Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density

A Randomized, Double-Blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of AMG 162 in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00043186

Enrollment

412

Registered

2002-08-07

Start date

2002-05-31

Completion date

2007-06-30

Last updated

2013-09-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Low Bone Mineral Density

Keywords

bone loss, osteoporosis

Brief summary

To determine the effect of denosumab treatment compared with placebo over 12 months on bone mineral density (BMD) of the lumbar spine in postmenopausal women with low BMD. The clinical hypothesis is that denosumab subcutaneous injections administered every 3 or 6 months for 12 months will significantly increase lumbar spine bone mineral density and will be well tolerated.

Interventions

DRUGPlacebo

Placebo subcutaneous injection

DRUGDenosumab

Denosumab for subcutaneous injection

DRUGAlendronate

Alendronate 70 mg tablets

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

No minimum to 80 Years

Healthy volunteers

Inclusion criteria

* women not more than 80 years of age on date of randomization * ≥ 1 year postmenopausal on date of randomization * ambulatory * if ≤ 60 years of age, or had or would require a bilateral oophorectomy, serum follicle stimulating hormone (FSH) \> 50 mU/mL or serum estradiol \< 20 pg/mL * low BMD (BMD T-score ≤ -1.8 at any 1 of the following sites: lumbar spine, femoral neck, or total hip; BMD T-scores must not have been \< -4.0 at the lumbar spine or - 3.5 at the femoral neck or total hip) * before any study-specific procedure, including the screening dual X-ray absorptiometry (DXA) scan, gave informed consent for participation in the study.

Exclusion criteria

* fluoride treatment for osteoporosis within the 2 years before the enrollment date * bisphosphonate use within the 12 months before the enrollment date * administration of the following medications within the 6 months before the enrollment date * tibolone * Parathyroid hormone (PTH) (or any derivative) * systemic glucocorticosteroids (\> 5 mg oral prednisone equivalent per day for \> 10 days) * inhaled corticosteroids (\> 2000 μg per day for \> 10 days) * anabolic steroids or testosterone * administration of the following medications within the 3 months before the enrollment date * systemic hormone replacement therapy * selective estrogen receptor modulators * calcitonin * calcitriol * current hyper- or hypothyroidism (allowed if stable on thyroid replacement therapy and thyroid-stimulating hormone was within the normal range) * current hyper- or hypoparathyroidism * albumin-adjusted serum calcium \< 8.5 mg/dL (\< 2.125 mol/L) * osteomalacia * rheumatoid arthritis * Paget's disease * malignancy within the 5 years before enrollment (except cervical carcinoma in situ or basal cell carcinoma, which were acceptable) * renal disease; ie, creatinine clearance ≤ 35 mL/min * any bone disease, other than osteoporosis, which could interfere with the interpretation of the findings (eg, osteogenesis imperfecta or osteopetrosis) * malabsorption syndrome * weight, height, or girth that could preclude accurate DXA measurements * \< 2 lumbar vertebrae (L1 through L4) evaluable by DXA * recent long bone fracture (within 6 months) * osteoporotic-related fracture (ie, crush or wedge vertebral fracture or hip fracture) known or suspected to have occurred within 2 years of randomization * \> 1 single, grade 1 vertebral fracture * currently enrolled in or had participated within the previous 30 days in other investigational device or drug trial(s) (For some trials, this may have been allowed after discussion and written approval from Amgen.) * known sensitivity to mammalian-derived drug preparations (eg, Herceptin®) * any organic or psychiatric disorder, serum chemistry, or hematology that, in the opinion of the investigator, could have prevented the subject from completing the study or have interfered with the interpretation of the study results * self-reported alcohol or drug abuse within the previous 12 months * any disorder that compromised the ability to give truly informed consent for participation in the study * previous administration of denosumab * known sensitivity or contraindication to alendronate * known sensitivity or contraindication to tetracycline derivatives (subjects in the biopsy substudy only).

Design outcomes

Primary

Measure	Time frame	Description
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms	Baseline and Month 12	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Secondary

Measure	Time frame	Description
Urine NTX/Creatinine Percent Change From Baseline at Month 12	Baseline and Month 12	Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm	Baseline and Month 12	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	Baseline and 24 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	Baseline and 36 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	Baseline and 42 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	Baseline and 48 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Serum CTX Percent Change From Baseline at Month 24	Baseline and 24 months	Serum C-Telopeptide (CTX). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Serum CTX Percent Change From Baseline at Month 36	Baseline and 36 months	Serum C-Telopeptide (CTX). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Serum CTX Percent Change From Baseline at Month 42	Baseline and 42 months	Serum C-Telopeptide (CTX). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Serum CTX Percent Change From Baseline at Month 48	Baseline and 48 months	Serum C-Telopeptide (CTX). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Urine NTX/Creatinine Percent Change From Baseline at Month 24	Baseline and 24 months	Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Urine NTX/Creatinine Percent Change From Baseline at Month 36	Baseline and 36 months	Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Urine NTX/Creatinine Percent Change From Baseline at Month 42	Baseline and 42 months	Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Urine NTX/Creatinine Percent Change From Baseline at Month 48	Baseline and 48 months	Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	Baseline and 12 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	Baseline and 24 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	Baseline and 36 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Serum CTX Percent Change From Baseline at Month 12	Baseline and Month 12	Serum C-Telopeptide (CTX). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	Baseline and 48 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	Baseline and 12 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	Baseline and 24 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	Baseline and 36 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	Baseline and 42 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	Baseline and 48 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Total Body Bone Mineral Density Percent Change From Baseline at Month 12	Baseline and 12 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Total Body Bone Mineral Density Percent Change From Baseline at Month 24	Baseline and 24 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Total Body Bone Mineral Density Percent Change From Baseline at Month 36	Baseline and 36 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Total Body Bone Mineral Density Percent Change From Baseline at Month 42	Baseline and 42 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Total Body Bone Mineral Density Percent Change From Baseline at Month 48	Baseline and 48 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	Baseline and 12 months	Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	Baseline and 24 months	Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	Baseline and 36 months	Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	Baseline and 42 months	Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.
Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	Baseline and 48 months	Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.
Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	Baseline and 42 months	Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Participant flow

Recruitment details

First Subject Enrolled: 11-May-2002 Last Subject Enrolled: 30-Apr-2003

Participants by arm

Arm	Count
Placebo Participants received double-blind subcutaneous (SC) placebo injections every 3 months until month 21 and then placebo SC injections once every 6 months from Month 24 through Month 42.	46
Denosumab 6 mg Q3M Participants received denosumab 6 mg SC every 3 months (Q3M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.	44
Denosumab 14 mg Q3M Participants received denosumab 14 mg SC every 3 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.	44
Denosumab 30 mg Q3M Participants received denosumab 30 mg SC every 3 months until Month 21 then placebo SC every 6 months at Month 24 and Month 30 and then denosumab 60 mg SC every 6 months at Month 36 and Month 42.	41
Denosumab 14 mg Q6M Participants received denosumab 14 mg SC every 6 months (Q6M) until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.	54
Denosumab 60 mg Q6M Participants received denosumab 60 mg SC every 6 months until Month 42.	47
Denosumab 100 mg Q6M Participants received denosumab 100 mg SC every 6 months until Month 21 and then denosumab 60 mg every 6 months from Month 24 through Month 42.	42
Denosumab 210 mg Q6M Participants received denosumab 210 mg SC every 6 months until Month 21 and then placebo every 6 months from Month 24 through Month 42.	47
Alendronate 70 mg Participants received open-label alendronate 70 mg tablets orally once a week through Month 24. From Month 24 to Month 48 participants received no treatment.	47
Total	412

