Aplastic Bone Disease Research Articles

Fragility Fractures in Hemodialysis Patients. Uremic bone disease:the effect of medical treatment until now.

In the 1970s, severe osteoarticular lesion appeared to the patients from a relatively early stage after initiation of dialysis. It was recognized as dialysis osteodystrophy and was an important threat of the patients. The main causes of the lesion were osteitis fibrosa due to secondary hyperparathyroidism and osteomalacia including an aluminum bone disease. But it is now occasional to encounter these typical bone lesion by the development of subsequent active vitamin D preparation, a non-calcium-containing phosphate binder and calcimimetics, and the complete removal of aluminum from the dialysis field. However, ectopic calcification due to aplastic bone disease and the progression of osteoporosis with the aging population are the upcoming problems. To overcome these problems, researches for pathophysiology and mechanism, establishment of the management tools and the development of effective drug are expected.

Clinical Outcomes of Recipients With Aplastic Bone Disease After Renal Transplantation

ObjectivesWe expect that if chronic renal failure (CRF) is improved after renal transplantation (RTx), dialysis osteopathy bone lesions would also recover to normal. Nevertheless, it is controversial whether bone lesions really improve after RTx. In this study, we evaluated whether pathological dialysis osteopathy improved after RTx. Materials and MethodsThe 84 patients who had undergone living related RTx had also undergone a bone biopsy (Bx) since January 2004, including 13 (16.0%) with a diagnosis of aplastic osteopathy. They included 7 men and 6 women. The average hemodialysis (HD) period was 40.3 months. The immunosuppression was tacrolimus (FK); mycophenalate mofetil (MMF) and steroid. We examined Ca, P, intact-PTH (i-PTH), metabolic bone markers, and bone density (DXA) before and 1 year after RTx. In addition, a Bx was performed after having osteal labeling twice before Bx. In addition 2 cases (15.3%) also underwent a Bx after RTx. ResultsAll cases survive with well functioning renal grafts. The mean levels of Ca and P before RTx were 8.7 mg/mL and 6.6 mg/dL, respectively. The mean i-PTH level was 137.8 pg/mL before RTx and of alkaline phosphatase (ALP) was 202.1 U/L before RTx. The total density and % age match of DXA before RTx averaged 398.7 mg/ccm and 96.7%, respectively. The mean bone volume fraction (BV/TV: Bone Volume/Tissue Volume) before RTx was 17.2%. The mean osteoid volume (OV/TV) before RTx was 2.7%. The mean fibrosis volume (Fb.V/TV) before RTx was 0%. The mean bone formation rate (BFR/BV) before RTx was 2.1 %/y. Two cases were also pathologically diagnosed as renal osteodystrophy at 1 year after RTx: 1 case was mixed type, and another was osteomalacia, which was accompanied by a lumbar compression fracture (Fx) during the clinical course. ConclusionsBone metabolism in patients with aplastic ROD histologically improved at 1 year after RTx, presumably due to good renal transplant function. However, it is unknown whether both hypophosphatemia and decrease of FGF-23 improved bone However, patients with aplastic ROD were not completely normalized histologically at 1 year after RTx.

Intact Parathyroid Hormone in Egyptian Type 2 Diabetics with Chronic Hemodialysis: Impact of Glycaemic Control

Osteodystrophy is one of the long-term haemodialysis complications. In diabetic end stage renal failure patients, it mainly occurs as an aplastic or low-turnover bone disease due to their low serum intact parathyroid hormone (iPTH) levels. The aim of the present study is to evaluate intact PTH level in in Egyptian type 2 diabetics with chronic hemodialysis and its relation to glycaemic control .patients. 140 Egyptian patients, their mean age was 60.4 ± 10.6 years were evaluated. They were maintained on regular hemodialysis (HD); 3 times/week, and the patients were divided into two groups according to primary kidney disease, diabetic (98 patients) and non-diabetic (42 patients) groups. Diabetic group was furtherly subdivided according to glycated hemoglobin to controlled (32 patients) and non-controlled diabetics (66 patients). Intact parathyroid hormone (iPTH), glycated hemoglobin (HbA1c), serum bone specific alkaline phosphatase, Albumin, Glucose, calcium, phosphorus and magnesium were estimated. Urea reduction ratio (URR) was estimated to evaluate the hemodialysis adequacy. The diabetic group had significantly lower values of iPTH and serum magnesium than non-diabetic group (p < 0.03 and p < 0.001 respectively). The uncontrolled diabetics had significantly lower values of iPTH, serum magnesium and serum albumin (p < 0.002, p < 0.002& p < 0.03 respectively) than the controlled group. The serum HbA1c levels were strongly correlated with the serum iPTH levels (P < 0.003). intact PTH was lower in diabetic hemodialysis patients; also, glycaemic control was associated with higher PTH levels.

