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Ten Years’ Experience with Alendronate Ten Years’ Experience with Alendronate for the Treatment of Osteoporosis for the Treatment of Osteoporosis in Postmenopausal Womenin Postmenopausal Women

Adapted from Bone HG, Hosking D, Devogelaer J-P, Tucci JR, Emkey Adapted from Bone HG, Hosking D, Devogelaer J-P, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA, for the Alendronate Phase III Osteoporosis Treatment AC, Liberman UA, for the Alendronate Phase III Osteoporosis Treatment Study Group. Study Group. N Engl J MedN Engl J Med 2004;350:1189–1199. 2004;350:1189–1199.

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IntroductionIntroductionIntroductionIntroduction• Postmenopausal women havePostmenopausal women have11

– increased bone turnoverincreased bone turnover

– higher rates of bone resorption than formationhigher rates of bone resorption than formation

– decreases in BMDdecreases in BMD

– greater susceptibility to fracturegreater susceptibility to fracture

• Alendronate is a potent bone resorption inhibitorAlendronate is a potent bone resorption inhibitor22

• 3-Year study showed that alendronate3-Year study showed that alendronate11

– increased BMDincreased BMD

– decreased bone turnover rate to within normal premenopausal range. decreased bone turnover rate to within normal premenopausal range.

– reduced the risk of vertebral fracturesreduced the risk of vertebral fractures

• The initial 3-year trials were extended for a total of 10 years – the longest study The initial 3-year trials were extended for a total of 10 years – the longest study of any osteoporosis treatmentof any osteoporosis treatment3,43,4

• Postmenopausal women havePostmenopausal women have11

– increased bone turnoverincreased bone turnover

– higher rates of bone resorption than formationhigher rates of bone resorption than formation

– decreases in BMDdecreases in BMD

– greater susceptibility to fracturegreater susceptibility to fracture

• Alendronate is a potent bone resorption inhibitorAlendronate is a potent bone resorption inhibitor22

• 3-Year study showed that alendronate3-Year study showed that alendronate11

– increased BMDincreased BMD

– decreased bone turnover rate to within normal premenopausal range. decreased bone turnover rate to within normal premenopausal range.

– reduced the risk of vertebral fracturesreduced the risk of vertebral fractures

• The initial 3-year trials were extended for a total of 10 years – the longest study The initial 3-year trials were extended for a total of 10 years – the longest study of any osteoporosis treatmentof any osteoporosis treatment3,43,4

Adapted from Liberman UA et al Adapted from Liberman UA et al N Engl J Med N Engl J Med 2004;333:1437–1443 and Bone HG et al 2004;333:1437–1443 and Bone HG et al N Engl J MedN Engl J Med 2004;350:1189–1199. 2004;350:1189–1199.

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Study ObjectiveStudy ObjectiveStudy ObjectiveStudy Objective

To examine the effects of prolonged alendronate To examine the effects of prolonged alendronate

therapy as well as its discontinuation, this therapy as well as its discontinuation, this

multinational, randomized double-blind study was multinational, randomized double-blind study was

extended for a total of 10 yearsextended for a total of 10 years

To examine the effects of prolonged alendronate To examine the effects of prolonged alendronate

therapy as well as its discontinuation, this therapy as well as its discontinuation, this

multinational, randomized double-blind study was multinational, randomized double-blind study was

extended for a total of 10 yearsextended for a total of 10 years

Adapted from Bone HG et al Adapted from Bone HG et al N Engl J MedN Engl J Med 2004;350:1189–1199. 2004;350:1189–1199.

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MethodsMethodsMethodsMethods• 994 Postmenopausal Osteoporotic Women (Initial 3-Year Study)994 Postmenopausal Osteoporotic Women (Initial 3-Year Study)

– First 2-Year, Double-Blind Extension (N = 727)First 2-Year, Double-Blind Extension (N = 727)

– Second 2-Year, Double-Blind Extension (N = 350)Second 2-Year, Double-Blind Extension (N = 350)

– Third 3-Year, Double-Blind Extension (N = 247)Third 3-Year, Double-Blind Extension (N = 247)

• Bone Mineral Density (BMD): DXABone Mineral Density (BMD): DXA

– Lumbar Spine (Primary), Femoral Neck, Trochanter, Total Hip, Lumbar Spine (Primary), Femoral Neck, Trochanter, Total Hip, Total Body, ForearmTotal Body, Forearm

