Osteoporosis Residents 7 11 12 late.ppt - srfmr.org · 7/12/2012 1 OSTEO POROSIS Resident Lecture...
7
7/12/2012 1 OSTEO OSTEO POROSIS POROSIS Resident Lecture Resident Lecture Lisa Ward, MD, MSPH, MS Lisa Ward, MD, MSPH, MS July 11, 2012 July 11, 2012 Outline for Osteoporosis Outline for Osteoporosis Epidemiology Epidemiology Guidelines for Screening Guidelines for Screening Screening Tools and Pitfalls Screening Tools and Pitfalls Treatment Options Treatment Options Vitamin Supplements & Other Vitamin Supplements & Other Prevention Prevention Poole, K. E S et al. BMJ 2006;333:1251-1256 Figure 1. Epidemiology of osteoporotic fractures Figure 1. Epidemiology of osteoporotic fractures in men and women. in men and women. Impact of Fractures Impact of Fractures Fractures caused by osteoporosis Fractures caused by osteoporosis affect 1 in 2 women and 1 in 5 men affect 1 in 2 women and 1 in 5 men over 50 years of age over 50 years of age Results in permanent disability in Results in permanent disability in over 30% of those with fracture over 30% of those with fracture After hip fracture, nearly 20% will die After hip fracture, nearly 20% will die within 1 year within 1 year Prevalence of death is twice as high in Prevalence of death is twice as high in men men Over 50% of survivors will not return Over 50% of survivors will not return to independent living to independent living A Case of Osteoporosis… A Case of Osteoporosis… 57 year old Caucasian woman with breast 57 year old Caucasian woman with breast cancer s/p left lumpectomy & chemotherapy at cancer s/p left lumpectomy & chemotherapy at 35; then right breast cancer s/p mastectomy and 35; then right breast cancer s/p mastectomy and chemotherapy at 40. chemotherapy at 40. Early menopause started at 40 years of age. Early menopause started at 40 years of age. Normal DEXA at age 45, then diagnosed with Normal DEXA at age 45, then diagnosed with osteoporosis by heel scan at age 50 years. osteoporosis by heel scan at age 50 years. DEXA May 2012 DEXA May 2012 Osteopenia T Osteopenia T-score score -1.6 to 2.0) 1.6 to 2.0) FRAX Score June 2012 FRAX Score June 2012 1.0% @ hip, 7.6% total 1.0% @ hip, 7.6% total Screening Screening
Transcript of Osteoporosis Residents 7 11 12 late.ppt - srfmr.org · 7/12/2012 1 OSTEO POROSIS Resident Lecture...
7/12/2012
1
OSTEOOSTEOPOROSISPOROSIS
Resident LectureResident Lecture
Lisa Ward, MD, MSPH, MSLisa Ward, MD, MSPH, MS
July 11, 2012July 11, 2012
Outline for OsteoporosisOutline for Osteoporosis
�� EpidemiologyEpidemiology
�� Guidelines for ScreeningGuidelines for Screening
�� Screening Tools and PitfallsScreening Tools and Pitfalls
�� Treatment OptionsTreatment Options
�� Vitamin Supplements & Other Vitamin Supplements & Other PreventionPrevention
Poole, K. E S et al. BMJ 2006;333:1251-1256
Figure 1. Epidemiology of osteoporotic fractures Figure 1. Epidemiology of osteoporotic fractures in men and women.in men and women.
Impact of FracturesImpact of Fractures
�� Fractures caused by osteoporosis Fractures caused by osteoporosis affect 1 in 2 women and 1 in 5 men affect 1 in 2 women and 1 in 5 men over 50 years of ageover 50 years of age
�� Results in permanent disability in Results in permanent disability in over 30% of those with fractureover 30% of those with fracture
�� After hip fracture, nearly 20% will die After hip fracture, nearly 20% will die within 1 yearwithin 1 year�� Prevalence of death is twice as high in Prevalence of death is twice as high in
menmen
�� Over 50% of survivors will not return Over 50% of survivors will not return to independent living to independent living
A Case of Osteoporosis…A Case of Osteoporosis…
�� 57 year old Caucasian woman with breast 57 year old Caucasian woman with breast cancer s/p left lumpectomy & chemotherapy at cancer s/p left lumpectomy & chemotherapy at 35; then right breast cancer s/p mastectomy and 35; then right breast cancer s/p mastectomy and chemotherapy at 40.chemotherapy at 40.
