Prevalence Of Adynamic Bone Disease Research Articles

Prevalence and biochemical profile of adynamic bone disease in a hemodialysis population

Introduction and Aim: The number of patients suffering from end stage renal disease (ESRD) requiring dialysis has increased worldwide. Mineral bone disorders (MBD) commonly occur in ESRD patients. MBD is classified into high turnover bone disease and low turnover bone disease. Biochemical parameters play a key role in classifying MBD. Data on adynamic bone disease (ABD) in hemodialysis (HD) patients is sparse. The aim is to study the prevalence and biochemical profile of ABD in hemodialysis patients. Materials and Methods: This study was done as a cross sectional study in HD patients of a tertiary care hospital in South India. Baseline demographic data of the study population was collected. Biochemical data such as serum creatinine, blood urea nitrogen (BUN), bone markers for the diagnosis of CKD-MBD including serum calcium, phosphorus, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were collected. Based on the biochemical values, patients who had parameters suggestive of ABD were grouped as a separate cohort. Prevalence of ABD was calculated. Descriptive analysis of ABD cohort was done. Correlation of various bone markers with iPTH was carried out. Results: The study population (n=150) included 96 male (64%) and 54 female (36%) HD patients. The mean age of the study population is 54.54±14.81 years. 32.7% (n=49) of our study population had ABD. Serum calcium was found to be significantly higher in the ABD group. ALP and phosphorus were significantly lower in the ABD group. Conclusion: The prevalence of ABD in our HD population was 32.7%. The prevalence of ABD was the same among males and females. There was significant correlation of iPTH levels with ALP, calcium, and phosphorus levels.

Prevalence of Adynamic Bone Disease among Hemodialysis Patients

Objective: Aim of current study is to determine the association of adynamic bone disease among patients of hemodialysis. Study Design: Cross sectional Place and Duration: Institute of Kidney Diseases Hayatabad Peshawar during the period from January 2021 to June 2021. Methods: There were 82 patients of both genders had chronic kidney disease were presented. Patients on maintenance HD had their treatments administered by a Fresenius machine 4008S connected to a polysulfone membrane dialyzer and a dialysate solution comprising 32 mmol/L of bicarbonate and 1.75 mmol/L of calcium. All of the patients in the study had been on dialysis for over a year, and none of them had any signs of acute sickness or active liver disease. SPSS 22.0 was used to analyze all data. Results: Mean age of the patients was 43.4±8.26 years and had mean BMI 22.4±6.30 kg/m2. There were 48 (58.5%) males and 34 (41.5%) females. Mean duration of hemodialysis was 4.6±5.19 years. Frequency of DM was found in 24 (29.3%) cases. Frequency of vitamin D therapy was found in 55 (67.1%) cases. We found that 29 (35.4%) patients had adynamic bone disease and 21 (25.6%) cases had hyperparathyroidism. Significantly higher number of patients had bone pain among all cases. Conclusion: We concluded in this study that the prevalence of adynamic bone disease was 35.4%. Among patients of ABD most were ages between 25-45 years and were males with severe bone pain. Keywords: Hemodialysis, Diabetes Mellitus, Adynamic Bone Disease, Hyperparathyroidism

Adynamic bone disease: Revisited

The bone and mineral disorders form an integral part of the management of a chronic kidney disease (CKD) patient. Amongst various types of bone pathologies in chronic kidney disease-mineral bone disorder (CKD-MBD), the prevalence of adynamic bone disease (ABD) is increasing. The present review discusses the updated pathophysiology, risk factors, and management of this disorder.

Adynamic bone disease: Revisited

The bone and mineral disorders form an integral part of the management of a chronic kidney disease (CKD) patient. Amongst various types of bone pathologies in chronic kidney disease-mineral bone disorder (CKD-MBD), the prevalence of adynamic bone disease (ABD) is increasing. The present review discusses the updated pathophysiology, risk factors, and management of this disorder.

