[Bone alkaline phosphatase: characteristic and its clinical applications]. / Kostna frakcja fosfatazy alkalicznej: charakterstyka i przydatnosckliniczna jej oznaczania. doniesienie i.

Bone alkaline phosphatase (BALP) is one of the most frequently used biochemical markers of bone formation. The presented paper describes the enzyme's specificity, physiological values during normal growth and development as well as its clinical applications in various diseases. The main interest concerns the ability of BALP to predict bone loss in primary (postmenopausal and senile osteoporosis) and secondary osteoporosis associated with metabolic diseases (galactosemia, cystic fibrosis, celiac disease), renal osteodystrophy, Paget disease and others. The determination of BALP activity seems to be also helpful in diagnosis of the diseases and in monitoring of antiresorptive therapy. Further studies on BALP are needed to elucidate whether this bone formation marker reflect the therapy outcome of individual patients with primary osseus tumours and metastases.

Biochemical parameters of bone turnover in kidney transplant recipients.

Impairment of bone remodelling due to chronic renal failure persists even after successful kidney transplantation. Bone turnover was assessed in 22 kidney transplant recipients by measurement of serum bone markers: total (tALP) and bone alkaline phosphatase (bALP), osteocalcin (OC), procollagen I C-terminal propeptide (PICP), collagen I C-terminal telopeptide (ICTP), and iPTH. The patients were on dialysis 56.6 +/- 43.1 months before transplantation (mean +/- SD) and 34.2 +/- 23.0 months had elapsed after transplantation. The bone markers were within the reference range in 23% of patients for iPTH, 73% for tALP and 82% for bALP, 41% for OC, 73% for PICP and 50% for ICTP. A positive correlation was found between dialysis duration and ICTP, and iPTH and bone formation markers (OC, bALP). The obtained results indicate that bone turnover was increased after kidney transplantation, with prevailing bone resorption, which seems to be influenced by dialysis duration.

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 alkaline phosphatase isoenzyme in renal osteodystrophy.

Serum total alkaline phosphatase is the most commonly used biochemical marker of bone disease in renal patients, but alkaline phosphatase originates from different organs and sometimes lacks specificity. Bone isoenzyme measurement is considered superior to total alkaline phosphatase for the assessment of bone metabolism. We have studied the value of bone isoenzyme, determined by a new. IRMA (Tandem-R-Ostase), in haemodialysis patients with secondary hyperparathyroidism and renal osteodystrophy. Fifty-six haemodialysis patients were studied. Intact parathyroid hormone (PTH), osteocalcin, total alkaline phosphatase and bone alkaline phosphatase were determined. A transiliac bone biopsy was performed in 20 of the 56 patients after double tetracycline labelling. There was a significant correlation between bone alkaline phosphatase and PTH (r = 0.79, P < 0.001) and between bone and total alkaline phosphatase (r = 0.84, P < 0.001) in all patients. The patients who underwent a bone biopsy showed osteitis fibrosa in 17, mixed lesion in one, adynamic bone disease in one and normal bone in one. Bone alkaline phosphatase showed a significant correlation with static and dynamic histomorphometric indices similar to that obtained with PTH and better than those of total alkaline phosphatase and osteocalcin. It is concluded that bone alkaline phosphatase (ostase) seems to be a useful non-invasive marker of bone metabolism in patients on haemodialysis with high turnover bone disease. More studies are necessary to know its value in low turnover bone disease.

[Loss of bone substance in long-term dialysis--the value of serochemical parameters]. / Knochensubstanzverlust bei Langzeitdialyse--Wertigkeit serochemischer Parameter.

During long-term hemodialysis therapy a loss of bone substance--an osteopenia--may occur. The diagnosis is possible by bone biopsy. We have analyzed the bone metabolism-associated serochemical parameters in patients suffering from osteopenia in comparison with patients with normal bone volume. 21 patients were analyzed: 14 females, 7 males, duration of dialysis 44 +/- 29.9 months, age 47.3 +/- 12.5 years. The serum values of calcium, anorganic phosphate, alkaline phosphatase, pH and c-terminal parathormone are determined. The histological bone examination according to the Delling classification did show following distribution: Type I--0, type II--10, type III--10 (without renal osteopenia--1). A quarter of the patients did show a reduction of the bone mass. The parathormone value was significantly reduced in these patients in comparison with patients without osteopenia. No significant changes could observed in the comparison of alkaline phosphatase, serum calcium, anorganic phosphate and pH value. Our results show that in patients with osteopenia the serum parathormone level is reduced relatively.

Nature of mononuclear cells positive for acid phosphatase activity in bone marrow of patients with renal osteodystrophy.

Fifty two of 63 patients with renal osteodystrophy had one or more mononuclear cells positive for acid phosphatase in the marrow. These cells are also tartrate resistant and non-specific esterase negative, and are believed to be precursors to osteoclasts and other acid phosphatase positive cells resorbing bone on the trabecular surface.

Plasma levels of bone Gla-protein reflect bone formation in patients on chronic maintenance dialysis.

