The objective is to study the effect of beta-agonist and beta-antagonist treatment on human bone remodeling.
ID
Source
Brief title
Condition
- Bone, calcium, magnesium and phosphorus metabolism disorders
- Bone disorders (excl congenital and fractures)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the difference in change of serum concentrations of
bone turnover markers (procollagen type I N propeptide (P1NP) and C-terminal
crosslinking telopeptides of collagen type I (CTX)) compared in the treatment
and control groups(4).
Secondary outcome
A secondary parameter is the change in number of circulating stem cells and
osteogenic cells(7).
Background summary
Osteoporosis is a common disease, characterized by low bone mass and skeletal
fragility resulting in an increased risk of fracture. The most prevalent cause
of osteoporosis is estrogen deficiency in postmenopausal women(1). Estrogen
replacement therapy and bisphosphonates effectively reduce fracture risk, but
there are concerns about the long-term safety of these treatments(2). Bone mass
is controlled by the balance between bone formation and resorption. The
anabolic effects of estrogen on bone are presumed to be mediated by the
estrogen receptor in bone. However, a recent breakthrough in experimental
animals indicates an important role for the sympathetic nervous system (SNS) in
bone remodelling mediated by the beta-2-adrenergic receptor(3). Furthermore,
there are reports that the SNS is involved in the mobilization of hematopoietic
stem cells (4;5).
Study objective
The objective is to study the effect of beta-agonist and beta-antagonist
treatment on human bone remodeling.
Study design
Randomized intervention trial.
Intervention
The participants will be randomized to receive hormonal replacement therapy
(HRT) (zumenon 1dd 2 mg), HRT and beta-agonist (terbutaline 1dd 5 mg),
beta-antagonist (propranolol SR 1dd 80 mg) or no treatment during twelve weeks.
Study burden and risks
During the intervention, participants will have to take medication daily.
Beta-agonist and beta-antagonist treatment are widely prescribed and have an
excellent safety profile(5;6). Hormonal replacement therapy is associated with
an increase in hormone-sensitive cancers, cardiovascular disease (CVD) and
venous thrombo-embolism (VTE). However, large meta-analyses confirm that these
effects occur after prolonged treatment (>1 year), whereas this study
discontinues treatment after 12 weeks(7). Therefore the risks seem
insignificant. DXA radiation exposure poses a negligible risk. Every 4 weeks
fasting venous blood samples will be drawn (at home or in the AMC), the total
volume of blood samples will not exceed 100 ml.
Postbus 22660
1100 DD Amsterdam
NL
Postbus 22660
1100 DD Amsterdam
NL
Listed location countries
Age
Inclusion criteria
female sex
last menstrual cycle 12-60 months ago
Exclusion criteria
Contraindications to HRT, beta-agonist or beta-antagonist treatment, such as cardiovascular disease, astma, COPD, renal or hepatic insufficiency
Any medication or disease influencing bone turnover
Prior VTE or breast cancer
Current osteoporosis defined by a DXA Z-score >-2.5
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-000929-71-NL |
| CCMO | NL35737.018.11 |
| OMON | NL-OMON25589 |