Understanding Bone Disease in Patients with Diabetic Kidney Disease: a Narrative Review.

Both diabetes and kidney disease associate with the development of bone disease and an increased risk of fragility fractures. The etiologies of bone disease in patients with diabetic kidney disease (DKD) are multiple and complex. This review explores the association between DKD and bone disease and discusses how the presence of both diabetes and kidney disease may impair bone quality and increase fracture risk. Diagnostic tools as well as future research areas are also discussed. Patients with DKD have an increased risk of fragility fracture, most pronounced in patients with type 1 diabetes, and in DKD a high prevalence of adynamic bone disease is found. Recent studies have demonstrated disturbances in the interplay between bone regulating factors in DKD, such as relative hypoparathyroidism and alterations of bone-derived hormones including fibroblast growth factor-23 (FGF-23), sclerostin and klotho, which lead to bone disease. This review examines the current knowledge on bone disease in patients with DKD, clinical considerations for patient care, as well as subjects for future research.

New peritoneal dialysates, for which benefits ?

The ideal peritoneal dialysis solution should allow efficient withdrawal of waste products of the metabolism and water and solutes equilibrium with minimal side effects for the patient and the peritoneal membrane. Glucose degradation products (GDP) resulting from the manufacturing process play a major toxic role and new biocompatible PD solutions with low GDP content and a more physiological bicarbonate or bicarbonate/lactate buffer have brought a clear benefit in experimental studies; however, in clinical cohorts and meta-analysis, the benefits of these solutions appear limited to better preservation of residual renal function and of diuresis. Glucose is the principal osmotic agent although hypertonic glucose solutions have a deleterious effect on PD, and their use should be restrained. Dialysate concentrations of sodium, calcium and magnesium are close to plasma; their diffusive transport is thus limited and their net peritoneal transport mainly depends on the ultrafiltration volume. A dialysate calcium concentration above 1.25 mmol/l generates a calcium load which may contribute to the high prevalence of adynamic bone disease in PD patients; this should be avoided. Low sodium dialysis solutions experimentally improve sodium diffusive transport and extraction in PD patients; the clinical benefit of this approach has to be confirmed.

Osteoporosis in patients with diabetes after kidney transplantation.

Preexisting diabetes increases risk of fractures after kidney transplantation (KT). However, little is known about mechanisms and prevention of increased fragility in these patients. Pathophysiology of osteoporosis after KT is complex and characterized by high prevalence of adynamic bone disease. Despite high prevalence of preexisting diabetes in KT recipients, diabetes patients were underrepresented in the studies that explored mechanisms and treatments of osteoporosis after KT. Therefore, caution should be exercised before considering conventional fracture prevention strategies in this unique group of patients. Many traditional osteoporosis medications reduce bone turnover and, hence, can be ineffective or even harmful in diabetic patients after KT. Contrary to predictions, evidence from the studies conducted in mostly non-diabetic subjects demonstrated that bisphosphonates failed to reduce fracture rates after KT. Therefore, bisphosphonates use should be limited in diabetic patients until more evidence supporting their post-transplant efficacy is available. We recommend the following strategies that may help reduce fracture risk in diabetes subjects after KT such as adequate management of calcium, parathyroid hormone, and vitamin D levels, optimization of glycemic control, use of steroid-sparing immunosuppressive regimens, and fall prevention.

Treatment of adynamic bone disease in a haemodialysis patient with teriparatide.

Prevalence of adynamic bone disease (ABD), characterized by low bone turnover and absence or a reduced number of osteoblasts and osteoclasts, is increasing steadily over the last years. We present a dialysis patient, with recurrent bone fractures and biopsy-proven ABD, who was treated with teriparatide. Nine months after initiation of treatment, iPTH plasma levels increased to 520 pg/mL and a second bone biopsy revealed high bone turnover, normal mineralization and normal bone volume. Two years later, iPTH was 250–350 pg/dL and bone metabolism parameters within normal range. The probable utility of teriparatide in the treatment of ABD in dialysis patients is discussed.

