WO1999003456A2 - Method for prophylaxis or treatment of bone density loss - Google Patents
Method for prophylaxis or treatment of bone density loss Download PDFInfo
- Publication number
- WO1999003456A2 WO1999003456A2 PCT/EP1998/004187 EP9804187W WO9903456A2 WO 1999003456 A2 WO1999003456 A2 WO 1999003456A2 EP 9804187 W EP9804187 W EP 9804187W WO 9903456 A2 WO9903456 A2 WO 9903456A2
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- Prior art keywords
- unsaturated fatty
- mono
- fatty acids
- bone density
- use according
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
- A61K31/231—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having one or two double bonds
Definitions
- This invention relates to a method for the prophylaxis or treatment of bone density loss in an animal or human, and to substances for use in the prophylaxis or treatment of bone density loss.
- Osteoporosis is a public health problem of major proportions in many developed countries. The condition is characterized by low bone density and microarchitectural deterioration of bone tissue. This results in increased bone fragility. The bone fragility manifests itself in an increased risk of bone fracture; particularly hip fracture. For example, in the US, where more than a third of post-menopausal women are believe to have femoral osteopenia, the probability of a post-menopausal woman experiencing a hip fracture is reported to be almost 20% (Ross et al; 1991 ; American Journal of Epidemiology, 133:801-809). In Switzerland and Finland, hip fractures account for nearly 10% of acute surgery hospitalization.
- osteoporosis is more common in women and the aged; especially elderly women.
- certain hormones is associated with increased bone density; for example estrogens, androgens and calcitonin.
- physical activity and body mass index are positively associated with increased bone density.
- drugs including glucocorticosteroids, have been reported to adversely affect bone density.
- smoking and alcohol intake may adversely affect bone density.
- Prostaglandins are also reported to have an effect on bone density (Pilbeam et al; 1996; Principles of Bone Biology, Academic Press, Chapter 51, pages 715- 728). Certain prostaglandins, such as PGF 2 ⁇ and PGE 2 , are reported to have a positive effect on bone density while other prostaglandins are believed to have an adverse effect.
- this invention provides a method for the prophylaxis or treatment of bone density loss in an animal or human, the method comprises administering to the animal or human an effective amount of a mono-unsaturated fatty acid.
- mono-unsaturated fatty acids provide a suitable means for the prophylaxis or treatment of bone density loss in an animal or human. Further, the mono-unsaturated fatty acids are readily incorporated into foods which are consumed daily; greatly facilitating acceptance. Also the mono-unsaturated fatty acids act synergistically action with other nutrients for bone formation and growth, such as calcium. Preferably the mono-unsaturated fatty acid form part of a lipid mixture which contains at least about 50% by weight of mono-unsaturated fatty acids.
- the lipid mixture may also include poly-unsaturated fatty acids; for example about 10% to about 40% by weight of poly-unsaturated fatty acids.
- a poly-unsaturated fatty acid mixture which is enriched in ⁇ -3 fatty acids is preferred.
- a ratio of ⁇ -6 to ⁇ -3 fatty acids of about 3: 1 to about 9: 1 may be used.
- the method further comprises administering a source of vitamin
- this invention provides a method for the prophylaxis or treatment of bone density loss in an animal or human, the method comprising administering to the animal or human, as part of daily diet, an effective amount of a mono-unsaturated fatty acid.
- this invention provides a method for the prophylaxis or treatment of bone density loss in an animal or human, the method comprising administering to the animal or human an effective amount of a fat mixture containing mono-unsaturated fatty acid and poly-unsaturated fatty acids enriched in ⁇ -3 fatty acids.
- this invention provides the use of mono-unsaturated fatty acids in the preparation of a medicament or functional food for the prophylaxis or treatment of bone density loss in an animal or human.
- the functional food is suitable for daily consumption.
- Embodiments of the invention are now described by way of example only. This invention is based upon the finding that the consumption of mono- unsaturated fatty acids over time has a positive affect on bone density. Without wishing to be bound by theory, it is believed that the mono-unsaturated fatty acids stimulate the endogenous release of prostaglandins PGF 2 ⁇ and PGE 2 (Srivastava et al; 1982; Prostaglandins Leukotrienes and Medicine. 9, 669-684). These prostaglandins, in turn, form a long term stimulus for increase in osteoblastic activity and both periosteal and endosteal bone formation (Pilbeam supra).
