acid-phosphatase and Hyperparathyroidism--Secondary

To evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum parathyroid hormone (PTH) and bone resorption markers (BRM) as compared to iso-caloric and iso-protein dairy products in aged white women at risk of fragility fractures.. A randomized double-blind controlled trial.. A community dwelling home.. Forty-eight women over 60 years (mean age 73.4).. Consumption during 84 days of two 125 g servings of either vitamin D and calcium-fortified yogurts (FY) at supplemental levels of 10 µg vitamin D3/d and 520 mg/d of calcium (total=800 mg/d), or non fortified control yogurts (CY) providing 280 mg/d of calcium.. Serum changes from baseline (D0) to D28, D56 and D84 in 25OHD, PTH and in two BRM: Tartrate-resistant-acid-phosphatase-isoform-5b (TRAP5b) and carboxy-terminal-cross-linked-telopeptide of type-I-collagen (CTX).. The 10 years risk of major and hip fractures were 13.1 and 5.0%, and 12.9 and 4.2 %, in FY and CY groups, respectively. From D0 to D84, serum 25OHD increased (mean±SE) from 34.3±2.4 to 56.3±2.4 nmol/L in FY (n=24) and from 35.0±2.5 to 41.3±3.0 nmol/L in CY (n=24), (P=0.00001). The corresponding changes in PTH were from 64.1±5.1 to 47.4±3.8 ng/L in FY and from 63.5±4.6 to 60.7±4.2 ng/L in CY (P=0.0011). After D84, TRAP5b was reduced significantly (P=0.0228) and CTX fell though not significantly (P=0.0773) in FY compared to CY.. This trial in aged white women living in a community dwelling home at risk for osteoporotic fractures confirms that fortification of dairy products with vitamin D3 and calcium should provide a greater prevention of secondary hyperparathyroidism and accelerated bone resorption as compared to non-fortified equivalent foods.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers; Bone Resorption; Calcium, Dietary; Cholecalciferol; Collagen Type I; Double-Blind Method; Female; Food, Fortified; Hip Fractures; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Middle Aged; Nursing Homes; Osteoporotic Fractures; Parathyroid Hormone; Risk; Tartrate-Resistant Acid Phosphatase; White People; Yogurt

Nutritional prevention of bone deterioration with fortified foods seems particularly suitable in institutionalized elderly women at risk of vitamin D deficiency, secondary hyperparathyroidism, increased bone resorption, and osteoporotic fracture.. The objective was to evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum PTH and bone resorption markers as compared with isocaloric and isoprotein dairy products in elderly women.. A randomized double-blind controlled-trial, 56-day intervention was conducted in institutionalized women (mean age 85.5 years) consuming 2 125-g servings of either vitamin D- and calcium-fortified yogurt (FY) at supplemental levels of 10 μg/d vitamin D₃ and 800 mg/d calcium or nonfortified control yogurt (CY) providing 280 mg/d calcium.. The endpoints were serum changes from baseline (day 0) to day 28 and day 56 in 25-hydroxyvitamin-D (25OHD), PTH, and bone resorption markers tartrate-resistant acid phosphatase isoform-5b (TRAP5b), the primary outcome, and carboxyl-terminal cross-linked telopeptide of type I collagen (CTX).. At day 56, serum 25OHD increased (mean ± SEM) by 25.3 ± 1.8 vs 5.2 ± 2.5 nmol/L in FY (n = 29) and CY (n = 27), respectively (P < .0001). The corresponding changes in PTH were -28.6% ± 7.2% vs -8.0% ± 4.3% (P = .0003); in TRAP5b, -21.9% ± 4.3% vs 3.0% ± 3.2% (P < .0001); and in CTX, -11.0% ± 9.7% vs -3.0% ± 4.1% (P = .0146), in FY and CY, respectively. At day 28, these differences were less pronounced but already significant for 25OHD, PTH, and TRAP5b.. This study in institutionalized elderly at high risk for osteoporotic fracture suggests that fortification of dairy products with vitamin D₃ and calcium provides a greater prevention of accelerated bone resorption as compared with nonfortified equivalent foods.

