A randomized trial comparing hormone replacement therapy (HRT) and HRT plus calcitriol in the treatment of postmenopausal osteoporosis with vertebral fractures: benefit of the combination on total body and hip density.
We report a prospective, randomized, multicenter, open-label 2-year trial of 81 postmenopausal women aged 53-79 years with at least one minimal-trauma vertebral fracture (VF) and low (T-score below - 2) lumbar bone mineral density (BMD). Group HRT received piperazine estrone sulfate (PES) 0.625 - 1.25 mg/d +/- medroxyprogesterone acetate (MPA) 2.5 - 5 mg/d; group HRT/D received HRT plus calcitriol 0.25 microg bd. All with a baseline dietary calcium (Ca) of < 1 g/ d received Ca carbonate 0.6 g nocte. Final data were on 66 - 70 patients. On HRT/D, significant (P < 0.001) BMD increases from baseline by DXA were at total body - head, trochanter, Ward's, total hip, intertrochanter and femoral shaft (% group mean delta 4.2, 6.1, 9.3, 3.7, 3.3 and 3.3%, respectively). On HRT, at these 6 sites, significant deltaS were restricted to the trochanter and Wards. Significant advantages of HRT/D over HRT were in BMD of total body (- head), total hip and trochanter (all P = 0.01). The differences in mean delta at these sites were 1.3, 2.6 and 3.9%. At the following, both groups improved significantly -lumbar spine (AP and lateral), forearm shaft and ultradistal tibia/fibula. The weightbearing, site - specific benefits of the combination associated with significant suppression of parathyroid hormone-suggest a beneficial effect on cortical bone. Suppression of bone turnover was significantly greater on HRT/D (serum osteocalcin P = 0.024 and urinary hydroxyproline/creatinine ratio P = 0.035). There was no significant difference in the number of patients who developed fresh VFs during the trial (HRT 8/36, 22%; HRT/D 4/34, 12% - intention to treat); likewise in the number who developed incident nonvertebral fractures. This is the first study comparing the 2 treatments in a fracture population. The results indicate a significant benefit of calcitriol combined with HRT on total body BMD and on BMD at the hip, the major site of osteoporotic fracture.
D015502:Absorptiometry, Photon; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density / Q000187:drug effects; D002117:Calcitriol / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D004970:Estrone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006621:Hip Joint / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D011788:Quality of Life; D012720:Severity of Illness Index; D016037:Single-Blind Method; D016103:Spinal Fractures / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
D015415:Biomarkers; D004966:Estrogens, Conjugated (USP); D015675:Osteocalcin; D004970:Estrone; D017258:Medroxyprogesterone Acetate; D002117:Calcitriol; D006909:Hydroxyproline; C009927:estropipate