�� Early menopause started at 40 years of age.Early menopause started at 40 years of age.
�� Normal DEXA at age 45, then diagnosed with Normal DEXA at age 45, then diagnosed with osteoporosis by heel scan at age 50 years.osteoporosis by heel scan at age 50 years.
�� DEXA May 2012 DEXA May 2012 �� Osteopenia TOsteopenia T--score score --1.6 to 2.0)1.6 to 2.0)
�� FRAX Score June 2012 FRAX Score June 2012 �� 1.0% @ hip, 7.6% total1.0% @ hip, 7.6% total
ScreeningScreening
7/12/2012
2
Guidelines for Screening for Guidelines for Screening for Osteoporosis in WomenOsteoporosis in Women
National
OsteoporosisFoundation
2008
•Screen all women > 65 years regardless of risk•Screen all men > 70 years regardless of risk
•Screen postmenopausal women & men 50-69
years with significant risk factors
North American
Menopause Association
2010
•Screen all women at 65 years
•Screen women at 50 years of age if ↑ risk•Screen postmenopausal women age with medical
causes of bone loss
•Screen postmenopausal women with a fragility fracture
USPSTF
2001
•Screen all women > 65 years •Screen women at 60 years if ↑ risk
•Insufficient evidence to support screening younger
women
Are we following the guidelines?Are we following the guidelines?
Study: 615 women who were screened with Study: 615 women who were screened with
DXA between 2007 and 2009DXA between 2007 and 2009
Question 1: Should these women have Question 1: Should these women have been screened?been screened?
�� 41% did not meet criteria for screening41% did not meet criteria for screening
Question 2: Of those who met criteria for Question 2: Of those who met criteria for
treatment, were they treated?treatment, were they treated?
�� With an indication, 35% were treatedWith an indication, 35% were treated
�� With no indication, 18% were treatedWith no indication, 18% were treated
Schnatz PF, et al. Menopause 2011 Oct; 18:1072
Risk Factors that Prompt Risk Factors that Prompt ScreeningScreening
�� Personal history of fracture as an adult Personal history of fracture as an adult
�� History of fragility fracture in a firstHistory of fragility fracture in a first--degree degree
relative relative
�� Use of oral corticosteroid therapy for more Use of oral corticosteroid therapy for more
than 3than 3--6 months 6 months
�� Estrogen deficiency at an early age Estrogen deficiency at an early age
�� (<45 yrs, e.g. Early menopause)(<45 yrs, e.g. Early menopause)
Other Risk Factors To Prompt Other Risk Factors To Prompt ScreeningScreening
�� Alcohol in amounts >2 drinks per dayAlcohol in amounts >2 drinks per day�� Current smoking Current smoking �� Increased fall riskIncreased fall risk
�� Impaired visionImpaired vision�� Use of sedatives/hypnoticsUse of sedatives/hypnotics�� FrailtyFrailty�� History of falls History of falls �� DementiaDementia
�� Low body weight (<about 127 lbs = BMI Low body weight (<about 127 lbs = BMI <<19) 19) �� Low physical activity Low physical activity �� Low calcium intake (lifelong)Low calcium intake (lifelong)
Conditions that Reduce Bone Conditions that Reduce Bone Mineral Density and Prompt Mineral Density and Prompt
ScreeningScreening�� Cushing diseaseCushing disease
�� Malabsorption Malabsorption
�� Gastric bypass surgeryGastric bypass surgery
�� IBDIBD
�� Pernicious anemiaPernicious anemia
�� Celiac diseaseCeliac disease
�� HyperparathyroidismHyperparathyroidism
�� Hyperthyroidism Hyperthyroidism
