Logo - Rejuvenal
Bone Mineral Density and bisphosphonates
Role of vitamin K2 in the treatment of postmenopausal osteoporosis.
Iwamoto J, Takeda T, Sato Y.Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan. jiwamoto@sc.itc.keio.ac.jp Curr Drug Saf. 2006 Jan;1(1):87-97.
Vitamin K2, raloxifene, and bisphosphonates, such as etidronate, alendronate, and risedronate, are widely used in the treatment of postmenopausal osteoporosis in Japan. A meta-analysis study has demonstrated the efficacy of anti-resorptive agents: raloxifene and etidronate have been shown to reduce the incidence of vertebral fractures, and alendronate and risedronate have been shown to reduce the incidence of both vertebral and hip fractures. Furthermore, a report of the World Health Organization (WHO) has provided evidence from a randomized controlled trial suggesting that vitamin K2, which may stimulate bone formation via gamma-carboxylation of osteocalcin and/or steroid and xenobiotic receptors (SXRs), reduces the incidence of vertebral fractures, despite having only modest effects on the bone mineral density (BMD). Based on the weight of the currently available evidence, it is recommended that alendronate and risedronate, rather than vitamin K2, should be chosen initially for the treatment of postmenopausal osteoporosis, because these agents have been shown to be the most efficacious for reducing the incidence of both vertebral and hip fractures among the current range of commercially available agents.
However, the more potent anti-fracture efficacy of combined treatment with the anti-resorptive and commercially available anabolic agents may need to be established. Some studies have shown that combined treatment with a bisphosphonate and vitamin K2 may be more effective than treatment with a bisphosphonate alone in preventing vertebral fractures. On the other hand, the results of a preclinical study do suggest the possible efficacy of combined treatment with vitamin K2 and raloxifene in the prevention of vertebral and hip fractures in postmenopausal women, although no clinical studies have reported on the effects of combined treatment with vitamin K2 and raloxifene in postmenopausal women with osteoporosis. Vitamin K deficiency, as indicated by high serum levels of undercarboxylated osteocalcin, has been shown to contribute to the occurrence of hip fractures in elderly women. Thus, we propose that the important role of vitamin K2 used in combination with bisphosphonates or raloxifene should not be underestimated in the prevention of fractures in postmenopausal women with osteoporosis with vitamin K deficiency.
Daily practice using the guidelines for prevention and treatment of osteoporosis. Utilization of metabolic markers of bone in daily osteoporosis practice
[Article in Japanese] Clin Calcium. 2008 Aug;18(8):1127-34.Miki T, Masaki H.
Osaka City University Medical School, Postgraduate School of Medicine, Geriatric Medicine.
The evaluation of metabolic state is thought to be useful for the risk evaluation of fractures and early evaluation of treatment effects. The evaluation may also be useful to maintain adherence to osteoporosis treatment, especially in patients without symptoms. The most markers are reimbursed, although number and timing of the evaluation are limited. The guidelines are published, and it is common practice to evaluate metabolic conditions of osteoporotic patients. They are especially useful to decision making for treatment not only in patients but also in physicians. The follow-up evaluation of the markers is useful in patients treated with bisphosphonate, raloxifene and/or vitamin K2 to maintain adherence.
Effects of vitamin K(2) and risedronate on bone formation and resorption, osteocyte lacunar system, and porosity in the cortical bone of glucocorticoid-treated rats.
Iwamoto J, Matsumoto H, Takeda T, Sato Y, Liu X, Yeh JK.Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan. jiwamoto@sc.itc.keio.ac.jp Calcif Tissue Int. 2008 Aug;83(2):121-8. Epub 2008 Jun 10.
The purpose of the present study was to examine the effects of vitamin K(2) and risedronate on bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of glucocorticoid (GC)-treated rats. Forty-nine female Sprague-Dawley rats, 3 months of age, were randomized into five groups according to the following treatment schedule: age-matched control, GC administration, and GC administration with concomitant administration of vitamin K(2), risedronate, or vitamin K(2) + risedronate. At the end of the 8-week experiment, classical bone histomorphometric analysis was performed, and the osteocyte lacunar system and porosity were evaluated on the cortical bone of the tibial diaphysis.
GC administration decreased percent cortical bone area and increased percent marrow area as a result of decreased periosteal bone formation, and increased endocortical bone erosion, and increased cortical porosity. Vitamin K(2) prevented a reduction in periosteal bone formation but did not affect percent cortical bone and marrow areas. Risedronate prevented a reduction in periosteal bone formation and an increase in endocortical bone erosion, resulting in prevention of alterations in percent cortical bone and marrow areas. Both vitamin K(2) and risedronate increased osteocyte density and lacunar occupancy and prevented a GC-induced increase in cortical porosity.
Vitamin K(2) and risedronate had additive effects on osteocyte density and lacunar occupancy and a synergistic effect on cortical porosity. The present study showed the efficacy of vitamin K(2) and risedronate for bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of GC-treated rats.
Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women.
Tsugawa N, Shiraki M, Suhara Y, Kamao M, Ozaki R, Tanaka K, Okano T. J Bone Miner Metab. 2008;26(1):79-85. Epub 2008 Jan 10. Department of Hygienic Sciences, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.It has been reported that vitamin K supplementation effectively prevents fractures and sustains bone mineral density in osteoporosis. However, there are only limited reported data concerning the association between vitamin K nutritional status and bone mineral density (BMD) or fractures in Japan. The objectives were to evaluate the association between plasma phylloquinone (K1) or menaquinone (MK-4 and MK-7) concentration and BMD or fracture in Japanese women prospectively.
A total of 379 healthy women aged 30-88 years (mean age, 63.0 years) were consecutively enrolled. Plasma K1, MK-4, MK-7, and serum undercarboxylated osteocalcin (ucOC) concentrations, BMD, and incidence of vertebral fractures were evaluated. In stepwise multiple linear regression analyses, L2-4 BMD and a bone turnover marker, log K1, concentrations were independently correlated with vertebral fracture incidence. When subjects were divided into low and high K1 groups by plasma K1 concentration, the incidence of vertebral fracture in the low K1 group (14.4%) was significantly higher than that in the high K1 group (4.2%), and its age-adjusted RR was 3.58 (95% CI, 3.26-3.93). L2-4 BMD was not different between the two groups. These results suggest that subjects with vitamin K1 insufficiency in bone have increased susceptibility for vertebral fracture independently from BMD.
Studies:
Studie1