Osteoporosis
Conditions
Keywords
osteoporosis, bisphosphonate, biomarker, zoledronic acid, alendronate, postmenopausal
Brief summary
The aim of this study was to examine the effect of zoledronic acid and alendronate on bone metabolism as measured by biomarkers in postmenopausal women with osteoporosis.
Interventions
DRUGZoledronic acid 5 mg solution
Zoledronic acid was supplied as a concentrate of 5.33 mg zoledronic acid monohydrate in a 100 ml solution. 5.33 mg zoledronic acid monohydrate equals 5 mg zoledronic acid.
Patients received an alendronate 70 mg tablet once weekly with 200 ml of tap water in the morning on an empty stomach at least 30 minutes before the first meal.
Combined elemental calcium / vitamin D chewable tablets. Participants took 2 tablets a day, for a daily dose of calcium 1200 mg/vitamin D 800 IU.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
\- Low bone mineral density (as indicated by a t-score of -2.0 or lower) postmenopausal women
Exclusion criteria
\- Previous use of oral and iv bisphosphonates, parathormone, strontium ranelate, sodium fluoride. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Intent-to-Treat Population | Screening to end of study (Month 12) | The level of bone activity as measured by NTx over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study. |
| Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Per Protocol Population | Screening to end of study (Month 12) | The level of bone activity as measured by NTx over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With a Clinical Fracture From Baseline to Month 12 | Baseline to end of study (Month 12) | A diagnosis of clinical fracture was based on physical examination findings, ie, swelling, tenderness, limited movement, pain. |
| Change of Procollagen Type I Nitrogenous Propeptide (P1NP) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 | Screening to end of study (Month 12) | The level of bone activity as measured by P1NP over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study. |
| Therapy Preference at End of Study (Month 12) | Month 12 | Patients were administered a questionnaire at the end of the study in which they were asked which type of therapy, weekly oral or yearly iv, they preferred. |
| Change in Body Height From Baseline to Month 12 | Baseline to end of study (Month 12) | Body height was measured at Baseline and at the end of the study (Month 12) and the change in height calculated. |
| Change in the Qualeffo-41 Quality of Life (QoL) Questionnaire Score From Baseline to Month 12 | Baseline to end of study (Month 12) | The Qualeffo-41 QoL questionnaire was completed by the patient at Baseline and at Month 12. The questionnaire includes 41 questions covering 7 domains (pain, physical function and activities of daily living, physical function and jobs around the house, physical function and mobility, leisure and social activities, general health perception, mental function). Scores on each question range from 1 to 3, 4, or 5. The total score summed over all questions ranges from 41-205 points; the lower the score the higher the quality of life. A negative change score indicates improvement. |
Countries
Germany
Participant flow
Recruitment details
The study was conducted in Germany; first patient enrolled October 2006 and completed December 2008.
Participants by arm
| Arm | Count |
|---|---|
| Zoledronic Acid 5 mg Patients received zoledronic acid 5 mg in 100 ml solution in a 15 minute intravenous (iv) infusion once per year. The peripheral iv infusion was preceded by and followed by a 10 ml normal saline flush of the intravenous line. In addition to study therapy, all participants received 1200 mg elemental calcium and 800 IU of vitamin D daily. Calcium and vitamin D were supplied in a chewable tablet that was to be taken twice daily. | 408 |
| Alendronate 70 mg Patients received an alendronate 70 mg tablet once weekly with 200 ml of tap water in the morning on an empty stomach at least 30 minutes before the first meal. Patients were to remain in an upright position for 30 minutes after swallowing the tablet. In addition to study therapy, all participants received 1200 mg elemental calcium and 800 IU of vitamin D daily. Calcium and vitamin D were supplied in a chewable tablet that was to be taken twice daily. | 194 |
| Total | 602 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 2 | 0 |
| Overall Study | Adverse Event | 4 | 16 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 7 | 3 |
| Overall Study | Other | 0 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Zoledronic Acid 5 mg | Alendronate 70 mg | Total |
|---|---|---|---|
| Age Continuous | 67.6 years STANDARD_DEVIATION 8.1 | 68.2 years STANDARD_DEVIATION 7.9 | 67.8 years STANDARD_DEVIATION 8 |
| Sex: Female, Male Female | 408 Participants | 194 Participants | 602 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 267 / 408 | 94 / 194 |
| serious Total, serious adverse events | 43 / 408 | 21 / 194 |
Outcome results
Primary
Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Intent-to-Treat Population
The level of bone activity as measured by NTx over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study.
Time frame: Screening to end of study (Month 12)
Population: Intent-to-treat sample (ITT) population: All patients who received at least 1 dose of study medication and who had at least 1 post-baseline determination of cross-linked N-telopeptide of type I collagen (NTx) level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoledronic Acid 5 mg | Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Intent-to-Treat Population | 0.282 ng/ml | Standard Deviation 0.195 |
| Alendronate 70 mg | Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Intent-to-Treat Population | 0.270 ng/ml | Standard Deviation 0.266 |
Primary
Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Per Protocol Population
The level of bone activity as measured by NTx over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study.