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008
Overall Study	Adverse Event	2	2	2	3	2	1	2	1	3
Overall Study	Death	0	0	1	0	0	0	2	0	0
Overall Study	Disease progression	1	0	0	3	0	0	0	4	0
Overall Study	Ineligibility determined	0	0	0	0	0	0	0	0	1
Overall Study	Lost to Follow-up	3	5	1	1	1	1	1	1	2
Overall Study	Noncompliance	0	0	1	1	0	0	0	0	0
Overall Study	Other	0	0	1	1	0	0	0	0	0
Overall Study	Physician Decision	0	0	3	0	1	0	0	1	1
Overall Study	Withdrawal by Subject	11	8	11	13	14	6	12	9	10

Baseline characteristics

Characteristic	Alendronate 70 mg	Total	Placebo	Denosumab 6 mg Q3M	Denosumab 14 mg Q3M	Denosumab 30 mg Q3M	Denosumab 14 mg Q6M	Denosumab 60 mg Q6M	Denosumab 100 mg Q6M	Denosumab 210 mg Q6M
Age Continuous	62.8 Years STANDARD_DEVIATION 8.2	62.5 Years STANDARD_DEVIATION 8.1	63.7 Years STANDARD_DEVIATION 9.1	62.8 Years STANDARD_DEVIATION 8.6	62.3 Years STANDARD_DEVIATION 6	61.2 Years STANDARD_DEVIATION 8.5	61.4 Years STANDARD_DEVIATION 8.1	63.1 Years STANDARD_DEVIATION 8.1	64.9 Years STANDARD_DEVIATION 8.2	60.5 Years STANDARD_DEVIATION 7.8
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian	0 Participants	4 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Black or African American	3 Participants	12 Participants	0 Participants	1 Participants	1 Participants	2 Participants	1 Participants	1 Participants	3 Participants	0 Participants
Race/Ethnicity, Customized Hispanic or Latino	4 Participants	39 Participants	8 Participants	8 Participants	1 Participants	3 Participants	3 Participants	5 Participants	2 Participants	5 Participants
Race/Ethnicity, Customized Japanese	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized White or Caucasian	40 Participants	355 Participants	37 Participants	33 Participants	42 Participants	36 Participants	49 Participants	39 Participants	37 Participants	42 Participants
Sex: Female, Male Female	47 Participants	412 Participants	46 Participants	44 Participants	44 Participants	41 Participants	54 Participants	47 Participants	42 Participants	47 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	43 / 46	38 / 43	39 / 44	35 / 40	44 / 53	42 / 47	38 / 41	41 / 46	42 / 46
serious Total, serious adverse events	5 / 46	7 / 43	13 / 44	9 / 40	7 / 53	5 / 47	9 / 41	6 / 46	8 / 46

Outcome results

Primary

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and Month 12

Population: Randomized participants with non-missing Baseline and non-missing value at Month 12.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms	-0.81 Percent change	Standard Error 0.48
Denosumab 6 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms	4.41 Percent change	Standard Error 0.5
Denosumab 14 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms	4.71 Percent change	Standard Error 0.5
Denosumab 30 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms	6.69 Percent change	Standard Error 0.54
Denosumab 14 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms	3.03 Percent change	Standard Error 0.43
Denosumab 60 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms	4.55 Percent change	Standard Error 0.47
Denosumab 100 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms	5.52 Percent change	Standard Error 0.49
Denosumab 210 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms	5.07 Percent change	Standard Error 0.47

p-value: <0.00195% CI: [4.07, 6.64]ANCOVA

p-value: <0.00195% CI: [2.6, 5.07]ANCOVA

p-value: <0.00195% CI: [6.13, 8.87]ANCOVA

p-value: <0.00195% CI: [4.59, 7.16]ANCOVA

p-value: <0.00195% CI: [5.01, 7.65]ANCOVA

p-value: <0.00195% CI: [4.19, 6.85]ANCOVA

p-value: <0.00195% CI: [3.88, 6.55]ANCOVA

Secondary

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12

Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 12 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 12.

Arm	Measure	Value (MEDIAN)
Placebo	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	-4.609 Percent change
Denosumab 6 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	-62.716 Percent change
Denosumab 14 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	-60.098 Percent change
Denosumab 30 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	-70.256 Percent change
Denosumab 14 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	-39.474 Percent change
Denosumab 60 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	-65.215 Percent change
Denosumab 100 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	-61.979 Percent change
Denosumab 210 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	-67.634 Percent change
Alendronate 70 mg	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12	-61.059 Percent change

p-value: <0.001Wilcoxon (Mann-Whitney)

Secondary

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24

Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 24.

Arm	Measure	Value (MEDIAN)
Placebo	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	16.464 Percent change
Denosumab 6 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	-41.225 Percent change
Denosumab 14 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	-47.597 Percent change
Denosumab 30 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	-57.905 Percent change
Denosumab 14 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	-22.350 Percent change
Denosumab 60 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	-43.448 Percent change
Denosumab 100 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	-50.176 Percent change
Denosumab 210 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	-48.833 Percent change
Alendronate 70 mg	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24	-48.778 Percent change

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.002Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

Secondary

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36

Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 36.

Arm	Measure	Value (MEDIAN)
Placebo	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	1.955 Percent change
Denosumab 6 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	-39.012 Percent change
Denosumab 14 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	-56.021 Percent change
Denosumab 30 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	22.343 Percent change
Denosumab 14 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	-47.500 Percent change
Denosumab 60 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	-42.541 Percent change
Denosumab 100 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	-47.418 Percent change
Denosumab 210 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	61.747 Percent change
Alendronate 70 mg	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36	-8.209 Percent change

p-value: 0.049Wilcoxon (Mann-Whitney)

p-value: 0.008Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.146Wilcoxon (Mann-Whitney)

p-value: 0.001Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

Secondary

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42

Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 42.

Arm	Measure	Value (MEDIAN)
Placebo	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	1.288 Percent change
Denosumab 6 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	-40.182 Percent change
Denosumab 14 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	-40.819 Percent change
Denosumab 30 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	-52.684 Percent change
Denosumab 14 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	-53.763 Percent change
Denosumab 60 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	-44.892 Percent change
Denosumab 100 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	-48.303 Percent change
Denosumab 210 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	17.841 Percent change
Alendronate 70 mg	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42	-22.069 Percent change

p-value: 0.061Wilcoxon (Mann-Whitney)

p-value: 0.058Wilcoxon (Mann-Whitney)

p-value: 0.001Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.003Wilcoxon (Mann-Whitney)

p-value: 0.002Wilcoxon (Mann-Whitney)

Secondary

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48

Bone specific alkaline phosphatase (BSAP). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 48.

