Effects of Continuous Combined Hormone Replacement Therapy and Clodronate on Bone Mineral Density (BMD) in Osteoporotic Women (Osteo)
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.
Drug: Klodronate and Kliogest
Procedure: Placebo+ Kliogest
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|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.|
- BMD once a year [ Time Frame: 1996-2002 ] [ Designated as safety issue: Yes ]
- bone markers once a year [ Time Frame: 1996-2002 ] [ Designated as safety issue: No ]
|Study Start Date:||July 1996|
|Study Completion Date:||February 2009|
|Primary Completion Date:||December 2002 (Final data collection date for primary outcome measure)|
Clodronate 800 mg / day + estradiol 2 mg + norethisterone acetate 1 mg / day for five years.
|Drug: Klodronate and Kliogest|
Placebo Comparator: 2
Placebo 2 tablets/ day + estradiol 2 mg + norethisterone acetate 1 mg / day for five years.
|Procedure: Placebo+ Kliogest|
Active Comparator: 3
Clodronate 800 mg / day for five years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00877097
|Principal Investigator:||Marjo T Tuppurainen, MD, PhD||Dept. of Obstetrics and Gynecology, Kuopio University Hospital|