Review Article Diabetic Osteoporosis: A Review of Its ...mineral density (BMD) in patients with DOP. Shang et al. [, ] found that Bushen Tongluo decoction had the ability ... Yushanjiang

Review ArticleDiabetic Osteoporosis A Review of Its Traditional ChineseMedicinal Use and Clinical and Preclinical Research

Rufeng Ma1 Ruyuan Zhu1 Lili Wang1 Yubo Guo1 Chenyue Liu2 Haixia Liu1

Fengwei Liu3 Hongjun Li3 Yu Li1 Min Fu4 and Dongwei Zhang5

1Preclinical Medicine School Beijing University of Chinese Medicine Beijing 100029 China2Chinese Materia Medica School Beijing University of Chinese Medicine Beijing 100029 China3Henan Luoyang Orthopedic Traumatological Hospital Luoyang 471000 China4The Research Institute of McGill University Health Center Montreal QC Canada H4A 3J15Diabetes Research Center Beijing University of Chinese Medicine Beijing 100029 China

Correspondence should be addressed to Dongwei Zhang dongwei1006gmailcom

Received 3 April 2016 Revised 15 July 2016 Accepted 18 July 2016

Academic Editor Khalid Rahman

Copyright copy 2016 Rufeng Ma et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Aim The incidence of diabetic osteoporosis (DOP) is increasing due to lack of effective management over the past few decadesThis review aims to summarize traditional Chinese medicine (TCM) suitability in the pathogenesis and clinical and preclinicalmanagement of DOP Methods Literature sources used were from Medline (Pubmed) CNKI (China Knowledge ResourceIntegratedDatabase) andCSTJ (China Science andTechnology Journal Database) online databases For the consultation keywordssuch as diabetic osteoporosis (DOP) TCM clinical study animal experiment toxicity and research progress were used in variouscombinations Around 100 research papers and reviews were visited Results Liver-spleen-kidney insufficiency may result indevelopment of DOP 18 clinical trials are identified to use TCM compound prescriptions for management of patients with DOPTCM herbs and their active ingredients are effective in preventing the development of DOP in streptozotocin (STZ) and alloxan aswell as STZ combined with ovariectomy insulted rats Among them most frequently used TCM herbs in clinical trials are RadixAstragali Radix et Rhizoma Salviae Miltiorrhizae Radix Rehmanniae Preparata and Herba Epimedii Some of TCM herbs alsoexhibit toxicities in clinical and preclinical research Conclusions TCM herbs may act as the novel sources of anti-DOP drugs byimproving bone and glucolipid metabolisms However the pathogenesis of DOP and the material base of TCM herbs still meritfurther study

1 Introduction

Diabetic osteoporosis (DOP) is a chronic bone metabolicdisease induced by diabetes mellitus (DM) and its patho-genesis involves an increase in osteoclast activity a decreasein osteoblast activity aggravation of bone microcirculationan increase in adipogenic differentiation of mesenchymalmultipotential stem cells (MMSCs) and an increase inadvanced glycation end products (AGEs) [1 2] With theincreasing incidence of DM in the world the number ofpatients with DOP increased accordingly [3] Clinical studieshave shown that about 12 to 23 of diabetic patients sufferedfromdecreasing bone strength andor increasing incidence offractures of whom nearly 13 were diagnosed as osteoporosis

[4] In recent years traditional Chinese medicine (TCM) hasattracted increasing attention in prevention and treatment ofDOP This review highlights the pathogenetical clinical andexperimental advances in management of DOP in TCM andalso provides a strong scientific evidence for understandingand improving the treatment of DOP

2 DOP Pathogenesis in TCM

DOP belongs to the secondary osteoporosis whose conceptwas first proposed in 1948 [2 46] In TCM there is nocorresponding term to describe DOP However the clinicalperformances are similar to the TCM symptoms of ldquoatrophicdebility of bonesrdquo ldquoGubirdquo ldquodryness of bonerdquo or ldquopain inwaist

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2016 Article ID 3218313 13 pageshttpdxdoiorg10115520163218313

2 Evidence-Based Complementary and Alternative Medicine

and lower extremitiesrdquo [47] According to TCM theories andclinical symptoms of DOP the etiology of DOP is mainlyattributed to the insufficiency of the spleen liver and kidneyIn traditional Chinese physiology the spleen (as is wellknown all the organs inTCMbear the least resemblance to itswestern counterpart) is assumed to be responsible for assim-ilation of nutrients and maintenance of physical strengthThe spleen governs blood digestion transformation andtransportation in the body [48] So the spleen has the abilityof transforming food into Qi and blood and transportingthem throughout the body Proper functioning of the organis essential to maintain muscle mass and strengthen limbsAlso in traditional Chinese physiology the liver (Gan) storesblood ensures the smooth flow ofQi and controls the actionand nutrition of tendon [49] And the kidney (Shen) storesessence and controls the growth and development of bone[50 51] Meanwhile Qi (Qi is the term used in TCM todescribe the bodyrsquos vital life energy [52]) deficiency and bloodstasis also contributed to the development of DOP

Xiao-Ke is an official terminology for diabetes in TCM[53] TCM believes that Xiao-Ke mainly resulted from thedysfunctions of kidney spleen and liver [54] As kidneycontrols bone growth and development via neuroendocrine-immune network and osteoclast regulatory pathway oste-oprotegerin- (OPG-) receptor activator of nuclear factorkappa-B ligand- (RANKL-) RANK [51 55] the deficiencyof the kidney caused by Xiao-Ke further results in bonemalnutrition The liver dredges and smooths the routeof something and produces blood by promoting circula-tion of blood and metabolism of body fluid and assist-ing the spleen and the stomach to digest food (httpoldtcmwikicomwikithe-liver) The loss of liver Yin in thedevelopment of Xiao-Ke causes blood deficiency which leadsto blood stasis tendon and vessels undernutrition [56]The spleen has the function to transport and transformnutrients by digesting food absorbing nutrients of food andwater and then transporting them to the heart and thelung (httpoldtcmwikicomwikithe-spleen) If the essencetransportation and transformation fails in spleen dampnessand circulation disorders of Qi and blood will occur to thebody [57] Further the bone is loss of nutrition which maycause insufficiency of bone marrow and bone pain [58]The codysfunctions of liver spleen and kidney lead to Qideficiency and blood stasis which further contributes toinsufficiency of blood and essence [57 59] All the abnor-malities lead to bone lesions and occurrence of DOP Theviews on the pathogenesis of DOP have been also discussedin the ancient Chinesemedicine works such as ldquoInner Canonof Huangdirdquo ldquoClinic Guideline of Medical Recordsrdquo andldquoXue Zheng Lunrdquo Therefore prevention and treatment ofDOP should focus on regulation and tonification of the liverspleen and kidney The proper function of liver spleen andkidney promotes Qi to disperse stagnation and reinforcekidney to replenish Yin which beneficially contributes toimproving bone metabolism

In recent years great achievements have been made inprevention and treatment of DOP in TCM The results havedemonstrated that TCM herbs not only had the abilities ofincreasing the bone quality by enhancing the mechanical

strength of bone but also exhibited the effect on improving theprimary disease by regulating glycaemia metabolism Nextwe review the clinical and preclinical research advances ofusing TCM in the treatment of DOP

3 Clinical Advances of DOP in TCM

As mentioned previously the clinical guidelines for TCMtreatment of DOP are tonifying liver spleen and kidneyas well as promoting Qi flow and removing blood stasisWe summarized the TCM compound prescriptions used inthe clinical trials of DOP as shown in Table 1 Till nowthere are around 18 TCM prescriptions that have been usedin managing patients with DOP in which clinical studieshave been performed by different investigators with variousprescriptions Zhang et al [5] found that Tanggukang treat-ment reduced serum malondialdehyde (MDA) and bloodglucose and increased the activity of superoxide dismutase(SOD) that contributed to controlling the glycaemia andsuppressing osteoporosis in patients with DOP In additionboth Tanggukang [6] and Qianggubao granule treatmentsalso had significant effects on patients with DOP evidencedby improving calcium and phosphorus metabolism andhydroxyproline level as well In addition Ji et al [7] foundthat Bushen Huoxue decoction treatment not only controlledglycaemia and lipidemia but also obviously improved bonemineral density (BMD) in patients with DOP Shang et al[8 9] found that Bushen Tongluo decoction had the abilityof improving BMD and reducing the risk of bone fractures inpatients with DOP Gong and Li [10] found that Jiawei Qingrsquoepill treatment improved DOP patients in blood glycosylatedhemoglobin (HbA1C) calcium and phosphorus level andfasting urine Cacreatine ratio which beneficially contributedto the balance of bone metabolism Yushanjiang and Halida[11] showed that the Xihongkang treatment prevented thedevelopment of DOP by tonifying Qi nourishing Yin andpromoting blood circulation Deng [12] demonstrated thatYishen Zhuanggu decoction treatment increased serum bonegla-protein (BGP) and 125-(OH)

2D3levels and BMD value

in patients with DOPFurthermore treatments with TCM formulas such as

Huqian pills [13] Gusong decoction [14 15] Tangmaikanggranules [16] Bushen Huoxue decoction [17] Jiawei Gutong-xian capsule [18] Qianggubao granule [19] Jiangu decoction[20] Jiangtang Bushen formulation [21] Huolisu oral liquid[22] Migu decoction [23] and Xianling Gubao [24] havealso been demonstrated to improve BMD decrease serumC-reactive protein (CRP) level and attenuate lumbar painevidenced by decreasing visual analogue scale pain score invertebra and back in the patients with DOP

Most of prescriptions used in management of DOPconsist of 4 to 14 herbs Eight of most appearing Chineseherbs in the clinical studies are compiled in Table 2 Allof these herbs possess the functions of invigorating Qiactivating blood circulation and replenishing vital essenceto tonify kidney [60] The applications also conform to theTCM pathogenesis of DOP The prescriptions are helpful forthe investigators to screen the active ingredients against DOPfrom these herbs in the future

Evidence-Based Complementary and Alternative Medicine 3

Table1Clinicalused

TCM

prescriptio

nsfortreatmento

fpatientsw

ithDOP

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Tang

gukang

decoction

7a

Fastingbloo

dglucose(FB

G)glycosylated

hemoglobin(H

bA1C

)bo

nemineral

density

(BMD)superoxide

dism

utase(SO

D)malon

dialdehyde

(MDA)bo

negla-protein(BGP)C

aand

Pin

serumand

urine

FBGandHbA

1ClevelsdecreasedBM

DB

GPandserum

SOD

levelsincreasedserum

MDAdecreasedurineC

aand

Pdecreased

Con

troltreatmentu

singoyste

rshellcalcium

chew

abletablet

[56]

Bushen

Huo

xue

decoction

11b

Sign

ificant

effectBM

Dincreasedclinicalsym

ptom

sand

painsd

isapp

eared

Effectiv

eclinicalsym

ptom

salleviatedB

MDremainedthes

ame

Ineffectiv

eBM

Dandclinicalsym

ptom

srem

ainedthes

ame

Markedlyim

proved

(24)

Mod

erately

improved

(4)

Ineffectiv

e(2)

Overalleffi

cacy933

Con

troltreatmentQiang

gucapsule

[7]

Bushen

Tong

luo

decoction

9cBroadb

andultrasou

ndattenu

ation(BUA

)soun

dof

speed(SOS)C

aand

Pin

serumalkalinep

hosphatase

(ALP

)FB

Gand

HbA

1C

BUAandSO

Ssig

nificantly

increasedFB

GandHbA

1Clevels

redu

ced

Con

troltreatmentu

singcaltrateD

[89]

JiaweiQingrsquoe

Pill

9dCa

Pcreatinine(Cr

)ratiosinbloo

dandurine

Markedlyim

proved

(25)

Mod

erately

improved

(11)

Ineffectiv

e(4)

Overalleffi

cacy90

Serum

Cadecreasedby

048

mMLserum

Pincreasedby

044

mMLurin

eCaCr

ratio

decreasedby

029

Con

troltreatmentu

singalfacalcidolandcaltrateD

[10]

Xiho

ngkang

7e

Sign

ificant

effectclinicalsym

ptom

sdisa

ppearedFB

Glt72

mMtwo-ho

urpo

stprand

ialblood

glucose(2h

PG)lt

83m

MH

bA1Clt6

orHbA

1Cdecreased

by⩾30B

MDincreasedby⩾20

Effectiv

eclinicalsym

ptom

salleviatedFBGlt83m

ML2

hPGlt100mML

HbA

1Clt8

orHbA

1Cdecreasedby⩾10B

MDincreasedby⩾10

Ineffectiv

eno

significantimprovem

entinsymptom

sHbA

1CandBM

Dremained

thes

ame

Markedlyim

proved

(56)

Mod

erately

improved

(68)

Ineffectiv

e(16)

Overalleffi

cacy886

Con

troltreatmentu

singalfacalcidolglip

izideandcaltrateD

[11]

Yishen

Zhuang

gucompo

und

9f

Sign

ificant

effectpain

disapp

earedBM

Dincreasedby

005

gcm2

Effectiv

epain

significantly

alleviatedB

MDremainedthes

ameo

rdecreased

bylt005

gcm2

Ineffectiv

eno

improvem

entinsymptom

s

Markedlyim

proved

(14)

Mod

erately

improved

(17)

Ineffectiv

e(1)

Overalleffi

cacy968

Con

troltreatmentu


[12]

Huq

ianpill

8g

Sign

ificant

effectsymptom

andph

ysicalsig

ndisapp

eared23

mMd⩽urineP⩽

48mMd25mMd⩽urineC

a⩽75

mMd167m

Md⩽urineM

g2+⩽100m

Md

096

mML⩽serum

P⩽14

5mML08mM⩽serum

Mg2+⩽12

mMX

-ray

appeared

norm

al

Effectiv

eclinicalsym

ptom

salleviatedurin

eCar

emained65plusmn

25m

moldurin

ePremained38plusmn15mmoldurin

eMg2+remained80plusmn40

mmoldX

-ray

with

out

obviou

slyabno

rmal

Ineffectiv

eno

improvem

entinsymptom

sand

signs

aswell

asotherb

iomarkers

Markedlyim

proved

(23)

Mod

erately

improved

(28)

Ineffectiv

e(5)

Overalleffi

cacy910

7Nocontrols

[13]


Table1Con

tinued

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Guson

gdecoction

13h

Sign

ificant

effectsymptom

sand

physicalsig

nsscored

ecreased

by⩾70B

MD

increasedby⩾2

significantimprovem

entinbo

nemetabolism

indexFP

Gand

2hPG

returned

tothen

ormalor

decreasedby⩾40

H

bA1C⩽62

ordecreased

by⩾30

Effectiv

esymptom

sand

physicalsig

nsscored

ecreased

between30and70

BMDincreasedbetween1

and2

bon

emetabolism

indexim

provedFPG

and

2hPG

decreasedby⩾20H

bA1C

decreasedbetween10and30

Ineffectiv

eno

significantchangeinclinicalsym

ptom

ssymptom

sand

physical

signs

scored

ecreased

bylt30B

MDincreasedbylt1

noim

provem

entinbo

nemetabolism

indexFP

Gand2h

PGand

HbA

1C

Markedlyim

proved

(15)

Mod

erately

improved

(22)

Ineffectiv

e(3)

Overalleffi

cacy925

Con

troltreatmentu

singvitamin

D3calcium

carbon

atetabletsand

alendron

ates

odium

tablets

[14]

Guson

gdecoction

4i

Sign

ificant

effectlumbarv

ertebrap

ainandotherc

linicalsymptom

sdisa

ppearedor

totalscoresd

ecreased

bymorethan23

Effectiv

elumbarv

ertebrap

ainandotherc

linicalsymptom

smarkedlyalleviated

ortotalscoresd

ecreased

bymorethan13

Ineffectiv

eno

improvem

entinclinicalsym

ptom

stotalscoresd

idno

treach

the

effectiv

evalue

Markedlyim

proved

(21)

Mod

erately

improved

(14)

Ineffectiv

e(3)

Overalleffi

cacy9211

Con

troltreatmentu

singglipizidea

ndalendron

ates

odium

tablets

[15]

Tang

maikang

granules

combined

with

alendron

ate

sodium

tablets

9j

Sign

ificant

effectlumbarv

ertebrap

aindisapp

earedsig

nificantincreaseinBM

D

Effectiv

elumbarv

ertebrap

ainalleviated

with

nosig


D

Ineffectiv

elumbarv

ertebrap

ainstillexistedB

MDremainedthes

ame

Markedlyim

proved

(24)

