Relationship between aortic mineral elements and osteodystrophy in mice with chronic kidney disease.

In chronic kidney disease (CKD), osteodystrophy and arterial calcification often coexist. However, arterial alterations have not been addressed in CKD unaccompanied by evidence of calcification. We investigated the association of phosphate (P) and calcium (Ca) accumulation in calcification-free aortas with CKD-induced osteodystrophy. Aortic accumulation of magnesium (Mg), an inhibitor of calcification, was also examined. Male mice aged 26 weeks with CKD characterized by hyperparathyroidism and hyperphosphatemia (Nx, n = 8) and age-matched healthy male mice (shams, n = 8) were sampled for blood, and thoracic vertebrae and aortas were harvested. Bone structure and chemicals were analyzed by microcomputed tomography and infrared microspectroscopy, respectively, and aortic accumulation of P, Ca, and Mg was evaluated by plasma-atomic emission spectrometry. Volume fractions of cortical and trabecular bones were smaller in Nx than in sham animals (P < 0.05), attributed to cortical thinning and reduction in trabecular number, respectively. Bone chemicals were not different between the groups. No calcification was found in either group, but P, Ca, and Mg contents were higher in Nx than in shams (P < 0.05). The mass ratio of Ca/P was lower in Nx than in shams (P < 0.05), but that of Mg/Ca and Mg/P was not different between the groups. Aortic P and Ca contents were inversely correlated with the volume fraction of cortical bone (P < 0.05). In conclusion, the relationship of osteodystrophy with aortic P and Ca accumulation suggests the existence of a bone-vascular axis, even in calcification-free arteries in CKD. The preservation of ratios of Mg/Ca and Mg/P despite CKD development might contribute to calcification resistance.

Vascular calcifications and renal osteodystrophy in chronic hemodialysis patients: what is the relationship between them?

INTRODUCTION: Vascular calcifications (VCs) and renal osteodystrophy (ROD) are frequently seen together and represent the major causes of morbidity and mortality in hemodialysis (HD) patients. Some studies suggest a pathogenic link between them, but there is no consensus as yet regarding this issue. The main objective of our study was to establish whether there is any relation between VCs and ROD in our HD patients. We evaluated the prevalence of VCs and ROD and the relationship between VCs and some clinical and biochemical characteristics of HD patients. METHODS: We examined radiological signs of VCs and ROD on hands and pelvis bone radiographs in 81 chronic HD patients, and we calculated a VC score on this basis. RESULTS: We found a significant relation between radiological signs of ROD and those of VC (P = 0.019). The patients with ROD had a higher mean VC score (P = 0.02). By linear regression, the VC score correlated directly with serum calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH) and CaxP product and inversely with serum albumin. The logistic regression model revealed that ROD, male gender and treatment with calcium salts were predictive of VCs development. There were no associations between VCs and age, HD vintage, diabetes, dialysate Ca concentration, vitamin D treatment, spKt/V, URR and C-reactive protein (CRP) levels. CONCLUSION: There seems to be a pathogenetic link between bone and artery diseases in chronic HD patients. Both VCs and ROD have a high prevalence. ROD, male gender and treatment with calcium salts are risk factors for VCs.

Osteodystrophy in Indonesian haemodialysis patients.

A preliminary study of the intact-parathyroid hormone (i-PTH) measurements from haemodialysis patients was conducted to determine the prevalence of renal bone diseases at the Dr Soetomo Hospital. The objective of this study is to evaluate the osteodystrophy renal pattern in haemodialysis patients using i-PTH and radiological parameters. The selected populations of 48 (32 males and 16 females), the mean age 48 +/- 10.3 years, was evaluated to conduct a cross-sectional study. The calorimetric method was applied to measure serum P and Ca, while a radioimmunoassay was used to assay the i-PTH level. Of those 48 patients receiving haemodialysis, with a duration ranging from 4 to 432 weeks, 61% had hypocalcaemia and 10% had hypercalcaemia. The i-PTH levels below 100 pg/mL (normal, 10-65 pg/mL) suggested 'aplastic' bone, and values of 100-200 pg/mL most commonly indicated 'normal' bone turnover. The i-PTH levels over 200 pg/mL suggested hyperparathyroidism. The results of this study demonstrated that 42% of those patients had <100 pg/mL (low turnover bone presumed, no biopsy), 23% had 100 - <200 pg/mL ('normal' bone turnover) and 35% of them had >200 pg/mL ('hyperparathyroidism'). In addition, the radiological study showed that 10% of those patients were positive for renal bone diseases. In conclusion, this study shows that the common type of renal osteodystrophy was of a low turnover type, which was different from the findings in other previous studies. It is postulated that this difference is likely to be caused by some factors such as the general health condition of the population those patients belong to and, in particular, the nutritional status of those patients.

