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

Phase 2

Completed

Conditions: Erosive Osteoarthritis

Interventions: Drug: Alendronate Effervescent Oral Tablet

Registration Number: NCT04403698

Lead Sponsor: University Hospital, Ghent

Brief 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
48 weeks	Alendronate Effervescent Oral Tablet	Subject receiving alendronate treatment for 48 weeks (n = 20)
24 weeks	Alendronate Effervescent Oral Tablet	Subject receiving alendronate treatment for 24 weeks (n = 20)

Primary Outcome Measures

Name	Time	Method
CTX-I (C-terminal Telopeptide of Type I Collagen ) Bone Turnover Marker Levels	48 weeks	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
PINP (N-terminal Propeptide of Type I Procollagen) Bone Turnover Marker Levels	48 weeks	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.

Secondary Outcome Measures

Name	Time	Method
The Number of Patients PINP (N-terminal Propeptide of Type I Procollagen) Above Reference Range at Week 48	48 weeks	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
Number of Patients With CTX-I (C-terminal Telopeptide of Type I Collagen )Levels Above the Reference Range at Week 48	48 weeks	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.
Bone Mass Density at the Spine After 48 Weeks	48 weeks	Difference in bone mass density at the spine after 48 Weeks. Comparisons are made both within and between both treatment arms
Bone Mass Density at the Hip After 48 Weeks	48 weeks	Difference in Bone Mass Density at the hip After 48 Weeks. Comparisons are made both within and between both treatment arms.