Calcified Tissue International

, Volume 54, Issue 5, pp 370–376 | Cite as

Effects of 1α-hydroxyvitamin D3 on lumbar bone mineral density and vertebral fractures in patients with postmenopausal osteoporosis

  • H. Orimo
  • M. Shiraki
  • Y. Hayashi
  • T. Hoshino
  • T. Onaya
  • S. Miyazaki
  • H. Kurosawa
  • T. Nakamura
  • N. Ogawa
Clinical Investigations


The effects of 1α-hydroxyvitamin D3 [1α(OH)D3] on bone mineral density, fracture incidence, and bone metabolism were evaluated by a double-blind, placebo-controlled study. Eighty postmenopausal osteoporotic Japanese women (71.9±7.3 years, mean±SD) were randomly assigned to 1 μg of 1α(OH)D3 daily or inactive placebo for 1 year. All patients were given supplemental calcium (300 mg of elemental calcium daily). Lumbar (L2–L4) bone mineral density (BMD) determined by dual energy X-ray absorptiometry increased 0.65% with 1α(OH)D3 treatment and decreased 1.14% with placebo (P=0.037). BMD in both the femoral neck and Ward's triangle did not yield any significant differences between the two groups, whereas trochanter BMD in the 1α(OH)D3-treated group increased 4.20% and decreased 2.37% with placebo (P=0.055). X-ray analysis demonstrated that new vertebral fractures occurred in two patients with 1α(OH)D3 and in seven patients with placebo. The vertebral fracture rate in the treated group was significantly less (75/1000 patient years) than in the control group (277/1000 patient years; P=0.029). Hypercalcemia (12.1 mg/100 ml) occurred in one patient receiving 1α(OH)D3; however, the serum calcium level in this patient promptly decreased to the reference range after cessation of the treatment. There were no significant changes in serum creatinine level in either group. A significant increase in urinary excretion of calcium was found but there was no significant change in urinary excretion of hydroxyproline in the treated group. The serum level of bone-derived alkaline phosphatase activity significantly decreased by−26±26 (mU/ml) after the treatment (P=0.003). These results indicate that 1α(OH)D3 treatment is effective for maintaining trabecular bone mass and prevents further vertebral fractures without any serious adverse effects in postmenopausal osteoporosis.