Arm	Measure	Value (MEDIAN)
Placebo	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	18.122 Percent change
Denosumab 6 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	-34.727 Percent change
Denosumab 14 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	-45.779 Percent change
Denosumab 30 mg Q3M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	-47.770 Percent change
Denosumab 14 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	-46.286 Percent change
Denosumab 60 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	-34.361 Percent change
Denosumab 100 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	-42.653 Percent change
Denosumab 210 mg Q6M	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	21.053 Percent change
Alendronate 70 mg	Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48	-17.891 Percent change

p-value: 0.142Wilcoxon (Mann-Whitney)

p-value: 0.218Wilcoxon (Mann-Whitney)

p-value: 0.003Wilcoxon (Mann-Whitney)

p-value: 0.01Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.01Wilcoxon (Mann-Whitney)

p-value: 0.02Wilcoxon (Mann-Whitney)

Secondary

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 12 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 12.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	-1.97 Percent change	Standard Error 0.5
Denosumab 6 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	0.89 Percent change	Standard Error 0.52
Denosumab 14 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	0.40 Percent change	Standard Error 0.53
Denosumab 30 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	1.10 Percent change	Standard Error 0.55
Denosumab 14 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	0.94 Percent change	Standard Error 0.46
Denosumab 60 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	1.29 Percent change	Standard Error 0.48
Denosumab 100 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	1.07 Percent change	Standard Error 0.5
Denosumab 210 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	1.09 Percent change	Standard Error 0.51
Alendronate 70 mg	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12	-0.53 Percent change	Standard Error 0.47

p-value: 0.03395% CI: [0.11, 2.76]ANCOVA

p-value: <0.00195% CI: [1.69, 4.42]ANCOVA

p-value: <0.00195% CI: [1.68, 4.4]ANCOVA

p-value: <0.00195% CI: [1.94, 4.57]ANCOVA

p-value: <0.00195% CI: [1.6, 4.21]ANCOVA

p-value: <0.00195% CI: [1.65, 4.49]ANCOVA

p-value: <0.00195% CI: [0.99, 3.76]ANCOVA

p-value: <0.00195% CI: [1.47, 4.24]ANCOVA

Secondary

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 24.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	-2.78 Percent change	Standard Error 0.56
Denosumab 6 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	1.31 Percent change	Standard Error 0.57
Denosumab 14 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	0.62 Percent change	Standard Error 0.58
Denosumab 30 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	1.30 Percent change	Standard Error 0.63
Denosumab 14 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	2.48 Percent change	Standard Error 0.52
Denosumab 60 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	1.89 Percent change	Standard Error 0.51
Denosumab 100 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	1.48 Percent change	Standard Error 0.56
Denosumab 210 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	0.81 Percent change	Standard Error 0.56
Alendronate 70 mg	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24	-0.78 Percent change	Standard Error 0.55

p-value: 0.00995% CI: [0.49, 3.49]ANCOVA

p-value: <0.00195% CI: [2.06, 5.1]ANCOVA

p-value: <0.00195% CI: [2.73, 5.78]ANCOVA

p-value: <0.00195% CI: [2.55, 5.62]ANCOVA

p-value: <0.00195% CI: [3.23, 6.11]ANCOVA

p-value: <0.00195% CI: [3.78, 6.73]ANCOVA

p-value: <0.00195% CI: [2.48, 5.68]ANCOVA

p-value: <0.00195% CI: [1.86, 4.93]ANCOVA

Secondary

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 36.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	-3.64 Percent change	Standard Error 0.63
Denosumab 6 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	1.99 Percent change	Standard Error 0.6
Denosumab 14 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	1.06 Percent change	Standard Error 0.69
Denosumab 30 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	1.05 Percent change	Standard Error 0.71
Denosumab 14 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	2.08 Percent change	Standard Error 0.55
Denosumab 60 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	2.69 Percent change	Standard Error 0.55
Denosumab 100 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	1.92 Percent change	Standard Error 0.62
Denosumab 210 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	0.12 Percent change	Standard Error 0.57
Alendronate 70 mg	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36	-0.95 Percent change	Standard Error 0.61

p-value: 0.00295% CI: [1.01, 4.38]ANCOVA

p-value: <0.00195% CI: [2.14, 5.39]ANCOVA

p-value: <0.00195% CI: [3.87, 7.26]ANCOVA

p-value: <0.00195% CI: [4.75, 7.92]ANCOVA

p-value: <0.00195% CI: [4.12, 7.33]ANCOVA

p-value: <0.00195% CI: [2.89, 6.5]ANCOVA

p-value: <0.00195% CI: [2.92, 6.49]ANCOVA

p-value: <0.00195% CI: [3.96, 7.3]ANCOVA

Secondary

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 42.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	-6.59 Percent change	Standard Error 3
Denosumab 6 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	1.00 Percent change	Standard Error 3.26
Denosumab 14 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	0.82 Percent change	Standard Error 2.92
Denosumab 30 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	-3.91 Percent change	Standard Error 3.39
Denosumab 14 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	1.29 Percent change	Standard Error 2.14
Denosumab 60 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	-0.87 Percent change	Standard Error 2.93
Denosumab 100 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	0.02 Percent change	Standard Error 5
Denosumab 210 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	0.59 Percent change	Standard Error 2.52
Alendronate 70 mg	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42	-3.32 Percent change	Standard Error 3.95

p-value: 0.49695% CI: [-7.16, 13.7]ANCOVA

p-value: 0.52795% CI: [-6.38, 19.59]ANCOVA

p-value: 0.50395% CI: [-2.9, 14.33]ANCOVA

p-value: 0.52795% CI: [-6.54, 11.89]ANCOVA

p-value: 0.50395% CI: [-2.19, 17.01]ANCOVA

p-value: 0.50395% CI: [-1.85, 17.03]ANCOVA

p-value: 0.50395% CI: [-2.45, 16.81]ANCOVA

p-value: 0.23395% CI: [0.78, 14.97]ANCOVA

Secondary

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Population: Randomized participants with non-missing baseline and non-missing value at Month 48.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	-4.67 Percent change	Standard Error 0.75
Denosumab 6 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	1.04 Percent change	Standard Error 0.73
Denosumab 14 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	1.42 Percent change	Standard Error 0.84
Denosumab 30 mg Q3M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	1.77 Percent change	Standard Error 0.91
Denosumab 14 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	1.74 Percent change	Standard Error 0.66
Denosumab 60 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	1.71 Percent change	Standard Error 0.65
Denosumab 100 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	1.37 Percent change	Standard Error 0.75
Denosumab 210 mg Q6M	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	-0.94 Percent change	Standard Error 0.74
Alendronate 70 mg	Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48	-2.67 Percent change	Standard Error 0.75

p-value: <0.00195% CI: [4.48, 8.34]ANCOVA

p-value: <0.00195% CI: [4.19, 8.7]ANCOVA

p-value: <0.00195% CI: [3.91, 8.26]ANCOVA

p-value: <0.00195% CI: [3.7, 7.73]ANCOVA

p-value: 0.05495% CI: [-0.04, 4.04]ANCOVA

p-value: <0.00195% CI: [1.71, 5.77]ANCOVA

p-value: <0.00195% CI: [4, 8.1]ANCOVA

p-value: <0.00195% CI: [4.49, 8.28]ANCOVA

Secondary

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and Month 12

Population: Randomized participants with non-missing Baseline and non-missing value at Month 12.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm	4.59 Percent change	Standard Error 0.45

