Clinical trial NCT00252408: Danish Osteoporosis Prevention Study
Official title: Danish Osteoporosis Prevention Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoporosis
Keywords: Fracture
Osteoporosis
Bone mineral density
Hormone replacement therapy
Estrogen
Breast cancer
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Karen Elise Jensen Foundation
name: Novo Nordisk A/S
name: LEO Pharma
name: Novartis
First posted: 2005-11-11
Enrollment: 2000
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 58
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Hypothesis: Use of hormone replacement therapy (HRT) decreases the incidence of fractures in early postmenopausal women.

The project was initiated in 1990, and the inclusion ended in 1993. A total of 2,016 early postmenopausal women were divided into two groups: The first group accepted randomisation to HRT or not, and the second group was allowed to choose HRT or not.

The study was not blinded. Main measurements were fracture risk over 20 years, changes in bone mineral density over 20 years, and side effects, mainly breast cancer.

Detailed description: Aim: To study the ability of hormone replacement early after menopause on risk of fractures and changes in bone mineral density, and side effects.

The project was designed as a comprehensive cohort trial. One group accepted randomisation, and was randomised to hormone replacement therapy (HRT) or not (no placebo used).

502 were randomised to HRT, and 504 were randomised to no HRT) One group was allowed to choose HRT or not. A total of 221 chose HRT, and 789 chose no HRT.

First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women.

The study was initiated in 1990, and inclusion ended in 1993.

Eligibility criteria: Inclusion Criteria:

* Women aged 45-58 years with an intact uterus
* Three to 24 month past last menstrual bleeding
* Hysterectomised women aged 45-52 years and having elevated FSH

Exclusion Criteria:

* Metaboliv bone disease including osteoporosis defined as non-traumatic vertebral fractures on X-ray
* Current estrogen use or estrogen use within the past three month
* Current or past treatment with glucocorticoids for more than 6 month
* Current or past malignancy
* Newly diagnosed or uncontrolled chronic disease
* Alcohol or drug addiction

Primary outcomes:
measure: Fracture
measure: Bone mineral density
Secondary outcomes:
measure: Breast cancer
measure: Menopausal symptoms
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: The Osteoporosis Clinic, Aarhus Sygehus
Study officials:
affiliation: department of Endocrinology and Metabolism C, Aarhus University Hospital, Denmark
name: Leif Mosekilde, Professor MD DrMedSc
role: STUDY_CHAIR
affiliation: The Osteoporosis Clinic, Hvidovre Hospital, Copenhagen
name: Jens Erik Beck Jensen, MD PhD
role: STUDY_DIRECTOR
affiliation: Department of Endocrinology and Metabolism C, Aarhus University Hospital, Denmark
name: Peder Charles, MD DrMedSc
role: STUDY_DIRECTOR
affiliation: Department of Clinical Physiology and Nuclear Medicine, Hillerød Hospital, Hillerød, Denmark
name: Stig Pors Nielsen, MD DrMedSc
role: STUDY_DIRECTOR
affiliation: Odense University Hospital
name: Henning Beck Nielsen, MD DrMedSc
role: STUDY_DIRECTOR
affiliation: Odense University Hospital
name: Kim Brixen, MD PhD
role: STUDY_DIRECTOR
affiliation: The Osteoporosis Clinic, Hvidovre Hospital, Copenhagen, Denmark
name: Ole Helmer Sørensen, MD DrMedSc
role: STUDY_DIRECTOR
References:
citation: Mosekilde L, Beck-Nielsen H, Sorensen OH, Nielsen SP, Charles P, Vestergaard P, Hermann AP, Gram J, Hansen TB, Abrahamsen B, Ebbesen EN, Stilgren L, Jensen LB, Brot C, Hansen B, Tofteng CL, Eiken P, Kolthoff N. Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study. Maturitas. 2000 Oct 31;36(3):181-93. doi: 10.1016/s0378-5122(00)00158-4.
citation: Torekov SS, Harslof T, Rejnmark L, Eiken P, Jensen JB, Herman AP, Hansen T, Pedersen O, Holst JJ, Langdahl BL. A functional amino acid substitution in the glucose-dependent insulinotropic polypeptide receptor (GIPR) gene is associated with lower bone mineral density and increased fracture risk. J Clin Endocrinol Metab. 2014 Apr;99(4):E729-33. doi: 10.1210/jc.2013-3766. Epub 2014 Jan 21.
citation: Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, Kober L, Jensen JE. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012 Oct 9;345:e6409. doi: 10.1136/bmj.e6409.