Topics: Acid Phosphatase; Aged, 80 and over; Biomarkers; Bone Density Conservation Agents; Bone Resorption; Calcium, Dietary; Cholecalciferol; Collagen Type I; Double-Blind Method; Female; Food, Fortified; France; Homes for the Aged; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Nursing Homes; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone; Peptides; Risk; Tartrate-Resistant Acid Phosphatase; Vitamin D Deficiency; Yogurt

Secondary hyperparathyroidism (SHP) is characterized by high bone turnover, which may, in turn, result in increased release of lead from bone stores. This study investigated the effects of intravenous calcitriol on blood lead (BL) levels in patients with SHP.. Intravenous calcitriol therapy was administered for 16 wk to 28 patients who were on maintenance hemodialysis (HD) and had intact parathyroid hormone (iPTH) plasma levels of >300 pg/mL. Blood was drawn at baseline and every 4 wk for 16 wk to determine the levels of iPTH; bone remodeling markers, including bone-specific alkaline phosphatase (bAP) and type 5b tartrate-resistant acid phosphatase (TRAP); and BL.. Of the 28 patients, 25 responded to calcitriol therapy; they exhibited significant decrements in serum iPTH levels by the end of 4 wk of therapy and thereafter. After 16 wk of therapy, these patients had significant reductions in serum iPTH levels (p<0.01) and significant and parallel decreases in the levels of bAP (p<0.01), TRAP (p<0.01), and BL (p<0.01). Further analysis showed a significant positive correlation between the levels of BL and serum iPTH (r=0.34, p<0.01) and BL and serum TRAP (r=0.22, p<0.05). However, there was no significant correlation between the levels of BL and serum bAP.. Elevated levels of BL and serum bone remodeling markers, which are common features of SHP, can be effectively suppressed by calcitriol therapy. This indicates that hyperparathyroidism not only accelerates bone remodeling but may also enhance bone lead mobilization in patients on maintenance HD.

Topics: Acid Phosphatase; Biomarkers; Bone and Bones; Calcitriol; Female; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Lead; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis; Tartrate-Resistant Acid Phosphatase

Cinacalcet hydrochloride is a calcimimetic agent that activates the calcium-sensing receptor on the surface of parathyroid cells and inhibits parathyroid hormone (PTH) secretion. To manage secondary hyperparathyroidism, cinacalcet, which lowers PTH levels without increasing serum calcium, phosphorus and calcium-phosphorus product (Ca x P) levels, may provide a new potential therapy. To identify the optimal starting dose of cinacalcet for Japanese hemodialysis patients with secondary hyperparathyroidism, this double-blind, placebo-controlled, parallel, dose-finding study was conducted. One hundred and twenty Japanese hemodialysis patients with intact PTH levels greater than or equal to 300 pg/mL were randomized into four groups: placebo, and 12.5, 25 and 50 mg of cinacalcet. The treatment period was three weeks followed by a two-week follow-up observation period. Cinacalcet decreased serum intact PTH levels in a dose-dependent manner, and also decreased serum calcium, phosphorus, Ca x P, tartrate-resistant acid phosphatase and osteocalcin levels. The treatment with cinacalcet was generally well tolerated in this study. However, the incidence of treatment-related adverse events, such as gastrointestinal disorders and hypocalcemia, and the rate of withdrawal from the study due to treatment-related adverse events were higher in the 50 mg dose group than in the other groups. On the basis of both efficacy and safety results, 25 mg has been identified as the optimal starting dose of cinacalcet for Japanese hemodialysis patients with secondary hyperparathyroidism.

Topics: Acid Phosphatase; Aged; Asian People; Calcium; Cinacalcet; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Japan; Kidney Failure, Chronic; Male; Middle Aged; Naphthalenes; Osteocalcin; Parathyroid Hormone; Phosphorus; Renal Dialysis; Tartrate-Resistant Acid Phosphatase

