Serum Total Osteocalcin Research Articles

The effect of initiation of exercise training in young horses on vitamin K status.

Twelve Quarter Horses, 18 to 24 mo of age and having an average body weight of 460+/-12 kg, were randomly assigned to one of two exercise treatments (control and exercise) to study the effect of initiation of exercise training in young horses on vitamin K status. The control treatment consisted of hand-walking the horses 7 min/d and 5 d/wk for 180 d. Exercise consisted of the following treadmill exercise regimen: 2 min at 4.5 to 5.4 m/s, 3 min at 13.4 to 14.3 m/s, and 2 min at 4.5 to 5.4 m/s on 5 d/wk for 180 d. Both groups were allowed free access to brome grass hay (273 mg of phylloquinone/100 g) individually. Additionally, the exercise group was fed .45 kg of a grain-mix concentrate (40 mg of phylloquinone/100 g) on the days they were exercised. Jugular venous blood samples were collected at d 0, 30, 60, 90, 120, 150, and 180. Blood samples were analyzed for total serum osteocalcin and vitamin K status via the hydroxyapatite binding capacity of serum osteocalcin calculated as follows: Hydroxyapatite binding capacity of serum osteocalcin = [(total serum osteocalcin - serum osteocalcin following extraction of serum with hydroxyapatite)/total serum osteocalcin] x 100. All horses were killed with an overdose of sodium pentobarbital on d 180. Computed tomographic osteoabsorptiometry was used to measure relative bone density distribution on the surface of the distal radial carpal bone, proximal third carpal bone, and the distal third metacarpal condyle. Relative bone density distribution was measured in Hounsfield units and categorized as low-, medium-, and high-density bone corresponding to 800 to 1,199, 1,200 to 1,299, and 1,300 to 3,000 Hounsfield units, respectively. Carpal and metacarpophalangeal joints were assigned a score of 0 (normal) to 3 (severe) that reflected the presence and severity of joint lesions. Hydroxyapatite binding capacity of serum osteocalcin and serum osteocalcin were unchanged over the 180-d period in both groups. Exercised horses had a higher percentage of high density bone (P < .01) and a lower percentage of low density bone (P < .01) on the surface of the third metacarpal condyle and a higher cumulative gross lesion score (P < .01) in the metacarpophalangeal joint than controls. There were no differences between treatments in relative bone density distribution in the carpal bones, or cumulative gross lesion score of the carpal joints. No significant correlation was present between the serum measures, osteocalcin and hydroxyapatite binding capacity of serum osteocalcin, and the bone measures, relative bone density distribution and joint gross lesion score.

Biochemical markers can predict the response in bone mass during alendronate treatment in early postmenopausal women

Data from the Danish cohort (n = 67) of a multicenter trial of oral alendronate in the prevention of postmenopausal osteoporosis were used to evaluate the capacity of the biochemical markers to predict changes in bone mineral density (BMD). A panel of markers were measured: serum N-terminal midfragment osteocalcin (N-MID OC); serum total osteocalcin (total OC); bone-specific alkaline phosphatase (BSAP); serum and urine C-telopeptides of type I collagen (sCL and uCL); urine N-telopeptide crosslinks of type I collagen (NTX); and deoxypyridinoline (dPyr). The correlation between change from baseline at months 3–12 in total OC, N-MID OC, sCL, uCL, and NTX and 2 year response in spine BMD ranged from r = −0.45 to r = −0.78 (p < 0.001), and from r = −0.38 to r = 0.10 (n.s. to p < 0.002) for BSAP and dPyr. Sensitivity and specificity were used to assess the accuracy of change from baseline at month 6 in the biochemical markers for predicting prevention of bone loss in the spine over 2 years. The cutpoints used were a 30% (N-MID OC) or 50% (all other markers) decrease from baseline. Sensitivity levels were 82% (N-MID OC), 98% (total OC), 78% (sCL and NTX), and 89% (uCL). Specificities were 91% (N-MID OC), 59% (total OC), 100% (sCL), 71% (uCL), and 84% (NTX). Positive predictive values were 95% (N-MID OC), 82% (total OC), 100% (sCL), 87% (uCL), and 90% (NTX). In comparison, the predictive capacities of change from baseline at year 2 in hip BMD in predicting prevention of bone loss at the spine were similar: sensitivity, 82%; specificity, 55%; and positive predictive value, 79%. In conclusion, short-term changes in biochemical markers were valid predictors of long-term changes in BMD. Short-term changes in the sensitive biochemical markers revealed a predictive capacity similar to bone densitometry at the hip measured over 2 years. The sensitive biochemical markers offered a fast and valid alternative to bone densitometry for monitoring of alendronate treatment.