Non Invasive Diagnosis to Predict Adynamic Bone Disease in Haemodialysed Patients

Precise evaluation of the underlying type of bone disease in hemodialysed patients frequently requires bone histomorphometry (including static and kinetic variables after double tetracycline labeling) which is an invasive and costly method. Due to the prevalence of adynamic bone disease in hemodialysis patients, different biochemical non invasive markers such as (serum intact osteocalcin, serum intact parathyroid hormone (iPTH) and bone specific alkaline phospha- tase (bAP) have been shown to be helpful in differentiation between low and high bone turnover. Our study was conducted to detect the usefulness of measuring serum intact osteocalcin and its correlation with serum iPTH and bAP to distinguish adynamic bone disease from other forms of renal osteodystrophy in hemodialysed patients. The study included 60 patients and 20 normal control subjects, presented at renal dialysis units, Ain Shams University hospitals. The hemodialysed patients were classified according to the results serum iPTH and bAP into two groups :  Group I : Included 18 patients (30%) with serum iPTH level 150 pg/ml and serum bAP  27 ng/ml.  Group II : Included 42 patients (70%) with serum iPTH level > 150 pg/ml and serum bAP > 27 ng/ml. The serum level of intact osteocalcin was measured for the control group and for all hemodialysed patients. The results revealed highly significant stastical differences in serum level of intact osteocalcin between all patients group and the control subjects being lower in control group. Also, the results revelaed that 30% of all patients group had adynamic bone disease and comparison between serum level of intact osteocalcin in adynamic bone disease group versus other patients group was highly significant, being higher in other patients group. There was no significant difference between adynamic bone disease patients and other patients as regard serum phosphorus, and serum calcium but there was a sigificant difference as regard age, while highly significant difference as regard sex, duration of hemodialysis, serum intact osteocalin, iPTH and bAP. These results suggest that combined estimation of serum iPTH, serum intact osteocalcin, and bAP can provide a useful information on the bone status in uremic patients and repesent reliable non invasive diagnostic tools for the prediction of adynamic bone disease.

The importance of bone health in end-stage renal disease: out of the frying pan, into the fire?

In the early stages of renal failure, hyperparathyroidism develops as a compensatory mechanism to control serum levels of calcium, phosphorus and calcitriol. As kidney disease progresses, this ability to maintain mineral homeostasis is lost, leading to the development of renal osteodystrophy (ROD). Over the past decade, the pattern of ROD seen in patients with chronic kidney disease (CKD) has changed. Previously, the majority of patients had mixed uraemic osteodystrophy or aluminium-related osteomalacia. The decreased use of aluminium-based phosphate binders, coupled with improvements in the management of hyperphosphataemia, led to a reduction in the prevalence of these types of ROD. Since the mid-1990s, there has been an increase in the prevalence of adynamic bone disease as a result of increased suppression of parathyroid hormone through the use of calcium-based phosphate binders and calcitriol therapy. Adynamic bone disease is also associated with several clinical factors, such as older age, use of continuous ambulatory peritoneal dialysis and the presence of diabetes mellitus, as well as the use of calcitriol therapy. Studies of calcium metabolism in patients with CKD have shown that adynamic bone disease is a distinct clinical condition that leads to hypercalcaemia via mechanisms different from that seen in high-turnover bone disease. As high calcium x phosphorus product has been associated with soft tissue and vascular calcifications, and increased mortality, optimizing bone health may be an important way of reducing cardiovascular risk in patients with CKD. To do this, novel, effective, non-calcium, non-aluminium phosphate binders will be necessary.

