osteoporosis update

8/9/2019 Osteoporosis Update

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Osteoporosis Review



#ailure $o %ianose and $reat

• Studies show failure to dianosis and treatosteoporosis in older patients who ha&esuffered a fracture

• !n study of ' Midwestern health systems:

– ()* – ()' of hip fracture pts recei&ed +M%

testin – , - were i&en calcium)% supplements

– , ()(. treated with antiresorpti&e medications

US Department of Health and Human Services: Bone Health andOsteoporosis: A Report of the Surgeon General, Oce of theSurgeon General, 2004



/is" #actors

Ma0or • 1istory of fracture as an

adult

• #raility fracture in firstderee relati&e

• Caucasian)2sianpostmenopausal woman

• Low body weiht 3, (45 lb6

• Current smo"in

• 7se of oral corticosteroids 8

9 mo

2dditional• !mpaired &ision

• ;stroen deficiency at earlyae 3, '< =O6

• %ementia

• >oor health)frailty• /ecent falls

• Low calcium inta"e 3lifelon6

• Low physical acti&ity

• 8 4 alcoholic drin"s per day



#actors 2ssociated with +one Loss in Men

• ?enetics

• Smo"in)alcohol

• Calcium inta"e

• >hysicalacti&ity)strenth

• $estosteroneproduction

• ;stroen production



Medical Conditions 2ssociated with!ncreased /is" of Osteoporosis

• CO>%

• Cushin@s syndrome

• ;atin disorders

• 1yperparathyroidism

• 1ypophosphatasia

• !+S

• /2A other autoimmuneconnecti&e tissuedisorders

• !nsulin dependentdiabetes

• Multiple sclerosis

• Multiple myeloma

• Stro"e 3CB26

• $hyrotoicosis

•Bitamin % deficiency• Li&er diseases

Dot an inclusi&e list



%rus 2ssociated with/educed +one Mass

• 2luminum

• 2nticon&ulsants

• Cytotoic drus

• ?lucocorticosteroids3oral)hih dose inhaled6

• !mmunosuppresants

•?onadotropinEreleasinhormone 3e Lupron6

• Lithium

• 1eparin 3chronic use6

• Supraphysioloic

thyroine doses

• 2romatase inhibitors

• %epoE>ro&era

Dot an inclusi&e list



/is" 2ssessment)%ianosis

• 2fter menopauseA all women should be e&aluated clinicallyfor osteoporosis ris" to determine need for +M% testin

• <.EF.G of men with osteoporosis ha&e disorders "nown toreduce bone lossA such as hyperparathyroidismA intestinal

disordersA malinanciesA conditions resultin inimmobilization

• +M% recommended in men with "nown ris" factors andwho ha&e lost 8 (< inches in heiht

• %ianosis can be established in patients who ha&e ne&erhad a fraility fracture by +M% measurement



Horld 1ealth Oranization%ianostic Criteria

%!2?DOS!S +M% C/!$;/!2I• Normal within ( S% of a “youn normal”

adult 3$Escore at E(. and abo&e6

• Osteopenia between ( and 4< S% below

that of a “youn normal” adult3$Escore between E( and E4<6

• Osteoporosis 4< S% or more below that of a “younnormal” adult 3$Escore at or below E4<6

• Severe Osteoporosis 4< S% or more below that of a “youn normal”adult and fracture3s6

• $Escore is the number of S%s abo&e or below the a&erae +M% &alue for younAnormal adults of the same se

+M% J +one mineral density S% J Standard de&iation

IMeasured at the hipA spineA or wrist



Hho Should be $estedK

• %ecision to test based on indi&idual ris" profileAne&er indicated unless results influencetreatment decision

• +M% testin should be performed on:( 2ll women F< =O2 and older reardless of ris"factorsI

4 =ouner postmenopausal women with one or moreris" factors 3other than bein whiteA postmenopausal

and female69 >ostmenopausal women who present with fractures

3confirm dianosisA determine disease se&erity6

IMedicare permits repeat +M% testin e&ery 4 years



DO# – Clinician’s Guide to Prevention

and Treatment of Osteoporosiswww.nof.org

• /eleased 4)4().* 3pre&ious update in 4..96

• ?uidelines epanded to include 2fricanE2mericanA 2sianA

Latina and other postmenopausal womenA also addressesmen <. years and older

• %ramatically alters approach to assessin fracture ris" andtreatment

• Hill help identify people at hih ris" for de&elopinosteoporosis)fractures and ensure appropriate treatment

