Emerging Trends in Emerging Trends in Osteoporosis Osteoporosis Scioto County Medical Society Scioto County Medical Society Current Therapy Seminar Current Therapy Seminar 10/26/2007 10/26/2007 Steven Ing, MD, MSCE Steven Ing, MD, MSCE Division of Endocrinology, Diabetes, Division of Endocrinology, Diabetes, & Metabolism & Metabolism Ohio State University Medical Center Ohio State University Medical Center
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Emerging Trends in Osteoporosis Scioto County Medical Society Current Therapy Seminar 10/26/2007 Steven Ing, MD, MSCE Division of Endocrinology, Diabetes,
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Emerging Trends in Emerging Trends in OsteoporosisOsteoporosis
Scioto County Medical SocietyScioto County Medical SocietyCurrent Therapy SeminarCurrent Therapy Seminar
10/26/200710/26/2007
Steven Ing, MD, MSCESteven Ing, MD, MSCEDivision of Endocrinology, Diabetes, & Division of Endocrinology, Diabetes, &
MetabolismMetabolismOhio State University Medical CenterOhio State University Medical Center
ObjectivesObjectives1.1. Review nonpharmacologic and Review nonpharmacologic and
pharmacologic therapy in the pharmacologic therapy in the management of osteoporosismanagement of osteoporosis
2.2. Review secondary causes of osteoporosisReview secondary causes of osteoporosis3.3. Review risk factors for fractureReview risk factors for fracture
From Mosekilde, LI, Bone 1988; 9:247
Question #1: Can I just Question #1: Can I just take Calcium and Vitamin D take Calcium and Vitamin D
to treat osteoporosis?to treat osteoporosis? 49 year-old woman without prior fracture49 year-old woman without prior fracture Menopause @ age 47Menopause @ age 47 2003 DXA 2003 DXA 2006 DXA 2006 DXA ΔΔ
R Hip 0.720 (-2.3, -1.8) R Hip 0.720 (-2.3, -1.8) 0.694 (-2.5, -1.9) 0.694 (-2.5, -1.9)-5.2%-5.2%
L Hip 0.804 (-1.6, -1.1) L Hip 0.804 (-1.6, -1.1) 0.762 (-2.0, -1.4) 0.762 (-2.0, -1.4)-3.6%-3.6%
Felt “devastated” about falling BMDFelt “devastated” about falling BMD
WHI: Ca + Vitamin DWHI: Ca + Vitamin D Multicenter, placebo-controlled, randomized clinical Multicenter, placebo-controlled, randomized clinical
trial of 36,282 healthy postmenopausal women, ages trial of 36,282 healthy postmenopausal women, ages 50-79, follow up 7 years50-79, follow up 7 years Not recruited on basis of low BMD or fracture risk factorsNot recruited on basis of low BMD or fracture risk factors
500 mg Ca-200 IU Vitamin D bid with meals vs. 500 mg Ca-200 IU Vitamin D bid with meals vs. PlaceboPlacebo
Reduced bone loss at hip: Reduced bone loss at hip: Hip BMD 1% higher in treated groupHip BMD 1% higher in treated group
Kidney stone HR: 1.17 (1.02-1.34)Kidney stone HR: 1.17 (1.02-1.34) 4 per 1000 women treated for 7 years4 per 1000 women treated for 7 years
Baseline calcium intake > 1000 mg dailyBaseline calcium intake > 1000 mg daily Vitamin D dose may have been too lowVitamin D dose may have been too low
Jackson, RD et. al. NEJM 2006;543:669-683
Institute of Medicine Institute of Medicine Dietary Recommendations (1997)Dietary Recommendations (1997)
Ca (mg/day) Ca (mg/day) Vit D Vit D (IU/day)(IU/day)
•Recommendations for healthy Recommendations for healthy populationpopulation•Optimal intake in disease is Optimal intake in disease is uncertainuncertain
**AI, Adequate IntakeAI, Adequate Intake**UL, Tolerable Upper Intake LevelUL, Tolerable Upper Intake Level****UL may change soonUL may change soon
Start with 300 mg (from non-Ca rich foods)Start with 300 mg (from non-Ca rich foods) Add 300 mg for each 8 oz serving milk or Add 300 mg for each 8 oz serving milk or