�� Vitamin D DeficiencyVitamin D Deficiency
�� Chronic renal diseaseChronic renal disease�� Impaired Vit D metabolismImpaired Vit D metabolism
�� Chronic liver diseaseChronic liver disease�� Impaired protein synthesisImpaired protein synthesis
�� COPD or asthmaCOPD or asthma
�� Rheumatoid arthritisRheumatoid arthritis
�� ImmobilityImmobility
Medications that Reduce Bone Medications that Reduce Bone Mineral DensityMineral Density
�� Oral glucocorticoid therapyOral glucocorticoid therapy�� 33--6 months use6 months use
�� Aromatase inhibitorsAromatase inhibitors�� Anastrozole (Arimidex), Letrozole (Femara), Exemestane (Aromasin)Anastrozole (Arimidex), Letrozole (Femara), Exemestane (Aromasin)
�� Androgen deprivation therapyAndrogen deprivation therapy
�� AntiAnti--convulsantsconvulsants�� Phenytoin, phenobarbitolPhenytoin, phenobarbitol
�� HeparinHeparin
�� Cytotoxic agents Cytotoxic agents
�� MYTH: DepoproveraMYTH: Depoprovera
7/12/2012
3
Summary: Who To ScreenSummary: Who To Screen
�� All Women >65 years, Men >70 yearsAll Women >65 years, Men >70 years
�� Postmenopausal Women and Men 50Postmenopausal Women and Men 50--69 69
years with a risk factoryears with a risk factor
�� Diagnostic DEXADiagnostic DEXA
�� Those with a hip or verterbral fracture to Those with a hip or verterbral fracture to characterize disease severitycharacterize disease severity
Screening TestsScreening Tests
Alternatives to DEXA ScanAlternatives to DEXA Scan
�� Ultrasound of forearms, heels, & fingersUltrasound of forearms, heels, & fingers�� Predictive of vertebral and global fracture riskPredictive of vertebral and global fracture risk
�� Less predictive of hip fracture Less predictive of hip fracture
�� Less predictive Less predictive oof future fractureof future fracture
�� Not validated in menNot validated in men
�� CheaperCheaper
�� Quantitative CTQuantitative CT�� Some limitations in cross site applicationsSome limitations in cross site applications
�� Not validated in menNot validated in men
�� Quantitative USQuantitative US�� Predicts hip, vertebral and global risk in post menopausal Predicts hip, vertebral and global risk in post menopausal
womenwomen
�� Predicts hip, nonPredicts hip, non--vertebral risk in men >65 yearsvertebral risk in men >65 years
DiagnosisDiagnosis
Diagnostic Criteria by WHODiagnostic Criteria by WHO
�� ZZ--score=age matched adult mean BMDscore=age matched adult mean BMD
�� TT--score=young adults ages 25 to 45 year olds score=young adults ages 25 to 45 year olds mean BMDmean BMD
Diagnosis BMD Criteria
Normal BMD w/i 1 SD of the T-score
Osteopenia BMD b/t -1 & -2.5 SD below the T-score
Osteoporosis BMD at least -2.5 below the T-score
Severe Osteoporosis Fragility fracture & BMD <-2.5
WHO Risk Model: FRAX ®WHO Risk Model: FRAX ®
www.shef.ac.uk/FRAX
Only valid for people who are untreated, only >50 years, and post menopausal
7/12/2012
4
When to ReWhen to Re--Screen for Screen for Osteoporosis Osteoporosis
DEXA Result T-Score Interval
No Osteopenia -1.0 or higher 15 years
Mild Osteopenia -1.5 to -1.0 15 years
Moderate Osteopenia -1.5 to -1.99 5 years
Severe Osteopenia -2.0 to -2.49 1 year
Adapted from N Engl J Med 2012:366:225-33
TreatmentTreatment
When to Treat OsteoporosisWhen to Treat Osteoporosis
�� OsteoporosisOsteoporosis by BMDby BMD >> --2.5 SD away from T2.5 SD away from T--score meanscore mean