Secondary

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 24.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	-1.25 Percent change	Standard Error 0.68
Denosumab 6 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	7.42 Percent change	Standard Error 0.69
Denosumab 14 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	7.21 Percent change	Standard Error 0.68
Denosumab 30 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	8.83 Percent change	Standard Error 0.76
Denosumab 14 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	3.94 Percent change	Standard Error 0.6
Denosumab 60 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	7.19 Percent change	Standard Error 0.62
Denosumab 100 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	7.31 Percent change	Standard Error 0.67
Denosumab 210 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	7.86 Percent change	Standard Error 0.65
Alendronate 70 mg	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24	6.09 Percent change	Standard Error 0.63

p-value: <0.00195% CI: [5.56, 9.12]ANCOVA

p-value: <0.00195% CI: [7.31, 10.91]ANCOVA

p-value: <0.00195% CI: [6.71, 10.41]ANCOVA

p-value: <0.00195% CI: [6.69, 10.19]ANCOVA

p-value: <0.00195% CI: [3.43, 6.94]ANCOVA

p-value: <0.00195% CI: [8.14, 12.01]ANCOVA

p-value: <0.00195% CI: [6.62, 10.3]ANCOVA

p-value: <0.00195% CI: [6.8, 10.53]ANCOVA

Secondary

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 36.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	-1.80 Percent change	Standard Error 0.82
Denosumab 6 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	8.57 Percent change	Standard Error 0.8
Denosumab 14 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	9.17 Percent change	Standard Error 0.89
Denosumab 30 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	1.94 Percent change	Standard Error 0.94
Denosumab 14 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	7.99 Percent change	Standard Error 0.72
Denosumab 60 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	9.04 Percent change	Standard Error 0.74
Denosumab 100 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	10.63 Percent change	Standard Error 0.82
Denosumab 210 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	0.85 Percent change	Standard Error 0.72
Alendronate 70 mg	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36	4.70 Percent change	Standard Error 0.78

p-value: <0.00195% CI: [4.32, 8.67]ANCOVA

p-value: 0.01395% CI: [0.55, 4.75]ANCOVA

p-value: <0.00195% CI: [10.19, 14.68]ANCOVA

p-value: <0.00195% CI: [8.74, 12.94]ANCOVA

p-value: <0.00195% CI: [7.69, 11.89]ANCOVA

p-value: <0.00195% CI: [1.37, 6.12]ANCOVA

p-value: <0.00195% CI: [8.63, 13.32]ANCOVA

p-value: <0.00195% CI: [8.16, 12.59]ANCOVA

Secondary

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 42.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	1.09 Percent change	Standard Error 1.7
Denosumab 6 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	7.21 Percent change	Standard Error 2.13
Denosumab 14 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	10.04 Percent change	Standard Error 1.86
Denosumab 30 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	5.06 Percent change	Standard Error 2.13
Denosumab 14 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	9.46 Percent change	Standard Error 1.24
Denosumab 60 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	9.59 Percent change	Standard Error 1.4
Denosumab 100 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	9.99 Percent change	Standard Error 1.93
Denosumab 210 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	1.06 Percent change	Standard Error 1.8
Alendronate 70 mg	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42	6.51 Percent change	Standard Error 1.51

p-value: 0.0295% CI: [0.89, 9.95]ANCOVA

p-value: 0.99295% CI: [-5.07, 5.02]ANCOVA

p-value: 0.00495% CI: [3.72, 14.09]ANCOVA

p-value: 0.00195% CI: [4.15, 12.86]ANCOVA

p-value: 0.00195% CI: [4.11, 12.63]ANCOVA

p-value: 0.29295% CI: [-1.42, 9.37]ANCOVA

p-value: 0.00495% CI: [3.94, 13.96]ANCOVA

p-value: 0.09495% CI: [0.57, 11.67]ANCOVA

Secondary

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 48.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	-2.39 Percent change	Standard Error 1.11
Denosumab 6 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	9.35 Percent change	Standard Error 1.09
Denosumab 14 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	9.93 Percent change	Standard Error 1.2
Denosumab 30 mg Q3M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	9.03 Percent change	Standard Error 1.33
Denosumab 14 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	10.10 Percent change	Standard Error 0.96
Denosumab 60 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	10.34 Percent change	Standard Error 0.96
Denosumab 100 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	11.76 Percent change	Standard Error 1.13
Denosumab 210 mg Q6M	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	2.50 Percent change	Standard Error 1.07
Alendronate 70 mg	Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48	4.54 Percent change	Standard Error 1.06

p-value: <0.00195% CI: [3.97, 9.89]ANCOVA

p-value: <0.00195% CI: [1.92, 7.85]ANCOVA

p-value: <0.00195% CI: [11.08, 17.21]ANCOVA

p-value: <0.00195% CI: [9.94, 15.52]ANCOVA

p-value: <0.00195% CI: [9.66, 15.32]ANCOVA

p-value: <0.00195% CI: [8.12, 14.73]ANCOVA

p-value: <0.00195% CI: [9.15, 15.49]ANCOVA

p-value: <0.00195% CI: [8.72, 14.76]ANCOVA

Secondary

Serum CTX Percent Change From Baseline at Month 12

Serum C-Telopeptide (CTX). Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and Month 12

Population: Randomized participants with non-missing Baseline and non-missing value at Month 12

Arm	Measure	Value (MEDIAN)
Placebo	Serum CTX Percent Change From Baseline at Month 12	-4.699 Percent change
Denosumab 6 mg Q3M	Serum CTX Percent Change From Baseline at Month 12	-61.366 Percent change
Denosumab 14 mg Q3M	Serum CTX Percent Change From Baseline at Month 12	-77.989 Percent change
Denosumab 30 mg Q3M	Serum CTX Percent Change From Baseline at Month 12	-87.238 Percent change
Denosumab 14 mg Q6M	Serum CTX Percent Change From Baseline at Month 12	-12.054 Percent change
Denosumab 60 mg Q6M	Serum CTX Percent Change From Baseline at Month 12	-70.757 Percent change
Denosumab 100 mg Q6M	Serum CTX Percent Change From Baseline at Month 12	-78.617 Percent change
Denosumab 210 mg Q6M	Serum CTX Percent Change From Baseline at Month 12	-84.107 Percent change
Alendronate 70 mg	Serum CTX Percent Change From Baseline at Month 12	-72.603 Percent change

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.166Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

Secondary

Serum CTX Percent Change From Baseline at Month 24

Serum C-Telopeptide (CTX). Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 24.

