Asthi Kshaya - Asthi sousirya (osteoporosis)

as per ayurvedic kayachikitsa syllabus

1. 1
ProfSriramChandraMishra
KayachikitsaDepartment
VYDSAyurvedMahavidyalaya,Khurja

2. ASTHIKSHAYA
•Kshayameansloss,decline,decay,diminutionorwaning.
•Asthikshayaismentionedasanindependentconditionwhichcanbe
correlatedwith“decreaseinthebonetissue”.
•Dalhanahasaptlydefinedkshayaas‘Swapramanhaani’(S.Su.
15/24)whereasChakrapaniduttadescribesitas
“Swagunakriyanasat“(Ch.Su.17/63-72).
2

3. ASTHISOUSHIRYA
•Varioustermssuchasasthi-soushirya,asthi-daurbalya,asthi-shieeran,asthi-
laghav,asthi-shunyata/riktataandasthi-mardava(Osteomalacia)appearin
Ayurvedatextstodescribeasthi-kshaya.
•AsthisoushiryaisnotmentionedasaseparateconditionbutinMajjakshaya
symptomsVagbhattaelaborateabouttheterm‘Soushirya’.
•Hemadricommented‘Saushirya’as‘SARANDHRATVAM ’whichmeans
“withpores”.(Asthisoushiryameans‘porousbones’)
अस्थ्नांसौषिर्ये-सरन्ध्रत्वम्॥(हेमाद्रि-आयुर्वेदरसायनonA.H.Su.11/19)
•TheporosityofboneisduetoVayuandAakashamongstotherfactors(C.
Chi.15/33)(Aashrayaashrayeebhava)
(A.H.Su. 11/19)
3

4. SYMPTOMS OF ASTHIKSHAYA
(SU. Su. 15/9)
(A.H. Su. 11/19)
(Cha. Su. 17/67)
4
•दन्त–नखभंग(brittlenessofteethandnails),शदनयागगरना(falling)
•अस्थितोद/अस्थिशूल(paininbones)
•के श(hairs),लोम(bodyhairs),श्मश्रुयादाढ़ी(beard)पतनयागगरना(falling)
•श्रमअिाात्शऱीरमेंिकार्वट(lassitude)
•सस्न्ियोंमेंशशगिलता(laxityofjoints)
•त्र्वचामेंरूखापन(roughnessofskins)

5. MANAGEMENT OF ASTHIKSHAYA
5
•Treatmentprinciple
अस्स्िसांक्षर्यनत्।
जनतन््क्षीरघृतैस्स्तक्तसांर्युतैर्बस्स्तभिस्तिन।।(अ.हृ.सू.11/31)
अस्थिक्षयजन्यवर्वकारोंकीगचककत्साक्षीर(milk)एर्वंघृत(ghee)तिाततक्तिव्यों
(pungentdrugs)सेयुक्तबस्थतयों(enematherapy)सेकरनीचाद्रहये।
•Nidanaparivarjanam
AvoidSteroids,sedentarylifestyle,smokingetc.
•Medication
Calciumcontainingdrugs–Sudhavargadravyas
DrugsHelpfulinOsteogenesis–Aswagandha,Shatavari,Amalaki

6. •PropernutritionwithAgniDeepan
AdequateDietaryCalcium-MASHA(blackgram),TILA(sesameseeds),milk,milk
products,banana,pear,appleandotherdietaryarticlesrichincalcium,
AdequatevitaminD
Skinexposuretosunlight
NaturalsourceslikeOilyfish/Fishoils,Butter,Eggs(yolk–vitamins,minerals,
Proteins)
•VataShamanawithvariousmeasures
Abhyanga(Ksheerabala,Murivennaoiletc)
Swedana
Pizichil
SasthikasaliPindasweda
Panchatiktaksheerabastietc
•Yoga–Pranayama,Vrikshasana,Trikonasana,Virabhadrasana,Ustrasana,Savasana
•Physiotherapy-Rehabilitation,strengthenofboneandmuscles 6

7. 7
SUDHAVARGADRAVYAS(Calciumcontainingdrugs)
Badarashma, Vamshalochana, Swetanjana, Hastidanta