�� Osteopenia +FRAX® Model OutputOsteopenia +FRAX® Model Output
� women and men >50 years of age with 10-year risk of hip fracture >3% or any fracture >20%
�� Fracture of the hip or vertebraFracture of the hip or vertebra
�� History of lowHistory of low--impact fractureimpact fracture
�� Loss of height > 1.5 inches regardless of BMDLoss of height > 1.5 inches regardless of BMD
Osteoporosis Prevention & Osteoporosis Prevention & Treatment with BisphosphonatesTreatment with BisphosphonatesMedication Regimen Prevention Treatment
Alendronate (Fosmax)
35 mg/week
70 mg/week10 mg/day
√√√
Risedronate (Actonel)
150 mg/month
35 mg/week
√√
√√
Ibandronate (Boniva)
150 mg/month
2.5 mg/day3 mg IV/q3 mo
√√√
Zoledronic Acid* (Reclast)
5 mg IV/q12 mo
5 mg IV/q24 mo √√
* 3 years MAX
Bisphosphonate Dosing Bisphosphonate Dosing
FactoidsFactoids�� All have equivalent efficacy for reducing All have equivalent efficacy for reducing
vertebral and nonvertebral and non--vertebral fracturesvertebral fractures
�� Take on empty stomach with 8 oz water, Take on empty stomach with 8 oz water,
then sit upright for 30 minutesthen sit upright for 30 minutes
�� Risk for erosive esophagitisRisk for erosive esophagitis
�� WEEKLY dosing has BEST adherenceWEEKLY dosing has BEST adherence
�� Ideal duration UNCLEAR: 5 Ideal duration UNCLEAR: 5 --10 years?10 years?
�� Renal dosing required if CLcr <30 mL/minRenal dosing required if CLcr <30 mL/min
Osteoporosis Prevention & Osteoporosis Prevention & Treatment with Other Treatment with Other
MedicationsMedicationsMedication Regimen Prevent’n Treatm’nt Frx ↓
Raloxifene*
(Evista)
60 mg/day √ √ Vertebral
Denosumab
(Prolia)
60 mg SC q6 mo
√ Vertebral
Non-vert
Calcitonin 200 IU IN/day100 IU SC/day
100 IU IM/qod
√√√
Vertebral
PTH
(Forteo)
20 mcg SC/day
√ Vertebral
Non-vert
*anti-estrogen effects on uterus and breast, ↑ VTE, CVAIN=intranasal
7/12/2012
5
Osteoporosis Prevention with Osteoporosis Prevention with Estrogen PreparationsEstrogen Preparations
�� Oral EstrogensOral Estrogens�� Estradiol, Esterified estrogens, Estopipate, CEEEstradiol, Esterified estrogens, Estopipate, CEE
�� Oral EstrogenOral Estrogen--Progestin CombinationsProgestin Combinations�� Estradiol + norgestimate or northindroneEstradiol + norgestimate or northindrone
�� CEE+medroxyprgesteroneCEE+medroxyprgesterone
�� Transdermal EstrogensTransdermal Estrogens�� EstradiolEstradiol
�� Transdermal EstrogenTransdermal Estrogen--Progestin Progestin CombinationsCombinations�� Estradiol + levonorgestrelEstradiol + levonorgestrel
Other SupplementsOther Supplements
Institute of MedicineInstitute of MedicineVitamin D and CalciumVitamin D and Calcium
CalciumCalcium�� Adults 19Adults 19--50 years 1000 mg/day50 years 1000 mg/day�� Men >50 years of age 1000 mg/day Men >50 years of age 1000 mg/day �� Women >50 years of age 1200 mg/dayWomen >50 years of age 1200 mg/day�� Men >70 years of age 1200 mg/dayMen >70 years of age 1200 mg/day
Vitamin DVitamin D�� Adults up to age 70 years 600 IU/dayAdults up to age 70 years 600 IU/day�� Adults above age 70 years 800 IU/dayAdults above age 70 years 800 IU/day
NOTE:NOTE:�� Consider Consider calcium citrate calcium citrate because less dependent on because less dependent on
stomach acid for absorption (NOF, 2008)stomach acid for absorption (NOF, 2008)�� AdherenceAdherence of about 80% shows best BMD (WHI)of about 80% shows best BMD (WHI)
