Effects of continuous combined hormone replacement therapy and clodronate on bone mineral density in osteoporotic postmenopausal women: a 5-year follow-up.
OBJECTIVE
To determine the effects of HRT with or without clodronate on bone mineral density (BMD) change and bone turnover markers.


METHODS
Prospective, partly randomized trial.


METHODS
Kuopio University Hospital, Finland.


METHODS
167 osteoporotic women (61+/-2.7 years; T-score<or=-2.5 SD).


METHODS
Estradiol 2 mg+NETA 1 mg, randomization to additional 800 mg clodronate (n=55, HT+C-group) or placebo (n=55, HT-group); if contraindications to HRT, clodronate (n=57, C-group).


METHODS
BMD by DXA after 1, 3 and 5 years, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) at the baseline and after 3 years.


RESULTS
After 5 years, adjusted lumbar BMD increased by 4.2% in the HT-group and 3.7% in the HT+C-group. The C-group showed a decrease of -1.1%, the total difference being 5.3% and 4.8% between HT, HT+C vs. C-group, respectively (p<0.001). In the femoral neck, the adjusted 5-year BMD benefit was 1.3% and 2.4% in the HT- and HT+C-groups, respectively, the net loss of BMD in the C-group was -3.3% (p<0.05 between HT+C vs. C). By 3 years, OC decreased by 55.0%, 70.3% and 53.8% in the HT-, HT+C- and C-groups, respectively (p<0.001 vs. baseline). The significant decreases of BAP were 39.4% in the HT-group, 42.1% in the HT+C-group and 30.2% in the C-group with no significant differences between the groups after adjustments.


CONCLUSIONS
In postmenopausal women with osteoporosis, HRT increased spinal and femoral BMD, but the combination of HRT and clodronate did not offer an extra gain of bone mass.
Tuppurainen
Marjo
M
Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland. marjo.tuppurainen@kuh.fi
Härmä
Kirsi
K
Komulainen
Marja
M
Kiviniemi
Vesa
V
Kröger
Heikki
H
Honkanen
Risto
R
Alhava
Esko
E
Jurvelin
Jukka
J
Saarikoski
Seppo
S
D000469:Alkaline Phosphatase / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004002:Clodronic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005269:Femur / Q000187:drug effects; D005387:Finland; D005500:Follow-Up Studies; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000077563:Norethindrone Acetate; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism; D017698:Postmenopause; D011446:Prospective Studies
D050071:Bone Density Conservation Agents; D004967:Estrogens; D004002:Clodronic Acid; D004958:Estradiol; D000077563:Norethindrone Acetate; D000469:Alkaline Phosphatase; D009640:Norethindrone