Osteocalcin Abstracts 2

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Vitamin K supplementation reduces serum concentrations of under-gamma-carboxylated osteocalcin in healthy young and elderly adults.
            (Binkley et al., 2000) Download
BACKGROUND:  Subclinical vitamin K insufficiency, manifested by under-gamma-carboxylation of the bone matrix protein osteocalcin, may be common. OBJECTIVE:  Our objective was to delineate the prevalence of submaximal gamma-carboxylation as assessed by response to phylloquinone supplementation and to evaluate the effect of this intervention on skeletal turnover in healthy North American adults. DESIGN:  Healthy subjects (n = 219), approximately equally distributed by sex and age (18-30 y and >/=65 y), received daily phylloquinone (1000 microg) or placebo for 2 wk. Serum undercarboxylated osteocalcin (ucOC) and total osteocalcin, N:-telopeptides of type I collagen (NTx), bone-specific alkaline phosphatase (BSAP), and phylloquinone concentrations were measured at baseline and after weeks 1 and 2. RESULTS:  At baseline, the mean serum phylloquinone concentration was lower in the young than in the old group; there was no effect of sex. Concomitantly, baseline %ucOC was highest in the young and lowest in the old men (P: < 0.0001) but did not differ significantly by age in women. After supplementation, serum phylloquinone concentration increased approximately 10-fold (P: < 0.0001) at week 1 (from 0.93 +/- 0.08 to 8.86 +/- 0.70 nmol/L, x+/- SEM); this was sustained through week 2. Among all supplemented groups, mean %ucOC decreased from 7.6% to 3. 4% without significant differences by age or sex; 102 of 112 subjects had a >1% decrease. Phylloquinone supplementation reduced serum osteocalcin but did not alter NTx or BSAP concentration. CONCLUSIONS:  Usual dietary practices in this population did not provide adequate vitamin K for maximal osteocalcin carboxylation. Phylloquinone supplementation reduced serum osteocalcin concentration but did not alter other markers of serum bone turnover.

Olive oil supplemented with menaquinone-7 significantly affects osteocalcin carboxylation.
            (Brugè et al., 2011)  Download
Menaquinone-7 (MK-7), a member of the vitamin K2 family, performs several functions, all related to its recognised effect on post-translational carboxylation of certain protein-bound glutamate residues. Due to its lipophilic structure MK-7 is soluble in olive oil, so the aim of the present study was to test whether extra-virgin (EV) olive oil enriched with MK-7 significantly increases MK-7 plasma levels and has an effect on osteocalcin and its carboxylation status. Healthy young volunteers (n 12) were administered 20 ml EV olive oil per d for 2 weeks, followed by 2 weeks of the same amount of olive oil enriched with 45 μg and then 90 μg MK-7, with an appropriate washout time in between. Blood was collected and plasma separated in each phase of the study. We found that integration of the diet with EV olive oil alone did not produce any significant variation of MK-7 plasma levels compared with baseline. Supplementation with MK-7-enriched olive oil resulted in a significant and dose-dependent increase in plasma levels. The high dose also significantly increased carboxylated osteocalcin (cOC) and decreased undercarboxylated osteocalcin (ucOC) plasma levels, resulting in a significant increase in the cOC:ucOC ratio. A significant correlation was also found between percentage variation of plasma cOCA:ucOC ratio and increase in plasma MK-7 levels. We conclude that regular consumption of MK-7-enriched olive oil may constitute a valid approach in order to preserve some key biochemical mechanisms controlling bone mineralisation.

Carboxylation of osteocalcin in post-menopausal osteoporotic women following vitamin K and D supplementation.
            (Douglas et al., 1995) Download
The effect of vitamin supplements on bone metabolism indices in patients with osteoporosis has received scant attention in the literature. Over a 2-week period, vitamin supplements of K and K+D were given to 20 post-menopausal osteoporotic women with previous Colles fractures. Osteoporosis was confirmed by bone mass measurements that demonstrated that broadband ultrasound attenuation (os calcis) was almost as discriminatory as dual energy X-ray absorptiometry (spine and hip) in Colles fracture patients compared with matched controls. Vitamin K corrected the carboxylation defect in osteocalcin and while less marked 4 weeks later, the improvement was still detectable. The result after K+D was similar. The level of carboxylation became the same as in premenopausal women. Total osteocalcin level (bound) osteocalcin. While there was vitamin K correctable undercarboxylation of osteocalcin, simultaneously there was no evidence of undercarboxylation of prothrombin.

