Response of Serum Carboxylated and Undercarboxylated Osteocalcin to Risedronate Monotherapy and Combined Therapy with Vitamin K2 in Corticosteroid-Treated Patients: A Pilot Study

Hozuki, Takayoshi; Imai, Tomihiro; Tsuda, Etsuko; Matsumura, Akihiro; Yamamoto, Daisuke; Toyoshima, Takanobu; Suzuki, Syuuichiro; Yamauchi, Rika; Hayashi, Takashi; Hisahara, Shin; Shimohama, Shun

doi:10.2169/internalmedicine.49.2551

Cited by 14 publications

(9 citation statements)

References 41 publications

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“…When treated with corticosterone, WT mice displayed a decrease in the level of both total and undercarboxylated osteocalcin but no change in the proportion of undercarboxylated osteocalcin. This mimics observations in humans treated with glucocorticoids (52). It has also been reported that both the vitamin K-dependent carboxylase activity and the biosynthesis of its substrates are enhanced by glucocorticoids (53,54).…”

Section: Figure 13supporting

confidence: 83%

Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism

Brennan‐Speranza

Henneicke²,

Gasparini³

et al. 2012

J. Clin. Invest.

172

123

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Long-term glucocorticoid treatment is associated with numerous adverse outcomes, including weight gain, insulin resistance, and diabetes; however, the pathogenesis of these side effects remains obscure. Glucocorticoids also suppress osteoblast function, including osteocalcin synthesis. Osteocalcin is an osteoblast-specific peptide that is reported to be involved in normal murine fuel metabolism. We now demonstrate that osteoblasts play a pivotal role in the pathogenesis of glucocorticoid-induced dysmetabolism. Osteoblast-targeted disruption of glucocorticoid signaling significantly attenuated the suppression of osteocalcin synthesis and prevented the development of insulin resistance, glucose intolerance, and abnormal weight gain in corticosterone-treated mice. Nearly identical effects were observed in glucocorticoid-treated animals following heterotopic (hepatic) expression of both carboxylated and uncarboxylated osteocalcin through gene therapy, which additionally led to a reduction in hepatic lipid deposition and improved phosphorylation of the insulin receptor. These data suggest that the effects of exogenous high-dose glucocorticoids on insulin target tissues and systemic energy metabolism are mediated, at least in part, through the skeleton.

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Section: Figure 13supporting

confidence: 83%

Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism

Brennan‐Speranza

Henneicke²,

Gasparini³

et al. 2012

J. Clin. Invest.

172

123

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show abstract

“…Further, inhibitors of bone resorption decrease serum unOC in patients with osteoporosis[36]. Overall, unOC is associated with bone turnover markers in adults and decreases with corticosteroid treatments[37, 38]. However, the associations of unOC with resorption in early development may be different than in adults.…”

Section: 0 Discussionmentioning

confidence: 99%

Tactile/kinesthetic stimulation (TKS) increases tibial speed of sound and urinary osteocalcin (U-MidOC and unOC) in premature infants (29–32weeks PMA)

Haley

Beachy

Ivaska

et al. 2012

Bone

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Preterm delivery (<37 wks post-menstrual age) is associated with suboptimal bone mass. We hypothesized that tactile/kinesthetic stimulation (TKS), a form of infant massage that incorporates kinesthetic movement, would increase bone strength and markers of bone accretion in preterm infants. Preterm, AGA infants (29-32 wks) were randomly assigned to TKS (N=20) or Control (N=20). Twice daily TKS was provided six days per week for two weeks. Control infants received the same care without TKS treatment. Treatment was masked to parents, health care providers, and study personnel. Baseline and week two measures were collected for tibial speed of sound (tSOS, m/sec), a surrogate for bone strength, by quantitative ultrasound (Sunlight8000) and urine markers of bone metabolism, pyridinium crosslinks and osteocalcin (U-MidOC and unOC). Infant characteristics at birth and study entry as well as energy/nutrient intake were similar between TKS and Control. TKS intervention attenuated the decrease in tSOS observed in Control infants (p<0.05). Urinary pyridinium crosslinks decreased over time in both TKS and CTL (p<0.005). TKS infants experienced greater increases in urinary osteocalcin (U-MidOC, p<0.001 and unOC, p<0.05). We conclude that TKS improves bone strength in premature infants by attenuating the decrease that normally follows preterm birth. Further, biomarkers of bone metabolism suggest a modification in bone turnover in TKS infants in favor of bone accretion. Taken together, we speculate that TKS improves bone mineralization.

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“…Finally, one of the major hormones to release energy-rich fuels from storage sites, namely glucocorticoid, reduces osteocalcin levels in that it inhibits osteoblast function [37]. This is another indication of the storage function of this hormone that can be switched off by a hormone of the energy expenditure network.…”

Section: Energy Storage Hormonesmentioning

confidence: 99%

Interaction of the endocrine system with inflammation: a function of energy and volume regulation

Straub

2014

Arthritis Res Ther

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During acute systemic infectious disease, precisely regulated release of energy-rich substrates (glucose, free fatty acids, and amino acids) and auxiliary elements such as calcium/phosphorus from storage sites (fat tissue, muscle, liver, and bone) are highly important because these factors are needed by an energy-consuming immune system in a situation with little or no food/water intake (sickness behavior). This positively selected program for short-lived infectious diseases is similarly applied during chronic inflammatory diseases. This review presents the interaction of hormones and inflammation by focusing on energy storage/expenditure and volume regulation. Energy storage hormones are represented by insulin (glucose/lipid storage and growth-related processes), insulin-like growth factor-1 (IGF-1) (muscle and bone growth), androgens (muscle and bone growth), vitamin D (bone growth), and osteocalcin (bone growth, support of insulin, and testosterone). Energy expenditure hormones are represented by cortisol (breakdown of liver glycogen/adipose tissue triglycerides/muscle protein, and gluconeogenesis; water retention), noradrenaline/adrenaline (breakdown of liver glycogen/adipose tissue triglycerides, and gluconeogenesis; water retention), growth hormone (glucogenic, lipolytic; has also growth-related aspects; water retention), thyroid gland hormones (increase metabolic effects of adrenaline/noradrenaline), and angiotensin II (induce insulin resistance and retain water). In chronic inflammatory diseases, a preponderance of energy expenditure pathways is switched on, leading to typical hormonal changes such as insulin/IGF-1 resistance, hypoandrogenemia, hypovitaminosis D, mild hypercortisolemia, and increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Though necessary during acute inflammation in the context of systemic infection or trauma, these long-standing changes contribute to increased mortality in chronic inflammatory diseases.

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Response of Serum Carboxylated and Undercarboxylated Osteocalcin to Risedronate Monotherapy and Combined Therapy with Vitamin K2 in Corticosteroid-Treated Patients: A Pilot Study

Abstract: Objective The aim of this study was to investigate the responses of serum osteocalcin (OC), undercarboxylated osteocalcin (ucOC)

Cited by 14 publications

References 41 publications

Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism

Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism

Tactile/kinesthetic stimulation (TKS) increases tibial speed of sound and urinary osteocalcin (U-MidOC and unOC) in premature infants (29–32weeks PMA)

Interaction of the endocrine system with inflammation: a function of energy and volume regulation

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