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CompletedNCT04403698Updated Dec 13, 2024Results posted

The Use of Steovess/Binosto After Denosumab Discontinuation to Prevent Increase in Bone Turnover

A Phase 2 interventional study of Alendronate Effervescent Oral Tablet in Erosive Osteoarthritis, sponsored by University Hospital, Ghent. Completed at 1 site in Belgium. Open to participants aged 30 Years and older. Per ClinicalTrials.gov, last updated 2024-12-13.

Sponsored by University Hospital, Ghent · Phase 2, Interventional, and Prevention

From the registry’s dates

  • Registered 6 months after the study started (first participant enrolled Nov 2019, registered May 2020).
Phase
Phase 2
Study type
Interventional
Enrollment
30
Allocation
Randomized
Ages
30 Years and older
Sex
All
01

Study summary

It is hypothesized that effervescent alendronate will be able to maintain bone turnover markers within the pre-menopausal reference range and thereby reducing the likelihood of bone turnover associated changes (rebound effect), after discontinuation of denosumab treatment in a non-osteoporotic population.

Read the detailed description

Denosumab discontinuation is associated with a rebound effect in bone turnover and loss in bone mass density. These changes resulted in an increase of fracture incidence in patients with postmenopausal osteoporosis back to background levels. However, no excess in fracture incidence was observed. Amongst patients who presented with vertebral fractures after treatment discontinuation, there was a slightly higher incidence of multiple vertebral fractures in patients discontinuing Prolia versus those who discontinued the placebo treatment.

A 2 year, randomized, crossover study demonstrated that alendronate intake after discontinuing denosumab treatment, lead to remaining stable bone mass densitometry (BMD) values in postmenopausal women.

In a study within a non-osteoporotic study population, ongoing at our department, increases in bone turnover are to be expected as soon as patients end study participation (i.e. open label treatment with denosumab, Prolia, anti-RANK ligand inhibition).

It is currently recommended that alternative anti-resorptive therapy may be warranted after Prolia discontinuation. One study describes the use of oral alendronate after denosumab therapy to maintain bone mineral density. However, gastro-intestinal upset and tolerability, as well as difficulty in swallowing pills may limit oral alendronate compliance. To attenuate this concern, buffered soluble (effervescent) alendronate 70 mg, developed with the aim to improve the gastrointestinal tolerability through full dissolution of alendronate in buffered palatable solution before ingestion, will be used.

This study wants to provide a follow up and study wether the use of effervescent alendronate after previous denosumab treatment can prevent a rebound effect in bone turnover that is to be expected when denosumab is discontinued. Subjects that completed our erosive hand osteoarthritis (OA) study and therefore discontinued denosumab 60 mg/every 3 months, will receive alendronate. Moreover, the study wants to asses if there is difference between using alendronate for six or twelve months, starting at the earliest three months but no later than four months after the last injection of denosumab.

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Conditions studied

  • Erosive Osteoarthritis
03

In context

Lead sponsor

University Hospital, Ghent is the lead sponsor of 685 studies on the registry; 158 are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 4 (80%) have results posted.

Browse University Hospital, Ghent studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
30 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Subjects must have completed the 48 weeks of the randomised placebo-controlled study phase followed by the 96 weeks open label denosumab 60 mg SC every 3 months phase. (EudraCT number: 2015-003223-53)
  • Last denosumab injection minimal 3 months or maximum 4 months before baseline
  • Able and willing to give written informed consent and to comply with the requirements of the study protocol

Exclusion criteria

Exclusion Criteria:

  • Patients with clinically significant hypersensitivity to any of the components of effervescent alendronate.
  • Patient who is pregnant or planning pregnancy
  • Female subjects who are breast-feeding.
  • History of osteonecrosis of the jaw, and/or recent (within 3 months) tooth extraction or other unhealed dental surgery; or planned invasive dental work during the study
  • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
  • Hypocalcaemia.
  • Oesophageal disease, gastritis, duodenitis, ulcers, or with a recent history (within the previous year) of major gastro-intestinal disease such as peptic ulcer, or active gastro-intestinal bleeding, or surgery of the upper gastro-intestinal tract other than pyloroplasty.
  • Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achalasia.
  • Inability to stand or sit upright for at least 30 minutes.
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    24 weeks