Renal Osteodystrophy in Predialysis and Hemodialysis Patients: Comparison of Histologic Patterns and Diagnostic Predictivity of Intact PTH

Background: Comparison of renal osteodystrophy in predialysis and hemodialysis has been rarely reported. Distinct patterns of renal osteodystrophy could be found in these conditions. In addition the use of parathyroid hormone (PTH) and other markers for noninvasive diagnosis may result in different predictive values in predialysis and hemodialysis patients. Methods: 79 consecutive patients with conservative chronic renal failure and 107 patients on hemodialysis were studied. All patients were subjected to bone biopsy for histological and histomorphometric evaluation. The patients had no exposure to aluminium before dialysis and relatively low exposure while on hemodialysis. Results: In the predialysis patients, bone biopsies showed 9 cases of adynamic bone disease (ABD) and 8 cases of osteomalacia (OM), 50 patients with mixed osteodystrophy and 2 cases of hyperparathyroidism. Among the hemodialysis patients 12 cases had ABD, 3 cases OM, 30 mixed osteodystrophy, and 61 patients hyperparathyroidism. In the predialysis patients with chronic renal failure, bone aluminium was on average 4.5 mg/kg dry weight, while in dialysis patients the average value was 35.4 mg/kg dry weight. Discriminant analysis of low turnover osteodystrophy (ABD and OM) by intact PTH showed higher accuracy in dialysis than in predialysis patients. Correlation studies of intact PTH versus bone formation rate, osteoblast surface/bone surface and osteoclast surface/bone surface showed significantly steeper slopes in dialysis than in predialysis patients, which indicates that bone resistance to PTH is more marked in predialysis patients. Conclusions: The prevalence of ABD and OM in the geographic area investigated is lower than in other reports. Aluminium exposure does not seem to be the cause of low turnover osteodystrophy in the present population. The predictive value of intact PTH in the noninvasive diagnosis of renal bone disease is higher in hemodialysis patients than in predialysis patients. Predialysis chronic renal failure, when compared to the dialysis stage, seems to be characterized by resistance of bone tissue to PTH.

Parathormone secretion in peritoneal dialysis patients with adynamic bone disease

The prevalence of low-turnover lesions in patients undergoing peritoneal dialysis (PD) is high. Our aims are to evaluate the prevalence of adynamic bone disease (ABD) in PD patients, analyze risk factors, and define the association of serum parathyroid hormone (PTH) levels measured under different plasma calcium concentrations with this lesion. Fifty-seven patients were studied by bone biopsy (BB). ABD was found in 63.2%, and 36.8% showed high-turnover bone disease (HTBD). Patients with HTBD had a lower prevalence of diabetes, younger age, lower accumulated oral calcium salt intake, and greater calcitriol doses, serum osteocalcin level, and ultrafiltration than patients with ABD. Both mean baseline PTH levels from the previous year and PTH level at time of BB were greater in patients with HTBD than those with ABD (357 ± 267 pg/mL versus 89 ± 67 pg/mL; 390 ± 337 pg/mL versus 88 ± 78 pg/mL, respectively; P < 0.05). However, the magnitude of the increase from baseline serum PTH levels in response to hypocalcemia was greater in patients with ABD than in those with HTBD (166.4% ± 134% versus 83.5% ± 73.6%; P < 0.05). We found that PTH levels less than 150 pg/mL in patients with ABD showed a sensitivity of 91.6%, specificity of 95.2%, and positive predictive value (PPV) of 97%. In the HTBD group, PTH levels greater than 450 pg/mL had a specificity and PPV of 100%. Our data confirm that ABD is the most prevalent lesion in PD patients, and PTH secretion capacity is maintained in these patients. The definitive diagnosis and management strategies for many patients requires a BB, especially when HTBD is unlikely.

Transferrin-mediated uptake of aluminium by human parathyroid cells results in reduced parathyroid hormone secretion.