Compressive optic neuropathy caused by renal osteodystrophy. Case report.

Compressive optic neuropathy with acute or chronic vision loss has been associated with various skull base tumors, aneurysms, Graves disease, trauma, and, less commonly, fibrous dysplasia and osteopetrosis. The authors present a case of acute visual deterioration in a 25-year-old woman who had massive calvarial hypertrophy with optic canal stenosis secondary to renal osteodystrophy (uremic leontiasis ossea [ULO]: bighead disease). Significant visual field restoration was achieved with high-dose corticosteroids followed by optic nerve decompression. This is the first case report of cranial neuropathy associated with ULO.

Imaging of bone in the diagnostics of renal osteodystrophy in children with chronic renal failure.

BACKGROUND: In the last two decades considerable advances have been made in the development of imaging tests of the skeletal system. This progress in diagnostic techniques, along with the growing availability of the tests, renders it necessary to review and evaluate their suitability for daily clinical practice. The aim of this article is to compare the results of radiological testing of bone with densitometrical, histomorphometric, and biochemical tests in children with chronic renal failure. MATERIAL AND METHODS: The research involved 31 children with renal failure, of whom 10 were being treated conservatively, 17 by continuous ambulatory peritoneal dialysis (CADO), and 4 by hemodialysis (HD). In all these children, radiological examinations of bone were performed in the arms, knees, and hips, along with tests for the serum concentration of parathormone (iPTH), calcium (Ca), and phosphates (P), and for the activity of alkaline phosphatase (AP). Bone density tests by the DXA method and bone biopsies were also performed. On the basis of radiological evaluation, the patients were divided into two groups: Group I, consisting of 14 children with a normal bone structure image, and Group II, consisting of 17 children with bone atrophy. RESULTS: No statistically significant differences were discovered in the mean values of the tested biochemical parameters between the two groups. The mineral density of total body was normal in 9 of the 14 patients in Group I (64%), and in 7 of 17 (41%) from Group II. The mineral density of total lumbar spine gave similar results. Lower bone density results were obtained in Group II than in Group I, though only in the case of the lumbar spine were the differences statistically significant. In Group I, 5 cases were discovered of chronic osteodystrophy without osteomalacia and hyperparathyroidism (NB), 2 cases of adynamic bone disease (ABD), 4 cases of hyperparathyroidism (HP), 2 cases of moderate hyperparathyroidism (MHP), and one mixed form (Mix); in Group II, there were 6 NBs, 2 ABDs, 1 case of osteomalacia (OM), 5 HPs, and 3 mixed. Radiological examinations revealed one male in Group I with features of prior Perthes's disease, one with fibrous cortical defect, and four cases of valgity of the coxa valga. In Group II, there were 3 children with radiological changes typical for osteomalacia, and in 1 case typical radiological signs of hyperparathyroidism. CONCLUSIONS: Given the lack of consistency in the results of the tests here presented, an entire panel of available tests should be performed for the comprehensive evaluation of the status of the skeleton.

Refractory renal hyperparathyroidism: clinical features and outcome of surgical therapy.