- Suitable sources of mono-unsaturated fatty acids are vegetable oils which are rich in mono-unsaturated fatty acids.
- vegetable oils such as olive oil, apricot oil, and oleic-acid rich oils obtained from sunflower, safflower or rapeseed hybrids, may be used.
- the oleic-acid rich oils have a mono- unsaturated fatty acid content of more than about 60% by weight.
- a hybrid sunflower oil is described in US patent 4,743,402; the disclosure of which is incorporated by reference.
- Another example of an oil is the canola or rapeseed oil disclosed in European patent application 0 323 753, the disclosure of which is incorporated by reference.
- high oleic fractions of vegetable oils may be used; for example high oleic fractions obtained from palm oil.
- lipid mixtures which are enriched in mono-unsaturated fatty acids may be used as suitable sources of mono-unsaturated fatty acids.
- suitable lipid mixtures are described in US patent 5,518,753; the disclosure of which is incorporated by reference.
- the lipid mixtures described in this US patent have a fatty acid profile as follows:
- This lipid mixture has the advantage of the presence of essential, poly- unsaturated fatty acids; especially in the beneficial ratio of ⁇ -6: ⁇ -3 of about 3:1 to about 9: 1 ; for example about 4.5 : 1 to about 8.5: 1. Further, the lipid mixture has a total poly-unsaturated fatty acid content of about 10% to about 40% by weight; for example about 20% to about 35% by weight.
- the lipid mixture may contain vitamins, antioxidants and minerals as desired. Vitamins with antioxidant properties such as vitamin C and vitamin E are particularly preferred since these vitamins may reduce free radical production in osteoclasts. This may depress bone resorption and hence increase bone formation.
- a suitable calcium salt is preferably included as a mineral.
- the mono-unsaturated fatty acids may be consumed in the form of the vegetable oils or lipid mixtures described above.
- these vegetable oils and lipid mixtures may comprise all or part of the lipid component of foods such as salad dressings, mayonnaises, yogurts, milk substitutes, sauces, creams, ice creams, fat-based confectionery products, biscuits, and pet foods.
- the foods Preferably contain about 1% to about 80% of the vegetable oils and lipid mixtures; more preferably about 5% to about 60%> by weight.
- the amount of mono-unsaturated fatty acids required to be fed to a human or animal to obtain beneficial affects will vary depending upon factors such gender, health, body weight, age, and the like. However, in general, sufficient mono-unsaturated fatty acids should be administered to provide the human or animal with about 0.3 g to about 1 g mono-unsaturated fatty acids per kg of body weight per day. For example, an adult human may consume 0.4 g to about 0.6 g mono-unsaturated fatty acids per kg of body weight per day.
- the mono-unsaturated fatty acids are preferably consumed over long periods of time as part of daily or weekly nutrition. Of course, it is not essential to consume the mono-unsaturated fatty acids on a daily basis. However regular consumption is preferable for maximum effect.
- One hundred and fifty four healthy people are recruited for the study; 36 men and 1 18 women. Each person is asked to undergo bone mineral density determination of the non-dominant forearm using single photon absorptiometry.
- a abso ⁇ tiometer obtained from Nuclear Data (model 1 100a) and operated using a 125 I source (100 mCi) with a photopeak at 27 KeV, is used.
- Sociodemographic, reproductive and somatometric information is gathered for each person. Further, each people is asked to indicate the average frequency of consumption, during the year prior to the interview, of 115 different food items. The distribution of the study subjects is as follows:
- the frequency of consumption of different food items is quantified in terms of the number of time per month the food is consumed. Therefore the value for a daily consumption is multiplied by 30, the value for a weekly consumption is multiplied by 4, and a value of 0 is assigned to foods rarely or never consumed.
- the nutrient intakes for each person are estimated by multiplying the nutrient content of a selected typical portion of each food item by the frequency that the food item is consumed per month.