serving of other Ca-rich food (e.g. yogurt, serving of other Ca-rich food (e.g. yogurt, cheese)cheese) Ca-fortified juice: 300 mg per 8 ozCa-fortified juice: 300 mg per 8 oz Need 3-4 servings of dairy to get to AINeed 3-4 servings of dairy to get to AI
Using “Nutrition Facts” panel on Food Using “Nutrition Facts” panel on Food LabelLabel % Daily Value assumes 100% DV = 1000 mg % Daily Value assumes 100% DV = 1000 mg
CaCa
Sources of CalciumSources of Calcium Milk (whole, low fat, nonfat): Milk (whole, low fat, nonfat):
300 mg Ca-100 IU Vitamin D per 8 oz300 mg Ca-100 IU Vitamin D per 8 oz Ca-fortified soy milk, fruit juices, cerealsCa-fortified soy milk, fruit juices, cereals CheeseCheese Fruit-flavored yogurtFruit-flavored yogurt Milk-based pudding & shakesMilk-based pudding & shakes For lactose intolerant: For lactose intolerant:
15% Caucasian, 70% African American, 90% Asian 15% Caucasian, 70% African American, 90% Asian AmericanAmerican
lactase enzyme?)lactase enzyme?) Yogurt with live active cultures (bacterial lactase)Yogurt with live active cultures (bacterial lactase) Hard cheesesHard cheeses
Calcium SupplementsCalcium Supplements Many patients will not get adequate Ca from diet Many patients will not get adequate Ca from diet
Need Ca supplement to achieve 1200-1500 mg Need Ca supplement to achieve 1200-1500 mg elemental Ca dailyelemental Ca daily
Read the fine print:Read the fine print: mg elemental calcium vs. mg calcium saltmg elemental calcium vs. mg calcium salt How many tablets per serving size?How many tablets per serving size?
Maximum 500-600 mg elemental Ca at one timeMaximum 500-600 mg elemental Ca at one time Calcium carbonate Calcium carbonate
Most common form of Ca supplement, cheapestMost common form of Ca supplement, cheapest Take with mealTake with meal
Calcium citrateCalcium citrate Achlorhydria, e.g. PPI, H2 blockerAchlorhydria, e.g. PPI, H2 blocker Mealtime administration not necessaryMealtime administration not necessary
Separate from thyroid hormone & iron supplementsSeparate from thyroid hormone & iron supplements
Vitamin DVitamin D Food sourcesFood sources
Natural: oily fish (salmon, mackerel), fish liver oilsNatural: oily fish (salmon, mackerel), fish liver oils Fortified in milk: 100 IU per 8 ouncesFortified in milk: 100 IU per 8 ounces
Cutaneous synthesis is diminished in:Cutaneous synthesis is diminished in: Sunscreen use: SPF 8 ↓ 97.5% vitamin D synthesisSunscreen use: SPF 8 ↓ 97.5% vitamin D synthesis Darker skin: melanin competes with vitamin D Darker skin: melanin competes with vitamin D
precursor for photonsprecursor for photons High latitude regions: limited sunlight during High latitude regions: limited sunlight during
winterwinter Age: ↓ efficiency of vitamin D synthesis in older Age: ↓ efficiency of vitamin D synthesis in older
persons persons
Vitamin DVitamin D
Increase in 25 OH Vit D inversely Increase in 25 OH Vit D inversely proportional to starting levelproportional to starting level At low level, 400 IUAt low level, 400 IU ↑ 4.8 ng/ml↑ 4.8 ng/ml At higher level (28 ng/ml), 400 IUAt higher level (28 ng/ml), 400 IU2.8 ng/ml2.8 ng/ml Rough rule of thumb: 100 IU qd Rough rule of thumb: 100 IU qd ↑ 1 ng/ml ↑ 1 ng/ml
US National Academy of SciencesUS National Academy of Sciences 800-1000 IU daily to reach 25 OH Vit D 30 800-1000 IU daily to reach 25 OH Vit D 30
ng/mlng/ml ““safe upper limit” = 2000 IU dailysafe upper limit” = 2000 IU daily
Vitamin D Dose-Vitamin D Dose-ResponseResponse
Labeled Labeled DoseDose
(IU/day)(IU/day)
Measured Measured Dose Dose
(IU/day)(IU/day)
ΔΔ 25OH Vit 25OH Vit DD
(ng/ml ± (ng/ml ± SE)SE)
10,00010,000 11,00011,000 63.8 ± 763.8 ± 7