• 7ses absolute fracture ris" methodoloy to enhance treatment

decisions to indi&idualize plan for each patient



DO#@s Clinician’s Guide

• 2pplies the recently released alorithm on absolutefracture ris" call #/2M by the H1O

• 2lso called (.Eyear fracture ris" model and (.Eyearfracture probability

• ;stimates the li"elihood of a person to brea" a bone dueto low bone mass o&er a period of (. years

• Most useful to determine if treatment needed for thosewith low bone mass or osteopenia

• http:))wwwshefacu")#/2)tool0spKlocationBalueJ4



7ni&ersal /ecommendations

• 2deNuate inta"e of calciumA &itamin %

• HeihtEbearin and muscleEstrenthenin eercises toreduce ris" of falls)fracture

• >ro&ide strateies for fall pre&ention

• 2&oidance of tobacco use)ecessi&e alcohol use

• $al" to your pro&ider about bone health

• 1a&e a bone density test and ta"e medication whenappropriate



Calcium)% >roduct Selection

>roduct 3G elementalCa6 ;lementalCalcium3m6

Bitamin% 3units6 Comments

Calcium carbonate 3'.6

E$ums 7ltra

ECaltrate F.. >lusEOscal >lus %

EBiacti& Chews

'..

F..<..

<..

4..(4<

(..

/eNuires acidic en&ironment for dissolution anddisinteration +est to ta"e with meals

?reater ris" for constipation with carbonate

form

Calcium citrate 34'6

ECitracal >lus %

E Citracal >etites withBit%

9(<

4..

4..

4..

$a"e without reard to meals Ser&in sizeusually eNuals 4 capsules so label can be

misleadin to patients

Bitamin %

EMulti&itamin 3%96

EBitamin %

(4.E'<. '..

(..E'..



Bitamin % and #all /is"

• !n addition to its effect on +M%A may contribute to reduction in fractureris" – !mpro&ed muscle function – /eduction in ris" for falls

• MetaEanalyses of < clinical trials 38 F. =O26 showed sinificantreduction in ris" for fallin in those ta"in &itamin % plus calcium &ersusthose ta"in placebo

• Bitamin % deficiency pre&alent in older adult population – !nadeNuate sun eposureA use of sunscreen –

1omeboundA institutionalized – Dorthern latitudes

– Maintain 4<Ehydroy&itamin %9 at least 8 '. n)mL – $reatment: <.A... !7 &it% wee"ly FE* wee"sA then assess need for

chronic monthly therapy



/eular HeihtE+earin ;ercise

• %efined as those in which bones and muscleswor" aainst ra&ity as feet and les bear thebody@s weiht

• !nclude wal"inA 0oinA $aiEChiA stair climbinAdancinA tennisA yoa

• !mpro&e ailityA strenthA balance

• May increase bone density modestlyA reduce fallris"A enhance muscle strenthA impro&e balance



2&oidance of $obacco and 2lcohol

• $obacco products detrimental to s"eletonAo&erall health

• DO# stronly encouraes tobaccocessation prorams as osteoporosisinter&ention

• ;cessi&e alcohol inta"e also detrimental tobone health and reNuires treatment



Hho Should +e $reatedKNOF Recommendations – !!"

• !nitiate therapy to reduce fractures inpostmenopausal women)men 8 <. with:

( +M% $Escores , E4< at hip or spine

4 >rior &ertebral or hip fracture

9 Low bone mass 3$Escores E(. to E4< at hip orspine6 when:

– (.Eyear probability of hip fracture is 8 9G – (.Eyear probability of ma0or osteoporosisErelated