Despite improvements in medical management parathyroidectomy has an important role in treatment of refractory renal hyperparathyroidism (HPT). The medical records of all patients who underwent parathyroidectomy from 1991 through 2000 were reviewed to determine the clinical and laboratory features and outcomes of treatment in patients with renal versus primary HPT. Twenty-one of 92 patients who underwent parathyroidectomy had renal HPT with a mean age of 47+/-3 years compared with 56+/-2 years for patients with primary HPT (P < 0.05). Clinical manifestations included osteodystrophy (19), pruritus (six), extraosseous calcification (three), and calciphylaxis (one). Parathyroid hormone, phosphorus, and alkaline phosphatase levels and weights of excised glands were higher in renal versus primary HPT (P < 0.05). Supernumerary glands were found in three patients (14%) with renal HPT and none of nine patients with primary parathyroid hyperplasia. After surgical therapy persistent or recurrent HPT occurred in three (14%) patients with renal and one (1.4%) patient with primary HPT (P < 0.05). Postoperative hypocalcemia occurred in 20 (95%) patients with renal HPT all of whom required intravenous calcium, compared with 25 (35%) patients with primary HPT (P < 0.05) of whom only three (4%) required intravenous calcium (P < 0.05). In contrast to those with primary HPT patients with renal HPT are younger and more likely to have severe osteodystrophy, postoperative hypocalcemia, and persistent or recurrent HPT.

Diagnosis and monitoring of renal osteodystrophy.

A variety of biochemical investigations and radiological techniques are available to assist in the diagnosis and monitoring of renal osteodystrophy. Measurement of serum parathyroid hormone remains the single most useful biochemical test in predicting bone histology in an individual patient. Newer biochemical markers of bone turnover are unlikely to supplant this in everyday practice, but may provide useful supplementary information in the future. The present review discusses the role of radiological investigation, including bone densitometry and quantitative ultrasound. Bone biopsy remains the 'gold standard' investigation. Its invasive nature and the need for specialized processing and interpretation limits its use in clinical practice, although it still has a role particularly in the investigation of low turnover states. Also, as molecular biological techniques are increasingly being used, the evaluation of biopsy specimens will in the future provide new insights into the disordered bone cell function that occurs in renal osteodystrophy.

Microfocal radiography in the diagnosis of childhood renal osteodystrophy.

BACKGROUND: Renal osteodystrophy is common in children with chronic renal failure (CRF) and X-ray is an intensive method in the diagnosis of the disease. In this study we compared microfocal radiography with conventional method for the diagnosis of renal osteodystrophy. METHODS: The X-rays of left wrists of 21 children with CRF and chronic renal insufficiency were taken by conventional and microfocal methods. RESULTS: Both methods revealed osteopenia in all patients (100%), widening, fraying and cupping of ulnar and radial metaphysis in 10 (47.6%), osteosclerosis in three (14.2%) and pseudofracture in one (4.7%) patient. Microfocal radiography demonstrated osteosclerosis in one patient, pseudofracture in four and subperiosteal resorption in five patients that were not detected by conventional method. CONCLUSION: Two methods were found to be significantly different in demonstrating the changes due to rickets and hyperparathyroidism and it is concluded that microfocal radiography may be preferred in the diagnosis of childhood renal osteodystrophy.

Renal osteodystrophy in dialysis patients: diagnosis and treatment.

This article reviews the clinical, biological, radiological, and pathological procedures and their respective indications for the practical diagnosis of the following various histological patterns of renal osteodystrophy: osteitis fibrosa due to parathyroid hormone (PTH) hypersecretion: osteomalacia or rickets due to native vitamin D deficiency and/or aluminum overload; and adynamic bone disease (ABD) due to aluminum overload and/or PTH secretion oversuppression. Our advice regarding bone biopsy is to restrict it to patients with symptoms and hypercalcemia, especially those who have been previously exposed to aluminum. In other cases, we propose relying merely on the determination of the plasma concentrations of calcium, protide, phosphate, bicarbonate, intact PTH, aluminum, 25(OH)D3, and alkaline phosphatase (total and bony if hepatic disease is associated) to choose the appropriate treatment. Because of the danger of the desferrioxamine treatment necessary to chelate and remove aluminum, the suspicion of aluminic bone disease (osteomalacia or ABD) will always be confirmed by a bone biopsy. In the case of nonaluminic osteomalacia, correction of the vitamin D deficiency by native vitamin D or 25(OH)D3, and of the calcium deficiency and acidosis by alkaline salts of calcium and if necessary sodium bicarbonate are sufficient to cure the disease. In the case of nonaluminic ABD, the stimulation of PTH secretion by the discontinuation of 1alpha hydroxylated vitamin D and the induction of a negative calcium balance during dialysis by decreasing the calcium concentration in the dialysate will allow an increase of the CaCO3 dose to correct for hyperphosphatemia without inducing hypercalcemia. For hyperparathyroidism, i.e., plasma intact PTH levels greater than two- or four-fold the upper limit of normal levels (according to the absence or presence of previous aluminum exposure), the treatment will consist in increasing the CaCO3 dose to correct for hyperphosphatemia together with a decrease of the calcium concentration in the dialysate if the dose of CaCO3 is so high that it induces hypercalcemia. When the hyperphosphatemia has been corrected and there is still a low or normal corrected plasma calcium level, 1alpha(OH)D3 in an oral bolus 2 or 3 times a week should be given at the minimal dose of 1 microg. When the PTH level stays above 400 pg while hypercalcemia occurs and hyperphosphatemia persists, surgical subtotal parathyroidectomy is recommended or the injection of calcitriol into the big nodular hyperplastic parathyroid glands under sonography control in high surgical risk patients. Special recommendations are given for children.

