Bone Turnover In Patients Research Articles

Clinical utility of markers of bone turnover in children and adolescents

We review the past years' literature on biochemical markers of bone turnover. A general introduction to markers of bone formation and bone resorption is followed by reference values of bone turnover in neonates, infants, and prepubertal and pubertal children. We describe intervention with calcium and physical activity in healthy children and bone turnover in patients. The predictive value of a single measurement of bone markers in individuals is poor, due to the large biologic intraperson variation for bone markers in general. Serious osteoporosis can be diagnosed by the combined results of measurement of several bone formation and resorption markers.

Markers of bone turnover in patients with differentiated thyroid cancer with and following withdrawal of thyroxine suppressive therapy.

To study whether levothyroxine (LT4) suppressive therapy exposes patients with differentiated thyroid cancer (TC) to an increased risk of osteoporosis. Markers of bone formation (serum alkaline phosphatase (ALP), osteocalcin (OC), type I procollagen carboxyterminal (PICP) and aminoterminal (PINP) propeptide) and resorption (serum type I collagen carboxyterminal telopeptide (ICTP) and urine hydroxyproline (HOP)), as well as serum intact parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25(OH)2-D) were measured in 29 patients (25 women, 4 men) with a median age of 45 years, and in 38 age- and sex-matched controls. In a subgroup of 14 patients the measurements were repeated after 5 weeks' interruption of LT4 therapy. Since the primary treatment of TC the patients had used TSH suppressive doses of LT4 (a mean daily dose of 215 microg) for 9 to 11 years. The bone mineral density (BMD) of patients and controls was measured by dual energy X-ray absorptiometry. When on T4 therapy, patients had significantly higher mean levels of ALP (+21%, P < 0.05), OC (+35%, P < 0.01), PICP (+10%, P < 0.05), PINP (+46%, P < 0.001), ICTP (+21%, P < 0.05), and HOP (+37%, P < 0.001) compared with controls. After stopping treatment, OC (-42%, P < 0.001), PINP (-7%, P < 0.05), and ICTP (-54%, P < 0.001) decreased, whereas PICP (+24%, P < 0.001) and 1,25(OH)2D (+29%, P < 0.01) increased. BMD of the lumbar spine and the upper femur was similar in patients and controls. Patients with differentiated TC have high bone turnover when on LT4 suppressive therapy, After withdrawing treatment both bone formation and resorption decrease acutely. During development of hypothyroidism, serum PICP and PINP, which form from the same type I procollagen molecule and should change similarly, behaved differently. This may be due to different effects of hypothyroidism on their removal through separate receptors in the liver.

Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis.

In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of 96 patients (83 women and 13 men) were divided into three groups according to disease activity measured by serum levels of C-reactive protein (CRP). In the whole group, serum levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (P < 0.001) and PTH (P < 0.05) were negatively correlated to disease activity. The urinary excretion of collagen crosslinks--pyridinoline (Pyd) (P < 0.001) and deoxypyridinoline (Dpd) (P < 0.05)--showed a positive correlation with disease activity. The inverse correlation between serum 1,25(OH)2D3 and disease activity was separately evident in patients with (P < 0.001) and without (P < 0.01) glucocorticoid treatment, in pre- (P < 0.01) and postmenopausal (P < 0.001) women, and in men (P < 0.01). 1,25(OH)2D3 and PTH serum levels were positively correlated to serum bone alkaline phosphatase (ALP) (P < 0.01). The results indicate that high disease activity in patients with rheumatoid arthritis is associated with an alteration in vitamin D metabolism and increased bone resorption. The decrease of 1,25(OH)2D3 levels in these patients may contribute to a negative calcium balance and inhibition of bone formation. Furthermore, low levels of 1,25(OH)2D3 as an endogenous immunomodulator suppressing activated T cells and the proliferation of cells may accelerate the arthritic process in rheumatoid arthritis.

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.

Serum markers of bone and collagen turnover in patients with Cushing's syndrome and in subjects with adrenal incidentalomas.