Twelve-month consumption of a polyphenol extract from olive (Olea europaea) in a double blind, randomized trial increases serum total osteocalcin levels and improves serum lipid profiles in postmenopausal women with osteopenia.
            (Filip et al., 2015)  Download
OBJECTIVES:  Osteoporosis is a skeletal disorder characterized by impaired bone turnover and compromised bone strength, thereby predisposing to increased risk of fracture. Preclinical research has shown that compounds produced by the olive tree (Olea europaea), may protect from bone loss, by increasing osteoblast activity at the expense of adipocyte formation. The aim of this exploratory study was to obtain a first insight on the effect of intake of an olive extract on bone turnover in postmenopausal women with decreased bone mass (osteopenia). DESIGN AND SETTING:  For that, a double blind, placebo-controlled study was performed in which participants were randomly allocated to either treatment or placebo groups. PARTICIPANTS:  64 osteopenic patients, with a mean bone mineral density (BMD) T-score between -1.5 and -2.5 in the lumbar spine (L2-L4) were included in the study. INTERVENTION AND MEASUREMENTS:  PARTICIPANTS received for 12 months daily either 250 mg/day of olive extract and 1000 mg Ca (treatment) or 1000 mg Ca alone (placebo). Primary endpoints consisted of evaluation of bone turnover markers. Secondary endpoints included BMD measurements and blood lipid profiles. RESULTS:  After 12 months, the levels of the pro-osteoblastic marker osteocalcin were found to significantly increase in the treatment group as compared to placebo. Simultaneously, BMD decreased in the placebo group, while remaining stable in the treatment group. In addition, improved lipid profiles were observed, with significant decrease in total- and LDL-cholesterol in the treatment group. CONCLUSION:  This exploratory study supports preclinical observations and warrants further research by showing that a specific olive polyphenol extract (Bonolive®) affects serum osteocalcin levels and may stabilize lumbar spine BMD. Moreover, the improved blood lipid profiles suggest additional health benefits associated to the intake of the olive polyphenol extract.

The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects.
            (Hwang et al., 2009)  Download
BACKGROUND:  Recent human studies support the notion that serum osteocalcin increases beta-cell proliferation and insulin secretion, and improves insulin sensitivity. However, no study has examined the effects of serum osteocalcin gamma-carboxylation status on these associations or determined the role of uncarboxylated osteocalcin in glucose metabolism in humans. METHODS:  The aim of this study was to determine the association between uncarboxylated osteocalcin and beta-cell function and insulin sensitivity in humans. As many as 199 men, aged 25-60 years (mean age, 47 years), who had never been treated with glucose lowering agents, were enrolled in this cross-sectional study. OGTT was performed and other metabolic parameters, such as, BMI, BP, lipid profiles, and both uncarboxylated and carboxylated osteocalcin plasma levels were measured. RESULTS:  When subjects were divided into tertiles by uncarboxylated and carboxylated osteocalcin plasma concentrations, subjects in the upper tertile of each showed lower fasting and post-challenge glucose levels after adjusting for age and BMI (P < 0.05). The upper uncarboxylated osteocalcin tertile was associated with higher HOMA-B% levels, which are representative of beta-cell function (P < 0.05), and the upper carboxylated osteocalcin tertile was associated with lower HOMA-IR values, which are representative of insulin resistance (P < 0.05). CONCLUSIONS:  Elevated levels of both carboxylated and uncarboxylated forms of osteocalcin were associated with improved glucose tolerance. Moreover, the uncarboxylated form of osteocalcin was found to be associated with enhanced beta-cell function, and the carboxylated form was associated with improved insulin sensitivity in middle-aged male subjects.

Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study.
            (Iki et al., 2012)  Download
SUMMARY:  Recent animal studies have demonstrated that undercarboxylated osteocalcin upregulates insulin secretion via osteoblast-insulin signaling. However, it remains unclear whether such a pathway exists in humans. This study showed that serum undercarboxylated osteocalcin levels were inversely associated with fasting plasma glucose, hemoglobin A(1c), and homeostasis model assessment of insulin resistance (HOMA-IR) levels in community-dwelling elderly Japanese men. INTRODUCTION:  Undercarboxylated osteocalcin (ucOC) was reported to increase insulin secretion and improve glucose tolerance via osteoblast-insulin signaling in animal-based studies. Whether this pathway also exists in humans is unknown. We aimed to clarify whether serum ucOC levels are associated with glycemic status and insulin resistance in the general Japanese population. METHODS:  We included 2,174 Japanese men (≥65 years) who were able to walk without aid from others and lived at home in four cities of Nara Prefecture. We excluded participants with a history of diseases or medications that affect bone metabolism, other than type 2 diabetes mellitus (T2DM). Fasting plasma glucose, glycated hemoglobin A(1c), and HOMA-IR levels were determined as outcome measures. RESULTS:  Of the 1,597 participants included in the analysis, both intact OC (iOC) and ucOC levels showed significant inverse correlations with all outcome measures, even after adjusting for potential confounders. Mean values of outcome measures showed a significant decreasing trend with higher quintiles of iOC or ucOC after adjusting for confounders. This trend remained significant for ucOC quintiles after further adjustment for iOC levels, but was not significant for iOC quintiles after adjusting for ucOC levels. These results were attenuated, but still apparent, after excluding participants receiving drug therapy for T2DM. CONCLUSIONS:  Levels of ucOC, but not iOC, were inversely associated with glycemic index and insulin resistance in a population of Japanese men. These findings will need to be confirmed with longitudinal studies.


 

Vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old.
            (Je et al., 2011)  Download
There are inconsistent findings on the effects of vitamin K on bone mineral density (BMD) and undercarboxylated osteocalcin (UcOC). The present intervention study evaluated the effect in subjects over 60-yr-old. The vitamin K group (vitamin K + vitamin D + calcium supplement; 15 mg of vitamin K2 [menatetrenone] three times daily, 400 IU of vitamin D once a day, and 315 mg of calcium twice daily) and the control group (vitamin D + calcium supplement) were randomly assigned. During the six months of treatment, seventy eight women participated (38 in the vitamin K group and 40 in the control group) and 45 women completed the study. The baseline characteristics of study participants did not differ between the vitamin K and the control groups. In a per protocol analysis after 6 months, L3 bone mineral density has increased statistically significantly in the vitamin K group compared to the control group (0.01 ± 0.03 g/cm(2) vs -0.008 ± 0.04 g/cm(2), P = 0.049). UcOC concentration was also significantly decreased in the vitamin K group (-1.6 ± 1.6 ng/dL vs -0.4 ± 1.1 ng/dL, P = 0.008). In conclusion, addition of vitamin K to vitamin D and calcium supplements in the postmenopausal Korean women increase the L3 BMD and reduce the UcOC concentration.

Effects of risedronate alone or combined with vitamin K2 on serum undercarboxylated osteocalcin and osteocalcin levels in postmenopausal osteoporosis.
            (Kasukawa et al., 2014)  Download
Risedronate decreases osteoporotic fracture incidence; however, its effects remain unclear in elderly osteoporotic patients. Vitamin K mediates carboxylation of osteocalcin (OC), and high undercarboxylated osteocalcin (ucOC) levels indicate vitamin K deficiency and increased osteoporotic fracture risk. We aimed to evaluate the effects of risedronate alone or combined with vitamin K2 on serum ucOC, OC, and incidence of vertebral fractures in elderly osteoporotic patients. A total of 101 women with postmenopausal osteoporosis aged >60 years were randomly stratified into two groups-R group (n = 51), treated with risedronate alone; and R + K group (n = 50), treated with risedronate and vitamin K2. Serum ucOC, OC and incidence of vertebral fractures were evaluated before treatment and at 6 and 12 months post-treatment. Decreased ucOC rates at 6 and 12 months were not significant between groups. However, at 6 and 12 months, decreased OC rates in the R group (p < 0.01 and 0.05, respectively) were significantly higher than in the R + K group, and ucOC/OC change rates in the R group (p < 0.05 and 0.001, respectively) were significantly lower than in the R + K group. Vertebral fracture incidence was not significantly different between the groups at 6 and 12 months. ucOC levels in patients with incident vertebral fractures were significantly higher than in patients without incident vertebral fractures in the R group at 6 months (p < 0.05). Although no significant difference was observed for ucOC decrease rate and incidence of vertebral fractures between treatments, ucOC levels in patients with incident vertebral fractures were significantly greater than in patients without when using risedronate alone.