fracture is 8 4.G

– +ased on 7SEadapted H1O alorithm

wwwnofor



#%2E2ppro&ed %rus for Osteoporosis

• +isphosphonates – 2lendronateA 2lendronate

plus % 3#osamaA#osama >lus %6

– /isedronateA/isedronate withCalcium 32ctonel6

– !bandronate 3+oni&a6

• Selecti&e ;stroen/eceptor Modulators 3S;/Ms6 – /aloifene 3;&ista6

• Calcitonin 3MiacalcinMA#orticalMA Calcimar M6

• >arathyroid 1ormone >$1 3(E9'6AteriparatideP – #orteo

• ;stroen)1ormone$herapy 3;$)1$6 – >remarinA ;straceA

>rempro



+isphosphonates – 2ntiresorpti&e 2ents

• 2ents #%2Eappro&ed for: – >re&ention and treatment of osteoporosis in postmenopausal

women

– $reatment to increase bone mass in men with osteoporosis

– $reatment of lucocorticoidEinduced osteoporosis in men and

women recei&in lucocorticoids – $reatment of >aet@s disease of bone in men and women

• Mechanism: inhibits bone resorption by attachin to bonysurfaces underoin acti&e resorption and inhibitin actionof osteoclasts – Leads to increases in bone density and reduced fracture ris"



+isphosphonates – Clinical ;fficacy

• Controlled clinical trials indicate o&er 9E' year periodA alendronate Qbone mass and R incidence of &ertebralA hipA and all nonE&ertebralfractures by <.G

• Controlled clinical trials indicate risedronate Q bone mass and R ris" of&ertebral fractures by '.G and nonE&ertebral fractures by 9.G o&er9Eyear period

• !bandronate has been shown in controlled clinical trials to Q +M% andreduce the ris" of verte#ral fracture by <.G o&er 9Eyear period

• 2lendronate appears to be well tolerated and effecti&e for at least ten

years



+isphosphonates – %osin

• 2lendronateI – >re&ention

• < m >O daily• 9< m >O wee"ly

– $reatment• (. m >O daily• 5. m >O wee"ly• 5. m)4A*.. !7 &itamin

% >O wee"ly

• /isedronate

– >re&ention)$reatment• < m >O daily• 9< m >O wee"ly

• !bandronate – >re&ention)$reatment

• 4< m >O daily• (<. m >O monthly

– $reatment• 9 m !B e&ery 9 months

!"lendronate also availa#le in oral



+isphosphonates – 2dministration

• Must be ta"en at least oneEhalf hour before the first foodAbe&eraeA or medication of the day with plain water only3( hour prior for monthly ibandronate6

• Should only be ta"en upon arisin for the day

• $ablet should be swallowed with a full lass of water 3* oz6and patients should remain uprihtA wal"inA standinA orsittin for at least 9. minutes 3F. minutes for monthlyibandronate6

• Should supplement with calcium)&itamin % if dietary inta"einadeNuate



+isphosphonates – 2d&erse ;ffects

• 1ypocalcemia 3(*G6

• 1ypophosphatemia

3(.G6

• Musculos"eletal painAcramps – recent #%2

warnin

• ?astrointestinal – 2bdominal pain

– 2cid reflu

– %ypepsia – ;sophaeal ulcer

– ?astritis

• Osteonecrosis of the 0aw3!B bisphosphonates6

• Bisual disturbances 3rare6



+isphosphonates

Contraindications)>recautions• 2bnormalities of the esophaus which delay

esophaeal emptyinA such as stricture or achalasia

• !nability to stand or sit upriht for at least 9. minutes

• >atients at increased ris" of aspiration

• 1ypocalcemia – Should be corrected prior to initiatin therapy

• /enal insufficiency 3Dot recommended if CrCl , 9.E9< ml)min6



+isphosphonates – Missed %ose

• Once wee"ly alendronateA risedronate – $a"e on mornin after rememberinA then resume

once wee"ly on reularly chosen day

• Once monthly ibandronate – !f net dose 8 5 days awayA ta"e dose the mornin

followin the date remembered

• $hen return to oriinal schedule – !f net dose , 5 days awayA wait until net scheduled

dose• Must not ta"e two (<. m tablets within the same wee"



olendronic 2cid 3/eclast6

• 2ppro&ed for treatment of osteoporosis inpostmenopausal women in 2uust 4..5

• Sinle < m infusion i&en !B o&er 8 (< minutesAonce yearly

• Should still supplement with calcium)&itamin %

• May be ideal for those with ?! contraindications tothe oral formulations



>rice Comparison

%ru >rice

2lendronate 3#osama6

(. m once daily

5. m once wee"ly

5. m)4*.. !7 wee"ly

9. day supply: T54UU

9. day supply: T94UU3eneric6

9. day supply: T5U5.