Renal ostodystrophy during the developing stage of maintenance dialysis in Transylvania. Early development of periarticular calcifications and beta 2 microglobulin amyloidosis in spite of a relatively good prevention of secondary hyperparathyroidism.

BACKGROUND: Dialysis facilities have been introduced only recently in Transylvania with many limitations, in particular a standard high calcium dialysate, Al(OH)3 as phosphate binder and pharmacological doses of native vitamin D2, but neither CaCO3 nor 1 alpha hydroxylated vitamin D. Rheumatological complaints and metastatic calcifications were frequent, leading to suspect either overt hyperparathyroidism, adynamic bone disease or beta 2 microglobulin amyloidosis. AIMS OF THE STUDY: Evaluate the prevalence of radiological osteitis fibrosa, amyloid osteoarthropathy and periarticular calcification and their link with PTH secretion, phophocalcic disorders, acidosis, bone turn over, aluminum and beta 2 microglobulin accumulation in the dialysis population of Sibiu (Transylvania). METHODS: The clinical and radiological rheumatological data of the 49 uremic patients dialyzed in Sibiu since 1990 were reviewed as well as the monthly routine monitoring of their plasma phosphocalcic parameters. Furthermore in July 1994, 36 of them had an X rays of the hands for evaluation of subperiosteal resorption of the phalanges, periarticular calcifications and carpal cysts as well as a determination of plasma concentrations of intact PTH (normal range: 10-55; optimal range: 100-200 pg/ml), osteocalcin, bone alkaline phosphatase, aluminum and 25 OH vitamin D. RESULTS: The prevalence of subperiostal resorption of the phalanges was 8% and that of severe biological hyperparathyroidism (PTH > 400 pg/ml) 22%, whereas that of a relative hypoparathyroidism (PTH < 100 pg/ml) was 31%. Mean plasma concentrations of calcium was 2.07 +/- 0.15; of phosphate 2.50 +/- 0.35; of bicarbonate 15 +/- 2.0 mmol/l, of 25 OHD 30 +/- 20 ng/ml, of aluminum 1.1 +/- 0.5 mumol/l. Plasma PTH concentrations were negatively correlated to dialysis duration, and to plasma concentrations of aluminum, calcium and 25 OH vitamin D but not to those of phosphate and bicarbonate. Multivariate analysis showed however that only duration of dialysis and plasma aluminum concentration were independently and negatively correlated to plasma PTH concentrations. The prevalence of periarticular calcifications (26%) and of carpal cysts suggestive of beta 2 microglobulin amyloidosis (10%) were relatively high considering the young age of the population (42 years) and the short duration of dialysis (2.6 years). Patients with calcifications comparatively to those without calcifications were older, had longer duration on dialysis, higher prevalence of carpal cysts and higher plasma beta 2 microglobulin concentrations, lower plasma PTH (98 versus 313 pg/ml) and higher plasma aluminum concentration (1.3 versus 0.8 mumol/l). Patients with carpal cysts comparatively to those without cyst were older, had a longer duration on dialysis and a higher prevalence of periarticular calcifications. CONCLUSIONS: a) In spite of no use of 1 alpha hydroxylated vitamin D derivatives, and poor control of hyperphosphatemia and acidosis, hyperparathyroidism declined with duration of dialysis due to the use of a high dialysate calcium concentration, Al(OH)3 as sole phosphate binder and high supplement of native vitamin D. b) Considering the relative young age and short duration on dialysis, the prevalence of periarticular calcifications and carpal cysts were high. c) Calcifications were possibly favored by relative hypoparathyroidism and moderate aluminum overload. d) The association of periarticular calcifications and subchondrial cysts suggest a causal relationship.

