Ortho Bone™


With MCHA complex, a superior form of calcium

  • Provides active, effective forms of key bone-health nutrients
  • Improves bone growth & bone density while reducing bone loss
  • Demonstrated to produce smaller blood calcium spikes than other types of supplemental calcium
  • An unrivalled comprehensive bone formula exclusively available from AOR
Gluten Free

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Ortho Bone™ is an advanced bone health formula providing nutrients that are fundamental for mineral deposition in bone and for regulating the excretion of minerals. These nutrients are very important for those with osteoporosis, osteopenia or a history of bone fractures. Ortho Bone™ is unique because it serves not only to reduce bone loss but to maintain or even increase bone growth, something that most calcium supplements are unable to achieve. This is due to the key ingredient, a superior source of calcium called microcrystalline hydroxyapatite complex (MCHC), which comes from New Zealand bovine bone. MCHC contains more than calcium: it contains all of the minerals and proteins found in bone, is rich in phosphorus, and provides growth factors that stimulate bone growth. It is digested more slowly in the stomach than typical calcium supplements, resulting in smaller spikes in blood calcium levels, which allows the calcium to be better absorbed into the bones.

Ortho Bone™ also provides vitamins C, D3, K2, B12 and folate, and minerals boron, magnesium, manganese, silicon, zinc and copper. Together, these ingredients provide one of the best formulas available for promoting bone health and preventing osteoporosis and osteopenia. The most effective forms of vitamins D & K2 are found in Ortho Bone™, serving to enhance the body’s absorption and usage of calcium. Vitamin C and silicon support collagen production, which builds the framework for bone. Magnesium makes up a large part of the bone mineral matrix, while boron reduces magnesium loss, and trace minerals manganese, zinc and copper are co-factors for enzymes involved in bone metabolism. Vitamins B12 and folate help reduce homocysteine, a metabolic by-product that is thought to be toxic to bone fibers.

Ortho Bone™ is a serious bone health product for serious bone health support, with a dose of 10 capsules per day delivering 1000 mg of elemental calcium. Those with osteoporosis or osteopenia, frail post-menopausal women and elderly people in general will benefit the most from taking Ortho Bone™.

AOR Advantage

AOR’s Ortho Bone™ contains not just calcium, but all the key ingredients at the appropriate doses in the most effective forms to keep bones in optimal condition and to reduce bone loss. This is why 10 capsules a day provides your daily dose of calcium. The MCHC calcium source used in Ortho Bone™ also contains growth factors and proteins, which is why it actually stimulates bone development rather than just reducing calcium loss.




Ortho Bone™ contains important nutrients for optimal development of bones and teeth. It features calcium from microcrystalline hydroxyapatite (MCHA) complex; an extract of bovine bone derived from New-Zealand pasture-fed, free-range livestock not subjected to routine antibiotics or rBGH. MCHA complex is a superior form of calcium that is demonstrated to produce smaller harmful calcium spikes than other types of supplemental calcium. When combined with a healthy diet and regular exercise, Ortho Bone™ may reduce the risk factors of developing osteoporosis.


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

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 pregnant or breastfeeding or if you are taking blood thinners. Some people may experience diarrhea. This product contains corn and soy derived ingredients, do not use if you have such allergies.

Main Application
  • Bone health
  • Menopause

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
Calcium (from bone meal [MCHA] complex)*
1000 mg
Phosphorus (from bone meal [MCHA] complex)*
455 mg
Magnesium (from magnesium citrate, ascorbate)
420 mg
Vitamin D3 (as vegan Cholecalciferol)
1000 IU (25 mcg)
Vitamin K2
120 mcg
60 mcg
60 mcg
Boron (from boron citrate)
700 mcg
Zinc (from zinc citrate)
11 mg
Manganese (from manganese bisglycinate)
2.3 mg
Copper (from copper citrate)
1 mg
Silicon (HVP chelate from soy)
35 mg
Folic acid (as calcium L-5-MTHF)
400 mcg
Vitamin B12 (as Methylcobalamin)
24 mcg
Vitamin C (from magnesium ascorbate)
90 mg

*Guaranteed free of bovine spongiform encephalopathy.

Non-medicinal Ingredients: Microcrystaline cellulose, hydroxypropyl cellulose, tocopherols, acacia gum, starch (rice, corn &soy), sucrose, maltodextrin, tricalcium phosphate, sodium stearyl fumarate, silicon dioxide, medium chain triglycerides, citric acid, l-aspartic acid, glycine, sunflower oil and magnesium trisilicate.

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 now as both MK-4 & MK-7, whose revolutionary effects on bone health are now well-known. Ortho Bone™ offers all the essential vitamins and minerals for good bone health in their superior forms for optimal bone support.