5,0005,000 5,5005,500 36.6 ± 436.6 ± 4
1,0001,000 836836 4.8 ± 24.8 ± 2
NoneNone NoneNone -4.6 ± 2-4.6 ± 2
Heaney RP Am J Clin Nutr 2003(77):204-10
Vitamin D SupplementsVitamin D Supplements
Baseline Vitamin Baseline Vitamin D D
(ng/ml)(ng/ml)
Daily Oral dose Daily Oral dose
(IU)(IU)
8-168-16 22002200
16-2416-24 18001800
24-3224-32 11601160
>32>32 00
Estimated dose needed to reach and maintain a serum 25 OH Vit D of 32 ng/ml
Heaney R 2005 Steroid Biochem & Mol Biol
Calcium & Vitamin D Calcium & Vitamin D Supplements: $Supplements: $
You are considering oral bisphosphonate You are considering oral bisphosphonate therapy in a 60 year-old woman with therapy in a 60 year-old woman with postmenopausal osteoporosis with postmenopausal osteoporosis with hip T-score -2.6, spine T-score -2.5. hip T-score -2.6, spine T-score -2.5. She is seeing a dentist for a dental She is seeing a dentist for a dental cavity and tooth extraction is cavity and tooth extraction is recommended. She is fearful about recommended. She is fearful about “Osteonecrosis of the Jaw” which she “Osteonecrosis of the Jaw” which she read about in a magazine. read about in a magazine.
Osteonecrosis of the Jaw Osteonecrosis of the Jaw (ONJ)(ONJ)
Chart review - 63 patients with ONJ Chart review - 63 patients with ONJ Risk factors:Risk factors:
IV bisphosphonate therapy in patient with IV bisphosphonate therapy in patient with metastatic disease to bone: myeloma, breast cancermetastatic disease to bone: myeloma, breast cancer
Usually at site of prior dental surgery Usually at site of prior dental surgery Usually longer treatment duration of Usually longer treatment duration of
Nonhealing extraction sites with exposed alveolar bone
Ruggiero SL, Oral and Maxillofacial Surgery 2006;102:433-441
Signs & Symptoms of Signs & Symptoms of ONJONJ
Exposed bone Exposed bone PainPain SwellingSwelling ParesthesiaParesthesia SupporationSupporation Soft tissue ulceration Soft tissue ulceration Intra or extraoral sinus tracksIntra or extraoral sinus tracks Loosening of teethLoosening of teeth Case Definition: area of exposed bone in the Case Definition: area of exposed bone in the
mandible or maxilla that does not heal within 8 mandible or maxilla that does not heal within 8 weeks after identification by a health care weeks after identification by a health care provider in a patient receiving bisphosphonate provider in a patient receiving bisphosphonate and without radiation therapy to the craniofacial and without radiation therapy to the craniofacial regionregion
JBMR 2007;22(10):1479JBMR 2007;22(10):1479
ONJ IncidenceONJ Incidence
True incidence is unknown, limited by case True incidence is unknown, limited by case reportingreporting
Literature review: 57 ONJ cases in PMOLiterature review: 57 ONJ cases in PMO alendronate: 52 casesalendronate: 52 cases risedronate 2 casesrisedronate 2 cases alendronate + risedronate: 1 casealendronate + risedronate: 1 case IV pamidronate and/or zolendronate: 2 casesIV pamidronate and/or zolendronate: 2 cases Estimated incidence in PMO is low: 1/10,000 – Estimated incidence in PMO is low: 1/10,000 –
1/100,000 1/100,000 In cancer patients, estimated incidence 1-10%In cancer patients, estimated incidence 1-10%
JBMR 2007;22(10):1479JBMR 2007;22(10):1479
ONJ RecommendationsONJ Recommendations Patient about to start or already on bisphosphonate:Patient about to start or already on bisphosphonate:
Inform regarding low risk of ONJ: 1 in 10,000 to 100,000Inform regarding low risk of ONJ: 1 in 10,000 to 100,000 Patients expressing concern over ONJ should seek additional Patients expressing concern over ONJ should seek additional
