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PubMed1993

A cross-sectional study on osteocalcin levels in gingival crevicular fluid from periodontal patients.

The purpose of the present study was to determine the levels of osteocalcin, a bone specific matrix protein, in gingival crevicular fluid (GCF) from periodontal disease patients and to investigate the relationship between GCF osteocalcin levels and clinical parameters. Nineteen initial visit patients, 5 patients with gingivitis and 14 patients with adult periodontitis, participated in this study. The clinical parameters including probing depth, attachment level, gingival index, and tooth mobility were recorded following careful sampling of GCF with a filter paper strip harvested for 3 minutes. Osteocalcin adsorbed on a strip was extracted in a plastic tube containing 150 microliters of 10 mM sodium phosphate buffer (pH 6.5). GCF osteocalcin was determined by a newly-developed, high sensitive enzyme immunoassay which could recognize the N-terminal 20 residue peptide. In gingivitis patients, no significant amounts of osteocalcin were detected. In periodontitis patients, on the other hand, osteocalcin levels were detected, ranging between 0 and 540 pg/tube and positively correlated with these clinical parameters (P < 0.01). Moreover, in several sites in GI = 3 group, extremely higher levels of GCF osteocalcin were detected. These results strongly suggest that in addition to the presence of GCF osteocalcin the levels of osteocalcin may reflect the degree of the periodontal inflammation at the sampled sites.

Adolescent↗

PubMed1995

Measurement of a more stable region of osteocalcin in serum by ELISA with two monoclonal antibodies.

Intact human osteocalcin purified from femoral bones as well as tryptic fragments of the intact molecule [amino acids (aa) 1-19, 20-43, and 45-49] were used to raise and screen monoclonal antibodies (MAbs). A two-site ELISA for measurement of human osteocalcin in serum was developed with use of these MAbs. A MAb recognizing midregion human osteocalcin (aa20-43) was used as capture antibody, and an NH2 terminus (aa7-19)-specific peroxidase-conjugated MAb was used for detection. Human osteocalcin obtained from bone was used for calibration, and parallelism was observed for osteocalcin from serum samples, NH2-terminal midfragments (aa1-43), and synthetic human osteocalcin. Both inter- and intraassay variations were < 7%. Serum osteocalcin in healthy premenopausal women (n = 49) was 18.3 +/- 4.2 micrograms/L (mean +/- SD) and 28.6 +/- 9.7 micrograms/L in early postmenopausal women (n = 114). The mean serum concentration (n = 10) decreased by 10% after 7 days of storage at 4 degrees C, whereas the concentration of intact human osteocalcin was reduced 63%. The N-MID ELISA and an IRMA measuring intact human osteocalcin were used to monitor the effect of hormone replacement therapy in a retrospective study. A significant decrease to the premenopausal concentration was detected only in the N-MID ELISA.

Antibodies, Monoclonal↗

PubMed1990

Comparison of monoclonal and polyclonal antibody-based immunoassays for osteocalcin: a study of sources of variation in assay results.

We have compared two assays for osteocalcin (BGP, bone gla protein), one based on a monoclonal antibody, the other based on a polyclonal serum, in an effort to better understand the factors that contribute to the wide variation reported for osteocalcin normal ranges. The two assays compared well using serum samples, with a correlation coefficient of 0.9071 (n = 48). However, the monoclonal antibody assay returns values increased over the polyclonal assay by approximately 1.5-fold. Gel permeation studies indicate that these larger values are due primarily to increased reactivity in the monoclonal assay with high- and low-molecular-weight forms of osteocalcin in plasma; both assays give similar reactions to intact osteocalcin. Analysis of samples from individuals with increased bone resorption due to parathyroid hormone administration reveals that the decrease seen in osteocalcin values after hormone infusion occurs primarily in the fraction that corresponds to intact osteocalcin. During the course of these studies, we re-evaluated the extinction coefficient for osteocalcin, arriving at the value E = 1.33 mg/ml-1, cm-1. We also observed a significant negative interference in both assays (and a commercial assay) caused by hemolysis. This interference is due to proteolysis of osteocalcin by enzymatic activity released from the lysed red cells.

Animals↗

PubMed1991

Lower serum osteocalcin in ethanol-fed rats.