8. 8
Medication
•PravalaPisti •MuktaPisti •GodantiBhasma
•Kukuttandatwakbhasma •KurmapristhaBhasma •ShringaBhasma
•AjasthiBhasma •Khatika •Churnodaka
•Asthisrinkhala/asthisamharaka(Cissusquadrangularis)churna
•LakshaChurna
•Sudhashatakayoga(PravalaBhasma,MuktaBhasma,ShankhaBhasma,KapardikaBhasma,
KurmapristhaBhasma,andGodantiBhasma)-(250mg-1000mg)alongwithcowmilk
•Madhumalinivasantarasa-ShuddhaHingula,Kukkutanda,ShwetaMarich,Priyangu,
KachoraandDadim,Nimbu
•LakshadiGuggulu-Ashwagandha,Guggulu,Nagbala,Asthisamhari,ArjunaandLaksha
•PravalPanchamrutbhasma-Pravala,Mouktik,Shankha,Shouktik,,Kapardika
(Somemedicinesmaynotsuitableforvegetarianpeoples)

9. 9
•ShuktadiYoga(ShuktiBhasma,GodantiBhasma,YashadaBhasmaandTrikatu)
•GugguluTiktakaGhritam
•PanchatiktaKsheeraKwatha
•TrayodasangaGuggulu
•Gadhatailam
•Lakshaditailam
•BalaswagandhadiTaila
•DhanwantaraTaila
•TilaRasayanam
•NarasimhaRasayanam

10. 10
Vyavasthapatra
(SAMPLE PRESCRIPTION)
•MadhumalinivasataRasa–125mg
+Guduchisatva–500mg
+Pravalpanchamrita–62.5mg
…………………………………… ..
1dosetwicedailywithhoney
•Lakshadiguggulu–1tab
•Gadhatailam–1cap/10drops
…………………………………… ..
1dosetwicedailywithL.W.Water
•Aswagandhadichurna
…………………………………… ..
5gmtwicedailywithMilk
•Ahyanga–Dhanwantaratailam
•Yoga&Physiotherapy

11. Definition
•OSTEOPENIA-Amedicalconditioninwhichtheproteinandmineral
contentofbonetissueisreduced,butlessseverelythanin
osteoporosis.
•OSTEOPOROSIS -Osteoporosis,whichliterallymeansporous
bone,isasystematicskeletaldiseasecharacterizedbylowbone
massandmicroarchitecturaldeteriorationofbonetissue,witha
consequentincreaseinbonefragilityandsusceptibilitytofractures.
(API)
W.H.O.–Abonemineraldensity≤−2.5standardbelowthe
youngnormalmen.
11

12. W.H.O. definition
of Osteoporosis and
Osteopenia
Bone Mineral Density (BMD)
Category
T-scorerange
Expressed in grams per cm
2
(g/cm
2
)
Normal ≥−1.0
Osteopenia −1.0to−2.5
Osteoporosis ≤−2.5
Severeosteoporosis ≤−2.5withfragilityfracture
12

13. PhysiologyofBone
•Bonesconsistoflivingcellsembeddedinamineralizedorganicmatrix.
•Thismatrixconsistsof
1.Organiccomponents,mainlytypeIcollagen(40%).
2.Inorganiccomponents,primarilyhydroxyapatiteandothersalts
ofcalciumandphosphate(60%).
•Thecollagenfibersgiveboneitstensilestrength,andtheinterspersed
crystalsofhydroxyapatitegiveboneitscompressivestrength.
•Eachboneconstantlyundergoesmodelingduringlifetohelpitadaptto
changingbiomechanicalforces,aswellasremodelingtoremoveold,
microdamagedboneandreplaceitwithnew,mechanicallystrongerboneto
helppreservebonestrength.
13

14. TypesofBonecells
•Osteoprogenitorcells(stemcellsofmesenchymalorigin)-Osteoblastsand
osteocytesarederivedfromthesecells.
•Osteoblasts-Involvedinthecreationandmineralizationofbonetissue.
•Osteocytes-Respondtomechanicalstrainandsendsignalsofbone
formationorboneresorptiontothebonesurfaceandregulatebothlocaland
systemicmineralhomeostasis.
•Osteoclasts–Verylargemultinucleatecellsthatareresponsibleforthe
breakdownofbonesbytheprocessofboneresorption.Asitisderived
frommonocytestem-celllineage,theyareequippedwithphagocytic-like
mechanisms.
Hematopoieticstemcells–ThesearepresentWithinthebonemarrow.These
cellsgiverisetoothercells,includingwhitebloodcells,redbloodcells,
andplatelets. 14