The present study investigates whether aluminium-transferrin (Al-Tf) uptake by Tf receptor-mediated endocytosis induces hypoparathyroidism and thus might contribute to the increasing prevalence of adynamic bone disease (ABD) in the current dialysis population. Human parathyroid glands as well as in vitro cultured human parathyroid cells were shown to express Tf receptors. Five-day-old cultures of parathyroid cells were incubated for 48 h in serum-free DMEM/F12 supplemented with 12 microM apo-Tf: 12 microM Tf to which 150 microg/l Al or 150 microg/l Al-citrate (Al-ci) was bound. The amount of Al taken up by the parathyroid cells either as Al-Tf or Al-ci did not differ. However, incubation of cell cultures with Al-Tf showed a significant proportional decrease (mean+/-SEM, -23.1+/-4.5%) in iPTH secretion as compared to the reference apo-Tf cultures. Al-ci did not suppress PTH secretion (+3.4+/-6.5%). The Al uptake after incubation with Al-Tf was found to be dose-dependent. With regard to iPTH secretion, a tendency toward a dose response relationship was observed. Northern blot analysis of parathyroid cells incubated in 12 microM apo-Tf or 12 microM Al-Tf demonstrated that the PTH mRNA synthesis was unaffected by the Tf-mediated uptake of Al. These observations suggest an effect of Al on PTH release rather than on PTH synthesis. Since the cytoskeleton can play an important role in the release of secretory vesicles, the influence of Al on the structure of actin, beta-tubulin and vimentin was investigated by confocal microscopy. Comparison of cultures incubated with apo-Tf and Al-Tf revealed no difference in the organization of these cytoskeletal proteins in relation to the inhibitory effect of Al-Tf on PTH secretion. In summary, data in the present paper demonstrate that the (i) human parathyroid gland/parathyroid cells exhibit Tf receptors; (ii) Al-Tf complex is taken up by the parathyroid gland in a dose-dependent manner; and (iii) uptake of Al by Tf receptor-mediated endocytosis reduces the secretion of PTH but not its synthesis. These in vitro findings allow us to suggest that Tf receptor-mediated uptake of Al might, besides other factors such as vitamin D, high calcium dialysate or CaCO(3) intake, play a role in the development of hypoparathyroidism associated with ABD. The exact mechanism by which Al-Tf suppresses iPTH secretion remains to be elucidated.

Bone biopsy results and serum bone turnover parameters in uremic children

The aim of the study was to evaluate the prevalence of renal osteodystrophy types in children undergoing haemodialysis and continuous ambulatory peritoneal dialysis and to assess the usefulness of biochemical parameters in diagnosis of renal osteodystrophy. Bone biopsy and measurements of serum parathormone (iPTH) level, alkaline phosphatase (AP), osteocalcin (OC), procollagen 1C, calcium and phosphorus levels were performed in 51 children aged 11.5 +/- 2.9 y with end-stage renal failure. Renal osteodystrophy (ROD) was diagnosed as follows: adynamic bone disease (ABD) in 14 (27%); normal bone histology (NB) in 19 (37%), osteomalacia (OM) in 1 (2%), mixed lesion (Mix) in 5 (10%) and hyperparathyroidism (HP) in 12 (24%) children. There was no difference in prevalence of ROD types between children on CAPD and HD. We found significant differences in the mean value of iPTH, OC levels and AP activity in HP vs NB and HP vs ABD. The prevalence of ABD was significantly higher in patients with PTH below 50 pg/ml than in patients with PTH above 50 pg/ml (p < 0.05). In 69% of children with NB the iPTH level was between 50 and 150 pg/ml. Most HP cases (75%) were diagnosed in patients with iPTH above 200 pg/ml. A high correlation between BFR and iPTH, BFR and OC, AP levels was found. The biochemical markers of bone turnover have only limited value in the differentiation of renal osteodystrophy types.

