01 2013 Peptan Bone Joint Health English LR
Transcript of 01 2013 Peptan Bone Joint Health English LR
BonesBones, which makes up the skeleton, are
composed of cells embedded in hard intercel-
lular material (the matrix) made of mineralized
substances and collagen fibers. Like all body
tissues, bones are in a continuous state of flux.
The mechanical integrity of the skeleton and the
maintenance of appropriate mineral levels depend
on a dynamic process called bone remodeling or
bone turnover.
Skeletal mass increases progressively during
growth. The age at which bone loss starts is
uncertain but, it is generally believed to be during
the thirties in both sexes. Approximately 15%
of bone in healthy adults is replaced by bone
turnover each year. Irregular rates of bone resorp-
tion and formation – leading to more bone loss
than formation – are a hallmark to osteopenia.
According to the World Health Organiza-
tion (WHO), osteopenia is used to describe
individuals who have a low bone mass and some
increased risk of fracture. Their bone mass is not
so low that they are deemed to have osteoporosis.
The bone mass is measured on a point scale,
called a “T” score. The range defining osteopenia
or low bone mass is quite large, ranging from
-1 to -2.5 T-scores (that is, bone density levels
that are 1 to 2.5 standard deviations below the
average for young adults who have achieved
normal peak bone mass), which translates into
bone mass that is 10–30 percent below this
average level.
The main goal for screening and treating for
osteopenia is to maintain bone health and prevent
fractures. It has been demonstrated that an early
diagnosis and treatment of osteopenia reduces
fractures rates and improves life quality (3). In a
population-based random study (616 women
aged 60 - 94 years followed for a median 5.6
years) conducted by Pasco and published in
2006 in Osteoporosis journal (13), it has been
determinated that 73.1% of fractures occurred in
women without osteoporosis (56.5% in women
with osteopenia and 16.6% in women with normal
Bone Mineral Density).
Because life expectancy is increasing around the
world, the number of elderly individuals is rising
in every region. According to WHO, the number
of individuals aged 65 years or over will increase to
an estimated 1555 million by the year 2050. The
influence of such changes on the number and
regional distribution of hip fractures will be dramatic
as the population burden of fractures originates in
men and women with osteopenia.
As the population ages, the drawbacks of aging are becoming more
apparent. Osteoarthritis and osteopenia, two of the major health concerns,
are among the leading causes of pain and disability.
It is now well known that collagen peptides can help to maintain bone and
joint health to prevent osteopenia and osteoarthritis.
Hip
fra
ctu
res
(103 )
Joint & Bone HealthAging of the world’s population sees growth in bone and joint health problems.
2500
2000
1500
1000
500
0
Men WomenNorth
America
Men WomenEurope
Men WomenRussian
Federation
Men WomenEastern
Mediterranean
Men WomenAsia
Men WomenAfrica
1990
2025
2050
Number of hip fractures in 1990 and those predicted in different regions of the world for 2025 and 2050
+1,0 –– 0,0 ––
-1,0 –– -2,0 –– -2,5 –– -3,0 –– -4,0 ––
Normal bone density
Low bone mass
Presence of osteoporosis
Bone mineral T-score measure
Joints Cartilage consists of a single cell type, chondro-
cytes embedded in extracellular matrix made up
of two major components: type II collagen which
imparts tensile strength to the tissue and aggrecan
that provides the ability of cartilage to resist
compressive force. Orchestrated synthesis and
turnover ensures and maintains the biochemical
characteristic of the cartilage.
During osteoarthritis, the most common form of
arthritis, this regulation is disrupted by the expres-
sion of pro-inflammatory molecules that provides
the stimulus for the synthesis of matrix-degrading
enzymes. These enzymes degrade aggrecan and
collagen, resulting in the loss of cartilage and
function.
This chronic degeneration of the joints is already
considered by the World Health Organization as
one of the most disabling diseases in developed
countries. For those who are affected, the
consequences are important because 80% have
limitations in movement, and 25% can not
perform their major daily activities of life.
All joints can be affected, although it occurs more
often on knee and hip joints and in the vertebral
column. In advanced stages it is extremely painful.
Osteoarthritis is usually due to the
aging process, but osteoarthritis
due to external factors has
also been reported, for
example in people whose
activities involve joint
stress, such as sports
activities or even at work.
Severe overweight can
also cause osteoarthritis.