Ascorbic acid insufficiency induces the severe defect on bone formation via the down-regulation of osteocalcin production.
            (Kim et al., 2013)  Download
The L-gulono-γ-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo (-/-) mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo (-/-) mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo (-/-) mice, 3-week ascorbic acid-insufficient Gulo (-/-) mice, and 4-week ascorbic acid-insufficient Gulo (-/-) mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo (-/-) mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo (-/-) mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo (-/-) mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo (-/-). In summary, ascorbic acid insufficiency in Gulo (-/-) mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels.

Acute effect of 1,25-dihydroxyvitamin D3, prednisone, and 1,25-dihydroxyvitamin D3 plus prednisone on serum osteocalcin in normal individuals.
            (Nielsen et al., 1991) Download
Suppression of osteoblastic function plays an important pathogenic role for the development of glucocorticosteroid-induced osteoporosis. Serum osteocalcin (OC) is a sensitive marker of bone formation. The diurnal rhythm in serum OC can be changed by administration of single doses of either 1,25-(OH)2D3 or prednisone. However, the two steroids have opposing effects: 1,25-(OH)2D3 increases and prednisone decreases serum OC. The aim of the present study was to examine whether 1,25-(OH)2D3 can oppose the acute suppressive effect of prednisone on serum OC in normal subjects. We compared the effect of a combined dose of 2 micrograms 1,25-(OH)2D3 and 10 mg prednisone on the diurnal rhythm of serum OC with the effect of 2 micrograms 1,25-(OH)2D3 + placebo in a crossover study. Seven normal subjects aged 23-36 years were investigated twice at an interval of 1 week. Blood samples were collected every 60 minutes from 1900 until 1100 h the following day. Study drugs were given at 2000 h. The data from the present investigation were compared with data obtained from a similar study with placebo and prednisone in the same subjects. After administration of 1,25-(OH)2D3 serum OC followed the placebo curve during the first 8 h, but in contrast to the placebo curve it then continued to increase and remained elevated throughout the observation period (p less than 0.05). Prednisone inhibited and reversed the nocturnal rise in serum OC levels (p less than 0.01). The course of serum OC after administration of 1,25-(OH)2D3 + prednisone almost paralleled the course after placebo. We conclude that 1,25-(OH)2D3 and prednisone have opposing effects on serum OC.

Effect of DHEA supplementation on serum IGF-1, osteocalcin, and bone mineral density in postmenopausal, glucocorticoid-treated women.
            (Papierska et al., 2012)  Download
PURPOSE:  DHEA therapy increases bone formation in postmenopausal women. We have found only a few reports of dehydroepiandrosterone replacement therapy in women receiving long-term glucocorticoid medication. The purpose of this study was to establish whether DHEA replacement therapy may be useful in the treatment of steroid-induced osteoporosis in postmenopausal women. MATERIALS AND METHODS:  Nineteen women, aged 50-78 years, treated at least for three years with average daily doses of more than 7.5 mg prednisone, with T-score L2/L4<-1.5 and bisphosphonates intolerance, were enrolled to the study. For the first year of the study the patients were given calcium, vitamin D3 and thiazide diuretics. For another year the patients received orally micronized DHEA 25-50 mg daily. Before the study, after twelve months of Calcium/D3 therapy, then after six weeks and six months of DHEA therapy, serum concentrations of DHEAS, androstenedione, testosterone, estradiol, FSH, IGF-1 and osteocalcin were assessed. Bone mineral density (BMD) in lumbar spine and femoral neck was measured before the treatment, after a year on Calcium/D3 and after six and twelve months of DHEA replacement therapy. RESULTS:  In all treated women, DHEA significantly increased serum DHEAS, androstenedione and testosterone concentrations. A significant elevation of serum IGF-1 and osteocalcin concentrations was found as early as after six weeks of DHEA treatment. A significant increase of bone mineral density in the lumbar spine and femoral neck was observed after six and twelve months of DHEA treatment. CONCLUSION:  Our results suggest a beneficial role of DHEA replacement therapy in the treatment of steroid-induced osteoporosis.