15. 15

16. 16
(CYP2R1gene)
DIET
(25-hydroxyvitaminD) / Calcifediol
1,25-dihydroxyvitamin D
(↓Melanin↑)
Sources of Vitamin D3
(Natural
Cholecalciferol)
•Oily fish and fish oil
•Liver
•Egg yolk
•Butter
•Dietary supplements
Sources of Vitamin D2
(Ergosterol→ UVB→
Ergocalciferol)
•Mushrooms (grown
in UV light)
•Fortified foods
•Dietary supplements
UVA
UVB
UVC
(Cholecalciferol)
(Ergocalciferol)
(storage type of vitamin D , Measured in serum to vitamin D status)
•1,25(OH)2Dcirculating in blood as a hormone
•1,25-(OH)2Dfeedback negatively on itself
Inactive
water soluble
compound that is
excreted inbile
Vitamin D Metabolism

17. 17
Phosphate homeostasis
Fibroblast growth factor 23
(Calcidiol)
(Calcitriol)

18. PathophysiologyofOsteoporosis
•Underphysiologicconditions,boneformationandresorptionareina
fairbalance.
•Thehallmarkofosteoporosisisa
Reducedtotalbonemass.Normalhomeostaticboneturnover
isaltered.Followingchangemayresultinosteoporosis
→Increasedboneresorption(↑Osteoclastaction)
→Decreasedboneformation(↓Osteoblastsaction)
18

19. 19
OsteoclasticBone Resorption
(Bone Removal Performed by
Osteoclasts)
OsteoblasticBone Apposition
(Bone Formation Performed by
Osteoblasts)
Disbalance
Balance

20. 20
Progression.Thebonesbecomeporous,brittle,fragile;theyfracture
easilyunderstressesthatwouldnotbreaknormalbone.
Posturalchanges.Theposturalchangesresultinrelaxationofthe
abdominalmusclesandaprotrudingabdomen.
Age-relatedlosses.Calcitoninandestrogendecreasewithaging,
whileparathyroidhormoneincreases,increasingboneturnoverand
resorption.
Consequence.Theconsequenceofthesechangesisnetlossofbone
massovertime.

21. Etiology
PrimaryorSecondary
ClassificationofOsteoporosis
•Primaryosteoporosis(Idiopathicosteoporosis/doesnothavedirectcause)
Postmenopausalosteoporosis(typeI)
Age-associatedorsenileosteoporosis(typeII)
•Secondaryosteoporosis
Medicalconditions
Medications
21

22. Primaryosteoporosis
•Postmenopausalosteoporosis(typeI)
•Causedbylackofestrogen
•CausesPTHtooverstimulateosteoclasts
•Excessivelossoftrabecularbone(spongybonewhereallbloodcells
made)
•Age-associatedosteoporosis(typeII)
•Bonelossduetoincreasedboneturnover
•Malabsorption
•Mineralandvitamindeficiency
22

23. SECONDARYOSTEOPOROSIS
23
Acromegaly(pitutarygrowth hormone )
Addison’s disease (adrenal gland hormone)
Amyloidosis(abnormal protein)
Anorexia
COPD
Hemochromatosis(Iron)
Hyperparathyroidism
Lymphoma and leukemia
Malabsorptionstates
Multiple myeloma (plasma cell cancer)
Multiple sclerosis
Rheumatoid arthritis
Sarcoidosis (inflammatory cells)
Severe liver disease
Thalessemia
Thyrotoxicosis
A. Medical conditions / Disease states

24. B. Medications / Drugs
24
Aluminum
Anticonvulsants
Excessive thyroxine
Glucocorticoids (steroids)*
GnRHagonists
Heparin
Lithium
*Called as steroid induced or glucocorticoid-induced osteoporosis.

25. Riskfactors
Age.aspeoplegrowolderandtheirboneslosetissue.
Gender.Womenaresmallerandstartoutwithlessbone.Theyalsolose
bonetissuemorerapidlyastheyage.Whilewomencommonlylose30-50%
oftheirbonemassovertheirlifetimes,menloseonly20-33%.
Race.CaucasianandAsianwomenaremostatriskforthedisease,but
AfricanAmericanandHispanicwomencangetittoo.
Figuretype.Womenwithsmallbonesandthosewhoarethinaremore
liabletohaveosteoporosis.
Heavymetals:Astrongassociationbetweencadmiumandleadwithbone
diseasehasbeenestablished.Low-levelexposuretocadmiumisassociated
withanincreasedlossofbonemineraldensityreadilyinbothgenders,
leadingtopainandincreasedriskoffractures,especiallyintheelderlyandin
females.Highercadmiumexposureresultsinosteomalacia(softeningofthe
bone).
25