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™ contains vitamin D3 and vitamin K2 in the forms of MK-4 & MK-7, the most effective forms of these vitamins.

Get the Right Kind of Calcium

Calcium is critical to the body for more than bone health, in fact it is essential for many vital functions such as normal nerve transmission, blood clotting and muscle contraction. Every cell in the human body uses calcium for basic functions and for this reason, the amount of calcium circulating in the blood (the calcium balance) is tightly controlled within a very narrow range. It follows that disturbances in the sensitive calcium balance are serious. Therefore, the body has developed efficient mechanisms to deal with acute alterations in circulating calcium levels.  However, when the body needs to continually deal with either excessive (hypercalcaemia), or inadequate (hypocalcaemia) blood calcium, this can come at the expense of long term health. Indeed excessive calcium levels in the blood can result in a myriad of negative outcomes. At its extremes Hypercalcaemia is linked with kidney stones, bone pain, nausea, depression and insomnia. By contrast a shortage of circulating calcium will see the body strip the necessary calcium from the skeleton (the body’s natural reservoir). Over time this comes at a significant cost to overall bone health and can lead to osteopenia and, ultimately, osteoporosis which carries with it a much higher risk of bone fracture.  The correct balance is maintained by the parathyroid gland, mediated by Parathyroid Hormone (PTH), which, through a complex series of functions is able to manipulate blood calcium levels for optimal function.

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.

Problems with conventional calcium supplementation

Given the importance of the calcium balance it has been somewhat surprising that some of the most popular and widely accepted calcium supplements on the market have been promoted on the basis of rapid absorption and, or, efficient “once daily” dosing.

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. But MCHC’s bone-building powers do not lie in the calcium itself.

True MCHC is not just a form of calcium, but is a calcium-based crystalline nutrient complex, which is how the mineral is actually stored in your bones. MCHC’s unique support for the skeletal system is probably due to a combination of its intact crystalline structure, and the vibrant blend of peptides, mucopolysaccharides, and growth factors which accompany the calcium in true MCHC supplements – factors which are not present in conventional calcium supplements, in bone meal, or in pure, synthetic hydroxyapatite (also known as calcium orthophosphate). The bottom line is that the unique bone health support provided by MCHC derives from the whole supplement, and not just from its calcium content.

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.

The Phosphorus Paradox

It’s widely believed that Western diets are too rich in this mineral, and that excess phosphorus is bad for bone health. But phosphorus is an essential nutrient, which makes up more than half of the mineral content of bone and which is needed for osteoblast function. Nearly a third of older Americans don’t get the new RDA of this essential mineral. Good thing phosphorus is a natural component of MCHC.


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.




MCHC is, in effect, a full-spectrum multiple nutrient source in its own right. However, it is particularly rich in calcium, and the type of calcium in MCHC has been clinically proven in over 30 years of randomized, double-blind, controlled clinical trials to be the best calcium source for bone building and maintenance.

Current “official” recommendations suggest an intake of 1000 milligrams of calcium for younger adults, and 1200 milligrams for people over the age of 50. Some evidence suggests that a still higher intake (1300-1600 milligrams) of calcium is more effective for lowering fracture risk in the elderly. But remember that these numbers are your total calcium need. The more calcium you get in your diet, the less you need from supplements.

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.


A recent study compared the bone turnover effects of MCHC with conventional bone supplements and concluded the following:

MCHC  is clinically proven to deliver calcium without causing undesirable spikes in blood calcium levels.

Peak blood calcium levels after ingestion of MCHC by study participants were 45%-49% lower than peak blood calcium levels after ingestion of the same amount of calcium from either calcium carbonate or calcium citrate.

After ingestion of MCHC, average increase in blood calcium levels compared to the control group over an 8 hour period did not reach statistical significance. By contrast after ingestion of the same amount of calcium as either calcium carbonate or calcium citrate, average increase in blood calcium levels were statistically significantly different to control.

(Area under the curve data shows that) The total amount of calcium delivered to the blood over an 8 hour period after ingestion of MCHC did not differ significantly from the total amount of calcium delivered to the blood over the same time period after ingestion of either calcium citrate or calcium carbonate

MCHC is clinically proven to deliver the same levels of efficacy as both calcium carbonate and calcium citrate as measured by the ability to supress key markers of bone turnover (bone resorption).

After 90 days of continuous supplementation, MCHC supressed CTX and P1NP, two key makers of bone turnover, by an identical amount to calcium carbonate and calcium citrate.

MCHC is not artificially modified calcium, it does not rely on chemical coatings and additives which delay release but not the rate of release.

MCHC has been designed, developed and clinically proven to deliver calcium in a 100% natural protein complex which the body is able to digest, as it would a food, releasing the calcium slowly and steadily into the body without the undesirable spikes.

