Emerging Trends in Osteoporosis Scioto County Medical Society Current Therapy Seminar 10/26/2007 Steven Ing, MD, MSCE Division of Endocrinology, Diabetes,

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

Spine 1.107 (-0.6, -0.3) Spine 1.107 (-0.6, -0.3) 1.016 (-1.4, -0.8) 1.016 (-1.4, -0.8)-8.2%-8.2%

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

Hip fracture HR: (ITT): 0.88 (0.72-1.08)Hip fracture HR: (ITT): 0.88 (0.72-1.08) Adherence (>80%): HR 0.71 (0.52 – 0.97)Adherence (>80%): HR 0.71 (0.52 – 0.97) Older age (60+): HR 0.79 (0.64-0.98)Older age (60+): HR 0.79 (0.64-0.98)

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)

AIAI** ULUL** AIAI ULUL****

0-6 months: 0-6 months: 210210 NDND 200200 10001000 6-12 months: 6-12 months: 270270 NDND 200200 10001000 1-3 years:1-3 years: 500500 25002500 200200 20002000 4-8 years:4-8 years: 800 800 25002500 200200 20002000 9-18 years:9-18 years: 1300 1300 25002500 200200 20002000 19-50 years:19-50 years: 1000 1000 25002500 200200 20002000 51-70 years:51-70 years: 12001200 25002500 400400 20002000 >70 years:>70 years: 12001200 25002500 600600 20002000

•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

NOF RecommendationsNOF Recommendations

CalciumCalcium Age < 50 years: 1,000 mg calcium dailyAge < 50 years: 1,000 mg calcium daily Age ≥ 50 years: 1,200 mg calcium dailyAge ≥ 50 years: 1,200 mg calcium daily

Vitamin DVitamin D Age < 50 years: 400-800 IU vitamin D Age < 50 years: 400-800 IU vitamin D

dailydaily Age ≥ 50 years: 800-1000 IU vitamin D Age ≥ 50 years: 800-1000 IU vitamin D

dailydaily

http://www.nof.org/prevention/calcium_and_VitaminD.htmAccessed 7/27/2007

Estimating Dietary Estimating Dietary CalciumCalcium

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

Lactose-free productsLactose-free products Gradually increase lactose-containing foods (induce Gradually increase lactose-containing foods (induce

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: $

BrandBrand CalciuCalciumm

mgmg

Vitamin Vitamin DD

IUIU

# # tabstabs

$$ ¢/¢/tabtab

OscalOscal 500500 00 7575 $8.49$8.49 11.311.3¢¢

WalgreenWalgreen 600600 00 6060 $4.99$4.99 8.3¢8.3¢

WalgreenWalgreen 600600 00 400400 $13.9$13.999

3.5¢3.5¢

Tums EXTums EX 300300 00 9696 $4.99$4.99 5.2¢5.2¢


Oscal + DOscal + D 500500 200200 160160 $14.9$14.999

9.4¢9.4¢


Caltrate Caltrate + D+ D

600600 400400 6060 $7.99$7.99 13.313.3¢¢


CitracalCitracal 250250 200200 150150 $12.9$12.999

8.7¢8.7¢


Vitamin DVitamin D 00 10001000 100100 $6.25$6.25 6.3¢6.3¢

Question #2: What’s Question #2: What’s “ONJ”?“ONJ”?

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

bisphosphonatebisphosphonateRuggiero sl, J Oral Maxillofac Surg Ruggiero sl, J Oral Maxillofac Surg

2004;62:527-5342004;62:527-534

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

fractures fractures (JAMA 1998;280:2077-2082)(JAMA 1998;280:2077-2082)

NEJM 2004;350(12):1172-1174

Fracture Intervention Trial Fracture Intervention Trial Long-term Extension Long-term Extension

(FLEX)(FLEX) 1099 of FIT subjects on the alendronate 1099 of FIT subjects on the alendronate

arm (5 yrs)arm (5 yrs) Randomized to 5 more years: placebo vs. Randomized to 5 more years: placebo vs.