26. Softdrinks:Somestudiesindicatesoftdrinks(containphosphoricacid)
mayincreaseriskofosteoporosis,atleastinwomen.Others suggest
softdrinksmaydisplacecalcium-containingdrinksfromthedietratherthan
directlycausingosteoporosis.
Earlymenopause.Womenwhostopmenstruatingearlybecauseof
heredity/surgery/lotsofphysicalexercisemayloselargeamountsof
bonetissueearlyinlife.
Lifestyle.Peoplewhosmokeordrinktoomuch,ordonotgetenough
exercisehaveanincreasedchanceofosteoporosis.
Diet.Thosewhodonotgetenoughcalcium/proteinorhaveVitaminD
deficiencymaybemorelikelytohaveosteoporosis.
Genetics.ResearchinEuropereportedin2003thatvariationsofagene
onchromosome20mightmakesomepostmenopausalwomenmorelikely
tohaveosteoporosis.
26

27. Clinical Manifestations
Asymptomatic(Osteoporosisitselfhasnosymptoms)
Symptomsappearduetofracturedorcollapsedvertebra
AcuteandChronicpainintheelderly
FragilityFractures(Abonefracturethatoccursmuchmoreeasilythan
expected)
(Thefirstclinicalmanifestationofosteoporosismaybefractures,which
occurmostcommonlyascompressionfractures)
Astoopedposture/Kyphosis(Thegradualcollapseofavertebrais
asymptomatic,andiscalledprogressivekyphosisor“dowager’s
hump”associatedwithlossofheight.
Lossofheightovertime
Reductioninmobility
27
Even a sneeze or a sudden movementmay be enough to break a bone in someone with severe osteoporosis.

28. Osteoporosis
Micro Fractures
Normal bone Osteoporotic
bone
Micro-fracture
28

29. Posture change
(stooped posture)
Dowager's hump
29

30. The vertebrae
collapse down on
themselves,andthe
personactuallyloses
height.Thesechanges
bringaboutalossofas
muchas6to9inchesin
height
widow‘s hump
Hunchback
appearance
30

31. Osteoporoticfracturesoccurinsituationswherehealthy
peoplewouldnotnormallybreakabone.
Typicalfragilityfracturesoccursin
•VertebralColumn
•Rib
•Wrist
•Hip
Fragility fractures
31

32. Vertebra Fractures
32

33. Wrist Fractures (Colle’sfracture)
Fractureof the distal forearm in which the broken end of the radius is bent backwards.
33

34. Hip Fractures
Intertrochantericfracture
34

35. Investigations
•Radiography(X-rayofbones)
(Maybeundetectableonroutinex-raysuntiltherehasbeen25%to40%demineralization)
•BoneMineralDensity(BMD)
ThemostpopularmethodofmeasuringBMDisDual-energyx-rayabsorptiometry(DEXA).
•SerumCalcium,phosphate,VitaminD
•LFT,KFT,Protein,Albumin
•Bonemarkers
• Markersfortheboneformations(OsteocalcinBonespecificAlk.Phosphatase,Procollagen
extensionpeptides)
• Markersforboneresorption(Tartrate-resistantacidphosphatase,Urinarycalcium,Urinary
hydroxyproline,Urinaryhdroxyproline/creatinineratio,Urinarypyridinoline/deoxypyridinoline,
UrinaryN-telopeptide
•OtherBloodtestsaccordingtopathology(CBC,Electrolytes,Urineetc)
35

36. Ultrasound Densitometry
Dual-energy X-ray absorptiometry
36

37. W.H.O. Criteria for Diagnosis of Osteoporosis
Bone Mineral Density (BMD)
Category
T-scorerange
Expressed in grams per cm
2
(g/cm
2
)
Normal ≥−1.0
Osteopenia −1.0to−2.5
Osteoporosis ≤−2.5
Severeosteoporosis ≤−2.5withfragilityfracture
Tscore–numberofSDsapatient’sBMDdeviatesfromareference
populationofnormalyoungadults
Zscore–numberofSDsapatient’sBMDdeviatesfromareference
populationofsubjectsofthesameageandsex
ZscoresindicatewhethertheBMDresultisexpectedforthepatient’s
age.Ifitismuchlessthanexpected,suspectasecondarycauseof
osteoporosis(use–2asacutoff)
37