Serum osteocalcin was remarkably and significantly (-34 and -41% in two separate experiments; p less than 0.001) lower in rats fed an 8% (w/v) ethanol liquid diet (ELD) for 1 week than in rats fed an isocaloric control liquid diet (CLD). In a longer experiment that spanned 4 weeks, the ELD rats were given 6% ethanol on day 4, increased stepwise to 8% by day 9, and then maintained at 8% until day 28, when the experiment was terminated. Again, serum osteocalcin was much lower (-32%, p less than 0.001) in the ELD-fed rats than in CLD-fed rats. Even in rats fed only a 6% ELD for 12 days, serum osteocalcin was lower (-33%, p less than 0.001) than in controls. Also, the femora were weaker, more compliant, and more ductile in ELD-than in CLD-fed rats, findings that confirmed our earlier, related work. The fall in serum osteocalcin in ELD-fed rats is associated with a fall in femur ash weight and bone strength. There were significant correlations between serum osteocalcin and bone strength (r = 0.80; p less than 0.001) and between serum osteocalcin and bone stiffness (r = 0.83; p less than 0.001). Serum ionized calcium, like osteocalcin, was consistently lower in rats given ethanol for 1 or 4 weeks than in controls. From these experiments we conclude that excessive ethanol consumption inhibits osteoblastic activity as indicated by the reduced serum osteocalcin. The inhibition is also associated with other deleterious effects of ethanol on bone, including ash weight, bone strength, and bone stiffness.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Isolation and complete amino acid sequence of osteocalcin from canine bone.

Osteocalcin was purified in high yield and to homogeneity from the diaphysis of dog femora by the following steps: (1) acid demineralization of bone powder, (2) solid-phase extraction of acid-soluble proteins on Sep-Pak C18 cartridges, (3) gel filtration on Sephadex G-50, and (4) fast protein liquid chromatography on an Accell-QMA anion-exchange column. Starting from 30 g washed bone powder, approximately 7-10 mg pure protein was obtained in 2 days. The key step is the initial solid-phase extraction of osteocalcin from a large volume of a demineralized bone solution. The primary structure was established by automated sequence analyses of two tryptic peptides, of two endoproteinase Glu-C carboxy-terminal peptides, and of the first 30 amino acid residues of the intact protein. Dog osteocalcin contains 49 amino acids, has a molecular mass of 5654 daltons, contains no Thr, Met, Hyp, or Trp, has a disulfide bond between Cys 23 and 29, and is fully gamma-carboxylated at residues 17, 21, and 24. Dog osteocalcin does not contain a pair of basic amino acids found at positions 43-44 in most other osteocalcins from mammals and birds. A computer search for homology indicated 88, 90, 84, 88, 66, and 57% sequence identity of dog osteocalcin with human, bovine, cat, monkey, chicken, and swordfish osteocalcin, respectively, and weaker homologies with the gamma-carboxylated domains of blood-clotting proteins and the Pro-rich N-terminal extensions of myosin light-chain A1 and beta-crystalline B1. The possible relevance of these homologies to the structure and potential functions of osteocalcin is discussed.

Amino Acid Sequence↗

PubMed1994

Two-site enzyme immunoassay for measuring intact human osteocalcin in serum.

We developed a sensitive two-site sandwich ELISA for quantitative analysis of human osteocalcin in serum or plasma. Our method is based on two different highly specific antibodies recognizing epitopes at different ends of the protein so that only intact osteocalcin is detected. The method is fast (total analysis time less than 6 h/96 wells), precise (intraassay variation less than 2.3% at four different levels; n = 10, and interassay variation less than 2.5%, n = 5, respectively), and accurate, with a mean recovery of 105%. The detection limit in serum is approximately 0.1 micrograms/liter. The mean concentration of osteocalcin in normal serum with this assay is 3.3 micrograms/liter (SD 3.7 micrograms/liter; range 0.1-13.1 micrograms/liter; n = 41), and the reference range is 0.28-10.1 micrograms/liter (10 and 90% confidence limits). The method shows a reasonable positive linear correlation with other osteocalcin assays (Incstar, r = 0.55, p < 0.05, n = 13; Henning Oscatest, r = 0.52, p < 0.005, n = 34). A good correlation (r = 0.70, p < 0.001) between individual osteocalcin and bone-specific alkaline phosphatase serum concentrations was observed in normal subjects. We found a low or undetectable concentration of intact osteocalcin in serum of all four of our patients with acute primary hyperparathyroidism, and in all five patients with hypocalcemic secondary hyperparathyroidism, which suggests that PTH effectively inhibited the synthesis of osteocalcin in osteoblasts. The serum concentration of intact osteocalcin was elevated in two of three patients with chronic primary hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2003