Arm	Measure	Value (MEDIAN)
Placebo	Serum CTX Percent Change From Baseline at Month 24	-5.940 Percent change
Denosumab 6 mg Q3M	Serum CTX Percent Change From Baseline at Month 24	-50.687 Percent change
Denosumab 14 mg Q3M	Serum CTX Percent Change From Baseline at Month 24	-74.078 Percent change
Denosumab 30 mg Q3M	Serum CTX Percent Change From Baseline at Month 24	-83.985 Percent change
Denosumab 14 mg Q6M	Serum CTX Percent Change From Baseline at Month 24	-8.467 Percent change
Denosumab 60 mg Q6M	Serum CTX Percent Change From Baseline at Month 24	-68.437 Percent change
Denosumab 100 mg Q6M	Serum CTX Percent Change From Baseline at Month 24	-80.460 Percent change
Denosumab 210 mg Q6M	Serum CTX Percent Change From Baseline at Month 24	-85.680 Percent change
Alendronate 70 mg	Serum CTX Percent Change From Baseline at Month 24	-69.386 Percent change

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.622Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

Secondary

Serum CTX Percent Change From Baseline at Month 36

Serum C-Telopeptide (CTX). Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 36.

Arm	Measure	Value (MEDIAN)
Placebo	Serum CTX Percent Change From Baseline at Month 36	-16.577 Percent change
Denosumab 6 mg Q3M	Serum CTX Percent Change From Baseline at Month 36	-62.298 Percent change
Denosumab 14 mg Q3M	Serum CTX Percent Change From Baseline at Month 36	-53.643 Percent change
Denosumab 30 mg Q3M	Serum CTX Percent Change From Baseline at Month 36	56.286 Percent change
Denosumab 14 mg Q6M	Serum CTX Percent Change From Baseline at Month 36	-57.500 Percent change
Denosumab 60 mg Q6M	Serum CTX Percent Change From Baseline at Month 36	-54.418 Percent change
Denosumab 100 mg Q6M	Serum CTX Percent Change From Baseline at Month 36	-45.057 Percent change
Denosumab 210 mg Q6M	Serum CTX Percent Change From Baseline at Month 36	72.135 Percent change
Alendronate 70 mg	Serum CTX Percent Change From Baseline at Month 36	-33.982 Percent change

p-value: 0.011Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.026Wilcoxon (Mann-Whitney)

p-value: 0.003Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

Secondary

Serum CTX Percent Change From Baseline at Month 42

Serum C-Telopeptide (CTX). Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Population: Randomized participantswith non-missing Baseline and non-missing value at Month 42.

Arm	Measure	Value (MEDIAN)
Placebo	Serum CTX Percent Change From Baseline at Month 42	-16.279 Percent change
Denosumab 6 mg Q3M	Serum CTX Percent Change From Baseline at Month 42	-63.543 Percent change
Denosumab 14 mg Q3M	Serum CTX Percent Change From Baseline at Month 42	-40.827 Percent change
Denosumab 30 mg Q3M	Serum CTX Percent Change From Baseline at Month 42	-62.334 Percent change
Denosumab 14 mg Q6M	Serum CTX Percent Change From Baseline at Month 42	-46.408 Percent change
Denosumab 60 mg Q6M	Serum CTX Percent Change From Baseline at Month 42	-57.255 Percent change
Denosumab 100 mg Q6M	Serum CTX Percent Change From Baseline at Month 42	-56.377 Percent change
Denosumab 210 mg Q6M	Serum CTX Percent Change From Baseline at Month 42	33.999 Percent change
Alendronate 70 mg	Serum CTX Percent Change From Baseline at Month 42	-46.743 Percent change

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.012Wilcoxon (Mann-Whitney)

p-value: 0.002Wilcoxon (Mann-Whitney)

p-value: 0.012Wilcoxon (Mann-Whitney)

p-value: 0.004Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

Secondary

Serum CTX Percent Change From Baseline at Month 48

Serum C-Telopeptide (CTX). Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 48.

Arm	Measure	Value (MEDIAN)
Placebo	Serum CTX Percent Change From Baseline at Month 48	-14.561 Percent change
Denosumab 6 mg Q3M	Serum CTX Percent Change From Baseline at Month 48	-40.016 Percent change
Denosumab 14 mg Q3M	Serum CTX Percent Change From Baseline at Month 48	-34.999 Percent change
Denosumab 30 mg Q3M	Serum CTX Percent Change From Baseline at Month 48	-52.656 Percent change
Denosumab 14 mg Q6M	Serum CTX Percent Change From Baseline at Month 48	-39.899 Percent change
Denosumab 60 mg Q6M	Serum CTX Percent Change From Baseline at Month 48	-51.494 Percent change
Denosumab 100 mg Q6M	Serum CTX Percent Change From Baseline at Month 48	-36.480 Percent change
Denosumab 210 mg Q6M	Serum CTX Percent Change From Baseline at Month 48	7.067 Percent change
Alendronate 70 mg	Serum CTX Percent Change From Baseline at Month 48	-43.724 Percent change

p-value: 0.015Wilcoxon (Mann-Whitney)

p-value: 0.05Wilcoxon (Mann-Whitney)

p-value: 0.029Wilcoxon (Mann-Whitney)

p-value: 0.001Wilcoxon (Mann-Whitney)

p-value: 0.032Wilcoxon (Mann-Whitney)

p-value: 0.05Wilcoxon (Mann-Whitney)

p-value: 0.073Wilcoxon (Mann-Whitney)

Secondary

Total Body Bone Mineral Density Percent Change From Baseline at Month 12

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 12 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 12.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Total Body Bone Mineral Density Percent Change From Baseline at Month 12	-0.21 Percent change	Standard Error 0.46
Denosumab 6 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 12	1.82 Percent change	Standard Error 0.45
Denosumab 14 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 12	1.80 Percent change	Standard Error 0.46
Denosumab 30 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 12	2.74 Percent change	Standard Error 0.51
Denosumab 14 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 12	0.55 Percent change	Standard Error 0.41
Denosumab 60 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 12	2.51 Percent change	Standard Error 0.43
Denosumab 100 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 12	1.78 Percent change	Standard Error 0.46
Denosumab 210 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 12	2.08 Percent change	Standard Error 0.44
Alendronate 70 mg	Total Body Bone Mineral Density Percent Change From Baseline at Month 12	1.51 Percent change	Standard Error 0.44