Prevalence of osteoarthritis
Mill
ion
s o
f p
eop
le
160
140
120
100
80
60
40
20
0India China
2003
2008
2013
US JapanBrazil Germany France
Arthritis in the world
According to worldwide estimation, arthritis
affects 9.6% of men and 18% of women aged
over 60 years.
Moreover, according to Datamonitor (2009), the
arthritis prevalence has increased all over the
world since 2003, such as in India (+2.3% per
year) or Brazil (+2.1% per year), and will continue
to grow, possibly even reaching 2.5% per year in
India and 2.3% per year in Brazil.
Peptan®
Collagen peptides for bone health
Collagen, which represents 90% of organic
bone mass, has been identified as effective in the
treatment of osteopenia. Several studies show
that a daily intake of 10g of collagen peptides for
4 to 24 weeks increases bone mass density (1, 2).
Researchers have produced several keys for
understanding how collagen peptides work.
They have also shown that the extra-cellular
matrix in which cells grow is decisive in their
differentiation. Studies have demonstrated that
when collagen peptides metabolites are present in
this matrix, osteoblasts, the cells responsible for
bone formation, are preferentially stimulated,
instead of osteoclasts, the cells involved in bone
resorption, this triggers bone formation (4, 5, 6).
Studies conducted by Rousselot with Peptan® at
the Physiology and Ingestive Behavior Laboratory,
INRA-AgroParis Tech (Paris, France) and presented
below, confirm these scientific findings and
provide new information about the effect of
Peptan® on bone metabolism (7).
A culture of osteoblasts (star-shape cells) and osteoclasts (round black cells) with Peptan®.
Peptan® induces the differentiation of cells
into osteoblasts
In mixed cultures of osteoblasts and osteoclasts,
the levels of alkaline phosphatase (ALP), a marker
of bone formation, are increased when Peptan®
is present in the media. Since the number of cells
does not increase with Peptan® compared to the
control group, this means that Peptan® induces
the differentiation of cells into osteoblasts, rather
than osteoclasts.
Peptan® reduces bone resorption
Moreover, when the culture is performed on a system which allows measurement of
the osteoclast-mediated bone resorption, we can see that when Peptan® is present
the resorption area is reduced compared to the control.
Measures of Alkaline Phosphatase
mg
/mL/
min
/∆D
C
2,5
2
1,5
1
0,5
0BSA Peptan® B
1 mg/mL
0,5 mg/mL
Peptan® P Peptan® F
Measures of alkaline phosphatase (ALP) activity in bone cell culture with Peptan® B (bovine), Peptan® P (porcine) and Peptan® F (fish) for 14 days, compared to BSA (standard proteins).
*
** *
*
*
A B
Rousselot® in vitro results
Cell culture with BSA standard protein (A) or with Peptan® (B): osteoclasts activity is measured by the digestion of a calcium phosphate film (white spot).
Peptan® induces differentiation into osteoblast, at the same time reducing
the differentiation into osteoclast.
Rousselot® in vivo results
BMD increase
(g/c
m2 )
0,025
0,02
0,015
0,01
0,005
0Control
a
b
a
Ovx Ovx+Peptan®
Measure of the cortical area
(mm
2 )
1,25
1,2
1,15
1,1Control
ab
b
a
Ovx Ovx+Peptan®
Measure of CTX concentration
(µg
/mL)
15
10
5
0Control
b
a
b
Ovx Ovx+Peptan
Measure of ultimate strengthN
31
30
29
28
27
26
25Control
abb
a
Ovx Ovx+Peptan®
Increase of Bone Mineral Density (BMD) of the mice, in the control group (Control), the ovariectomized group fed without Peptan® (Ovx), and the ovariectomized group fed with Peptan® (Ovx + Peptan) after 12 weeks. Groups with different letters indicate significant difference (p<0.05).
The in vivo part of this study confirms but
also reveals some completely new findings.
In this part, ovariectomized mice were used to
simulate low bone mass density: osteopenia.
This surgery actually slows down the bone
mineral density increase during the growth of
the concerned mice. The mice were fed with or
without Peptan® for 12 weeks and various data
was collected. The Peptan® group had a 4g daily
diet containing 2.5% (0.1g) of Peptan®.
First, in ovariectomized mice fed with Peptan® for
12 weeks, measures show restoration of the bone
mineral density value close to the level of the
control group (which was not ovariectomized).
Moreover, growth of the cortical zone (external
area of the bone) of the femur, and a significant
increase in bone size, was measured in ovariec-
tomized mice fed with Peptan®, compared to
ovariectomized mice not fed with Peptan®.