9-cis retinoic acid accelerates calcitriol-induced osteocalcin production and promotes degradation of both vitamin D receptor and retinoid X receptor in human osteoblastic cells.

Abstract vitamin D receptor (VDR) and retinoid X receptor (RXR) heterodimerize to mediate the genomic actions of 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3), calcitriol), the biologically active form of vitamin D(3). In this study, we show that 9-cis retinoic acid (9-cisRA), the ligand for RXR, accelerates calcitriol-induced expression of osteocalcin gene, the marker for mature osteoblasts. Calcitriol and its synthetic analog KH1060 (1 nM) induced osteocalcin secretion after a 96-h incubation period as detected by radioimmunoassay. When these compounds were used together with 9-cisRA, osteocalcin protein secretion was, however, detected already after 72 and 48 h, respectively. Detection of osteocalcin mRNA with quantitative PCR revealed elevated mRNA levels already after a 4-h treatment of the cells with calcitriol, KH1060, or 9-cisRA compared with untreated cells. In combination treatments, 9-cisRA rapidly stimulated osteocalcin mRNA synthesis induced by the different vitamin D(3) compounds. In MG-63 cells treated with calcitriol or KH1060, the stimulation was maximal after the first 4 h and diminished thereafter. In fact, after the 48-h incubation 9-cisRA reduced osteocalcin mRNA levels in KH1060-treated cells, the amount of mRNA being only 44% of the levels obtained with KH1060 alone. The reduction was accompanied by an increased degradation rate of both VDR and RXRbeta in the presence of 9-cisRA. Furthermore, 9-cisRA increased the formation of RXRbeta-VDR-VDRE complex on the osteocalcin gene VDRE. These results suggest that 9-cisRA accelerates calcitriol-induced osteocalcin production in human osteoblastic cells through increased formation of transcriptionally active chromatin complexes and, subsequently, promotes degradation of the heterodimeric complex of VDR and RXR.

Alitretinoin↗

PubMed2000

Species-divergent regulation of human and mouse osteocalcin genes by calciotropic hormones.

Although osteocalcin is the most abundant noncollagenous protein in bone, its role remains undefined. Recent studies have reported diametrically opposing responses in the vitamin D regulation of the mouse vs the human and rat osteocalcin genes. The aim of this study was to increase the understanding of these differences and further elucidate the physiological function and regulation of osteocalcin. Direct comparison of the regulation of both the endogenous mouse osteocalcin gene (mOC) and a human osteocalcin promoter-chloramphenicol acetyl transferase (hOC-CAT) reporter as integrated templates was undertaken in primary osteoblastic cultures from OSCAT transgenic mice. Expression of both genes was up-regulated with the onset of mineralization. Long-term chronic 1, 25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) treatment and acute (2 day) PTH treatment inhibited both mOC and hOC-CAT expression. At all stages of osteoblastic development studied, hOC-CAT was up-regulated by acute 1,25-(OH)(2)D(3), whereas mOC was unaffected or inhibited. Mouse osteopontin was strongly up-regulated by acute 1, 25-(OH)(2)D(3) treatment. Thus, the divergence of the osteocalcin responses to 1,25-(OH)(2)D(3) is specific for the osteocalcin gene and for an acute 1,25-(OH)(2)D(3) treatment regime. Elucidation of this unique aspect of bone physiology will provide valuable insights into the still incompletely understood roles of osteocalcin and 1, 25-(OH)(2)D(3) in bone.

Animals↗

PubMed1995

Increasing serum osteocalcin after glycemic control in diabetic men.