Mod

erately

improved

(21)

Ineffectiv

e(3)

Overalleffi

cacy9375

Con

troltreatmentu

singalendron

ates

odium

tablets

[16]

Bushen

Huo

xue

decoction

0k

Sign

ificant

effectback

pain

disapp

earedsymptom

sand

physicalsig

nsscore

decreasedby

23sig

nificantimprovem

entinbo

nemetabolism

indexBM

Dincreasedby

morethan006

gcm2

Effectiv

eback

pain

obviou

slyalleviatedsym

ptom

sand

physicalsig

nsscores

decreasedby

13nochange

oraggravationwas

foun

din

theb

iomarkersandBM

D

Ineffectiv

eno

improvem

entinallthe

aspects

Markedlyim

proved

(3)

Mod

erately

improved

(26)

Ineffectiv

e(1)

Overalleffi

cacy967

Con

troltreatmentu

singcaltrateD

[17]

JiaweiGuton

gxian

capsule

14l

Curelum

barv

ertebrap

aindisapp

earedX-

rayappeared

norm

al

Sign

ificant

effectlumbarv

ertebrap

ainobviou

slyalleviatedsignificant

improvem

entinX-

ray

Effectiv

elumbarv

ertebrap

ainalleviatedimprovem

entinX-

ray

Ineffectiv

elumbarv

ertebrap

ainandX-

rayremainedthes

ame

Cure

(1)

Markedlyim

proved

(8)

Mod

erately

improved

(27)

Ineffectiv

e(4)

Overalleffi

cacy900

Con

troltreatmentu

singosteoform

capsule

[18]

Qiang

gubao

capsule

8mBa

ckpainB

MD

Markedlyim

proved

(24)

Mod

erately

improved

(13)

Ineffectiv

e(3)

Overalleffi

cacy925

[19]

Jiang

uform

ula

12n

Clinicalsymptom

aticscales

Markedlyim

proved

(18)

Mod

erately

improved

(28)

Ineffectiv

e(4)

Overalleffi

cacy920

Con

troltreatmentu

singosteoform

capsule

[20]

Evidence-Based Complementary and Alternative Medicine 5Ta

ble1Con

tinued

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Jiang

tang

Bushen

form

ula

10o

BMDserum

C-reactiv

eprotein

(CRP

)BM

Dandserum

CRPsig

nificantly

increased

Con

troltreatmentu

singcaltrateD

[21]

Huo

lisuoralliq

uid

5p

Sign

ificant

effectclinicalsym

ptom

smarkedlyim

provedB

MDsig

nificantly

increased

Effectiv

eclinicalsym

ptom

salleviatedB

MDslightly

increased

Ineffectiv

eclinicalsym

ptom

sand

BMDremainedthes

ame

Markedlyim

proved

(12)

Mod

erately

improved

(86)

Ineffectiv

e(14)

Overalleffi

cacy791

Con

troltreatmentu

singsalm

oncalcito

nin

[22]

Migudecoction

7qVisualanalogue

scale(VA

S)pain

scoreBM

DVA

Spain

scores

ignificantly

improvedB

MDsig

nificantly

increased

Con

troltreatmentu

singcalcium

carbon

ate

[23]

Xianlin

gGub

ao6r

Clinicalsymptom

scales

andBM

DClinicalsymptom

scales

andBM

Dsig

nificantly

improved

Con

troltreatmentu

singcaltrateD

[24]

a RadixRehm

anniae

PreparataFructusC

orniR

hizomaD

ioscoreaeHerba

CynomoriiCa

rapaxetPlastru

mTestu

dinisRh

izom

aChu

anxiongandRa

dixetRh

izom

aSalviae

Miltiorrhizae(do

sage

inform

ationisno

tavailable)

b Radix

Astra

gali30

gHerba

Epim

edii12gRh

izom

aPolyg

onati12g

CollaCo

rnus

Cervi(meltingin

boiledwater)15g

RhizomaDioscoreae3

0gSem

enAstra

galiCo

mplan

ati15g

Radix

PuerariaeL

obatae

30g

RadixPolyg

oniM

ultifl

ori15g

RadixetRh

izom

aSalviae

Miltiorrhizae3

0gR

adixetRh

izom

aRhei10g

and

SanguisD

raconis10g

c R

adixAstra

galiCollaCe

rviC

ornu

sRa

dixRehm

anniaeFructus

PsoraleaeHerba

Epim

ediiFructusL

igustri

Lucid

iRa

dixNo

toginsengRa

dixetRh

izom

aSalviae

MiltiorrhizaeandPh

eretim

a(dosageinformation

isno

tavailable)

d CortexEu

commiae12g

Fructus

Psoraleae12g

RadixAstra

gali30

gRa

dixNo

toginseng15gRh

izom

aDioscoreae15g

CollaCo

rnus

Cervi(meltingin

boiledwater)6

gRa

dixetRh

izom

aSalviae

Miltiorrhizae12g

OsD

raconis3

0gand

Concha

Ostreae3

0g

e RadixAstra

galiRa

dixetRh

izom

aRheiFructusL

igustri

Lucid

iFructusL

yciiHiru

doFlosC

artham

iandRa

dixetRh

izom

aRhodiolae

Crenulatae

(dosageinformationisno

tavailable)

f RadixRehm

anniae

Preparata15g

Fructus

Corni10g

RhizomaC

huan

xiong15gRh

izom

aDrynaria

e15g

Fructus

Psoraleae15g

Herba

Epim

edii12gRa

dixetRh

izom

aSalviae

Miltiorrhizae15g

RadixCy

athu

lae

15gandFructusL

ycii20

gg C

ortexP

hellodend

riCh

inensis

10gRa

dixR

ehmanniae

Preparata15g

Carapax

etPlastru

mTestu

dinis15g

RadixPa

eoniae

Alba12g

RhizomaA

nemarrhenae

9gPerica

rpiumCitri

Reticulatae

10gHerba

Cynomorii

10gandRh

izom

aZingiberis

4g

h RadixAstra

galiRa

dixC

odonopsisR

adixPolyg

oniM

ultifl

oriR

adixAn

gelicae

Sinensis

Rhizom

aAtra

ctylodisMacrocephalaePoriaC

arapax

etPlastru

mTestu

dinisCa

rapaxT

rionycisH

erba

TaxilliH

erba

Epim

edii

RadixDipsaci

CortexEu

commiaeandFructusA

urantii


tavailable)

i RhizomaD

rynaria

e20g

Herba

Epim

edii20

gRh

izom

aAtra

ctylodisMacrocephalae

15gandCortexEu

commiae15g

j RadixAstra

galiRa

dixR

ehmanniaeR

adixPa

eoniae

RubraRa

dixe

tRhizomaS

alviae

MiltiorrhizaeRa

dixC

yathulaeR

adixOphiopogonisRh

izom

aPolygonatiH

erba

Epim

ediiandRa

dixP

ueraria

eLob

atae

(dosage

inform

ationisno

tavailable)

k Prescrip

tionconstituentsa

nddo

sage

inform

ationaren

otavailable

l Radix

Rehm

anniae

Preparata

RadixMorindaeOfficinalisH

erba

Cista

nchesRh

izom

aDrynaria

ePy

ritum

RhizomaCu

rculiginis

Herba

Epim

edii

RadixAn

gelicae

Sinensis

Rhizom

aAn

emarrhenaeR

adix

NotoginsengCa

rapaxetPlastru

mTestu

dinisPlacenta

Hom

inis

RadixAstra

galiandEn

dothelium

Corneum

Gigeria

eGalli(dosageinformationisno

tavailable)

mRa

dixAstra

gali

FructusC

orniH

erba

Dendrobii

Rhizom

aDioscoreaeRh

izom

aDrynaria

eCollaCornu

sCervi

(meltingin

boiledwater)Ra

dixet

Rhizom

aSalviaeM

iltiorrhizaeandCo

ncha

Ostreae(

dosage

inform

ationisno

tavailable)

n Herba

Epim

edii10gHerba

Cista

nches10g

CortexEu

commiae18g

RadixDipsaci12gRa

dixPolyg

oniM

ultifl

ori10g

RadixRe

hmanniae

Preparata12gRh

izom

aDioscoreae15g

Fructus

Corni10g

Fructus

Lycii

12gRa

dixAn

gelicae

Sinensis10gRa

dixCy

athu

lae18g

and

Poria

12g

o RadixAstra

gali30

gRa

dixP

aeoniaeR

ubra

20gRa

dixe

tRhizomaS

alviae

Miltiorrhizae2

0gC

ortexM

ori10g

RadixTrich

osanthis20

gFructusL

ycii15gRa

dixS

crophu

laria

e20g

RadixRehm

anniae

20gSemen

Cuscutae

15gandRh

izom

aDrynaria

e15g

(mod

ificatio

naccordingto

symptom

sIfdiagno

sedas

Qid

eficiencyR

adixPseudoste

llaria

e(30

g)isaddedto

thea

bove

prescriptio

nandthed

osageo

fRadixAstra

galiis

mod

ified

from

30gto

50gIfdiagno

sedas

YindeficiencyHerba

Dendrobii(15g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

bloo

ddeficiencyRa

dixPa

eoniae

Alba

(20g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

bloo

dstasis

Rhizom

aCh

uanx

iong

(20g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

phlegm

-heatFructusT

richosanthis(15g)

andCa

ulisBa

mbu

saeinTaenia

(10g

)are

addedto

thea

bove

prescriptio

n)

p Herba

Epim

ediiRa

dixetRh

izom

aSalviae

MiltiorrhizaeRa

dixAstra

galiRa

dixOphiopogonisandFructusL

ycii(dosageinformationisno

tavailable)

q RadixRehm

anniae

Preparata15gHerba

Epim

edii10gFructusP

soralea

e15g

RadixNo

toginseng15gRh

izom

aDrynaria

e15g

Sem

enCu

scutae

15gandRh

izom

aDioscoreae12g

r H

erba

Epim

ediiRa

dixDipsaci

FructusP

soralea

eRa

dixRehm

anniaeR

adixetRh

izom

aSalviae

MiltiorrhizaeandRh

izom

aAnemarrhenae


tavailable)


Table 2 Medicinal herbs most frequently used in clinical trials ofDOP

Name of herb FrequencyRadix Astragali 11Herba Epimedii 10Radix et Rhizoma Salviae Miltiorrhizae 10Radix Rehmanniae Preparata 6Rhizoma Drynariae 6Fructus Lycii 5Cortex Eucommiae 4Rhizoma Dioscoreae 4

Based on the listed prescriptions from Table 1 it is foundthat TCM treatments improved DOP through multichanneland different levels in the clinical trials And the mostcommonly used herbs are Radix Astragali Radix et RhizomaSalviaeMiltiorrhizae HerbaEpimedii andRadixRehmanniaePreparata These four herbs have also been well evidencedto play a beneficial role in the treatment of diabetes byinhibiting AGEs formation [61] improving mitochondrialfunction and biogenesis interfering with cell cycle [62]increasing insulin sensitivity and glycogen synthesis [63ndash65] and improving 51015840 adenosine monophosphate-activatedprotein kinase signaling [66 67] as well as regulating tissueregeneration and angiogenesis to promote diabetic footulcer healing [68] Meanwhile these four herbs were alsodemonstrated to exhibit antiosteoporotic effect by inhibit-ing osteoclastogenesis and promoting osteoblastogenesisthrough regulating mitogen-activated protein kinase [69]Wnt120573-catenin bone morphogenetic proteinsSMAD andOPGRANKLcathepsin Knuclear factor kappa-B (NF-120581B)signaling [26 70 71]

However the current clinical studies are limited to smallscale of samples and regional hospitals Meanwhile theclinical trials do not fully conform to the rule of randomizeddouble-blind and parallel group which markedly impactedthe correct evaluation of clinical research results In additionclinical observation indexes are limited more in BMD thanin bone strength and fracture incidence The stability andrepeatability of the compound preparations used in clinicaltrials also remain open and should be studied furtherTherefore the credibility of the results needs to be furtherimproved So it is not conducive to developing standardizeddiagnosis method and treatment program as well as thedevelopment of new drugs

4 Preclinical Advances of DOP in TCM

41 The Applications of Single Chinese Herbs in the Treatmentof DOP in Animal Experiments Single herbs or their extractshave been extensively studied in the DOP animal models(Table 3) In an experiment performed by Zhang et althe water fraction of Fructus Ligustri Lucidi (FLL) ethanolextract (WF-EE 574mgkg ig) has been demonstratedto improve the trabecular bone deteriorations and inhibit

hypercalciuria and increase serum parathyroid hormone(PTH) and fibroblast growth factor-23 in streptozotocin(STZ 40mgkg) induced DBA2J mice [25] The underly-ing mechanism of WF-EE treatment may be attributed toincrease of gene expressions of transient receptor potentialvanilloid (TRPV) and calcium binding protein 9 K (CaBP-9K) in duodenum in DOP mice Further using alloxan(200mgkg) induced diabetic rats Radix et Rhizoma SalviaeMiltiorrhizae treatment (5 gkg for 8 weeks) [26 27] sig-nificantly improved serum calcium alkaline phosphatase(ALP) BGP and tartrate-resistant acid phosphatase levelsand increased BMD value in alveolar bone osteoporosisIn addition treatment with tetramethylpyrazine (100mgkgfor 15 weeks the active ingredients isolated from RhizomaChuanxiong) [28] markedly increased bone hydroxypro-line and collagen levels in streptozotocin (STZ 60mgkg)induced diabetic rats Treatment with the alcohol extractsof Eucommia ulmoides Oliv leaves [29] (6 gkg) improvedserumestradiol and increasedBMDvalues in STZ (50mgkg)induced diabetic and ovariectomized (OVX) rats FructusLigustri Lucidi [72] Rhizoma Chuanxiong [73] the leaves ofEucommia ulmoidesOliv [74] and Radix et Rhizoma SalviaeMiltiorrhizae [75] have been demonstrated with the functionof tonifying kidney and promoting blood circulation

Treatment with puerarin the active substance isolatedfrom Radix Puerariae with the function of improving bloodcirculation [76] significantly increased ALP level (40120583M for48 hours ip) [77] decreased expression of caspase-3 inosteoblasts (80mgkgday for 6 weeks ip) [30] and reducedblood glucose and improved empty lacunar and BMD(100mgkg for 6 weeks ip [31]) in STZ (65mgkg) induceddiabetic rats The results suggest that puerarin promotesosteoblast proliferation and inhibits osteoclast activation

Aralia echinocaulis Hand-Mazz has been documented todistribute to kidney channel based on TCM theories [78]The flavonoids isolated from the Aralia echinocaulis Hand-Mazz treatment (20mgkg) [32] significantly improved thebone metabolism evidenced by increasing BMD value bonestrength and bone mineral content in STZ (30mgkg)insulted male rats In addition the aqueous extract ofAralia echinocaulis Hand-Mazz (36 gkg for 14 days) wasevidenced to promote the expressions of fibroblast growthfactor receptor 2 Fms-like tyrosine kinase and fetal liverkinase which contributed to promoting angiogenesis andosteoblastogenesis in fracture healing model rats [78]

Treatment with quercetin increased serum osteocalcinALP and urinary deoxypyridinoline (quercetin at 5mgkgshowed little effect while quercetin at 30mgkg and 50mgkgexhibited good effects for 8 weeks) in STZ induced diabeticosteopenia in rats [33] The beneficial effect of quercetin alsoreflected on partially reversing the decreased biomechanicalquality and improving microarchitecture of the femurs inthe diabetic rats The underlying mechanism may be dueto its antioxidant capability In addition quercetin was alsodemonstrated to have a protective role in reducing 120573-celldamage and decreasing glycaemia in diabetic rats [79]Furthermore quercetin is widely embraced in TCM herbsand possessed the function of improving blood circulation[80 81]


Table 3 Single herb or herbal extracts used in the treatment of DOP animals

TCM name Active constituents Animal model Administration routeduration and dosage

Reference

Fructus Ligustri LucidiWater fraction of FructusLigustri Lucidi ethanol

extractSTZ (40mgKg)

Intragastric administration(ig) (574mgkg) for 6

weeks[25]

Radix et Rhizoma Salviamiltiorrhiza mdash Alloxan

(200mgkg) ig (5 gkg) for 8 weeks [26 27]