• Biochemical Markers of Bone Turnover (BSAP, NTx)Biochemical Markers of Bone Turnover (BSAP, NTx)

• Stature (Stadiometer)Stature (Stadiometer)

• Clinical and Laboratory Safety EvaluationsClinical and Laboratory Safety Evaluations

• 994 Postmenopausal Osteoporotic Women (Initial 3-Year Study)994 Postmenopausal Osteoporotic Women (Initial 3-Year Study)

– First 2-Year, Double-Blind Extension (N = 727)First 2-Year, Double-Blind Extension (N = 727)

– Second 2-Year, Double-Blind Extension (N = 350)Second 2-Year, Double-Blind Extension (N = 350)

– Third 3-Year, Double-Blind Extension (N = 247)Third 3-Year, Double-Blind Extension (N = 247)

• Bone Mineral Density (BMD): DXABone Mineral Density (BMD): DXA

– Lumbar Spine (Primary), Femoral Neck, Trochanter, Total Hip, Lumbar Spine (Primary), Femoral Neck, Trochanter, Total Hip, Total Body, ForearmTotal Body, Forearm

• Biochemical Markers of Bone Turnover (BSAP, NTx)Biochemical Markers of Bone Turnover (BSAP, NTx)

• Stature (Stadiometer)Stature (Stadiometer)

• Clinical and Laboratory Safety EvaluationsClinical and Laboratory Safety Evaluations


DXA = Dual-energy x-rayNTx = urinary N-telopeptides of type I collagenBSAP = serum bone-specific alkaline phosphatase

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Phase III Osteoporosis Treatment Studies Phase III Osteoporosis Treatment Studies Alendronate Treatment ScheduleAlendronate Treatment SchedulePhase III Osteoporosis Treatment Studies Phase III Osteoporosis Treatment Studies Alendronate Treatment ScheduleAlendronate Treatment Schedule

10 mg Ineligible Ineligible

5 mg 5 mg 5 mg

10 mg 10 mg 10 mg

5 mg 5 mg Placebo Placebo20 mg

3rd ExtensionYears 8 to 10

Year 1 Year 2 Year 31st ExtensionYears 4 and 5

10 mg

5 mg

Placebo

2nd ExtensionYears 6 and 7

Adapted from Bone HG et al Adapted from Bone HG et al N Engl J MedN Engl J Med 2004;350:1189– 2004;350:1189–1199.1199.

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Statistical AnalysesStatistical AnalysesStatistical AnalysesStatistical Analyses

• BMD:BMD:– Percent Change at Year 10:Percent Change at Year 10:

• From BaselineFrom Baseline• From Years 6 and 8From Years 6 and 8

– Modified Intention to TreatModified Intention to Treat

• NTx, BSAP:NTx, BSAP:– Percent Change from BaselinePercent Change from Baseline– Per-Protocol*Per-Protocol*

• Safety Profile:Safety Profile:– Adverse Experiences (Years 8–10)Adverse Experiences (Years 8–10)– Stature (Years 6–10)Stature (Years 6–10)– Fractures Reported as Adverse Experiences (Years 6–10)Fractures Reported as Adverse Experiences (Years 6–10)

• BMD:BMD:– Percent Change at Year 10:Percent Change at Year 10:

• From BaselineFrom Baseline• From Years 6 and 8From Years 6 and 8

– Modified Intention to TreatModified Intention to Treat

• NTx, BSAP:NTx, BSAP:– Percent Change from BaselinePercent Change from Baseline– Per-Protocol*Per-Protocol*

• Safety Profile:Safety Profile:– Adverse Experiences (Years 8–10)Adverse Experiences (Years 8–10)– Stature (Years 6–10)Stature (Years 6–10)– Fractures Reported as Adverse Experiences (Years 6–10)Fractures Reported as Adverse Experiences (Years 6–10)

*Included study participants compliant with protocol*Included study participants compliant with protocolAdapted from Bone HG et al Adapted from Bone HG et al N Engl J MedN Engl J Med 2004;350:1189–1199. 2004;350:1189–1199.