38. 38
Comparison of Bone pathology
Condition Calcium Phosphate
Alkaline
phosphatase
Parathyroid
hormone
Comments
Osteopenia Unaffected Unaffected Normal Unaffected
Decreased Bone
Mass
Osteopetrosis
(extremely
rareinheriteddisorder)
Unaffected Unaffected Elevated Unaffected
Thick Dense Bones
Also Known As
Marble Bone
Osteomalacia
andRickets
(Vitamin D deficiency)
Decreased Decreased Elevated Elevated Soft Bones
Osteitisfibrosa
cystica
(overproduction of PTH)
Elevated Decreased Elevated Elevated Brown Tumors
Paget's disease of
bone
(Viral/ Genetic)
Unaffected Unaffected
Variable (Depending
On Stage Of Disease)
Unaffected
Abnormal Bone
Architecture
Inosteoporosis,thebonesareporousandbrittle,whereasinosteomalacia,thebonesaresoft.Thisdifferenceinbone
consistencyisrelatedtothemineral-to-organicmaterialratio.Inosteoporosis,themineral-to-collagenratioiswithinthereferencerange,
whereasinosteomalacia,theproportionofmineralcompositionisreducedrelativetoorganicmaterialcontent.(normalhumanskeletonis
composedofamineralcomponent,calciumhydroxyapatite(60%),andorganicmaterial,mainlycollagen(40%).)

39. Management
39
1.Preventiveaspectofosteoporosis
2.Therapeuticaspectofosteoporosis
20
th
Oct
WorldOsteoporosis Day
APIMedicine-
• Bonesubstanceismadeoutofproteinandmineral
• So.thefoundationofanypreventiveortherapeuticregimenisanadequatedietaryintakeof:
 Highqualityprotein
 Calcium
 Phosphorus
• Thevariousantiresorptiveandanabolicagentsavailabletodatearenotcapableofstopping
bonelossorproducingbonegainifthepatientisinnegativenitrogenandmineralbalance
becauseofinadequateintakeofthesenutrients

40. PREVENTION OF OSTEOPOROSIS
•Exposuretosunlight–30minsperday,5days/week
•Diet-Adequateinprotein,totalcalories,calciumandvitaminD.
Proteinintake1gm/kgbodyweight/day
Phosphorus(700mg/day)
•Cessationofsmoking-Tobaccosmokinghasbeenproposedtoinhibittheactivityof
osteoblasts.Smokingalsoresultsinincreasedbreakdownofexogenousestrogen,lowerbodyweight
andearliermenopause,allofwhichcontributetolowerbonemineraldensity.
•Decreasedcaffeineintake-≤2.5cupsofcoffeeor≤5cupsofteaperday
•StoporreduceAlcoholintake-Althoughsmallamountsofalcoholareprobablybeneficial(bone
densityincreaseswithincreasingalcoholintake),chronicheavydrinking(alcoholintakegreaterthan
threeunits/day)probablyincreasesfractureriskdespiteanybeneficialeffectsonbonedensity.
•Fallprevention
AdequateSpinalSupport–avoidbracesorcorsets,rigidandexcessiveimmobilization
UseofhipProtectors
40

41. 41
WOMEN AND MEN 1 mcg = 40 units
Under age 50 400-800 international units (IU) daily**
Age 50 and older 800-1,000 IUdaily**
**The safe upper limit of vitamin D is 4,000 IUper day for most adults
VITAMIN D
•ERGOCALCIFEROL -D2
•CHOLECALCIFEROL -D3
VitaminDandAnalogs
•Antihypocalcemic—Alfacalcidol;Calcifediol;Calcitriol;Dihydrotachysterol;
Ergocalciferol;
•Nutritionalsupplement(vitamin)—Calcifediol;Calcitriol;Ergocalciferol;
•Antihypoparathyroid—Calcitriol;Dihydrotachysterol;Ergocalciferol;
•Antihyperparathyroid—Doxercalciferol;Paricalcitol;