Rhizoma Chuanxiong Tetramethylpyrazine STZ (60mgKg) ig (100mgkg) for 15 weeks [28]

Cortex EucommiaeEthanol extracts of

Eucommia ulmoides Olivleaves

STZ combinedwith OVX ig (6 gkg) for 8 weeks [29]

Radix Puerariae Puerarin STZ (65mgKg) ig (100mgkg) for 6 weeks [30 31]Aralia echinocaulisHand-Mazz

The flavonesof AraliaechinocaulisHand-Mazz STZ (30mgkg) ig (20mgkg) for 6 weeks [32]

mdash Quercetin STZ ig (5 30 and 50mgkg)for 8 weeks

[33]

Vitis vinifera L seeds mdash STZ (60mgkg) ig (0028mgkg everyother day) for 16 weeks

[34]

Nigella sativa L Thymoquinone STZ (50mgkg) ig (2mLkg) for 4 weeks [35ndash38]Note ldquomdashrdquo denotes that the content was not clearly stated in the cited reference

The combination treatments with polyphenols extractedfrom the seeds of Vitis vinifera L (0028mgkg every twodays for 16 weeks) [34] and the fruits of Sambucus nigra L(004 gkg every two days for 16 weeks) [35 36] statisticallyimproved BMD in STZ induced diabetic rats Further thecombination treatments with Nigella sativa L and parathor-mone [36 37] have also been demonstrated to improve thebone strength in diabetic rats

Taken together the herbs used in the treatment of DOPanimals usually have the functions of nourishing Yin andtonifying kidney promoting blood circulation which havebeen demonstrated to possess the ability of improving thebone metabolism in DOP [76 82] The most accepted phar-macologically active ingredients of these herbs are flavonoidspolyphenols alkaloids polysaccharides and so forth

42 The Advances of TCM Compounds in the Treatmentof DOP in Animal Experiments As is well known TCMcompounds are composed of 2 ormore Chinese drugs whichmay play a synergistic action during the treatment of diseasesAn experiment performed by Du et al [39] demonstratedthat Bushen Zhuanggu capsule (16 and 32 gkg) treatmentnot only decreased blood glucose but also increased bonecalcium and phosphorus as well as bone minerals in alloxan(120mgkg) induced diabetic rats Jiang et al [40] alsofound that Shenxiaokang concentrated pill (modified fromBawei Shenqi pill) treatment increased the thickness of boneepiphysis and improved trabecular nesh structure in STZ(25mgkg) induced diabetic male rats One formula namedBushen Jianpi Huoxue decoction [41] was also evidencedto significantly reduce blood glucose phosphorus and ALPlevel and improve insulin resistance as well as increase BMDvalue in high fat diet and STZ (30mgkg) induced rats

In addition Shuanghuang Yigu formula treatment [42] sig-nificantly reduced blood glucose and urine desoxypyirdoxinelevels and increased blood BGP level in ovariectomized ratwith STZ (50mgkg) injection

Emerging formulas have been demonstrated to play abeneficial role inmanagement of DOP animals Tangshukang[43] one formula invented by Guan et al was demonstratedto improve calcium and phosphorus metabolism increaseBGP level and reduce bone ALP level in STZ (60mgkg)induced diabetic osteoporosis rats The underlying mecha-nism may be attributed to improve mRNA levels of vitaminD receptor and CBP9K in the small intestine and increasemRNA level of transforming growth factor- (TGF-) 1205731 in thebone [83]

Furthermore Bushen Zhuanggu capsule [44] treatmentimproved blood glucose metabolism through regulatinginsulin secretion promoting bone TGF-1205731 expression andinhibiting caspase-3 expression in osteoblast andmodulatingthe metabolic disorder of calcium-regulating hormones suchas PTH calcitonin and vitamin D3 in alloxan (ip of120mgkg twice every other day) induced diabetic rats

In addition Qianggubao treatment [45] reduced theexpressions of interleukin-6 (IL-6) tumor necrosis factoralpha (TNF-120572) and carboxyterminal cross-linked telopep-tide of type I collagen (ICTP) and increased IGF-1 andcarboxyterminal propeptide of type I procollagen (PICP)production in alloxan (ip of 120mgkg twice every otherday) induced diabetic osteoporosis rats Further Qianggubao[84] treatment also inhibited the formation of AGEs whichwas unfavorable for bone formation [85]

Most of formulas used in management of DOP not onlyhave the function of improving bone metabolism but alsoafford effects on regulating glucose metabolism Howeveras shown in Table 4 the ingredients of the formulas are


Table 4 TCM prescriptions in the treatment of DOP animals

TCM compound prescriptionname Animal model Administration route duration

and dosageReference

Bushen Zhuanggu capsule2a

Alloxan (120mgkg twice everyother day) ig (8 16 and 32 gkg) for 8 weeks [39]

Shenxiaokang concentrated pill9b

STZ (25mgkg) once a day for 5days ig (158 g200 g) for 7 weeks [40]

Bushen Jianpi Huoxue decoction8c

high fat diet for 4 weeks ip ofSTZ (30mgkg) ig (15 gkg) for 12 weeks [41]

Shuanghuang Yigu formula9d

ip of STZ (50mgkg) combinedwith OVX ig (115 gkg) for 10 weeks [42]

Tangshukang capsule0e ip of STZ (60mgkg) ig (15 gkg) for 12 weeks [43]

Bushen Zhuanggu capsule0f

ip of alloxan (120mgkg twiceevery other day) ig (8 16 and 32 gkg) for 7 weeks [44]

Qianggubao10

gip of alloxan (120mgkg twice

every other day) ig (1mL100 g) for 12 weeks [45]

aRadix Rehmanniae Preparata and Carapax et Plastrum Testudinis (dosage information is not available)bRadix Rehmanniae Preparata Rhizoma Dioscoreae Fructus Corni Poria Rhizoma Alismatis Pericarpium Citri Reticulatae Radix Astragali and Hirudo(dosage information is not available)cRadix Rehmanniae Preparata Cortex Eucommiae Radix Astragali Fructus Lycii Colla Cornus Cervi (melting in boiled water) Radix et Rhizoma SalviaeMiltiorrhizae Rhizoma Anemarrhenae and Radix Cyathulae (dosage information is not available)dOs Draconis Radix Rehmanniae Preparata RadixAstragali Cortex Eucommiae RadixDipsaci RhizomaDrynariae Fructus Lycii Fructus Corni Poria RadixAngelicae Sinensis Radix Cyathulae Herba Artemisiae Anomalae (dosage information is not available)eTCM names and dosage information are not availablefTCM names and dosage information are not availablegRadixAstragali HerbaDendrobii Radix et Rhizoma SalviaeMiltiorrhizae CortexEucommiae FructusPsoraleae FructusCorni RhizomaDioscoreae RhizomaDrynariae Colla CornusCervi (melting in boiled water) and Concha Ostreae (dosage information is not available)

not constant and fixable And the commonly used TCMherbs also exhibit the effects of tonifying kidney promot-ing blood circulation and removing blood stasis whichis also consistent with the main pathogenesis of DOP inTCM

As is mentioned in Table 4 three types of DOP modelsare employed to evaluate the effect of TCM in the treatment ofDOP including STZ alloxan and STZ combined with OVXinduced animal models In addition pigs are also used as theexperimental DOP models [86]

5 The Toxicity of the Herbs

Toxicity is becoming a rising concern in the application ofTCM in the clinical trials Contrary to most of the moderntoxicity data derived from animal experiments the toxicitiesof TCM herbs in Chinese literature have been documentedthrough clinical experiences Before properly reviewing andstudying the toxicities of the species by modern medi-cal pharmacological andor pharmaceutical sciences theresearchers must bear in mind that the isolated chemicalsand the extracts from the herbs are not identical to theoriginal herbs or formulas while the traditional propertiesand indications of TCM herbs and formulas are the validatedsource of interpreting and extrapolating assessments of thetoxicities For knowing how to well understand the toxicitiesof TCM herbs we suggest that the interested readers consultDr Leungrsquos review [87]

In the above-mentioned species several of them wereevidenced to have toxicity issues for medicinal use Nigellasativa L extracts were demonstrated to possess the abilityof lowering blood glucose in the healthy subjects Thereforecaution must be excised when Nigella sativa L extracts wereapplied to treat pregnant women children and diabeticpatients [88] For children Nigella sativa L at doses below80mgkg was considered as safe dosages as there were noobserved side effects being reported [89] For detailed toxicityinformation of Nigella sativa L we suggest that the readersconsult Shuid et alrsquos review [35]

It has been revealed that Pueraria tuberosa Linn(Fabaceae) methanol extract of tubers showed LD50 at2275mg in acute study in rats For subchronic study repeatedchallenges (5ndash100mg100 g for 30 days) dose-dependentlyincreased hepatic enzymes in blood inflammatory cell infil-tration and hepatocellular necrosis Kinetic study (singledose at 2275mg100 g) revealed a decrease in GSH and anincrease in free-radical generation [90 91] Puerarin themajor component of Radix Puerariae has been demonstratedto cause hepatotoxicity as well as pathological changes injejunum and spleen by high dose administration of puerarinfreeze dried powder (100 and 200mgkg for 13 weeks iv)to SD rats [92] Interested readers are encouraged to consultZhang et alrsquos review [93]

The extracts of Radix Astragali which consist of Astraga-lus polysaccharide and Astragalus membranaceus saponinswere evidenced safe without any distinct toxicity and sideeffects in the subchronic toxicity study The safety dosage


Liver-spleen-kidney insufficiency

Etiology of DOP

Femur

LumbarTCM drugs

Micro-CT imagesof DOP rats

Traditional Chinese

(TCM)medicine

Scheme 1 Liver-spleen-kidney insufficiency is closely associated with the induction of DOP The most commonly used TCM herbs fortreatment of DOP are Radix Astragali Radix et Rhizoma Salviae Miltiorrhizae Radix Rehmanniae Preparata and Herba Epimedii Theseherbs are evidenced to improve the management of DOP in clinical and preclinical study

range is 285ndash1995 gkg for beagle dogs and 57ndash399 gkgfor rats [94] And so far no clinical toxicity data were re-ported

The major tanshinones (cryptotanshinone tanshinone Itanshinone IIA and dihydrotanshinone) isolated from Salviamiltiorrhiza Bunge were observed to induce HepG2 cellapoptosis in vitro [95] Flow cytometry results demonstratedthat tanshinone IIA (125 and 25 120583M) treatment increasedfragmented DNA in HepG2 cells Cryptotanshinone tan-shinone I and dihydrotanshinone elevated GSHGSSG ratioat low concentrations (156 and 313 120583M) and decreasedGSHGSSG ratio at high concentrations (625ndash25120583M) whichindicates that these compounds may disturb redox balancein HepG2 cells Another experiment performed by Xu et alclaimed that liposoluble components of Salvia miltiorrhizaBunge (IC50 = 2181 120583gmL) and tanshinone IIA (IC50 =6176 120583gmL) inhibited proliferation of rat retinal Muller cellin vitro by CCK-8 examination at 48 h [96] But the authorsdid not show the cell viabilities at various time points whichare useful to evaluate the drug toxicity

Cortex Eucommiae is also widely used in the treatment ofDOP In chronic toxicity experiments in rats the seeds andbarks of Eucommia ulmoides Oliv were found to affect theutilization rate of food the routine blood and liver functionand the organ coefficient of the liver spleen testis and ovaryBut the investigators did not find abnormalities in histologicalexamination They also did not discover abnormalities inacute toxicity bone marrow of mice micronuclear test andsperm deformity experiments [97 98]

6 Conclusions and Remarks

The clinical studies and basic research achievements sup-port that TCM offers a new strategy in prevention andtreatment of DOP (Scheme 1) TCM herbs and compoundshave effects on resolving DOP through invigorating kidneyQi promoting blood circulation and removing blood stasis

This is consistent with TCM belief that liver-spleen-kidneyinsufficiency is closely associated with the induction of DOPThe most commonly used TCM herbs for treatment of DOPare Radix Astragali Radix et Rhizoma Salviae MiltiorrhizaeRadixRehmanniae Preparata andHerba EpimediiThe inves-tigators also demonstrate that these herbs have the beneficialeffects on diabetes and osteoporosis Three types of DOPmodels (STZ alloxan and STZ plus OVX induced animaldisease models) are employed to evaluate the effect of TCMon DOP animals These results clearly support that TCMherbs treatment not only improves bone metabolism but alsoprevents the development of diabetes It is noticeable thatsome of TCM herbs and extracts may have the toxicities overthe thresholds Great care must be taken when TCM herbsare employed to treat DOP

However the basic research on single herbs and TCMcompounds in the treatment of DOP is still very weak andthere is still a long way to find the mechanisms and activeingredients in TCM herbs The researchers also need to payattention that the pathogenesis of DOP is a multifacetedchronic metabolic disease and a comprehensive study withmultidisciplinary technology and comprehensive usage ofvarious approaches should be employed to explore patho-genesis and to prevent the development of DOP The furtherunderstanding of these concerns will contribute to providinga more scientific basis for management of DOP

Disclosure

These funding agencies have no roles in study design indata collection analysis and interpretation in the writingof the report and in the decision to submit the paper forpublication

Competing Interests

The authors declare that they have no competing interests


Authorsrsquo Contributions

Rufeng Ma Ruyuan Zhu and Lili Wang equally contributedto this work

Acknowledgments

This work was supported by grants from National Nat-ural Science Foundation of China (NSFC81274041 andNSFC81273995) International Cooperation projects of MOE(2011DFA30920) and Key Drug Development Program ofMOST (20122X09103201-005) as well as the 111 project ofMOE (B07007)

References

[1] S Epstein G Defeudis S Manfrini et al ldquoDiabetes and dis-ordered bone metabolism (diabetic osteodystrophy) time forrecognitionrdquo Osteoporosis International vol 27 no 6 pp 1931ndash1951 1931

[2] W-L Zhang H-Z Meng and M-W Yang ldquoRegulation ofDMT1 on bonemicrostructure in type 2 diabetesrdquo InternationalJournal of Medical Sciences vol 12 no 5 pp 441ndash449 2015

[3] B Roy ldquoBiomolecular basis of the role of diabetes mellitus inosteoporosis and bone fracturesrdquoWorld Journal of Diabetes vol4 no 4 pp 101ndash113 2013

[4] P Piscitelli C Neglia A Vigilanza and A Colao ldquoDiabetes andbone biological and environmental factorsrdquoCurrent Opinion inEndocrinology Diabetes and Obesity vol 22 no 6 pp 439ndash4452015

[5] Y ZhangW-H Yu and X-LWang ldquoEffects of Tanggukang onserum free radical metabolism in patients with diabetic osteo-porosisrdquo Journal of Clinical Rehabilitative Tissue EngineeringResearch vol 12 no 7 pp 1251ndash1254 2008

[6] W H Yu and Y Zhang ldquoEffect of Tanggukang Decoction onthe metabolism of calcium and phosphourous in the patients ofdiabetes with osteoporosisrdquo Zhongguo Zhongyi Jizheng vol 18no 1 pp 45ndash46 2009

[7] B Ji J Guan X Chen et al ldquoClinical research of self-madekidney-tonifying and blood circulation-promoting Chinesemedicine in patients with diabetic osteoporosisrdquoGuide of ChinaMedicine vol 10 no 17 pp 3ndash4 2012

[8] X Shang S Xu Q Zhou et al ldquoClinical observations on theeffect of Bushen Tongluo capsule for treatment of diabeticosteoporosisrdquo China Pharmacist vol 13 no 9 pp 1329ndash13302010

[9] X Shang P Xie XGuo andT Zhang ldquoThe influence of BushenTongluo Compound on bone mineral density and balanceability of patients with diabetic osteoporosisrdquo Captial Medicinevol 17 no 16 pp 60ndash61 2010

[10] Z D Gong andC J Li ldquoClinical research ofmodifiedQingrsquoe pillon diabetic osteoporosisrdquoZhongguo Zhongyi Jizheng vol 21 no9 pp 1391ndash1402 2012

[11] A Yushanjiang and M Halida ldquoClinical study on effect ofXihongkang for the treatment diabetic osteoporosisrdquo ChineseJournal of Basic Medicine in Traditional Chinese vol 18 no 9pp 1001ndash1002 2012

[12] M Deng ldquoClinical studies on the effect of Yishen ZhuangguCompound for the treatment of type 2 diabetes inducedosteoporosisrdquo Guiyang Journal of TCM College vol 35 no 1pp 58ndash59 2013