The pathogenesis of diabetic osteopenia is unclear. The markers of bone metabolism may show some changes in diabetic patients. In this study, we investigated the effect of glycemic control on serum osteocalcin level and urinary hydroxyproline excretion and the relations of these markers to duration of diabetes, C-peptide status, and body mass index. Twenty-seven men with poorly controlled diabetes mellitus (DM) (HbA1 > 9%, fasting plasma glucose > 7.8 mmol/liter) between ages 25 and 60 years (means +/- SD 46.6 +/- 10.4) were included in the study. Duration of diabetes was 5.8 +/- 4.7 years, body mass index (BMI) was 25 +/- 3.5 kg/m2, and fasting C-peptide was 2.33 (1.05-3.21) micrograms/liter. None of the patients had a disease or were treated with drugs that would interfere with calcium or phosphate metabolism and/or bone structure. They were free from chronic diabetic complications. Of these patients, 11 were lost to follow-up before metabolic control was achieved. The remaining 16 patients obtained good glycemic control (HbA1 < 8.3%, fasting plasma glucose < 7.8 mmol/liter) and completed the study. Serum osteocalcin level and urinary hydroxyproline excretion were determined before and after glycemic control. Urinary hydroxyproline excretion was not significantly changed by glycemic control [17.8 (7.1-23.2) versus 18.1 (10.9-28.1) mg/m2 day, P > 0.05]. However, serum osteocalcin level was significantly elevated (5.04 +/- 1.43 versus 4.17 +/- 1.83 micrograms/liter, P = 0.04). We found no correlation among fasting plasma glucose, HbA1, and fasting serum C-peptide levels with urinary hydroxyproline excretion. There was also no correlation between serum osteocalcin and fasting plasma glucose or serum C-peptide, but HbA1 was negatively correlated with serum osteocalcin (P = 0.01). No correlation was found between DM duration and BMI in the patients with serum osteocalcin level and urinary hydroxyproline excretion. To eliminate the possible effect of exogenous insulin on bone metabolism, the correlation analysis between the markers and C-peptide was further repeated in oral agents-treated patients. Serum C-peptide was not correlated to serum osteocalcin or urinary hydroxyproline in this subgroup of patients. Knowing that serum osteocalcin is a marker of bone formation, we concluded that osteoblast function may improve by glycemic control in diabetic patients; this may be due to correction of metabolic abnormalities associated with insulinopenia.

Adult↗

PubMed1986

Evaluation of serum osteocalcin as an index of altered bone metabolism.

Recent evidence suggests that the protein osteocalcin is like the bone alkaline phosphatase produced by osteoblasts and circulates in human blood. With the introduction of a radioimmunoassay for serum osteocalcin it was hoped that this test would provide a useful index of altered bone metabolism. Therefore serum osteocalcin was measured in 88 controls and 112 patients with disorders of calcium and phosphate metabolism, isolated elevation of alkaline serum phosphatase in the absence of disease (isolated hyperphosphatasaemia) and children prone to osteopenia. In the controls serum osteocalcin was higher in children less than 15 years (median and range: 11.9, 7.7-15.3 ng/ml) than in adults (3.7, 2.6-5.2 ng/ml) and was highly correlated to alkaline serum phosphatase activity (r = 0.87, n = 88, P less than 0.01). Osteocalcin was elevated in primary hypoparathyroidism, low in untreated hypoparathyroidism but normal in hypoparathyroidism (including pseudohypoparathyroidism) during vitamin D treatment. The bone protein was low-normal and increased to high-normal levels during vitamin D therapy in vitamin D deficiency rickets and familial hypophosphataemic rickets, but remained low in patients with end organ resistance to 1,25-dihydroxyvitamin D. Osteocalcin (and urinary hydroxyproline) were not elevated in isolated hyperphosphatasaemia, indicating that mechanisms other than increased bone turnover may account for the markedly elevated serum alkaline phosphatase activity in these subjects. Osteocalcin was decreased in children with diabetes mellitus type I and in patients on glucocorticoid treatment, indicating decreased bone formation. It is concluded that the measurement of serum osteocalcin seems to be a reliable index of bone formation provided that the vitamin D status and renal function are normal.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Carboxyglutamic Acid↗

PubMed1990

Influence of sex, age, and menopause in serum osteocalcin (BGP) levels.

