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

Abstract

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.

The efficacy of calcitriol therapy in the management of bone loss and fractures: a qualitative review

“…Three studies used calcitriol in combination with HRT among postmenopausal women [53, 96, 99]. The first lasted only 5 days and found subjects assigned to calcitriol plus HRT experienced a significant drop in PTH compared to subjects given HRT alone [96].…”

“…No difference in bone resorption between the two groups was observed. The other two studies noted significant decreases in osteocalcin levels for the HRT/calcitriol combination group when compared to HRT alone [53, 99]. In one study, the combination of calcitriol and HRT significantly reduced bone resportion and PTH levels compared to the placebo group [53].…”

“…Four of the studies reported calcitriol had a synergistic effect in combination with the therapeutic agent that was used [53, 95, 99, 101]. Hypercalcemia was a reported side-effect of calcitriol therapy in four studies [53, 97, 99, 101]. Overall, calcitriol in combination with other bone agents was well-tolerated and had favorable effects on bone biomarkers across different populations (Table 2).…”

“…Eleven studies evaluated the effect of calcitriol in combination with various therapeutic bone agents on BMD changes among a variety of populations [53, 95, 97, 99–106]. Study durations ranged from 6 months to 3 years, with the majority lasting between 1 and 2 years.…”

“…All of the studies administered daily doses of 0.5 μg of calcitriol, except one study that used a mean dose of 0.6 μg of calcitriol [101] and another study that gave participants only 0.25 μg of calcitriol every other day [105]. Ten studies measured BMD changes in the lumbar region [53, 95, 97, 99–103, 105, 106], five studies used femoral BMD [53, 101, 102, 105, 106], four studies used radial BMD [97, 101, 102, 104], three studies used total body BMD [53, 99, 102], and two studies used hip BMD [95, 99]. All of the studies enrolled postmenopausal women with osteoporosis, except one study that enrolled participants with corticosteroid-induced osteoporosis [101] and another that enrolled healthy postmenopausal women [53].…”