[13] L Zhang ldquoClinical observation on 56 cases of patients withdiabetic osteoporosis in using Huqian Pillrdquo Hebei Journal ofTCM vol 25 no 3 p 180 2013

[14] R Liu Observe the Safety and Efficacy of TCM Gu-SongDecoction to Diabetic Osteoporosis (DOP) Patients ChengduUniversity of Chinese Medicine Chengdu China 2013

[15] C Hao ldquoClinical Study on the effect of Gusong decoction onpatient with dibetic osteoporosisrdquo Asia Pacific TraditionalMedicine vol 11 no 10 pp 117ndash118 2015

[16] M Gao ldquoClinical observation of tangmaikang granules com-bined with alendronate sodium tablets in the treatment of bonemetabolism in elderly patients with type 2 diabetesrdquo ChinaPharmacy vol 23 no 28 pp 2658ndash2660 2012

[17] Z Feng X Yue F Li Y Wei and Z Li ldquoClinical study ofthe effect of Bushen Huoxue principle on bone metabolism ofpatients with daibetic osteoporosisrdquo in Proceedings of the 14thTCM Diabtes Conference Diabetes Sub-society of China Chi-nese Medicine Assocation Zhengzhou China 2012

[18] W Jia Z Wu and Q Dong ldquoClinical observation of the effectof Jiawei GutongxianCapasule on the treatment of patients withdiabetic osteoporosisrdquoHebei Journal of TCM vol 28 no 11 pp822ndash823 2006

[19] Y Su S Qian Z Dong J Guo and A Zhang ldquoClinical obser-vation on QIANGGUBAO for treating 40 cases of diabeticosteoporosisrdquo Journal of Fujian College of TCM vol 11 no 3pp 23ndash25 2001

[20] L Zhao ldquo50 cases of clinical trials in the treatment of diabeticbone metabolism by self-made Jiangu decoctionrdquo Hei LongJiang Journal of TCM vol 29 no 1 p 46 2000

[21] L Huang ldquoClinical study of the effect of Jiangtang Bushenformulation on bone mineral density and serum C reactiveprotein on patients with diabetic osteoporosisrdquo Fujian Journalof TCM vol 40 no 6 pp 15ndash16 2009

[22] H Shen J Huang and Y Wang ldquoClinical observation of theeffect of combination of huolisu oral liqiud and salmon calci-tonin on the treatment of old patients with diabetic osteoporo-sisrdquo Chinese Journal of Information on TCM vol 15 no 1 pp78ndash79 2009

[23] F Yan Y Zhang and Z Wang ldquoThe effect of Migu decoctionon the treatment of patients with type 2 diabetes osteoporosisrdquoHebei Medicinal Journal vol 34 no 21 pp 3340ndash3341 2002

[24] Y You R Zhuang H Zhao and Y Xie ldquoClinical therapeuticaleffect of xianling gubao on patients with diabetic osteoporosisrdquoJournal of Pharmaceutical Research vol 33 no 4 pp 113ndash1152014

[25] Y Zhang T-Y Diao LWang C-T Che andM-SWong ldquoPro-tective effects of water fraction of Fructus Ligustri Lucidi extractagainst hypercalciuria and trabecular bone deterioration inexperimentally type 1 diabetic micerdquo Journal of Ethnopharma-cology vol 158 pp 239ndash245 2014

[26] Y Guo Y Li L Xue et al ldquoSalvia miltiorrhiza an ancientChinese herbal medicine as a source for anti-osteoporoticdrugsrdquo Journal of Ethnopharmacology vol 155 no 3 pp 1401ndash1416 2014

[27] B Miao J Wang Y Zhu C Yue and M Chen ldquoExperi-mental study on effect of Salvia miltiorrhiza on alveolar bonemetabolism and variation in bone mass in diabetic ratsrdquo ChinaJournal of Chinese Materia Medica vol 37 no 11 pp 1659ndash16622012

[28] X Chen Z Lin H Chen and X Chen ldquoThe protection oftetramethylpyrazine on bone in diabetic osteoporosis ratrdquo Jour-nal of Putian University vol 15 no 5 pp 46ndash49 2008


[29] L Zhang H Ge and L Zhao ldquoEffects of eucommia leaveslavoids on osteoporosis in castrated rat with diabetes mellirdquoChinese Journal of Gerontology vol 23 no 6 pp 370ndash372 2003

[30] J LiangHChenW Pan andCXu ldquoPuerarin inhibits caspase-3 expression in osteoblasts of diabetic ratsrdquoMolecular MedicineReports vol 5 no 6 pp 1419ndash1422 2012

[31] Y Li H Pan and Y Liang ldquoExperiment study on protectionof Puerarin in diabetic osteoporosisrdquo Chinese Archives of Tradi-tional Chinese Medicine vol 30 no 4 pp 848ndash850 2012

[32] L Pei ldquoThe effect of flavonoids of Aralia echinocaulis Hand-Mazz on bone metabolism in the diabteic ratsrdquo in Proceedingsof the in 4th International Chinese Medicine and DiabetesConferences p 7 Beijing China 2009

[33] Z LuoW Liang Z Luo et al ldquoOral administration of quercetininhibits bone loss in ratmodel of diabetic osteopeniardquoEuropeanJournal of Pharmacology vol 670 no 1 pp 317ndash324 2011

[34] C Pohaci M Groza L Mares M Ciocoiu and M BadesculdquoBeneficial dexa-related effects of natural polyphenols onexperimentally-induced diabetes mellitus complicationsrdquoRevista medico-chirurgicala a Societatii de Medici si Naturalistidin Iasirsquos vol 113 no 3 pp 838ndash844 2009

[35] A N Shuid N Mohamed I N Mohamed et al ldquoNigella sativaa potential antiosteoporotic agentrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 2012 Article ID 6962306 pages 2012

[36] M F Altan ldquoEffects of Nigella sativa and human parathyroidhormone on bonemass and strength in diabetic ratsrdquo BiologicalTrace Element Research vol 116 no 3 pp 321ndash328 2007

[37] M F Altan M Kanter S Donmez M E Kartal and SBuyukbas ldquoCombination therapy of Nigella sativa and humanparathyroid hormone on bone mass biomechanical behaviorand structure in streptozotocin-induced diabetic ratsrdquo ActaHistochemica vol 109 no 4 pp 304ndash314 2007

[38] L Badescu O Badulescu M Badescu andM Ciocoiu ldquoMech-anism by Sambucus nigra extract improves bone mineral den-sity in experimental diabetesrdquo Evidence-based Complementaryand Alternative Medicine vol 2012 Article ID 848269 6 pages2012

[39] L Du L YinM Chen and Y Liu ldquoEffects of Bushen Zhuanggucapsule on bone mineral metabolism and bone density ofrats with diabetes osteoporosisrdquo Chinese Journal of TraditionalMedical Science and Technology vol 17 no 4 pp 293ndash295 2010

[40] D Jiang B Wang Y Chen C Liu and Z Liu ldquoResearch on theeffects of Shen-xiaokang on the morphology of osteoporosis inDaibetic RatsrdquoLiaoNing Zhongyi Zazhi vol 33 no 10 pp 1252ndash1254 2006

[41] J Xu N Liang and Z Chen ldquoResearch on the effect of bushenjianpi huoxue decoction on bonemetabolism in rats due to type2 diabetes with osteoporosisrdquo Shanxi Journal of TCM vol 31 no5 pp 48ndash50 2015

[42] S Li M Xiong C Chen et al ldquoExperimental studies on pre-ventive effect of ShuanghuangYigu prescription onmenopausaldiabetses osteoporosisrdquo Traditional Chinese Drug Research andClinical Pharmacology vol 14 no 5 pp 296ndash298 2003

[43] Z Guan H Dong and Q Dong ldquoExperimental study onthe effect of Tangshukang on the bone metabolism BMD andbone biomechanics in diabetic osteoporosis ratsrdquo Informationon Traditional Chinese Medicine vol 27 no 6 pp 80ndash82 2010

[44] Y Jiang Experimental Study on the Effect of Bushen ZhuangguCapsule on Bone Resorption-Formation Couple Links in DiabeticOsteoporosis Rats Chengdu University of Chinese MedicineChengdu China 2002

[45] Y Su H Xing L Zheng J Lin and X Chen ldquoExperiment onthe effect of QIANGGUBAOonmetabolism of bone collagen inthe diabetic osteoporosis ratsrdquo Chinese Journal of Osteoporosisvol 12 no 3 pp 289ndash291 2006

[46] I Takamoto and T Kadowaki ldquoDiabetes and osteoporosisrdquoClinical Calcium vol 14 no 2 pp 255ndash261 2004

[47] Y B Guo L L Wang R F Ma et al ldquoEtiology pathology andprospects of TCM in osteoporosis treatmentrdquoModernization ofTraditional ChineseMedicine andMateriaMedica-World Scienceand Technology vol 17 no 4 pp 768ndash772 2015

[48] ldquoPreliminary exploration of the TCM theory lsquospleen governsdigestion and transportationrsquordquo Journal of Traditional ChineseMedicine vol 2 no 4 pp 285ndash288 1982

[49] W-H Chen X-X Liu P-J Tong and H-S Zhan ldquoDiagnosisand management of knee osteoarthritis Chinese medicineexpert consensus (2015)rdquo Chinese Journal of Integrative Medi-cine vol 22 no 2 pp 150ndash153 2016

[50] Y G Tian Y Li J S Li et al ldquoEffects of therapies for regulatingand reinforcing lung and kidney on osteoporosis in rats withchronic obstructive pulmonary diseaserdquo Journal of TraditionalChinese Medicine vol 35 no 2 pp 175ndash183 2015

[51] D Ju M Liu H Zhao and J Wang ldquoMechanisms of lsquokidneygoverning bonesrsquo theory in traditional Chinese medicinerdquoFrontiers of Medicine in China vol 8 no 3 pp 389ndash393 2014

[52] C-HHsu C-J Lee T-J Chien et al ldquoThe relationship betweenqi deficiency cancer-related fatigue and quality of life in cancerpatientsrdquo Journal of Traditional and Complementary Medicinevol 2 no 2 pp 129ndash135 2012

[53] Z-Z YangW Liu F Zhang Z Li and Y-Y Cheng ldquoDecipher-ing the therapeutic mechanisms of Xiao-Ke-An in treatmentof type 2 diabetes in mice by a Fangjiomics approachrdquo ActaPharmacologica Sinica vol 36 no 6 pp 699ndash707 2015

[54] D D Zhao S H Gao Q Q Mu P J Qin and F F MoldquoTheoretical study on treating type 2 diabetes by regulating theliver spleen and kidneyrdquo Chinese Medicine vol 55 no 3 pp205ndash208 2014

[55] D-A Zhou Y-N Deng L Liu and J-J Li ldquoEffect ofkidney-reinforcing and marrow-beneficial traditional Chinesemedicine-intervened serum on the proliferation and osteogenicdifferentiation of bonemarrow stromal cellsrdquo Experimental andTherapeutic Medicine vol 9 no 1 pp 191ndash196 2015

[56] K Su F Zhu LGuo Y ZhuW Li andX Xiong ldquoRetrospectivestudy on Professor Zhongying Zhoursquos experience in TraditionalChinese Medicine treatment on diabetic nephropathyrdquo Journalof Traditional ChineseMedicine vol 33 no 2 pp 262ndash267 2013

[57] X Liu L Liu P Chen et al ldquoClinical trials of traditionalChinese medicine in the treatment of diabetic nephropathymdasha systematic review based on a subgroup analysisrdquo Journal ofEthnopharmacology vol 151 no 2 pp 810ndash819 2014

[58] L Wang Y Li Y Guo et al ldquoHerba Epimedii an ancient Chi-nese herbal medicine in the prevention and treatment ofosteoporosisrdquo Current Pharmaceutical Design vol 22 no 3 pp328ndash349 2016

[59] L Zhang Q-M Zhang Y-G Wang D-L Yu and W ZhangldquoThe TCM pattern of the six-zang and six-fu organs can besimplified into the pattern of five-zang and one-fu organsrdquoJournal of Traditional Chinese Medicine vol 31 no 2 pp 147ndash151 2011

[60] J K Chen Chinese Medical Herbology and Pharmacology Artof Medicine Press Industry Calif USA 2010


[61] K Nakashima H Miyashita H Yoshimitsu Y Fujiwara RNagai and T Ikeda ldquoTwo new prenylflavonoids from EpimediiHerba and their inhibitory effects on advanced glycation end-productsrdquo Journal of Natural Medicines vol 70 no 2 pp 290ndash295 2016

[62] W Yuan Y Zhang Y Ge M Yan R Kuang and X ZhengldquoAstragaloside IV inhibits proliferation and promotes apoptosisin rat vascular smooth muscle cells under high glucose concen-tration in vitrordquo Planta Medica vol 74 no 10 pp 1259ndash12642008

[63] S Raoufi T Baluchnejadmojarad M Roghani T GhazanfariF Khojasteh and M Mansouri ldquoAntidiabetic potential ofsalvianolic acid B in multiple low-dose streptozotocin-induceddiabetesrdquo Pharmaceutical Biology vol 53 no 12 pp 1803ndash18092015

[64] M Huang P Wang S Xu et al ldquoBiological activities ofsalvianolic acid B from Salvia miltiorrhiza on type 2 diabetesinduced by high-fat diet and streptozotocinrdquo PharmaceuticalBiology vol 53 no 7 pp 1058ndash1065 2015

[65] X Li Z Xu Z Jiang et al ldquoHypoglycemic effect of catalpol onhigh-fat dietstreptozotocin-induced diabetic mice by increas-ing skeletal muscle mitochondrial biogenesisrdquo Acta Biochimicaet Biophysica Sinica vol 46 no 9 pp 738ndash748 2013

[66] M A Carai G Colombo B Loi et al ldquoHypoglycemic effectsof a standardized extract of Salvia miltiorrhiza roots in ratsrdquoPharmacognosy Magazine vol 11 no 44 supplement 4 ppS545ndashS549 2015

[67] G Qiang X Yang L Shi et al ldquoAntidiabetic effect of salvianolicacid a on diabetic animal models via AMPK activation andmitochondrial regulationrdquo Cellular Physiology and Biochem-istry vol 36 no 1 pp 395ndash408 2015

[68] T W Lau F F Y Lam K M Lau et al ldquoPharmacologicalinvestigation on the wound healing effects of Radix Rehman-niae in an animal model of diabetic foot ulcerrdquo Journal ofEthnopharmacology vol 123 no 1 pp 155ndash162 2009

[69] H B Kwak D Yang H Ha et al ldquoTanshinone IIA inhibitsosteoclast differentiation through down-regulation of c-Fos andNFATc1rdquo Experimental and Molecular Medicine vol 38 no 3pp 256ndash264 2006

[70] L Wang Y Li Y Guo et al ldquoHerba epimedii an ancientChinese herbal medicine in the prevention and treatment ofosteoporosisrdquo Current Pharmaceutical Design vol 22 no 3 pp328ndash349 2015

[71] Q Bian J-H Huang Q-Q Liang et al ldquoThe osteogenetic effectof astragaloside IV with centrifugating pressure on the OCT-1cellsrdquo Pharmazie vol 66 no 1 pp 63ndash68 2011

[72] Q Li Y-S Fan Z-Q Gao K Fan and Z-J Liu ldquoEffect ofFructus Ligustri Lucidi on osteoblastic like cell-lineMC3T3-E1rdquoJournal of Ethnopharmacology vol 170 pp 88ndash95 2015

[73] L Wang J Zhang Y Hong Y Feng M Chen and Y WangldquoPhytochemical and pharmacological review of da Chuanxiongformula a famous herb pair composed of chuanxiong rhizomaand gastrodiae rhizoma for headacherdquo Evidence-based Comple-mentary and Alternative Medicine vol 2013 Article ID 42536916 pages 2013

[74] Y Zhang H Zhang F Wang D Yang K Ding and J FanldquoThe ethanol extract of Eucommia ulmoidesOliv leaves inhibitsdisaccharidase and glucose transport in Caco-2 cellsrdquo Journal ofEthnopharmacology vol 163 pp 99ndash105 2015

[75] C-Y Su Q-L Ming K Rahman T Han and L-P QinldquoSalvia miltiorrhiza traditional medicinal uses chemistry and

pharmacologyrdquoChinese Journal of NaturalMedicines vol 13 no3 pp 163ndash182 2015