- the nutrient intakes analyzed are protein, saturated fats, mono-unsaturated fats, poly-unsaturated fats, mono-, di- and poly- saccharides, crude fiber, calcium and total energy.
- the data are analyzed using multiple linear regression.
- the bone mineral density is regressed on non-nutritional variables, energy intake and mono-unsaturated fat.
- each other nutrient is substituted for mono-unsaturated fat; in each case adjusting for energy intake.
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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Abstract
A method for the prophylaxis or treatment of bone density loss in an animal or human. The method includes the step of administering to the animal or human an effective amount of a mono-unsaturated fatty acid. The mono-unsaturated fatty acid may form part of a lipid mixture which includes poly-unsaturated fatty acids.
Description
Method for Prophylaxis or Treatment of Bone Density Loss Field of the Invention
This invention relates to a method for the prophylaxis or treatment of bone density loss in an animal or human, and to substances for use in the prophylaxis or treatment of bone density loss.
Background to the Invention
Osteoporosis is a public health problem of major proportions in many developed countries. The condition is characterized by low bone density and microarchitectural deterioration of bone tissue. This results in increased bone fragility. The bone fragility manifests itself in an increased risk of bone fracture; particularly hip fracture. For example, in the US, where more than a third of post-menopausal women are believe to have femoral osteopenia, the probability of a post-menopausal woman experiencing a hip fracture is reported to be almost 20% (Ross et al; 1991 ; American Journal of Epidemiology, 133:801-809). In Switzerland and Finland, hip fractures account for nearly 10% of acute surgery hospitalization.
Several parameters have been identified as being risk factors for osteoporosis. For example, gender and age are parameters. Osteoporosis is more common in women and the aged; especially elderly women. Further, the presence of certain hormones is associated with increased bone density; for example estrogens, androgens and calcitonin. Similarly, physical activity and body mass index are positively associated with increased bone density. On the contrary, several drugs including glucocorticosteroids, have been reported to adversely affect bone density. Similarly it has been reported that smoking and alcohol intake may adversely affect bone density.
Prostaglandins are also reported to have an effect on bone density (Pilbeam et al; 1996; Principles of Bone Biology, Academic Press, Chapter 51, pages 715- 728). Certain prostaglandins, such as PGF2α and PGE2, are reported to have a positive effect on bone density while other prostaglandins are believed to have an adverse effect.
General diet is also reported to be linked to bone density. However there is little in the way of strong evidence of diet having a positive affect on bone density. The primary exception relates to calcium intake and factors that
facilitate its absorption and deposition. However most evidence seems to point to calcium being a factor mainly during the early stages of life.
To date, methods for the prophylaxis of bone density decrease have centered on the use of diet or supplements rich in calcium during early life. Physical exercise is also recommended. Treatment generally takes the form of the administration of medicaments such as calcitonin and analogs. However, it would be preferable to use diet as a means of preventing or limiting decrease in bone density throughout life and for treating loss in bone density.
Summary of the Invention
In one aspect, this invention provides a method for the prophylaxis or treatment of bone density loss in an animal or human, the method comprises administering to the animal or human an effective amount of a mono-unsaturated fatty acid.
It has now been found that the consumption of mono-unsaturated fatty acids over a period of time decreases bone density loss. Therefore of mono- unsaturated fatty acids provide a suitable means for the prophylaxis or treatment of bone density loss in an animal or human. Further, the mono-unsaturated fatty acids are readily incorporated into foods which are consumed daily; greatly facilitating acceptance. Also the mono-unsaturated fatty acids act synergistically action with other nutrients for bone formation and growth, such as calcium. Preferably the mono-unsaturated fatty acid form part of a lipid mixture which contains at least about 50% by weight of mono-unsaturated fatty acids. The lipid mixture may also include poly-unsaturated fatty acids; for example about 10% to about 40% by weight of poly-unsaturated fatty acids. A poly-unsaturated fatty acid mixture which is enriched in ω-3 fatty acids is preferred. A ratio of ω-6 to ω-3 fatty acids of about 3: 1 to about 9: 1 may be used. Preferably, the method further comprises administering a source of vitamin
E, or vitamin C, or both, to the human or animal.