 

Vitamin D supplementation during short-term caloric restriction in healthy overweight/obese older women: Effect on glycemic indices and serum osteocalcin levels.
            (Sukumar et al., 2015)  Download
The effect of vitamin D supplementation and caloric restriction (CR) on glycemic indices and osteocalcin (OC) is not clear. In this randomized controlled double blind trial, we examined whether vitamin D3 supplementation at 2500 IU/d (D) or placebo has differential effects on markers of insulin sensitivity and bone turnover in overweight/obese postmenopausal women during 6 weeks of caloric restriction (weight loss; WL, n = 39) compared to weight maintenance (WM, n = 37). Seventy-six women (57 ± 6 years) completed this study and the WL groups lost 4 ± 1% of body weight. Baseline serum 25-hydroxyvitamin D (25OHD) was 24.8 ± 5.6 ng/mL at baseline; the rise was greatest in WL-D group (p < 0.05). There was an interaction between vitamin D intake and weight on serum OC, insulin, glucose and markers of insulin sensitivity (p < 0.05). The change in OC was explained by changes in serum 25OHD and insulin (model R(2) = 25.6%). Overall, vitamin D supplementation and CR influence serum osteocalcin levels and modestly favor improvements in insulin sensitivity.

The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children.
            (van Summeren et al., 2009)  Download
Vitamin K contributes to bone health, probably through its role as cofactor in the carboxylation of osteocalcin. Intervention studies in adults have demonstrated that markedly higher osteocalcin carboxylation is obtained by intakes of vitamin K well above the current recommended dietary intake. However, the relationship between increased vitamin K2 intake and enhanced osteocalcin carboxylation has never been shown in healthy children. The objective was to study the effect of 45 microg menaquinone-7 (MK-7; one of the vitamin K2 species) on the circulating levels of undercarboxylated osteocalcin (ucOC) and carboxylated osteocalcin (cOC) in healthy prepubertal children. We hypothesised that MK-7 supplementation will reduce the ucOC:cOC ratio (UCR), indicating an improved vitamin K status. The present study is a double-blind randomised placebo-controlled trial examining the effect of 8 weeks MK-7 supplementation on the carboxylation of osteocalcin in healthy children (n 55). Serum levels of ucOC, cOC and MK-7 were measured at baseline and after 8 weeks, together with bone markers and coagulation parameters. The UCR was used as an indicator of vitamin K status. In the MK-7-supplemented group (n 28), the circulating concentration of inactive ucOC reduced and the UCR improved whereas the concentration of MK-7 increased. Within the placebo group, ucOC, cOC, UCR and MK-7 did not significantly change over time. In both groups, bone markers and coagulation parameters remained constant over time. These findings demonstrate that in healthy, prepubertal children, modest supplementation with MK-7 increases circulating concentrations of MK-7 and increases osteocalcin carboxylation.