Diagnosis of renal osteodystrophy

Chronic Kidney Disease (CKD) is commonly associated with alterations in bone and mineral metabolism (renal osteodystrophy). To date, bone biopsy remains the gold standard for the diagnosis and classification of the various types of renal osteodystrophy, namely: osteitis fibrosa, mixed uremic osteodystrophy, osteomalacia, aplastic and adynamic bone disease. However, due to its invasive nature and the fact that it is quite expensive, there has been a clamor for a search for other tests. Traditionally, the level of parathyroid hormone (PTH) has been considered a surrogate of bone turnover. At this time, the search continues for a specific and sensitive biochemical marker for monitoring bone turnover in CKD., e.g., alkaline phosphatase, osteocalcin, collagen degradation products, etc. In this chapter, we also present the common radiographic findings that are commonly seen in patients with renal osteodystrophy. Other radiographic techniques such as, dual energy x-ray absorptiometry (DEXA) and deferoxamine challenge test (DFO) are also briefly discussed.

Variant of Adynamic Bone Disease in Hemodialysis Patients: Fact or Fiction?

Adynamic bone disease is a type of renal osteodystrophy characterized by low bone turnover and paucity of bone cells. It was proposed that a new type of this disease featuring high osteoclastic resorption without parathyroid hormone stimulus and designated adynamic bone disease variant occurs in hemodialysis patients. The present study is designed to evaluate the frequency and characteristics of both diseases in a large series of bone biopsy specimens. We reviewed 1,160 bone biopsy specimens from hemodialysis patients. Specimens in which adynamic bone disease was diagnosed were selected and categorized as classic or variant based on osteoclastic surface. In 218 bone biopsy specimens (18.8%), adynamic bone disease was identified, whereas the variant form was identified in 35 specimens (38.8%). Biopsy specimens categorized as the variant form were from patients who were younger and had greater phosphorus and parathyroid hormone levels. Histologically, the variant form presented greater osteoid volume, fibrosis volume, osteoid surface, osteoblast surface, and eroded surface. Similarly, values for all dynamic parameters were greater in the variant group. Osteoclastic surface correlated with phosphorus level, parathyroid hormone level, and osteoblast surface. Age and osteoblast surface were identified as independent determinants of the variant form. Adynamic bone disease variant seems to occur in younger hemodialysis patients with greater levels of parathyroid hormone, which acts on cell-covered bone surfaces. It probably is a transitional phase from low- to high-turnover status, rather than a true entity within the spectrum of renal osteodystrophy.

Renal osteodystrophy with diabetic bone disease

Renal osteodystrophy (ROD) in chronic renal failure (CRF) patients with diabetes mellitus (DM) is characterized by lower degree of secondary hyperparathyroidism and higher prevalence of low turnover bone disorders than that in non-DM CRF patients. Particularly, aplastic bone disease is frequently observed (30 - 40 %). Compared to non-DM CRF patients, serum levels of osteocalcin are significantly decreased, and bone mineral density of trabecular bones is significantly decreased in DM CRF patients. Dietary calcium intake is often less than daily requirement, and hypovitaminosis D is frequently observed. Although persistent hyperglycemic state and impairment of insulin action are major contributors to diabetic osteodystrophy, many factors complicate the feature of DM-CRF. Control of blood glucose levels is the most important to alleviate abnormal bone metabolism in DM-CRF patients, and dietary calcium intake should be normalized. Further, therapeutic strategy of appropriate vitamin D administration should be established, in addition to appropriate exercise therapy, in order to prevent the progression of ROD in DM CRF patients.