alendronatealendronate Excluded: very low T-score (<-3.5), BMD Excluded: very low T-score (<-3.5), BMD

lower than baseline FIT BMDlower than baseline FIT BMD Primary outcome: total hip BMD (power Primary outcome: total hip BMD (power

to detect 0.9% difference)to detect 0.9% difference) Secondary outcome: BMD at other sitesSecondary outcome: BMD at other sites Exploratory outcome: fracture incidence Exploratory outcome: fracture incidence

(detect ≥ 13.5% risk ↓)(detect ≥ 13.5% risk ↓)

Black DM et. al., JAMA 2006;296:2927-2938


FLEX (cont’d)FLEX (cont’d)


SiteSite PlacePlacebobo

N=42N=4288

AlendronaAlendronatete**

N=643N=643

DifferencDifference e

(95% CI)(95% CI)

P-P-valuevalue

Total hip Total hip BMDBMD

--3.38%3.38%

-1.02%-1.02% 2.36% 2.36%

(1.81-(1.81-2.90)2.90)

<0.001<0.001

Lumbar Lumbar spine spine BMDBMD

+1.52+1.52%%

+5.26%+5.26% 3.74% 3.74%

(3.03-(3.03-4.45)4.45)

<0.001<0.001* Alendronate group pooled: 5 mg daily and 10 mg daily

FLEX (cont’d)FLEX (cont’d)Fracture SiteFracture Site PlaceboPlacebo

N (%)N (%)AlendronatAlendronatee

N (%)N (%)

RRRR

Morphometric Morphometric SpineSpine

46 (11.3)46 (11.3) 60 (9.8)60 (9.8) 0.86 (0.60-0.86 (0.60-1.22)1.22)

Clinical SpineClinical Spine 23 (5.3)23 (5.3) 16 (2.4)16 (2.4) 0.45 (0.24-0.45 (0.24-0.85)0.85)

HipHip 13 (3.0)13 (3.0) 20 (3.0)20 (3.0) 1.02 (0.51-1.02 (0.51-2.10)2.10)

ForearmForearm 19 (4.3)19 (4.3) 31 (4.7)31 (4.7) 1.09 (0.62-1.09 (0.62-1.96)1.96)

NonspineNonspine 83 (19.0)83 (19.0) 125 (18.9)125 (18.9) 1.00 (0.76-1.00 (0.76-1.32)1.32)

AnyAny 93 (21.3)93 (21.3) 132 (19.9)132 (19.9) 0.93 (0.71-0.93 (0.71-1.21)1.21)Black DM et. al., JAMA 2006;296:2927-2938

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


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

toleratedtolerated Review oral bisphosphonate instructions Review oral bisphosphonate instructions

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

three monthsthree months Placebo Placebo

Placebo (SD)Placebo (SD)

N=975N=975Daily (SD)Daily (SD)

N=977N=977Intermittent Intermittent (SD)(SD)

N=977N=977

Age (SD)Age (SD) 69 (6)69 (6) 69 (6)69 (6) 69 (6)69 (6)

LS T-LS T-scorescore

-2.8 (0.9)-2.8 (0.9) -2.8 (0.9)-2.8 (0.9) -2.7 (0.9)-2.7 (0.9)

Hip T-Hip T-scorescore

-1.7 (0.9)-1.7 (0.9) -1.7 (0.8)-1.7 (0.8) -1.7 (0.9)-1.7 (0.9)

NTXNTX(nmol/mmol (nmol/mmol Cr)Cr)

61 (34)61 (34) 64 (40)64 (40) 64 (32)64 (32)

BONE Study ResultsBONE Study Results

PlaceboPlacebo 2.5 mg Daily2.5 mg Daily IntermittentIntermittent

ΔΔLS BMDLS BMD +1.3%+1.3% +6.5%+6.5% +5.7%+5.7%

New New morphometric morphometric spine fracture spine fracture (1°)(1°)

9.6% (7.5-11.7)9.6% (7.5-11.7) 4.7% (3.2-6.2)4.7% (3.2-6.2)

RR 0.38 RR 0.38 (p=0.0001)(p=0.0001)

4.9% (3.4-6.4)4.9% (3.4-6.4)

RR 0.50 RR 0.50 (p=0.0006)(p=0.0006)

