Diet- or Warfarin-Induced Vitamin K Insufficiency Elevates Circulating Undercarboxylated Osteocalcin Without Altering Skeletal Status in Growing Female Rats

Haffa, A.; Krueger, Diane; Bruner, J.; Engelke, Jean A.; Gundberg, Caren M.; Akhter, Mohammed P.; Binkley, Neil

doi:10.1359/jbmr.2000.15.5.872

Cited by 46 publications

(28 citation statements)

References 23 publications

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“…This HAP method was also used by Lee, et al (20) and others (67–69) to assess the percentage of undercarboxylated osteocalcin in rodent models. As discussed by Gundberg, et al (66), the ability of the assay to identify ucOC depends on the concentration of total OC.…”

Section: Clinical Studiesmentioning

confidence: 99%

“…However, trials of vitamin K supplementation have generally failed to demonstrate an effect on fracture risk (88). Similarly, treatment with warfarin, a potent vitamin K antagonist that increases ucOC levels, has generally not been found to decrease BMD or bone strength in animal models (69, 89, 90). Clinical studies investigating warfarin use have had mixed results with some reporting increased risk of fracture (91, 92) or lower bone density (93, 94) but others reporting no discernable effect (95, 96).…”

Section: Clinical Studiesmentioning

confidence: 99%

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Bone and glucose metabolism: A two-way street

Motyl

McCabe

Schwartz

2010

Archives of Biochemistry and Biophysics

100

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Evidence from rodent models indicates that undercarboxylated osteocalcin (ucOC), a product of osteoblasts, is a hormone affecting insulin production by the pancreas and insulin sensitivity in peripheral tissues, at least in part through enhanced secretion of adiponectin from adipocytes. Clinical research to test whether this relationship is found in humans is just beginning to emerge. Cross-sectional studies confirm associations between total osteocalcin (OC), ucOC and glucose metabolism but cannot distinguish causality. To date, longitudinal studies have not provided a consistent picture of the effects of ucOC or OC on fasting glucose and insulin sensitivity. Further exploration into the physiological and mechanistic effects of ucOC and OC, in rodent models and clinical studies, is necessary to determine to what extent the skeleton regulates energy metabolism in humans.

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Section: Clinical Studiesmentioning

confidence: 99%

Section: Clinical Studiesmentioning

confidence: 99%

Bone and glucose metabolism: A two-way street

Motyl

McCabe

Schwartz

2010

Archives of Biochemistry and Biophysics

100

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show abstract

“…The sensitivity of the osteocalcin assay is Ϯ0.1 ng/ml, and the intraassay coefficient of variation for osteocalcin was 4.6%. Uncarboxylated osteocalcin was measured using a hydroxyapatite assay in the laboratory of Dr. Caren Gundberg (28).…”

Section: Serum Osteocalcinmentioning

confidence: 99%

Gender-Specific Changes in Bone Turnover and Skeletal Architecture in Igfbp-2-Null Mice

et al. 2008

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IGF-binding protein-2 (IGFBP-2) is a 36-kDa protein that binds to the IGFs with high affinity. To determine its role in bone turnover, we compared Igfbp2(-/-) mice with Igfbp2(+/+) colony controls. Igfbp2(-/-) males had shorter femurs and were heavier than controls but were not insulin resistant. Serum IGF-I levels in Igfbp2(-/-) mice were 10% higher than Igfbp2(+/+) controls at 8 wk of age; in males, this was accompanied by a 3-fold increase in hepatic Igfbp3 and Igfbp5 mRNA transcripts compared with Igfbp2(+/+) controls. The skeletal phenotype of the Igfbp2(-/-) mice was gender and compartment specific; Igfbp2(-/-) females had increased cortical thickness with a greater periosteal circumference compared with controls, whereas male Igfbp2(-/-) males had reduced cortical bone area and a 20% reduction in the trabecular bone volume fraction due to thinner trabeculae than Igfbp2(+/+) controls. Serum osteocalcin levels were reduced by nearly 40% in Igfbp2(-/-) males, and in vitro, both CFU-ALP(+) preosteoblasts, and tartrate-resistant acid phosphatase-positive osteoclasts were significantly less abundant than in Igfbp2(+/+) male mice. Histomorphometry confirmed fewer osteoblasts and osteoclasts per bone perimeter and reduced bone formation in the Igfbp2(-/-) males. Lysates from both osteoblasts and osteoclasts in the Igfbp2(-/-) males had phosphatase and tensin homolog (PTEN) levels that were significantly higher than Igfbp2(+/+) controls and were suppressed by addition of exogenous IGFBP-2. In summary, there are gender- and compartment-specific changes in Igfbp2(-/-) mice. IGFBP-2 may regulate bone turnover in both an IGF-I-dependent and -independent manner.

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“…Vitamin K acts as a coenzyme of γ-carboxylase, which converts glutamate in osteocalcin into γ-carboxyglutamate (Gla) (7). It is clear that vitamin K is an essential component in ossification (8, 9). Undercarboxylated osteocalcin (ucOC) has been used as hip fracture indicator, since it is related to vitamin K and the observed amount of ucOC increases in osteoporosis patients (6, 10).…”

Section: Introductionmentioning

confidence: 99%

Correlation of Undercarboxylated Osteocalcin (ucOC) Concentration and Bone Density with Age in Healthy Korean Women

Kim

et al. 2010

J Korean Med Sci

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Uncarboxylated osteocalcin (ucOC) is important in evaluating vitamin K status and it is inversely associated with bone mineral density (BMD). We studied the correlationship between ucOC and BMD in healthy Korean women. This study recruited 337 healthy women between ages 20-70 were recruited. Serum ucOC, calcium, alkaline phosphatase, body mass index (BMI), and BMD were measured and compared. Mean BMI was lowest (20.3±1.9 kg/m2) in the 20 yr old group and highest (24.8±2.6 kg/m2) in the 60 yr old group. Women age 20-70 yr old had ucOC inversely related to BMD independent of other factors that may influence BMD. Serum ucOC concentration and BMD of lumbar spine showed a significant inverse relationship. Serum mean alkaline phosphatase was lowest (122±30 IU/L) in the age 30 group and highest (190.3±55.8 IU/L) in the age 60 group. Serum ucOC was inversely associated with BMI, and positively associated with alkaline phosphatase. Uncarboxylated osteocalcin (ucOC) was inversely associated with spinal BMD in healthy Korean women. Serum mean ucOC was highest in the age 20 group, followed by age 50 group, which may indicate vitamin K insufficiency could be related to high bone turnover in these groups. These results suggest that vitamin K supplement may be considered to help both bone growth and bone loss during these periods.

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Diet- or Warfarin-Induced Vitamin K Insufficiency Elevates Circulating Undercarboxylated Osteocalcin Without Altering Skeletal Status in Growing Female Rats

Abstract: To further characterize the skeletal role of vitamin K (K), markers of bone turnover, density, and strength were evaluated in rats with diet-or warfarin (W)-induced K insufficiency. One hundred two, 7-week-old, female rats were randomly assigned to low K

Cited by 46 publications

References 23 publications

Bone and glucose metabolism: A two-way street

Bone and glucose metabolism: A two-way street

Gender-Specific Changes in Bone Turnover and Skeletal Architecture in Igfbp-2-Null Mice

Correlation of Undercarboxylated Osteocalcin (ucOC) Concentration and Bone Density with Age in Healthy Korean Women

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