In another aspect, this invention provides a method for the prophylaxis or treatment of bone density loss in an animal or human, the method comprising administering to the animal or human, as part of daily diet, an effective amount of a mono-unsaturated fatty acid.
In a further aspect, this invention provides a method for the prophylaxis or treatment of bone density loss in an animal or human, the method comprising administering to the animal or human an effective amount of a fat mixture containing mono-unsaturated fatty acid and poly-unsaturated fatty acids enriched in ω-3 fatty acids.
In another aspect, this invention provides the use of mono-unsaturated fatty acids in the preparation of a medicament or functional food for the prophylaxis or treatment of bone density loss in an animal or human.
Preferably the functional food is suitable for daily consumption.
Detailed Description of Preferred Embodiments
Embodiments of the invention are now described by way of example only. This invention is based upon the finding that the consumption of mono- unsaturated fatty acids over time has a positive affect on bone density. Without wishing to be bound by theory, it is believed that the mono-unsaturated fatty acids stimulate the endogenous release of prostaglandins PGF2α and PGE2 (Srivastava et al; 1982; Prostaglandins Leukotrienes and Medicine. 9, 669-684). These prostaglandins, in turn, form a long term stimulus for increase in osteoblastic activity and both periosteal and endosteal bone formation (Pilbeam supra).
Suitable sources of mono-unsaturated fatty acids are vegetable oils which are rich in mono-unsaturated fatty acids. For example, vegetable oils such as olive oil, apricot oil, and oleic-acid rich oils obtained from sunflower, safflower or rapeseed hybrids, may be used. The oleic-acid rich oils have a mono- unsaturated fatty acid content of more than about 60% by weight. One example of a hybrid sunflower oil is described in US patent 4,743,402; the disclosure of which is incorporated by reference. Another example of an oil is the canola or rapeseed oil disclosed in European patent application 0 323 753, the disclosure of which is incorporated by reference. Similarly, high oleic fractions of vegetable oils may be used; for example high oleic fractions obtained from palm oil.
Further, lipid mixtures which are enriched in mono-unsaturated fatty acids may be used as suitable sources of mono-unsaturated fatty acids. Examples of suitable lipid mixtures are described in US patent 5,518,753; the disclosure of which is incorporated by reference. The lipid mixtures described in this US patent have a fatty acid profile as follows:
This lipid mixture has the advantage of the presence of essential, poly- unsaturated fatty acids; especially in the beneficial ratio of ω-6:ω-3 of about 3:1 to about 9: 1 ; for example about 4.5 : 1 to about 8.5: 1. Further, the lipid mixture has a total poly-unsaturated fatty acid content of about 10% to about 40% by weight; for example about 20% to about 35% by weight.
The lipid mixture may contain vitamins, antioxidants and minerals as desired. Vitamins with antioxidant properties such as vitamin C and vitamin E are particularly preferred since these vitamins may reduce free radical production in osteoclasts. This may depress bone resorption and hence increase bone formation. A suitable calcium salt is preferably included as a mineral.
The mono-unsaturated fatty acids may be consumed in the form of the vegetable oils or lipid mixtures described above. However, it is also possible to formulate these vegetable oils and lipid mixtures into other suitable forms. For example, these vegetable oils and lipid mixtures may comprise all or part of the lipid component of foods such as salad dressings, mayonnaises, yogurts, milk substitutes, sauces, creams, ice creams, fat-based confectionery products, biscuits, and pet foods. Preferably the foods contain about 1% to about 80% of the vegetable oils and lipid mixtures; more preferably about 5% to about 60%> by weight.
The amount of mono-unsaturated fatty acids required to be fed to a human or animal to obtain beneficial affects will vary depending upon factors such gender, health, body weight, age, and the like. However, in general, sufficient
mono-unsaturated fatty acids should be administered to provide the human or animal with about 0.3 g to about 1 g mono-unsaturated fatty acids per kg of body weight per day. For example, an adult human may consume 0.4 g to about 0.6 g mono-unsaturated fatty acids per kg of body weight per day. The mono-unsaturated fatty acids are preferably consumed over long periods of time as part of daily or weekly nutrition. Of course, it is not essential to consume the mono-unsaturated fatty acids on a daily basis. However regular consumption is preferable for maximum effect.
