Use of KidneyTonifying Traditional Chinese Medicine for Prevention and Treatment of Osteoporosis

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Use of Kidney-Tonifying Traditional Chinese
Medicine for Prevention and Treatment of
Osteoporosis

• Man-Sau Wong, Ph.D.
• Associate Director
• Institute of Modern Chinese Medicine
• The Hong Kong Polytechnic University

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Osteoporosis a worldwide public health problem

• 2 billion women worldwide are suffering from
  osteoporosis.
• One-third of women of age 60 to 70 and two-third
  of women of age 80 or above are suffering from
  osteoporosis.
• In Europe and USA, 650,000 patients are suffering
  from hip fracture each year, the mortality rate
  are increasing at a rate of 10-20 per year. 19
  of these patients require long-term care
  thereafter.
• According to the Chinese Osteoporosis Foundation,
  the estimated number of patients with
  osteoporosis in China is 84 million which
  accounted for 6.6 of the total population.

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Osteoporosis ????

• A systemic skeletal disease ????????
• Low bone mass
• Microarchitectural deterioration of bone tissue
• Fragility Fractures ??
• Vertebral and Hip Fractures
• Morbidity Mortality

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Pathogenesis of osteoporosis ??

• Estrogen deficiency
• ?????
• caused by menopause and aging
• Secondary hyperparathyroidism
• ?????????? caused by age-related abnormalities
  in extraskeletal calcium homeostasis.

Pictures was supplied by Dr. Louis Avioli
extracted from Mundy GR, Bone remodeling and
its disorder 2nd edition, 1999
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Current approach for management of osteoporosis

• Bone resorption inhibitors
• Estrogen
• Bisphosphonates
• Calcitonin

• Bone formation stimulators
• Parathyroid hormone
• Growth factors
• Fluoride
• HMG coenzyme A reductase inhibitors (i.e. the
  statins)

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The Kidney The Bones (???)
Kidney-Tonifying ??
The Kidney dominates the bones ???
Treatment of bone diseases ??
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Kidney-Tonifying Traditional Chinese Medicine
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Kidney-Tonifying Traditional Chinese Medicine
Formula

• A kidney-tonifying traditional Chinese medicine
  (Plus 40 for Women, the Revitalizer, ??????)
  invented by Prof. Min-Ru Liu, Chengdu University
  of Traditional Chinese Medicine and Deputy
  Director of China Association of Traditional
  Chinese Medicine.
• Manufactured under GMP conditions by Han Sheng
  Tang Ltd.
• This formula is indicated for relief of menopause
  discomfort such as aches and pains, hot flashes
  and sweats, insomnia and irritability,
  forgetfulness, headaches, palpitation, blurry
  vision, shortness of breath, fatigue and loss of
  skin tone, water distention and loss of hair.

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Kidney-Tonifying Traditional Chinese Medicine
Formula

• Previous clinical research by Prof. Liu showed
  that this formula can improve ovarian blood
  circulation, maintain vaginal health during
  menopause and slows down the aging of ovaries.
• This formula can also protect blood vessels of
  the heart and brain.
• It has anti-oxidative activity and can increase
  serum superoxide dismutase level.

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Kidney Tonifying formula modulates
hypothalamus-pituitary gland-ovary axis
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Kidney-tonifying Herbal Formula
Beneficial to Bone Health ? Treatment of
Postmenopausal Osteoporosis ?
Herba Epimedii ???? (Epimedium) Leaf of
Epimedium leptorrhizum Epimedium wushanense T.
S. Ying
Kidney tonifying formula Plus 40 for Women, the
Revitalizer ??????
Fructus Ligustri Lucidi ??? (Ligustrum) Fruit
of Ligustrum lucidum Ait.
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Animal Study
Design 3-Month-old female SD rats Ovariectomy
/ Sham operation
OVX or Sham Operation
Start feeding with H2O, estradiol or the herbal
extracts of Kidney-tonifying herbs / herbal
formula
12 Weeks
Baseline
-4 Weeks

• Serum and Urine biochemical markers
• Calcium balance study
• Bone histomorphometry

