Case report: Electron microscopic evaluation of bone from a patient treated with cinacalcet hydrochloride, maxacalcitol, and alfacalcidol for hyperparathyroid bone disease with secondary hyperparathyroidism.

Evaluation of bone is of great importance in chronic kidney disease patients, as these patients are at an increased risk for fractures. We treated a hemodialysis patient suffering from hyperparathyroid bone disease with cinacalcet hydrochloride and concurrent administration of maxacalcitol and alfacalcidol for a year. Hyperparathyroid bone disease is characterized by cortical thinning, increased cortical porosity, reduced trabecular bone volume, and increased hypomineralized matrix volume, and there is little information to date about the effects of treatment with cinacalcet hydrochloride on the bone fragility in patients with hyperparathyroid bone disease. In the present study, histological and backscattered electron microscopic evaluation of this combination treatment revealed an excellent improvement of both bone volume and bone morphology. This treatment improved cortical thinning, cortical porosity, and trabecular thinning. Furthermore, the treatment also reduced hypomineralized matrix volume, indicative of improved mineralization by osteocytes. We speculate that the intermittent maxacalcitol administration may have effectively stimulated the vitamin D receptors expressed on osteocytes and osteoblasts, resulting in increased mineralization. Our approach for evaluating the bone in patients with chronic kidney disease by backscattered electron microscopy is novel.

Expression dynamics of CXCL12 and CXCR4 during the progression of mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) classically presents from patch stage to plaque stage over a number of years and finally progresses to tumour stage with nodal or visceral involvement. The mechanism of progression remains incompletely elucidated. Chemokines and their receptors are known to be involved in disease mechanisms, with CXCL12 and CXCR4 playing a critical role in carcinogenesis, invasion and cancer cell migration in various carcinomas. OBJECTIVES: To investigate the expression of CXCL12 and CXCR4 in different cutaneous stages of MF. METHODS: Formalin-fixed, paraffin-embedded skin samples from 40 patients with MF (21 patch stage, 10 plaque stage, nine tumour stage) and 30 non-neoplastic control skin samples were analysed. CXCL12 and CXCR4 were assessed by quantitative reverse-transcription polymerase chain reaction and immunohistochemical staining. RESULTS: The expression level of mRNA for CXCL12 in plaque-stage MF was significantly higher than in control skin (P = 0.0035), or patch-stage (P = 0.0108) or tumour-stage disease (P = 0.0089). The CXCR4 mRNA expression level in plaque-stage disease was significantly higher than in control skin (P = 0.0090) or patch-stage disease (P = 0.0387). CXCL12- and CXCR4-positive cell rates in patch-stage and plaque-stage MF were significantly higher than those in control skin (P < 0.0001). CXCL12- and CXCR4-positive cell rates in tumour-stage MF were significantly lower than those in patch- and plaque-stage disease (P = 0.0274 and P = 0.0492, respectively). CONCLUSIONS: Our data suggest that neoplastic T cells in MF are exposed to the microenvironment, given the abundance of CXCL12 during its progression, and also that neoplastic T cells express CXCR4, especially in the pretumour stage. We reveal that the CXCL12-CXCR4 axis plays a critical role in MF progression.

Ganglioglioma originating in the cerebellum with a large cyst--a case report and review of the literature.

Here we report a rare case of cerebellar ganglioglioma accompanied by a large cyst, and present a review of the reported 28 cases with cerebellar ganglioglioma. An otherwise healthy 46-year-old woman complained of gradual headache and truncal ataxia. MRI revealed a huge cystic lesion with a mural nodule in the left cerebellar hemisphere. The tumor was resected totally. Histologically, it was composed of neuronal and glial elements, and was accordingly diagnosed as ganglioglioma.

Localization of Fas and Fas ligand in bone marrow cells demonstrating myelodysplasia.

