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 µg 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, Wards, total hip, intertrochanter and femoral shaft (% group mean 4.2, 6.1, 9.3, 3.7, 3.3 and 3.3%, respectively). On HRT, at these 6 sites, significant s 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 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.D. H. Gutteridge, M. L. Holzherr, R. W. Retallack, R. I. Price, R. K. Will, S. S. Dhaliwal, D. L. Faulkner, G. O. Stewart, B. G. A. Stuckey, R. L. Prince, R. A. Criddle, P. J. Drury, L. Tran, C. I. Bhagat, G. N. Kent and K. Jamrozi