Ectopic calcification in patients with aplastic bone disease undergoing dialysis

Aplastic bone disease (adynamic bone disease) has been attracted attention as the most frequent type of renal osteodystrophy in patients undergoing dialysis, and relatively low serum parathyroid hormone level is considered to be the major cause of aplastic bone disease. In aplastic bone disease, both the number of osteoblast and osteoclast are few and the speed of bone turnover is low, therefore, buffering action of bone for calcium and phosphorus is extremely disturbed. Hypercalcemia due to a prescription of large dose calcium carbonate and hyperphosphatemia derived by high protein diet in this occasion induce high serum calcium and phosphorus product level, and ectopic calcification is likely to occur. When ectopic calcification occur at artery it might develop ischemic change of visceral organ. Recently, the strong association between coronary arterial calcification and high serum calcium and phosphorus products is clarified by a method of electron-beam computed tomography. Based on these findings, high calcium and phosphorus product is now believed as a risk for poor patients' survival. Thus, we should pay attention to calcium and phosphorus product in patients suffering from aplastic bone disease.

Renal Osteodystrophy in Pre-Dialysis Patients: Ethnic Difference?

The purpose of the present study is to investigate whether an ethnic difference exists in the incidence of renal osteodystrophy between Asian and Western countries in end-stage renal disease (ESRD) patients. We evaluated bone histology in 58 pre-dialysis patients (28 male, 30 female; mean age: 47.7 years). All patients had bone biopsies with quantitative histomorphometry and serological parameters such as intact PTH, osteocalcin, total alkaline phosphatase, and basal and deferoxamine-stimulated serum aluminum levels. We observed that 91.4% of all evaluated patients showed renal osteodystrophy before the start of dialytic therapy. Mild osteitis fibrosa were observed in 21 patients (36.2%), severe osteitis fibrosa in 5 patients (8.6%), mixed lesions in 7 patients (12.1%), osteomalacia in 6 patients (10.3%), aplastic bone disease in 14 patients (24.1%), and normal bone in 5 patients (8.6%). Among the bone histomorphometric parameters, fibrosis area rate (%) showed the best correlation with intact PTH, and osteocalcin and osteoid area rate (%) with total alkaline phosphatase. Aluminum-related bone disease was not observed. Among patients with aplastic bone disease, only 14.3% showed aluminum deposition of any significance (5% < stainable bone surface aluminum < 25%). In the diabetic patients, aplastic bone disease was most common, but no case was related to aluminum intoxication. In conclusion, the distribution of renal osteodystrophy in our study was different from that of Western countries in pre-dialysis patients. Our patients tended to have more mild-form osteitis fibrosa and normal findings, and less severe-form osteitis fibrosa and aplastic bone disease. Aluminum-related bone disease was not observed.

Histomorphometric analysis of aplastic bone disease in chronic renal failure at initiation of haemodialysis: Relation to aluminum and parathormone

SUMMARY: We studied bone histology of 134 uraemic patients without a history of vitamin D administration at the start of haemodialysis. Patients were categorized according to bone histology as follows: aplastic bone disease (ABD), ostitis fibrosa, mixed type, mild hyperparathyroidism and osteomalacia. On initiation of haemodialysis, ABD was observed in 48.5% of patients. the average age of the ABD group (50.8 ± 12.5 years) was significantly higher than that of patients with other histologies (P&lt;0.01). Serum parathyroid hormone (PTH) and alkaline phosphatase (ALP) concentrations were lower (P&lt;0.01) in the ABD group, especially in patients with diabetes mellitus. Patients with diabetes mellitus and ABD had lower serum concentrations of PTH and ALP than non‐diabetic patients, suggesting that depressed PTH may be related to ABD. Eleven (55%) of the 20 patients who were receiving A1(OH)3 also had ABD. A direct relationship was observed between serum aluminum concentration and aluminum‐positive bone surface (r=0.60; P&lt;0.01). Aluminum staining was more frequently observed in the ABD group than in the non‐ABD group (P&lt;0.01). Because serum intact‐PTH concentrations correlate with osteoid surface area, fibrosis volume and bone formation rate, it may be a useful marker of bone histology in renal osteodystrophy. These results suggest that, in addition to conservative treatment with A1(OH)3, other factors may be involved in the formation of ABD which is often present at the start of haemodialysis.