Bone biopsy results and serum bone turnover parameters in uremic children

The aim of the study was to evaluate the prevalence of renal osteodystrophy types in children undergoing haemodialysis and continuous ambulatory peritoneal dialysis and to assess the usefulness of biochemical parameters in diagnosis of renal osteodystrophy. Bone biopsy and measurements of serum parathormone (iPTH) level, alkaline phosphatase (AP), osteocalcin (OC), procollagen 1C, calcium and phosphorus levels were performed in 51 children aged 11.5 ± 2.9y with end-stage renal failure. Renal osteodystrophy (ROD) was diagnosed as follows: adynamic bone disease (ABD) in 14 (27%); normal bone histology (NB) in 19 (37%), osteomalacia (OM) in 1 (2%), mixed lesion (Mix) in 5 (10%) and hyperparathyroidism (HP) in 12 (24%) children. There was no difference in prevalence of ROD types between children on CAPD and HD. We found significant differences in the mean value of iPTH, OC levels and AP activity in HP vs NB and HP vs ABD. The prevalence of ABD was significantly higher in patients with PTH below 50 pg/ml than in patients with PTH above 50 pg/ml (p < 0.05). In 69% of children with NB the iPTH level was between 50 and 150 pg/ml. Most HP cases (75%) were diagnosed in patients with iPTH above 200 pg/ml. A high correlation between BFR and iPTH, BFR and OC, AP levels was found. Conclusion: The biochemical markers of bone turnover have only limited value in the differentiation of renal osteodystrophy types.

High prevalence of adynamic bone disease diagnosed by biochemical markers in a wide sample of the European CAPD population.

Adynamic bone disease (ABD) has been described in the current dialysis population to have an unexpectedly high prevalence. Moreover, it is clearly more prevalent in CAPD patients, compared to haemodialysis patients. Recently we demonstrated that both a low (< or = 27 U/1) level of bone alkaline phosphatase (BAP) as determined by an optimized agarose gel electrophoretic technique and a low (< or = 150 pg/ml ) level of iPTH are good markers of ABD with sensitivities of 78.1% and 80.6% and specificities of 86.4% and 76.2% respectively. In this study (n = 212), the prevalence of ABD in the European CAPD population was evaluated by means of these biochemical markers. Clinical data on the patients included were recorded at the moment of blood sampling. In patients under CAPD treatment for longer than 9 months, we calculated an index of calcium exposure through PD fluid. In this population with a low exposure to aluminium, the prevalence of ABD as indicated by either a low level of BAP or PTH was 43%. The following risk factors could be identified: advanced age, shorter time on renal replacement therapy, male gender, and high calcium content of PD fluid. The index of calcium exposure was significantly higher in the patients with low BAP and low iPTH levels compared to those with either BAP > or = 27 U/1 or iPTH > 150 pg/ml. The latter finding gives further support to the hypothesis that a high calcium load administered to renal failure patients may lead to 'oversuppressed' parathyroids in ABD. In a subgroup of patients with a high level of BAP associated with a low iPTH level a profile previously shown to be associated in the presence of aluminium overload, significantly higher serum aluminium levels were noted. suggesting that even in patients with low exposure to aluminium, this element still can affect bone metabolism. A high prevalence of ABD--as diagnosed by biochemical markers--was observed in the European CAPD population. A number of risk factors could be put forward. The aetiology and pathogenesis of this type of renal osteodystrophy remain to be elucidated, but appear, however, to be multifactorial.

Adynamic bone disease: pathogenesis, diagnosis and clinical relevance.

In the past several years significant attention has been directed to the study of adynamic bone disease in uremic patients. Several reports have provided additional information about the prevalence of adynamic bone disease in different countries. It has now become clear that the pathogenesis of adynamic bone disease cannot be ascribed to one single aetiological factor, but rather to a host of complex factors. From recently published papers we have learned about the mechanism of downregulation of the parathyroid hormone/parathyroid hormone-related peptide receptor on osteoblast-like cells, which may be a very important step in the pathogenesis of adynamic bone disease. A provocative hypothesis attempts to link the widespread use of erythropoietin to the emergence of adynamic bone disease-lacking excessive aluminium accumulation. It appears from some studies that bone-specific alkaline phosphatase might become a valuable tool in differentiating high turnover from low/normal turnover bone disease; however, further studies are needed to establish the role of this marker in the diagnosis of adynamic bone disease. Several papers discussed the pros and cons of lowering the calcium concentration of the dialysate in order to prevent adynamic bone disease. The results of these studies help us to understand the pathogenesis and the clinical relevance of this lesion in attempts to provide better care for our patients.

Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in haemodialysis patients

Adynamic bone disease was recently described to be increasingly prevalent in the dialysis population. At present the diagnosis of this type of renal osteodystrophy can only be made by bone histomorphometry. We assessed the value of different biochemical serum markers in the diagnosis of adynamic bone disease.In 103 haemodialysis patients a bone biopsy was performed after double tetracycline labelling, and the serum levels of intact PTH, osteocalcin, and the bone isoenzyme of alkaline phosphatase were determined. Bone alkaline phosphatase was measured by an optimized agarose gel electrophoretic method, recently shown to have a high accuracy, precision and reproducibility, also in the lower range.In 38 (37%) of the patients the diagnosis of adynamic bone disease was histologically established. Constructing receiver operator curves optimal cut-off levels for the diagnosis of adynamic bone disease were determined, being <=27 U/litre for the bone isoenzyme of alkaline phosphatase, <=14 microg/litre for osteocalcin and <=150 pg/ml for intact PTH. Concentrations of bone alkaline phosphatase or intact PTH below these cut-off levels, were shown to be the best performing tests in the detection of adynamic bone disease as indicated by a sensitivity of 78.1 and 80.6% and a specificity of 86.4 and 76.2% respectively. Applying Bayes' theorema, it was calculated that in the current haemodialysis population in which a prevalence of adynamic bone disease up to 35% has been described, the positive predictive values for the proposed cut-off values are 75% for bone alkaline phosphatase, 65% for intact PTH and 55% for osteocalcin. Moreover, in this population, levels of bone alkaline phosphatase and intact PTH below the optimal cut-off excluded hyperparathyroid bone disease.In view of the relative easy and accurate methodology for bone alkaline phosphatase determination, the closer physiological link with osteoblast function and the lesser expense for its determination we suggest that this marker is a useful tool in the non-invasive diagnosis of the adynamic type of bone disease in the individual patient.

Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in haemodialysis patients

Adynamic bone disease was recently described to be increasingly prevalent in the dialysis population. At present the diagnosis of this type of renal osteodystrophy can only be made by bone histomorphometry. We assessed the value of different biochemical serum markers in the diagnosis of adynamic bone disease. In 103 haemodialysis patients a bone biopsy was performed after double tetracycline labelling, and the serum levels of intact PTH, osteocalcin, and the bone isoenzyme of alkaline phosphatase were determined. Bone alkaline phosphatase was measured by an optimized agarose gel electrophoretic method, recently shown to have a high accuracy, precision and reproducibility, also in the lower range. In 38 (37%) of the patients the diagnosis of adynamic bone disease was histologically established. Constructing receiver operator curves optimal cut-off levels for the diagnosis of adynamic bone disease were determined, being <=27 U/litre for the bone isoenzyme of alkaline phosphatase, <=14 microg/litre for osteocalcin and <=150 pg/ml for intact PTH. Concentrations of bone alkaline phosphatase or intact PTH below these cut-off levels, were shown to be the best performing tests in the detection of adynamic bone disease as indicated by a sensitivity of 78.1 and 80.6% and a specificity of 86.4 and 76.2% respectively. Applying Bayes' theorema, it was calculated that in the current haemodialysis population in which a prevalence of adynamic bone disease up to 35% has been described, the positive predictive values for the proposed cut-off values are 75% for bone alkaline phosphatase, 65% for intact PTH and 55% for osteocalcin. Moreover, in this population, levels of bone alkaline phosphatase and intact PTH below the optimal cut-off excluded hyperparathyroid bone disease. In view of the relative easy and accurate methodology for bone alkaline phosphatase determination, the closer physiological link with osteoblast function and the lesser expense for its determination we suggest that this marker is a useful tool in the non-invasive diagnosis of the adynamic type of bone disease in the individual patient.