Serum OC Research Articles

Biochemical markers of bone metabolism after short and long time ethanol withdrawal in alcoholics.

The etiology of ethanol-associated osteopenia is not fully understood. A direct inhibitory effect of ethanol on osteoblast function has been suggested by in vitro and in vivo studies. In this study, we measured biochemical markers for bone formation (osteocalcin, bone specific alkaline phosphatase, procollagen-1-c-terminal peptide) and resorption (c-terminal telopeptide and urine deoxypyridinoline) in 18 otherwise healthy, but severely alcoholic men during a 10-day period of alcohol withdrawal. The same tests were performed in a group of 18 male abstainers, with more than 5 years of proven alcohol withdrawal. The results were compared with 29 male controls, randomly selected. In the group of alcoholics, osteocalcin (Oc) was significantly decreased at day 1 (p > 0.001; compared with controls). The low serum Oc levels normalized during the observation period and no significant difference was seen after 10 days. After a 5-year withdrawal, the bone-specific alkaline phosphatase was increased (p = 0.040) and there was a tendency, but not significant, of a persistent high level of Oc when compared with controls. A significant increase in fasting urinary secretion of deoxypyrodinoline was seen among the alcoholics (p = 0.001 compared with controls). The increase did not normalize during the 10-day observation period. Also, the abstainers had a significantly higher fasting urinary secretion of deoxypyridinoline after a 5-year alcohol withdrawal (p = 0.022 compared with controls). The present study suggests that there is an imbalance between bone formation and bone resorption among alcoholics that could result in rapid bone loss. Although most directions tended to normalize shortly after alcohol withdrawal, biochemical data suggest that there may still be a persistent high bone turnover after more than 5 years.

Bone mineral density and parameters of bone metabolism in patients with acromegaly.

To assess the effect of chronically elevated plasma growth hormone (GH) levels on bone metabolism and bone mineral density (BMD), 16 patients (10 females and 6 males) with a mean age of 49.1 +/- 13.2 years (range 33-68) with active acromegaly were studied and compared to a control group of 16 sex- and age-matched subjects. BMD of the lumbar spine and two different sites of the proximal femur were measured by dual-energy x-ray absorptiometry (Norland XR-26). In the acromegalic patients the mean plasma GH concentration was 30.1 +/- 11.1 micrograms/liter, and the mean plasma somatomedin C (SMC) concentration was 6.5 +/- 1.5 U/liter. Mean serum osteocalcin (OC) levels (14.3 +/- 1.1 versus 7.2 +/- 0.4 ng/ml, p < 0.001) as well as the urinary hydroxyproline excretion (OHP; 8.8 +/- 1.4 versus 2.7 +/- 0.3 mg, p < 0.0001) were significantly higher in the acromegalic patients than in the control subjects. In the acromegalic patients BMD was significantly elevated in the two examined regions of the proximal femur, that is, the femoral neck (1.06 +/- 0.05 versus 0.86 +/- 0.03 g/cm2, p < 0.05) and Ward's triangle (0.92 +/- 0.06 versus 0.76 +/- 0.03 g/cm2, p < 0.02), whereas the BMD of the lumbar spine was not significantly different from that of control subjects. Among the patients with acromegaly a significant positive correlation between serum OC concentrations, on the one hand, and urinary OHP excretion (r = 0.7, p < 0.004) as well as BMD in the proximal femur (r = 0.64, p < 0.007), on the other hand, could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone metabolism in rheumatoid arthritis; relation to disease activity.

Biochemical parameters of bone metabolism were investigated in 105 ambulant, non-steroid treated patients with RA and compared with parameters of disease activity. Urinary calcium (Ca) and hydroxyproline (OHP) excretions, as parameters of bone resorption and serum alkaline phosphatase (AP), as a parameter of bone formation, were positively related to parameters of disease activity. Serum osteocalcin, another parameter of bone formation, was not related to parameters of disease activity. Patients with active disease (ESR > or = 28 mm and Ritchie articular index > or = 8) had a significant higher urinary Ca and OHP excretion (62 and 42% higher, respectively) than patients with inactive disease. Serum AP and OC were slightly higher (19 and 16%, respectively) in patients with active disease. These results suggest that in RA patients bone metabolism is related to disease activity. In active disease bone resorption seems to be increased more than bone formation, suggesting that prolonged disease activity may contribute to generalized and/or localized osteopenia.

Changes in Biochemical Markers of Osteoblastic Activity during the Menstrual Cycle*

