Prior treatment with vitamin K(2) significantly improves the efficacy of risedronate.
Prior 8-week treatment with menatetrenone, MK-4, followed by 8-week risedronate prevented the shortcomings of individual drugs and significantly increased the strength of ovariectomized ICR mouse femur compared to the ovariectomized (OVX) controls. Neither MK-4 following risedronate nor the concomitant administration may be recommended because they brought the least beneficial effect.


BACKGROUND
The objective of this study was to determine the best combinatory administration of risedronate at 0.25 mg/kg/day (R) with vitamin K(2) at approximately 100 microg MK-4/kg/day (K) to improve strength of osteoporotic mouse bone.


METHODS
Thirteen-week-old ICR mice, ovariectomized at 9-week, were treated for 8 weeks with R, K, or R plus K (R/K), and then, either the treatment was withdrawn (WO) or switched to K or R in the case of R and K. After another 8 weeks, the mice were killed, and mechanical tests and analyses of femur properties by peripheral quantitative computed tomography, microfocus X-ray tube computed tomography, and confocal laser Raman microspectroscopy were carried out.


RESULTS
The K to R femur turned out superior in parameters tested such as material properties, bone mineral density, BMC, trabecular structure, and geometry of the cortex. The increased cross-sectional moment of inertia, which occurred after K withdrawal, was prevented by risedronate in K to R. In addition to K to R, some properties of R to WO diaphysis and K to WO epiphysis were significantly better than OVX controls.


CONCLUSIONS
Prior treatment with MK-4 followed by risedronate significantly increased femur strength in comparison to the OVX controls.
Matsumoto
Y
Y
Division of Radiology, Department of Maxillofacial Diagnostic Science, Kanagawa Dental College, 82 Inaokacho, Yokosuka, Kanagawa, 238-8580, Japan.
Mikuni-Takagaki
Y
Y
Kozai
Y
Y
Miyagawa
K
K
Naruse
K
K
Wakao
H
H
Kawamata
R
R
Kashima
I
I
Sakurai
T
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004359:Drug Therapy, Combination; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005269:Femur / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008813:Mice, Inbred ICR; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D010052:Ovariectomy; D000068296:Risedronic Acid; D024482:Vitamin K 2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D050071:Bone Density Conservation Agents; D024482:Vitamin K 2; C030814:menatetrenone; D000068296:Risedronic Acid; D012968:Etidronic Acid