Effect of vitamin K2 treatment on carboxylation of osteocalcin in early postmenopausal women

Objective. We examined the serum level of undercarboxylated osteocalcin (uc OC), which is a sensitive marker of vitamin K status, and levels of bone turnover markers in early postmenopausal women receiving vitamin K2 treatment with or without vitamin D3. Methods. Thirty-four postmenopausal women with a mean age of 53 years whose bone mineral density (BMD) was less than 0.809 g/cm2 (osteopenia and osteoporosis) were treated with vitamin K2 or with a combination of vitamin K2 and vitamin D3. Seventeen women received daily oral administration of 45 mg vitamin K2 and 17 women received daily oral administration of 45 mg vitamin K2 plus 0.75 µg 1α-hydroxyvitamin D3. Serum levels of uc OC, intact osteocalcin (OC) and bone alkaline phosphatase (BAP), urinary deoxypyridinoline (DPD) levels and BMD at the lumbar spine were measured before and at 1 and 2 years after the start of treatment. Results. Serum uc OC levels in women treated with vitamin K2 alone and with both vitamin K2 and vitamin D3 decreased significantly (p < 0.05). Serum levels of intact OC and BAP in women treated with vitamin K2 did not show significant changes, while those in women who received the combined treatment decreased significantly (p < 0.05). On the other hand, urinary DPD level in women treated with vitamin K2 did not change, while that in women who received the combined treatment tended to decrease (p < 0.1). Conclusion. Serum uc OC levels in early postmenopausal women who received vitamin K2 decreased due to carboxylation of uc OC. Combined treatment with vitamin K2 and vitamin D3 may be effective for sustaining BMD in early postmenopausal women whose bone turnovers are highly activated.

[1]  K. Chihara,et al.  Time-dependent effects of vitamin K2 (menatetrenone) on bone metabolism in postmenopausal women. , 2002, Endocrine journal.

[2]  T. Ushiroyama,et al.  Effect of continuous combined therapy with vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis function in postmenopausal women. , 2002, Maturitas.

[3]  J. Iwamoto,et al.  Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate , 2001, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association.

[4]  Y. Ouchi,et al.  Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. , 2001, Nutrition.

[5]  T. Ohishi,et al.  Effect of vitamin K and/or D on undercarboxylated and intact osteocalcin in osteoporotic patients with vertebral or hip fractures , 2001, Clinical endocrinology.

[6]  D. Kiel,et al.  Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. , 2000, The American journal of clinical nutrition.

[7]  E. Ogata,et al.  Alfacalcidol Inhibits Bone Resorption and Stimulates Formation in an Ovariectomized Rat Model of Osteoporosis: Distinct Actions from Estrogen , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[8]  M. Shiraki,et al.  Vitamin K2 (Menatetrenone) Effectively Prevents Fractures and Sustains Lumbar Bone Mineral Density in Osteoporosis , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  T. Sakou,et al.  The Effect of Vitamin K and D Supplementation on Ovariectomy-Induced Bone Loss , 1999, Calcified Tissue International.

[10]  M. Fukunaga,et al.  Diagnostic criteria of primary osteoporosis , 1998, Journal of Bone and Mineral Metabolism.

[11]  M. Shearer The roles of vitamins D and K in bone health and osteoporosis prevention , 1997, Proceedings of the Nutrition Society.

[12]  E. Ogata,et al.  1-α-Hydroxyvitamin D3 treatment decreases bone turnover and modulates calcium-regulating hormones in early postmenopausal women , 1997 .

[13]  Y. Koshihara,et al.  Vitamin K2 Enhances Osteocalcin Accumulation in the Extracellular Matrix of Human Osteoblasts In Vitro , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[14]  P. Garnero,et al.  Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study. , 1997, The Journal of clinical endocrinology and metabolism.

[15]  J. Bilezikian,et al.  Serum undercarboxylated osteocalcin and the risk of hip fracture. , 1997, The Journal of clinical endocrinology and metabolism.

[16]  M. Shiraki,et al.  Vitamin K2 promotes 1α,25(OH)2 vitamin D3-induced mineralization in human periosteal osteoblasts , 1996, Calcified Tissue International.

[17]  T. Kameda,et al.  Vitamin K2 inhibits osteoclastic bone resorption by inducing osteoclast apoptosis. , 1996, Biochemical and biophysical research communications.

[18]  Farley,et al.  Monoclonal antibody assay for measuring bone-specific alkaline phosphatase activity in serum. , 1995, Clinical chemistry.

[19]  H. Woitge,et al.  Direct, enzyme‐linked immunoassay for urinary deoxypyridinoline as a specific marker for measuring bone resorption , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[20]  P. Delmas,et al.  Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[21]  I. Morita,et al.  Effect of vitamin K2 (menatetrenone) on osteoclast-like cell formation in mouse bone marrow cultures. , 1994, European journal of pharmacology.

[22]  P. Delmas,et al.  Circulating levels of vitamins K1 and K2 decreased in elderly women with hip fracture , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[23]  M. Shiraki,et al.  Menatetrenone inhibits bone resorption partly through inhibition of PGE2 synthesis in vitro , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[24]  P. Delmas,et al.  Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. , 1993, The Journal of clinical investigation.

[25]  Y. Ouchi,et al.  Vitamin K2 modulates proliferation and function of osteoblastic cells in vitro. , 1992, Biochemical and biophysical research communications.

[26]  P. Delmas,et al.  Circulating levels of vitamin K1 and K2 are decreased in elderly women with hip fracture , 1992 .

[27]  P. Delmas,et al.  Impairment of gamma carboxylation of circulating osteocalcin (bone gla protein) in elderly women , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[28]  G. Colditz,et al.  Vitamin K intake and hip fractures in women: a prospective study. , 1999, The American journal of clinical nutrition.

[29]  H. Uemura,et al.  Combination of automatic HPLC‐RIA method for determination of estrone and estradiol in serum , 1999, Journal of clinical laboratory analysis.

[30]  P. Meunier Calcium, Vitamin D and Vitamin K in the Prevention of Fractures due to Osteoporosis , 1999, Osteoporosis International.

[31]  E. Ogata,et al.  Circulating bone Gla protein in end-stage renal disease determined by newly developed two-site immunoradiometric assay. , 1991, Contributions to nephrology.