Serum levels of osteocalcin [OC; bone Gla protein (BGP)] and bone alkaline phosphatase (B-AP) are both correlated to osteoblastic activity, which may be regulated by several hormones, including estrogen, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and PTH. Estrogen shows reproducible variations during the menstrual cycle, while available data on variations in serum 1,25-(OH)2D3 and serum immunoreactive PTH show midcyclic increases or no changes. In the present study we evaluated osteoblastic activity by measuring serum OC and B-AP during the menstrual cycle in eight healthy women, aged 20-47 yr. The cycles were synchronized by LH peaks, and follicular and luteal periods were normalized by lengths. Repeated measures analysis of variance showed that serum OC varied significantly (P less than 0.05), with highest levels during the luteal period. Although the same pattern was seen for serum B-AP, the variation just failed to reach significance (P less than 0.10), but the mean level was significantly higher during the luteal than during the follicular period (P less than 0.05). Gonadotropins and ovarian sex hormones showed significant variations. There were no significant changes in serum vitamin D-binding protein, serum total and free 1,25-(OH)2D3 index, or serum immunoreactive PTH-(1-84), but serum levels of somatomedin-C showed a significant variation, with the highest level during the luteal period (P less than 0.05). Blood levels and urinary excretion of minerals exhibited no significant variations. Cross-correlation studies between OC and estradiol showed the highest correlation coefficient, when OC was lagged about 7 days after estradiol (r = 0.69; P less than 0.05). Moreover, a high correlation was found between OC and somatomedin-C when matched at concurrent time points (r = 0.76; P less than 0.01). No significant correlations were found between the other calcium-regulating hormones and OC when matched at concurrent time points. In conclusion, we found a significant effect of the menstrual cycle on the serum levels of two osteoblastic bone markers, OC and B-AP. The changes indicated that osteoblastic activity is higher during the luteal period. However, whether the changes are caused by direct or indirect effects of the fluctuations in calciotropic hormones is still unresolved.

The circadian rhythm of serum osteocalcin concentrations: Effects of 1,25 dihydroxyvitamin D administration

The effects of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) administration on serum osteocalcin (Oc) concentrations were determined. 2.0 micrograms doses of 1,25(OH)2D3 were administered orally and intravenously to four healthy adult males. Blood was sampled hourly for 24 hours on four occasions: once prior to the two treatment days (i.v. and p.o.), on each of the treatment days, and during a second nontreatment day 2 years later. Mean circadian Oc rhythms of the four subjects on each study day were compared with each other and with a previously derived mathematical representation of the normative Oc rhythm, the circadian Oc rhythm model. We found overall conservation of the mean Oc pattern across time and 1,25(OH)2D3 treatment. However, 1,25(OH)2D3 administration resulted in a rapid rise (within 6 hours) in Oc concentrations that blunted or eliminated the morning fall in Oc levels. The increased Oc levels were sustained for the remainder of the 24 hour period though pattern shapes converged with those of the nontreatment days and the model. We conclude that serum Oc levels are rapidly responsive to near physiological doses of 1,25(OH)2D3 in healthy adult males and that the effects are maintained for at least 24 hours.

EVALUATION OF SERUM OSTEOCALCIN (OC) AS AN INDEX OF ALTERED BONE METABOLISM IN CHILDREN AND ADULTS

Recent evidence suggests that OC is like the bone alkaline phosphatase (AP) produced by osteoblasts and circulates in human blood. With the introduction of a RIA for serum OC by Price et al. (J Clin Invest 66:878,1980) it was hoped that this test would provide a sensitive index of altered bone metabolism. We therefore measured serum OC in 88 controls and 112 patients with (1) disorders of Ca metabolism (2)isolated hyperphosphatasemia in the absence of disease (IH)and (3) children prone to osteopenia. Results: Controls:OC was higher in children <15 yr (x±2 SD: 8.2-14.8 ng/ml) than adults (2.5-5.5 ng/ml) and correlated with serum AP (r = 0.87, n = 88, p < 0.01). Patients: (1) OC was high in primary hyperparathyroidism, low in untreated hypoparathyroidism (HP) but normal in HP on vit. D. OC was low-normal in rickets and increased during vit. D therapy except in patients with end organ resistance to 1,25-(OH)2D3. (2) OC (and urinary hydroxproline) were not elevated in IH, indicating that other mechanisms than increased bone turnover may account for the markedly elevation of serum AP in these subjects. (3) OC was decreased in children with diabetes mellitus type I and in patients on glucocorticoid treatment, indicating decreased bone formation. Conclusion: Serum OC (1) seems to be dependent on the circulating 1,25-(OH)2 D levels and normal action of the vit. D hormone, (2) may be of value in the differential diagnosis of unexplained AP elevation, (3) appears to be a sensitive index of bone formation.

24-HOUR VARIATIONS IN SERUM OSTEOCALCIN (Oc) CONCENTRATIONS IN TEENAGE MALES

Oc (bone-gla protein), a calcium-binding protein found in bone, has been used as a marker for metabolic bone disease. Serum concentrations of Oc are known to peak during adolescence. Since blood ionized calcium concentrations (Ca++) undergo circadian rhythmicity in teenagers, we examined the possibility that time of sampling may be an important factor in interpreting Oc levels. 2 healthy adolescent males, aged 15 and 17, had blood sampled q 30' for 24 hours via an indwelling venous catheter. Blood Ca++ and serum Oc, total calcium (CaT) and phosphate (Pi) concentrations were determined.Marked variations in Oc concentrations were found in both subjects throughout the day. No significant correlations were found between Oc and mineral patterns. However, the intersubject correlation between 24-hour Oc concentrations was .46, p<.01. Conclusions: 1) Daily fluctuations in serum Oc concentration from individuals must be taken into account in interpreting the results from randomly obtained blood samples; 2) Correlation in Oc patterns between 2 subjects suggests the presence of circadian rhythmicity in serum Oc.