information from their dentist.information from their dentist. Optimize dental health: regular brushing and flossing, dental Optimize dental health: regular brushing and flossing, dental
visitsvisits Due to low risk and relation to duration of Tx, no Due to low risk and relation to duration of Tx, no
recommendation to perform dental exam before starting or recommendation to perform dental exam before starting or alter dental managementalter dental management
Patients on long-term bisphosphonate (>3 yrs) without Patients on long-term bisphosphonate (>3 yrs) without ONJ:ONJ: Patients with periodontal disease should receive appropriate Patients with periodontal disease should receive appropriate
nonsurgical therapynonsurgical therapy Current data suggests bisphosphonate therapy is not a Current data suggests bisphosphonate therapy is not a
contraindication for dental implantscontraindication for dental implants Endodontic treatment preferable to extractionEndodontic treatment preferable to extraction ? Stopping bisphosphonate if an invasive dental procedure ? Stopping bisphosphonate if an invasive dental procedure
anticipatedanticipated
JBMR 2007;22(10):1479JBMR 2007;22(10):1479
ONJ RecommendationsONJ Recommendations Patients with ONJ Patients with ONJ
Report case to manufacturerReport case to manufacturer (? Avoid tartar control toothpaste – Kalmar, OSU)(? Avoid tartar control toothpaste – Kalmar, OSU)
Managed by dentist and/or oral surgeonManaged by dentist and/or oral surgeon Chlorhexidine 0.12% oral antimicrobial rinseChlorhexidine 0.12% oral antimicrobial rinse Oral antibiotics tailored to culture data from necrotic bone Oral antibiotics tailored to culture data from necrotic bone
and wound exudateand wound exudate Surgical treatment should be conservative or delayed since Surgical treatment should be conservative or delayed since
debridement of necrotic bone is not uniformly effectivedebridement of necrotic bone is not uniformly effective Removal of sharp bone edges is recommended to prevent Removal of sharp bone edges is recommended to prevent
trauma to adjacent soft tissuetrauma to adjacent soft tissue Loose bony segments should be removed without exposing Loose bony segments should be removed without exposing
uninvolved boneuninvolved bone Segmental jow resection may be required for symptomatic Segmental jow resection may be required for symptomatic
patients with large sements of necrotic bone or pathologic patients with large sements of necrotic bone or pathologic fracturefracture
? Stop IV bisphosphonate in cancer patients if situation ? Stop IV bisphosphonate in cancer patients if situation permits (case by case basis)permits (case by case basis)
Ruggiero SL, Oral and Maxillofacial Surgery 2006;102:433-441
Question #3: Can I stop Question #3: Can I stop Bisphosphonate Therapy?Bisphosphonate Therapy?
A 65 year old woman with osteoporosis by A 65 year old woman with osteoporosis by DXADXA Baseline DXA 8 years ago: LS T-score -2.5, TH -Baseline DXA 8 years ago: LS T-score -2.5, TH -
2.22.2 Treated with alendronate x 7 yearsTreated with alendronate x 7 years 8% increase at spine, 5% increase at total hip8% increase at spine, 5% increase at total hip No prior fracture, no fracture on therapyNo prior fracture, no fracture on therapy
““I would like to come off the medicine. I’m I would like to come off the medicine. I’m having trouble paying for it. Do I need to having trouble paying for it. Do I need to stay on Fosamax?”stay on Fosamax?”
To Continue or Stop To Continue or Stop Antiresorptive Treatment?Antiresorptive Treatment?