The aim of this study was to assess serum levels of some markers of bone turnover and collagen synthesis in 22 patients with adrenal incidentalomas (AI), a model of silent glucocorticoid excess, and to compare the results with those obtained in 18 patients with Cushing's syndrome (CS). Osteocalcin (BGP), bone isoenzyme of alkaline phsophatase, carboxy-terminal propeptide of type I procollagen, and carboxy-terminal cross-linked telopeptide of type I collagen were measured as biochemical indexes of bone turnover, and amino-terminal propeptide of type III procollagen was determined as an index of collagen synthesis. Two groups of healthy volunteers evenly matched for sex, age, and menstrual status were used for a case-control analysis of AI and CS groups, respectively. Patients with AI showed a slight, albeit significant, reduction in serum BGP and a mild increase in carboxy-terminal cross-linked telopeptide of type I collagen levels compared with controls [median, 6.6 vs. 7.8 ng/mL (P < 0.05) and 4.2 vs. 3.1 micrograms/L (P < 0.01), respectively]. No significant differences were found when comparing the other markers. Patients with CS had BGP, bone isoenzyme of alkaline phosphatase, and amino-terminal propeptide of type III procollagen levels significantly lower than control values [median, 3.0 vs. 7.3 ng/mL (P < 0.0001); 4.4 vs. 11.5 micrograms/L (P < 0.01); 2.2 vs. 4.3 micrograms/L (P < 0.0001), respectively], but no significant difference in the other markers. These results confirm a clear inhibition of osteoblastic activity in CS and could suggest an enhanced bone metabolism in patients with AI. The degree of impairment of bone turnover in patients with AI does not seem enough to recommend surgery (removal of the adrenal adenoma) in the absence of other indications.

Serum concentration of the aminopropeptide of type I procollagen in patients on haemo- and peritoneal dialysis.

Using an ELISA technique, the aminopropeptide of type I procollagen (PINP) was measured in serum from patients with chronic renal failure treated with haemodialysis (HD) (n = 19) or continuous ambulatory peritoneal dialysis (CAPD) (n = 14), and compared to the commonly used bone markers. The serum concentrations for PINP, compared to healthy controls were significantly increased in both the HD-group (p < 0.00001) and the CAPD-group (p < 0.00001). In the HD-group a close correlation was found between PINP and parathyroid hormone (PTH) (R(s) = 0.745; p = 0.00026) and between PINP and total alkaline phosphatase (R(s) = 0.623; p = 0.004), but in the CAPD-group the corresponding p-values were 0.17 and 0.06 only. No significant difference was found between the HD and CAPD patients with respect to serum levels of PINP, PTH, total alkaline phosphatase, or ionized calcium. In the HD-patients, a significantly higher level of serum phosphate was found compared to in the CAPD-patients. The present study demonstrates a close correlation between PTH, total alkaline phosphatase and PINP, which indicates that PINP might be used as a marker for evaluating increased bone turnover in patients with chronic renal failure treated with haemodialysis, and perhaps also in patients treated with peritoneal dialysis, and that the ideal biochemical parameters to analyse changes in bone metabolism in these patients may be a combination of the initiating hormone (PTH) and PINP as a marker of the effect of PTH on bone metabolism.

Effects of prednisolone on bone turnover in patients with corticosteroid resistant asthma

Although corticosteroid resistant (CR) bronchial asthma is associated with impaired in vitro an din vivo glucocorticoid (GC) responsiveness in mononuclear cell function, it is not known whether this is a cell specific phenomenon or whether these patients are at risk of glucocorticoid side-effects as corticosteroid-sensitive (CS) subjects. In order to address this question we have examined the effects of GCs on biochemical indices of bone turnover in vivo. Six CS and six CR subjects received prednisolone 40 mg orally at 09.00 daily for 5 days. At 08.30 on day 1 and day 6 a fasting blood was taken for estimation of serum osteocalcin, tartrate resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP; total and bone isoenzyme), and a urine sample taken for estimation of free deoxy-pyridinoline crosslinks. TRAP and ALP were measured by a colorimetric method and osteocalcin and deoxy-pyridinoline crosslinks by ELISA. Serum osteocalcin (nmol/L) decreased from 1.39 +/- 0.09 (mean +/- SEM) to 1.14 +/- 0.07 (P = 0.023) and from 1.19 +/- 0.05 to 0.96 +/- 0.1 (P = 0.037) in the CS and CR groups respectively. There was no difference between baseline and post-treatment levels in either group. Serum total ALP (units/L) decreased from 178 +/- 7 to 168 +/- 4 (P = 0.02) and from 195 +/- 22 to 175 +/- 16 (P = 0.04) in the CS and CR groups, respectively. There was no difference between baseline and post-treatment levels in either group. There was no significant elevation of deoxy-pyridinoline crosslinks or TRAP and no suppression of bone ALP in either group. We suggest that CR asthmatics may be equally at risk from the metabolic side-effects of glucocorticoids.