New clinical New clinical spine fracture spine fracture (2°)(2°)

5.3% (3.7-6.9)5.3% (3.7-6.9) 2.8% (1.6-3.9)2.8% (1.6-3.9)

RR 0.51 RR 0.51 (p=0.01)(p=0.01)

2.8% (1.6-3.9)2.8% (1.6-3.9)

RR 0.52 RR 0.52 (p=0.01)(p=0.01)

New New nonvertebral nonvertebral fracture (2°)fracture (2°)

8.2%8.2% 9.1%9.1%

NSNS8.9%8.9%

NSNS

Chestnut CH, et. al. JBMR 2004;19:1241-1249

BONE: Fem Neck T-score BONE: Fem Neck T-score <-3.0<-3.0

PLA

Daily

Intermittent

Chestnut CH, et. al. JBMR 2004;19:1241-1249

Intermittent Oral DosingIntermittent Oral Dosing

BisphosphonBisphosphonateate

DosageDosage FDA FDA ApprovalApproval

ibandronateibandronate 150 mg 150 mg monthlymonthly

(2.5 mg (2.5 mg daily)daily)

20052005

(2003)(2003)

risedronaterisedronate 35 mg 35 mg weeklyweekly

(5 mg daily)(5 mg daily)

20022002

(1998)(1998)

alendronatealendronate 70 mg 70 mg weeklyweekly

(10 mg (10 mg daily)daily)

20012001

(1995)(1995)

Dosing Intravenous Dosing Intravenous Administration Study Administration Study

(DIVA): IV Ibandronate(DIVA): IV Ibandronate Randomized, double-blind, double-Randomized, double-blind, double-

placebo, non-inferiority studyplacebo, non-inferiority study Inclusion: Inclusion:

♀♀, age 55-80, ≥5 years postmenopausal, age 55-80, ≥5 years postmenopausal LS T-score <-2.5LS T-score <-2.5

Primary endpoint: Primary endpoint: ΔΔ LS BMD at 1 LS BMD at 1 yearyear

Secondary endpoint: Secondary endpoint: ΔΔ Hip BMD, Hip BMD, CTX, safetyCTX, safety

Delmas PD, et. al. Arthritis & Rheum 2006

Dosing Intravenous Dosing Intravenous Administration Study Administration Study

(DIVA): IV Ibandronate(DIVA): IV Ibandronate2 mg IV q 2 2 mg IV q 2 monthsmonths

N=353N=353

3 mg IV q 3 3 mg IV q 3 monthsmonths

N=365N=365

2.5 mg PO 2.5 mg PO dailydaily

N=377N=377

ΔΔ L2-4 BMD L2-4 BMD +5.1% (4.7, +5.1% (4.7, 5.5)5.5)

p<0.001 vs p<0.001 vs oraloral

+4.8% (4.5, +4.8% (4.5, 5.2)5.2)

p<0.001 vs p<0.001 vs oraloral

+3.8% +3.8%

(3.4, 4.2) (3.4, 4.2)

ΔΔ Total Hip Total Hip BMDBMD

+2.6%+2.6%

p<0.05 vs oralp<0.05 vs oral+2.4%+2.4%

p<0.05 vs oralp<0.05 vs oral1.8%1.8%

ΔΔ CTX CTX -64.6%-64.6%

(-67.2, -62.5)(-67.2, -62.5)-58.6%-58.6%

(-61.4, -55.4)(-61.4, -55.4)-62.6%-62.6%

(-66.0, -58.9)(-66.0, -58.9)

FractureFracture 1313 1313 1717


IV Ibandronate: Adverse IV Ibandronate: Adverse EffectsEffects


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

facture facture

Baseline Baseline characteristicscharacteristics

PlaceboPlacebo ZolendronateZolendronate

# Subjects# Subjects 38613861 38753875

AgeAge 73.073.0 73.173.1

Fem neck T-score < -Fem neck T-score < -2.52.5

70.8%70.8% 72.6%72.6%

Vertebral fracture Vertebral fracture

0035.8%35.8% 37.6%37.6%

11 27.9%27.9% 28.2%28.2%

≥ ≥ 22 36.3%36.3% 34.1%34.1%Black DM, NEJM 2007;356(18):1809-1822

IV ZolendronateIV ZolendronatePlaPla

%%ZolZol

%%RRRR P-P-

valuevaluePrimary Primary

EndpointEndpointss

Radiographic Radiographic spine fracturespine fracture

10.910.9 3.33.3 0.30 (0.24-0.30 (0.24-0.38)0.38)