42. 42
• WOMEN
Age 50 & younger 1,000 mg* daily
Age 51 & older 1,200 mg* daily
• MEN
Age 70 & younger 1,000 mg* daily
Age 71 & older 1,200 mg* daily
*The safe upper limit of Calciumis 2000 mg for adults ages > 19 years
CALCIUM
•Calciumrichedfoods-Milk,yogurt,Butter(cheese),Kale,broccoli,Greenleafyvegetables,almonds,Fish(withsoft
bones,Oilyfish,Fishoils)
•Avail-Calciumcarbonate,Calciumsulphate,Calciumcitratemaleate,Ioniccalcium,MCHC(microcrystalline
hydroxyapatite–aunicformofcalciumfromwholeanimalbone)
•Allcalciumsaltsmustbetakeninterruptedat3weeksforaintervalof10days&continuedfor3weeks.
•Calciumcarbonateandcalciumcitratearethetwomostcommonlyusedformsofcalcium.
•Calciumcitrateproductscanbetakenonanemptystomachorwithfood,whilecalciumcarbonateproductsshouldbe
takenwithmeals.
•Calciumcarbonateprovides40percentelementalcalcium;theother60percentisthecarbonateingredient.Therefore,
600milligrams(mg)ofcalciumcarbonateprovides240mgelementalcalcium.
•Calciumcitrateis20percentelementalcalcium;600mgofcalciumcitrateprovides120mgelementalcalcium.
•Osteoporosisbycorticosteroid:Divideddailydosesof0.5-1gramofelementalcalciumdaily.

43. 43
Weight-bearing physical activity
and exercises
Improvesbalanceandposturecanstrengthenbonesand
reducethechanceofafracture.
Themoreactiveandfityouareasyouage,thelesslikelyyou
aretofallandbreakabone.
HighImpactPhysicalActivity:
Jogging–Significantlyincreasesbonedensityinmen
andwomen
Stairclimbing–increasesbonedensityinwomen
RegularExercises–helpstoincreasestrengthand
reducetheriskoffalling
WeightTraining–helpfultoincreasemusclestrengthas
wellasbonedensity
BalanceExercises-reducefalls.
Corner
stretch
Hip abductor strengthening
Prone leg lifts
Toe raises/heel raises
Wall slide

44. 44
MODERN MANAGEMENT
OF OSTEOPOROSIS
•AntiresorptiveMedications-Acategoryofmedicationsthatslowsthebreakdownof
bone.Thesemedicationsprotectbonemineraldensityandreducetheriskoffractures.
Bisphosphonates-Etidronate,Alendronate,Risendronate,Ibandronate,
PamidronatemZolidronate
RANKligand(RANKL)inhibitor-Denosumab
Calcitonin-Salmoncalcitonin
HormoneReplacementTherapy-Estrogen
SERMs(selectiveestrogenreceptormodulators/Estrogenagonist-antagonist)-
Raloxifene
TissueSpecificEstrogenComplex(TSEC)-Estrogen/Bazodoxifene
•AnabolicMedications-Acategoryofmedicationsthathelpsbuildbone.
ParathyroidHormone(PTH)Analog–Teriparatide
SclerostinInhibitor-Romosozumab-aqqg
ParathyroidHormone-RelatedProtein(PTHrp)Analog-Abaloparatide
(Drug Therapy)

45. 45

46. 46
Bisphosphonatesshouldbeusedasfirst-linepharmacologictreatment.Inpatientswhocannot
tolerateorwhosesymptomsdonotimprovewithbisphosphonatetherapy,teriparatide(Forteo)
anddenosumab(Prolia)areeffectivealternativemedicationstopreventosteoporoticfractures.
Bisphosphonates
Theyarecompoundsthatspecificallybindtothehydroxyapatite
crystalsonbonesurfacesandinhibitosteoclastfunctions.
•Etidronate-Firstbisphosphonate(Avail-200mg,400mg)
Dose-11–20mg/kg/day;max3months,Retreatafter3etidronate-freemonths
Giveoncedaily(preferred)orindivideddosesatleast2hrsbeforeorafterfood.
Takewithafullglassofwaterinuprightposition;donotliedownafterwards.
Use-TreatmentofsymptomaticPaget'sdiseaseofbone.Preventionandtreatmentof
heterotopicossificationaftertotalhipreplacementorduetospinalcordinjury.
Adv.Effect-Diarrhea,nausea,musculoskeletalpain,esophagitis,esophageal
ulcers/erosions,gastritis(maybesevere);osteomalacia,bonefractures,jaw
osteonecrosis.