[76] W Xie Y Zhao and L Du ldquoEmerging approaches of traditionalChinese medicine formulas for the treatment of hyperlipi-demiardquo Journal of Ethnopharmacology vol 140 no 2 pp 345ndash367 2012

[77] Y Li H Pan and Y Liang ldquoExperimental study on the effect ofpuerarin injection in high glucose treated osteoblastrdquo ChineseJournal of Traditional Medical Science and Technology vol 19no 4 pp 318ndash319 2012

[78] X Yin L Li L-L Zheng et al ldquoInfluence of aqueous extractofAralia echinocaulisHand-Mazz on the expression of fracturehealing-related factor receptorsrdquo Zhongguo Gu Shang vol 24no 9 pp 761ndash765 2011

[79] O Coskun M Kanter A Korkmaz and S Oter ldquoQuercetina flavonoid antioxidant prevents and protects streptozotocin-induced oxidative stress and 120573-cell damage in rat pancreasrdquoPharmacological Research vol 51 no 2 pp 117ndash123 2005

[80] J Sun and S Yu ldquoResearch progress of n pharmacological actionof quercetinrdquo Chinese Medicines Journal of Research and Prac-tice vol 25 no 3 pp 85ndash88

[81] M Luo D Luo and W Zhao ldquoResearch progress on pharma-cological action of quercetiinrdquoChinese Journal of Ethnomedicineand Ethnopharmacy vol 25 no 17 pp 12ndash14 2014

[82] A Teixeira N Baenas R Dominguez-Perles et al ldquoNaturalbioactive compounds from winery by-products as health pro-moters a reviewrdquo International Journal of Molecular Sciencesvol 15 no 9 pp 15638ndash15678 2014

[83] Z Guan and Q Dong ldquoStudy of the effect of Tangshukangfor the VDR TGF-1205731 CaBp-D9K mRNA expression on thediabetic osteoporosis ratsrdquo Modern Medicine Journal of Chinavol 12 no 4 pp 4ndash6 2010

[84] H Xing An Experimental Study on the Effect of Qianggubao onthe Metabolism of Bone Collagen in Diabetic Osteoporosis RatsChinese Internal Medicine Fujian College of TCM 2005

[85] X Yang A J Mostafa M Appleford L W Sun and X WangldquoBone formation is affected by matrix advanced glycation endproducts (AGEs) in vivordquo Calcified Tissue International 2016

[86] V Huovinen V Saunavaara R Kiviranta et al ldquoVertebralbone marrow glucose uptake is inversely associated with bonemarrow fat in diabetic and healthy pigs [18F]FDG-PET andMRI studyrdquo Bone vol 61 pp 33ndash38 2014

[87] A Y Leung ldquoTraditional toxicity documentation of Chinesemateria medicamdashan overviewrdquo Toxicologic Pathology vol 34no 4 pp 319ndash326 2006

[88] P M Le A Benhaddou-Andaloussi A Elimadi A SettafY Cherrah and P S Haddad ldquoThe petroleum ether extractof Nigella sativa exerts lipid-lowering and insulin-sensitizingactions in the ratrdquo Journal of Ethnopharmacology vol 94 no2-3 pp 251ndash259 2004

[89] UKalus A Pruss J Bystron et al ldquoEffect ofNigella sativa (blackseed) on subjective feeling in patients with allergic diseasesrdquoPhytotherapy Research vol 17 no 10 pp 1209ndash1214 2003

[90] A K Maji S Pandit P Banerji and D Banerjee ldquoPuerariatuberosa a review on its phytochemical and therapeutic poten-tialrdquo Natural Product Research vol 28 no 23 pp 2111ndash21272014

[91] N Santosh KMohan S Royana and T B Yamini ldquoHepatotox-icity of tubers of Indian Kudzu (Pueraria tuberosa) in ratsrdquo Foodand Chemical Toxicology vol 48 no 4 pp 1066ndash1071 2010


[92] Y Zhou X Su B Cheng J Jiang and H Chen ldquoComparativestudy on pharmacological effects of various species of PuerariardquoZhongguo Zhongyao Zazhi vol 20 no 10 pp 619ndash621 1995

[93] Z Zhang T-N Lam and Z Zuo ldquoRadix puerariae an overviewof its chemistry pharmacology pharmacokinetics and clinicaluserdquo Journal of Clinical Pharmacology vol 53 no 8 pp 787ndash8112013

[94] S-Y Yu H-T OuYang J-Y Yang et al ldquoSubchronic toxicitystudies of Radix Astragali extract in rats and dogsrdquo Journal ofEthnopharmacology vol 110 no 2 pp 352ndash355 2007

[95] W YW Lee L C M Chiu and J H K Yeung ldquoCytotoxicity ofmajor tanshinones isolated from Danshen (Salvia miltiorrhiza)on HepG2 cells in relation to glutathione perturbationrdquo Foodand Chemical Toxicology vol 46 no 1 pp 328ndash338 2008

[96] M Xu M Zhang H E Yao L Chen and X Xie ldquoStudy on thetoxic effect of the liposoluble components of Salvia on rat retinalMuller cellsrdquo West China Journal of Pharmaceutical Sciencesvol 28 no 5 pp 453ndash455 2013

[97] C Hu Y Huang X Wang C Sun T Luo and X Yang ldquoAtoxicity comparative study of eucommia ulmoides seed andbarkrdquo Journal of Jinggangshan University (Natural Science) vol36 no 1 pp 95ndash100 2015

[98] J Zhang H Du Q Li and Y Ding ldquoStudy advancement aboutpharmacological andtoxicological of Eucommia ulmoidesOlivrdquoJournal of Henan University (Medical Science) vol 33 no 3 pp217ndash222 2014

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


and lower extremitiesrdquo [47] According to TCM theories andclinical symptoms of DOP the etiology of DOP is mainlyattributed to the insufficiency of the spleen liver and kidneyIn traditional Chinese physiology the spleen (as is wellknown all the organs inTCMbear the least resemblance to itswestern counterpart) is assumed to be responsible for assim-ilation of nutrients and maintenance of physical strengthThe spleen governs blood digestion transformation andtransportation in the body [48] So the spleen has the abilityof transforming food into Qi and blood and transportingthem throughout the body Proper functioning of the organis essential to maintain muscle mass and strengthen limbsAlso in traditional Chinese physiology the liver (Gan) storesblood ensures the smooth flow ofQi and controls the actionand nutrition of tendon [49] And the kidney (Shen) storesessence and controls the growth and development of bone[50 51] Meanwhile Qi (Qi is the term used in TCM todescribe the bodyrsquos vital life energy [52]) deficiency and bloodstasis also contributed to the development of DOP

Xiao-Ke is an official terminology for diabetes in TCM[53] TCM believes that Xiao-Ke mainly resulted from thedysfunctions of kidney spleen and liver [54] As kidneycontrols bone growth and development via neuroendocrine-immune network and osteoclast regulatory pathway oste-oprotegerin- (OPG-) receptor activator of nuclear factorkappa-B ligand- (RANKL-) RANK [51 55] the deficiencyof the kidney caused by Xiao-Ke further results in bonemalnutrition The liver dredges and smooths the routeof something and produces blood by promoting circula-tion of blood and metabolism of body fluid and assist-ing the spleen and the stomach to digest food (httpoldtcmwikicomwikithe-liver) The loss of liver Yin in thedevelopment of Xiao-Ke causes blood deficiency which leadsto blood stasis tendon and vessels undernutrition [56]The spleen has the function to transport and transformnutrients by digesting food absorbing nutrients of food andwater and then transporting them to the heart and thelung (httpoldtcmwikicomwikithe-spleen) If the essencetransportation and transformation fails in spleen dampnessand circulation disorders of Qi and blood will occur to thebody [57] Further the bone is loss of nutrition which maycause insufficiency of bone marrow and bone pain [58]The codysfunctions of liver spleen and kidney lead to Qideficiency and blood stasis which further contributes toinsufficiency of blood and essence [57 59] All the abnor-malities lead to bone lesions and occurrence of DOP Theviews on the pathogenesis of DOP have been also discussedin the ancient Chinesemedicine works such as ldquoInner Canonof Huangdirdquo ldquoClinic Guideline of Medical Recordsrdquo andldquoXue Zheng Lunrdquo Therefore prevention and treatment ofDOP should focus on regulation and tonification of the liverspleen and kidney The proper function of liver spleen andkidney promotes Qi to disperse stagnation and reinforcekidney to replenish Yin which beneficially contributes toimproving bone metabolism

In recent years great achievements have been made inprevention and treatment of DOP in TCM The results havedemonstrated that TCM herbs not only had the abilities ofincreasing the bone quality by enhancing the mechanical

strength of bone but also exhibited the effect on improving theprimary disease by regulating glycaemia metabolism Nextwe review the clinical and preclinical research advances ofusing TCM in the treatment of DOP

3 Clinical Advances of DOP in TCM

As mentioned previously the clinical guidelines for TCMtreatment of DOP are tonifying liver spleen and kidneyas well as promoting Qi flow and removing blood stasisWe summarized the TCM compound prescriptions used inthe clinical trials of DOP as shown in Table 1 Till nowthere are around 18 TCM prescriptions that have been usedin managing patients with DOP in which clinical studieshave been performed by different investigators with variousprescriptions Zhang et al [5] found that Tanggukang treat-ment reduced serum malondialdehyde (MDA) and bloodglucose and increased the activity of superoxide dismutase(SOD) that contributed to controlling the glycaemia andsuppressing osteoporosis in patients with DOP In additionboth Tanggukang [6] and Qianggubao granule treatmentsalso had significant effects on patients with DOP evidencedby improving calcium and phosphorus metabolism andhydroxyproline level as well In addition Ji et al [7] foundthat Bushen Huoxue decoction treatment not only controlledglycaemia and lipidemia but also obviously improved bonemineral density (BMD) in patients with DOP Shang et al[8 9] found that Bushen Tongluo decoction had the abilityof improving BMD and reducing the risk of bone fractures inpatients with DOP Gong and Li [10] found that Jiawei Qingrsquoepill treatment improved DOP patients in blood glycosylatedhemoglobin (HbA1C) calcium and phosphorus level andfasting urine Cacreatine ratio which beneficially contributedto the balance of bone metabolism Yushanjiang and Halida[11] showed that the Xihongkang treatment prevented thedevelopment of DOP by tonifying Qi nourishing Yin andpromoting blood circulation Deng [12] demonstrated thatYishen Zhuanggu decoction treatment increased serum bonegla-protein (BGP) and 125-(OH)

2D3levels and BMD value

in patients with DOPFurthermore treatments with TCM formulas such as

Huqian pills [13] Gusong decoction [14 15] Tangmaikanggranules [16] Bushen Huoxue decoction [17] Jiawei Gutong-xian capsule [18] Qianggubao granule [19] Jiangu decoction[20] Jiangtang Bushen formulation [21] Huolisu oral liquid[22] Migu decoction [23] and Xianling Gubao [24] havealso been demonstrated to improve BMD decrease serumC-reactive protein (CRP) level and attenuate lumbar painevidenced by decreasing visual analogue scale pain score invertebra and back in the patients with DOP

Most of prescriptions used in management of DOPconsist of 4 to 14 herbs Eight of most appearing Chineseherbs in the clinical studies are compiled in Table 2 Allof these herbs possess the functions of invigorating Qiactivating blood circulation and replenishing vital essenceto tonify kidney [60] The applications also conform to theTCM pathogenesis of DOP The prescriptions are helpful forthe investigators to screen the active ingredients against DOPfrom these herbs in the future


Table1Clinicalused

TCM

prescriptio

nsfortreatmento

fpatientsw

ithDOP

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Tang

gukang

decoction

7a

Fastingbloo

dglucose(FB

G)glycosylated

hemoglobin(H

bA1C

)bo

nemineral

density

(BMD)superoxide

dism

utase(SO

D)malon

dialdehyde

(MDA)bo

negla-protein(BGP)C

aand

Pin

serumand

urine

FBGandHbA

1ClevelsdecreasedBM

DB

GPandserum

SOD


MDAdecreasedurineC

aand

Pdecreased

Con

troltreatmentu

singoyste

rshellcalcium

chew

abletablet

[56]

Bushen

Huo

xue

decoction

11b

Sign

ificant

effectBM


ptom

sand

painsd

isapp

eared

Effectiv

eclinicalsym

ptom

salleviatedB

MDremainedthes

ame

Ineffectiv

eBM

Dandclinicalsym

ptom

srem

ainedthes

ame

Markedlyim

proved

(24)

Mod

erately

improved

(4)

Ineffectiv

e(2)

Overalleffi

cacy933

Con

troltreatmentQiang

gucapsule

[7]

Bushen

Tong

luo

decoction

9cBroadb

andultrasou

ndattenu

ation(BUA

)soun

dof

speed(SOS)C

aand

Pin

serumalkalinep

hosphatase

(ALP

)FB

Gand

HbA

1C

BUAandSO

Ssig

nificantly

increasedFB

GandHbA

1Clevels

redu

ced

Con

troltreatmentu

singcaltrateD

[89]

JiaweiQingrsquoe

Pill

9dCa

Pcreatinine(Cr

)ratiosinbloo

dandurine

Markedlyim

proved

(25)

Mod

erately

improved

(11)

Ineffectiv

e(4)

Overalleffi

cacy90

Serum

Cadecreasedby

048

mMLserum

Pincreasedby

044

mMLurin

eCaCr

ratio

decreasedby

029

Con

troltreatmentu


[10]

Xiho

ngkang

7e

Sign

ificant

effectclinicalsym

ptom

sdisa

ppearedFB

Glt72

mMtwo-ho

urpo

stprand

ialblood

glucose(2h

PG)lt

83m

MH

bA1Clt6

orHbA

1Cdecreased

by⩾30B

MDincreasedby⩾20

Effectiv

eclinicalsym

ptom

salleviatedFBGlt83m

ML2

hPGlt100mML

HbA

1Clt8

orHbA

1Cdecreasedby⩾10B

MDincreasedby⩾10

Ineffectiv

eno

significantimprovem

entinsymptom

sHbA

1CandBM

Dremained

thes

ame

Markedlyim

proved

(56)

Mod

erately

improved

(68)

Ineffectiv

e(16)

Overalleffi

cacy886

Con

troltreatmentu


izideandcaltrateD

[11]

Yishen

Zhuang

gucompo

und

9f

Sign

ificant

effectpain

disapp

earedBM

Dincreasedby

005

gcm2

Effectiv

epain

significantly

alleviatedB

MDremainedthes

ameo

rdecreased

bylt005

gcm2

Ineffectiv

eno

improvem

entinsymptom

s

Markedlyim

proved

(14)

Mod

erately

improved

(17)

Ineffectiv

e(1)

Overalleffi

cacy968

Con

troltreatmentu


[12]

Huq

ianpill

8g

Sign

ificant

effectsymptom

andph

ysicalsig

ndisapp

eared23

mMd⩽urineP⩽

48mMd25mMd⩽urineC

a⩽75

mMd167m

Md⩽urineM

g2+⩽100m

Md

096

mML⩽serum

P⩽14

5mML08mM⩽serum

Mg2+⩽12

mMX

-ray

appeared

norm

al

Effectiv

eclinicalsym

ptom

salleviatedurin

eCar

emained65plusmn

25m

moldurin



mmoldX

-ray

with

out

obviou

slyabno

rmal

Ineffectiv

eno

improvem

entinsymptom

sand

signs

aswell

asotherb

iomarkers

Markedlyim

proved

(23)

Mod

erately

improved

(28)

Ineffectiv

e(5)

Overalleffi

cacy910

7Nocontrols

[13]


Table1Con

tinued

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Guson

gdecoction

13h

Sign

ificant

effectsymptom

sand

physicalsig

nsscored

ecreased

by⩾70B

MD

increasedby⩾2

significantimprovem

entinbo

nemetabolism

indexFP

Gand

2hPG

returned

tothen

ormalor

decreasedby⩾40

H

bA1C⩽62

ordecreased

by⩾30

Effectiv

esymptom

sand

physicalsig

nsscored

ecreased

between30and70


and2

bon

emetabolism

indexim

provedFPG

and

2hPG

decreasedby⩾20H

bA1C


Ineffectiv

eno


ptom

ssymptom

sand

physical

signs

scored

ecreased

bylt30B

MDincreasedbylt1

noim

provem

entinbo

nemetabolism

indexFP

Gand2h

PGand

HbA

1C

Markedlyim

proved

(15)