Bone disease in moderate renal failure: cause, nature and prevention.

There are two primary types of bone disorders observed in patients with end-stage renal disease: a high-turnover osteodystrophy characterized by osteitis fibrosa, and a low-turnover osteodystrophy characterized initially by osteomalacia and, more recently, by adynamic or aplastic bone disease. This article reviews the clinical presentation, pathogenesis, and laboratory findings of patients with these two disorders. It discusses the important roles of phosphorous binding, vitamin D administration, and correction of acidosis in prevention and treatment of bone disease in patients with moderate renal insufficiency.

The aplastic form of renal osteodystrophy.

That bone disease accompanies renal failure has been known for over 100 years. This bone disease (renal osteodystrophy) has been variously attributed to hyperparathyroidism, vitamin D deficiency, aluminium toxicity, iron toxicity, uraemia, and a host of other aetiologies. In addition, the form the bone disease takes has been variously described as osteitis fibrosa, osteomalacia, mixed uraemic osteodystrophy and the aplastic (adynamic) lesion. In this manuscript we will focus on the aetiology, consequences, diagnosis and possible management of the aplastic form of the disease. The renal osteodystrophy study was a prospective, cross-sectional study of renal bone disease in a largely unselected population of patients receiving dialysis in three hospitals in Toronto. A variety of non-invasive data (parathyroid hormone (PTH), aluminium, etc.) and bone histology were obtained and analysed to assess pathogenesis, diagnostic criteria and management. We have defined the aplastic lesion as having low bone formation without a marked increase in unmineralized osteoid (i.e. excluding osteomalacia). We have noted that it may be associated with increased aluminium or little to no aluminium. With increased aluminium the patients have a poorer prognosis both with regards to bone disease and mortality, and they should be managed appropriately to alleviate aluminium toxicity. With lesser amounts of aluminium, morbidity and mortality are less severely impacted, but not normal. We have shown that the low bone formation, of the aplastic lesion without aluminium may be "normalized' by increasing PTH levels. It is concluded that aplastic bone disease carries adverse consequences both in terms of bone problems and survival. In the absence of aluminium toxicity the stimulation of PTH effectively corrects the bone formation abnormality. Whether this will alleviate the adverse consequences will be difficult to study. Avoiding the problem by not over-suppressing PTH seems a reasonable approach at this point.

Bone disease in predialysis, hemodialysis, and CAPD patients: Evidence of a better bone response to PTH

The spectrum of bone disease in predialysis and dialysis patients has changed during the last decade. The incidence of aplastic bone disease has increased and this can not be attributed to bone aluminum deposition; moreover, low bone cellular activity is present despite a moderate elevation in PTH levels. This study compares PTH levels and types of bone disease in both predialysis and dialysis patients from the same geographical area. We prospectively studied 119 unselected end-stage renal disease patients: 38 were immediately predialysis (PreD), 49 on hemodialysis (HD), and 32 on CAPD. A bone biopsy was performed in all patients. Aplastic bone disease with < 5% bone surface aluminum was a common finding (48%, 32%, and 48%, in PreD, HD, and CAPD, respectively). In all groups, an intact PTH level below 120 pg/ml was highly predictive of low bone turnover. Conversely, a PTH level above 450 pg/ml was always associated with histologic features of hyperparathyroid bone disease. Among the bone histomorphometric parameters, osteoblast surface showed the best correlation with intact PTH in each group, and the slope of the regression line for this correlation was significantly steeper in HD and CAPD than PreD patients. Thus, the range of PTH (95% confidence limit bands) needed to obtain a normal osteoblast surface of 1.5% was greater in preD than in HD and CAPD patients (300 to 500 vs. 75 to 260 pg/ml, respectively). In all groups some degree of marrow fibrosis was observed when PTH levels were greater than 250 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adynamic bone disease in patients with uremia