p-value: 0.00195% CI: [1.09, 3.51]ANCOVA

p-value: 0.00595% CI: [0.52, 2.93]ANCOVA

p-value: 0.00495% CI: [0.74, 3.25]ANCOVA

p-value: <0.00195% CI: [1.54, 3.91]ANCOVA

p-value: 0.20295% CI: [-0.41, 1.95]ANCOVA

p-value: <0.00195% CI: [1.65, 4.26]ANCOVA

p-value: 0.00495% CI: [0.78, 3.26]ANCOVA

p-value: 0.00495% CI: [0.8, 3.27]ANCOVA

Secondary

Total Body Bone Mineral Density Percent Change From Baseline at Month 24

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 24.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Total Body Bone Mineral Density Percent Change From Baseline at Month 24	-1.64 Percent change	Standard Error 0.53
Denosumab 6 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 24	2.59 Percent change	Standard Error 0.54
Denosumab 14 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 24	2.91 Percent change	Standard Error 0.53
Denosumab 30 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 24	4.44 Percent change	Standard Error 0.62
Denosumab 14 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 24	0.89 Percent change	Standard Error 0.49
Denosumab 60 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 24	2.57 Percent change	Standard Error 0.49
Denosumab 100 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 24	3.00 Percent change	Standard Error 0.53
Denosumab 210 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 24	2.75 Percent change	Standard Error 0.53
Alendronate 70 mg	Total Body Bone Mineral Density Percent Change From Baseline at Month 24	1.50 Percent change	Standard Error 0.52

p-value: <0.00195% CI: [1.71, 4.56]ANCOVA

p-value: <0.00195% CI: [2.95, 5.84]ANCOVA

p-value: <0.00195% CI: [3.19, 6.09]ANCOVA

p-value: <0.00195% CI: [2.85, 5.58]ANCOVA

p-value: <0.00195% CI: [1.13, 3.94]ANCOVA

p-value: <0.00195% CI: [4.53, 7.64]ANCOVA

p-value: <0.00195% CI: [3.12, 5.98]ANCOVA

p-value: <0.00195% CI: [2.76, 5.69]ANCOVA

Secondary

Total Body Bone Mineral Density Percent Change From Baseline at Month 36

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 36.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Total Body Bone Mineral Density Percent Change From Baseline at Month 36	-1.61 Percent change	Standard Error 0.94
Denosumab 6 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 36	3.14 Percent change	Standard Error 0.88
Denosumab 14 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 36	3.04 Percent change	Standard Error 0.98
Denosumab 30 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 36	2.34 Percent change	Standard Error 1.09
Denosumab 14 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 36	2.04 Percent change	Standard Error 0.83
Denosumab 60 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 36	2.80 Percent change	Standard Error 0.8
Denosumab 100 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 36	2.59 Percent change	Standard Error 0.94
Denosumab 210 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 36	-0.29 Percent change	Standard Error 0.83
Alendronate 70 mg	Total Body Bone Mineral Density Percent Change From Baseline at Month 36	4.55 Percent change	Standard Error 0.94

p-value: <0.00195% CI: [3.63, 8.68]ANCOVA

p-value: 0.27595% CI: [-1.06, 3.7]ANCOVA

p-value: 0.00595% CI: [1.65, 6.75]ANCOVA

p-value: 0.00295% CI: [2.07, 6.75]ANCOVA

p-value: 0.00995% CI: [1.25, 6.05]ANCOVA

p-value: 0.00995% CI: [1.22, 6.68]ANCOVA

p-value: 0.00395% CI: [2.05, 7.24]ANCOVA

p-value: 0.00195% CI: [2.28, 7.22]ANCOVA

Secondary

Total Body Bone Mineral Density Percent Change From Baseline at Month 42

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 42.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Total Body Bone Mineral Density Percent Change From Baseline at Month 42	1.61 Percent change	Standard Error 1.76
Denosumab 6 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 42	1.90 Percent change	Standard Error 3.71
Denosumab 14 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 42	4.05 Percent change	Standard Error 1.7
Denosumab 30 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 42	8.85 Percent change	Standard Error 3.07
Denosumab 14 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 42	3.72 Percent change	Standard Error 1.97
Denosumab 60 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 42	4.92 Percent change	Standard Error 1.83
Denosumab 100 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 42	3.79 Percent change	Standard Error 3.63
Denosumab 210 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 42	-0.75 Percent change	Standard Error 1.5
Alendronate 70 mg	Total Body Bone Mineral Density Percent Change From Baseline at Month 42	2.85 Percent change	Standard Error 2.67

p-value: 0.94995% CI: [-8.73, 13.1]ANCOVA

p-value: 0.94995% CI: [-2.7, 9.31]ANCOVA

p-value: 0.70995% CI: [-6.81, 9.29]ANCOVA

p-value: 0.94995% CI: [-8.55, 3.83]ANCOVA

p-value: 0.94995% CI: [-4.51, 8.72]ANCOVA

p-value: 0.48495% CI: [-0.83, 15.3]ANCOVA

p-value: 0.94995% CI: [-3.77, 8.66]ANCOVA

p-value: 0.94995% CI: [-10.82, 11.4]ANCOVA

Secondary

Total Body Bone Mineral Density Percent Change From Baseline at Month 48

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 48.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Total Body Bone Mineral Density Percent Change From Baseline at Month 48	-2.54 Percent change	Standard Error 0.99
Denosumab 6 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 48	3.68 Percent change	Standard Error 0.98
Denosumab 14 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 48	3.38 Percent change	Standard Error 1.07
Denosumab 30 mg Q3M	Total Body Bone Mineral Density Percent Change From Baseline at Month 48	3.76 Percent change	Standard Error 1.27
Denosumab 14 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 48	3.42 Percent change	Standard Error 0.86
Denosumab 60 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 48	3.43 Percent change	Standard Error 0.87
Denosumab 100 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 48	3.68 Percent change	Standard Error 1.03
Denosumab 210 mg Q6M	Total Body Bone Mineral Density Percent Change From Baseline at Month 48	-0.29 Percent change	Standard Error 0.96
Alendronate 70 mg	Total Body Bone Mineral Density Percent Change From Baseline at Month 48	4.49 Percent change	Standard Error 1

p-value: <0.00195% CI: [4.35, 9.69]ANCOVA

p-value: 0.09295% CI: [-0.37, 4.87]ANCOVA

p-value: <0.00195% CI: [3.5, 8.94]ANCOVA

p-value: <0.00195% CI: [3.51, 8.43]ANCOVA

p-value: <0.00195% CI: [3.44, 8.48]ANCOVA

p-value: <0.00195% CI: [3.25, 9.34]ANCOVA

p-value: <0.00195% CI: [3.13, 8.7]ANCOVA

p-value: <0.00195% CI: [3.58, 8.87]ANCOVA

Secondary

Total Hip Bone Mineral Density Percent Change From Baseline at Month 12

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 12 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 12.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	-0.56 Percent change	Standard Error 0.37
Denosumab 6 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	2.89 Percent change	Standard Error 0.38
Denosumab 14 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	2.45 Percent change	Standard Error 0.39
Denosumab 30 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	3.32 Percent change	Standard Error 0.42
Denosumab 14 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	1.94 Percent change	Standard Error 0.33
Denosumab 60 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	3.56 Percent change	Standard Error 0.36
Denosumab 100 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	2.53 Percent change	Standard Error 0.38
Denosumab 210 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	2.33 Percent change	Standard Error 0.36
Alendronate 70 mg	Total Hip Bone Mineral Density Percent Change From Baseline at Month 12	2.11 Percent change	Standard Error 0.35

