Calcitriol prevented bone mineral density loss of the spine and increased total body calcium in postmenopausal osteoporosis
ACP J Club. 1991 Mar-Apr;114:48. doi:10.7326/ACPJC-1991-114-2-048
Gallagher JC, Goldgar D. Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. A randomized controlled study. Ann Intern Med. 1990;113:649-55.
To study the efficacy and safety of high-dose synthetic 1,25 dihydroxyvitamin D2 (calcitriol) in the treatment of osteoporosis.
2-year randomized, placebo-controlled clinical trial.
University medical center bone clinic in Nebraska.
50 postmenopausal women with nontraumatic vertebral fractures were recruited after referral to the clinic. Patients were excluded if they had other serious chronic disease; vitamin D deficiency; had been immobilized for a prolonged period; had taken corticosteroids for longer than 3 months; or had taken anticonvulsants, estrogen, calcium supplements, or vitamin D in the previous 6 months. 80% of the women completed the study.
All patients were given multivitamin tablets containing a daily dose of 400 IU of vitamin D2, and calcium intake was adjusted to 25 mmol/d (1000 mg/d) at baseline. Patients were then randomized to twice-daily treatment with either calcitriol (Rocaltrol, Hoffmann La Roche), 0.25-µg capsules, or placebo. During the study, calcium intake was reduced to 15 mmol/d (600 mg/d), and the dose of calcitriol was adjusted to maintain serum calcium < 2.75 mmol/L (< 11.0 mg/dL) and urine calcium < 10 mmol/d (< 400 mg/d).
Main outcome measures
Bone density and total body calcium were measured by dual photon absorptiometry at 6-month intervals. Vertebral fracture rate was calculated from spine radiographs. Baseline bone biopsies were repeated after 2 years.
7 patients dropped out of the treatment group and 3 out of the placebo group. After 2 years, the mean dose of calcitriol in the treated group was 0.62 µg/d. Bone mineral density of the spine increased 1.94% with calcitriol therapy compared with a decrease of 3.92% with placebo (P = 0.001). Total body calcium increased 0.21% with calcitriol therapy compared with a decrease of 1.86% with placebo (P = 0.004). Patients receiving placebo had significant decreases in spine density (P < 0.001) and in total body calcium (P < 0.001). No differences existed in vertebral fracture rates between the calcitriol and placebo groups (8 vs 9 fractures). Renal function studies were not statistically different between the groups at the end of 2 years.
The treatment of postmenopausal women who had osteoporosis with individually adjusted doses of synthetic calcitriol for 2 years was associated with increased spine density and total body calcium. No adverse effects on renal function were observed.
Source of funding: Hoffman La Roche.
Address for article reprint: Dr. J.C. Gallagher, Creighton University Medical Center, 601 North 30th Street, Suite 5730, Omaha, NE 68131, USA.
Safe and effective therapy for postmenopausal osteoporosis is an elusive goal. Recent work suggests that estrogens increase the risk for breast cancer, and some progesterone preparations given in combination with estrogens may decrease the beneficial effect of estrogen on LDL concentrations. Alternative therapies proposed for preventing osteoporosis include the bisphosphonates, calcium, exercise, and vitamin D or its analog calcitriol. This study by Gallagher and Goldgar and recent reports by Aloia and colleagues (1) and Ott and Chestnut (2), using the same study protocol, examine the effects of calcitriol. These studies show a small positive effect on bone density, no observable effect on fracture risk, and a narrow therapeutic range. Daily doses of calcitriol ranged from a mean of 0.43 µg (1) to 0.8 µg (2). Ott and Chestnut found a 0.4% (P > 0.3) increase in total body calcium as compared with a net increase of 2% in the trial by Aloia and colleagues and 1.7% in the trial by Gallagher and Goldgar. None of the three trials showed a beneficial effect on vertebral fracture rates. Aloia and colleagues reported a clear decrease in renal function in 2 (of 12) calcitriol-treated patients, one of whom developed nephrolithiasis. Severe hypercalcemia (to 14 mg/dL) developed in one patient treated simultaneously with thiazide diuretics. Gallagher and Goldgar reported an increase in serum creatinine and 2 episodes of hypercalciuria; however, these effects appeared transient.
At present, cost of monitoring, and minimal benefit on bone density indicate that calcitriol is not a useful alternative therapy of postmenopausal osteoporosis.
Richard L. Bauer, MD
The University of TexasSan Antonio, Texas, USA