Trial Outcomes & Findings for Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate (NCT NCT03051620)

NCT ID: NCT03051620

Last Updated: 2021-03-18

Results Overview

We constructed receiver operating characteristic (ROC) curves to evaluate if carboxy-terminal collagen crosslinks (CTX) three and six months after stopping alendronate predicted TH BMD loss above the least significant change (LSC) at month 12 at the individual level.

• Recruitment status: COMPLETED
• Target enrollment: 142 participants
• Primary outcome timeframe: Baseline and one year after baseline
• Results posted on: 2021-03-18

Participant Flow

Participant milestones

Measure	Study Population Postmenopausal women (postmenopausal for at least 2 years) and men above 50 years, who had been treated with alendronate for at least five years and had a total hip bone mineral density (BMD) T-score \> -2.5 and lumbar spine BMD (L1-L4) T-score \> -4. We excluded patients with any low-energy fracture within the previous 5 years during alendronate treatment (not including fingers, toes, or skull), low-energy vertebral fracture or hip fracture at any time, on-going treatment with systemic glucocorticoids, metabolic bone disease, hormone replacement therapy, cancer and other conditions affecting bone metabolism.
Overall Study STARTED	142
Overall Study COMPLETED	124
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Measure	Study Population Postmenopausal women (postmenopausal for at least 2 years) and men above 50 years, who had been treated with alendronate for at least five years and had a total hip bone mineral density (BMD) T-score \> -2.5 and lumbar spine BMD (L1-L4) T-score \> -4. We excluded patients with any low-energy fracture within the previous 5 years during alendronate treatment (not including fingers, toes, or skull), low-energy vertebral fracture or hip fracture at any time, on-going treatment with systemic glucocorticoids, metabolic bone disease, hormone replacement therapy, cancer and other conditions affecting bone metabolism.
Overall Study Lost to Follow-up	6
Overall Study n=124 enrolled in extension (all completed)	12

Baseline Characteristics

Predictive Value of Bone Turnover Markers During Discontinuation With Alendronate

Baseline characteristics by cohort

Measure	Study Population n=142 Participants Postmenopausal women and men
Age, Continuous	68 years STANDARD_DEVIATION 6 • n=5 Participants
Sex: Female, Male Female	122 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	142 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Bone mineral density (BMD) lumbar spine	0.806 g/cm3 STANDARD_DEVIATION 0.09 • n=5 Participants
Bone mineral density (BMD) total hip	0.780 g/cm3 STANDARD_DEVIATION 0.09 • n=5 Participants
Baseline CTX	0.21 ug/L STANDARD_DEVIATION 0.1 • n=5 Participants
Baseline PINP	28 ug/L STANDARD_DEVIATION 9.5 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and one year after baseline

Population: None of the ROC curves investigating the ability of change in CTX to predict BMD loss beyond LSC at any site at month 12 at the individual level had AUC above 60% meaning that it was not possible to identify a specific cut-off value that could predict significant bone loss at the individual level.

We constructed receiver operating characteristic (ROC) curves to evaluate if carboxy-terminal collagen crosslinks (CTX) three and six months after stopping alendronate predicted TH BMD loss above the least significant change (LSC) at month 12 at the individual level.

Outcome measures

Measure	Study Population n=142 Participants Study population
If Carboxy-terminal Collagen Crosslinks (CTX) Three and Six Months After Stopping Alendronate Predicted TH BMD (Total Hip BMD) Loss Above the Least Significant Change at Month 12 at the Individual Level. Mean change in CTX from baseline to month 3	49 percentage change Standard Deviation 43
If Carboxy-terminal Collagen Crosslinks (CTX) Three and Six Months After Stopping Alendronate Predicted TH BMD (Total Hip BMD) Loss Above the Least Significant Change at Month 12 at the Individual Level. Mean change in CTX from baseline to month 6	64 percentage change Standard Deviation 62
If Carboxy-terminal Collagen Crosslinks (CTX) Three and Six Months After Stopping Alendronate Predicted TH BMD (Total Hip BMD) Loss Above the Least Significant Change at Month 12 at the Individual Level. Mean change in TH BMD from baseline to month 12	1.14 percentage change Standard Deviation 0.14

SECONDARY outcome

Timeframe: one and two years after baseline

Population: None of the ROC curves investigating the ability of change in bone turnover markers to predict BMD loss beyond LSC at any site at month 12 or month 24 at the individual level had AUC above 60% meaning that it was not possible to identify a specific cut-off value that could predict significant bone loss at the individual level.

We constructed receiver operating characteristic (ROC) curves to evaluate if changes in p-CTX or p-PINP measured three and six months after stopping alendronate predicted TH BMD loss above the least significant change at month 12 and/or month 24 at the individual level.