<0.001<0.001

Hip fractureHip fracture 2.52.5 1.41.4 0.59 (0.42-0.59 (0.42-0.83)0.83)

0.0020.002

SecondaSecondary ry EndpointEndpointss

Clinical Clinical vertebral vertebral fracturefracture

2.62.6 0.50.5 0.23 (0.14-0.23 (0.14-0.37)0.37)

<0.001<0.001

≥ ≥ 2 2 morphometric morphometric fracturefracture

2.32.3 0.20.2 0.11 (0.05-0.11 (0.05-0.23)0.23)

<0.001<0.001

Nonvertebral Nonvertebral fracturefracture

10.710.7 8.08.0 0.75 (0.64-0.75 (0.64-0.87)0.87)

<0.001<0.001

Any clinical Any clinical fracturefracture

12.812.8 8.48.4 0.67 (0.58-0.67 (0.58-0.77)0.77)

<0.001<0.001

Black DM, NEJM 2007;356(18):1809-1822

IV ZolendronateIV ZolendronatePlacebo (%)Placebo (%) Zol (%)Zol (%) P-valueP-value

ONJONJ 11 11

Transient ↑SCr Transient ↑SCr

> 0.5 mg/dl> 0.5 mg/dl10 (0.4)10 (0.4) 31 (1.2)31 (1.2) 0.0010.001

Post-dose flu-like Post-dose flu-like symptoms symptoms

After 1After 1stst infusion infusion

237 (6.2)237 (6.2) 1221 1221 (31.6)(31.6)

<0.001<0.001

After 2After 2ndnd infusion infusion 79 (2.1)79 (2.1) 253 (6.6)253 (6.6) <0.001<0.001

After 3After 3rdrd infusion infusion 42 (1.1)42 (1.1) 108 (2.8)108 (2.8) <0.001<0.001

Atrial fibrillation: Atrial fibrillation: serious AEserious AE

20 (0.5)20 (0.5) 50 (1.3)50 (1.3) <0.001<0.001

Black DM, NEJM 2007;356(18):1809-1822

IV Zolendronate: IV Zolendronate: SummarySummary

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

IndicationsIndications PMOPMO PMO, Paget’sPMO, Paget’s

DoseDose 3 mg q 3 months3 mg q 3 months 5 mg q 12 months5 mg q 12 months

AdministrationAdministration 15-30 second “IV push”15-30 second “IV push”

Prefilled syringe & Prefilled syringe & butterfly needlebutterfly needle

15 minute IV infusion15 minute IV infusion

5 mg in 100 mL solution5 mg in 100 mL solution

CostCost ~$2,000/year~$2,000/year ~$1,000/year~$1,000/year

ContraindicatiContraindications/ons/

PrecautionsPrecautions

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,

depressiondepression Meds: Fosamax, Caltrate 600-200 AM, OsCal 500 PM, MVI, Meds: Fosamax, Caltrate 600-200 AM, OsCal 500 PM, MVI,

Synthroid, Paxil, Claritin, Flonase, Aleve, glucosamineSynthroid, Paxil, Claritin, Flonase, Aleve, glucosamine ROS: intermittent loose bowel movementsROS: intermittent loose bowel movements

DXA dateDXA date L1-4L1-4 RFNRFN RTHRTH

4/3/19974/3/1997 0.826 (-2.9, -0.826 (-2.9, -1.6)1.6)

0.657 (-2.7, -0.657 (-2.7, -1.6)1.6)

0.668 (-2.6, -0.668 (-2.6, -1.7)1.7)

10/18/199910/18/1999 0.789 (-3.3, -0.789 (-3.3, -1.8)1.8)

