Oral anticoagulant treatment: friend or foe in cardiovascular disease?

Insulin Signaling in Osteoblasts Integrates Bone Remodeling and Energy Metabolism

Osteocalcin acts as a hormone in the body, causing beta cells in the pancreas to release more insulin, and at the same time directing fat cells to release the hormone adiponectin, which increases sensitivity to insulin (R).

Recent studies found a clear association between long-term oral (or intravenous) anticoagulant treatment (OAC) and reduced bone quality due to reduction of active osteocalcin. OAC might lead to an increased incidence of fracture, reduced bone mineral density or content, osteopenia, and increased serum levels of undercarboxylated osteocalcin.

Relation of Oral Anticoagulation to Cardiac Valvular and Coronary Calcium Assessed by Multislice Spiral Computed Tomography

Vitamin K Treatment Reduces Undercarboxylated Osteocalcin but Does Not Alter Bone Turnover, Density, or Geometry in Healthy Postmenopausal North American Women

Low vitamin K status is associated with low BMD and increased fracture risk. Additionally, a specific menaquinone, menatetrenone (MK4), may reduce fracture risk.

Vitamin K-Dependent Carboxylation of Osteocalcin: Friend or Foe?

In humans, the percentage of the circulating osteocalcin that is not γ-carboxylated (percent ucOC) is used as a biomarker of vitamin K status. In contrast, when ucOC is not corrected for total osteocalcin, the interpretation of this measure is confounded by osteoblastic activity, independent of vitamin K.

vitamin K decreases ucOC.

Regulation of male fertility by the bone-derived hormone osteocalcin

Osteocalcin acts on Leydig cells of the testis to stimulate testosterone biosynthesis and therefore affect male fertility (R).

Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise

«The growing number of functions ascribed to osteocalcin (Karsenty and Olson, 2016) raises the question of whether the circulating levels of this hormone change in various physiological situations. This analysis revealed that a single bout of endurance aerobic-based exercise (40 minutes run on a treadmill at 30cm/s, 80% VO₂ max, thereafter referred to as exercise) increased circulating osteocalcin levels of total and undercarboxylated and bioactive two-fold in 3 month-old wild-type (WT) mice while at same time the circulating levels of insulin decreased. This increase in the circulating levels of bioactive osteocalcin was due in part to an increase in bone resorption, the arm of bone remodeling that is responsible of osteocalcin decarboxylation and activation (Ferron et al., 2010) (Figure 1A–C). Circulating osteocalcin levels also significantly increased in young women after a 45 minute-long exercise (Figure 1D).»

Changes in bone density after exposure to oral anticoagulants: a meta-analysis.

Oral anticoagulants are putative risk factors for osteoporosis, but observational cross-sectional studies describing their effects on bone mineral density have reported conflicting results, prospective studies are not available, and randomized trials are not feasible.

Keywords: Administration, Oral;Aged;Anticoagulants;Bone Density;Cross-Sectional Studies;Female;Femur;Femur Neck;Humans;Lumbar Vertebrae;Male;Middle Aged;Radius;Time Factors

Bone mineral densities in individuals with Gilbert's syndrome: a cross-sectional, case-control pilot study.

«RESULTS: A total of 17 GS and 30 control subjects were studied. Overall, there were no significant differences in BMD, PTH, CTX or osteocalcin levels between the two groups. However, when older (older than 40 years of age) and younger (40 years of age and younger) cohorts were considered separately, the older GS cohort had significantly decreased total hip BMD, T scores and Z scores, and femoral neck BMD, T scores and Z scores (P<0.005 for each parameter, respectively) compared with older control subjects. Serum osteocalcin levels were lower in the older versus younger GS cohort (P=0.006). An inverse correlation existed between all subjects' serum unconjugated bilirubin levels and total body BMD determinations (r=-0.42; P=0.04). On univariate analysis, the association between serum unconjugated bilirubin and total body BMD was not significant (P=0.066), nor was serum unconjugated bilirubin identified as a risk factor for low BMD when entered into multivariate analyses.

CONCLUSIONS: The results of the present pilot study warrant further research involving larger numbers of subjects and longitudinal measurements to determine whether GS is associated with decreased BMD, particularly in older GS subjects.»

Regulation of male fertility by the bone-derived hormone osteocalcin.

Osteocalcin acts on Leydig cells of the testis to stimulate testosterone biosynthesis and therefore affect male fertility (R).

Keywords: Animals;Bone and Bones;Fertility;Hormone;Humans;Male;Osteocalcin;Reproduction;Testosterone

RbAp48 Protein Is a Critical Component of GPR158/OCN Signaling and Ameliorates Age-Related Memory Loss.

«Precisely deciphering the molecular mechanisms of age-related memory loss is crucial to create appropriate therapeutic interventions. We have previously shown that the histone-binding protein RbAp48/Rbbp4 is a molecular determinant of Age-Related Memory Loss. By exploring how this protein regulates the genomic landscape of the hippocampal circuit, we find that RbAp48 controls the expression of BDNF and GPR158 proteins, both critical components of osteocalcin (OCN) signaling in the mouse hippocampus. We show that inhibition of RbAp48 in the hippocampal formation inhibits OCN's beneficial functions in cognition and causes deficits in discrimination memory. In turn, disruption of OCN/GPR158 signaling lead to the downregulation of RbAp48 protein, mimicking the discrimination memory deficits observed in the aged hippocampus. We also show that activation of the OCN/GPR158 pathway increases the expression of RbAp48 in the aged dentate gyrus and rescues age-related memory loss.»