Vitamin k2 therapy for postmenopausal osteoporosis.
Vitamin K may play an important role in the prevention of fractures in postmenopausal women with osteoporosis. Menatetrenone is the brand name of a synthetic vitamin K2 that is chemically identical to menaquinone-4. The present review study aimed to clarify the effect of menatetrenone on the skeleton in postmenopausal women with osteoporosis, by reviewing the results of randomized controlled trials (RCTs) in the literature. RCTs that investigated the effect of menatetrenone on bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and fracture incidence in postmenopausal women with osteoporosis, were identified by a PubMed search for literature published in English. Eight studies met the criteria for RCTs. Small RCTs showed that menatetrenone monotherapy decreased serum undercarboxylated osteocalcin (ucOC) concentrations, modestly increased lumbar spine BMD, and reduced the incidence of fractures (mainly vertebral fracture), and that combined alendronate and menatetrenone therapy enhanced the decrease in serum ucOC concentrations and further increased femoral neck BMD. This review of the literature revealed positive evidence for the effects of menatetrenone monotherapy on fracture incidence in postmenopausal women with osteoporosis. Further studies are required to clarify the efficacy of menatetrenone in combination with bisphosphonates against fractures in postmenopausal women with osteoporosis.
One interesting passage from the full text talks about the unpublished dose range study from Japan:
Orimo, H., et al. “Clinical evaluation of soft capsule menatetrenone (Ea-0167) in the treatment of osteoporosis: late phase II dose study.” J New Remedies Clinics 41 (1992): 1249-79.
A dose-finding study of menatetrenone in Japan  administered daily doses of 15, 45, 90, and 135 mg and revealed that 45 mg was the minimum effective dose for improving bone mass parameters evaluated by microdensitometry and/or single photon absorptiometry in postmenopausal women with osteoporosis. This optimal dose (45 mg/day) for the treatment of osteoporosis is about 150–180 times greater than the recommended daily dietary intake of vitamin K (250–300 μg) . No toxic effects of menatetrenone (45 mg/day) have been reported . High-dose vitamin K is needed to prevent fractures in postmenopausal women with osteoporosis . However, the effect of menatetrenone on the skeleton remains a matter of controversy [10–17], and the role of menatetrenone in the treatment of osteoporosis therefore needs to be clarified.