Secondary hyperparathyroidism (SHP) is characterized by high bone turnover and elevated serum bone remodeling markers. Elevation of serum interleukin-6 (IL-6) levels is also characteristic of end-stage renal disease. This study investigates the effects of intravenous calcitriol on serum bone resorptive markers, namely, type 5b tartrate-resistant acid phosphatase (TRACP5b) and IL-6 in patients with SHP.. Intravenous calcitriol therapy was given for 16 weeks to 24 patients on maintenance hemodialysis with plasma intact parathyroid hormone (iPTH) levels >300 pg/ml. Blood was drawn at baseline and every 4 weeks for 16 weeks for determination of the levels of biochemical parameters, iPTH, IL-6 and bone remodeling markers, including bone-specific alkaline phosphatase (bAP) and TRACP5b.. Only 21 patients responded to the calcitriol therapy, with significant decrements in serum iPTH after 4 weeks of therapy and thereafter. After 16 weeks of calcitriol therapy, 21 patients had significant decrements in serum iPTH (707.9 +/- 317.8 vs. 205.0 +/- 63.1 pg/ml, p < 0.01). Prior to treatment, a significant correlation was found between increased levels of serum iPTH and IL-6 levels (r = 0.45, p < 0.05). After treatment, there was also a significant and parallel lowering of levels of serum iPTH, IL-6 (8.52 +/- 3.59 vs. 7.24 +/- 2.81 pg/ml, p < 0.01), bAP (54.68 +/- 36.17 vs. 24.55 +/- 13.84 U/l, p < 0.01) and TRACP5b (3.41 +/- 1.89 vs. 1.80 +/- 0.55 U/l, p < 0.01). Our results additionally showed significant positive correlationsbetween baseline levels of serum IL-6 and those of iPTH, bAP and TRACP5b. After 16 weeks of calcitriol treatment, the correlation between IL-6 and iPTH levels lost significance but levels of serum IL-6, bAP and TRACP5b remained significantly correlated.. Elevated levels of serum IL-6 and bone remodeling markers, namely, bAP and TRACP5b which are common features of SHP, are effectively suppressed by calcitriol therapy. This indicates that hyperparathyroidism not only accelerates bone remodeling but may also aggravate inflammation in patients on maintenance hemodialysis.

Topics: Acid Phosphatase; Aged; Biomarkers; Bone Density Conservation Agents; Bone Resorption; Calcitriol; Female; Humans; Hyperparathyroidism, Secondary; Inflammation; Interleukin-6; Isoenzymes; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Time Factors

The dose-response relationships and the safety of administering 22-oxacalcitriol (OCT) to patients with secondary hyperparathyroidism (2HPT) under regular three-times-weekly hemodialysis (HD) were evaluated by double-blind parallel group design. A total of 203 patients with 2HPT were randomly allocated into four groups, and 5 microg (Group L), 10 microg (Group M), or 15 microg (Group H) OCT, or placebo (Group P) was administrated at the end of every HD for 12 weeks. Reductions of intact-parathyroid hormone (iPTH) concentration greater than 30% from baseline were observed in 7.7% of Group P as compared to 77.3% of the pooled OCT groups after 12 weeks of treatment (Mantel test: P < 0.001). Time-trends (slopes) of log-iPTH concentration calculated by least-squares line fitting to each patient's data during treatment differed between Group P and the pooled OCT groups (t-test: P < 0.001) and these iPTH slopes decreased dose-dependently (linear trend by t-test: P < 0.001). Slopes of serum calcium corrected for albumin (corrected-sCa) concentrations also differed between Group P and the pooled OCT groups (t-test: P < 0.001), and increased dose-dependently (linear trend by t-test: P < 0.0001). Serum phosphorus and Ca x P product increased significantly only in high dose groups. Slopes of log(iPTH) and corrected-sCa concentrations were reciprocally related. Most adverse events were hypercalcemia and dose-related, but occasionally comprised pruritus or increased serum creatinine phosphokinase. These results indicate that OCT produced a strong and dose-dependent suppression of PTH and an increase of corrected-sCa concentration in patients with 2HPT. The recommended initial dosages of OCT would appear to be 5 microg when pretreatment iPTH concentrations are less than 500 pg/mL, and 10 microg when greater than 500 pg/mL for safe and effective treatment. As in the case of PTH, calcium and phosphorus showed dose-dependent increases. It is therefore essential to take precautions as to possible increases in calcium and phosphorus.

Topics: Acid Phosphatase; Aged; Biomarkers; Calcitriol; Calcium; Dose-Response Relationship, Drug; Female; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Male; Middle Aged; Tartrate-Resistant Acid Phosphatase