Mod

erately

improved

(22)

Ineffectiv

e(3)

Overalleffi

cacy925

Con

troltreatmentu

singvitamin

D3calcium

carbon

atetabletsand

alendron

ates

odium

tablets

[14]

Guson

gdecoction

4i

Sign

ificant

effectlumbarv

ertebrap

ainandotherc

linicalsymptom

sdisa

ppearedor

totalscoresd

ecreased

bymorethan23

Effectiv

elumbarv

ertebrap

ainandotherc

linicalsymptom

smarkedlyalleviated

ortotalscoresd

ecreased

bymorethan13

Ineffectiv

eno

improvem

entinclinicalsym

ptom

stotalscoresd

idno

treach

the

effectiv

evalue

Markedlyim

proved

(21)

Mod

erately

improved

(14)

Ineffectiv

e(3)

Overalleffi

cacy9211

Con

troltreatmentu

singglipizidea

ndalendron

ates

odium

tablets

[15]

Tang

maikang

granules

combined

with

alendron

ate

sodium

tablets

9j

Sign

ificant

effectlumbarv

ertebrap

aindisapp

earedsig


D

Effectiv

elumbarv

ertebrap

ainalleviated

with

nosig


D

Ineffectiv

elumbarv

ertebrap

ainstillexistedB

MDremainedthes

ame

Markedlyim

proved

(24)

Mod

erately

improved

(21)

Ineffectiv

e(3)

Overalleffi

cacy9375

Con

troltreatmentu

singalendron

ates

odium

tablets

[16]

Bushen

Huo

xue

decoction

0k

Sign

ificant

effectback

pain

disapp

earedsymptom

sand

physicalsig

nsscore

decreasedby

23sig

nificantimprovem

entinbo

nemetabolism

indexBM

Dincreasedby

morethan006

gcm2

Effectiv

eback

pain

obviou

slyalleviatedsym

ptom

sand

physicalsig

nsscores

decreasedby

13nochange

oraggravationwas

foun

din

theb

iomarkersandBM

D

Ineffectiv

eno

improvem

entinallthe

aspects

Markedlyim

proved

(3)

Mod

erately

improved

(26)

Ineffectiv

e(1)

Overalleffi

cacy967

Con

troltreatmentu

singcaltrateD

[17]

JiaweiGuton

gxian

capsule

14l

Curelum

barv

ertebrap

aindisapp

earedX-

rayappeared

norm

al

Sign

ificant

effectlumbarv

ertebrap

ainobviou


improvem

entinX-

ray

Effectiv

elumbarv

ertebrap


entinX-

ray

Ineffectiv

elumbarv

ertebrap

ainandX-

rayremainedthes

ame

Cure

(1)

Markedlyim

proved

(8)

Mod

erately

improved

(27)

Ineffectiv

e(4)

Overalleffi

cacy900

Con

troltreatmentu

singosteoform

capsule

[18]

Qiang

gubao

capsule

8mBa

ckpainB

MD

Markedlyim

proved

(24)

Mod

erately

improved

(13)

Ineffectiv

e(3)

Overalleffi

cacy925

[19]

Jiang

uform

ula

12n

Clinicalsymptom

aticscales

Markedlyim

proved

(18)

Mod

erately

improved

(28)

Ineffectiv

e(4)

Overalleffi

cacy920

Con

troltreatmentu

singosteoform

capsule

[20]


ble1Con

tinued

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Jiang

tang

Bushen

form

ula

10o

BMDserum

C-reactiv

eprotein

(CRP

)BM

Dandserum

CRPsig

nificantly

increased

Con

troltreatmentu

singcaltrateD

[21]

Huo

lisuoralliq

uid

5p

Sign

ificant

effectclinicalsym

ptom

smarkedlyim

provedB

MDsig

nificantly

increased

Effectiv

eclinicalsym

ptom

salleviatedB

MDslightly

increased

Ineffectiv

eclinicalsym

ptom

sand

BMDremainedthes

ame

Markedlyim

proved

(12)

Mod

erately

improved

(86)

Ineffectiv

e(14)

Overalleffi

cacy791

Con

troltreatmentu

singsalm

oncalcito

nin

[22]

Migudecoction

7qVisualanalogue

scale(VA

S)pain

scoreBM

DVA

Spain

scores

ignificantly

improvedB

MDsig

nificantly

increased

Con

troltreatmentu

singcalcium

carbon

ate

[23]

Xianlin

gGub

ao6r

Clinicalsymptom

scales

andBM

DClinicalsymptom

scales

andBM

Dsig

nificantly

improved

Con

troltreatmentu

singcaltrateD

[24]

a RadixRehm

anniae

PreparataFructusC

orniR

hizomaD

ioscoreaeHerba

CynomoriiCa

rapaxetPlastru

mTestu

dinisRh

izom

aChu

anxiongandRa

dixetRh

izom

aSalviae

Miltiorrhizae(do

sage

inform

ationisno

tavailable)

b Radix

Astra

gali30

gHerba

Epim

edii12gRh

izom

aPolyg

onati12g

CollaCo

rnus

Cervi(meltingin

boiledwater)15g

RhizomaDioscoreae3

0gSem

enAstra

galiCo

mplan

ati15g

Radix

PuerariaeL

obatae

30g

RadixPolyg

oniM

ultifl

ori15g

RadixetRh

izom

aSalviae

Miltiorrhizae3

0gR

adixetRh

izom

aRhei10g

and

SanguisD

raconis10g

c R

adixAstra

galiCollaCe

rviC

ornu

sRa

dixRehm

anniaeFructus

PsoraleaeHerba

Epim

ediiFructusL

igustri

Lucid

iRa

dixNo

toginsengRa

dixetRh

izom

aSalviae

MiltiorrhizaeandPh

eretim

a(dosageinformation

isno

tavailable)

d CortexEu

commiae12g

Fructus

Psoraleae12g

RadixAstra

gali30

gRa

dixNo

toginseng15gRh

izom

aDioscoreae15g

CollaCo

rnus

Cervi(meltingin

boiledwater)6

gRa

dixetRh

izom

aSalviae

Miltiorrhizae12g

OsD

raconis3

0gand

Concha

Ostreae3

0g

e RadixAstra

galiRa

dixetRh

izom

aRheiFructusL

igustri

Lucid

iFructusL

yciiHiru

doFlosC

artham

iandRa

dixetRh

izom

aRhodiolae

Crenulatae


tavailable)

f RadixRehm

anniae

Preparata15g

Fructus

Corni10g

RhizomaC

huan

xiong15gRh

izom

aDrynaria

e15g

Fructus

Psoraleae15g

Herba

Epim

edii12gRa

dixetRh

izom

aSalviae

Miltiorrhizae15g

RadixCy

athu

lae

15gandFructusL

ycii20

gg C

ortexP

hellodend

riCh

inensis

10gRa

dixR

ehmanniae

Preparata15g

Carapax

etPlastru

mTestu

dinis15g

RadixPa

eoniae

Alba12g

RhizomaA

nemarrhenae

9gPerica

rpiumCitri

Reticulatae

10gHerba

Cynomorii

10gandRh

izom

aZingiberis

4g

h RadixAstra

galiRa

dixC

odonopsisR

adixPolyg

oniM

ultifl

oriR

adixAn

gelicae

Sinensis

Rhizom

aAtra


arapax

etPlastru

mTestu

dinisCa

rapaxT

rionycisH

erba

TaxilliH

erba

Epim

edii

RadixDipsaci

CortexEu

commiaeandFructusA

urantii


tavailable)

i RhizomaD

rynaria

e20g

Herba

Epim

edii20

gRh

izom

aAtra


15gandCortexEu

commiae15g

j RadixAstra

galiRa

dixR

ehmanniaeR

adixPa

eoniae

RubraRa

dixe

tRhizomaS

alviae

MiltiorrhizaeRa

dixC

yathulaeR

adixOphiopogonisRh

izom

aPolygonatiH

erba

Epim

ediiandRa

dixP

ueraria

eLob

atae

(dosage

inform

ationisno

tavailable)

k Prescrip

tionconstituentsa

nddo

sage

inform

ationaren

otavailable

l Radix

Rehm

anniae

Preparata


erba

Cista

nchesRh

izom

aDrynaria

ePy

ritum

RhizomaCu

rculiginis

Herba

Epim

edii

RadixAn

gelicae

Sinensis

Rhizom

aAn

emarrhenaeR

adix

NotoginsengCa

rapaxetPlastru

mTestu

dinisPlacenta

Hom

inis

RadixAstra

galiandEn

dothelium

Corneum

Gigeria


tavailable)

mRa

dixAstra

gali

FructusC

orniH

erba

Dendrobii

Rhizom

aDioscoreaeRh

izom

aDrynaria

eCollaCornu

sCervi

(meltingin

boiledwater)Ra

dixet

Rhizom

aSalviaeM

iltiorrhizaeandCo

ncha

Ostreae(

dosage

inform

ationisno

tavailable)

n Herba

Epim

edii10gHerba

Cista

nches10g

CortexEu

commiae18g

RadixDipsaci12gRa

dixPolyg

oniM

ultifl

ori10g

RadixRe

hmanniae

Preparata12gRh

izom

aDioscoreae15g

Fructus

Corni10g

Fructus

Lycii

12gRa

dixAn

gelicae

Sinensis10gRa

dixCy

athu

lae18g

and

Poria

12g

o RadixAstra

gali30

gRa

dixP

aeoniaeR

ubra

20gRa

dixe

tRhizomaS

alviae

Miltiorrhizae2

0gC

ortexM

ori10g

RadixTrich

osanthis20

gFructusL

ycii15gRa

dixS

crophu

laria

e20g

RadixRehm

anniae

20gSemen

Cuscutae

15gandRh

izom

aDrynaria

e15g

(mod

ificatio

naccordingto

symptom

sIfdiagno

sedas

Qid

eficiencyR

adixPseudoste

llaria

e(30

g)isaddedto

thea

bove

prescriptio

nandthed

osageo

fRadixAstra

galiis

mod

ified

from

30gto

50gIfdiagno

sedas

YindeficiencyHerba

Dendrobii(15g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

bloo

ddeficiencyRa

dixPa

eoniae

Alba

(20g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

bloo

dstasis

Rhizom

aCh

uanx

iong

(20g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

phlegm

-heatFructusT

richosanthis(15g)

andCa

ulisBa

mbu

saeinTaenia

(10g

)are

addedto

thea

bove

prescriptio

n)

p Herba

Epim

ediiRa

dixetRh

izom

aSalviae

MiltiorrhizaeRa

dixAstra

galiRa



tavailable)

q RadixRehm

anniae

Preparata15gHerba

Epim

edii10gFructusP

soralea

e15g

RadixNo

toginseng15gRh

izom

aDrynaria

e15g

Sem

enCu

scutae

15gandRh

izom

aDioscoreae12g

r H

erba

Epim

ediiRa

dixDipsaci

FructusP

soralea

eRa

dixRehm

anniaeR

adixetRh

izom

aSalviae

MiltiorrhizaeandRh

izom

aAnemarrhenae


tavailable)















Reference


extractSTZ (40mgKg)


weeks[25]










[33]


[34]













and dosageReference












Qianggubao10













Etiology of DOP

Femur

LumbarTCM drugs


Traditional Chinese

(TCM)medicine









Disclosure


Competing Interests





Acknowledgments


References












































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Clinicalused

TCM

prescriptio

nsfortreatmento

fpatientsw

ithDOP

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Tang

gukang

decoction

7a

Fastingbloo

dglucose(FB

G)glycosylated

hemoglobin(H

bA1C

)bo

nemineral

density

(BMD)superoxide

dism

utase(SO

D)malon

dialdehyde

(MDA)bo

negla-protein(BGP)C

aand

Pin

serumand

urine

FBGandHbA

1ClevelsdecreasedBM

DB

GPandserum

SOD


MDAdecreasedurineC

aand

Pdecreased

Con

troltreatmentu

singoyste

rshellcalcium

chew

abletablet

[56]

Bushen

Huo

xue

decoction

11b

Sign

ificant

effectBM


ptom

sand

painsd

isapp

eared

Effectiv

eclinicalsym

ptom

salleviatedB

MDremainedthes

ame

Ineffectiv

eBM

Dandclinicalsym

ptom

srem

ainedthes

ame

Markedlyim

proved

(24)

Mod

erately

improved

(4)

Ineffectiv

e(2)

Overalleffi

cacy933

Con

troltreatmentQiang

gucapsule

[7]

Bushen

Tong

luo

decoction

9cBroadb

andultrasou

ndattenu

ation(BUA

)soun

dof

speed(SOS)C

aand

Pin

serumalkalinep

hosphatase

(ALP

)FB

Gand

HbA

1C

BUAandSO

Ssig

nificantly

increasedFB

GandHbA

1Clevels

redu

ced

Con

troltreatmentu

singcaltrateD

[89]

JiaweiQingrsquoe

Pill

9dCa

Pcreatinine(Cr

)ratiosinbloo

dandurine

Markedlyim

proved

(25)

Mod

erately

improved

(11)

Ineffectiv

e(4)

Overalleffi

cacy90

Serum

Cadecreasedby

048

mMLserum

Pincreasedby

044

mMLurin

eCaCr

ratio

decreasedby

029

Con

troltreatmentu


[10]

Xiho

ngkang

7e

Sign

ificant

effectclinicalsym

ptom

sdisa

ppearedFB

Glt72

mMtwo-ho

urpo

stprand

ialblood

glucose(2h

PG)lt

83m

MH

bA1Clt6

orHbA

1Cdecreased

by⩾30B

MDincreasedby⩾20

Effectiv

eclinicalsym

ptom

salleviatedFBGlt83m

ML2

hPGlt100mML

HbA

1Clt8

orHbA

1Cdecreasedby⩾10B

MDincreasedby⩾10

Ineffectiv

eno

significantimprovem

entinsymptom

sHbA

1CandBM

Dremained

thes

ame

Markedlyim

proved

(56)

Mod

erately

improved

(68)

Ineffectiv

e(16)

Overalleffi

cacy886

Con

troltreatmentu


izideandcaltrateD

[11]

Yishen

Zhuang

gucompo

und

9f

Sign

ificant

effectpain

disapp

earedBM

Dincreasedby

005

gcm2

Effectiv

epain

significantly

alleviatedB

MDremainedthes

ameo

rdecreased

bylt005

gcm2

Ineffectiv

eno

improvem

entinsymptom

s

Markedlyim

proved

(14)

Mod

erately

improved

(17)

Ineffectiv

e(1)

Overalleffi

cacy968

Con

troltreatmentu


[12]

Huq

ianpill

8g

Sign

ificant

effectsymptom

andph

ysicalsig

ndisapp

eared23

mMd⩽urineP⩽

48mMd25mMd⩽urineC

a⩽75

mMd167m

Md⩽urineM

g2+⩽100m

Md

096

mML⩽serum

P⩽14

5mML08mM⩽serum

Mg2+⩽12

mMX

-ray

appeared

norm

al

Effectiv

eclinicalsym

ptom

salleviatedurin

eCar

emained65plusmn

25m

moldurin



mmoldX

-ray

with

out

obviou

slyabno

rmal

Ineffectiv

eno

improvem

entinsymptom

sand

signs

aswell

asotherb

iomarkers

Markedlyim

proved

(23)

Mod

erately

improved

(28)

Ineffectiv

e(5)

Overalleffi

cacy910

7Nocontrols

[13]


Table1Con

tinued

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Guson

gdecoction

13h

Sign

ificant

effectsymptom

sand

physicalsig

nsscored

ecreased

by⩾70B

MD

increasedby⩾2

significantimprovem

entinbo

nemetabolism

indexFP

Gand

2hPG

returned

tothen

ormalor

decreasedby⩾40

H

bA1C⩽62

ordecreased

by⩾30

Effectiv

esymptom

sand

physicalsig

nsscored

ecreased

between30and70


and2

bon

emetabolism

indexim

provedFPG

and

2hPG

decreasedby⩾20H

bA1C


Ineffectiv

eno


ptom

ssymptom

sand

physical

signs

scored

ecreased

bylt30B

MDincreasedbylt1

noim

provem

entinbo

nemetabolism

indexFP

Gand2h

PGand

HbA

1C

Markedlyim

proved

(15)