Osteocalcin (bone Gla protein) is a promising marker of bone turnover useful in the diagnosis and follow-up of high turnover osteoporosis. Conflicting results have been reported about its physiological variations according to sex, age, and menopause. Several, but not all, authors have found increased levels in males, with aging, and after menopause. We measured serum osteocalcin in 126 healthy subjects, 57 males and 69 females, aged between 45 and 88 years. Osteocalcin was higher (P less than 0.01) in males (6.24 +/- 0.36) than in females (4.32 +/- 0.34). This sexual difference was significant, too, in subjects younger and older than 60 years. Osteocalcin increased with age, linearly in males (P less than 0.05), and exponentially in females (P less than 0.05). Although there was a difference in age (P less than 0.05), no difference in osteocalcin levels between premenopausal women and women in their first two postmenopausal years was detected, while osteocalcin was significantly increased in women more than two years into menopause. We conclude that osteocalcin in healthy subjects is higher in males than in females and increases with age after 45 years in both sexes. Osteocalcin levels increase in women more than two years beyond menopause, but not only as an effect on aging.

Age Factors↗

PubMed1991

Normal bone particles are preferentially resorbed in the presence of osteocalcin-deficient bone particles in vivo.

In an in vivo model of osteoclastic bone resorption, we previously showed that osteocalcin-deficient bone particles (BPs), derived from warfarin-treated rats, were resorbed 50% as well as normal BPs and that they recruited fewer osteoclastic cells with decreased tartrate-resistant acid phosphatase (TRAP) activity. In order to determine the specificity of the resorption response, we evaluated the fate of implanted mixtures of normal and osteocalcin-deficient BPs. Normal and warfarin-treated donor rats were prelabeled in vivo with oxytetracycline to permit identification of BPs from either source. Normal, osteocalcin-deficient, and 50:50 mixtures of BPs (either labeled or unlabeled) were implanted into normal rats and recovered 12 days later for enzymatic (TRAP) and nondecalcified histomorphometric analyses. The incorporated oxytetracycline had no significant effect on resorption of bone particles. The recovered osteocalcin-deficient BPs were surrounded by fewer osteoclastic cells, were resorbed less, and contained less extractable TRAP activity than normal BPs. In mixed BP implants with normal and osteocalcin-deficient BPs, each type of bone particle elicited the same tissue response as when implanted separately. Remarkably, the different particles evoked dissimilar osteoclastic responses and were resorbed to different extents, even when adjacent within the same implant. These data suggest that osteocalcin may act as a substrate signal for resorption and that osteocalcin in the normal BPs does not influence the cellular response to adjacent osteocalcin-deficient BPs.

Acid Phosphatase↗

PubMed1985

The effect of osteocalcin on in vitro lipid-induced hydroxyapatite formation and seeded hydroxyapatite growth.

Osteocalcin, the bone gamma-carboxy glutamic acid containing protein, is one of the major noncollagenous proteins both synthesized and localized in bony tissue. Previously, investigators have suggested, based on the in vitro and in vivo properties of this protein, that it may be involved in controlling initiation of mineralization and/or hydroxyapatite (HA) growth. In this study, the in vitro effects of osteocalcin on lipid-induced HA formation, and HA seeded growth were compared. Although osteocalcin inhibited the growth of HA, as indicated by the osteocalcin concentration-dependent decreases in the first order rate constant, kCa, osteocalcin had no effect on lipid-induced calcification, kCa remaining constant at .033 h-1. Binding studies revealed that osteocalcin did not associate with the lipid macromolecules tested (phosphatidyl serine, phosphatidyl inositol, and the Ca-acidic phospholipid-phosphate (Ca-PL-PO4) complexes prepared from these phospholipids) although the protein bound to HA with high affinity. These data suggest that a) osteocalcin is quite distinct from the gamma carboxy glutamic acid containing clotting proteins which have a high affinity for both the acidic phospholipids and for HA, and b) that osteocalcin has little effect on the initial Ca-PL-PO4-dependent formation of HA.

Calcium-Binding Proteins↗

PubMed1991

Effects of estrogen and tamoxifen on serum osteocalcin levels in ovariectomized rats.