47. 47
•Alendronate(Alendronicacid)-Avail-70mg;35mg;40mg;5mg;10mg;70mg/75mL
Dose–Treatment-10mgorallyonceadayor70mgorallyonceaweek
Prevention-5mgorallyonceadayor35mgorallyonceaweek\
(Alendronate/cholecalciferol-70mgplus2,800IUor5,600IUperweek,oral)
USE-Osteoporosiscausedbymenopause,steroiduse,orgonadalfailure,Paget's
diseaseofbone,highriskofbonefractureduetoosteoporosis.
Adv.Effect-Decreasedserumcalciumanddecreasedserumphosphate.Abdominal
orstomachpain,arthralgia,myalgiaetc.
•Risendronate
Dose–Orally5mg/day0r35mg/weekor75mgtwoconsecutivedays/monthor150mg/month(Risedronate
withcalcium-35mgperweek(day1)plus1,250mgcalciumperday-days2to7eachweek)
Risedronatewithcalcitriol+calciumcarbonate+Zinc
•Ibandronate(Ibandronicacid)–Avail-2.5mg;150mg;3mg/3mL
Dose–Orally150mg/monthor2.5mg/day
IV–3mgevery3months(over15to30seconds)
Ibandronicacid(150mg)withcalciumcarbonate(1250mg)+calcitrion(0.25mg)+VitMK(50mcg)+Zinc
(7.5mg)

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•Pamidronate-Avail-30mg/10mLor90mg/10mL
Dose–60to90mggivenasaSINGLE-DOSEIVinfusionover2to24hours
Paget’sDisease–IV30mgdaily,for3consecutivedays(totaldoseof90mg)
OsteolyticBoneLesionsofMultipleMyeloma–IV90mg/monthly
OsteolyticBoneMetastasesofBreastCancer–IV90mg/every3to4weeks.
USE-HypercalcemiaofMalignancy,OsteolyticBoneMetastasesofBreastCancer
andOsteolyticLesionsofMultipleMyeloma,Paget’sDisease
Adv.Effect-Flu-likesymptoms;mildfeversometimesaccompaniedbymalaise,
chills,fatigueandflushingetc
•Zolidronate-Avail-4mg;4mg/5mL;5mg/100mL;4mg/100mL
Dose–5mgIVinfusionovernolessthan15minutes,onceayear
HypercalcemiaofMalignancy-Singledoseof4mgIVinfusion
OsteolyticBoneMetastasesofSolidTumors-4mgIVevery3to4weeks
Adv.Effect–Agitation,black/tarrystools,blurredvision,chestpain,coma,confusion,
convulsionsetc

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RANKligand(RANKL)inhibitor
RANK(ReceptoractivatorofnuclearfactorκB)isactivatedbytheRANK-Ligand
(RANKL),whichexistsascellsurfacemoleculesonosteoblasts.ActivationofRANKby
RANKLpromotesthematurationofpre-osteoclastsintoosteoclasts.Denosumabinhibits
thismaturationofosteoclastsbybindingtoandinhibitingRANKL.
•Denosumab
Dose–60mgSCevery6months,Supplementwithcalcium1000mg/day
andvitaminD400IU/day
(HypercalcemiaofMalignancy120mgSCevery4weeks,Give2additional120
mgdosesduringthefirstmonthoftherapyonDays8and15)
USE–Osteoporosis,Womenwithbreastcancer,HypercalcemiaofMalignancy
Adv.Effect-Backpain,Seriousinfectionofabdomen,UTI,Pancreatitisetc

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CALCITONIN
Calcitoninproducedinhumansbytheparafollicularcells/C-cellsofthethyroid
gland.Itinhibitsboneresorptionbyosteoclastsandpromotesboneformationbyosteoblasts.
Thisleadstoanetincreaseinbonemassandareductioninplasmacalciumlevels.Italso
promotestherenalexcretionofionssuchascalcium,phosphate,sodium,magnesium,and
potassiumbydecreasingtubularreabsorption.
•CalcitoninSalmon(Calcitoninwasextractedfromtheultimobranchialglands
(thyroid-likeglands)offish,particularlysalmonfish)
Avail-Nasalspray,Injection(SC/IM)
USE&DOSE-Hypercalcemia(4-8IU/kgevery12hours)
Post-menopausalosteoporosisinwomen>5yearspost-menopause(100IU/day)
SymptomaticPaget'sdisease(100IU/day)
Spray-onceaday,alternatingnostrilseveryday
Adv.Effect–Runnynose,nosebleed,sinuspain,Hivesetc
Addcalcium(1000mg/day)andvitaminD(400IU/day)withthis.

