title: Vitamin K supplementation does not affect ovariectomy-induced bone loss in rats.
abstract: Vitamin K may be important in bone metabolism. Notably, high-dose menaquinone-4 (menatetrenone, MK4) has been reported to reduce ovariectomy (ovx)-induced bone loss in rats and to decrease osteoporotic fracture in postmenopausal women. However, it is unclear whether these beneficial effects reflect a physiologic effect of vitamin K, or indicate direct pharmacologic activity of MK4. To further evaluate this, 60 6-month-old nulliparous Sprague-Dawley rats were randomized by distal femur bone mineral density (BMD) in a 3:1 ratio to ovx or sham groups. The sham and one ovx group's diet contained 1% calcium and 1300 microg/kg of vitamin K1, phylloquinone. Diets of the other two ovx groups were supplemented with 882 mg phylloquinone or MK4 per kilogram chow. Distal femur bone mineral density (DFBMD) in an 8 mm region of interest was measured at baseline, 1 and 3 months postoperatively, utilizing dual-energy X-ray absorptiometry (DXA). All animals were killed at 3 months, their right femurs excised, ex vivo BMD measured by DXA, and biomechanical testing performed. No effect of phylloquinone or MK4 supplementation on ovx-induced bone loss was observed. Specifically, DFBMD declined 10.5%, 9.2%, and 11.2% at 1 month and 14.4%, 10.6%, and 13.9% at 3 months in the ovx control, high phylloquinone, and high MK4 groups, respectively. In addition, serum osteocalcin was elevated by ovx; this was not altered by phylloquinone or MK4. Finally, femoral biomechanical properties were not affected by phylloquinone or MK4. To conclude, in this study, neither high-dose phylloquinone nor MK4 reduced the ovx-associated increase in bone turnover or decline in DFBMD.
authors.affiliation: Institute on Aging, University of Wisconsin-Madison, 53706, USA. nbinkley@facstaff.wisc.edu
authors.forename: N
authors.initials: N
authors.lastname: Binkley
authors.forename: D
authors.initials: D
authors.lastname: Krueger
authors.forename: J
authors.initials: J
authors.lastname: Engelke
authors.forename: T
authors.initials: T
authors.lastname: Crenshaw
authors.forename: J
authors.initials: J
authors.lastname: Suttie
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014812:Vitamin K / Q000494:pharmacology* / Q000627:therapeutic use; D010837:Vitamin K 1 / Q000494:pharmacology / Q000627:therapeutic use; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D010837:Vitamin K 1