BMD = bone mineral densityNTx = urinary N-telopeptides of type I collagenBSAP = serum bone-specific alkaline phosphatase

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ALN 20/5/PBO ALN 5 mg ALN 10 mgALN 20/5/PBO ALN 5 mg ALN 10 mg

n=83n=83 n=78 n=78 n=86 n=86

Mean ±SDMean ±SD Mean ±SDMean ±SD Mean ±SDMean ±SD

Age (years) 63 ±6.2 64 ±7.2 63 ±6.0Age (years) 63 ±6.2 64 ±7.2 63 ±6.0

Years since Menopause 16 ±7.6 16 ±7.7 15 ±7.7Years since Menopause 16 ±7.6 16 ±7.7 15 ±7.7

Body Mass Index (kg/mBody Mass Index (kg/m22) 25 ±3.5 24 ±3.6 24 ±2.9 ) 25 ±3.5 24 ±3.6 24 ±2.9

Estimated Calcium Intake (mg/day) 704 ±459 838 ±516 747 ±563Estimated Calcium Intake (mg/day) 704 ±459 838 ±516 747 ±563

Baseline Spine BMD (g/cmBaseline Spine BMD (g/cm22)** )**

-Hologic, Norland 0.71 ±0.1 0.70 ±0.1 0.70 ±0.1-Hologic, Norland 0.71 ±0.1 0.70 ±0.1 0.70 ±0.1

-Lunar-Lunar 0.81 ±0.1 0.80 ±0.1 0.82 ±0.1 0.81 ±0.1 0.80 ±0.1 0.82 ±0.1

ALN 20/5/PBO ALN 5 mg ALN 10 mgALN 20/5/PBO ALN 5 mg ALN 10 mg

n=83n=83 n=78 n=78 n=86 n=86

Mean ±SDMean ±SD Mean ±SDMean ±SD Mean ±SDMean ±SD

Age (years) 63 ±6.2 64 ±7.2 63 ±6.0Age (years) 63 ±6.2 64 ±7.2 63 ±6.0

Years since Menopause 16 ±7.6 16 ±7.7 15 ±7.7Years since Menopause 16 ±7.6 16 ±7.7 15 ±7.7

Body Mass Index (kg/mBody Mass Index (kg/m22) 25 ±3.5 24 ±3.6 24 ±2.9 ) 25 ±3.5 24 ±3.6 24 ±2.9

Estimated Calcium Intake (mg/day) 704 ±459 838 ±516 747 ±563Estimated Calcium Intake (mg/day) 704 ±459 838 ±516 747 ±563

Baseline Spine BMD (g/cmBaseline Spine BMD (g/cm22)** )**

-Hologic, Norland 0.71 ±0.1 0.70 ±0.1 0.70 ±0.1-Hologic, Norland 0.71 ±0.1 0.70 ±0.1 0.70 ±0.1

-Lunar-Lunar 0.81 ±0.1 0.80 ±0.1 0.82 ±0.1 0.81 ±0.1 0.80 ±0.1 0.82 ±0.1* Pre-treatment status of patients enrolled in the third, 3-year double-blind extension study, N = 247** Mean baseline T-score = -3.1ALN = Alendronate; PBO = Placebo

Baseline Characteristics*Baseline Characteristics*Baseline Characteristics*Baseline Characteristics*


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Continuous Increases in Lumbar Spine BMD with Continuous Increases in Lumbar Spine BMD with Alendronate 10 mg over 10 YearsAlendronate 10 mg over 10 YearsContinuous Increases in Lumbar Spine BMD with Continuous Increases in Lumbar Spine BMD with Alendronate 10 mg over 10 YearsAlendronate 10 mg over 10 Years

0 1 2 3 4 5 6 7 8 9 100

2

4

6

8

10

12

14

Year

Mea

n P

erce

nt C

hang

e (±

SE

)

ALN 5 mg (n=78)

ALN 10 mg (n=86)ALN 20 mg/ALN 5 mg/Placebo (n=83)


The mean percent change from baseline to year 10 appears in parentheses following each treatment group.The mean percent change from baseline to year 10 appears in parentheses following each treatment group.