Outcome measures

Measure	Study Population n=142 Participants Study population
Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years Mean change in PINP from baseline to month 3	36 percentage change Standard Deviation 40
Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years Mean change in PINP from baseline to month 6	54 percentage change Standard Deviation 45
Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years Mean change in TH BMD from baseline to month 12	-1.14 percentage change Standard Deviation 0.14
Percent Change in Bone Turnover Markers Measured Three and Six Months After Stopping Alendronate Treatment and BMD After One and Two Years Mean change in TH BMD from baseline to month 24	-2.65 percentage change Standard Deviation 0.39

SECONDARY outcome

Timeframe: From baseline to month 24

Number of participants in which CTX increased above the least significant change.

The Department of Clinical Biochemistry, Rigshospitalet, Glostrup, Denmark provided the the least significant change for p-CTX > 30%.

Outcome measures

Measure	Study Population n=124 Participants Study population
Number of Participants in Which CTX Increased Above the Least Significant Change	85 participants

SECONDARY outcome

Timeframe: from baseline to month 24

the number of patients who lost BMD beyond the LSC at the lumbar spine (>3%) and total hip (>5%)

Outcome measures

Measure	Study Population n=124 Participants Study population
The Number of Participants Who Lost BMD Beyond the Least Significant Change (LSC) at the Lumbar Spine and Total Hip. Spine	21 participants
The Number of Participants Who Lost BMD Beyond the Least Significant Change (LSC) at the Lumbar Spine and Total Hip. Total hip	26 participants

SECONDARY outcome

Timeframe: Changes in TH BMD after one and two years.

Population: None of the ROC curves investigating the ability of baseline bone turnover markers to predict BMD loss beyond LSC at any site at month 12 or month 24 at the individual level had AUC above 60% meaning that it was not possible to identify a specific cut-off value that could predict significant bone loss at the individual level.

We constructed receiver operating characteristic (ROC) curves to evaluate if baseline p-CTX or baseline p-PINP at the time of alendronate discontinuation predicted TH BMD loss above the least significant change at month 12 and/or month 24 at the individual level.

Outcome measures

Measure	Study Population n=142 Participants Study population
If Baseline Bone Turnover Markers at the Time of Alendronate Discontinuation Predict Changes in BMD After One and Two Years. Mean change in TH BMD after one year	-1.14 percentage change Standard Deviation 0.14
If Baseline Bone Turnover Markers at the Time of Alendronate Discontinuation Predict Changes in BMD After One and Two Years. Mean change in TH BMD after two years	-2.65 percentage change Standard Deviation 0.39

Adverse Events

Study Population

Serious events: 7 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Measure

Study Population n=142 participants at risk Postmenopausal women (postmenopausal for at least 2 years) and men above 50 years, who had been treated with ALN for at least five years and had a THBMD T-score \> -2.5 and LSBMD (L1-L4) T-score \> -4. We excluded patients with any low-energy fracture within the previous 5 years during ALN treatment (not including fingers, toes, or skull), low-energy VFx or hip fracture at any time, on-going treatment with systemic glucocorticoids, metabolic bone disease, hormone replacement therapy, cancer and other conditions affecting bone metabolism.

Investigations Cancer

4.9% 7/142 • Number of events 7 • From baseline to month 24

Other adverse events

Measure	Study Population n=142 participants at risk Postmenopausal women (postmenopausal for at least 2 years) and men above 50 years, who had been treated with ALN for at least five years and had a THBMD T-score \> -2.5 and LSBMD (L1-L4) T-score \> -4. We excluded patients with any low-energy fracture within the previous 5 years during ALN treatment (not including fingers, toes, or skull), low-energy VFx or hip fracture at any time, on-going treatment with systemic glucocorticoids, metabolic bone disease, hormone replacement therapy, cancer and other conditions affecting bone metabolism.
Musculoskeletal and connective tissue disorders Fracture	10.6% 15/142 • Number of events 15 • From baseline to month 24
Cardiac disorders Arrhythmia, acute myocardial infarction, hypertension	7.0% 10/142 • Number of events 10 • From baseline to month 24
Eye disorders Cataract, glaucoma	6.3% 9/142 • Number of events 9 • From baseline to month 24
Renal and urinary disorders Lower urinary symptoms, infection and kidney stones	6.3% 9/142 • Number of events 9 • From baseline to month 24
Musculoskeletal and connective tissue disorders Arthralgia, osteoarthritis, back pain	10.6% 15/142 • Number of events 15 • From baseline to month 24
Respiratory, thoracic and mediastinal disorders Upper and lower respiratory tract infection, pneumonia, bronchitis	7.0% 10/142 • Number of events 10 • From baseline to month 24

Additional Information

Anne Sophie Sølling

Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark

Phone: +45 78 45 54 75

Email: annesoel@rm.dk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place