Serum osteocalcin levels were measured in ovariectomized rats treated for 35 days with either estrogens (ethynylestradiol administered orally or 17 beta-estradiol administered by subcutaneous injection) or the antiestrogenic compound tamoxifen (administered both orally and subcutaneously). Tamoxifen is a non-steroidal compound that has mixed agonist/antagonist actions in several biological models, but is commonly referred to as an 'antiestrogen'. Administration of tamoxifen, like estrogen, caused a reduction in the increases in animal body weight and femur length during the test period, and greater bone density in the distal femur metaphysis compared to ovariectomized control animals. Both the estrogens and tamoxifen caused a dose-dependent decrease in serum osteocalcin as compared to the levels in the serum of ovariectomized control rats; however, tamoxifen displayed both reduced potency and efficacy compared to estrogens. Serum osteocalcin levels declined in a linear fashion throughout the estrogen dose range, and at the highest doses tested (400 micrograms/kg/d ethynylestradiol; 100 micrograms/kg/d 17 beta-estradiol), osteocalcin levels were reduced by 45-50% compared to those found in ovariectomized control animals. The reduction in serum osteocalcin concentrations in tamoxifen-treated animals, on the other hand, was reduced maximally by about 30% compared to those found in the ovariectomized controls at a dose of 100 micrograms/kg/d. Further reduction in serum osteocalcin beyond this level was not observed with increasing doses of tamoxifen. We conclude that tamoxifen acts as an estrogen agonist with respect to effects on serum osteocalcin levels, but fails to reduce serum levels of osteocalcin to the extent observed with steroidal estrogens.

Animals↗

PubMed1990

Comparative effects of a novel vitamin D analogue MC-903 and 1,25-dihydroxyvitamin D3 on alkaline phosphatase activity, osteocalcin and DNA synthesis by human osteoblastic cells in culture.

MC-903 is a novel vitamin D analogue which has been shown to promote epidermal cell differentiation but is 100 times less active than 1,25 dihydroxyvitamin D3 (1,25(OH)2D) in causing hypercalcemia. In order to determine the activity of this compound on bone cells, we have compared the effects of MC-903 and 1,25 dihydroxyvitamin D3 (1,25(OH)2D) on parameters of cell proliferation and differentiation in cultured normal human osteoblastic cells derived by migration from trabecular bone fragments. Dose response curves showed that MC-903 was 10 to 100 times less effective than 1,25(OH)2D in stimulating the synthesis of the osteoblast specific protein osteocalcin by human bone cells depending on the basal osteocalcin production. In cells showing high basal osteocalcin synthesis, 1,25(OH)2D (10(-8) M) was 2- to 3-fold more potent than MC-903 (10(-8) M) in inducing osteocalcin from 48 to 96 h of treatment. The greater activity of 1,25(OH)2D over MC-903 was observed in human bone cell cultures with elevated basal osteocalcin levels, indicating that the response to 1,25(OH)2D but not to MC-903 was amplified in cells with the higher osteoblastic characteristics. The effects of MC-903 and 1,25(OH)2D on alkaline phosphatase activity were not markedly different. Transforming Growth Factor-beta (TGF beta) (0.5 ng/mL, 48 h) was found to completely suppress the osteocalcin synthesis induced by 1,25(OH)2D (10(-8) and 10(-9) M), whereas the MC-903-induced osteocalcin synthesis was not affected, suggesting a negative interaction between TGF beta and 1,25(OH)2D but not MC-903 on osteocalcin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

PubMed1990

Serum osteocalcin concentrations in children with chronic renal insufficiency who are not undergoing dialysis. Growth Failure in Children with Renal Diseases Study.