MCHC has demonstrated ability to promote bone matrix deposition and mineralisation (bone formation).

Proteins extracted from MCHC demonstrated osteo inductivity, the ability to stimulate bone formation, as measured by osteoblast (bone cell) differentiation and mineralisation in vitro.

Independent testing has verified the presence of critically important bone stimulating growth factors and bone matrix proteins in MCHC.

Unlike conventional calcium supplements, such as calcium citrate and calcium carbonate, MCHC contains protein (25% on average) rich in essential bone matrix components, including Type I collagen and Osteocalcin, and bone stimulating growth factors.

Specifically, testing has verified the presence of the osteo inductive growth factors IGF I and 2, and TGFb 1 and 2.

Vitamin D: 800 IUs

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.



Bristow SM, Gamble GD, Stewart A, Horne L, House ME, Aati O, Mihov B, Horne AM, Reid IR. Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women. Br J Nutr. 2014 Nov 28;112(10):1611-20.

Castelo-Branco C, Ciria-Recasens M, Cancelo-Hidalgo MJ, Palacios S, Haya-Palazuelos J, Carbonell-Abelló J, Blanch-Rubió J, Martínez-Zapata MJ, Manasanch J, Pérez-Edo L. Efficacy of ossein-hydroxyapatite complex compared with calcium carbonate to prevent bone loss: a meta-analysis. Menopause. 2009 Sep-Oct;16(5):984-91.

Castelo-Branco C, Dávila Guardia J. Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review. Climacteric. 2015 Feb;18(1):29-37.

Castelo-Branco C, Pons F, Vicente JJ, Sanjuan A, Vanrell JA. “Preventing postmenopausal bone loss with ossein-hydroxyapatite compounds. Results of a two-year, prospective trial.” J Reprod Med. 1999 Jul; 44(7): 601-5.

Ciria-Recasens M, Blanch-Rubió J, Coll-Batet M, Del Pilar Lisbona-Pérez M, Díez-Perez A, Carbonell-Abelló J, Manasanch J, Pérez-Edo L. Comparison of the effects of ossein-hydroxyapatite complex and calcium carbonate on bone metabolism in women with senile osteoporosis: a randomized, open-label, parallel-group, controlled, prospective study.  Clin Drug Investig. 2011 Dec 1;31(12):817-24.

Durance RA, Parsons V, Atkins CJ, Hamilton EB, Davies C. A trial of calcium supplements (Ossopan) and ashed bone. Clin Trials J. 1973 Nov; 10(3): 67-73.

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.

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.

Ruegsegger P, Keller A, Dambacher MA. Comparison of the treatment effects of ossein-hydroxyapatite compound and calcium carbonate in osteoporotic females. Osteoporos Int. 1995 Jan; 5(1): 30-4.

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

Stellon A, Davies A, Webb A, Williams R. Microcrystalline hydroxyapatite compound in prevention of bone loss in corticosteroid-treated patients with chronic active hepatitis. Postgrad Med J.1985 Sep; 61(719): 791-6.

Stepan JJ, Mohan S, Jennings JC, Wergedal JE, Taylor AK, Baylink DJ. Quantitation of growth factors in ossein-mineral-compound. Life Sci. 1991; 49(13): PL79-84.

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



Use of ossein-hydroxyapatite complex in the prevention of bone loss: a review.

Climacteric. 2015 Feb;18(1):29-37.

Castelo-Branco C, Dávila Guardia J.

Background and objective The ossein-hydroxyapatite complex (OHC) is a microcrystalline form of calcium which provides a number of additional minerals (magnesium, phosphorus, potassium, zinc), and proteins (osteocalcin, type I collagen, type I insulin growth factor I and II, transforming growth factor beta) associated with bone metabolism. The objective of this review is to examine the role of OHC in preventing bone loss in different conditions.

Material and methods A review of clinical trials assessing the relationship between OHC and bone loss was made using the following data sources: Medline (from 1966 to December 2013), the Cochrane Controlled Clinical Trials Register, Embase (up to December 2013), contact with companies marketing the supplements studied, and reference lists.

Results Different randomized, clinical trials and meta-analysis suggest that OHC is more effective than calcium supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss. In addition, OHC improves pain symptoms and accelerates fracture consolidation in patients with osteopenia or osteoporosis.

Conclusion The ossein-hydroxyapatite complex is significantly more effective in preventing bone loss than calcium carbonate.


Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women.

Br J Nutr. 2014 Nov 28;112(10):1611-20.

Bristow SM, Gamble GD, Stewart A, Horne L, House ME, Aati O, Mihov B, Horne AM, Reid IR.

Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate-carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate-carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate-carbonate dose; however, it raised the concentrations of phosphate and the Ca-phosphate product. The citrate-carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.