Vitamin D and Calcium:Vitamin D and Calcium:Low DosesLow Doses
�� WHIWHI--Vitamin 36,000 women 59 to70 yearsVitamin 36,000 women 59 to70 years�� 7 year follow7 year follow--up up
�� Vitamin D 200IU + Calcium 500mgVitamin D 200IU + Calcium 500mg
�� No difference in hip, total fracture rate or BMDNo difference in hip, total fracture rate or BMD
�� SubSub--group analysis on women with group analysis on women with >> 80% 80% adherence showed PROTECTIONadherence showed PROTECTION
�� WHIWHI--RCT 36,000 women 59 to70 yearsRCT 36,000 women 59 to70 years�� 7 year follow7 year follow--upup
�� Vitamin D 400IU + Calcium 1000mgVitamin D 400IU + Calcium 1000mg
�� No difference in fracture rate, Increased BMDNo difference in fracture rate, Increased BMD
�� Low dose of Vitamin DLow dose of Vitamin D
Vitamin D and Calcium:Vitamin D and Calcium:High Doses as MonotherapyHigh Doses as Monotherapy
�� RCTRCT--1460 women >70 years old for 5 years1460 women >70 years old for 5 years�� 1200 mg calcium only1200 mg calcium only
�� SubSub--group analysis on women with group analysis on women with >> 80% adherence 80% adherence showed PROTECTIONshowed PROTECTION
�� MetaMeta--analysis 700analysis 700--800 IU vitamin D only800 IU vitamin D only� Hip fracture reduction by 26%
• RR=0.74 (95% CI, 0.61–0.88)
� Non-vertebral fracture reduction by 23%• RR=0.77 (95% CI, 0.68–0.87)
� Bischoff-Ferrari, 2005
MetaMeta--Analysis: Hip Fracture RatesAnalysis: Hip Fracture RatesEvidence for Calcium
Doses 1200mg or more
Boonen, J Internal Med, 2006
7/12/2012
6
MetaMeta--Analysis: Hip Fracture RatesAnalysis: Hip Fracture Rates
Evidence for
Vitamin D does700-800IU
Boonen, J Internal Med, 2006
�� WHI: Calcium and Vitamin D WHI: Calcium and Vitamin D
Supplementation StudySupplementation Study
�� Followed 32,282 women for 7 yearsFollowed 32,282 women for 7 years
�� RCT: Calcium 1000mg and Vitamin D 400 RCT: Calcium 1000mg and Vitamin D 400
IU versus personal supplementationIU versus personal supplementation
�� Risk of MIRisk of MI
•• HR 1.14 (p=0.05)HR 1.14 (p=0.05)
�� Risk of CVA plus MIRisk of CVA plus MI
•• HR 1.22 (p=0.04)HR 1.22 (p=0.04)
Calcium and Vitamin D Calcium and Vitamin D
Associated with Risk for CHDAssociated with Risk for CHD
Reducing Falls Reduces Reducing Falls Reduces Fracture Risk…Fracture Risk…
�� 90% of fractures associated with a fall 90% of fractures associated with a fall eventevent�� Alcohol intake reductionAlcohol intake reduction
�� Poor visionPoor vision
�� Physical therapyPhysical therapy
�� WeightWeight--baring exercisebaring exercise
�� Impaired transferringImpaired transferring
�� Home safety evaluationHome safety evaluation
�� Treat pain, go easy on the sedativesTreat pain, go easy on the sedatives
A Clinical Case…Part 1A Clinical Case…Part 1
�� 57 year old Caucasian woman with the 57 year old Caucasian woman with the
followingfollowing
�� Diagnosed with DCIS 1991 (age 35) Diagnosed with DCIS 1991 (age 35)
•• s/p Left lumpectomy, chemotherapy & radiations/p Left lumpectomy, chemotherapy & radiation
�� Diagnosed with second primary 1995 (age 40) Diagnosed with second primary 1995 (age 40)
•• s/p right mastectomy with chemotherapy s/p right mastectomy with chemotherapy
�� Early menopause since age 40 yearsEarly menopause since age 40 years
When should this woman be screened for osteoporosis?When should this woman be screened for osteoporosis?And why?And why?