The increased awareness of the potential role played by mineral and bone disorder in the appearance of cardiovascular disease in renal patients has produced research efforts aimed at discovering possible pathogenic links. Accordingly, the diagnostic significance of the classic bone markers of mineral disorders and of the new markers in the setting of chronic kidney disease-mineral and bone disorders (CKD-MBD) needs to be re-evaluated along with increasing information. In this article we include classic markers of bone metabolism and some of the noncollagenous bone proteins that are gaining experimental and clinical significance in CKD-MBD. Among classic markers of secondary hyperparathyroidism and of renal osteodystrophy, we analyzed parathyroid hormone, alkaline phosphatase, tartrate-resistant acid phosphatase, and bone collagen-derived peptides. We underlined, for each, the relevance of parent proteins (peptides or isoforms) that affect assay methods and, eventually, the diagnostic or prognostic significance. Also, we considered their relationship with cardiovascular mortality. Among the numerous noncollagenous bone proteins, we examined matrix Gla protein (MGP), osteocalcin (OC), osteoprotegerin, and the small integrin-binding ligand N-linked glycoprotein family. For MGP and OC we report the relevant involvement with the process of calcification (MGP) and with glucose and energy metabolism (OC). Both of these proteins require vitamin K to become active and this is a specific problem in renal patients who frequently are deficient of this vitamin. Finally, recent acquisitions on the fascinating family of the small integrin-binding ligand N-linked glycoprotein proteins are recapitulated briefly to underline their potential clinical interest and their complex involvement with all aspects of CKD-MBD. Their diagnostic role in clinical practice awaits further studies.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biomarkers; Calcium-Binding Proteins; Chronic Kidney Disease-Mineral and Bone Disorder; Extracellular Matrix Proteins; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Matrix Gla Protein; Osteocalcin; Osteoprotegerin; Parathyroid Hormone; Peptide Fragments; Procollagen; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Renal Insufficiency, Chronic; Tartrate-Resistant Acid Phosphatase

Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT), which causes varying degrees of bone mass loss. This condition is treated with parathyroidectomy (PTX). We investigated whether serial serum bone turnover markers could predict changes in bone mineral density (BMD) after PTX.. Renal patients on maintenance haemodialysis who received PTX for refractory SHPT (n = 26, male/female: 13/13; mean age: 48·6 ± 10·7 year) and control subjects without SHPT (n = 25) were prospectively followed for 1 year at two tertiary hospitals in Taiwan.. Serum intact parathyroid hormone (iPTH), bone-specific alkaline phosphatase (BAP) and type 5b tartrate-resistant acid phosphatase (TRAP) were measured serially. Additionally, femoral neck (FN) and lumbar spine (LS) BMD were measured before and 1 year after PTX.. After PTX, iPTH levels decreased markedly and persistently. BMDs increased in both the FN and LS, but particularly in the LS. Serum BAP progressively increased to a peak at 2 weeks after PTX. Serum TRAP levels progressively decreased over 6 months after PTX. In univariate correlation analyses, baseline iPTH correlated positively with T-score changes in FN (r = 0·45, P = 0·021) and LS (r = 0·48, P = 0·013). In multivariate regression models, changes in FN T-scores were negatively predicted by baseline BAP levels (r = -0·615, P = 0·005) and baseline FN T-scores (r = -0·563, P = 0·012), and they were positively predicted by baseline TRAP(r = 0·6, P =  0·007). Changes in LS T-scores were positively predicted by baseline TRAP values (r = 0·528, P = 0·01) and negatively predicted by the percentage change in BAP after 2 weeks (r = -0·501, P = 0·015).. Parathyroidectomy provided marked, sustained improvements in BMD for up to 1 year. Furthermore, markers of bone turnover predicted 1-year changes in FN and LS BMDs after PTX.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Analysis of Variance; Biomarkers; Bone and Bones; Bone Density; Female; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Male; Middle Aged; Parathyroid Hormone; Parathyroidectomy; Prospective Studies; Regression Analysis; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Time Factors

Secondary hyperparathyroidism (SHPT) is characterized by high bone turnover and may result in increased release of lead (Pb) from bone stores. Parathyroidectomy (PTX) drastically changes bone remodeling. This study investigated the effects of PTX on the levels of blood lead (blood Pb) in patients with refractory SHPT.. The study included 30 patients on long-term hemodialysis (HD) who underwent PTX in the nephrology units of two Taiwanese hospitals. Changes in serum levels of intact parathyroid hormone (iPTH), bone-specific alkaline phosphatase (BAP), type 5b tartrate-resistant acid phosphatase (TRAP), total calcium (tCa), and blood Pb were analyzed.. After PTX, serum iPTH was markedly decreased while serum BAP was progressively increased and peaked 2weeks after PTX. Serum TRAP levels were progressively decreased during the 4week follow-up period. Serum tCa and blood Pb levels decreased sharply immediately after PTX. There was a positive correlation between the percentage of decrease in tCa and blood Pb at one day after PTX. Further analysis indicated a significant positive correlation between levels of blood Pb and serum iPTH (r=0.378, p<0.001), blood Pb and serum TRAP (r=0.180, p<0.05), and a negative correlation between blood Pb and serum BAP (r=-0.205, p<0.05).. PTX effectively suppressed the elevated levels of blood Pb and serum bone remodeling markers, which are common features of SHPT. In addition to decreased Pb release from bone, an increased store of Pb in bone may play a role in decreasing serum blood Pb levels. These findings suggest that patients undergoing PTX for refractory SHPT should strictly avoid environmental exposure to Pb.