/isedronate 32ctonel6

< m once daily

9< m once wee"ly

9. day supply: TF<UU

9. day supply: TF9UU

!bandronate 3+oni&a6

4< m once daily

(<. m once monthly

9. day supply: TF<UU

9. day supply: T5<UU

$$$drugstorecom



+isphosphonates

• Bery well tolerated in patients who adhere toproper administration techniNues

• >roper patient counselin for correctadministration is V;= to reduce ris" of ad&erseeffects and increase tolerability

• >lace in $herapy: should be considered firstElinefor pre&ention)treatment of osteoporosis inpatients with no contraindications



S;/Ms – /aloifene

• #%2Eappro&ed for: – >re&ention and treatment of osteoporosis in

postmenopausal women

• Mechanism: tissueEselecti&e acti&ityA actsas an estroen aonist on bone

– ;stroen antaonist on breastA uterus



/aloifene – Clinical ;fficacy

• /educes ris" of &ertebral fracture by 9.G inpatients with pre&ious spinal fractureA <<G inpatients without prior spinal fracture o&er 9 years

• !ncreases +M% at all s"eletal sites and reducestotal and L%L cholesterol

• Less potent antiresorpti&e aent thanbisphosphonatesA althouh direct comparisonstudies lac"in



/aloifene – %osin)2dministration

• #or pre&ention and treatment

– F. m >O once daily

• Can be ta"en any time of day withoutreard to meals

• Should supplement with calcium)&itamin %if dietary inta"e inadeNuate



/aloifene – 2d&erse ;ffects

• #reNuency 8 (.G – 1ot flashes

– 2rthralias

– Sinusitis

• #reNuency (E(.G – Chest pain

– !nsomnia

– Miraines

– >eripheral edema

– %iaphoresis

II1as been associated with increased ris" of thromboembolism3%B$A >;6 and superficial thrombophlebitisW ris" is similar to reportedris" of 1/$



/aloifene

Contraindications)>recautions• 1istory of %B$)>; or at hih ris"

• Cardio&ascular disease

• 1istory of uterine)cer&ical carcinoma• %iscontinue at least 54 hours prior to anddurin proloned immobilization

• >rice – 9.Eday supply J T*FUU

• Do eneric a&ailable



/aloifene

• >lace in $herapy: considered firstEline in womenwho cannot tolerate bisphosphonates and ha&eno contraindications to therapy

• Combination therapy 3usually a bisphosphonatewith a nonEbisphosphonate6 can pro&ideadditional small increases in +M% whencompared to monotherapy

• !mpact of combination therapy on fracture rateun"nown



;stroen)1ormone $herapy 3;$)1$6

• #%2 appro&ed for: – >re&ent osteoporosis

– $reatment of moderate)se&ere &asomotor

symptoms of menopause – $reatment of moderate)se&ere symptoms of

&ul&ar and &ainal atrophy associated withmenopause

– Consider topical preparations to treat &ainalsymptoms rather than oral ;$)1$



#%2 /ecommendations – ;$)1$

• Hhen prescribin medications for osteoporosisAphysicians should consider all nonEestroentherapies first

• Hhen prescribin ;$)1$A use smallest dose forshortest amount of time to achie&e treatmentoals

• >rescribe ;$)1$ products only when benefitsbelie&ed to outweih ris"s for a specific patient



Calcitonin

• #%2Eappro&ed for: – $reatment of osteoporosis in women who are 8 < years

postmenopausal – $reatment of >aet@s disease of bone

– 2d0uncti&e therapy for hypercalcemia

• Mechanism: – >eptide composed of 94 amino acids which binds to

osteoclasts and inhibits bone resorption – >romotes the renal ecretion of calciumA phosphateA

sodiumA manesium and potassium by decreasintubular reabsorption



Calcitonin – Clinical ;fficacy

• 1as been shown to increase spinal bone massand may decrease ris" of &ertebral fracture