0.768 (-1.8, -0.768 (-1.8, -0.6)0.6)

0.668 (-2.8, -0.668 (-2.8, -1.8)1.8)

4/10/20024/10/2002 0.788 (-3.3, -0.788 (-3.3, -1.5)1.5)

0.687 (-2.4, -0.687 (-2.4, -1.0)1.0)

0.669 (-2.8, -0.669 (-2.8, -1.6)1.6)

5/10/20045/10/2004 0.836 (-2.9, -0.836 (-2.9, -0.9)0.9)

0.692 (-2.4, -0.692 (-2.4, -0.9)0.9)

0.676 (-2.7, -0.676 (-2.7, -1.5)1.5)

Secondary Causes of Secondary Causes of OsteoporosisOsteoporosis

EndocrineEndocrineHypogonadismHypogonadismHyperparathyroidism (1Hyperparathyroidism (100 and and

2200))HyperthyroidismHyperthyroidismHypercortisolism (endogenous Hypercortisolism (endogenous

and exogenous)and exogenous)Vitamin D Vitamin D

deficiency/insufficiencydeficiency/insufficiency

Other DisordersOther DisordersGastrointestinal: sprue, IBD, Gastrointestinal: sprue, IBD,

PBC, PSC, bariatric surgeryPBC, PSC, bariatric surgeryHematologic: myeloma, Hematologic: myeloma,

mastocytosis, leukemia, mastocytosis, leukemia, lymphomalymphoma

Rheumatologic: RA, SLE, ASRheumatologic: RA, SLE, ASRenal: CKDRenal: CKDGenetic: OIGenetic: OI

Medications/Medications/LifestyleLifestyleGlucocorticoidGlucocorticoidCyclosporinCyclosporinAromatase inhibitorAromatase inhibitorGnRH agonistGnRH agonistAnticonvulsantAnticonvulsantHeparinHeparinMethotrexate (high dose)Methotrexate (high dose)EthanolEthanolCigarettesCigarettesImmobilizationImmobilizationDietary calcium (lactose Dietary calcium (lactose

intolerance)intolerance)Hypervitaminosis AHypervitaminosis A

MiscellaneousMiscellaneousHypercalciuriaHypercalciuriaTransplantationTransplantation

Evaluation for 2Evaluation for 200 CausesCauses

Chemistry panel (Ca, POChemistry panel (Ca, PO44, alkaline , alkaline phosphatase, albumin, ALT, AST, Cr)phosphatase, albumin, ALT, AST, Cr)

TSH TSH (hyperthyroidism)(hyperthyroidism) 25-OH vitamin D 25-OH vitamin D (hypovitaminosis D)(hypovitaminosis D) Testosterone Testosterone (male hypogonadism)(male hypogonadism) 24 hour urinary Ca and Cr 24 hour urinary Ca and Cr (hypercalciuria)(hypercalciuria) SPEP, UPEP SPEP, UPEP (myeloma)(myeloma) iPTH iPTH (1(100 or 2º hyperparathyroidism) or 2º hyperparathyroidism) 24 hour urinary free cortisol 24 hour urinary free cortisol (suspect Cushings’ (suspect Cushings’

syndrome)syndrome) Fe and ferritin Fe and ferritin (suspect malabsorption, (suspect malabsorption,

hemochromatosis)hemochromatosis) Antigliadin, antiendomysial Ab Antigliadin, antiendomysial Ab (suspect celiac (suspect celiac

disease)disease) Karotype analysisKarotype analysis (Turner, Klinefelter) (Turner, Klinefelter)

Lab ResultsLab Results Ca 9.1 mg/dl (8.6-10.0)Ca 9.1 mg/dl (8.6-10.0) Phos 3.6 mg/dl (2.7-4.5)Phos 3.6 mg/dl (2.7-4.5) Intact PTH 32.7 pg/ml (14-72)Intact PTH 32.7 pg/ml (14-72) 25 OH Vitamin D 44 ng/ml (>30)25 OH Vitamin D 44 ng/ml (>30) TSH 4.194 uIU/ml (0.35-5.50)TSH 4.194 uIU/ml (0.35-5.50) CBC: Hb 13.2 g/dl (11.7-15.5)CBC: Hb 13.2 g/dl (11.7-15.5) Urinary Ca 114 mg/24 hours (100-300)Urinary Ca 114 mg/24 hours (100-300) SPEP/UPEP: no monoclonal gammopathy, SPEP/UPEP: no monoclonal gammopathy,

albumin 3.4 g/dlalbumin 3.4 g/dl Transglutaminase IgA Ab 92.1 U (0-30)Transglutaminase IgA Ab 92.1 U (0-30)