Mod

erately

improved

(22)

Ineffectiv

e(3)

Overalleffi

cacy925

Con

troltreatmentu

singvitamin

D3calcium

carbon

atetabletsand

alendron

ates

odium

tablets

[14]

Guson

gdecoction

4i

Sign

ificant

effectlumbarv

ertebrap

ainandotherc

linicalsymptom

sdisa

ppearedor

totalscoresd

ecreased

bymorethan23

Effectiv

elumbarv

ertebrap

ainandotherc

linicalsymptom

smarkedlyalleviated

ortotalscoresd

ecreased

bymorethan13

Ineffectiv

eno

improvem

entinclinicalsym

ptom

stotalscoresd

idno

treach

the

effectiv

evalue

Markedlyim

proved

(21)

Mod

erately

improved

(14)

Ineffectiv

e(3)

Overalleffi

cacy9211

Con

troltreatmentu

singglipizidea

ndalendron

ates

odium

tablets

[15]

Tang

maikang

granules

combined

with

alendron

ate

sodium

tablets

9j

Sign

ificant

effectlumbarv

ertebrap

aindisapp

earedsig


D

Effectiv

elumbarv

ertebrap

ainalleviated

with

nosig


D

Ineffectiv

elumbarv

ertebrap

ainstillexistedB

MDremainedthes

ame

Markedlyim

proved

(24)

Mod

erately

improved

(21)

Ineffectiv

e(3)

Overalleffi

cacy9375

Con

troltreatmentu

singalendron

ates

odium

tablets

[16]

Bushen

Huo

xue

decoction

0k

Sign

ificant

effectback

pain

disapp

earedsymptom

sand

physicalsig

nsscore

decreasedby

23sig

nificantimprovem

entinbo

nemetabolism

indexBM

Dincreasedby

morethan006

gcm2

Effectiv

eback

pain

obviou

slyalleviatedsym

ptom

sand

physicalsig

nsscores

decreasedby

13nochange

oraggravationwas

foun

din

theb

iomarkersandBM

D

Ineffectiv

eno

improvem

entinallthe

aspects

Markedlyim

proved

(3)

Mod

erately

improved

(26)

Ineffectiv

e(1)

Overalleffi

cacy967

Con

troltreatmentu

singcaltrateD

[17]

JiaweiGuton

gxian

capsule

14l

Curelum

barv

ertebrap

aindisapp

earedX-

rayappeared

norm

al

Sign

ificant

effectlumbarv

ertebrap

ainobviou


improvem

entinX-

ray

Effectiv

elumbarv

ertebrap


entinX-

ray

Ineffectiv

elumbarv

ertebrap

ainandX-

rayremainedthes

ame

Cure

(1)

Markedlyim

proved

(8)

Mod

erately

improved

(27)

Ineffectiv

e(4)

Overalleffi

cacy900

Con

troltreatmentu

singosteoform

capsule

[18]

Qiang

gubao

capsule

8mBa

ckpainB

MD

Markedlyim

proved

(24)

Mod

erately

improved

(13)

Ineffectiv

e(3)

Overalleffi

cacy925

[19]

Jiang

uform

ula

12n

Clinicalsymptom

aticscales

Markedlyim

proved

(18)

Mod

erately

improved

(28)

Ineffectiv

e(4)

Overalleffi

cacy920

Con

troltreatmentu

singosteoform

capsule

[20]


ble1Con

tinued

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Jiang

tang

Bushen

form

ula

10o

BMDserum

C-reactiv

eprotein

(CRP

)BM

Dandserum

CRPsig

nificantly

increased

Con

troltreatmentu

singcaltrateD

[21]

Huo

lisuoralliq

uid

5p

Sign

ificant

effectclinicalsym

ptom

smarkedlyim

provedB

MDsig

nificantly

increased

Effectiv

eclinicalsym

ptom

salleviatedB

MDslightly

increased

Ineffectiv

eclinicalsym

ptom

sand

BMDremainedthes

ame

Markedlyim

proved

(12)

Mod

erately

improved

(86)

Ineffectiv

e(14)

Overalleffi

cacy791

Con

troltreatmentu

singsalm

oncalcito

nin

[22]

Migudecoction

7qVisualanalogue

scale(VA

S)pain

scoreBM

DVA

Spain

scores

ignificantly

improvedB

MDsig

nificantly

increased

Con

troltreatmentu

singcalcium

carbon

ate

[23]

Xianlin

gGub

ao6r

Clinicalsymptom

scales

andBM

DClinicalsymptom

scales

andBM

Dsig

nificantly

improved

Con

troltreatmentu

singcaltrateD

[24]

a RadixRehm

anniae

PreparataFructusC

orniR

hizomaD

ioscoreaeHerba

CynomoriiCa

rapaxetPlastru

mTestu

dinisRh

izom

aChu

anxiongandRa

dixetRh

izom

aSalviae

Miltiorrhizae(do

sage

inform

ationisno

tavailable)

b Radix

Astra

gali30

gHerba

Epim

edii12gRh

izom

aPolyg

onati12g

CollaCo

rnus

Cervi(meltingin

boiledwater)15g

RhizomaDioscoreae3

0gSem

enAstra

galiCo

mplan

ati15g

Radix

PuerariaeL

obatae

30g

RadixPolyg

oniM

ultifl

ori15g

RadixetRh

izom

aSalviae

Miltiorrhizae3

0gR

adixetRh

izom

aRhei10g

and

SanguisD

raconis10g

c R

adixAstra

galiCollaCe

rviC

ornu

sRa

dixRehm

anniaeFructus

PsoraleaeHerba

Epim

ediiFructusL

igustri

Lucid

iRa

dixNo

toginsengRa

dixetRh

izom

aSalviae

MiltiorrhizaeandPh

eretim

a(dosageinformation

isno

tavailable)

d CortexEu

commiae12g

Fructus

Psoraleae12g

RadixAstra

gali30

gRa

dixNo

toginseng15gRh

izom

aDioscoreae15g

CollaCo

rnus

Cervi(meltingin

boiledwater)6

gRa

dixetRh

izom

aSalviae

Miltiorrhizae12g

OsD

raconis3

0gand

Concha

Ostreae3

0g

e RadixAstra

galiRa

dixetRh

izom

aRheiFructusL

igustri

Lucid

iFructusL

yciiHiru

doFlosC

artham

iandRa

dixetRh

izom

aRhodiolae

Crenulatae


tavailable)

f RadixRehm

anniae

Preparata15g

Fructus

Corni10g

RhizomaC

huan

xiong15gRh

izom

aDrynaria

e15g

Fructus

Psoraleae15g

Herba

Epim

edii12gRa

dixetRh

izom

aSalviae

Miltiorrhizae15g

RadixCy

athu

lae

15gandFructusL

ycii20

gg C

ortexP

hellodend

riCh

inensis

10gRa

dixR

ehmanniae

Preparata15g

Carapax

etPlastru

mTestu

dinis15g

RadixPa

eoniae

Alba12g

RhizomaA

nemarrhenae

9gPerica

rpiumCitri

Reticulatae

10gHerba

Cynomorii

10gandRh

izom

aZingiberis

4g

h RadixAstra

galiRa

dixC

odonopsisR

adixPolyg

oniM

ultifl

oriR

adixAn

gelicae

Sinensis

Rhizom

aAtra


arapax

etPlastru

mTestu

dinisCa

rapaxT

rionycisH

erba

TaxilliH

erba

Epim

edii

RadixDipsaci

CortexEu

commiaeandFructusA

urantii


tavailable)

i RhizomaD

rynaria

e20g

Herba

Epim

edii20

gRh

izom

aAtra


15gandCortexEu

commiae15g

j RadixAstra

galiRa

dixR

ehmanniaeR

adixPa

eoniae

RubraRa

dixe

tRhizomaS

alviae

MiltiorrhizaeRa

dixC

yathulaeR

adixOphiopogonisRh

izom

aPolygonatiH

erba

Epim

ediiandRa

dixP

ueraria

eLob

atae

(dosage

inform

ationisno

tavailable)

k Prescrip

tionconstituentsa

nddo

sage

inform

ationaren

otavailable

l Radix

Rehm

anniae

Preparata


erba

Cista

nchesRh

izom

aDrynaria

ePy

ritum

RhizomaCu

rculiginis

Herba

Epim

edii

RadixAn

gelicae

Sinensis

Rhizom

aAn

emarrhenaeR

adix

NotoginsengCa

rapaxetPlastru

mTestu

dinisPlacenta

Hom

inis

RadixAstra

galiandEn

dothelium

Corneum

Gigeria


tavailable)

mRa

dixAstra

gali

FructusC

orniH

erba

Dendrobii

Rhizom

aDioscoreaeRh

izom

aDrynaria

eCollaCornu

sCervi

(meltingin

boiledwater)Ra

dixet

Rhizom

aSalviaeM

iltiorrhizaeandCo

ncha

Ostreae(

dosage

inform

ationisno

tavailable)

n Herba

Epim

edii10gHerba

Cista

nches10g

CortexEu

commiae18g

RadixDipsaci12gRa

dixPolyg

oniM

ultifl

ori10g

RadixRe

hmanniae

Preparata12gRh

izom

aDioscoreae15g

Fructus

Corni10g

Fructus

Lycii

12gRa

dixAn

gelicae

Sinensis10gRa

dixCy

athu

lae18g

and

Poria

12g

o RadixAstra

gali30

gRa

dixP

aeoniaeR

ubra

20gRa

dixe

tRhizomaS

alviae

Miltiorrhizae2

0gC

ortexM

ori10g

RadixTrich

osanthis20

gFructusL

ycii15gRa

dixS

crophu

laria

e20g

RadixRehm

anniae

20gSemen

Cuscutae

15gandRh

izom

aDrynaria

e15g

(mod

ificatio

naccordingto

symptom

sIfdiagno

sedas

Qid

eficiencyR

adixPseudoste

llaria

e(30

g)isaddedto

thea

bove

prescriptio

nandthed

osageo

fRadixAstra

galiis

mod

ified

from

30gto

50gIfdiagno

sedas

YindeficiencyHerba

Dendrobii(15g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

bloo

ddeficiencyRa

dixPa

eoniae

Alba

(20g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

bloo

dstasis

Rhizom

aCh

uanx

iong

(20g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

phlegm

-heatFructusT

richosanthis(15g)

andCa

ulisBa

mbu

saeinTaenia

(10g

)are

addedto

thea

bove

prescriptio

n)

p Herba

Epim

ediiRa

dixetRh

izom

aSalviae

MiltiorrhizaeRa

dixAstra

galiRa



tavailable)

q RadixRehm

anniae

Preparata15gHerba

Epim

edii10gFructusP

soralea

e15g

RadixNo

toginseng15gRh

izom

aDrynaria

e15g

Sem

enCu

scutae

15gandRh

izom

aDioscoreae12g

r H

erba

Epim

ediiRa

dixDipsaci

FructusP

soralea

eRa

dixRehm

anniaeR

adixetRh

izom

aSalviae

MiltiorrhizaeandRh

izom

aAnemarrhenae


tavailable)















Reference


extractSTZ (40mgKg)


weeks[25]










[33]


[34]













and dosageReference












Qianggubao10













Etiology of DOP

Femur

LumbarTCM drugs


Traditional Chinese

(TCM)medicine









Disclosure


Competing Interests





Acknowledgments


References












































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Con

tinued

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Guson

gdecoction

13h

Sign

ificant

effectsymptom

sand

physicalsig

nsscored

ecreased

by⩾70B

MD

increasedby⩾2

significantimprovem

entinbo

nemetabolism

indexFP

Gand

2hPG

returned

tothen

ormalor

decreasedby⩾40

H

bA1C⩽62

ordecreased

by⩾30

Effectiv

esymptom

sand

physicalsig

nsscored

ecreased

between30and70


and2

bon

emetabolism

indexim

provedFPG

and

2hPG

decreasedby⩾20H

bA1C


Ineffectiv

eno


ptom

ssymptom

sand

physical

signs

scored

ecreased

bylt30B

MDincreasedbylt1

noim

provem

entinbo

nemetabolism

indexFP

Gand2h

PGand

HbA

1C

Markedlyim

proved

(15)

Mod

erately

improved

(22)

Ineffectiv

e(3)

Overalleffi

cacy925

Con

troltreatmentu

singvitamin

D3calcium

carbon

atetabletsand

alendron

ates

odium

tablets

[14]

Guson

gdecoction

4i

Sign

ificant

effectlumbarv

ertebrap

ainandotherc

linicalsymptom

sdisa

ppearedor

totalscoresd

ecreased

bymorethan23

Effectiv

elumbarv

ertebrap

ainandotherc

linicalsymptom

smarkedlyalleviated

ortotalscoresd

ecreased

bymorethan13

Ineffectiv

eno

improvem

entinclinicalsym

ptom

stotalscoresd

idno

treach

the

effectiv

evalue

Markedlyim

proved

(21)

Mod

erately

improved

(14)

Ineffectiv

e(3)

Overalleffi

cacy9211

Con

troltreatmentu

singglipizidea

ndalendron

ates

odium

tablets

[15]

Tang

maikang

granules

combined

with

alendron

ate

sodium

tablets

9j

Sign

ificant

effectlumbarv

ertebrap

aindisapp

earedsig


D

Effectiv

elumbarv

ertebrap

ainalleviated

with

nosig


D

Ineffectiv

elumbarv

ertebrap

ainstillexistedB

MDremainedthes

ame

Markedlyim

proved

(24)

Mod

erately

improved

(21)

Ineffectiv

e(3)

Overalleffi

cacy9375

Con

troltreatmentu

singalendron

ates

odium

tablets

[16]

Bushen

Huo

xue

decoction

0k

Sign

ificant

effectback

pain

disapp

earedsymptom

sand

physicalsig

nsscore

decreasedby

23sig

nificantimprovem

entinbo

nemetabolism

indexBM

Dincreasedby

morethan006

gcm2

Effectiv

eback

pain

obviou

slyalleviatedsym

ptom

sand

physicalsig

nsscores

decreasedby

13nochange

oraggravationwas

foun

din

theb

iomarkersandBM

D

Ineffectiv

eno

improvem

entinallthe

aspects

Markedlyim

proved

(3)

Mod

erately

improved

(26)

Ineffectiv

e(1)

Overalleffi

cacy967

Con

troltreatmentu

singcaltrateD

[17]

JiaweiGuton

gxian

capsule

14l

Curelum

barv

ertebrap

aindisapp

earedX-

rayappeared

norm

al

Sign

ificant

effectlumbarv

ertebrap

ainobviou


improvem

entinX-

ray

Effectiv

elumbarv

ertebrap


entinX-

ray

Ineffectiv

elumbarv

ertebrap

ainandX-

rayremainedthes

ame

Cure

(1)

Markedlyim

proved

(8)

Mod

erately

improved

(27)

Ineffectiv

e(4)

Overalleffi

cacy900

Con

troltreatmentu

singosteoform

capsule

[18]

Qiang

gubao

capsule

8mBa

ckpainB

MD

Markedlyim

proved

(24)

Mod

erately

improved

(13)

Ineffectiv

e(3)

Overalleffi

cacy925

[19]

Jiang

uform

ula

12n

Clinicalsymptom

aticscales

Markedlyim

proved

(18)

Mod

erately

improved

(28)

Ineffectiv

e(4)

Overalleffi

cacy920

Con

troltreatmentu

singosteoform

capsule

[20]


ble1Con

tinued

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Jiang

tang

Bushen

form

ula

10o

BMDserum

C-reactiv

eprotein

(CRP

)BM

Dandserum

CRPsig

nificantly

increased

Con

troltreatmentu

singcaltrateD

[21]

Huo

lisuoralliq

uid

5p

Sign

ificant

effectclinicalsym

ptom

smarkedlyim

provedB

MDsig

nificantly

increased

Effectiv

eclinicalsym

ptom

salleviatedB

MDslightly

increased

Ineffectiv

eclinicalsym

ptom

sand

BMDremainedthes

ame

Markedlyim

proved

(12)

Mod

erately

improved

(86)

Ineffectiv

e(14)

Overalleffi

cacy791

Con

troltreatmentu

singsalm

oncalcito

nin

[22]

Migudecoction

7qVisualanalogue

scale(VA

S)pain

scoreBM

DVA

Spain

scores

ignificantly

improvedB

MDsig

nificantly

increased

Con

troltreatmentu

singcalcium

carbon

ate

[23]

