Long-term effect of 1 alpha-hydroxyvitamin D, calcium and thiazide administration on glucocorticoid-induced osteoporosis

Abstract

Thirty-eight patients with collagen diseases undergoing chronic glucocorticoid treatment were studied to assess the effect of a 24 month administration of oral 1 alpha-hydroxyvitamin D (1 alpha-OHD), calcium and thiazide on bone and mineral metabolism. All patients were premenopausal women (mean age = 35 y.o.) and had been treated with prednisolone (mean dose = 11 mg/day). Patients were randomly divided into three groups. Fourteen patients were treated with 0.75 micrograms of 1 alpha-OHD and 400 mg of calcium daily (1 alpha-OHD group). Eleven patients were treated with 1 alpha-OHD, calcium and 4 mg of trichlormethiazide (thiazide group). Thirteen patients did not have any treatment for osteoporosis and served as a patient control group. There were no significant differences in age, underlying disease, dose of glucocorticoid, or pretreatment values of indices of osteoporosis among the three groups. Twenty-four hour urinary calcium excretion had increased above 300 mg/g creatinine at 12 or 24 months after the start of the treatment in 9 patients of the 1 alpha-OHD group, and asymptomatic renal stones developed in 2 of them. However, neither hypercalciuria nor renal stones developed in the thiazide group or the control group. Serum iPTH levels were suppressed significantly in the thiazide group, but did not change in the 1 alpha-OHD group or the control group. Metacarpal index (MCI) and sigma GS/D, indices of microdensitometry method which indicate bone mineral content, had significantly increased after 12 and 24 months in the thiazide group, while these indices did not change significantly in the 1 alpha-OHD group and deteriorated in the control group at 24 months. Seven patients of the control group and 4 of the 1 alpha-OHD group showed deteriorations in Singh's grade compared to only 2 in the thiazide group. Vertebral bone fractures developed in 5 vertebras of the 2 patients in the control group and 4 of the 3 patients in the 1 alpha-OHD group during the 24 months. But none of the thiazide group suffered from bone fractures. It may be concluded that combination therapy with 1 alpha-OHD, calcium and thiazide is effective in the prevention of glucocorticoid-induced osteoporosis. Long-term administration of 1 alpha-OHD and calcium should be avoided in patients undergoing chronic glucocorticoid therapy because of the risk of the development of nephrolithiasis.