Topics: Acid Phosphatase; Biomarkers; Bone Remodeling; Calcium; Case-Control Studies; Female; Humans; Hyperparathyroidism, Secondary; Interleukin-6; Isoenzymes; Lead; Male; Middle Aged; Parathyroid Hormone; Parathyroidectomy; Renal Dialysis; Tartrate-Resistant Acid Phosphatase

In cinacalcet treatment of hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT), not only intact parathyroid hormone (I-PTH), whole PTH (W-PTH), and bone markers, but also W-PTH/I-PTH ratio as proportion of active PTH(1-84) molecules were decreased. Changes in W-PTH/I-PTH ratio significantly correlated and predicted changes in bone marker.. Cinacalcet partly suppresses the secretion of PTH by enhancing PTH(1-84) degradation into N-truncated fragments. The objectives of this study is to investigate the significance of the N-truncated PTH/PTH(1-84) ratio for the prediction of the effect of cinacalcet in HD patients.. Serum parameters were measured during 12 weeks of oral cinacalcet administration at 25 mg daily in 39 HD patients with SHPT.. Serum Ca, Pi, W-PTH, I-PTH, and W-PTH/I-PTH ratio all decreased significantly in a time-dependent manner during cinacalcet administration. Serum tartrate-resistant acid phosphatase (TRAP) 5b reflected these changes more precisely than serum N-telopeptide of type-I collagen. At 1 week, changes in I-PTH and W-PTH correlated significantly with those in serum Pi, but not Ca. Changes in serum Pi (but not Ca) and serum W-PTH also correlated significantly with changes in serum TRAP5b at both 4 and 12 weeks, while changes in serum I-PTH correlated significantly with those in serum TRAP5b only at 12 weeks. Changes in the serum W-PTH/I-PTH ratio correlated significantly with those in serum TRAP5b at both 4 and 12 weeks, and changes in serum W-PTH/I-PTH ratio at 4 weeks showed a tendency for a correlation with changes in serum TRAP5b at 12 weeks. HD patients with a reduced W-PTH/I-PTH ratio after 4 weeks had a significantly greater reduction of TRAP5b over 12 weeks.. W-PTH and the W-PTH/I-PTH ratio allow estimation of the potency of cinacalcet in enhancement of PTH degradation, and thus no less reliable markers than I-PTH for reflecting cinacalcet-induced bone resorption.

Topics: Acid Phosphatase; Adult; Aged; Bone Remodeling; Calcium; Cinacalcet; Collagen Type I; Female; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Longitudinal Studies; Male; Middle Aged; Naphthalenes; Parathyroid Hormone; Peptides; Phosphorus; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Uremia

According to the new KDIGO (Kidney Disease Improving Global Outcomes) guidelines, the term of renal osteodystrophy, should be used exclusively in reference to the invasive diagnosis of bone abnormalities. Due to the low sensitivity and specificity of biochemical serum markers of bone remodelling,the performance of bone biopsies is highly stimulated in dialysis patients and after kidney transplantation. The tartrate-resistant acid phosphatase (TRACP) is an iso-enzyme of the group of acid phosphatases, which is highly expressed by activated osteoclasts and macrophages. TRACP in osteoclasts is in intracytoplasmic vesicles that transport the products of bone matrix degradation. Being present in activated osteoclasts, the identification of this enzyme by histochemistry in undecalcified bone biopsies is an excellent method to quantify the resorption of bone. Since it is an enzymatic histochemical method for a thermolabile enzyme, the temperature at which it is performed is particularly relevant. This study aimed to determine the optimal temperature for identification of TRACP in activated osteoclasts in undecalcified bone biopsies embedded in methylmethacrylate. We selected 10 cases of undecalcified bone biopsies from hemodialysis patients with the diagnosis of secondary hyperparathyroidism. Sections of 5 μm were stained to identify TRACP at different incubation temperatures (37º, 45º, 60º, 70º and 80ºC) for 30 minutes. Activated osteoclasts stained red and trabecular bone (mineralized bone) was contrasted with toluidine blue. This approach also increased the visibility of the trabecular bone resorption areas (Howship lacunae). Unlike what is suggested in the literature and in several international protocols, we found that the best results were obtained with temperatures between 60ºC and 70ºC. For technical reasons and according to the results of the present study, we recommended that, for an incubation time of 30 minutes, the reaction should be carried out at 60ºC. As active osteoclasts are usually scarce in a bone section, the standardization of the histochemistry method is of great relevance, to optimize the identification of these cells and increase the accuracy of the histomosphometric results. Our results, allowing an increase in osteoclasts contrast, also support the use of semi-automatic histomorphometric measurements.

