalcin ratio and urine deoxypyridinoline levels at follow-up compared to the CaD and CG groups (P = 0.001 and P = 0.047, respectively). Significant increases in total-body BMD were observed in all intervention groups compared to CG (P < 0.05), while significant increases in lumbar spine BMD were observed only for CaDK1 and CaDK2 compared to CG (P < 0.05) after controlling for changes in serum 25(OH)D levels and dietary calcium intake. In conclusion, the present study revealed more favorable changes in bone metabolism and bone mass indices for the two vitamin K-supplemented groups, mainly reflected in the suppression of serum levels of bone remodeling indices and in the more positive changes in lumbar spine BMD for these two study groups.


Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells.

J Mol Endocrinol. 2007 Oct;39(4):239-47.

Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S.

Vitamin K is known as a critical nutrient required for bone homeostasis and blood coagulation, and it is clinically used as a therapeutic agent for osteoporosis in Japan. Besides its enzymatic action as a cofactor of vitamin K-dependent gamma-glutamyl carboxylase (GGCX), we have previously shown that vitamin K(2) is a transcriptional regulator of bone marker genes and extracellular matrix-related genes, by activating the steroid and xenobiotic receptor (SXR). To explore a novel action of vitamin K in osteoblastic cells, we identified genes up-regulated by a vitamin K(2) isoform menaquinone-4 (MK-4) using oligonucleotide microarray analysis. Among these up-regulated genes by MK-4, growth differentiation factor 15 (GDF15) and stanniocalcin 2 (STC2) were identified as novel MK-4 target genes independent of GGCX and SXR pathways in human and mouse osteoblastic cells. The induction of GDF15 and STC2 is likely specific to MK-4, as it was not exerted by another vitamin K(2) isoform MK-7, vitamin K(1), or the MK-4 side chain structure geranylgeraniol. Investigation of the involved signaling pathways revealed that MK-4 enhanced the phosphorylation of protein kinase A (PKA), and the MK-4-dependent induction of both GDF15 and STC2 genes was reduced by the treatment with a PKA inhibitor H89 or siRNA against PKA. These results suggest that vitamin K(2) modulates its target gene expression in osteoblastic cells through the PKA-dependent mechanism, which may be distinct from the previously known vitamin K signaling pathways.


Vitamin D and Calcium Supplementation among Aged Residents in Nursing Homes.

J Nutr Health Aging. 2007 Sep-Oct;11(5):433-7.

Suominen MH, Hosia Randell HM, Muurinen S, Peiponen A, Routasalo P, Soini H, Suur Uski I, Pitkala KH.

Background: Aged residents in nursing homes are at particularly high risk of fractures. Vitamin D and calcium have a preventative role. Objective: To describe the use of vitamin D and calcium supplementations, and their association with nutritional factors among nursing home residents.

Methods: Our study is a cross-sectional assessment of long-term residents in all nursing homes in Helsinki during February 2003. We collected residents’ background information, nutritional status (Mini Nutritional Assessment, MNA), and data on daily nursing routines in institutions, including nutritional care. Vitamin D and calcium supplementations were inquired after in the questionnaire and retrieved from residents’ medication lists.

Results: 2 114 (87%) of all 2424 eligible residents had available data on the use of vitamin D and calcium supplementation. Their mean age was 83 years, and 80.7% were female. Of all participants, 32.9% received vitamin D supplementation and 27.7% calcium supplementation. Altogether 20.0% received both. However, only 21.3% received vitamin D in the therapeutic dose of 10mg (400 IU) or more, and 3.6% in the recommended dose of 20microg (800 IU) or more. In logistic regression analysis, residents who received vitamin D supplementation also had better nutritional status (MNA), ate snacks between meals, did not have constipation and their weight was checked more frequently.

Conclusions: Regardless of the known benefit and recommendation of vitamin D supplementation for the elderly residing mostly indoors, the proportion of nursing home residents receiving vitamin D and calcium was surprisingly low.


Potential benefit of oral calcium/vitamin d administration for prevention of symptomatic hypocalcemia after total thyroidectomy.