Predictive value of plasma levels of bone Gla-protein (BGP) for bone histology was evaluated in 30 chronically dialyzed patients. All patients underwent bone biopsies and serum biochemical parameters, including BGP, parathyroid hormone, and alkaline phosphatase; calcium and phosphate were measured at the time of biopsy. Bone histology showed renal osteodystrophy with low bone turnover and osteomalacia (LT-ROD) in 13 patients, and renal osteodystrophy with high bone turnover and prevailing hyperparathyroid bone disease (HT-ROD) in 17 patients. Values for BGP were above normal in LT-ROD (47.3 +/- 7.9 vs. 6.8 +/- 0.2 ng/ml) and extremely elevated in HT-ROD (831 +/- 170 ng/ml). Similar differences were not found with the other serum biochemical parameters, even though BGP correlated with parathyroid hormone (r = 0.64) and alkaline phosphatase (r = 0.85). There were significant correlations between BGP and cellular and non-cellular parameters of bone formation (r = 0.73 to 0.91). Weaker or no correlations were found between BGP and histologic parameters of bone, reflecting mainly mineralization or resorption. These correlations and the finding of significant differences in plasma BGP between LT-ROD and HT-ROD indicate that plasma levels of BGP reflect bone formation in uremia and predict underlying bone histology.

An investigation of biochemical and radiographic signs of hyperparathyroidism in chronic renal disease.

One hundred and twelve randomly selected patients with renal disease (22 on conservative treatment, 35 on haemodialysis and 55 with functioning kidney transplants) were subjected to a longitudinal and follow-up study of biochemical and radiographic signs of secondary hyperparathyroidism (HPT). Special interest was directed towards diagnostic criteria leading to the decision to perform parathyroid surgery, which had been undertaken in 18 patients. The five patients selected for parathyroidectomy while on conservative treatment were clearly distinguishable from the rest of the patients in this group, on the basis of hypercalcaemia, massive elevation of serum parathyroid hormone and radiographic abnormalities, findings which did not occur in patients in whom parathyroid surgery had not been considered. Six patients underwent parathyroidectomy while on haemodialysis. Preoperatively hypercalcaemia was observed in five and this was the only finding separating these patients from non-operated patients. Radiographic abnormalities were observed in only one operated patient. After kidney transplantation, long-standing hypercalcaemia was observed in 27% of patients. Seven patients underwent parathyroidectomy, hypercalcaemia being the indication for surgery in all cases. Hypercalcaemic patients could not be separated from normocalcaemic patients regarding any other determined biochemical variable, or regarding the incidence of osteonecrosis of weight-bearing joints, which was found in 18% of transplanted patients, and which was the only cause of major symptomatic bone disease observed in this study. The findings of hypercalcaemia as a major deciding factor for parathyroid surgery, a low incidence of radiographic bone disease, and absence of major symptomatic bone disease referable to HPT, are in keeping with a more liberal attitude to parathyroidectomy in chronic renal disease than has been stated in other recent reports. With a more expectant attitude and with more active medical treatment some of the operations performed on the patients in this study might have been avoided but, in general, the favourable outcome after surgery and the low overall incidence of clinical problems referable to bone disease at our unit would seem to support our active approach to parathyroid surgery.

Serum alkaline phosphatase in azotemic and hemodialysis osteodystrophy: a study of isoenzyme patterns, their correlation with bone histology, and their changes in response to treatment with 1alphaOHD3 and 1,25(OH)2D3.

One hundren seventy-eight azotemic patients, 114 on hemodialysis, had measurements of total serum ALP, and definition of isoenzyme patterns on acrylamide gel electrophoresis. In addition, bone histomorphometry was defined in all of the patients by means of transiliac bone biopsies. Serial estimations over 2 years were carried out on several patients, including some being treated with vitamin D2, 1alphaOHD3, and 1,25(OH)2D3. (1) In both nondialyzed and dialyzed patients, serum ALP showed a significant positive correlation with osteitis fibrosa due to secondary hyperparathyroidism irrespective of the presence or absence of concurrent osteomalacia. Increases in the bone isoenzyme were largely responsible for the rise in total ALP. (2) A higher incidence of osteomalacia (p less than 0.001) was observed in patients on hemodialysis in Newcastle Upon Tyne. In hemodialyzed patients where osteomalacia was accompanied by either no secondary hyperparathyroidism (21 patients) or minimal secondary hyperparathyroidism (14 patients), serum ALP remained within normal limits, giving no indication of the existing osteomalacic bone disease. Isoenzyme studies revealed a high prevalence of the intestinal type and also varied combinations of hepatic, intestinal, and bone types. (3) Good response to vitamin D depended on the presence of significant amounts of the bone isoenzyme. Azotemic osteodystrophy characterized by a raised serum ALP and a prominent bone isoenzyme predicted a good response to vitamin D, and the decrease in serum ALP following vitamin D was the result of a reduction in the bone isoenzyme. Patients with symptomatic dialysis osteomalacic bone disease, accompanied by normal total serum ALP and no elevation of the bone isoenzyme, responded less well.

[Immunoreactive parathyroid hormone, 25-hydroxycalciferol and bone histology in renal osteodystrophy (author's transl)]. / Immunoreaktives Parathormon, 25-Hydroxycalciferol und Knochenhistologie bei renaler Osteopathie

Immunoreactive parathyroid hormone (iPTH) and 25-hydroxycalciferol (25(OH)D) serum levels were determined in 32 patients with renal osteopathy, they were correlated with the results of bone biopsy and other clinical parameters. iPTH was closely related to bone histology, it did not correspond to serum calcium and alkaline phosphatase, but the correlation to serum phosphate was statistically significant. 25(OH)D levels were not related to the histological findings of osteomalacia or increased bone resorption, while a correlation between the vitamin D metabolite and serum calcium could be observed. Since iPTH and 25(OH)D levels exhibited a significant correlation, an inhibitory effect of 25(OH)D on parathyroid gland function in renal failure was discussed.