    Subject receiving alendronate treatment for 24 weeks (n = 20)

    Drug: Alendronate Effervescent Oral Tablet

  • Experimental
    48 weeks

    Subject receiving alendronate treatment for 48 weeks (n = 20)

    Drug: Alendronate Effervescent Oral Tablet

Interventions

  • DrugAlendronate Effervescent Oral Tablet

    At the earliest three months but no later than four months after the last denosumab injection, subjects will be randomized to effervescent alendronate administered for either 24 or 48 weeks

06

What researchers measure

Primary outcomes

  1. CTX-I (C-terminal Telopeptide of Type I Collagen ) Bone Turnover Marker Levels

    Difference in bone turnover marker C-terminal telopeptide of type I collagen (CTX-I) after 48 weeks. Comparisons made within and between both treatment arms

    Time frame: 48 weeks

  2. PINP (N-terminal Propeptide of Type I Procollagen) Bone Turnover Marker Levels

    Difference in Bone Turnover Marker N-terminal propeptide of type I procollagen (PINP) After 48 Weeks. Comparisons are made both within and between both treatment arms.

    Time frame: 48 weeks

Secondary outcomes

  1. Number of Patients With CTX-I (C-terminal Telopeptide of Type I Collagen )Levels Above the Reference Range at Week 48

    The number of patients that do not maintain C-terminal telopeptide of type I collagen (CTx-I) levels within the bone turnover marker reference range at week 48.

    Time frame: 48 weeks

  2. The Number of Patients PINP (N-terminal Propeptide of Type I Procollagen) Above Reference Range at Week 48

    The number of patients that do not maintain N-terminal propeptide of type I procollagen (PINP) levels within the bone turnover marker reference range at week 48

    Time frame: 48 weeks

  3. Bone Mass Density at the Spine After 48 Weeks

    Difference in bone mass density at the spine after 48 Weeks. Comparisons are made both within and between both treatment arms

    Time frame: 48 weeks

  4. Bone Mass Density at the Hip After 48 Weeks

    Difference in Bone Mass Density at the hip After 48 Weeks. Comparisons are made both within and between both treatment arms.

    Time frame: 48 weeks

07

Results

Posted Dec 13, 2024
Limitations and caveats
The target number of participants was not reached and therefore underpowered. The study should be repeated on a higher number of participants and with a longer follow-up time to estimate clinical consequences on long term.

Participant flow

Participant flow — Overall Study
MilestoneTreatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 Weeks
Started1515
Completed1313
Not completed22
Withdrew: Adverse event11
Withdrew: Lost to follow-up10
Withdrew: Protocol violation01

Outcome measures

PrimaryCTX-I (C-terminal Telopeptide of Type I Collagen ) Bone Turnover Marker Levels

Difference in bone turnover marker C-terminal telopeptide of type I collagen (CTX-I) after 48 weeks. Comparisons made within and between both treatment arms

Time frame:
48 weeks
Reported as:
Geometric mean · ng/ml
CTX-I (C-terminal Telopeptide of Type I Collagen ) Bone Turnover Marker Levels
ng/ml24 Weeks48 Weeks
Baseline0.05 ± 0.060.06 ± 0.06
Week 480.63 ± 0.330.33 ± 0.33
Statistical analysis
  • 24 Weeks vs 48 Weeks · Mixed Models Analysis · p = <0.01
PrimaryPINP (N-terminal Propeptide of Type I Procollagen) Bone Turnover Marker Levels

Difference in Bone Turnover Marker N-terminal propeptide of type I procollagen (PINP) After 48 Weeks. Comparisons are made both within and between both treatment arms.

Time frame:
48 weeks
Reported as:
Geometric mean · microgram/L
PINP (N-terminal Propeptide of Type I Procollagen) Bone Turnover Marker Levels
microgram/L24 Weeks48 Weeks
Baseline8.1 ± 0.414.6 ± 0.41
Week 4878.9 ± 0.4439.5 ± 0.44
Statistical analysis
  • 24 Weeks vs 48 Weeks · Mixed Models Analysis · p = 0.05
SecondaryNumber of Patients With CTX-I (C-terminal Telopeptide of Type I Collagen )Levels Above the Reference Range at Week 48

The number of patients that do not maintain C-terminal telopeptide of type I collagen (CTx-I) levels within the bone turnover marker reference range at week 48.