Xianlin

gGub

ao6r

Clinicalsymptom

scales

andBM

DClinicalsymptom

scales

andBM

Dsig

nificantly

improved

Con

troltreatmentu

singcaltrateD

[24]

a RadixRehm

anniae

PreparataFructusC

orniR

hizomaD

ioscoreaeHerba

CynomoriiCa

rapaxetPlastru

mTestu

dinisRh

izom

aChu

anxiongandRa

dixetRh

izom

aSalviae

Miltiorrhizae(do

sage

inform

ationisno

tavailable)

b Radix

Astra

gali30

gHerba

Epim

edii12gRh

izom

aPolyg

onati12g

CollaCo

rnus

Cervi(meltingin

boiledwater)15g

RhizomaDioscoreae3

0gSem

enAstra

galiCo

mplan

ati15g

Radix

PuerariaeL

obatae

30g

RadixPolyg

oniM

ultifl

ori15g

RadixetRh

izom

aSalviae

Miltiorrhizae3

0gR

adixetRh

izom

aRhei10g

and

SanguisD

raconis10g

c R

adixAstra

galiCollaCe

rviC

ornu

sRa

dixRehm

anniaeFructus

PsoraleaeHerba

Epim

ediiFructusL

igustri

Lucid

iRa

dixNo

toginsengRa

dixetRh

izom

aSalviae

MiltiorrhizaeandPh

eretim

a(dosageinformation

isno

tavailable)

d CortexEu

commiae12g

Fructus

Psoraleae12g

RadixAstra

gali30

gRa

dixNo

toginseng15gRh

izom

aDioscoreae15g

CollaCo

rnus

Cervi(meltingin

boiledwater)6

gRa

dixetRh

izom

aSalviae

Miltiorrhizae12g

OsD

raconis3

0gand

Concha

Ostreae3

0g

e RadixAstra

galiRa

dixetRh

izom

aRheiFructusL

igustri

Lucid

iFructusL

yciiHiru

doFlosC

artham

iandRa

dixetRh

izom

aRhodiolae

Crenulatae


tavailable)

f RadixRehm

anniae

Preparata15g

Fructus

Corni10g

RhizomaC

huan

xiong15gRh

izom

aDrynaria

e15g

Fructus

Psoraleae15g

Herba

Epim

edii12gRa

dixetRh

izom

aSalviae

Miltiorrhizae15g

RadixCy

athu

lae

15gandFructusL

ycii20

gg C

ortexP

hellodend

riCh

inensis

10gRa

dixR

ehmanniae

Preparata15g

Carapax

etPlastru

mTestu

dinis15g

RadixPa

eoniae

Alba12g

RhizomaA

nemarrhenae

9gPerica

rpiumCitri

Reticulatae

10gHerba

Cynomorii

10gandRh

izom

aZingiberis

4g

h RadixAstra

galiRa

dixC

odonopsisR

adixPolyg

oniM

ultifl

oriR

adixAn

gelicae

Sinensis

Rhizom

aAtra


arapax

etPlastru

mTestu

dinisCa

rapaxT

rionycisH

erba

TaxilliH

erba

Epim

edii

RadixDipsaci

CortexEu

commiaeandFructusA

urantii


tavailable)

i RhizomaD

rynaria

e20g

Herba

Epim

edii20

gRh

izom

aAtra


15gandCortexEu

commiae15g

j RadixAstra

galiRa

dixR

ehmanniaeR

adixPa

eoniae

RubraRa

dixe

tRhizomaS

alviae

MiltiorrhizaeRa

dixC

yathulaeR

adixOphiopogonisRh

izom

aPolygonatiH

erba

Epim

ediiandRa

dixP

ueraria

eLob

atae

(dosage

inform

ationisno

tavailable)

k Prescrip

tionconstituentsa

nddo

sage

inform

ationaren

otavailable

l Radix

Rehm

anniae

Preparata


erba

Cista

nchesRh

izom

aDrynaria

ePy

ritum

RhizomaCu

rculiginis

Herba

Epim

edii

RadixAn

gelicae

Sinensis

Rhizom

aAn

emarrhenaeR

adix

NotoginsengCa

rapaxetPlastru

mTestu

dinisPlacenta

Hom

inis

RadixAstra

galiandEn

dothelium

Corneum

Gigeria


tavailable)

mRa

dixAstra

gali

FructusC

orniH

erba

Dendrobii

Rhizom

aDioscoreaeRh

izom

aDrynaria

eCollaCornu

sCervi

(meltingin

boiledwater)Ra

dixet

Rhizom

aSalviaeM

iltiorrhizaeandCo

ncha

Ostreae(

dosage

inform

ationisno

tavailable)

n Herba

Epim

edii10gHerba

Cista

nches10g

CortexEu

commiae18g

RadixDipsaci12gRa

dixPolyg

oniM

ultifl

ori10g

RadixRe

hmanniae

Preparata12gRh

izom

aDioscoreae15g

Fructus

Corni10g

Fructus

Lycii

12gRa

dixAn

gelicae

Sinensis10gRa

dixCy

athu

lae18g

and

Poria

12g

o RadixAstra

gali30

gRa

dixP

aeoniaeR

ubra

20gRa

dixe

tRhizomaS

alviae

Miltiorrhizae2

0gC

ortexM

ori10g

RadixTrich

osanthis20

gFructusL

ycii15gRa

dixS

crophu

laria

e20g

RadixRehm

anniae

20gSemen

Cuscutae

15gandRh

izom

aDrynaria

e15g

(mod

ificatio

naccordingto

symptom

sIfdiagno

sedas

Qid

eficiencyR

adixPseudoste

llaria

e(30

g)isaddedto

thea

bove

prescriptio

nandthed

osageo

fRadixAstra

galiis

mod

ified

from

30gto

50gIfdiagno

sedas

YindeficiencyHerba

Dendrobii(15g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

bloo

ddeficiencyRa

dixPa

eoniae

Alba

(20g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

bloo

dstasis

Rhizom

aCh

uanx

iong

(20g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

phlegm

-heatFructusT

richosanthis(15g)

andCa

ulisBa

mbu

saeinTaenia

(10g

)are

addedto

thea

bove

prescriptio

n)

p Herba

Epim

ediiRa

dixetRh

izom

aSalviae

MiltiorrhizaeRa

dixAstra

galiRa



tavailable)

q RadixRehm

anniae

Preparata15gHerba

Epim

edii10gFructusP

soralea

e15g

RadixNo

toginseng15gRh

izom

aDrynaria

e15g

Sem

enCu

scutae

15gandRh

izom

aDioscoreae12g

r H

erba

Epim

ediiRa

dixDipsaci

FructusP

soralea

eRa

dixRehm

anniaeR

adixetRh

izom

aSalviae

MiltiorrhizaeandRh

izom

aAnemarrhenae


tavailable)















Reference


extractSTZ (40mgKg)


weeks[25]










[33]


[34]













and dosageReference












Qianggubao10













Etiology of DOP

Femur

LumbarTCM drugs


Traditional Chinese

(TCM)medicine









Disclosure


Competing Interests





Acknowledgments


References












































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















ble1Con

tinued

Com

poun

dprescriptio

nname

Treatm

entaim

andbiom

arkere

xamination

Results

(of

patie

nts)

References

Jiang

tang

Bushen

form

ula

10o

BMDserum

C-reactiv

eprotein

(CRP

)BM

Dandserum

CRPsig

nificantly

increased

Con

troltreatmentu

singcaltrateD

[21]

Huo

lisuoralliq

uid

5p

Sign

ificant

effectclinicalsym

ptom

smarkedlyim

provedB

MDsig

nificantly

increased

Effectiv

eclinicalsym

ptom

salleviatedB

MDslightly

increased

Ineffectiv

eclinicalsym

ptom

sand

BMDremainedthes

ame

Markedlyim

proved

(12)

Mod

erately

improved

(86)

Ineffectiv

e(14)

Overalleffi

cacy791

Con

troltreatmentu

singsalm

oncalcito

nin

[22]

Migudecoction

7qVisualanalogue

scale(VA

S)pain

scoreBM

DVA

Spain

scores

ignificantly

improvedB

MDsig

nificantly

increased

Con

troltreatmentu

singcalcium

carbon

ate

[23]

Xianlin

gGub

ao6r

Clinicalsymptom

scales

andBM

DClinicalsymptom

scales

andBM

Dsig

nificantly

improved

Con

troltreatmentu

singcaltrateD

[24]

a RadixRehm

anniae

PreparataFructusC

orniR

hizomaD

ioscoreaeHerba

CynomoriiCa

rapaxetPlastru

mTestu

dinisRh

izom

aChu

anxiongandRa

dixetRh

izom

aSalviae

Miltiorrhizae(do

sage

inform

ationisno

tavailable)

b Radix

Astra

gali30

gHerba

Epim

edii12gRh

izom

aPolyg

onati12g

CollaCo

rnus

Cervi(meltingin

boiledwater)15g

RhizomaDioscoreae3

0gSem

enAstra

galiCo

mplan

ati15g

Radix

PuerariaeL

obatae

30g

RadixPolyg

oniM

ultifl

ori15g

RadixetRh

izom

aSalviae

Miltiorrhizae3

0gR

adixetRh

izom

aRhei10g

and

SanguisD

raconis10g

c R

adixAstra

galiCollaCe

rviC

ornu

sRa

dixRehm

anniaeFructus

PsoraleaeHerba

Epim

ediiFructusL

igustri

Lucid

iRa

dixNo

toginsengRa

dixetRh

izom

aSalviae

MiltiorrhizaeandPh

eretim

a(dosageinformation

isno

tavailable)

d CortexEu

commiae12g

Fructus

Psoraleae12g

RadixAstra

gali30

gRa

dixNo

toginseng15gRh

izom

aDioscoreae15g

CollaCo

rnus

Cervi(meltingin

boiledwater)6

gRa

dixetRh

izom

aSalviae

Miltiorrhizae12g

OsD

raconis3

0gand

Concha

Ostreae3

0g

e RadixAstra

galiRa

dixetRh

izom

aRheiFructusL

igustri

Lucid

iFructusL

yciiHiru

doFlosC

artham

iandRa

dixetRh

izom

aRhodiolae

Crenulatae


tavailable)

f RadixRehm

anniae

Preparata15g

Fructus

Corni10g

RhizomaC

huan

xiong15gRh

izom

aDrynaria

e15g

Fructus

Psoraleae15g

Herba

Epim

edii12gRa

dixetRh

izom

aSalviae

Miltiorrhizae15g

RadixCy

athu

lae

15gandFructusL

ycii20

gg C

ortexP

hellodend

riCh

inensis

10gRa

dixR

ehmanniae

Preparata15g

Carapax

etPlastru

mTestu

dinis15g

RadixPa

eoniae

Alba12g

RhizomaA

nemarrhenae

9gPerica

rpiumCitri

Reticulatae

10gHerba

Cynomorii

10gandRh

izom

aZingiberis

4g

h RadixAstra

galiRa

dixC

odonopsisR

adixPolyg

oniM

ultifl

oriR

adixAn

gelicae

Sinensis

Rhizom

aAtra


arapax

etPlastru

mTestu

dinisCa

rapaxT

rionycisH

erba

TaxilliH

erba

Epim

edii

RadixDipsaci

CortexEu

commiaeandFructusA

urantii


tavailable)

i RhizomaD

rynaria

e20g

Herba

Epim

edii20

gRh

izom

aAtra


15gandCortexEu

commiae15g

j RadixAstra

galiRa

dixR

ehmanniaeR

adixPa

eoniae

RubraRa

dixe

tRhizomaS

alviae

MiltiorrhizaeRa

dixC

yathulaeR

adixOphiopogonisRh

izom

aPolygonatiH

erba

Epim

ediiandRa

dixP

ueraria

eLob

atae

(dosage

inform

ationisno

tavailable)

k Prescrip

tionconstituentsa

nddo

sage

inform

ationaren

otavailable

l Radix

Rehm

anniae

Preparata


erba

Cista

nchesRh

izom

aDrynaria

ePy

ritum

RhizomaCu

rculiginis

Herba

Epim

edii

RadixAn

gelicae

Sinensis

Rhizom

aAn

emarrhenaeR

adix

NotoginsengCa

rapaxetPlastru

mTestu

dinisPlacenta

Hom

inis

RadixAstra

galiandEn

dothelium

Corneum

Gigeria


tavailable)

mRa

dixAstra

gali

FructusC

orniH

erba

Dendrobii

Rhizom

aDioscoreaeRh

izom

aDrynaria

eCollaCornu

sCervi

(meltingin

boiledwater)Ra

dixet

Rhizom

aSalviaeM

iltiorrhizaeandCo

ncha

Ostreae(

dosage

inform

ationisno

tavailable)

n Herba

Epim

edii10gHerba

Cista

nches10g

CortexEu

commiae18g

RadixDipsaci12gRa

dixPolyg

oniM

ultifl

ori10g

RadixRe

hmanniae

Preparata12gRh

izom

aDioscoreae15g

Fructus

Corni10g

Fructus

Lycii

12gRa

dixAn

gelicae

Sinensis10gRa

dixCy

athu

lae18g

and

Poria

12g

o RadixAstra

gali30

gRa

dixP

aeoniaeR

ubra

20gRa

dixe

tRhizomaS

alviae

Miltiorrhizae2

0gC

ortexM

ori10g

RadixTrich

osanthis20

gFructusL

ycii15gRa

dixS

crophu

laria

e20g

RadixRehm

anniae

20gSemen

Cuscutae

15gandRh

izom

aDrynaria

e15g

(mod

ificatio

naccordingto

symptom

sIfdiagno

sedas

Qid

eficiencyR

adixPseudoste

llaria

e(30

g)isaddedto

thea

bove

prescriptio

nandthed

osageo

fRadixAstra

galiis

mod

ified

from

30gto

50gIfdiagno

sedas

YindeficiencyHerba

Dendrobii(15g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

bloo

ddeficiencyRa

dixPa

eoniae

Alba

(20g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

bloo

dstasis

Rhizom

aCh

uanx

iong

(20g

)isa

dded

tothea

bove

prescriptio

nIfdiagno

sedas

phlegm

-heatFructusT

richosanthis(15g)

andCa

ulisBa

mbu

saeinTaenia

(10g

)are

addedto

thea

bove

prescriptio

n)

p Herba

Epim

ediiRa

dixetRh

izom

aSalviae

MiltiorrhizaeRa

dixAstra

galiRa



tavailable)

q RadixRehm

anniae

Preparata15gHerba

Epim

edii10gFructusP

soralea

e15g

RadixNo

toginseng15gRh

izom

aDrynaria

e15g

Sem

enCu

scutae

15gandRh

izom

aDioscoreae12g

r H

erba

Epim

ediiRa

dixDipsaci

FructusP

soralea

eRa

dixRehm

anniaeR

adixetRh

izom

aSalviae

MiltiorrhizaeandRh

izom

aAnemarrhenae


tavailable)















Reference


extractSTZ (40mgKg)


weeks[25]










[33]


[34]













and dosageReference












Qianggubao10













Etiology of DOP

Femur

LumbarTCM drugs


Traditional Chinese

(TCM)medicine









Disclosure


Competing Interests





Acknowledgments


References












































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






























Reference


extractSTZ (40mgKg)


weeks[25]










[33]


[34]













and dosageReference












Qianggubao10













Etiology of DOP

Femur

LumbarTCM drugs


Traditional Chinese

(TCM)medicine









Disclosure


Competing Interests





Acknowledgments


References












































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















Reference


extractSTZ (40mgKg)


weeks[25]










[33]


[34]













and dosageReference












Qianggubao10













Etiology of DOP

Femur

LumbarTCM drugs


Traditional Chinese

(TCM)medicine









Disclosure


Competing Interests





Acknowledgments


References












































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















and dosageReference












Qianggubao10













Etiology of DOP

Femur

LumbarTCM drugs


Traditional Chinese

(TCM)medicine









Disclosure


Competing Interests





Acknowledgments


References












































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















Etiology of DOP

Femur

LumbarTCM drugs


Traditional Chinese

(TCM)medicine









Disclosure


Competing Interests





Acknowledgments


References












































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















Acknowledgments


References












































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of































































































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






























































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Documents

Review Article Diabetic Osteoporosis: A Review of Its ...mineral density (BMD) in patients with DOP. Shang et al. [, ] found that Bushen Tongluo decoction had the ability ... Yushanjiang