Topics: Acid Phosphatase; Histocytochemistry; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Macrophages; Osteoclasts; Sensitivity and Specificity; Staining and Labeling; Tartrate-Resistant Acid Phosphatase; Temperature

Cinacalcet, an allosteric modulator of a calcium (Ca)-sensing receptor, significantly suppresses parathyroid hormone (PTH) secretion and bone turnover rate in chronic hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). In this study, bone metabolism after cinacalcet treatment was examined, because hungry bone syndrome is sometimes experienced after parathyroidectomy in severe SHPT. We conducted a prospective observational study in 17 HD patients with SHPT. Cinacalcet was started at 25 mg/day, and the dose was increased step by step based on serum calcium level. A significant decrease in serum Ca and intact PTH concentration was found within 2 weeks. Tartrate-resistant acid phosphatase 5b, a good bone resorption marker, was significantly decreased at week 2 of the study. Serum bone alkaline phosphatase, a marker of bone formation, was increased at week 2 compared with the basal level. It became, however, gradually decreased until week 14. Only one patient whose bone turnover was considerably high had a mild numbness feeling. These results suggest that cinacalcet treatment might transiently accelerate bone formation with rapid suppression of bone resorption. This uncoupling could be involved in a mechanism by which cinacalcet decreases serum Ca level.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Regeneration; Bone Remodeling; Bone Resorption; Calcium; Cinacalcet; Drug Administration Schedule; Female; Hormone Antagonists; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Male; Middle Aged; Naphthalenes; Parathyroid Hormone; Phosphorus; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Time Factors

To evaluate whether Pakistanis have increased bone turnover compared with ethnic Norwegians due to their high prevalence of vitamin D deficiency and secondary hyperparathyroidism, and whether the relation between bone turnover and bone mineral density (BMD) differs between Pakistanis and ethnic Norwegians.. A cross-sectional, population-based study conducted in the city of Oslo in 2000-2001. Random samples of 132 community-dwelling Pakistani men and women of ages 40, 45, and 59-60 years, and 580 community-dwelling Norwegian men and women of ages 45 and 59-60 years are included in this substudy.. Venous serum samples were drawn for measurements of markers of the vitamin D endocrine system and the bone turnover markers osteocalcin (s-OC), bone alkaline phosphatase (s-bone ALP), and tartrate-resistant acid phosphatase (s-TRACP). BMD was measured at the forearm by single-energy X-ray absorptiometry.. Pakistanis had higher s-bone ALP compared with Norwegians. Mean (95% CI) age-adjusted levels were 22.5 (21.0, 24.1) U/l in Pakistani men versus 19.3 (18.6, 20.1) U/l in Norwegian men, P < 0.0005, and 20.3 (18.4, 22.1) U/l in Pakistani women versus 16.7 (16.0, 17.4) U/l in Norwegian women, P = 0.001. There tended to be an inverse association between bone turnover and BMD in men and women of both ethnic groups, and it was strongest for s-bone ALP. Overall mean (95% CI) distal BMD decrease was -16 (-20, -11) mg/cm(2) per 1 s.d. increase in s-bone ALP (P < 0.0005) when adjusting for age, sex, and ethnicity.. Except for somewhat higher s-bone ALP levels in Pakistanis, there were only minor ethnic differences in bone turnover, despite a strikingly different prevalence of secondary hyperparathyroidism. Bone turnover was inversely associated with forearm BMD in both ethnic groups.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Density; Bone Resorption; Cross-Sectional Studies; Female; Forearm; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Male; Middle Aged; Norway; Osteocalcin; Osteogenesis; Pakistan; Tartrate-Resistant Acid Phosphatase; Vitamin D Deficiency