(9.3%) p<0.001

(13.7%) p<0.001

(9.3%) p<0.001

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Sustained Increases in Total Hip BMD with Sustained Increases in Total Hip BMD with Alendronate 10 mg over 10 Years Alendronate 10 mg over 10 Years Sustained Increases in Total Hip BMD with Sustained Increases in Total Hip BMD with Alendronate 10 mg over 10 Years Alendronate 10 mg over 10 Years

ALN 5 mg (n=78)

ALN 10 mg (n=86)

ALN 20 mg/ALN 5 mg/Placebo (n=83)


The mean percent change from baseline to year 10 appears in parentheses following each treatment group.The mean percent change from baseline to year 10 appears in parentheses following each treatment group.

0 1 2 3 4 5 6 7 8 9 10

9

0

1

2

3

4

5

6

7

8

Year

Mea

n P

erce

nt C

hang

e (±

SE

)

(2.9%) p<0.05

(6.7%) p<0.001

(3.4%) p<0.001

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Mea

n P

erce

nt C

hang

e

Urine NTx BSAP

Bone Turnover MarkersBone Turnover MarkersBone Turnover MarkersBone Turnover Markers

-70

-60

-50

-40

-30

-20

-10

0

Year0 1 2 3 4 5 6 7 8 9 10

ALN 10 mg ALN 20 mg/ALN 5 mg/PlaceboALN 5 mgYear

0 1 2 3 4 5 6 7 8 9 10

-90

-80

-70

-60

-50

-40

-30

-20

-10

0


NTx = urinary N-telopeptides of type I collagenBSAP = serum bone-specific alkaline phosphatase

• Reduced turnover to within normal premenopausal range.Reduced turnover to within normal premenopausal range.4,54,5

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Height Loss with Alendronate 10 mg in Years 6–10 Height Loss with Alendronate 10 mg in Years 6–10 Was Similar to Alendronate in Years 1–3*Was Similar to Alendronate in Years 1–3*Height Loss with Alendronate 10 mg in Years 6–10 Height Loss with Alendronate 10 mg in Years 6–10 Was Similar to Alendronate in Years 1–3*Was Similar to Alendronate in Years 1–3*

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

Placebo(n=397)

All ALN(n=597)

ALN/20/5/PBO(n=65)

ALN 5 mg(n=57)

ALN 10 mg(n=73)

Years 1–3 Years 6–10

Hei

ght L

oss

(mm

/yea

r)

*Years 1–3 included all alendronate-treated women*Years 1–3 included all alendronate-treated women Adapted from Bone HG et al Adapted from Bone HG et al N Engl J MedN Engl J Med 2004;350:1189–1199 2004;350:1189–1199

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Wom

en w

ith F

ract

ure

per

100

Pat

ient

-Yea

rs

0

1

2

3

4

5

Placebo(n=397)

All ALN(n=597)

Estimated Placebo

ALN20/5/PBO

(n=83)

ALN 5 mg

(n=78)

ALN 10 mg(n=86)

Years 1–3 Years 6–10

Nonvertebral Fracture Reduction Sustained Nonvertebral Fracture Reduction Sustained through 10 Yearsthrough 10 YearsNonvertebral Fracture Reduction Sustained Nonvertebral Fracture Reduction Sustained through 10 Yearsthrough 10 Years


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Gastrointestinal Adverse ExperiencesGastrointestinal Adverse ExperiencesYears 8–10Years 8–10Gastrointestinal Adverse ExperiencesGastrointestinal Adverse ExperiencesYears 8–10Years 8–10

PUBs = Perforations, Ulcers or Bleeds

% Of women with % Of women with adverse experiences:adverse experiences:

Any Upper GIAny Upper GI Serious Serious Withdrawn Withdrawn

EsophagealEsophagealPUBsPUBs

24.124.1 1.2 1.2 2.4 2.4

7.27.2 0 0

ALN/20/5/PBOALN/20/5/PBO (n=83)(n=83)

27.927.9 0 0 2.3 2.3

2.32.3 0 0

ALN 10 mgALN 10 mg(n=86)(n=86)

14.114.1 1.3 1.3 1.3 1.3

1.31.3 1.3 1.3

ALN 5 mgALN 5 mg(n=78)(n=78)


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SummarySummarySummarySummary

• Significant increases in BMD from baseline up to 10 years Significant increases in BMD from baseline up to 10 years

Lumbar spine: 13.7% increaseLumbar spine: 13.7% increase

Total hip: 6.7% increaseTotal hip: 6.7% increase

• Sustained reduction of bone turnover to within the Sustained reduction of bone turnover to within the premenopausal rangepremenopausal range