Adynamic (or aplastic) bone disease is a bone histologic pattern characterized by decreased bone formation rate, low cellularity, and normal or decreased osteoid thickness. It was first described in symptomatic patients undergoing dialysis who were overloaded with aluminum because of contaminated dialysate or chronic ingestion of aluminic phosphate binders; the evidence of the overload was extensive coloration (more than 25%) with aurin tricarboxylic acid, whereas the Perls stain coloration for iron was negative. We have, however, reported these histologic changes in asymptomatic patients with uremia who were never exposed to aluminum, in two patients before end-stage renal failure and in six patients undergoing dialysis. The main step in the prevention of adynamic bone disease is the absolute exclusion of aluminum exposition even by so-called "safe doses" of aluminum phosphate binders because in the long term they are never actually safe. Because idiopathic adynamic bone disease may nevertheless occur, parathyroid hormone suppressive treatment by oral calcium taken with meals as phosphate binders (+/- 1 alpha-hydroxyvitamin D3 derivatives) should be carefully monitored by measurements of plasma concentrations of not only calcium and phosphate but also of intact parathyroid hormone levels. In order to have normal bone formation rate levels, patient intact parathyroid hormone levels should be between one and three times the upper limit of the normal level. Although adynamic bone disease may not be a true bone disease when not due to aluminum, it is a risk factor for increased incidence of hypercalcemia and hyperphosphatemia and therefore for metastatic calcifications. Therefore, when hypercalcemia occurs with hyperphosphatemia and normal intact parathyroid hormone in patients treated with 1 alpha-hydroxyvitamin D3, it is proposed that the latter drug should be discontinued first, whereas oral calcium is increased to correct hyperphosphatemia, and calcium concentration is decreased in the dialysate to prevent hypercalcemia, even though plasma parathyroid hormone may increase up to three times the upper limit of the normal level. In patients previously exposed to aluminum, a deferoxamine test should be performed and a deferoxamine treatment started if the test is positive.

Adynamic bone disease with negative aluminium staining in predialysis patients: prevalence and evolution after maintenance dialysis.

Aplastic bone disease (ABD) is a common form of renal osteodystrophy and is characterized by a defect in bone matrix formation and mineralization without an increase in osteoid thickness. The prevalence and pathogenesis of ABD in predialysis patients is largely unknown. We prospectively studied 92 unselected predialysis patients with a creatinine clearance < 10 ml/min/1.73 m2 and a mean age of 45 +/- 2 years (61 M, 31 F). None of the study patients had received any form of vitamin D therapy, and CaCO3 was the primary phosphate binder. Aplastic bone disease was observed in 30 (32%) patients. Stainable bone aluminium surface was < 3% in all ABD patients. Patients with ABD were older (52 +/- 3 versus 42 +/- 2 years; P < 0.01) and had reduced serum intact PTH compared to non-ABD patients (199 +/- 25 versus 561 +/- 87 pg/ml; P < 0.001). Patients with diabetes mellitus showed lower PTH values (179 +/- 31 versus 432 +/- 62 pg/ml; P < 0.001) and a lower incidence of advanced hyperparathyroidism bone lesions (16% versus 46%; P < 0.05) than non-diabetic patients. However, diabetes was not clearly associated with low bone turnover disease (56% in diabetics versus 41% in non-diabetics; P = 0.1). A second bone biopsy was obtained in eleven ABD patients after a period of 16.6 +/- 2.2 months on maintenance dialysis with a dialysate calcium of 7 mg/dl. Bone histology was unchanged in 10 patients, and one evolved to mild hyperparathyroidism. Trabecular bone volume did not change (22.7 +/- 1.7 versus 20.7 +/- 1.7%), and the stainable bone aluminium surface remained < 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone histomorphometry in chronic renal failure

Thirty uremic patients were classified to 5 subgroups according to histological criteria as osteitis fibrosa (OF), mixed OF plus osteomalacia (OM), mild hyperparathyroidism, aplastic bone disease and OM. Serum level of PTH was elevated in OF while it was lowered in aplastic bone disease. Serum level of PTH and ALP well correlated with bone formation parameters of histomorphometry suggesting that these parameters could predict turnover of bone in uremic patients. Serum level of aluminum was correlated with the duration of hemodialysis and aluminum positive bone surface. This might correspond to the aluminum hydroxide consumption. No double tetracycline uptake was observed in the diabetic patients and their serum PTH level was considerably low, suggesting that lowered PTH might be partly responsible for the low bone turnover status.