Example 1
One hundred and fifty four healthy people are recruited for the study; 36 men and 1 18 women. Each person is asked to undergo bone mineral density determination of the non-dominant forearm using single photon absorptiometry. A absoφtiometer obtained from Nuclear Data (model 1 100a) and operated using a 125I source (100 mCi) with a photopeak at 27 KeV, is used. Sociodemographic, reproductive and somatometric information is gathered for each person. Further, each people is asked to indicate the average frequency of consumption, during the year prior to the interview, of 115 different food items. The distribution of the study subjects is as follows:
For analysis, the frequency of consumption of different food items is quantified in terms of the number of time per month the food is consumed.
Therefore the value for a daily consumption is multiplied by 30, the value for a weekly consumption is multiplied by 4, and a value of 0 is assigned to foods rarely or never consumed. The nutrient intakes for each person are estimated by multiplying the nutrient content of a selected typical portion of each food item by the frequency that the food item is consumed per month. The nutrient intakes analyzed are protein, saturated fats, mono-unsaturated fats, poly-unsaturated fats, mono-, di- and poly- saccharides, crude fiber, calcium and total energy.
The data are analyzed using multiple linear regression. First, the bone mineral density is regressed on non-nutritional variables, energy intake and mono-unsaturated fat. In subsequent analyses, each other nutrient is substituted for mono-unsaturated fat; in each case adjusting for energy intake.
The results indicate a significant association between mono-unsaturated fatty acid and increased bone mineral density in both men and women (for men, p=0.01 and for women, p=0.03). This association is independent of total energy intake.
High energy intake, which reflects physical activity, is significantly associated with increased bone mineral density in both men and women (for men, p=0.003 and for women, p=0.04).
A marginally significant association (p=0.06) between increasing age and decreasing bone mineral density in women is determined. For men, there is no significant association.
No other statistically significant associations are determined. The results provide firm evidence that the regular consumption of mono- unsaturated fatty acids has a positive effect on bone density.
Claims
1. The use of a mono-unsaturated fatty acid in the preparation of an enteral composition for the prophylaxis or treatment of bone density loss in an animal or human.
2. The use according to claim 1 in which the enteral composition is a nutritional composition forming part of daily diet.
3. The use according to claim 1 in which the mono-unsaturated fatty acid forms part of a lipid mixture which contains at least 50% by weight of mono- unsaturated fatty acids.
4. The use according to claim 3 in which the lipid mixture includes poly- unsaturated fatty acids.
5. The use according to claim 4 in which the lipid mixture includes about 10% to about 40% by weight of poly-unsaturated fatty acids.
6. The use according to claim 5 in which the lipid mixture includes about 20%) to about 35% by weight of linoleic acid.
7. The use according to claim 5 in which the lipid mixture includes about 2% to about 10% by weight of ω-3 fatty acids.
8. The use according to claim 4 in which the poly-unsaturated fatty acids have a ratio of ω-6:ω-3 fatty acids of 3 : 1 to 9: 1.
9. The use according to claim 1 in which the enteral composition further comprises a source of vitamin C, or vitamin E, or both.