Tartrate-resistant acid phosphatase (TRAP) is known as a marker of bone resorption. The purpose of this study was the development of a sensitive and specific immunoassay for TRAP.. We have developed two types of immunoassays, enzyme-linked immunosorbent assay (ELISA) and immunoselective enzyme immunoassay (ISEA) using monoclonal antibodies to recombinant TRAP, for determination of TRAP in human serum. To evaluate assay performance, recovery and dilution tests were performed. Further, we determined serum TRAP levels of patients with secondary hyperparathyroidism at different pH conditions.. The detected ranges of ELISA and ISEA were between 0.08 and 5 microg/l and between 0.063 and 4 U/l. Different concentrations of TRAP added were recovered on average at 98.0% in ELISA and 102.9% in ISEA. In the serial dilution test, serum TRAP levels were on average at 101.6% and 109.6% of the expected values in ELISA and ISEA, respectively. The serum TRAP levels of patients with secondary hyperparathyroidism were significantly higher than those of normal controls in ELISA and ISEA. Similar TRAP levels were obtained in the conditions at pH 5.5 and 6.1 in ISEA.. The present findings suggest that our assay methods are applicable for clinical tests, and strengthen the idea that serum TRAP is useful as a marker for bone resorption.

Topics: Acid Phosphatase; Adult; Animals; Antibodies, Monoclonal; Cell Line; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hybridomas; Hyperparathyroidism, Secondary; Immunoassay; Immunoenzyme Techniques; Isoenzymes; Male; Mice; Mice, Inbred BALB C; Recombinant Proteins; Tartrate-Resistant Acid Phosphatase; Uremia

Very few studies have evaluated both parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D] and their effects on bone mass in children.. We studied the associations of serum 25(OH)D and intact PTH (iPTH) with bone mineral content (BMC) and bone mineral density (BMD) at different bone sites and the relation between serum 25(OH)D and iPTH in early pubertal and prepubertal Finnish girls.. The subjects were 10-12-y-old girls (n = 193) at Tanner stage 1 or 2, who reported a mean (+/- SD) dietary calcium intake of 733 +/- 288 mg/d. 25(OH)D, iPTH, tartrate-resistant acid phosphatase 5b (TRAP 5b), urinary calcium excretion, BMC, areal BMD, and volumetric BMD were assessed by using different methods.. Thirty-two percent of the girls were vitamin D deficient [serum 25(OH)D < or = 25 nmol/L], and 46% of the girls had an insufficient concentration (26-40 nmol/L). iPTH and TRAP 5b concentrations were significantly higher in the deficient group than in the insufficient and sufficient groups [iPTH: 43.9 +/- 15.7 compared with 38.6 +/- 11.2 pg/L (P = 0.049) and 32.7 +/- 12.1 pg/L (P < 0.001), respectively; TRAP 5b: 12.2 +/- 2.9 compared with 11.0 +/- 2.8 U/L (P = 0.009) and 10.9 +/- 1.9 U/L (P = 0.006), respectively]. The girls in the deficient group also had significantly lower cortical volumetric BMD of the distal radius (P < 0.001) and tibia shaft (P = 0.002). High iPTH concentrations were also associated with low total-body apparent mineral density and urinary calcium excretion (P < 0.007).. Vitamin D-deficient girls have low cortical BMD and high iPTH concentrations, which are consistent with secondary hyperparathyroidism. A low vitamin D concentration accompanied by high bone resorption (TRAP 5b) may limit the accretion of bone mass in young girls.