A Comparison of Parathyroid-Gland Function in Haemodialysis Patients with Different Forms of Renal Osteodystrophy

Parathyroid function was studied in three different histological forms of renal osteodystrophy: osteitis fibrosa (OF), low-turnover aluminium-associated bone disease (LTAABD), and aplastic bone disease without aluminium (ABD). Parathyroid function was determined by the evaluation of the sigmoidal parathyroid hormone-(PTH)-calcium curve, which was obtained by the performance of a reduced calcium and an increased calcium haemodialysis. Parameters of the sigmoidal PTH-calcium curve evaluated included maximally stimulated (PTHMax) and inhibited (PTHMin) PTH, the set point of calcium for PTH (ICA50), defined as the ionised calcium concentration at which PTHMax was reduced by 50%, the ratio of basal PTH to maximally stimulated PTH (PTHBase:PTHMax), the ionised calcium concentration at which basal (ICABase), maximally stimulated (ICAMax), and maximally inhibited (ICAMin) PTH values were observed, and the slope of the PTH-calcium curve. Both PTHMax and PTHMin were greater in OF than the other two groups (P less than 0.02). The ratio of basal to maximally stimulated PTH was greater (P less than 0.02) in OF (61 +/- 7%) than LTAABD (33 +/- 5%) and ABD (36 +/- 7%). The ICA50 and the ICAMax were greater (P less than 0.03) in OF than the other two groups; however, no differences were observed in the ICABase and ICAMin. The slope of the PTH-calcium curve (% maximal PTH), which should indicate the sensitivity of parathyroid cells, was greater in OF than LTAABD (P less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of high parathyroid hormone levels on the development of aluminum-induced osteomalacia in the rat.

A relative deficiency of parathyroid hormone (PTH) is generally observed in dialysis patients with aluminum-associated osteomalacia or aplastic bone disease. It has been suggested that high PTH levels may protect against the development of aluminum-associated bone disease. Through the use of a previously established model of aluminum-induced osteomalacia in the rat, the protective effect of PTH was evaluated. Aluminum was administered intraperitoneally at doses of 0, 5, 10, and 20 mg during a 2-day period, and rats were sacrificed 5 and 12 days after aluminum administration. PTH (bovine 1-34) was administered via a subcutaneously implanted Alzet pump at 2 U/h starting 4 days before aluminum administration and continuing until sacrifice. As the aluminum dose was increased to 20 mg, the osteoblast surface and the bone formation rate decreased. PTH supplementation increased the osteoblast surface at all doses of aluminum and increased the bone formation rate at 0 and 5 mg of aluminum. However, even with PTH supplementation, osteoblast surface decreased as the aluminum dose increased. In the absence of PTH supplementation, osteoblast surface was markedly reduced when the serum aluminum concentration was greater than 400 micrograms/liter or stainable trabecular aluminum surface exceeded 15%. When the stainable trabecular aluminum surface was greater than 12%, the bone formation rate was zero even during supplemental PTH administration. A significant correlation was observed between serum aluminum and stainable trabecular aluminum surface (r = 0.80 at 5 days and r = 0.86 at 12 days; P less than 0.001). However, after PTH administration, less stainable trabecular aluminum was present for the same serum aluminum concentration. Both with and without PTH, the slope of the correlation between serum aluminum and stainable trabecular aluminum surface was steeper at 5 days after aluminum administration than at 12 days. In conclusion, for an equivalent aluminum exposure, high PTH levels protected against the development of low turnover aluminum bone disease in the rat.