Bone turnover in patients on home parenteral nutrition: alongitudinal observation by biochemical markers

In order to characterize biochemical markers of bone turnover in home parenteral nutrition(HPN) patients, 8 adult patients on HPN for benign intestinal failure were studied at 0, 6 and 12 months by evaluating serum osteocalcin (bone formation marker), urinary hydroxylysyl pyridinoline, lysyl pyridinoline and β-galactosyl hydroxylysine (bone resorption markers), serum PTH, Calcitonin, 25 vitD, 1–25vitD, serum and urinary minerals, body weight, rehabilitation degree and HPN characteristics. Three patients entered the study 2–3 months after the beginning of HPN. Their features of bone turnover were homogeneous, characterized by increased resorption associated with normal or increased formation, at baseline, and normalization of resorption associated with an increase or a parallel decrease of formation, at 6 months. At 12 months, the patterns were similar to those observed at 6 months. The patients were not of the same sex and age and had different underlying diseases and types of intestinal failure, HPN composition and serum vitamin D levels. They had weight gain that was already present at baseline and the positive outcomes of the rehabilitation and clinical status in common. Five patients entered the study more than 1 year after the beginning of HPN. They showed heterogeneous features of bone turnover that were stable throughout the study, characterized by increased resorption associated with low or normal formation in two cases, low normal resorption associated with low or normal formation in three. In one patient, who had increased resorption and low formation, the bone turnover appeared to be explained by the nutritional and clinical outcomes, which were negative. These results appeared consistent with those obtained in previous studies by bone histomorphometry, indicating that bone turnover of short-term HPN patients differed from that of long-term patients, and suggesting that the early months of HPN were associated with increased bone resorption.

Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients.

Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. Plasma bone-specific alkaline phosphatase (bAP) has been demonstrated to be more reliable than total alkaline phosphatases (tAP) in providing information about bone turnover in patients with metabolic bone diseases. This study surveyed 42 hemodialysis patients who underwent a systematic transiliac bone biopsy for histomorphometry study. Plasma bAP was determined by using a new immunoassay (Tandem-R Ostase, Hybritech, Liège, Belgium). Plasma bAP values were compared with those of two other plasma markers of bone metabolism, namely tAP and intact parathyroid hormone (iPTH), for the correlations with bone histomorphometric parameters. Patients with high-turnover bone disease (HTBD) (N = 32) had significantly higher plasma bAP levels than patients with normal or low bone turnover (N/LTBD) (N = 10) (66.9 +/- 63.5 ng/mL versus 10.8 +/- 4.2 ng/mL, respectively). Bone formation and resorption were highly correlated in these patients, and plasma bAP levels were positively correlated with bone resorption parameters, including osteoclast surface (r = 0.39, P < 0.0001) and osteoclast number/mm2 (r = 0.36, P < 0.001), and with bone formation parameters, osteoblast surface (r = 0.50, P < 0.005), and bone formation rate (r = 0.91, P < 0.0001). The bone formation rate was better correlated with plasma bAP levels than with either plasma tAP or iPTH concentrations. Plasma bAP level equal or higher than 20 ng/mL, either alone or combined with plasma iPTH of 200 pg/mL, had the highest sensitivity, specificity, and predictability values for the diagnosis of high-turnover bone disease, and formally excluded patients with normal or LTBD. In conclusion, plasma bAP can be measured with a reliable immunoassay in hemodialysis patients. It represents a highly sensitive and specific biochemical marker of skeletal remodeling in these patients. Therefore, both serum iPTH and bAP are complementary in diagnoses of the type of renal osteodystrophy.