FIT I & II: Alendronate therapy in postmenopausal women with: FIT I & II: Alendronate therapy in postmenopausal women with: Prior vertebral fracture Prior vertebral fracture ↓ risk for vertebral and hip fractures (Lancet ↓ risk for vertebral and hip fractures (Lancet
1996;348:1535-1541)1996;348:1535-1541) T-score ≤ -2.5 without prior fracture T-score ≤ -2.5 without prior fracture lowers vertebral and all clinical lowers vertebral and all clinical
FLEX ConclusionsFLEX Conclusions Stopping alendronate for 5 years after 5 years of therapy Stopping alendronate for 5 years after 5 years of therapy
did not increase risk of nonvertebral fracture did not increase risk of nonvertebral fracture did not increase risk of x-ray detected vertebral fracturedid not increase risk of x-ray detected vertebral fracture did increase risk of clinically detected vertebral fracturedid increase risk of clinically detected vertebral fracture
Women at high risk of vertebral fractures such as those Women at high risk of vertebral fractures such as those with prevalent vertebral fracture or very low BMD(T-with prevalent vertebral fracture or very low BMD(T-score <-3.5) may benefit from continuing alendronate score <-3.5) may benefit from continuing alendronate beyond 5 yearsbeyond 5 years
Consider a “drug holiday” up to 5 years if there was a Consider a “drug holiday” up to 5 years if there was a good response to 5 years of alendronate: 3-5% increase good response to 5 years of alendronate: 3-5% increase hip and 8-10% increase in spine BMD, T-score >-3.5, no hip and 8-10% increase in spine BMD, T-score >-3.5, no new fracturesnew fractures
Monitor with DXAMonitor with DXA Rapid hip BMD loss >8% at 1 year, >10% at 2 year, (or fractures) Rapid hip BMD loss >8% at 1 year, >10% at 2 year, (or fractures)
resume bisphosphonate or switch to an alternative resume bisphosphonate or switch to an alternative
Black DM et. al., JAMA 2006;296:2927-2938
Question #4: I can’t Question #4: I can’t tolerate bisphosphonate tolerate bisphosphonate
pillspills
60 year old postmenopausal woman60 year old postmenopausal woman Fragility fractures: forearm, spineFragility fractures: forearm, spine Spine T-score -2.5Spine T-score -2.5 Hip T-score -2.8Hip T-score -2.8 Oral alendronate and risedronate not Oral alendronate and risedronate not
and rechallenge and rechallenge UGI symptoms UGI symptoms
iiBBandronate andronate OOsteoporosis steoporosis vertebral fracture trial in vertebral fracture trial in NNorth orth
America and America and EEurope (BONE)urope (BONE) Multicenter (73) clinical trial of 2946 postmenopausal ♀ Multicenter (73) clinical trial of 2946 postmenopausal ♀ Inclusion: LS T-score ≤-2.0 & history of 1-4 vertebral fractures Inclusion: LS T-score ≤-2.0 & history of 1-4 vertebral fractures Randomization: 3 years ofRandomization: 3 years of
Ibandronate 2.5 mg dailyIbandronate 2.5 mg daily Cyclical Ibandronate - 20 mg every other day for 12 doses every Cyclical Ibandronate - 20 mg every other day for 12 doses every
IV Ibandronate: Adverse IV Ibandronate: Adverse EffectsEffects
Delmas PD, et. al. Arthritis & Rheum 2006
2 mg IV 2 mg IV 3 mg IV3 mg IV 2.5 mg 2.5 mg POPO
