[Effects of long-term administration of alfacalcidol on bone mass and bone metabolism in patients with primary osteoporosis--comparison with calcium preparations].
Long-term administration of active vitamin D3 can reduce the loss of bone mass and the incidence of fractures in Japanese whose intake of calcium (Ca) is low. In a crossover study, we examined the safety and efficacy of 1 alpha (OH)D3 and combination therapy with a Ca preparation. We measured bone mass, the incidence of fractures and bone metabolism in 33 elderly patients with a high risk of fracture (mean age: 77.5 %/- 7.8 (SD) years). Subjects were randomly assigned to receive calcium lactate alone for 12 months after 12 months of combination therapy with 1 alpha (OH)D3 (1 microgram/day) (A-C group, 17 patients) or to take calcium lactate alone for 12 months and then undergo 12 months of combination therapy with 1 alpha(OH)D3 (C-A group, 16 patients). These subjects were followed for 24 months. In the A-C group, the bone mineral density (BMD) of the lumbar spine (L2-4 BMD) measured 6 months after the start of 1 alpha (OH)D3 administration was 3% higher than the baseline value. In the C-A group, L2-4 BMD measured 6 months after the start of calcium lactate administration had decreased by approximately 2%. The rate of decrease was the same 12 months after the start of administration. The differences in L2-4 BMD between the two groups 6 and 12 months after the start of administration were significant (p = 0.023 and p = 0.005, respectively). In the A-C group, the mean BMD of the distal one-third radius measured 6 months after the start of administration had increased by 5%, but the increase was 1% when measured 12 months after the start of administration. In the C-A group, there were no such changes. The incidence of vertebral fracture during combination therapy with 1 alpha(OH) D3 and Ca preparations in the A-C group was significantly lower than that in the C-A group (chi square test, p < 0.05). The serum Ca level in the C-A group gradually increased, as measured 6 and 12 months after the start of combination therapy with 1 alpha(OH) D3 and Ca preparations, although these changes were within the reference range. There was no hypercalciuria. Serum intact parathyroid hormone levels had decreased from 26.5 +/- 11.3 pg/ml and 30.7 +/- 10.3 pg/ml to 19.8 +/- 9.7 pg/ml and 25.5 +/- 9.6 pg/ml in the A-C group and the C-A group, respectively, by 6 months after the start of administration. The rate of decrease was significantly higher in the A-C group (p = 0.004). These findings suggest that long-term administration of 1 alpha(OH)D3 is safe even when combined with administration of Ca preparations, and that this agent inhibits parathyroid function, and thus prevents loss of bone mass and reduces the incidence of vertebral fracture.
Nakatsuka
K
K
Second Department of Internal Medicine, Osaka City University Medical School.
Inaba
M
M
Aratani
H
H
Iba
K
K
Sato
T
T
Koike
T
T
Miki
T
T
Nishizawa
Y
Y
Morii
H
H
D000368:Aged; D015519:Bone Density; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D005598:Fractures, Spontaneous / Q000209:etiology; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology
D006887:Hydroxycholecalciferols; D002118:Calcium; C008088:alfacalcidol