p-value: <0.00195% CI: [1.7, 3.64]ANCOVA

p-value: <0.00195% CI: [1.9, 3.89]ANCOVA

p-value: <0.00195% CI: [2.07, 4.11]ANCOVA

p-value: <0.00195% CI: [3.13, 5.11]ANCOVA

p-value: <0.00195% CI: [1.55, 3.46]ANCOVA

p-value: <0.00195% CI: [2.83, 4.95]ANCOVA

p-value: <0.00195% CI: [1.99, 4.04]ANCOVA

p-value: <0.00195% CI: [2.43, 4.48]ANCOVA

Secondary

Total Hip Bone Mineral Density Percent Change From Baseline at Month 24

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 24.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	-1.92 Percent change	Standard Error 0.44
Denosumab 6 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	4.04 Percent change	Standard Error 0.45
Denosumab 14 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	3.55 Percent change	Standard Error 0.44
Denosumab 30 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	5.03 Percent change	Standard Error 0.5
Denosumab 14 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	2.62 Percent change	Standard Error 0.39
Denosumab 60 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	4.96 Percent change	Standard Error 0.4
Denosumab 100 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	3.67 Percent change	Standard Error 0.44
Denosumab 210 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	4.18 Percent change	Standard Error 0.43
Alendronate 70 mg	Total Hip Bone Mineral Density Percent Change From Baseline at Month 24	3.27 Percent change	Standard Error 0.41

p-value: <0.00195% CI: [4.04, 6.34]ANCOVA

p-value: <0.00195% CI: [4.93, 7.27]ANCOVA

p-value: <0.00195% CI: [4.4, 6.78]ANCOVA

p-value: <0.00195% CI: [5.76, 8.01]ANCOVA

p-value: <0.00195% CI: [3.41, 5.67]ANCOVA

p-value: <0.00195% CI: [5.69, 8.21]ANCOVA

p-value: <0.00195% CI: [4.29, 6.67]ANCOVA

p-value: <0.00195% CI: [4.76, 7.17]ANCOVA

Secondary

Total Hip Bone Mineral Density Percent Change From Baseline at Month 36

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 36.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	-2.84 Percent change	Standard Error 0.6
Denosumab 6 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	4.79 Percent change	Standard Error 0.58
Denosumab 14 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	4.41 Percent change	Standard Error 0.65
Denosumab 30 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	-1.23 Percent change	Standard Error 0.68
Denosumab 14 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	4.31 Percent change	Standard Error 0.52
Denosumab 60 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	5.83 Percent change	Standard Error 0.54
Denosumab 100 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	4.33 Percent change	Standard Error 0.6
Denosumab 210 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	-1.43 Percent change	Standard Error 0.53
Alendronate 70 mg	Total Hip Bone Mineral Density Percent Change From Baseline at Month 36	0.93 Percent change	Standard Error 0.57

p-value: <0.00195% CI: [2.19, 5.36]ANCOVA

p-value: 0.0795% CI: [-0.12, 2.94]ANCOVA

p-value: <0.00195% CI: [5.54, 8.8]ANCOVA

p-value: <0.00195% CI: [7.13, 10.21]ANCOVA

p-value: <0.00195% CI: [5.62, 8.69]ANCOVA

p-value: 0.0795% CI: [-0.12, 3.35]ANCOVA

p-value: <0.00195% CI: [5.56, 8.95]ANCOVA

p-value: <0.00195% CI: [6.02, 9.24]ANCOVA

Secondary

Total Hip Bone Mineral Density Percent Change From Baseline at Month 42

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 42.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	-1.96 Percent change	Standard Error 1.16
Denosumab 6 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	5.01 Percent change	Standard Error 1.43
Denosumab 14 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	3.98 Percent change	Standard Error 1.28
Denosumab 30 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	2.37 Percent change	Standard Error 1.46
Denosumab 14 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	4.54 Percent change	Standard Error 0.85
Denosumab 60 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	6.34 Percent change	Standard Error 0.98
Denosumab 100 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	4.70 Percent change	Standard Error 1.32
Denosumab 210 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	-2.67 Percent change	Standard Error 1.23
Alendronate 70 mg	Total Hip Bone Mineral Density Percent Change From Baseline at Month 42	2.98 Percent change	Standard Error 1.03

p-value: 0.00295% CI: [1.86, 8.02]ANCOVA

p-value: 0.67795% CI: [-4.1, 2.68]ANCOVA

p-value: 0.00195% CI: [3.14, 10.18]ANCOVA

p-value: <0.00195% CI: [5.26, 11.33]ANCOVA

p-value: <0.00195% CI: [3.59, 9.41]ANCOVA

p-value: 0.04795% CI: [0.61, 8.05]ANCOVA

p-value: 0.00395% CI: [2.53, 9.36]ANCOVA

p-value: 0.00195% CI: [3.28, 10.66]ANCOVA

Secondary

Total Hip Bone Mineral Density Percent Change From Baseline at Month 48

Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 48.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	-3.52 Percent change	Standard Error 0.65
Denosumab 6 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	5.45 Percent change	Standard Error 0.63
Denosumab 14 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	4.03 Percent change	Standard Error 0.7
Denosumab 30 mg Q3M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	3.86 Percent change	Standard Error 0.77
Denosumab 14 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	4.82 Percent change	Standard Error 0.56
Denosumab 60 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	6.06 Percent change	Standard Error 0.56
Denosumab 100 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	4.99 Percent change	Standard Error 0.66
Denosumab 210 mg Q6M	Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	-1.37 Percent change	Standard Error 0.62
Alendronate 70 mg	Total Hip Bone Mineral Density Percent Change From Baseline at Month 48	1.17 Percent change	Standard Error 0.62

p-value: <0.00195% CI: [2.97, 6.41]ANCOVA

p-value: 0.01595% CI: [0.43, 3.89]ANCOVA

p-value: <0.00195% CI: [6.74, 10.3]ANCOVA

p-value: <0.00195% CI: [7.95, 11.21]ANCOVA

p-value: <0.00195% CI: [6.7, 9.99]ANCOVA

p-value: <0.00195% CI: [5.45, 9.31]ANCOVA

p-value: <0.00195% CI: [5.72, 9.38]ANCOVA

p-value: <0.00195% CI: [7.23, 10.72]ANCOVA

Secondary

Urine NTX/Creatinine Percent Change From Baseline at Month 12

Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 12 calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and Month 12

Population: Randomized participants with non-missing Baseline and non-missing value at Month 12.

Arm	Measure	Value (MEDIAN)
Placebo	Urine NTX/Creatinine Percent Change From Baseline at Month 12	24.300 Percent change
Denosumab 6 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 12	-40.018 Percent change
Denosumab 14 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 12	-54.688 Percent change
Denosumab 30 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 12	-60.652 Percent change
Denosumab 14 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 12	-2.027 Percent change
Denosumab 60 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 12	-36.523 Percent change
Denosumab 100 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 12	-51.256 Percent change
Denosumab 210 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 12	-58.502 Percent change
Alendronate 70 mg	Urine NTX/Creatinine Percent Change From Baseline at Month 12	-45.409 Percent change

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.02Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

Secondary

Urine NTX/Creatinine Percent Change From Baseline at Month 24

Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 24 calculated using ((Month 24 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 24 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 24.