Different effects of oral conjugated equine estrogens and transdermal estrogen on undercarboxylated osteocalcin concentration in postmenopausal women.
            (Yasui et al., 2006)  Download
OBJECTIVE:  Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin K status, and triglyceride (TG) has been shown to be the main transporter of vitamin K. In the present study, we examined the difference between ucOC concentrations in postmenopausal women receiving hormone therapy (HT) with oral conjugated equine estrogens (CEE) and transdermal estradiol (TE2). We also examined the associations of ucOC concentration with estradiol concentration and TG. DESIGN:  Ninety-two postmenopausal women were recruited for this study. Serum concentrations of ucOC, intact osteocalcin, estradiol, and TG were measured before and after 12 months of HT. Forty-six women received oral administration of 0.625 mg of CEE and 2.5 mg of medroxyprogesterone acetate daily, and 46 women received transdermal administration of 50 mug of 17beta-estradiol twice weekly and 2.5 mg of medroxyprogesterone acetate daily. RESULTS:  The ucOC concentration in women during HT with oral CEE was significantly (P < 0.01) lower than that in women during HT with TE2. Serum estradiol concentrations during HT with CEE showed a significant inverse correlation with ucOC concentrations and the ratio of ucOC/OC during HT (P < 0.05 and P < 0.01, respectively). In addition, the serum ucOC concentration in women with an increased percentage of change in TG was significantly (P < 0.01) lower than that in women with a decreased percentage of change in TG during HT with oral CEE. CONCLUSION:  The effect of HT with TE2 on ucOC concentration in women is weaker than the effect of HT with oral CEE. Suppression of ucOC concentration in postmenopausal women during HT with oral CEE might be associated with the effect of vitamin K through increased TG induced by oral CEE.

 


References

Binkley, NC, et al. (2000), ‘Vitamin K supplementation reduces serum concentrations of under-gamma-carboxylated osteocalcin in healthy young and elderly adults.’, Am J Clin Nutr, 72 (6), 1523-28. PubMed: 11101481
Brugè, F, et al. (2011), ‘Olive oil supplemented with menaquinone-7 significantly affects osteocalcin carboxylation.’, Br J Nutr, 106 (7), 1058-62. PubMed: 21736837
Douglas, AS, et al. (1995), ‘Carboxylation of osteocalcin in post-menopausal osteoporotic women following vitamin K and D supplementation.’, Bone, 17 (1), 15-20. PubMed: 7577153
Filip, R, et al. (2015), ‘Twelve-month consumption of a polyphenol extract from olive (Olea europaea) in a double blind, randomized trial increases serum total osteocalcin levels and improves serum lipid profiles in postmenopausal women with osteopenia.’, J Nutr Health Aging, 19 (1), 77-86. PubMed: 25560820
Hwang, YC, et al. (2009), ‘The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects.’, Diabetes Metab Res Rev, 25 (8), 768-72. PubMed: 19877133
Iki, M, et al. (2012), ‘Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study.’, Osteoporos Int, 23 (2), 761-70. PubMed: 21437719
Je, SH, et al. (2011), ‘Vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old.’, J Korean Med Sci, 26 (8), 1093-98. PubMed: 21860562
Kasukawa, Y, et al. (2014), ‘Effects of risedronate alone or combined with vitamin K2 on serum undercarboxylated osteocalcin and osteocalcin levels in postmenopausal osteoporosis.’, J Bone Miner Metab, 32 (3), 290-97. PubMed: 23846118
Kim, W, et al. (2013), ‘Ascorbic acid insufficiency induces the severe defect on bone formation via the down-regulation of osteocalcin production.’, Anat Cell Biol, 46 (4), 254-61. PubMed: 24386598
Nielsen, HK, et al. (1991), ‘Acute effect of 1,25-dihydroxyvitamin D3, prednisone, and 1,25-dihydroxyvitamin D3 plus prednisone on serum osteocalcin in normal individuals.’, J Bone Miner Res, 6 (5), 435-41. PubMed: 2068950
Papierska, L, et al. (2012), ‘Effect of DHEA supplementation on serum IGF-1, osteocalcin, and bone mineral density in postmenopausal, glucocorticoid-treated women.’, Adv Med Sci, 57 (1), 51-57. PubMed: 22430044
Sukumar, D, SA Shapses, and SH Schneider (2015), ‘Vitamin D supplementation during short-term caloric restriction in healthy overweight/obese older women: Effect on glycemic indices and serum osteocalcin levels.’, Mol Cell Endocrinol, 410 73-77. PubMed: 25576857
van Summeren, MJ, et al. (2009), ‘The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children.’, Br J Nutr, 102 (8), 1171-78. PubMed: 19450370
Yasui, T, et al. (2006), ‘Different effects of oral conjugated equine estrogens and transdermal estrogen on undercarboxylated osteocalcin concentration in postmenopausal women.’, Menopause, 13 (4), 651-59. PubMed: 16837887