Growth of children following the initiation of dialysis: a comparison of three dialysis modalities.

Maintenance dialysis usually serves as an interim treatment for children with end-stage renal disease (ESRD) until transplantation can take place. Some children, however, may require dialytic support for an extended period of time. Although dialysis improves some of the problems associated with growth failure in ESRD (acidosis, uremia, calcium, and phosphorus imbalance), many children continue to grow poorly. Therefore, three different dialysis modalities, continuous ambulatory peritoneal dialysis (CAPD), cycler/intermittent peritoneal dialysis (CPD), and hemodialysis (HD), were evaluated with regard to their effects on the growth of children initiating dialysis and remaining on that modality for 6-12 months. Growth was best for children undergoing CAPD when compared with the other two modalities with regard to the following growth parameters: incremental height standard deviation score for chronological age [-0.55 +/- 2.06 vs. -1.69 +/- 1.22 for CPD (P < 0.05) and -1.80 +/- 1.13 for HD (P < 0.05)]; incremental height standard deviation score for bone age [-1.68 +/- 1.71 vs. -2.45 +/- 1.43 for CPD (P = NS) and -2.03 +/- 1.28 for HD (P = NS)]; change in height standard deviation score during the dialysis period [0.00 +/- 0.67 vs. -0.15 +/- .29 for CPD (P = NS) and -0.23 +/- .23 for HD (P = NS)]. The reasons why growth appears to be best in children receiving CAPD may be related to its metabolic benefits: lower levels of uremia, as reflected by the blood urea nitrogen [50 +/- 12 vs. 69 +/- 16 mg/dl for CPD (P < 0.5) and 89 +/- 17 for HD (P < 0.05)], improved metabolic acidosis, as indicated by a higher serum bicarbonate concentration [24 +/- 2 mEq/l vs. 22 +/- 2 for CPD (P < 0.05) and 21 +/- 2 for HD (P < 0.05)]. In addition, children undergoing CAPD receive significant supplemental calories from the glucose absorbed during dialysis. CAPD, and possibly, other types of prolonged-dwell daily peritoneal dialysis appear to be most beneficial for growth, which may be of particular importance for the smaller child undergoing dialysis while awaiting transplantation.

Clinical and radiological features of bone disease in long-term (15 or more years) hemodialysis patients.

Fifteen patients on regular dialytic treatment for more than 15 years were given X-rays of the skull, spine, shoulders, wrists, pelvis and knees with the purpose of studying the principal skeletal and articular alterations due or not due to the uraemic status. Serum calcium, phosphorus, parathyroid hormone, alkaline phosphatase and basal aluminium were recorded. Osteopenia was evident in all the patients. Ten of whom (67%) showed alterations due to hyperparathyroidism. Nine patients presented the marks of dialysis spondyloarthropathy; in 14/15 cases geodes were present in the wrists, humeral heads or hip-joints; in ten patients there were multiple amyloid lesions. Two patients with serum basal aluminum above 100 micrograms/L showed the typical radiographic marks of osteomalacia. The majority of the long-term survivors showed multifactorial osteo-articular alterations resulting mainly from the combination of hyperparathyroidism and dialysis-related amyloidosis. The less frequent joint alterations were represented by arthrosis, enthesopathy and chondrocalcinosis. Disability and decreased articular mobility resulted in being mainly due to amyloid osteo-arthropathy.

[Therapy success in the treatment of severe renal osteopathy as the result of effective interdisciplinary team work. Case report]. / Therapieerfolg in der Behandlung einer schweren renalen Osteopathie im Ergebnis einer effektiven interdisziplinären Zusammenarbeit. Ein Fallbericht.

Report about therapy of a severe renal osteopathy, a case of tertiary hyperparathyroidism. It will be shown the good team work between paediatrics, surgery and orthopaedics. Only on this way the patient get the ability for a later dialysis or kidney transplantation.

[X-ray diagnosis of renal osteopathy in dialysis patients with reference to clinical aspects]. / Röntgendiagnostik der renalen Osteopathie bei Dialysepatienten unter Berücksichtigung klinischer Aspekte.