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HORMONE REPLACEMENT THERAPY(HRT)
•Estrogentherapy(ET)aloneorEstrogen+Progesterone
HRTrestorestheCa2+balance,Bonelossisprevented
HRTisparticularlyusefulforwomenwhohaveundergoneearlymenopause(before
45yearsofage)
Administeredorallyortransdermally
Doses:Oralestrogens(Lowesteffectivedose)+Progesterone2.5mg/d(ifuterus
present)
Esterifiedestrogens-0.3mg/d
Conjugatedequineestrogens-0.625mg/d
Ethinylestradiol–5mcg/d
Transdermalestrogen-50mcgestradiolperday.
Adv.Effect–Bloating,Breastswellingortenderness,Headaches,Mood
changes,Nausea,Vaginalbleeding

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SERMs(selectiveestrogenreceptormodulators)
SERMsare"selective"—thismeansthataSERMthatblocksestrogen'saction
inbreastcellscanactivateestrogen'sactioninothercells,suchasbone,liver,anduterine
cells.
•Raloxifene
Raloxifenemediatesanti-estrogeniceffectsonbreastanduterinetissues,
andestrogeniceffectsonbone,lipidmetabolismandbloodcoagulation.
Dose-60mg/dayOral(tablet)
Use-Osteoporosisinpostmenopausalwomen,Osteoporosiscausedby
glucocorticoidandbreastcancer.
Adv.Effect–Hotflashes,flusyndrome,cramps/musclespasm,infection,
insomniaetc
Anti-estrogeniceffectsonbreast-Thecelldoesn'treceiveestrogen'ssignalstogrowandmultiply.

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Tissueselectiveestrogencomplex(TSEC)
Atissue-selectiveestrogencomplex(TSEC)isacombinationof
anestrogen,suchasestradiolorconjugatedestrogens,andaselectiveestrogen
receptormodulator(SERM),suchastamoxifen,raloxifene,orbazedoxifene
•Bazedoxifene(BZA)withconjugatedEstrogens(CE)
BZA20mg/CE0.45mgandBZA20mg/CE0.625mghaveshownefficacyin
reducingthefrequencyandseverityofhotflushes,relievingVulvovaginal
atrophy,andmaintainingbonemasswhileprotectingtheendometriumand
breast.

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ParathyroidHormone(PTH)Analog
•Parathyroidhormoneanalogsarethesyntheticformofparathyroidhormone
•Highlevelsofparathyroidhormonetriggerstransferofcalciumfromthebonestothe
blood.Itincreasesabsorptionofcalciumbytheintestineandincreasesreabsorptionof
calciumbytherenaltubules.Alowlevelofparathyroidhormonereducescalciumlevels
intheblood.
•Teriparatide
Dose–20mcgsubcutaneouslyonceadayintothethighorabdominalwall
USE–Osteoporosis,Osteoporosiscausedbyglucocorticoid,Primary
Osteoporosis
Adv.Effect–nausea,jointaches,painetc

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SclerostinInhibitor
Sclerostinisanosteocyte-derivedglycoproteinthatinhibitsWnt/β-cateninsignalingand
activationofosteoblastfunction,therebyinhibitingboneformation.Inhibitorsof
sclerostincanstimulateboneformationbyallowingWnttobindtoLDLreceptor-related
proteins5and6
•Romosozumab
Use-Osteoporosisinpostmenopausalwomenathighriskoffractures.
Dose-210mgSConceamonth(administeredas2separateinjectionsof105mg
each-oneaftertheother)
Durationoftherapy:12months
Adv.Effect–Fastheartbeat,fever,hives,itching,skinrash,hoarseness,irritationetc

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ParathyroidHormone-RelatedProtein(PTHrp)Analog
•PTHrPactsasanendocrine,autocrine,paracrine,andintracrinehormone.
•Itregulatesendochondralbonedevelopmentbymaintainingtheendochondralgrowth
plateataconstantwidth.
•Italsoregulatesepithelial–mesenchymalinteractionsduringtheformationofthe
mammaryglands.
•Abaloparatide
Primarilyregulatescalciumhomeostasisandboneresorption
Use-Postmenopausalwomenwithosteoporosisathighriskforfracture
Dose-80mcgsubcutaneouslyonceaday
Adv.Effect–Constipation,depression,lossofappetite,lossofweight,muscle
weakness

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SURGERY
VertebroplastyandKyphoplasty(stabilizingcompressionfracturesinthespine)
•Vertebroplasty-Bonecementisinjectedintobackbones(vertebrae)thathave
crackedorbroken.Thecementhardens,stabilizingthefracturesandsupportingthe
spine.
•Kyphoplasty-Itinvolvesinsertingaballoondeviceintoafracturedvertebraand
inflatingittorestoretheheightofthevertebra.Thespaceisthenfilledwithbone
cement.

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