A clinical case…Part 2A clinical case…Part 2
�� 57 year old Caucasian woman with breast 57 year old Caucasian woman with breast
cancer & chemotherapy twice with early cancer & chemotherapy twice with early menopause from age 40 years.menopause from age 40 years.
�� She reports a loss of height She reports a loss of height >> 1.5 inches1.5 inches
Does this change your management?Does this change your management?
Would isolated height loss without the other risks Would isolated height loss without the other risks make you screen her?make you screen her?
A clinical case…Part 3A clinical case…Part 3
�� 57 year old Caucasian woman with breast 57 year old Caucasian woman with breast
cancer & chemotherapy twice with early cancer & chemotherapy twice with early menopause from age 40 years.menopause from age 40 years.
�� Diagnosed with osteoporosis by heel scan Diagnosed with osteoporosis by heel scan in 2005 at age 50 years.in 2005 at age 50 years.
Would you treat her based on this information?Would you treat her based on this information?
If yes, then for how long?If yes, then for how long?
7/12/2012
7
A clinical case…Part 4A clinical case…Part 4
�� 57 year old Caucasian woman with breast 57 year old Caucasian woman with breast
cancer & chemotherapy twice with early cancer & chemotherapy twice with early menopause from age 40 years.menopause from age 40 years.
�� DEXA May 2012 DEXA May 2012
�� Osteopenia TOsteopenia T--score score --1.6 to 2.0)1.6 to 2.0)
�� FRAX Score June 2012 FRAX Score June 2012
�� 1.0% @ hip, 7.6% total1.0% @ hip, 7.6% total
Should she be treated now?Should she be treated now?
When should she be reWhen should she be re--screened?screened?
SummarySummary
�� Screen women Screen women >> 65 years, Men 65 years, Men >> 70 70
yearsyears
�� Risk stratify younger womenRisk stratify younger women
�� Treat women with bisphosphonates when Treat women with bisphosphonates when
indicatedindicated
�� Give ENOUGH vitamin supplementationGive ENOUGH vitamin supplementation
�� REDUCE fall riskREDUCE fall risk
Fracture CalculatorsFracture Calculators
�� FRAX from the UNFRAX from the UN
�� www.shef.ac.uk/FRAX/tool.jspwww.shef.ac.uk/FRAX/tool.jsp
�� Hip CalculatorHip Calculator
�� http://hipcalculator.fhcrc.orghttp://hipcalculator.fhcrc.org
�� UK population basedUK population based
�� http://www.qfracture.orghttp://www.qfracture.org
ReferencesReferences1.1. National Osteoporosis Society www.nos.org.uk National Osteoporosis Society www.nos.org.uk
2.2. North American Menopause SocietyNorth American Menopause Society
3.3. US Preventive Health Services Task ForceUS Preventive Health Services Task Force
4.4. Schnatz PF, et al. Osteoporosis screening and Schnatz PF, et al. Osteoporosis screening and treatment guidelines: Are they being followed? treatment guidelines: Are they being followed? Menopause 2011 Oct; 18:1072.Menopause 2011 Oct; 18:1072.
5.5. Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: a metainhibitors and risk of fractures: a meta--analysis of 11 analysis of 11 international studies. Am J Med 2011 international studies. Am J Med 2011
6.6. Cummings SR, Bates D, Black DM. Cummings SR, Bates D, Black DM. Clinical Use of Clinical Use of Bone Densitometry Scientific Review. Bone Densitometry Scientific Review. JAMA.JAMA. 2002;288:18892002;288:1889--1897. 1897.
7.7. Shoback D.Shoback D. Update in Osteoporosis and Metabolic Update in Osteoporosis and Metabolic Bone Disorders.Bone Disorders. The Journal of Clinical Endocrinology The Journal of Clinical Endocrinology & Metabolism. 2007;92(3):747& Metabolism. 2007;92(3):747--753.753.