Endocr Regul. 2007 Mar;41(1):35.

Kurukahvecioglu O, Karamercan A, Akin M, Tezel E, Ege B, Taneri F, Onuk E.

Objective:To evaluate routine oral calcium and vitamin D administration for preventing symptoms of hypocalcemia after total thyroidectomy.

Subjects and methods: A total of 487 consecutive patients were prospectively randomized into two groups in terms of routine oral calcium and vitamin D supplementation: In the control group (244 patients) the treatment was not routinely started after surgery, whereas the treated group (243 patients) received routine supplementation that started on postoperative day 1.

Results: Patients of treated group had only minor hypocalcemia symptoms, whereas 7 patients of control group experienced carpopedal spasm as a major symptom (p

Conclusions: Routine postoperative calcium and vitamin D supplementation therapy may be useful for the prevention of symptomatic hypocalcemia after total thyroidectomy and may allow for a safe and early discharge from the hospital. Key words: Thyroidectomy Hypocalcemia Calcium – Vitamin D – Dietary supplementation.


Prevention of Osteoporosis: Four-Year Follow-Up of a Cohort of Postmenopausal Women Treated with an Ossein-Hydroxyapatite Compound.

Clinical Drug Investigation. 27(4):227-232, 2007.

Fernandez-Pareja A, Hernandez-Blanco E, Perez-Maceda JM, Riera Rubio VJ, Palazuelos JH, Dalmau JM.

BACKGROUND: The long-term effects of ossein-hydroxyapatite compound (OHC), a drug used for osteoporosis prevention, have not been previously reported. The aim of this study was to assess the long-term efficacy of OHC in postmenopausal women with bone mineral density (BMD) in the osteopenia range.

METHODS: We performed a retrospective 4-year follow-up study in a primary-care setting to assess changes in BMD in a cohort of 112 postmenopausal women included in an osteoporosis programme that included health and dietary advice and who were treated with OHC 1660mg every 12 hours. BMD was measured annually in the distal part of the forearm, with T- and Z-score values being calculated for trabecular and total bone.

RESULTS: A progressive and statistically significant increase in BMD was observed in trabecular and total T- and Z-score mean values. At baseline, mean /- SD trabecular T- and Z-scores were -1.27 /- 0.7 and -1.03 /- 0.7, respectively, and -0.86 /- 0.7 and -0.62 /- 0.7, respectively, at the end of the 4-year follow-up period (both p < 0.0001). Mild constipation was observed in 3.2% of patients during the follow-up period.

CONCLUSION: Ossein-hydroxyapatite compound could be an effective and safe agent for the prevention of bone loss in postmenopausal osteopenic women, with significant increases in BMD being observed in this group of patients.


Calcium retention in adolescent boys on a range of controlled calcium intakes.

Am J Clin Nutr. 2006 Aug;84(2):414-8.

Braun M, Martin BR, Kern M, McCabe GP, Peacock M, Jiang Z, Weaver CM.

BACKGROUND: National calcium requirements in the United States for boys are based on data from girls. On average, boys develop larger skeletons than do girls, yet it is unknown whether the additional skeletal accretion in boys requires additional dietary calcium intake.

OBJECTIVE: The objective was to determine calcium retention in adolescent boys in response to a range of controlled intakes and to compare the intake needed for maximal retention in boys with that needed in adolescent girls studied under the same conditions.

DESIGN: Thirty-one boys aged 12-15 y participated in 3-wk metabolic balance studies testing a range (700-2100 mg/d) of calcium intakes in a crossover study design with a 2-wk washout period. Calcium intake was varied by using a beverage fortified with calcium citrate malate. After a 1-wk equilibration period, calcium retention was calculated as dietary calcium intake minus the calcium excreted in the feces and urine over the following 2 wk. The dietary intake at which maximal calcium retention occurred was determined by using a nonlinear regression model. The results in boys were compared with those obtained in 35 adolescent girls previously studied under the same protocol.