Topics: Acid Phosphatase; Biomarkers; Bone Density; Bone Resorption; Calcium; Calcium, Dietary; Child; Cross-Sectional Studies; Female; Finland; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Parathyroid Hormone; Puberty; Seasons; Tartrate-Resistant Acid Phosphatase; Vitamin D; Vitamin D Deficiency

Serum levels of the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the carboxy-terminal propeptide of type I procollagen (PICP) were measured in 95 patients with renal hyperparathyroidism who had undergone a total parathyroidectomy and autotransplantation of a small portion of the resected gland. The results were compared with the serum levels of other bone metabolic markers and bone mineral densities in the distal radius (R-BMD) and lumbar vertebrae (L-BMD), which were measured by dual energy x-ray absorptiometry and converted to the percentage of the mean value of sex- and age-matched healthy controls. The preoperative mean values of ICTP and PICP were 142.4 ng/ml and 187.8 ng/ml, respectively. Although the serum levels of PICP levels exceeded the normal range in 42.1% of the patients, those of ICTP exceeded it in all of them. The serum levels of ICTP correlated positively not only with those of tartrate-resistant acid phosphatase (TRACP), total alkaline phosphatase (ALP), and osteocalcin but also negatively with the values of %R-BMD and %L-BMD and seemed to manifest specifically the disturbance of bone metabolism. On the other hand, the serum levels of PICP correlated with those of ALP and TRACP but not with values of %BMDs. After surgery, the serum levels of ICTP decreased gradually, but those of PICP increased immediately up to peak values at 7 days and then decreased gradually after 14 days, reaching the normal range at 3 months. These changes in the bone metabolic markers seemed to reflect the change in bone metabolism that was converting from bone resorption to bone formation. The percent change in the PICP/ICTP ratio at 7 days correlated significantly with the percent change in R-BMD at 12 months, and it was suggested that postoperative bone gain might be predicted using a combination of postoperative changes in PICP and ICTP.

Topics: Absorptiometry, Photon; Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Density; Bone Resorption; Case-Control Studies; Collagen; Collagen Type I; Female; Forecasting; Humans; Hyperparathyroidism, Secondary; Isoenzymes; Kidney Failure, Chronic; Lumbar Vertebrae; Male; Middle Aged; Osteocalcin; Osteogenesis; Parathyroid Glands; Parathyroidectomy; Peptide Fragments; Peptides; Procollagen; Radius; Tartrate-Resistant Acid Phosphatase; Transplantation, Autologous

The effects of internal treatment were compared with those of surgical procedures on secondary hyperparathyroidism as a complication of chronic renal failure patients in order to study their applications and problems. Maintenance hemodialysis patients complicated with 2HPT were selected as test subjects. The following internal treatment was administered. 1) Elcitonine to 6 cases and 2) Ipriflavon to 5 cases respectively and applied 3) pulse therapy of 1.25(OH)2D3 to 12 cases. On the other hand, total parathyroidectomy and autotransplantation were carried out as surgical procedures. The results of the treatment were evaluated by comparing serological data including tartrate resistant acid phosphatase (TAP) measured with the passage of time, bone scintigram findings, and change of bone mineral content (BMC) measured by single photon absorptiometry and dual photon absorptiometry. In the pulse therapy group, an oral tolerance test of 6 micrograms of 1.25(OH)2D3 was carried out to investigate its relation to long term prognosis. Furthermore, in both the pulse therapy group and PTX group, serum aluminum (A1) and delta A1 calculated by Defferoxamine (DFO) tolerance test were measured. The results are as follows. 1) In Elcitonine and Ipriflavon administration groups, increase of ALP and PTH and decrease of BMC (p less than 0.05) were recognized. 2) In the pulse therapy group, although the patients with PTH-C less than 30 ng/ml showed decrease in PTH both in short and long terms, cases with PTH-C more than 30 ng/ml kept the same level in PTH. Regardless of the change of PTH and ALP, there was no significant change observed in BMC. 3) In the PTX group, ALP/TAP ratio rose by 900% temporarily and BMC increased (p less than 0.01) in all regions measured. 4) Serum A1 and delta A1 were decreased (p less than 0.01) in PTX cases and in the pulse therapy cases in which ALP was decreased. In recent years, internal treatments on 2HPT patients have become diversified. However, exacerbation of 2HPT considered as an escape phenomenon caused the decrease in BMC after exclusive calcitonine preparatives administration. Pulse therapy, which is regarded at present as most effective in reducing PTH, ALP, did not work to increase BMC efficiently. In other word, in order to attain efficient BMC increase action, it is necessary to transfer from bone resorption phase to formative phase rapidly with drastic decrease of PTH and TAP observed in PTX.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Acid Phosphatase; Alkaline Phosphatase; Aluminum; Bone Density; Calcitonin; Calcitriol; Drug Administration Schedule; Drug Evaluation; Humans; Hyperparathyroidism, Secondary; Isoflavones; Kidney Failure, Chronic; Parathyroid Hormone