Bone mineraldensity and biochemical markers of bone turnover in patients following heart transplantation

Bone mineraldensity and biochemical markers of bone turnover in patients following heart transplantation

Bone mineral density and biochemical markers of bone turnover in patients with chronic liver failure

Bone mineral density and biochemical markers of bone turnover in patients with chronic liver failure

279 Effects of prednisolone on bone turnover in patients with corticosteroid resistant asthma

279 Effects of prednisolone on bone turnover in patients with corticosteroid resistant asthma

Bone mineraldensity and biochemical markers of bone turnover in patients with hyperthyroidism

Bone mineraldensity and biochemical markers of bone turnover in patients with hyperthyroidism

Biochemical markers of bone turnover in patients with metastatic bone disease

Several biochemical markers of bone formation and bone resorption have recently been developed. These markers have been evaluated for clinical utility in patients with metabolic bone disease, including Paget disease and osteoporosis, and for their potential use in cancer patients whose disease has metastasized to bone. We have evaluated seven markers of bone turnover in the plasma and urine of 94 patients with newly diagnosed or progressive malignancy with and without clinical evidence of bone metastases. As determined by a positive bone scan and (or) bone survey, 30 patients had metastases to bone; 51 patients had metastatic cancer without overt bony involvement; and 13 patients had local disease without bone metastases. To evaluate the predictive value of these markers in the metastatic population, we utilized a "Z-score" and logistic regression analysis to distinguish patients with documented bone metastatic disease from those patients without clinical evidence of bone metastases. The higher the Z-score, the better the marker predicts the presence of bone metastases. With this statistical approach, urine N-telopeptide measurements had the highest Z-score and the most significant association with the probability of bone metastases. Urine deoxypyridinoline was the second most predictive marker of bone metastases. Thus, biochemical markers of bone resorption might be of use to predict the presence of bone metastases in cancer patients and to monitor the efficacy of antiresorptive therapy in patients treated for metastatic bone disease.

Biochemical markers of bone turnover in patients on home parenteral nutrition (HPN): A follow up study

Biochemical markers of bone turnover in patients on home parenteral nutrition (HPN): A follow up study

Effect of rectal salmon calcitonin treatment on bone mass and bone turnover in patients with established postmenopausal osteoporosis: A 1-year crossover study

A new suppository formulation of salmon calcitonin (sCT) is now available to increase the choices for the clinician in the treatment of osteoporotic patients. To test this new formulation, we studied the efficacy and tolerability of rectal sCT in 40 patients with postmenopausal osteoporosis. According to a double-blind, placebo-controlled design, the patients were divided into two groups and treated with a daily dose of 100 IU of sCT administered by suppository or matching placebo for 6 months. After 6 months, patients were crossed over so that the sCT-treated group received placebo for the subsequent 6 months and vice versa. Bone mineral density (BMD), measured at the distal radius by dual photon absorptiometry and at the lumbar spine by dual energy X-ray absorptiometry, increased by 3.3% and 3.0%, respectively, after 6 months in the sCt-treated group. The placebo group showed a significant ( P < 0.05) decrease only at the lumbar spine. The differences between the two groups were significant, as determined by one-way analysis of variance. After the crossover period, only the group receiving the active treatment showed an increase in BMD. No significant changes were observed in the biochemical indexes of bone turnover (serum osteocalcin and hydroxyproline/creatinine ratio) in both groups, although during the sCT treatment periods a reduction of bone turnover rate was observed, as demonstrated by the reduction of these markers. This new formulation was well tolerated. Our results indicate that a 6-month treatment with sCT, at a daily dose of 100 IU administered by suppositories, is able to increase bone mass and to exert an inhibitory effect on bone turnover.

Osteocalcin in patients with rheumatoid arthritis--effect of anatomical stages, inflammatory activity and therapy.