• Conflictin data on efficacy of calcitonin at sitesother than the spine

• Less effecti&e than bisphosphonates in treatmentof osteoporosis

• +eneficialA shortEterm effect on acute bone painafter osteoporotic fracture 3&ertebral6



Calcitonin – %osin)2dministration

• !ntranasal – 4.. units 3( spray6 alternatin nares daily – Store unopened bottles in refrieratorA protect from freezin – Can store open bottles at room temperature for up to 9< days – 2cti&ate pump of new bottles until full spray produced 3allow to reach

room temperature before primin6

– ;ach bottle contains at least 9. doses

• !M)SX – (.. units)e&ery other day 3minimum effecti&e dose not wellEdefined6 – Should perform s"in test prior to initiatin therapy

• Should supplement with calcium)&itamin % if dietary inta"einadeNuate



Calcitonin – 2d&erse ;ffects

• Most common: – Dasal spray: rhinitis 3(4G6A irritation of nasal

mucosa 3UG6A epistais 39<G6A sinusitis

349G6A bac" painA arthraliaA headache – !n0ection: nausea 3(.G6A flushin 34E<G6

• $emporarily withdraw use of nasal spray if

ulceration of nasal mucosa occurs• >eriodic nasal eaminations recommended



Calcitonin

• Contraindications – Clinical allery to calcitoninEsalmon

• >recautions

– Dasal ulcerations – $achyphylais 3parenteral dosae forms6

• %ru interactions – Do formal studies desined to e&aluate %!

• >rice per month – 4.. units)mL 346: T'4.*

– 4.. units)2C$ 3956: T*(<U



Calcitonin

• Balid option for treatment of establishedosteoporosisA especially when accompanied byfracture pain

• >lace in therapy: because of costA ad&erseeffectsA incon&enience of nasal administrationA

recommend usin calcitonin until pain is no lonera problem and then switchin to abisphosphonate for lonEterm therapy



>arathyroid 1ormone >$1 3(E9'6P $na#olic agent

• #%2Eappro&ed for: – $reatment of osteoporosis in postmenopausal women at hih ris"

for fracture• pre&ious osteoporotic fractureA multiple ris" factors for fractureA

etremely low +M% 3, E4<6A or failed)intolerant to pre&ious treatment

– $reatment of primary or hypoonadal osteoporosis in men at hihris" of fracture

• Mechanism: recombinant formulation of endoenous

parathyroid hormone 3>$16 – stimulates osteoblast functionA increases astrointestinal calciumabsorptionA increases renal tubular reabsorption of calcium

– ;nhances bone turno&er by initiatin reater bone formation



>$1 3(E9'6 – Clinical ;fficacy

• Shown to decrease the ris" of new &ertebralfractures by F<G and non&ertebral fractures by<9G &ersus placebo after median eposure of (Umonths

• !ncreases lumbar spine +M% as well as at thefemoral nec"A total hipA and total body

• SafetyA efficacy of >$1 3(E9'6 has not beendemonstrated beyond 4 years of treatment



>$1 3(E9'6 – %osin)2dministration

• 4. Y SX once daily for treatment of osteoporosis – $hih or abdominal wall

• #orteoM

prefilled pen contains 4* daily doses

• !mportant to read Medication ?uide and 7ser Manualbefore startin and each time medication refilled

• Should be administered initially under circumstanceswhere the patient can immediately sit or lie downA in thee&ent of orthostasis 3dizzinessA palpitations are transient6



>$1 3(E9'6 – 2d&erse ;ffects

• Most common – %izzinessA rashA nauseaA headacheA le crampsA arthraliaA rhinitisA

transient hypercalcemia

• S)s of hypercalcemia: nauseaA &omitinA constipationA loweneryA or muscle wea"ness

• Most ad&erse effects in the clinical trials were mild andenerally did not lead to the discontinuation of the dru

• Osteosarcoma ris" in animals – Lead to blac" bo warnin by #%2



>$1 3(E9'6 – Harnins)>recautions

• !ncreased ris" of osteosarcoma 3rats6 – clinicalrele&ance un"nown 3no ecess reports inhumans6