Effect of parathyroidectomy on aluminum toxicity and azotemic bone disease in the rat

In maintenance dialysis patients, low-turnover osteomalacia and aplastic bone disease are generally attributed to aluminum toxicity. Both groups of patients have a relative deficiency of PTH. The reason for the development of osteomalacia versus aplastic bone disease is unclear. The present study was performed to evaluate whether parathyroidectomy (PTX) modifies the effect of aluminum administration on bone histology in renal failure. Seven groups of pair-fed rats were studied: normals (N); renal failure (RF); RF + PTX; PTX; RF + aluminum (AL); RF + PTX + AL; and PTX + AL. Aluminum was administered intraperitoneally 5 days/week for 6 weeks. All groups were sacrificed at 6 weeks. Renal failure increased the serum calcium in both the parathyroid intact (RF versus N, 11 +/- 0.1 versus 10 +/- 0.3 mg/dl, X +/- SEM, P less than 0.05) and calcium-supplemented PTX groups (PTX + RF versus PTX, 9.7 +/- 0.2 versus 9.2 +/- 0.2 mg/dl, P less than 0.05). After PTX, aluminum administration increased the serum calcium (PTX + AL versus PTX, 9.8 +/- 0.3 versus 9.2 +/- 0.2, P less than 0.05, and PTX + RF + AL versus PTX + RF, 10.8 +/- 0.1 versus 9.7 +/- 0.2 mg/dl, P less than 0.05). In rats with renal failure receiving aluminum, PTX decreased osteoid volume and surface but not osteoid thickness. Rats receiving aluminum did not mineralize bone. Additionally, in PTX rats receiving aluminum, renal failure per se increased osteoblast surface, osteoid surface, osteoid volume, and osteoclast number.(ABSTRACT TRUNCATED AT 250 WORDS)

Desferrioxamine therapy in hemodialysis patients with aluminum-associated bone disease

Aluminum toxicity in dialysis patients is associated with decreased bone turnover and a relative parathyroid hormone (PTH) deficiency. Desferrioxamine (DFO), a chelating agent, has been reported to improve bone histology in aluminum associated, low turnover bone disease in dialysis patients not subjected to parathyroidectomy. Information on the effect of DFO therapy on parathyroid gland function is lacking. In the present study, in addition to changes in bone histology, parathyroid gland function was evaluated in 18 hemodialysis patients with aluminum associated, low turnover bone disease (osteomalacia and aplastic bone disease) before and after one year of DFO treatment (1 to 6 g/week). Parathyroid gland function was assessed by using a calcium free and high calcium (3.5 to 4 mEq/liter) hemodialysis bath.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for a toxic effect of aluminum on osteoblasts: a histomorphometric study in hemodialysis patients with aplastic bone disease.

To evaluate the potential role of aluminum (Al) in a subset of dialysis patients with aplastic bone disease, we have studied tetracycline-labeled bone biopsies of 32 patients (22 males and 10 females, 45-73 years) on maintenance hemodialysis. Selection criteria included normal resorption surfaces (RS) and osteoid thickness. Eleven patients (Group I) had no stainable bone Al (Al-; 61.7 +/- 7.2 years) and 21 (Group II) had stainable bone Al (Al+; 57.7 +/- 6.8 years). Serum Al was normal to slightly elevated in Group I, but significantly higher in Group II (p less than 0.01). Al surfaces (AlS), undetectable in Group I, were 67.8 +/- 17.9% in Group II. Bone Al content (BAC) was much lower in Group I than in Group II (14.8 +/- 3.7 vs. 113.8 +/- 100.2 micrograms/g, p less than 0.01), but higher in Group I than in controls (p less than 0.05). Extensive thin osteoid seams were present in Group II. AlS was correlated with OS (r = 0.56, p less than 0.001) and OV (r = 0.48, p less than 0.01). Labeled surfaces were decreased in both groups. Labeled osteoid surfaces (TLS/OS) were below 2 SD of the mean control values in 96% of patients and calcification rate (CR) was depressed below 0.20 micros/day in 44% of patients. Bone formation rate (BFR) was strikingly depressed, values being below one SD of the mean control value in 92-100% of patients at both levels and below 2 SD of the mean in 82% of patients at BMU levels. Mineralization lag time (OMP) was markedly prolonged above 2 SD of controls in 89% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)