This report describes the serum osteocalcin values in children with mild to moderate, but relatively stable, renal dysfunction followed in the Growth Failure in Children With Renal Diseases Study. This report is derived from data obtained during the control period (6 months) before the initiation of vitamin D therapy. Up to three measurements per patient were obtained. Serum osteocalcin concentration was compared with creatinine clearance (glomerular filtration rate) calculated by the Schwartz formula; with serum concentrations of alkaline phosphatase, parathyroid hormone, and bicarbonate; and with the percentages of the recommended dietary allowances of calories and protein ingested. By standard correlation techniques, there appeared to be an inverse correlation between calculated creatinine clearance and serum osteocalcin concentration, and a direct correlation between serum osteocalcin and parathyroid hormone values. However, when we employed a statistical technique that takes into account repeated measures in the same patient, no correlation was found between calculated glomerular filtration rate and serum osteocalcin concentration, and no direct correlation was found between serum osteocalcin and parathyroid hormone values. The lack of a correlation between calculated glomerular filtration rate and serum osteocalcin values may be due to large fluctuations in the serum osteocalcin concentration, even though renal function is relatively stable.

Alkaline Phosphatase↗

PubMed1993

Stress decreases the serum level of osteocalcin.

During a study undertaken to characterize the time course of the osteocalcin response to bone fractures, lower than normal values of serum osteocalcin (1.7 +/- 0.9 vs. 3.3 +/- 1.3 ng/ml, P < 0.001) were found in the basal samples (blood obtained 48-72 h after fracturing). Suspecting that such a decrease could be due to the stress response induced by the fracture, for corticosteroids are known to diminish serum osteocalcin, we extended our study to another two stressful situations of high stress: acute myocardial infarction and elective abdominal surgery. Indeed, the concentration of osteocalcin was also significantly diminished in both of these (2.0 +/- 0.9 ng/ml, P < 0.0005; 1.5 +/- 1.0 ng/ml, P < 0.0001). To further characterize this phenomenon, the time course of osteocalcin changes during the 24 h following abdominal surgery was studied in a second group of patients. The decrease was found to begin soon after surgery. In order to exclude the immobilization present in those three situations as the cause of the decrease in serum osteocalcin, a group of patients with retinal detachment was studied. Their serum osteocalcin levels were normal. It is concluded that serum osteocalcin levels decrease in stressful situations. Therefore, they should be interpreted cautiously when used as a marker of osteoblastic activity in this setting.

Abdomen↗

PubMed2001

Changes in osteocalcin response to 1,25-dihydroxyvitamin D(3) stimulation and basal vitamin D receptor expression in human osteoblastic cells according to donor age and skeletal origin.

Age-related osteopenia is known to occur differently throughout the skeleton. In the present study, we examine the influence of donor age (<50 and >50 years), and bone structure (cortical vs. trabecular) on osteocalcin and vitamin D receptor (VDR) expression in primary cultures of human osteoblastic cells (hOB) cells. Cells were isolated from trabecular bone samples obtained from donors undergoing either knee (mainly trabecular) (n = 22; 4 <50 years, 18 >50 years) or hip (mainly cortical) (n = 16; 6 <50 years, 10 >50 years) arthroplasty. Pooling the results from knee and hip hOB cell cultures, we found that secreted osteocalcin was higher in hOB cells from the younger donors, compared with that in older donors, and peaked after stimulation with 10(-6)--10(-8) mol/L 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. In cells from the latter donors, this secretion was maximal after 10(-6) mol/L 1,25(OH)(2)D(3) treatment. On the other hand, using reverse transcription followed by polymerase chain reaction, baseline osteocalcin mRNA was found to be lower in hOB cells from the older donors than in those from younger donors. After treatment with 10(-6)--10(-8) mol/L 1,25(OH)(2)D(3), osteocalcin mRNA increased over baseline in all groups of hOB cells studied. In age-matched cultures, both basal and 10(-6)--10(-8) mol/L 1,25(OH)(2)D(3)-stimulated osteocalcin mRNA showed similar values in hOB cells from both skeletal sites in younger donors. However, in the older donors, baseline as well as 10(-8) mol/L 1,25(OH)(2)D(3)-stimulated osteocalcin mRNA were higher in knee hOB cells than in hip hOB cells. Furthermore, baseline VDR mRNA expression was also higher in the former cells than in the latter cells in the older group. Considering the influence of donor age at each skeletal site of origin, we found lower baseline osteocalcin and VDR mRNA levels in hip hOB cells in the older group than in the younger group. Our findings indicate that the response of osteocalcin secretion and its mRNA to physiological doses of 1,25(OH)(2)D(3) decreases with aging and is associated with decreased VDR mRNA expression in hOB cells from mainly cortical bone.

Adult↗