Arm	Measure	Value (MEDIAN)
Placebo	Urine NTX/Creatinine Percent Change From Baseline at Month 24	14.422 Percent change
Denosumab 6 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 24	-19.699 Percent change
Denosumab 14 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 24	-37.691 Percent change
Denosumab 30 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 24	-49.907 Percent change
Denosumab 14 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 24	2.134 Percent change
Denosumab 60 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 24	-32.303 Percent change
Denosumab 100 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 24	-37.001 Percent change
Denosumab 210 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 24	-47.105 Percent change
Alendronate 70 mg	Urine NTX/Creatinine Percent Change From Baseline at Month 24	-44.482 Percent change

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.001Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.409Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.001Wilcoxon (Mann-Whitney)

p-value: 0.003Wilcoxon (Mann-Whitney)

Secondary

Urine NTX/Creatinine Percent Change From Baseline at Month 36

Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 36 calculated using ((Month 36 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 36 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 36.

Arm	Measure	Value (MEDIAN)
Placebo	Urine NTX/Creatinine Percent Change From Baseline at Month 36	0.508 Percent change
Denosumab 6 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 36	-33.294 Percent change
Denosumab 14 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 36	-47.752 Percent change
Denosumab 30 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 36	82.910 Percent change
Denosumab 14 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 36	-44.301 Percent change
Denosumab 60 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 36	-36.874 Percent change
Denosumab 100 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 36	-27.174 Percent change
Denosumab 210 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 36	70.997 Percent change
Alendronate 70 mg	Urine NTX/Creatinine Percent Change From Baseline at Month 36	-15.627 Percent change

p-value: 0.011Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.077Wilcoxon (Mann-Whitney)

p-value: 0.002Wilcoxon (Mann-Whitney)

p-value: <0.001Wilcoxon (Mann-Whitney)

p-value: 0.002Wilcoxon (Mann-Whitney)

p-value: 0.005Wilcoxon (Mann-Whitney)

Secondary

Urine NTX/Creatinine Percent Change From Baseline at Month 42

Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 42 calculated using ((Month 42 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 42 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 42.

Arm	Measure	Value (MEDIAN)
Placebo	Urine NTX/Creatinine Percent Change From Baseline at Month 42	-18.102 Percent change
Denosumab 6 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 42	-40.741 Percent change
Denosumab 14 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 42	-40.043 Percent change
Denosumab 30 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 42	-58.893 Percent change
Denosumab 14 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 42	-47.188 Percent change
Denosumab 60 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 42	-39.269 Percent change
Denosumab 100 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 42	-46.674 Percent change
Denosumab 210 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 42	26.277 Percent change
Alendronate 70 mg	Urine NTX/Creatinine Percent Change From Baseline at Month 42	-33.102 Percent change

p-value: 0.053Wilcoxon (Mann-Whitney)

p-value: 0.022Wilcoxon (Mann-Whitney)

p-value: 0.032Wilcoxon (Mann-Whitney)

p-value: 0.053Wilcoxon (Mann-Whitney)

p-value: 0.02Wilcoxon (Mann-Whitney)

p-value: 0.053Wilcoxon (Mann-Whitney)

Secondary

Urine NTX/Creatinine Percent Change From Baseline at Month 48

Urinary N-telopeptide (uNTX)/Creatinine. Percent change from Baseline to Month 48 calculated using ((Month 48 value - Baseline value) / Baseline value ) x 100.

Time frame: Baseline and 48 months

Population: Randomized participants with non-missing Baseline and non-missing value at Month 48.

Arm	Measure	Value (MEDIAN)
Placebo	Urine NTX/Creatinine Percent Change From Baseline at Month 48	-21.064 Percent change
Denosumab 6 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 48	-23.311 Percent change
Denosumab 14 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 48	-38.002 Percent change
Denosumab 30 mg Q3M	Urine NTX/Creatinine Percent Change From Baseline at Month 48	-50.864 Percent change
Denosumab 14 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 48	-46.128 Percent change
Denosumab 60 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 48	-40.375 Percent change
Denosumab 100 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 48	-41.998 Percent change
Denosumab 210 mg Q6M	Urine NTX/Creatinine Percent Change From Baseline at Month 48	7.884 Percent change
Alendronate 70 mg	Urine NTX/Creatinine Percent Change From Baseline at Month 48	-32.198 Percent change

p-value: 0.01Wilcoxon (Mann-Whitney)

p-value: 0.172Wilcoxon (Mann-Whitney)

p-value: 0.029Wilcoxon (Mann-Whitney)

p-value: 0.047Wilcoxon (Mann-Whitney)

p-value: 0.015Wilcoxon (Mann-Whitney)

p-value: 0.168Wilcoxon (Mann-Whitney)

p-value: 0.172Wilcoxon (Mann-Whitney)

Source: ClinicalTrials.gov · Data processed: Apr 12, 2026

Determine the Efficacy, Safety and Tolerability of Denosumab (AMG 162) in the Treatment of Postmenopausal Women With Low Bone Mineral Density

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Participant flow

Recruitment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Placebo and Denosumab Arms

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 12

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 24

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 36

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 42

Bone Specific Alkaline Phosphatase Percent Change From Baseline at Month 48

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 12

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 24

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 36

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 42

Distal 1/3 Radius Bone Mineral Density Percent Change From Baseline at Month 48

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 12 for the Alendronate Arm

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 24

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 36

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 42

Lumbar Spine Bone Mineral Density Percent Change From Baseline at Month 48

Serum CTX Percent Change From Baseline at Month 12

Serum CTX Percent Change From Baseline at Month 24

Serum CTX Percent Change From Baseline at Month 36

Serum CTX Percent Change From Baseline at Month 42

Serum CTX Percent Change From Baseline at Month 48

Total Body Bone Mineral Density Percent Change From Baseline at Month 12

Total Body Bone Mineral Density Percent Change From Baseline at Month 24

Total Body Bone Mineral Density Percent Change From Baseline at Month 36

Total Body Bone Mineral Density Percent Change From Baseline at Month 42

Total Body Bone Mineral Density Percent Change From Baseline at Month 48

Total Hip Bone Mineral Density Percent Change From Baseline at Month 12

Total Hip Bone Mineral Density Percent Change From Baseline at Month 24

Total Hip Bone Mineral Density Percent Change From Baseline at Month 36

Total Hip Bone Mineral Density Percent Change From Baseline at Month 42

Total Hip Bone Mineral Density Percent Change From Baseline at Month 48

Urine NTX/Creatinine Percent Change From Baseline at Month 12

Urine NTX/Creatinine Percent Change From Baseline at Month 24

Urine NTX/Creatinine Percent Change From Baseline at Month 36

Urine NTX/Creatinine Percent Change From Baseline at Month 42

Urine NTX/Creatinine Percent Change From Baseline at Month 48