The aim of this study was to investigate whether the degree of inflammatory activity, the anatomical stage and various treatments have an influence on bone turnover in patients with rheumatoid arthritis (RA). Osteocalcin (OC) and other parameters of bone turnover were measured in 131 patients with RA. The mean values of alkaline phosphatase (AP), but not of OC were significantly (P < 0.01) higher in our patients compared to controls. In contrast to AP, OC values increased and correlated significantly (r = +0.33, P < 0.01) with ascending anatomical stage in women not on glucocorticoid treatment. As regards therapy, we found significantly lower OC levels in women receiving steroids compared to controls (P < 0.03) and those being treated with non-steroidal anti-inflammatory drugs (NSAIDs) (P < 0.03), methotrexate (MTX) (P < 0.05), or gold (P < 0.01). Females treated with gold had higher OC levels than patients receiving no antirheumatic drugs (P < 0.03). Furthermore, there was a significantly negative correlation between OC and inflammatory activity [C-reactive protein (CRP)] (r = -0.25, P < 0.003). In conclusion, OC levels were significantly higher (P < 0.032) in patients with advanced (anatomical) stages of RA. In contrast to AP, changes in bone turnover, such as suppression of bone formation by steroids and high inflammatory activity in patients with RA, were easily detected.

Serum intact molecule of bone Gla-protein in patients with abnormal bone and calcium metabolism

A circulating level of bone Gla-protein (BGP) has been estimated one of the most promising markers for bone turnover in patients with metabolic bone diseases. Although previous bone histomorphometric studies have revealed that serum BGP levels are mainly related to osteoblastic bone formation, multiple immunoreactive forms of BGP present in uremic sera are attributed to both osteoclastic bone resorption and decreased renal metabolism itself. Chromatography and cross-reactivity tests showed that an immunoradiometric assay (IRMA) for BGP specifically recognizes intact molecules of BGP and excludes BGP fragments found in uremic sera. Serum levels of BGP determined by IRMA were found significantly higher than those determined by radioimmnoassay. Elevated serum BGP levels determined by IRMA in primary hyperparathyroidism decreased and returned within the reference range more than 1 year following successful parathyroidectomy. Intermittent oral administration of high dose of 1,25 (OH)2D3 enhanced elevated serum BGP levels determined by IRMA which significantly increased from the initial levels at week 4 and at week 8, afterwards gradually returning to the basal levels at week 16. In addition, similar treatment effects were observed in serum prcollagen type I c-terminal peptide (P1CP), a marker for bone matrix formation.

Serum Osteocalcin in Patients Takingl-Thyroxine who Have Subclinical Hyperthyroidism*

Serum osteocalcin, an index of osteoblastic activity, is increased in hyperthyroidism. Serum osteocalcin levels are negatively correlated with bone density in patients with overt hyperthyroidism. Osteocalcin levels are also elevated in patients with multinodular goiter and subclinical hyperthyroidism. We therefore measured serum osteocalcin levels in patients taking T4 to determine if they correlated with the degree of TSH suppression. Despite an upward trend in serum osteocalcin measurements with decreasing TSH concentrations, there was no significant difference in serum osteocalcin among groups of patients with normal (0.5-5.0 mu/L), mildly reduced (0.1-0.5 mU/L), or undetectable serum TSH (less than 0.01 mU/L). However, a weak negative correlation was seen between serum TSH and osteocalcin concentrations (r = 0.29, slope = -0.28, P less than 0.05). Osteocalcin did not correlate with either serum free T4 or free T3 concentrations. Serum PTH concentrations were not different among the three patient groups. Our data suggest that osteocalcin is not a useful clinical marker for increased bone turnover in patients with subclinical hyperthyroidism due to T4 therapy. However, the trend towards higher osteocalcin levels in patients with suppressed serum TSH values, and the weak negative correlation between serum TSH and osteocalcin are consistent with findings of reduced bone density in these patients.

Bone Metabolism in Patients with Functioning Kidney Grafts: Increased Serum Levels of Osteocalcin and Parathyroid Hormone Despite Normalisation of Kidney Function

In order to study bone metabolism after renal transplantation we measured serum levels of parathyroid hormone (PTH) and osteocalcin (OC), a specific biochemical parameter of bone formation, in 30 patients with functioning kidney grafts and 30 sex- and age matched control subjects. Serum levels of OC and PTH were markedly elevated in the kidney transplantation patients when compared with the control subjects (p less than 0.0001). Elevated levels of OC and PTH were present even in patients with very well functioning transplants. In the kidney transplantation patients, a significant positive correlation between serum OC and serum PTH levels could be found. Our data give evidence of persistent hyperparathyroidism and increased bone turnover in patients after renal transplantation.