Time frame: Screening to end of study (Month 12)
Population: Per Protocol population: All intent-to-treat patients who did not show major deviations from the protocol procedures that may have had an impact on the study outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoledronic Acid 5 mg | Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Per Protocol Population | 0.293 ng/ml | Standard Deviation 0.199 |
| Alendronate 70 mg | Change of Cross-linked N-telopeptide of Type I Collagen (NTx) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 in the Per Protocol Population | 0.294 ng/ml | Standard Deviation 0.175 |
Secondary
Change in Body Height From Baseline to Month 12
Body height was measured at Baseline and at the end of the study (Month 12) and the change in height calculated.
Time frame: Baseline to end of study (Month 12)
Population: Intent-to-treat sample (ITT) population: All patients who received at least 1 dose of study medication and who had at least 1 post-baseline determination of cross-linked N-telopeptide of type I collagen (NTx) level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoledronic Acid 5 mg | Change in Body Height From Baseline to Month 12 | -0.1 cm | Standard Deviation 1 |
| Alendronate 70 mg | Change in Body Height From Baseline to Month 12 | 0.0 cm | Standard Deviation 1.2 |
Secondary
Change in the Qualeffo-41 Quality of Life (QoL) Questionnaire Score From Baseline to Month 12
The Qualeffo-41 QoL questionnaire was completed by the patient at Baseline and at Month 12. The questionnaire includes 41 questions covering 7 domains (pain, physical function and activities of daily living, physical function and jobs around the house, physical function and mobility, leisure and social activities, general health perception, mental function). Scores on each question range from 1 to 3, 4, or 5. The total score summed over all questions ranges from 41-205 points; the lower the score the higher the quality of life. A negative change score indicates improvement.
Time frame: Baseline to end of study (Month 12)
Population: Intent-to-treat sample (ITT) population: All patients who received at least 1 dose of study medication and who had at least 1 post-baseline determination of cross-linked N-telopeptide of type I collagen (NTx) level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoledronic Acid 5 mg | Change in the Qualeffo-41 Quality of Life (QoL) Questionnaire Score From Baseline to Month 12 | -1.2 Units on a scale | Standard Deviation 8.8 |
| Alendronate 70 mg | Change in the Qualeffo-41 Quality of Life (QoL) Questionnaire Score From Baseline to Month 12 | -0.6 Units on a scale | Standard Deviation 9 |
Secondary
Change of Procollagen Type I Nitrogenous Propeptide (P1NP) Level Assessed as Standardized Area Under the Curve From Screening to Month 12
The level of bone activity as measured by P1NP over the course of 12 months was assessed using the standardized area under the curve. Blood samples were collected after an overnight fast of at least 8 hours between 7:00 and 11:00 AM at Screening and Months 1.5, 3, 6, 9, and 12 months after baseline. Serum was analyzed at a central lab using commercially available ELISA kits. Standardized AUC was calculated by the AUC divided by the number of days the patient participated in the study.
Time frame: Screening to end of study (Month 12)
Population: Intent-to-treat sample (ITT) population: All patients who received at least 1 dose of study medication and who had at least 1 post-baseline determination of cross-linked N-telopeptide of type I collagen (NTx) level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoledronic Acid 5 mg | Change of Procollagen Type I Nitrogenous Propeptide (P1NP) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 | 28.2 ng/ml | Standard Deviation 23 |
| Alendronate 70 mg | Change of Procollagen Type I Nitrogenous Propeptide (P1NP) Level Assessed as Standardized Area Under the Curve From Screening to Month 12 | 25.5 ng/ml | Standard Deviation 17.6 |
Secondary
Number of Patients With a Clinical Fracture From Baseline to Month 12
A diagnosis of clinical fracture was based on physical examination findings, ie, swelling, tenderness, limited movement, pain.
Time frame: Baseline to end of study (Month 12)
Population: Intent-to-treat sample (ITT) population: All patients who received at least 1 dose of study medication and who had at least 1 post-baseline determination of cross-linked N-telopeptide of type I collagen (NTx) level.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zoledronic Acid 5 mg | Number of Patients With a Clinical Fracture From Baseline to Month 12 | 10 Participants |
| Alendronate 70 mg | Number of Patients With a Clinical Fracture From Baseline to Month 12 | 4 Participants |
Secondary
Therapy Preference at End of Study (Month 12)
Patients were administered a questionnaire at the end of the study in which they were asked which type of therapy, weekly oral or yearly iv, they preferred.
Time frame: Month 12
Population: Intent-to-treat sample (ITT) population: All patients who received at least 1 dose of study medication and who had at least 1 post-baseline determination of cross-linked N-telopeptide of type I collagen (NTx) level.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zoledronic Acid 5 mg | Therapy Preference at End of Study (Month 12) | No data available | 30 Participants |
| Zoledronic Acid 5 mg | Therapy Preference at End of Study (Month 12) | Yearly iv | 330 Participants |
| Zoledronic Acid 5 mg | Therapy Preference at End of Study (Month 12) | Weekly oral | 48 Participants |
| Alendronate 70 mg | Therapy Preference at End of Study (Month 12) | Weekly oral | 93 Participants |
| Alendronate 70 mg | Therapy Preference at End of Study (Month 12) | No data available | 16 Participants |
| Alendronate 70 mg | Therapy Preference at End of Study (Month 12) | Yearly iv | 82 Participants |