• Nonvertebral fracture incidence in years 6–10 similar to that Nonvertebral fracture incidence in years 6–10 similar to that observed in patients treated with alendronate in years 1–3observed in patients treated with alendronate in years 1–3

• Significant increases in BMD from baseline up to 10 years Significant increases in BMD from baseline up to 10 years

Lumbar spine: 13.7% increaseLumbar spine: 13.7% increase

Total hip: 6.7% increaseTotal hip: 6.7% increase

• Sustained reduction of bone turnover to within the Sustained reduction of bone turnover to within the premenopausal rangepremenopausal range

• Nonvertebral fracture incidence in years 6–10 similar to that Nonvertebral fracture incidence in years 6–10 similar to that observed in patients treated with alendronate in years 1–3observed in patients treated with alendronate in years 1–3

Continuous treatment with daily oral alendronate 10 mg for Continuous treatment with daily oral alendronate 10 mg for 10 years resulted in the following:10 years resulted in the following:


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ConclusionsConclusionsConclusionsConclusions• Alendronate is the only osteoporosis therapy demonstrating Alendronate is the only osteoporosis therapy demonstrating

10 years of sustained efficacy10 years of sustained efficacy3,43,4

• Continuous alendronate for 10 years: Continuous alendronate for 10 years: – Progressively increases lumbar spine BMDProgressively increases lumbar spine BMD– Increases, then maintains hip BMDIncreases, then maintains hip BMD– Produces greater effects at 10 vs. 5 mg/dayProduces greater effects at 10 vs. 5 mg/day– Maintains stable reduction of bone turnoverMaintains stable reduction of bone turnover

• Risk of nonvertebral fractures years 6–10 similar to years 1–3 Risk of nonvertebral fractures years 6–10 similar to years 1–3 (10 mg dose)(10 mg dose)

• Discontinuation of alendronate after 5 years:Discontinuation of alendronate after 5 years:– Is associated with only partial resolution of effectIs associated with only partial resolution of effect– Does not lead to accelerated bone lossDoes not lead to accelerated bone loss

• Continuous therapy yields greater skeletal benefitsContinuous therapy yields greater skeletal benefits

• Alendronate is the only osteoporosis therapy demonstrating Alendronate is the only osteoporosis therapy demonstrating 10 years of sustained efficacy10 years of sustained efficacy3,43,4

• Continuous alendronate for 10 years: Continuous alendronate for 10 years: – Progressively increases lumbar spine BMDProgressively increases lumbar spine BMD– Increases, then maintains hip BMDIncreases, then maintains hip BMD– Produces greater effects at 10 vs. 5 mg/dayProduces greater effects at 10 vs. 5 mg/day– Maintains stable reduction of bone turnoverMaintains stable reduction of bone turnover

• Risk of nonvertebral fractures years 6–10 similar to years 1–3 Risk of nonvertebral fractures years 6–10 similar to years 1–3 (10 mg dose)(10 mg dose)

• Discontinuation of alendronate after 5 years:Discontinuation of alendronate after 5 years:– Is associated with only partial resolution of effectIs associated with only partial resolution of effect– Does not lead to accelerated bone lossDoes not lead to accelerated bone loss

• Continuous therapy yields greater skeletal benefitsContinuous therapy yields greater skeletal benefits


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BibliographyBibliographyBibliographyBibliography

1. 1. Liberman UA, Stuart RW, Broll J et al. Effect of alendronate on bone mineral density Liberman UA, Stuart RW, Broll J et al. Effect of alendronate on bone mineral density and the incidence of fractures in postmenopausal women. and the incidence of fractures in postmenopausal women. N Engl J MedN Engl J Med 1995;333:1437–1443.1995;333:1437–1443.

2. 2. Tonino RP, Meunier PJ, Emkey R et al. Skeletal benefits of alendronate: 7-Year Tonino RP, Meunier PJ, Emkey R et al. Skeletal benefits of alendronate: 7-Year treatment of postmenopausal osteoporotic women. treatment of postmenopausal osteoporotic women. J Clin Endocrinol MetabJ Clin Endocrinol Metab 2000;85:3109–3115.2000;85:3109–3115.