Due to this restoration, the ultimate strength of
the bones (strength required to lead to a break)
was significantly greater for ovariectomized mice
fed with Peptan®.
Finally, confirming the in vitro studies, in vivo
studies have demonstrated that the bone
resorption of ovariectomized mice fed Peptan®,
measured in terms of CTX production, is similar to
the control group.
Measure of the cortical area and the ultimate strength, in the control group (Control), the ovariectomized group fed without Peptan® (Ovx), and the ovariectomized group fed with Peptan® (Ovx + Peptan).Groups with different letters indicate significant difference (p<0.05) - ab is not significantly different from a or b.
Peptan® increases bone size and solidity
Measure of the Carboxy-Terminal collagen (CTX) peptides concentration, peptides fragments generated by collagen degradation, an important biochemical marker of bone resorption, in the control group (Control), the ovariectomized group fed without Peptan® (Ovx), and the ovariectomized group fed with Peptan® (Ovx + Peptan). Groups with different letters indicate significant difference (p<0.05).
Peptan® has been shown to be effective on
bone metabolism by inducing differentiation
and maturation of osteoblast and stimulat-
ing their activity. Bone turnover is thus
modulated, preventing bone resorption
during the natural phenomenon of bone loss
(osteopenia) and increasing bone solidity.
Peptan® restores bone mineral density
Peptan® decreases bone resorption
a placebo. At the end of the study, an assessment
of participants by physicians showed statistically
significant changes with the dietary supplement
collagen peptides: joint pain at rest, when walking,
standing or carrying objects was reduced (10).
Peptan® A bioactive ingredient that reduces joint pain
Collagen peptides offer proven efficacy
The beneficial effects of collagen peptides have
been reported in numerous research findings.
The clinical study conducted by Moskowitz (8),
performed on various populations for a period
ranging from 30 to 90 days, demonstrated a
positive effect on pain reduction with a dose of
10g of collagen peptides per day. The effect was
even more pronounced in patients suffering more
severe symptoms.
Another more recent study assessed the efficiency
of collagen peptides in a randomized, double
blind, controlled multicentre trial, in which 250
subjects with primary osteoarthritis
of the knee were given 10g of
collagen peptides daily. The results
showed a significant improvement in
knee joint comfort, and again subjects
with the greatest joint deterioration
benefited most (9).
The effectiveness of collagen peptides has been
also proven in athletes with activity-related joint
pain. In a 24-week study conducted in 2008, 147
subjects who compete as part of a varsity team or
club sport were recruited and randomly assigned
to two groups: one group received a liquid with
10g of collagen peptides, and the other received
Type ll collagen secretion by chondrocytes in culture
Typ
e ll
colla
gen
(μ
g/1
06 ch
on
dro
cyte
s)
Culture time (days)
1,8
1,6
1,4
1,2
1
0,8
0,6
0,4
0,2
06 8 11
Basal medium (control)
Medium containingcollagen peptides
Collagen peptides in cartilage
Rad
ioac
tivi
ty (
dm
p/1
00 m
g c
arti
lag
e)
Time (hours)
Control14C labeled collagen peptides
300
250
200
150
100
50
0
0 12 24 36 48 60 72 84 96
Collagen peptides are accumulated in cartilageSome explanations of this positive effect were revealed in the study by Oesser (11). He showed that more
than 95% of 14C labeled collagen peptides taken orally is absorbed. However, he also showed that an
important part is accumulated in cartilage of mice as early as 12 hours after ingestion. The radioactivity
level was more than twice as high in cartilage following 14C labeled collagen peptide administration
compared with the control group (14C labeled proline + collagen peptides).
Time course of radioactivity in cartilage of mice subsequent to absorption of 14C labeled collagen peptides and 14C labeled proline in the control group. The mice received 10mg collagen peptides/g body weight. *p<0.05 between collagen peptides and control (11).
Collagen peptides induce the production of type II collagen by chondrocytes
In another study (12), the same author explains that the chondrocytes (cells of the cartilage) are sensitive
to the products present in the extracellular matrix around them, and that the treatment of chondrocytes
with collagen peptides in the medium leads to a dose-dependent production of collagen by those cells.
Time course of type II collagen secretion into supernatant of bovine chondrocytes cultured in basal medium or in medium supplemented with 0.5 mg/mL of collagen peptides. After 11 days of culture, type II collagen secretion was almost 2.5-fold higher in collagen peptides cultures. *p<0.01 between collagen peptides and control cultures (12).