RESULTS: Maximal calcium retention in boys was achieved at an intake of 1140 mg/d. Calcium retention was higher (by 171 /- 38 mg/d) in boys than in girls at all calcium intakes studied.

CONCLUSION: The higher calcium retention in boys than in girls was attained through higher net calcium absorption and lower urinary excretion than in girls.


Calcium fortification systems differ in bioavailability.

J Am Diet Assoc. 2005 May;105(5):807-9.

Heaney RP, Rafferty K, Dowell MS, Bierman J.

The objective of this study was to compare the bioavailability of calcium from two fortification systems used in orange juice. The design was randomized crossover, within-subject. The subjects were 25 healthy premenopausal women in an academic health sciences center. Two commercially marketed calcium-fortified orange juices, ingested in an amount providing 500 mg calcium, were taken at breakfast after an overnight fast. The two fortification systems tested were calcium citrate malate and a combination of tricalcium phosphate and calcium lactate (tricalcium phosphate/calcium lactate). The main outcome measure was the area under the curve (AUC) for the increase in serum calcium from 0 to 9 hours after ingesting the test calcium source. Statistical analyses performed were repeated measures analysis of variance, testing source, and sequence. AUC 9 was 48% greater for calcium citrate malate than for tricalcium phosphate/calcium lactate ( P < .001); absorbed calcium calculated from AUC 9 values (mean /-standard error of the mean) was 148 /-9.0 mg and 100 /-8.9 mg for calcium citrate malate and tricalcium phosphate/calcium lactate, respectively. The results indicate that equivalent calcium contents on a nutritional label do not guarantee equivalent nutritional value. Nutritionists and dietetics professionals should encourage manufacturers of fortified products to provide information on bioavailability.


Calcium and protein in bone health.

Proc Nutr Soc. 2003 May;62(2):505-9.

Dawson-Hughes B.

Dietary protein has several opposing effects on Ca balance and its net effect on bone is not well established. It has long been recognized that increasing protein intake increases urinary Ca excretion. More recently, it has been observed that increasing dietary protein raises the circulating level of insulin-like growth factor-1, a growth factor that promotes osteoblast formation and bone growth. Other effects of protein on the Ca economy have been suggested in some studies, but they are less well established. Several studies have examined associations between protein intake and bone loss and fracture rates. In the original Framingham cohort subjects with lower total and animal protein intakes had greater rates of bone loss from the femoral neck and spine than subjects consuming more protein. In another study higher total (and animal) protein intakes were associated with a reduced incidence of hip fractures in post-menopausal women. In contrast, a high animal:plant protein intake has been associated with greater bone loss from the femoral neck and a greater risk of hip fracture in older women. Higher total and higher animal protein intakes have also been associated with increased risk of forearm fracture in younger post-menopausal women. In a recent study it was found that increasing dietary protein was associated with a favourable (positive) change in bone mineral density of the femoral neck and total body in subjects taking supplemental calcium citrate malate with vitamin D, but not in those taking placebo. The possibility that Ca intake may influence the impact of dietary protein on the skeleton warrants further investigation.


Comparative absorption of calcium sources and calcium citrate malate for the prevention of osteoporosis.

Altern Med Rev. 1999 Apr;4(2):74-85.

Patrick L.

Anthropologically speaking, humans were high consumers of calcium until the onset of the Agricultural Age, 10,000 years ago. Current calcium intake is one-quarter to one-third that of our evolutionary diet and, if we are genetically identical to the Late Paleolithic Homo sapiens, we may be consuming a calcium-deficient diet our bodies cannot adjust to by physiologic mechanisms. Meta-analyses of calcium and bone mass studies demonstrate supplementation of 500 to 1500 mg calcium daily improves bone mass in adolescents, young adults, older men, and postmenopausal women. Calcium citrate malate has high bioavailability and thus has been the subject of calcium studies in these populations. Positive effects have been seen in prepubertal girls, adolescents, and postmenopausal women. The addition of trace minerals and vitamin D in separate trials has improved the effect of calcium citrate malate on bone density and shown a reduction of fracture risk.

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