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

This study has been completed.
Information provided by:
Kuopio University Hospital
ClinicalTrials.gov Identifier:
First received: April 2, 2009
Last updated: April 6, 2009
Last verified: April 2009

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.

Condition Intervention
Drug: Klodronate and Kliogest
Procedure: Placebo+ Kliogest
Drug: Bonefos

Study Type: Interventional
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.

Resource links provided by NLM:

Further study details as provided by Kuopio University Hospital:

Primary Outcome Measures:
  • BMD once a year [ Time Frame: 1996-2002 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • bone markers once a year [ Time Frame: 1996-2002 ] [ Designated as safety issue: No ]

Enrollment: 167
Study Start Date: July 1996
Study Completion Date: February 2009
Primary Completion Date: December 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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.
Drug: Bonefos


Ages Eligible for Study:   50 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Postmenopausal
  • BMD T-score <-2.5sd

Exclusion Criteria:

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00877097

Sponsors and Collaborators
Kuopio University Hospital
Principal Investigator: Marjo T Tuppurainen, MD, PhD Dept. of Obstetrics and Gynecology, Kuopio University Hospital
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mari Ollikainen, Kuopio University Hospital
ClinicalTrials.gov Identifier: NCT00877097     History of Changes
Other Study ID Numbers: KUH5302410  Compliance 1x/year x5  BP 1x/year 5 yrs  endometrial sample 1x/yearx5  adverse effects 1x/year x5 
Study First Received: April 2, 2009
Last Updated: April 6, 2009
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by Kuopio University Hospital:
Bone mineral density

Additional relevant MeSH terms:
Bone Diseases
Bone Diseases, Metabolic
Musculoskeletal Diseases
Clodronic Acid
Bone Density Conservation Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2016