Effects of Continuous Combined Hormone Replacement Therapy and Clodronate on Bone Mineral Density (BMD) in Osteoporotic Women

Study Overview
=================
Brief Summary
-----------------
Recent studies suggest that the combination of two inhibitors of bone resorption may induce a greater increase in bone mineral density (BMD) than either agent alone. In this 5-year partly randomized study the investigators examined the effects of hormone therapy (HT) with or without bisphosphonate on BMD on osteoporotic women. In the Kuopio Osteoporosis Study (OSTPRE) a population based sample of 3200 women were selected for BMD measurement by Lunar DPX in 1995-1997. In all 167 women aged 61±2.7 years (11±4.9 years postmenopausal), and the T-score < -2.5 SD at either the lumbar spine or femoral neck were recruited for this sub-study. They received daily estradiol hemihydrate (E2) 2mg + norethisterone acetate (NETA) 1mg (Kliogest®, Novo Nordisk, Denmark) and were randomized to get additional Boneplac, which consisted of either 800mg clodronate (Bonefos®, Leiras Ltd, Finland) (n=55, KB-group) or placebo (n=55, K-group). In case of contraindications or refusal from HT, the women were offered clodronate 800 mg/day (n=57, B-group) to be taken to empty stomach with a glass of water 30 minutes to two hours before breakfast. BMD was measured at time intervals 0, 1, 3 and 5-years. All repeated BMD values were interviewed by one investigator and primarily the vertebrae L2-L4 were followed. In case of spinal deformities during the study (38.3%) other lumbar levels were followed. The baseline BMD values (lumbar spine BMD 0.839±0.072 g/cm², femoral neck BMD 0.759±0.094g/cm²) were similar between the groups.

Official Title
-----------------
Randomized Clinical Trial on the Effectts of Estradiol 2 mg + NETA 1 mg With or Without Clodronate on Bone Mineral Density and Bone Markers of Osteoporotic Postmenopausal 167 Finnish Women.

Conditions
-----------------
Osteoporosis

Intervention / Treatment
-----------------
* Drug: Klodronate and Kliogest
* Procedure: Placebo+ Kliogest
* Drug: Bonefos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Postmenopausal BMD T-score <-2.5sd Exclusion Criteria: None

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Clodronate 800 mg / day + estradiol 2 mg + norethisterone acetate 1 mg / day for five years. | Drug: Klodronate and Kliogest<br> <br> |
| Placebo Comparator: 2<br>Placebo 2 tablets/ day + estradiol 2 mg + norethisterone acetate 1 mg / day for five years. | Procedure: Placebo+ Kliogest<br> <br> |
| Active Comparator: 3<br>Clodronate 800 mg / day for five years. | Drug: Bonefos<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMD once a year |  | 1996-2002 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bone markers once a year |  | 1996-2002 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
osteoporosis, Bone mineral density, clodronate, HRT, postmenopausal