Time frame:
48 weeks
Reported as:
Count of participants · Participants
Number of Patients With CTX-I (C-terminal Telopeptide of Type I Collagen )Levels Above the Reference Range at Week 48
ParticipantsTreatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 Weeks
Number of Patients With CTX-I (C-terminal Telopeptide of Type I Collagen )Levels Above the Reference Range at Week 4850
Statistical analysis
  • Treatment Alendronate 70 mg Weekly for 24 Weeks vs Treatment Alendronate 70 mg Weekly for 48 Weeks · Fisher Exact · p = 0.042
SecondaryThe Number of Patients PINP (N-terminal Propeptide of Type I Procollagen) Above Reference Range at Week 48

The number of patients that do not maintain N-terminal propeptide of type I procollagen (PINP) levels within the bone turnover marker reference range at week 48

Time frame:
48 weeks
Reported as:
Count of participants · Participants
The Number of Patients PINP (N-terminal Propeptide of Type I Procollagen) Above Reference Range at Week 48
ParticipantsTreatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 Weeks
The Number of Patients PINP (N-terminal Propeptide of Type I Procollagen) Above Reference Range at Week 4850
Statistical analysis
  • Treatment Alendronate 70 mg Weekly for 24 Weeks vs Treatment Alendronate 70 mg Weekly for 48 Weeks · Fisher Exact · p = 0.042
SecondaryBone Mass Density at the Spine After 48 Weeks

Difference in bone mass density at the spine after 48 Weeks. Comparisons are made both within and between both treatment arms

Time frame:
48 weeks
Reported as:
Geometric mean · g/cm2
Bone Mass Density at the Spine After 48 Weeks
g/cm2Treatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 Weeks
Baseline1.16 ± 0.031.11 ± 0.03
Week 481.10 ± 0.031.11 ± 0.03
SecondaryBone Mass Density at the Hip After 48 Weeks

Difference in Bone Mass Density at the hip After 48 Weeks. Comparisons are made both within and between both treatment arms.

Time frame:
48 weeks
Reported as:
Geometric mean · g/cm2
Bone Mass Density at the Hip After 48 Weeks
g/cm2Treatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 Weeks
Baseline0.85 ± 0.030.80 ± 0.03
Week 480.85 ± 0.030.81 ± 0.03

Adverse events

Collected over Adverse events data was collected during the 48 weeks of the trial duration.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Alendronate 24 Weeks0/15 (0%)1/15 (6.7%)10/15 (66.7%)
Alendronate 48 Weeks0/15 (0%)0/15 (0%)12/15 (80%)
Most frequent serious events
Most frequent serious events
EventAlendronate 24 WeeksAlendronate 48 Weeks
Colonic ulcersGastrointestinal disorders1/150/15
Most frequent other events
Showing 10 of 15
Most frequent other events
EventAlendronate 24 WeeksAlendronate 48 Weeks
stomach and stool problemsGastrointestinal disorders5/156/15
muscular pain and joint painMusculoskeletal and connective tissue disorders4/155/15
InfectionsInfections and infestations3/154/15
Headache and dizzinessNervous system disorders3/151/15
Blurry vision and eye drynessEye disorders1/152/15
Arterial hypertensionCardiac disorders1/151/15
Cough (non-infectious)Respiratory, thoracic and mediastinal disorders0/151/15
ItchSkin and subcutaneous tissue disorders1/150/15
Throat painEar and labyrinth disorders1/150/15
General malaiseGeneral disorders0/151/15