Evidence that increased calcium intake does not prevent early postmenopausal bone loss

Calcium's ability to prevent bone loss in early postmenopausal women is controversial. We used data on 394 women from the placebo group of the Early Postmenopausal Interventional Cohort study, a clinical trial of alendronate, to investigate the relation of calcium intake to bone loss. Calcium intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm, and hip) and biochemical markers of bone turnover (serum total alkaline phosphatase, serum osteocalcin, and urinary n-telopeptide crosslink levels) were measured at baseline and annually thereafter. Women whose baseline calcium intake was <500 mg/d were advised to increase their calcium intake. Mean (±SE) BMD decreased by 1.9% ± 0.16% at the lumbar spine and 1.6% ± 0.14% at the hip over the 24-month period. Despite wide variations in baseline calcium intake and changes in calcium intake, these measures were not significantly associated with changes in BMD or bone turnover. Even women whose total calcium intake was > 1333 mg/d (the highest tertile of total calcium intake) showed a decline in BMD of almost 2%, similar to declines in the lower two tertiles of total calcium intake (<869 and 869–1333 mg/d, respectively). Increased calcium intake resulted in modest mean increases of approximately 200 mg/d. We were unable to demonstrate that increases of this magnitude or much greater (1 g/d) were protective against declines in BMD at any site, even in women who had the lowest calcium intake at baseline. In addition to adequate calcium intake, more effective therapy appears to be required when the therapeutic goal is to increase or maintain BMD.

Characteristics of Biochemical Markers in Patients with Metabolic Bone Disorders.

Biochemical markers of bone turnover are expected to have some different characteristics among bone metabolic disorders. We compared bone formation markers: serum total alkaline phosphatase (s-Alp), serum osteocalcin (s-OC) and serum carboxy-terminal propeptide of type I collagen (s-PICP); and bone resoiption markers: serum carboxy-terminal telopeptide of type I collagen (s-ICTP), urinary pyridinoline (u-Pyr) and urinary deoxypyridinoline (u-Dpyr) to examine which marker is the most suitable and reliable to evaluate bone turnover in patients with osteoporosis (n = 29), osteomalacia (n = 10), primary hyperparathyroidism (n = 6) and renal osteodystrophy (n = 21). The value of s-Alp in the osteomalacia group was significantly higher than those in the normal control group and the osteoporosis group (p<0.001), and T-score of s-Alp was significantly higher than those of s-OC and s-PICP in the osteomalacia group. The values of u-Pyr and u-Dpyr in the primary hyperparathyroidism group were significantly higher than those in the other groups (p < 0.001). S-PICP, which are not dependent upon renal function, was much higher in the renal osteodystrophy group man in all other groups. In the osteoporosis group, T-score of s-ICTP was significantly higher than those of s-OC. Thus, s-Alp was a good marker in osteomalacia, u-Pyr and u-Dpyr in primary hyperparathyroidism, s-PICP in renal osteodystrophy, and s-ICTP in osteoporosis.

Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects

The response of osteocalcin and other biochemical markers of vitamin K status to diets formulated to contain different amounts of phylloquinone was assessed in nine healthy subjects aged 20-33 y. Subjects resided in a metabolic ward for two 15-d cycles with a minimum of 6 wk between cycles. A mixed diet containing 100 micrograms phylloquinone/d was fed throughout both cycles; however, the phylloquinone content of one of the cycles was increased to a total of 420 micrograms/d on days 6 through 10 by fortifying corn oil in the diet with phylloquinone (supplemented diet). Total serum osteocalcin concentrations were not affected by either of the dietary treatments. The percentage of undercarboxylated osteocalcin increased an average of 28% over the 15-d cycle with the mixed diet (P < 0.05) and declined significantly an average of 41% with 5 d of the supplemented diet (day 6: 21.9 +/- 1.3%, day 11: 12.8 +/- 1.1%; P = 0.0001) with a rise after the return to the mixed diet (16.7 +/- 1.3%, P < 0.001). Plasma phylloquinone concentrations increased significantly with supplementation (day 6: 0.95 +/- 0.16 nmol/L, day 11: 1.40 +/- 0.29 nmol/L; P < 0.001) and then rapidly returned to presupplementation concentrations on returning to the mixed diet. Twenty-four-hour ratios of urinary gamma-carboxyglutamic acid to creatinine were unchanged with the supplemented diet; however, excretion declined to 91 +/- 2% of baseline after 10 d on the mixed diet (P = 0.01). These results show that undercarboxylated osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid excretion appear to be sensitive measures of vitamin K nutritional status because all of these variables were responsive to changes in dietary intake.

Relationship between serum &lt;italic&gt;β&lt;/italic&gt;&lt;sub&gt;2&lt;/sub&gt;-microglobulin bone histology, and dialysis membranes in uraemic patients

beta 2-Microglobulin (beta 2M) is the main constituent of osteoarticular amyloid deposits in haemodialysis patients. When dialysed with cellulosic (C) membrane such patients present a higher incidence of beta 2M-related amyloid arthropathy than with synthetic high-flux (SHF) membrane, and they have higher serum levels of beta 2M. This could favour beta 2M deposition as amyloid fibrils and/or modify bone and cartilage metabolism. We examined 56 uraemic patients dialysed in the same centre for 7.5 +/- 4.8 years (mean +/- SD). Based on bone histomorphometry criteria they were classified into either high-turnover bone disease (HTBD, 45 patients) or normal/low-turnover bone disease (N/LTBD, 11 patients). A subgroup of 30 patients had been dialysed with the same dialysis membrane for at least 18 months prior to study, 8 on C and 22 on SHF membrane. Serum intact parathyroid hormone levels were not different between the two patient subgroups. In contrast, serum beta 2M levels were higher in patients on C than on SHF membrane: 59.8 +/- 14.1 versus 32.8 +/- 8.7 mg/l, and so were serum total alkaline phosphatase and osteocalcin levels: 323 +/- 167 versus 173 +/- 50 IU/l, and 656 +/- 395 versus 288 +/- 263 ng/ml respectively. The increase of these serum markers of bone formation was associated with a higher bone cell number: osteoblast surface, 21.7 +/- 5.1 versus 9.8 +/- 11%; osteoclast surface, 4.27 +/- 1.86 versus 1.96 +/- 1.34%; and osteoclast number/mm2, 2.85 +/- 1.26 versus 1.27 +/- 0.88 respectively. Serum beta 2M was positively correlated with serum osteocalcin (r = 0.58, P < 0.001), bone-specific alkaline phosphatase (bAP) (r = 0.46, P < 0.008), and free pyridinoline (PYD) (r = 0.62, P < 0.002), and negatively correlated, only for HTBD, with osteoid volume: r = -0.40, P < 0.006. Serum beta 2M was higher in patients with HTBD than N/LTBD: The bone metabolism of chronic haemodialysis patients may be influenced by dialysis membrane biocompatibility. Moreover, the association of high serum beta 2M with increased bone cell number and serum markers of bone turnover suggests that beta 2M is either another marker of bone cell activity or an activator of bone cells.

Carefully monitored levothyroxine suppressive therapy is not associated with bone loss in premenopausal women.