Flu-likeFlu-like 5.1%5.1% 4.9%4.9% 1.1%1.1%
MyalgiaMyalgia 3.1%3.1% 1.3%1.3% 0.2%0.2%
ArthralgiaArthralgia 1.1%1.1% 1.3%1.3% 0.2%0.2%
RenalRenal
Continuous Continuous ↑ Cr↑ Cr
2%2%
003%3%
002%2%
00
IV Ibandronate: IV Ibandronate: SummarySummary
IV ibandronate is at least noninferior IV ibandronate is at least noninferior (actually superior) to oral ibandronate (actually superior) to oral ibandronate for increasing BMDfor increasing BMD
No fracture data on IV ibandronateNo fracture data on IV ibandronate Well-tolerated and similar safety Well-tolerated and similar safety
profile to oralprofile to oral GSK receives FDA approval January GSK receives FDA approval January
9, 2006 9, 2006
IV ZolendronateIV Zolendronate HHealth ealth OOutcomes and utcomes and RReduced educed IIncidence with ncidence with ZZoledronic Acid oledronic Acid ONONce Yearly ce Yearly
(HORIZON): IV zolendronate 5 mg IV q 12 months vs. placebo(HORIZON): IV zolendronate 5 mg IV q 12 months vs. placebo FN T-score ≤ -2.5 OR ≤ -1.5 with ≥ 2 mild or 1 moderate radiographic vertebral FN T-score ≤ -2.5 OR ≤ -1.5 with ≥ 2 mild or 1 moderate radiographic vertebral
Robust antifracture efficacy data for Robust antifracture efficacy data for spine, hip, nonspine, and total spine, hip, nonspine, and total fracture reductionfracture reduction
Annual IV administrationAnnual IV administration Novartis received FDA approval 8-Novartis received FDA approval 8-
17-200717-2007
IV BisphosphonatesIV BisphosphonatesIbandronateIbandronate ZolendronateZolendronate
Treat hypocalcemia, Treat hypocalcemia, vitamin D deficiency firstvitamin D deficiency first
GFR <30 mL/minGFR <30 mL/min
Pregnancy category CPregnancy category C
HypocalcemiaHypocalcemia
Ca: 1200 mg dailyCa: 1200 mg daily
Vit D 400-800 IU dailyVit D 400-800 IU daily
GFR < 35 ml/minGFR < 35 ml/min
Pregnancy, breast feedingPregnancy, breast feeding
MonitoringMonitoring Cr before doseCr before dose
Adverse Adverse effectseffects
Tylenol for flu-like symptomsTylenol for flu-like symptoms
Question #4: “I’m Question #4: “I’m fracturing on osteoporosis fracturing on osteoporosis
meds, what now?meds, what now? 66 66 ♀ started Fosamax after ♀ started Fosamax after 1997 DXA shows osteoporosis1997 DXA shows osteoporosis Menarche 11, menopause 55, on HRT, switched to Fosamax 1997 Menarche 11, menopause 55, on HRT, switched to Fosamax 1997
to present (3/2006)to present (3/2006) Atraumatic back pain 2/2006 Atraumatic back pain 2/2006 xrays compression fractures L1, xrays compression fractures L1,
L2, L3, T11 L2, L3, T11 PMH: Left hip replacement 1997 for arthritis, hypothyroidism, PMH: Left hip replacement 1997 for arthritis, hypothyroidism,
by fractures)by fractures) Total Hip: 0.676 Total Hip: 0.676 0.718 (+6.2%) 0.718 (+6.2%)
Consider secondary causes of osteoporosis:Consider secondary causes of osteoporosis: Low Z-score (cutoff ≤ -2.0 vs. ≤ -1.5 ?)Low Z-score (cutoff ≤ -2.0 vs. ≤ -1.5 ?) Fracturing on medicationFracturing on medication Falling BMD on medicationFalling BMD on medication
Question # 5: Does Question # 5: Does Osteopenia need Drug Osteopenia need Drug
Treatment?Treatment?
