[Long-term effect of 1 alpha-hydroxyvitamin D, calcium and thiazide administration on glucocorticoid-induced osteoporosis].
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.
Yamada
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
D000328:Adult; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000008:administration & dosage / Q000009:adverse effects / Q000652:urine; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007669:Kidney Calculi / Q000139:chemically induced; D010024:Osteoporosis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010281:Parathyroid Hormone / Q000097:blood; D011239:Prednisolone / Q000009:adverse effects*; D014237:Trichlormethiazide / Q000008:administration & dosage* / Q000627:therapeutic use
D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D011239:Prednisolone; D014237:Trichlormethiazide; D002118:Calcium; C008088:alfacalcidol