**
**
*
*
*
The action mechanism of collagen peptides
Regarding bones, Peptan® has been shown
to:
• Restore bone mineral density.
• Increase the bones size, making them less
brittle.
• Stimulate osteoblast activity in spite of
osteoclasts activity; the growth of the bone is
stimulated.
Regarding joints, collagen peptides have been
shown to:
• Significantly reduce joint pain, and subjects with
the greater deterioration benefit most.
• Orally taken collagen peptides are accumulated
in cartilage as soon as 12 hours after the inges-
tion and the cells of the joint, the chondrocytes,
are responding to these extern collagen by
producing a dose-dependant production of
intern collagen.
Conclusion
Peptan®
a completely characterized and scientifically objectivised bioactive ingredient that helps to:
•Prevent osteopenia
• Maintain bone health
• Prevent loss of bone solidity
•Prevent osteoarthritis
• Reduce joint pain
• Prevent joint matrix degeneration
These different studies demonstrate the benefits of collagen peptides on joint and bone health.
The results indicate that collagen peptides could be useful in the prevention and treatment of osteopenia
and osteoarthritis.
References
1. Nomura, Y., Oohashi, K., Watanabe, M. and Kasugai, S. 2005. Increase in bone mineral density through oral administration of shark gelatine to ovariectomized rats. Nutrition, 21: 1120-1126.
2. Wu, J., Fujioka, M., Sugimoto, K., Mu, G. and Ishimi, Y. 2004. Assessment of effectiveness of oral administration of collagen peptide on bone metabolism in growing and mature rats. Journal of bone and mineral metabolism, 22: 547-553.
3. Karaguzel, G., Holick, M. 2010. Diagnosis and treatment of osteopenia. Rev Endocr Metab Disord, 11: 237-251.4. Mizuno, M. and Kuboki, Y. 2001. Osteoblast-related gene expression of bone marrow cells during the osteoblastic differentiation induced by type I collagen. Journal of biochemistry,
129: 133-138.5. Andrianarivo, A.G., Robinson, J.A., Mann, K.G. and Tracy R.P. 1992. Growth on type I collagen promotes expression of the osteoblastic phenotype in human osteosarcoma MG-63 cells.
Journal of cellular physiology, 153: 256-265.6. Lynch, M.P., Stein, J.L., Stein, G.S. and Lian, J.B. 1995. The influence of type I collagen on the development and maintenance of the osteoblast phenotype in primary and passaged rat
calvarial osteoblasts: modification of expression of genes supporting cell growth, adhesion, and extracellular matrix mineralization. Experimental cell research, 216: 35-45.7. Guillerminet, F., Beaupied, H., Fabien-Soulé, V., Tomé, D., Benhamou, C-L., Blachier, F., Roux, C. and Blais, A. 2010. collagen peptides improves bone metabolism and biomechanical
parameters in ovariectomized mice: an in vitro and in vivo study. Bone. 8. Moskowitz, R. 2000. Role of collagen hydrolysate in bone and joint disease. Seminars in arthritis and rheumatism, 30 (2): 87-99. 9. Ruiz-Benito, P., Camacho-Zambrano, M.M., Carrillo-Arcentales, J.N., Mestanza-Peralta, M.A., Vallejo-Flores, C.A., Vargas-Lopez, S.V., Villacis-Tamayo, R.A. and Zurita-Gavilanes, L.A.
2009. A randomized controlled trial on the efficacy and safety of a food ingredient, collagen hydrolysate, for improving joint comfort. International journal of food sciences and nutrition, 12:1-15.
10. Clark, K.L., Sebastianelli, W., Flechsenhar, K.R., Aukermann, D.F., Meza, F., Millard, R.L., Deitch, J.R., Sherbondy, P.S. and Albert, A.. 2008. 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Current medical research and opinion, 24 (5): 1485-1496.
11. Oesser, S., Adam, M., Babel, W. and Seifert, J. 1999. Oral administration of 14C labelled gelatine hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL). Journal of nutrition, 129: 1891-1895.
12. Oesser, S. and Seifert, J. 2003. Stimulation of type II collagen biosynthesis and secretion in bovine chondrocytes cultured with degraded collagen. Cell tissue research, 311: 393-399. 13. Pasco, J.A, Seeman, E., Henry M.J, Merriman, E.N, Nicholson, G.C, Kotowicz, M.A. 2006. The population burden of fractures originates in women with osteopenia, not osteoporosis.
Osteoporosis Int, 17: 1404-1409.
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