BMD and Fracture RiskBMD and Fracture Risk 33.6 million in USA have osteopenia: 4:1 ♀:♂33.6 million in USA have osteopenia: 4:1 ♀:♂ (10 million with osteoporosis)(10 million with osteoporosis) Relationship between BMD and fracture is Relationship between BMD and fracture is
continuouscontinuous Normal T-score ≥ -1.0Normal T-score ≥ -1.0 Osteopenia T-score -1.1 to -2.4Osteopenia T-score -1.1 to -2.4 Osteoporosis: T-score ≤ -2.5Osteoporosis: T-score ≤ -2.5 Severe osteoporosis: T-score ≤ -2.5 with fragility fractureSevere osteoporosis: T-score ≤ -2.5 with fragility fracture
BMD predicts fracture better than BP predicts BMD predicts fracture better than BP predicts stroke: stroke: 1 SD ↓ hip BMD 1 SD ↓ hip BMD ↑ 2.6 RR hip fracture ↑ 2.6 RR hip fracture
History of fragility fracture = clinical osteoporosisHistory of fragility fracture = clinical osteoporosis
Guidelines for Treatment of Guidelines for Treatment of OsteopeniaOsteopenia
T-score ≤ -2.5 T-score ≤ -2.5 and or fragility and or fragility fracturefracture
OsteopeniaOsteopenia
National National Osteoporosis Osteoporosis FoundationFoundation
YesYes Consider if T-Consider if T-score score
≤ ≤ -1.5 + risk -1.5 + risk factorsfactors
Consider if T-Consider if T-score score
≤ ≤ -2.0 without -2.0 without risksrisks
American American Association Association of Clinical of Clinical EndocrinoloEndocrinologistsgists
YesYes Consider if T-Consider if T-score score
≤ ≤ -1.5 + risk -1.5 + risk factorsfactors
North North American American Menopause Menopause SocietySociety
YesYes Consider if T-Consider if T-score score
≤ ≤ -2.0 + risk -2.0 + risk factorsfactors
National Osteoporosis Risk National Osteoporosis Risk Assessment (NORA)Assessment (NORA)
Siris ES. Arch Intern Med 2004;164:1108-12
Risk Factors for Fracture Risk Factors for Fracture Independent of BMDIndependent of BMD
Advancing age Advancing age Previous fracture Previous fracture Long-term glucocorticoid therapy Long-term glucocorticoid therapy Low body weight (<127 lb) Low body weight (<127 lb) Family history of hip fracture Family history of hip fracture Cigarette smoking Cigarette smoking Excess alcohol intake (>2 drinks Excess alcohol intake (>2 drinks
daily) daily)
Hip Fracture Risk and Clinical Hip Fracture Risk and Clinical Risk FactorsRisk Factors
Risk FactorRisk Factor RRRR RR RR with with BMDBMD
Fragility fracture after Fragility fracture after age 50age 50
1.851.85 1.62 1.62
BMI (20 vs 25)BMI (20 vs 25) 1.951.95 1.421.42
Prior or current steroid Prior or current steroid useuse
WHO: 9 cohorts, 46,000 WHO: 9 cohorts, 46,000 ♀ and ♂♀ and ♂ Combine DXA with Clinical Risk FactorsCombine DXA with Clinical Risk Factors Derive absolute risk of fracture in next 10 Derive absolute risk of fracture in next 10
years years (similar to Framingham score for predicting CAD)(similar to Framingham score for predicting CAD) Low risk: <10% 10 year risk of fractureLow risk: <10% 10 year risk of fracture Mod risk: 10-20% 10 year risk of fractureMod risk: 10-20% 10 year risk of fracture High risk: >20% 10 year risk of fractureHigh risk: >20% 10 year risk of fracture
Currently: fracture risk calculator based on Currently: fracture risk calculator based on Study of Osteoporotic Fractures (SOF) data Study of Osteoporotic Fractures (SOF) data http://courses.washington.edu/bonephys/FxRiskCalc.swfhttp://courses.washington.edu/bonephys/FxRiskCalc.swf
Question 6 : What Question 6 : What diagnostic modalities are diagnostic modalities are
on the horizon?on the horizon?
““A skeletal disorder characterized by A skeletal disorder characterized by compromised bone strength compromised bone strength predisposed to an increased risk of predisposed to an increased risk of fracture. Bone strength reflects an fracture. Bone strength reflects an integration of two main features: integration of two main features: bone mass and bone quality.”bone mass and bone quality.”
NIH Consensus Development Panel NIH Consensus Development Panel JAMA 2001:285:785JAMA 2001:285:785
MicroarchitectureMicroarchitecture
From Mosekilde, LI, Bone 1988; 9:247
MRIMRI
Man with normal testosterone and normal trabecular bone connectivity
Hypogonadal man with deteriorated connectivity
MRI Research StudyMRI Research Study
Women ≥ 50Women ≥ 50 Postmenopausal ≥ 5 yearsPostmenopausal ≥ 5 years History of fragility fractureHistory of fragility fracture No osteoporosis medications x 2 No osteoporosis medications x 2