Pathophysiological histological and radiological findings in renal osteodystrophy are described. Special emphasis is laid on secondary hyperparathyroidism. Preliminary results of the authors' investigations show a good correlation between radiological findings in the phalanges of the hand and the concentration of parathyroid hormone (PTH) in 14 patients. The concentration of the hormone in the blood was measured by a new "two-site" immunoradiometric assay, which is specific for the intact, biologically active hormone. Patients with high concentrations of PTH in the blood tended to have more severe radiological changes. In 4 patients for whom radiographs of the hands revealed no pathologic findings, normal PTH concentrations in the blood were measured by this method, whereas the conventional assay gave elevated hormone concentrations for the same patients. This is due to the lack of specificity of the conventional method for the intact, biologically active hormone. Nevertheless, further investigations are needed to confirm these findings.

Radionuclide imaging in metabolic and systemic skeletal diseases.

Radionuclide imaging with Tc-99m diphosphonates is not an effective method for detecting or ruling out most osteoporotic diseases including senile osteoporosis or accelerated postmenopausal osteoporosis, and the slow loss of bone tissue generally remains undetected by this modality. Nonetheless, it frequently surpasses or supplements radiographic findings in evaluating the focal complications of metabolic bone disease, including fractures, microfractures, stress fractures, vertebral compressions, Milkman-Looser zones, aseptic necrosis, and acute infarction. In contrast to its secondary role in osteoporosis, bone imaging is of prime importance in investigating hypercalcemia, because the major cause of this abnormality is skeletal metastatic malignancy. In defective bone mineralization due to hyperparathyroidism or osteomalacia, a general increase in diphosphonate skeletal uptake is detected more frequently than radiographic abnormalities. However, normal skeletal images do not rule out metabolic bone disease. Biochemical testing is more reliable in detecting primary hyperparathyroidism. On the other hand, in renal osteodystrophy, biochemical abnormalities are variable and bone imaging is helpful in assessing the severity of skeletal involvement, but not its etiology. Many methods of quantitating the kinetics of Tc-99m diphosphonates have been explored, such as plasma clearance, bone-to-soft-tissue ratios, 24-hour total body retention and 24-hour urinary excretion. None of these have been widely accepted. The value of bone imaging is established in other systemic diseases, most notably in Paget's disease, hypertrophic pulmonary osteoarthropathy, sickle cell disease, fibrous dysplasia, and sympathetic dystrophy.

[X-ray features of fibrous osteodystrophy and osteomalacia in patients with chronic renal insufficiency under present-day treatment]. / Rentgenologicheskie osobennosti fibroznoi osteodistrofii i osteomaliatsii u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu v usloviiakh sovremennogo ee lecheniia.

The authors present the results of clinicoroentgenological and biochemical investigations in 102 patients with chronic renal insufficiency after hemodialysis and in 76 patients after kidney transplantation. The nature of secondary hyperparathyroid fibrous osteodystrophy and osteomalacia as main symptoms of nephrogenic osteodystrophy (NO), their interrelation and correlation are analysed. Of 178 patients pathological changes of the bone system were revealed in 94 (52.9%). The combination of fibrous osteodystrophy and osteomalacia (22%) is regarded as a contraindication for parathyroidectomy. Effective kidney transplantation does not prevent NO though its specificity changes: osteomalacia is more marked, osteonecrosis and soft tissue calcification are more common. The chief method of radiodiagnosis of NO is routine radiography of the skeleton supplemented by small feature contact radiography and x-ray image color analysis on the UAR and TELEVAN TV units. Comparative roentgenodensitometry of the bones and CT of the parathyroid glands contributed to obtaining objective information but was of applied value.

[Special radiology of the hand in renal osteopathy]. / Spezielle Radiologie der Hand bei renaler Osteopathie.

The different radiographical abnormalities of the hand with renal osteodystrophy are demonstrated. The soft tissue immersion low-energy X-ray technique allows early detection of macrostructural changes of spongy and compact bone, irregularities of the cortex, defects and pseudocysts, osteosclerosis as well as calcifications in the soft tissue and arterio sclerosis of patients with chronic renal failure. Possible erroneous interpretations will be discussed.