10. A method for the prophylaxis or treatment of bone density loss in an animal or human, the method comprising administering to the animal or human an effective amount of a mono-unsaturated fatty acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU88572/98A AU8857298A (en) | 1997-07-16 | 1998-07-06 | Method for prophylaxis or treatment of bone density loss |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5269197P | 1997-07-16 | 1997-07-16 | |
| US60/052,691 | 1997-07-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1999003456A2 true WO1999003456A2 (en) | 1999-01-28 |
| WO1999003456A3 WO1999003456A3 (en) | 1999-04-15 |
Family
ID=21979280
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1998/004187 WO1999003456A2 (en) | 1997-07-16 | 1998-07-06 | Method for prophylaxis or treatment of bone density loss |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU8857298A (en) |
| WO (1) | WO1999003456A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007061752A2 (en) * | 2005-11-17 | 2007-05-31 | Bioavailability, Inc. | Biocompatible latent emulsifiers |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0517425A1 (en) * | 1991-06-05 | 1992-12-09 | Efamol Holdings Plc | Fatty acids for the reduction of urinary calcium excretion and the treatment of osteoporosis |
| EP0585026A1 (en) * | 1992-08-21 | 1994-03-02 | Scotia Holdings Plc | Use of fatty acids for increasing gut calcium absorption |
-
1998
- 1998-07-06 WO PCT/EP1998/004187 patent/WO1999003456A2/en active Application Filing
- 1998-07-06 AU AU88572/98A patent/AU8857298A/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0517425A1 (en) * | 1991-06-05 | 1992-12-09 | Efamol Holdings Plc | Fatty acids for the reduction of urinary calcium excretion and the treatment of osteoporosis |
| EP0585026A1 (en) * | 1992-08-21 | 1994-03-02 | Scotia Holdings Plc | Use of fatty acids for increasing gut calcium absorption |
Non-Patent Citations (6)
| Title |
|---|
| BARTELS T ET AL: "ÄEffect of linoleic acid in food on spongioid bone density and prostaglandin biosynthesis in bonesÜ. Einfluss des Linolsauregehaltes der Nahrung auf Spongiosadichte und Prostaglandin--Biosynthese im Knochen." BEITRAGE ZUR ORTHOPADIE UND TRAUMATOLOGIE, (1988 AUG) 35 (8) 353-9. JOURNAL CODE: 9N4. ISSN: 0005-8149., XP002093684 GERMANY, EAST: German Democratic Republic * |
| HORROBIN, DAVID F.: "Essential fatty acid metabolism and bone." BONE (NEW YORK), (1997) VOL. 20, NO. 4 SUPPL., PP. 120S. MEETING INFO.: 25TH EUROPEAN SYMPOSIUM ON CALCIFIED TISSUES HARROGATE, ENGLAND, UK APRIL 25-29, 1997 ISSN: 8756-3282., XP002093685 * |
| KREIDER, R. (1) ET AL: "Effects of conjugated linoleic acid (CLA) supplementation during resistance-training on bone mineral content, bone mineral density and markers of immune stress." FASEB JOURNAL, (MARCH 17, 1998) VOL. 12, NO. 4, PP. A244. MEETING INFO.: ANNUAL MEETING OF THE PROFESSIONAL RESEARCH SCIENTISTS ON EXPERIMENTAL BIOLOGY 98, PART 1 SAN FRANCISCO, CALIFORNIA, USA APRIL 18-22, 1998 FEDERATION OF AMERICAN SOCIETIES FOR E, XP002093683 * |
| SEIFERT, MARK F. ET AL: "Role of dietary lipid and antioxidants in bone metabolism" NUTR. RES. (N. Y.) (1997), 17(7), 1209-1228 CODEN: NTRSDC;ISSN: 0271-5317, XP002093681 * |
| TRICHOPOULOU A. ET AL: "Energy intake and monounsaturated fat in relation to bone mineral density among women and men in Greece." PREVENTIVE MEDICINE, (1997) 26/3 (395-400). REFS: 58 ISSN: 0091-7435 CODEN: PVTMA3, XP002093682 United States * |
| WATKINS B A ET AL: "Dietary (n-3) and (n-6) polyunsaturates and acetylsalicylic acid alter ex vivo PGE2 biosynthesis, tissue IGF-I levels, and bone morphometry in chicks." JOURNAL OF BONE AND MINERAL RESEARCH, (1996 SEP) 11 (9) 1321-32. JOURNAL CODE: 130. ISSN: 0884-0431., XP002093680 United States * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007061752A2 (en) * | 2005-11-17 | 2007-05-31 | Bioavailability, Inc. | Biocompatible latent emulsifiers |
| WO2007061752A3 (en) * | 2005-11-17 | 2008-04-10 | Bioavailability Inc | Biocompatible latent emulsifiers |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999003456A3 (en) | 1999-04-15 |
| AU8857298A (en) | 1999-02-10 |
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