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Kidney-tonifying formula and herbs altered
calcium metabolism in ovariectomized rats
??????
p lt 0.05, p lt 0.01, plt 0.001
14
Kidney-tonifying formula and herbs suppressed
bone turnover in ovariectomized rats
??????
p lt 0.05, p lt 0.01, plt 0.001
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Kidney-Tonifying herbs improved bone architecture
in ovariectomized rats
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Kidney tonifying formula and epimedium extract
decreased ovariectomy-induced loss in trabecular
bone
??????
p lt 0.05, p lt 0.01
17
Kidney-tonifying formula and herbs did not alter
uterus weight in ovariectomized rats
??????
plt 0.001
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How does the kidney-tonifying formula work?
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Kidney tonifying formula and Ligustrum increased
intestinal Ca absorption in ovariectomized rats
??????
p lt 0.05, p lt 0.01, plt 0.001
20
Kidney tonifying formula increased intestinal
vitamin D receptor mRNA expression
??????
p lt 0.05, p lt 0.01
21
Epimedium extract stimulates cell proliferation
and ALP activities in osteoblast-like UMR 106
cells
p lt 0.05
22
Osteoblast differentiation
T Katagiri and N Takahashi Oral Dis. 2002
May8(3)147-59
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Epimedium stimulates osterix mRNA expression in
UMR 106 cells
RUNX 2
GAPDH
p lt 0.05, p lt 0.01
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OsteoclastogenesisRANKL/Osteoprotegrin
interaction
T Katagiri and N Takahashi Oral Dis. 2002
May8(3)147-59
25

• Epimedium extract might modulate
  osteoclastogenesis via its action in osteoblastic
  cells.

p lt 0.05, p lt 0.01
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Summary of the effects of kidney-tonifying herbs
on bone and mineral metabolism
In vivo effects on bone metabolism ?urinary
deoxypyridinoline ?serum alkaline
phosphatase ?bone turnover ? trabecular bone
area ?trabecular separation
In vivo effects on Ca metabolism ?urinary Ca
excretion ?intestinal Ca absorption ?Ca
balance ?intestinal VDR mRNA expression
In vitro effects on bone formation
cells ?osteoblastic cell growth ?osteoblastic
cell differentiation ?osterix mRNA
expression ?OPG mRNA expression ?RANKL mRNA
expression
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Conclusion

• Treatment of OVX rats with Epimedium reduced
  urinary Ca loss, suppressed bone resorption and
  reduced OVX-induced bone loss. The in vitro study
  indicated that effects of Epimedium might be
  mediated by its direct anabolic actions on bone.
• Treatment of OVX rats with Ligustrum reduced
  urinary Ca loss, increased intestinal Ca
  absorption and suppressed bone resorption.
• Treatment of OVX rats with kidney-tonifying
  formula reduced urinary Ca loss, increased
  intestinal Ca absorption, suppressed bone
  turnover and reduced OVX-induced bone loss.
• The results indicated that kidney-tonifying
  formula appears to have more prominent
  protective effects on bone than either extract of
  Epimedium or Ligustrum in OVX rats.

??????
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Future directions

• Systematically evaluate the synergistic effects
  of combining different kidney-tonifying herbs on
  bone and mineral metabolism
• Identify the mechanism of actions of each
  kidney-tonifying herb using modern technology
  such as cDNA microarray
• Develop in vitro screening system for
  identification of active ingredients in
  kidney-tonifying herbs.

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Acknowledgement

• The Hong Kong Polytechnic University
• Edith WP Lai
• Summi Lau
• Helen SK Mok
• Dr. Wenfang Chen
• Dr. Robbie YK Chan
• Dr. Belinda PY Cheung
• Funding Support
• The Open Laboratory of Chirotechnology (PolyU,
  AOE)
• Central Research Fund (PolyU)
• CERG RGC Fund
• NSFC-RGC Fund

• Collaborators
• Prof. Min-Yu Liu (Chengdu University of
  Traditional Chinese Medicine )
• Xiangkun Jiang
• Prof. Xin-Sheng Yao (ShenYang Pharmaceutical
  University)
• Fang Xie
• Yan Zhang
• Xujuan Yang
• Prof. Ping-Chung Leung (The Chinese University of
  Hong Kong)
• Yin-Mei Wong
• Prof. Murray J. Favus (The University of Chicago)