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.


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.


Comparison of the effects of ossein-hydroxyapatite complex and calcium carbonate on bone metabolism in women with senile osteoporosis: a randomized, open-label, parallel-group, controlled, prospective study.

Clin Drug Investig. 2011 Dec 1;31(12):817-24.

Ciria-Recasens M, Blanch-Rubió J, Coll-Batet M, Del Pilar Lisbona-Pérez M, Díez-Perez A, Carbonell-Abelló J, Manasanch J, Pérez-Edo L.

BACKGROUND AND OBJECTIVE: Calcium and vitamin D supplementation is recommended in patients with osteopenia and osteoporosis. One group that could benefit from this treatment is women with senile osteoporosis. Two sources of supplementary calcium are ossein-hydroxyapatite complex (OHC) and calcium carbonate, but, to date, their comparative effects on bone metabolism have not been studied in women with senile osteoporosis. The objective of this study was to compare the effects of OHC and calcium carbonate on bone metabolism in women with senile osteoporosis.

METHODS: This was a randomized, open-label, parallel-group, controlled, prospective study to compare the effects of OHC (treatment group) and calcium carbonate (control group) on bone metabolism. Patients were included between 2000 and 2004 and followed up for a maximum of 3 years. The study was carried out at the bone metabolism unit of two university hospitals in Barcelona, Spain. Subjects were women aged >65 years with densitometric osteoporosis of the lumbar spine or femoral neck. The treatment group received open-label OHC (Osteopor®) at a dose of two 830 mg tablets every 12 hours (712 mg elemental calcium per day). The control group received open-label calcium carbonate at a dose of 500 mg of elemental calcium every 12 hours (1000 mg elemental calcium per day). Both groups also received a vitamin D supplement (calcifediol 266 μg) at a dose of one vial orally every 15 days. Biochemical markers of bone remodelling (osteocalcin by electrochemiluminescence, tartrate-resistant acid phosphatase using colorimetry) were measured at baseline and annually for 3 years. Bone mineral density (BMD) at the lumbar spine and femoral neck was also measured.

RESULTS: One hundred and twenty women were included (55 in the OHC group and 65 in the calcium carbonate group), of whom 54 completed 3 years of follow-up. Levels of serum osteocalcin increased to a greater extent in the OHC group compared with the calcium carbonate group (by a mean ± SD of 0.84 ± 3.13 ng/mL at year 2 and 1.86 ± 2.22 ng/mL at year 3 in the OHC group compared with a mean ± SD decrease of 0.39 ± 1.39 ng/mL at year 2 and an increase of 0.31 ± 2.51 ng/mL at year 3 in the calcium carbonate group); the differences between treatment groups were statistically significant (p < 0.05) at both years. Changes over time in serum osteocalcin level were also statistically significant (p < 0.05) in the OHC group, but not in the calcium carbonate group. Changes in mean BMD at the lumbar spine and femoral neck between baseline and year 3 were -1.1% and 2.5% for OHC and -2.3% and 1.2% for calcium carbonate, respectively.

CONCLUSION: OHC had a greater anabolic effect on bone than calcium carbonate.


Efficacy of ossein-hydroxyapatite complex compared with calcium carbonate to prevent bone loss: a meta-analysis.

Menopause. 2009 Sep-Oct;16(5):984-91.

Castelo-Branco C, Ciria-Recasens M, Cancelo-Hidalgo MJ, Palacios S, Haya-Palazuelos J, Carbonell-Abelló J, Blanch-Rubió J, Martínez-Zapata MJ, Manasanch J, Pérez-Edo L.

OBJECTIVE: There is increasing evidence to suggest that ossein-hydroxyapatite complex (OHC) is more effective than calcium supplements in maintaining bone mass. The aim of this meta-analysis was to determine whether OHC has a different clinical effect on bone mineral density (BMD) compared with calcium carbonate (CC).

METHODS: A meta-analysis of randomized controlled clinical trials was carried out to evaluate the efficacy of OHC versus CC on trabecular BMD. We identified publications on clinical trials by a search of electronic databases, including MEDLINE (1966-November 2008), EMBASE (1974-November 2008), and the Cochrane Controlled Clinical Trials Register.The primary endpoint was percent change in BMD from baseline. Data were pooled in a random-effects model, and the weighted mean difference was calculated. A sensitivity analysis that excluded trials without full data was performed.

RESULTS: Of the 18 controlled trials initially identified, 6 were included in the meta-analysis. There was no significant heterogeneity among the included trials. The percent change in BMD significantly favored the OHC group (1.02% [95% CI, 0.63-1.41], P < 0.00001). These results were confirmed in the sensitivity analysis.

CONCLUSIONS: OHC is significantly more effective in preventing bone loss than CC.


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.

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