3.3. Data on file, MSD ________.Data on file, MSD ________.

4. 4. Bone HG, Hosking D, Devogelaer J-P et al. Ten years’ experience with alendronate Bone HG, Hosking D, Devogelaer J-P et al. Ten years’ experience with alendronate for the treatment of osteoporosis in postmenopausal women. for the treatment of osteoporosis in postmenopausal women. N Engl J MedN Engl J Med 2004;350:1189–1199.2004;350:1189–1199.

5. 5. Garnero P, Sornay-Rendu E, Chapuy M-C et al. Increased bone turnover in late Garnero P, Sornay-Rendu E, Chapuy M-C et al. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. postmenopausal women is a major determinant of osteoporosis. J Bone Miner ResJ Bone Miner Res 1996;11(3):337–349. 1996;11(3):337–349.

1. 1. Liberman UA, Stuart RW, Broll J et al. Effect of alendronate on bone mineral density Liberman UA, Stuart RW, Broll J et al. Effect of alendronate on bone mineral density and the incidence of fractures in postmenopausal women. and the incidence of fractures in postmenopausal women. N Engl J MedN Engl J Med 1995;333:1437–1443.1995;333:1437–1443.

2. 2. Tonino RP, Meunier PJ, Emkey R et al. Skeletal benefits of alendronate: 7-Year Tonino RP, Meunier PJ, Emkey R et al. Skeletal benefits of alendronate: 7-Year treatment of postmenopausal osteoporotic women. treatment of postmenopausal osteoporotic women. J Clin Endocrinol MetabJ Clin Endocrinol Metab 2000;85:3109–3115.2000;85:3109–3115.

3.3. Data on file, MSD ________.Data on file, MSD ________.

4. 4. Bone HG, Hosking D, Devogelaer J-P et al. Ten years’ experience with alendronate Bone HG, Hosking D, Devogelaer J-P et al. Ten years’ experience with alendronate for the treatment of osteoporosis in postmenopausal women. for the treatment of osteoporosis in postmenopausal women. N Engl J MedN Engl J Med 2004;350:1189–1199.2004;350:1189–1199.

5. 5. Garnero P, Sornay-Rendu E, Chapuy M-C et al. Increased bone turnover in late Garnero P, Sornay-Rendu E, Chapuy M-C et al. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. postmenopausal women is a major determinant of osteoporosis. J Bone Miner ResJ Bone Miner Res 1996;11(3):337–349. 1996;11(3):337–349.

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Protocol 035 InvestigatorsProtocol 035 Investigators

Mary Baker*Mary Baker* Jeffrey Miller Jeffrey Miller

Norman Bell*Norman Bell* Anthony Mulloy* Anthony Mulloy*

Michael Bliziotes*Michael Bliziotes* Robert Recker* Robert Recker*

Henry Bone* Henry Bone* Richard Tonino* Richard Tonino*

Robert Downs* Robert Downs* Joseph Tucci* Joseph Tucci*

Ronald Emkey*Ronald Emkey* Richard Wasnich* Richard Wasnich*

Murray Favus* Murray Favus* Nelson Watts* Nelson Watts*

C. Conrad Johnston* Robert WeinsteinC. Conrad Johnston* Robert Weinstein

Robert Marcus* Robert Marcus* Stuart Weiss* Stuart Weiss*

Harris McIlwain*Harris McIlwain*

* Participated in the 3rd Extension* Participated in the 3rd Extension

Protocol 037 InvestigatorsProtocol 037 Investigators

Johann Bröll*Johann Bröll* J.M. Kaufman* J.M. Kaufman*

Catherine CormierCatherine Cormier M.O.R. LeiteM.O.R. Leite

R. Correa-Rotter*R. Correa-Rotter* Uri Liberman*Uri Liberman*

David C. Cumming*David C. Cumming* Joel MenkesJoel Menkes

J. Dequeker *J. Dequeker * Pierre MeunierPierre Meunier

J-P. Devogelaer*J-P. Devogelaer* Ian Reid*Ian Reid*

P. GeusensP. Geusens Jose Rodriguez-Jose Rodriguez-Portales* Portales*

David Hosking*David Hosking* Ego Seeman* Ego Seeman*

Phillippe Jaeger*Phillippe Jaeger*

Phase III Osteoporosis Treatment Phase III Osteoporosis Treatment Study GroupStudy GroupPhase III Osteoporosis Treatment Phase III Osteoporosis Treatment Study GroupStudy Group

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