Key words

Osteoporosis 1α-Hydroxyvitamin D3 Bone mineral density Fracture rate 


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  1. 1.
    Nordin BEC, Morris HA (1992) Osteoporosis and vitamin D. J Cell Biochem 49:19–25Google Scholar
  2. 2.
    Aloia JF, Vaswani A, Yeh JK, Ellis K, Yasumura S, Cohn SH (1988) Calcitriol in the treatment of postmenopausal osteoporosis. Am J Med 84:401–408Google Scholar
  3. 3.
    Gallagher JC, Goldgar D (1990) Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. Ann Intern Med 113:649–655Google Scholar
  4. 4.
    Tilyard MW, Spears GFS, Thomson J, Dorey S (1992) Treatment of postmenopausal osteoporosis with calcitriol or calcium. N Engl J Med 326:357–362Google Scholar
  5. 5.
    Gallagher JC, Riggs BL, Recker RR, Goldgar D (1989) The effect of calcitriol on patients with postmenopausal osteoporosis with special reference to fracture frequency. Proc Soc Exp Biol Med 191:287–292Google Scholar
  6. 6.
    Christiansen C, Christiansen MS, Rodbro P, Hagen C, Transbol I (1981) Effect of 1,25-dihydroxy-vitamin D3 in itself or combined with hormone treatment in preventing postmenopausal osteoporosis. Eur J Clin Invest 11:305–309Google Scholar
  7. 7.
    Jensen GF, Meinecke B, Boesen J, Transbol IB (1985) Does 1,25(OH)2D3 accelerate spinal bone loss? A controlled therapeutic trial in 70-year-old women. Clin Orthop Rel Res 192:215–221Google Scholar
  8. 8.
    Falch JA, Odegaard OR, Finnager AM, Matheson I (1987) Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecalciferol. Acta Med Scand 221:199–204Google Scholar
  9. 9.
    Shiraki M, Ito H, Orimo H (1993) The ultra long-term treatment of senile osteoporosis with 1α-hydroxyvitamin D3. Bone Miner 20:223–234Google Scholar
  10. 10.
    Orimo H, Shiraki M, Hayashi Y, Nakamura T (1987) Reduced occurrence of vertebral crush fractures in senile osteoporosis treatment with 1α(OH)-vitamin D3. Bone Miner 3:47–52Google Scholar
  11. 11.
    Hayashi Y, Fujita T, Inoue T (1992) Decrease of vertebral fracture in osteoporotics by administration of 1α-hydroxy-vitamin D3. J Bone Miner Metab 10:184–188Google Scholar
  12. 12.
    Miki T, Nakatsuka K, Nishizawa Y, Emoto M, Morita A, Tabata T, Matsushita Y, Inoue T, Morii H (1991) Effect of intermittent oral 1,25(OH)2D3 therapy on bone gla protein in dialysis patients. Endocrinol Japon 38:479–483Google Scholar
  13. 13.
    Hamada N, Mimura T, Suzuki A, Nou J, Takazawa J, Iijima T, Ito K, Morii H (1989) Serum parathyroid hormone concentration measured by highly sensitive assay in post-thyroidectomy hypocalcemia of patients with Graves' disease. Endocrinol Jpn 36:281–288Google Scholar
  14. 14.
    Krauss S, Macy S, Ichuki AT (1981) A study of immunoreactive calcitonin (CT), adrenocorticotropic hormone (ACTH) and carcinoembryonic antigen (CEA) in lung cancer and other malignancies. Cancer 47:2485–2492Google Scholar
  15. 15.
    Schiele F, Artur Y, Floc'h AY, Slest G (1988) Total, tartrateresistant, and tartrate-inhibited acid phosphatases in serum: biological variations and reference limits. Clin Chem 34:685–690Google Scholar
  16. 16.
    Moss DW (1982) Alkaline phosphatase isozymes. Clin Chem 20:2007–2016Google Scholar
  17. 17.
    Kivikikko KI, Laitinen O, Prockop DJ (1967) Modification of a specific assay for hydroxyproline in urine. Anal Biochem 19: 249–255Google Scholar
  18. 18.
    Dokoh S, Pike JW, Chandler JS, Mancini JM, Haussler MR (1981) An improved radioreceptor assay for 1,25-dihydroxyvitamin D in human plasma. Anal Biochem 116:211–222Google Scholar
  19. 19.
    Kao PC, Heser DW (1984) Simultaneous determination of 25-dihydroxy-and 1,25-dihydroxyvitamin D from a single sample by dual-cartridge extraction. Clin Chem 30:56–61Google Scholar
  20. 20.
    Ott SM, Chesnut III CH (1989) Calcitriol treatment is not effective in postmenopausal osteoporosis. Ann Int Med 110:267–274Google Scholar
  21. 21.
    Ott SM, Chesnut III CH (1990) Tolerance to dose of calcitriol is associated with improved bone density in women with postmenopausal osteoporosis (abstract) J Bone Miner Res 5:449, S186Google Scholar
  22. 22.
    Jensen GF, Christiansen C, Transbol I (1982) Treatment of postmenopausal osteoporosis. A controlled therapeutic trial comparing oestrogen/gestagen, 1,25-dihydroxy-vitamin D3 and calcium. Clin Endocrinol 16:515–524Google Scholar
  23. 23.
    Christiansen C, Christiansen MS, McNair P, Hagen C, Stocklund E, Transbol IB (1980) Prevention of early postmenopausal bone loss: controlled 2-year study in 315 normal females. Eur J Clin Invest 10:273–279Google Scholar
  24. 24.
    Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ (1992) Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 327:1637–1642Google Scholar
  25. 25.
    Lips P, Wiersinga A, Ginkel FCV, Jongen MJM, Netelenbos JC, Hackeng WHL, Delmas PD, Vijgh WJFVD (1988) The effect of Vitamin D supplementation on Vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab 67:644–650Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1994

Authors and Affiliations

  • H. Orimo
    • 1
  • M. Shiraki
    • 2
  • Y. Hayashi
    • 3
  • T. Hoshino
    • 4
  • T. Onaya
    • 5
  • S. Miyazaki
    • 6
  • H. Kurosawa
    • 7
  • T. Nakamura
    • 1
  • N. Ogawa
    • 8
  1. 1.Department of Geriatrics, Faculty of MedicineUniversity of TokyoTokyo
  2. 2.Department of Laboratory MedicineTokyo Metropolitan Geriatric HospitalTokyo
  3. 3.Department of Orthopedic SurgeryTokyo Metropolitan Rehabilitation HospitalTokyo
  4. 4.Department of Orthopedic SurgeryJiseikai HospitalTokyo
  5. 5.Department of Third Internal MedicineYamanashi Medical SchoolYamanashi
  6. 6.Department of Internal MedicineTokyo Communication HospitalTokyo
  7. 7.Department of Orthopedic SurgeryTokyo Communication HospitalTokyo
  8. 8.Department of Pharmacology, Faculty of MedicineEhime UniversityEhimeJapan

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