Baseline characteristics

Age, Continuous
Age, Continuous(years)Treatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 WeeksTotal
Mean63.3 ± 7.764.7 ± 8.964.0 ± 8.2
Sex: Female, Male
Sex: Female, Male(Participants)Treatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 WeeksTotal
Female121123
Male347
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 WeeksTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White151530
More than one race000
Unknown or Not Reported000
mean treatment duration with denosumab (days)
mean treatment duration with denosumab (days)(days)Treatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 WeeksTotal
Mean813 ± 165751 ± 174782 ± 170
mean time since last denosumab injection (days)
mean time since last denosumab injection (days)(days)Treatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 WeeksTotal
Mean89 ± 794 ± 891 ± 8
N-terminal propeptide of type I procollagen (PINP)
N-terminal propeptide of type I procollagen (PINP)(microgram/L)Treatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 WeeksTotal
Mean10.15 ± 5.58.97 ± 10.69.56 ± 8.3
C-terminal telopeptide of type I collagen (CTX-I)
C-terminal telopeptide of type I collagen (CTX-I)(ng/ml)Treatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 WeeksTotal
Mean0.057 ± 0.030.071 ± 0.060.064 ± 0.05
Bone mineral density hip
Bone mineral density hip(g/cm2)Treatment Alendronate 70 mg Weekly for 24 WeeksTreatment Alendronate 70 mg Weekly for 48 WeeksTotal
Mean0.85 ± 0.100.80 ± 0.080.83 ± 0.11

1 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Ghent University Hospital
    Ghent, 9000, Belgium
09

References and documents

Publications

  • Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone. 2008 Aug;43(2):222-229. doi: 10.1016/j.bone.2008.04.007. Epub 2008 Apr 26. PubMed 18539106 ↗
  • Brown JP, Roux C, Torring O, Ho PR, Beck Jensen JE, Gilchrist N, Recknor C, Austin M, Wang A, Grauer A, Wagman RB. Discontinuation of denosumab and associated fracture incidence: analysis from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. J Bone Miner Res. 2013 Apr;28(4):746-52. doi: 10.1002/jbmr.1808. PubMed 23109251 ↗
  • Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JB, McClung M, Roux C, Torring O, Valter I, Wang AT, Brown JP. Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension. J Bone Miner Res. 2018 Feb;33(2):190-198. doi: 10.1002/jbmr.3337. Epub 2017 Nov 22. PubMed 29105841 ↗
  • Freemantle N, Satram-Hoang S, Tang ET, Kaur P, Macarios D, Siddhanti S, Borenstein J, Kendler DL; DAPS Investigators. Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int. 2012 Jan;23(1):317-26. doi: 10.1007/s00198-011-1780-1. Epub 2011 Sep 17. PubMed 21927922 ↗
  • Hodges LA, Connolly SM, Winter J, Schmidt T, Stevens HN, Hayward M, Wilson CG. Modulation of gastric pH by a buffered soluble effervescent formulation: A possible means of improving gastric tolerability of alendronate. Int J Pharm. 2012 Aug 1;432(1-2):57-62. doi: 10.1016/j.ijpharm.2012.04.073. Epub 2012 May 4. PubMed 22564778 ↗

Study documents

  • Study protocol · Aug 9, 2019
  • Statistical analysis plan · Dec 4, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — All collected IPD that underlie results in a publication will be shared

Supporting information: Study protocol, Statistical analysis plan, Informed consent form

Time frame: 6 months after publication. Data will stay available for 3 years after publication

Access criteria: acces will be provided upon reasonable request from researchers with a sound clinical research question

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Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Nov 2019 to primary completion in Mar 2022, 27 months.

Results were first posted in Dec 2024, 2 years 9 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
May 19, 2020
First posted
May 27, 2020
StartActual
Nov 13, 2019
Primary completionActual
Mar 9, 2022
CompletionActual
Mar 9, 2022
Results first posted
Dec 13, 2024
Last update
Dec 13, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Dec 13, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT04403698
Lead sponsor
University Hospital, Ghent
Collaborators
Amgen, EffRx Pharmaceuticals SA
Responsible party
Sponsor
First posted
May 27, 2020
Start date
Nov 13, 2019
Primary completion
Mar 9, 2022
Completion
Mar 9, 2022
Results posted
Dec 13, 2024
Last update
Dec 13, 2024

Study contacts

Ruth Wittoek, Prof. dr.
principal investigator · Ghent Universitary Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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