• 2&oid in: – >aet@s disease of bone

– >rior radiation therapy to s"eleton

– +one metastases – 1ypercalcemia

– 1istory of s"eletal malinancy

– >renant)nursin



>$1 3(E9'6 – >rice

• OneEmonth supply T<9UUU

• Lilly offers #orteo >atient 2ssistance >roram for MedicareEeliible3LillyMedicare2nswers6 and nonEMedicare eliible patients

• LillyMedicare2nswers intended for patients who are enrolled in anyMedicare >art % prescription dru plan and who meet certaineliibility reNuirements – ;pected to start early 4..5

• #or nonEMedicare patientsA application process includes paper

application and income restrictions

• Call (E*55E5U<E'<<U or &isit wwwlillycom for more details



>$1 3(E9'6

• %ue to safety concernsA >$1 treatment should belimited to those most se&erely affected and for amaimum of two years

• Combination therapy with a bisphosphonate notrecommended as effects do not appear additi&e

• CostA daily SX in0ection may be prohibiti&e forsome patients



>$1 3(E9'6

>lace in $herapy:

• /ecommend >$1 for women or men with se&ere osteoporosis 3lowbone mineral density $Escore , E4<P and at least one frailityfracture6 who are refractory to or unable to tolerate bisphosphonatetherapy

• !n patients considered to be bisphosphonate ZfailuresAZ >$1 may bestarted approimately 9 months after bisphosphonates arediscontinued

• 2ntiresorpti&e therapy may be considered after discontinuation of>$1 to maintain ains in +M% acNuired with >$1 alone in those athih ris" for subseNuent fracture



2pproaches to Monitorin $herapy

• 2lways important to as" patients about adherenceAencourae continuation of therapies to reduce fracture ris"

• Monitorin of therapy should be consideredA as up to ()Fof women ta"in effecti&e therapies continue to lose boneAespecially if they smo"e

• May measure bone mineral density at a sinle site afterone year of therapyA but results may be misleadinW

usually done e&ery 4 years

• %rus may decrease a patient@s ris" for fracture e&enwhen there is no apparent increase in +M%



• 2C/ recommends the followin inter&entions inpatients ta"in prednisone doses of < m)day orhiher for more than 9 months

– Calcium)&itamin % 3(<..m)dayA *.. !7)day6 – Hee"ly formulations of bisphosphonate therapy

– /eplacement of onadal steroids in menA if deficient

– Calcitonin therapyA if bisphosphonates contraindicatedor not tolerated

– #ollow +M% to assess if bone loss continues

?lucocorticoidE!nduced Osteoporosis –/ecommendations



1ow Can 1ealth >rofessionals !mpro&e+one 1ealthK

To help patients maintain strong, healthy bones, health care professionals should:

• !ndentify and assist in recommendin appropriate treatment forindi&iduals at hih ris" for osteoporosis and other bone disorders

• /econize ris" factors that warrant osteoporosis screenin

• 2ssess diet)lifestyle for effect on bone health

• 2d&ise patients to ta"e acti&e steps to ensure bone health

• +e familiar with treatment of osteoporosis)low bone mass

• 2cti&ely loo" for other bone disease that can lead to bone loss)fractures



/eferences

• 2ctonelM >rescribin !nformation 3wwwactonelcom6• 2nn !ntern Med (UU.W((4:9<4

• 2nn !ntern Med 4..FW('':5<9

• +oni&aM >rescribin !nformation 3wwwboni&acom6

• Clinical /e&iews in +one and Mineral Metabolism4..'W43'6:4U(

• ;&istaM >rescribin !nformation 3wwwe&istacom6

• #orteoM >rescribin !nformation 3wwwforteocom6

• #orticalM >rescribin !nformation 3wwwforticalcom6

• #osamaM >rescribin !nformation 3wwwfosamacom6



/eferences

• [2M2 4..'W4U(3(F6:(UUU• [ Clin %ensitom 4..'W53(6:(EF

• [ 2m 2cad Orthop Sur 4..FW(':9'5

• MiacalcinM >rescribin !nformation 3wwwmiacalcincom6

• /eclastM >rescribin !nformation 3wwwreclastcom6• Dational Osteoporosis #oundation 3http:))wwwnofor6

• D;[M 4..9W9'*:((*5

• D;[M 4..'W9<.3(46:((*UEUU

• Osteoporosis !nt (UU*W*:(

osteoporosis update

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