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

Kuopio University Hospital

Status: Completed

Conditions: Osteoporosis

Treatments: Drug: Klodronate and Kliogest; Procedure: Placebo+ Kliogest; Drug: Bonefos

Study type: Interventional

Funder types: Other

Identifiers

NCT00877097

KUH5302410

adverse effects 1x/year x5

BP 1x/year 5 yrs

Compliance 1x/year x5

endometrial sample 1x/yearx5

Details and patient eligibility

About

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.

Enrollment: 167 patients

Sex: Female

Ages: 50 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Postmenopausal
• BMD T-score <-2.5sd

Exclusion criteria

• None

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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167 participants in 3 patient groups, including a placebo group

1

Experimental group

Description:

Clodronate 800 mg / day + estradiol 2 mg + norethisterone acetate 1 mg / day for five years.

Treatment:

Drug: Klodronate and Kliogest

2

Placebo Comparator group

Description:

Placebo 2 tablets/ day + estradiol 2 mg + norethisterone acetate 1 mg / day for five years.

Treatment:

Procedure: Placebo+ Kliogest

3

Active Comparator group

Description:

Clodronate 800 mg / day for five years.

Treatment:

Drug: Bonefos