We measured total body and regional (lumbar spine, femoral neck, Ward's triangle, and trochanter) bone mineral density (BMD) in 47 premenopausal women chronically treated with suppressive doses of levothyroxine (L-T4). Treatment was administered to 7 patients with nontoxic goiter or, after thyroidectomy, to 38 patients with differentiated thyroid cancer and 2 with nontoxic goiter. Patients were followed at our institution and treated with the minimal amount of L-T4 necessary to suppress TSH. At the time of evaluation, free T3 was normal in all cases, whereas free T4 was increased in 17 (36.2%). The mean daily dose of L-T4 was 154.3 +/- 5 micrograms, and the mean duration of treatment was 10.1 yr. We found no significant difference between patients and age- and weight-matched controls in BMD at any site of measurement. BMD was not correlated with duration of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free T3, and osteocalcin. There was no difference between patients and controls in serum total calcium, intact PTH, osteocalcin, or carboxy-terminal cross-linked telopeptide of type I collagen or in the concentrations of two markers of thyroid hormone action (sex hormone-binding globulin and amino-terminal propeptide of type III procollagen). Our data suggest that L-T4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion has no significant effect on bone metabolism or bone mass.

Suppression by calcium of serum levels of intact parathyroid hormone in patients with primary hyperparathyroidism.

Primary hyperparathyroidism (pHPT) is associated with a right-shifted relation between parathyroid hormone (PTH) secretion and calcium. However, it is also possible that a decreased suppressibility of PTH secretion by calcium is important for maintaining hypercalcemia in pHPT. We therefore compared the suppression of serum levels of intact PTH induced by a 1.5-gram oral calcium load in patients with mild pHPT with that in healthy subjects. The calcemic response to the oral calcium load was the same in the two groups and did not correlate with the degree of PTH suppression or to serum levels of vitamin D metabolites. It was found that serum levels of intact PTH were less suppressed by the oral calcium load in patients than in healthy subjects (p < 0.01), but with a considerable overlap between the two groups. The suppression of serum levels of intact PTH was correlated both to baseline serum total calcium levels (r = -0.55; p < 0.05) and osteocalcin levels (r = -0.69; p < 0.05) in the patients, but no such correlations were seen in the controls. We conclude that patients with pHPT have a decreased suppressibility of PTH secretion by calcium. Although this reduced suppressibility could be important for maintaining hypercalcemia in some patients with pHPT, it does not aid in the differential diagnosis between patients with mild pHPT and healthy subjects.

Impairment of gamma carboxylation of circulating osteocalcin (bone gla protein) in elderly women.

Osteocalcin, also called bone gla protein, is a unique noncollagenous protein of the extracellular matrix of bone that circulates in blood. Oseteocalcin contains three residues of the vitamin K-dependent gamma-carboxyglutamic acid (gla) responsible for the affinity of osteocalcin for bone mineral. In animals treated with the vitamin K antagonist warfarin, the osteocalcin content of bone is markedly reduced and the fraction of osteocalcin released into the circulation is increased. Most studies have shown that osteocalcin increases with aging in women, reflecting an increase in bone turnover, especially after the menopause. To determine if this increase in osteocalcin could be associated with impaired carboxylation, we measured total and noncarboxylated osteocalcin in the serum of 72 women of various ages: 22 premenopausal (31 +/- 7 years old), 20 early postmenopausal (54 +/- 3 years), and 30 elderly women (85 +/- 8 years). As previously reported, total serum osteocalcin was significantly increased in early postmenopausal and elderly women. Noncarboxylated serum osteocalcin was slightly increased in early postmenopausal women (0.95 +/- 0.4 versus 0.65 +/- 0.5 ng/ml in premenopausal women), markedly elevated in elderly women (1.59 +/- 1.1 ng/ml, p less than 0.001), and correlated with age (r = 0.47, p less than 0.001). Elderly women had values of the same magnitude as in 10 patients on chronic warfarin therapy (1.94 +/- 1.1 ng/ml). As a consequence, the increase in carboxylated serum osteocalcin was significant in early postmenopausal women but not in elderly women. Serum levels of vitamin K1 and of menaquinones 6, 7, and 8 were measured in some of the young and elderly women.(ABSTRACT TRUNCATED AT 250 WORDS)