ConclusionConclusion Small bowel biopsy: villous blunting, increased chronic Small bowel biopsy: villous blunting, increased chronic

inflammation, increased intraepithelial lymphocytes, inflammation, increased intraepithelial lymphocytes, Tx: stop Fosamax, start gluten free dietTx: stop Fosamax, start gluten free diet Lumbar spine: 0.836 Lumbar spine: 0.836 0.917 (+9.7%, but confounded 0.917 (+9.7%, but confounded

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



North North American American Menopause Menopause SocietySociety



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

2.312.31 2.252.25

Rheumatoid arthritisRheumatoid arthritis 1.951.95 1.731.73

Parental hx of hip Parental hx of hip fracturefracture

2.272.27 2.282.28

Current smokingCurrent smoking 1.841.84 1.601.60

Alcohol >2 drinks dailyAlcohol >2 drinks daily 1.681.68 1.701.70Kanis JA. Osteoporos Int 2002;13:527-36

Coming Soon: Absolute Coming Soon: Absolute Fracture RiskFracture Risk

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

Osteoporosis Prevention (FDA Osteoporosis Prevention (FDA Approved)Approved)

BisphosphonatesBisphosphonates alendronate (Fosamax) 35 weekly or 5 mg dailyalendronate (Fosamax) 35 weekly or 5 mg daily risendronate (Actonel) 35 mg weekly or 5 mg risendronate (Actonel) 35 mg weekly or 5 mg

dailydaily ibandronate (Boniva) 150 mg monthly or 2.5 mg ibandronate (Boniva) 150 mg monthly or 2.5 mg

dailydaily Selective estrogen-receptor modulatorsSelective estrogen-receptor modulators

raloxifene (Evista) 60 mg dailyraloxifene (Evista) 60 mg daily EstrogenEstrogen

conjugated equine estrogens 0.3-1.25 mg dailyconjugated equine estrogens 0.3-1.25 mg daily estradiol 0.014-0.1 mg daily (oral or skin patch)estradiol 0.014-0.1 mg daily (oral or skin patch)

Osteoporosis Treatment (FDA Osteoporosis Treatment (FDA Approved)Approved)

% Fracture Risk Reduction % Fracture Risk ReductionVertebraVertebra

llNonvertebNonverteb

ralralHipHip

Alendronate 70 mg Alendronate 70 mg weekly or 10 mg weekly or 10 mg dailydaily

45-5045-50 25-5025-50 20-5020-50

Risedronate 35 mg Risedronate 35 mg weekly or 5 mg weekly or 5 mg dailydaily

40-5040-50 20-4020-40 20-4020-40

Ibandronate 150 Ibandronate 150 mg monthly or 3 mg monthly or 3 mg IV quarterlymg IV quarterly

5050 NSNS Not Not studiedstudied

Zolendronate 5 mg Zolendronate 5 mg IV annuallyIV annually 7070 2525 4040Estrogen 0.625 mg Estrogen 0.625 mg (± MPA)(± MPA) 35-4035-40 20-3020-30 35-4035-40Raloxifene 60 mg Raloxifene 60 mg dailydaily 35-5035-50 NSNS NSNSTeriparatide 20 Teriparatide 20 mcg SQmcg SQ 6565 3535 Not Not

studiedstudiedCummings SR, JAMA 2006;296(21):2601-2610

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

yearsyears [email protected]@osumc.edu

Happy HalloweenHappy Halloween

Documents

Emerging Trends in Osteoporosis Scioto County Medical Society Current Therapy Seminar 10/26/2007 Steven Ing, MD, MSCE Division of Endocrinology, Diabetes,