Frequent apoptosis in the bone marrow of patients with myelodysplastic syndromes (MDS) was demonstrated on frozen sections using the terminal deoxytransferase (TdT)-mediated dUTP nick end labeling (TUNEL) method. The overall mean percentage of TUNEL-positive cells was about 17% in the bone marrow of MDS, while bone marrow from control cases exhibited a mean of 3.4% (P < 0.001). To elucidate the mechanism of apoptosis in bone marrow cells of MDS, the expression of Fas antigen and Fas ligand (FasL) was examined by RT-PCR and immunohistochemistry. All MDS cases showed expression of Fas mRNA (12/12) and most exhibited an expression of FasL mRNA (10/12) by RT-PCR. Basically, control cases did not show positive signals for Fas and FasL mRNA, however, a very weak band was detected in three cases (3/10) for Fas and in one case (1/10) for FasL mRNA by RT-PCR. Immunohistochemical examination revealed positive staining for Fas (11/12) and FasL (12/12) in the bone marrow of MDS, while all the bone marrow samples from control cases were negative for anti-Fas (0/15) and for anti-FasL (0/15) antibody. Double staining clarified that TUNEL-positive apoptotic cells expressed Fas antigen on the cell surface, although not all Fas-positive cells were TUNEL positive. The Fas-positive cells of MDS bone marrow included hematopoietic cells expressing CD34 antigen, neutrophil elastase, a marker for myeloid series of cells, or glycophorin A, a marker for erythroid cells. However, CD68-positive cells which were macrophage lineage cells, did not express Fas antigen strongly. In contrast, positive staining for FasL was detected in hematopoietic cells and CD68-positive cells in the bone marrow of MDS. These results suggest that the Fas-FasL system plays an important role in inducing apoptosis in the bone marrow of MDS and works in an autocrine (hematopoietic cell-hematopoietic cell interaction) and/or paracrine (hematopoietic cell-stromal cell interaction) manner.

Overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma by bone marrow cells from patients with myelodysplastic syndromes.

To clarify whether regulatory cytokines inhibit hematopoiesis in patients with myelodysplastic syndromes (MDS), malignancies characterized by the formation of cytopenias despite the presence of cellular bone marrow, expression of TNF-alpha and IFN-gamma by bone marrow cells was investigated using specific reverse transcriptase-polymerase chain reaction assays. An enhanced expression of the mRNA for TNF-alpha was observed in most of the samples from MDS patients (11/14, 79%), whereas no enhancement was observed in bone marrow samples from AML (0/6), CML (0/2) or control cases (0/8). The expression of IFN-gamma was also enhanced in some of MDS cases (5/12, 42%) while AML (0/5), CML (0/2) and control cases (0/6) showed very low levels of IFN-gamma mRNA expression. Immunohistochemical examination confirmed the scattered presence of TNF-alpha or IFN-gamma producing cells in the bone marrow of MDS patients. The majority of these cells were CD68-positive macrophage lineage cells. These results suggested that disruption of hematopoiesis in MDS might be caused by enhanced production of inhibitory regulatory cytokines especially TNF-alpha and occasionally IFN-gamma by bone marrow macrophages.

Optimization of network robustness to waves of targeted and random attacks.

We study the robustness of complex networks to multiple waves of simultaneous (i) targeted attacks in which the highest degree nodes are removed and (ii) random attacks (or failures) in which fractions p(t) and p(r) , respectively, of the nodes are removed until the network collapses. We find that the network design which optimizes network robustness has a bimodal degree distribution, with a fraction r of the nodes having degree k2 = ((k)-1+r)/r and the remainder of the nodes having degree k1=1, where k is the average degree of all the nodes. We find that the optimal value of r is of the order of p(t)/p(r) for p(t)/p(r) << 1.

Maintaining bone mass by bisphosphonate incadronate disodium (YM175) sequential treatment after discontinuation of intermittent human parathyroid hormone (1-34) administration in ovariectomized rats.

Intermittent treatment with human parathyroid hormone (1-34) [hPTH(1-34)] stimulates bone formation and increases cancellous bone mass in ovariectomized (OVX) rats. But PTH-induced cancellous bone rapidly disappears upon cessation of treatment. The fate of cortical bone treated by PTH has not been well characterized. Incadronate disodium (disodium cycloheptylaminomethylenedisphosphonate monohydrate, YM175) was expected to be antiresorptive without inhibiting bone formation. The purposes of this study were to determine (1) whether PTH treatment increases new cancellous and cortical bone mass and bone formation, (2) whether the new bone could be maintained by YM175 sequential treatment, and (3) whether the maintenance effect is persistent after YM175 withdrawal. Eighty-eight 11-week-old Sprague-Dawley rats were divided into sham operation and OVX groups. The OVX rats were treated for 8 weeks with the subcutaneous intermittent injection of 30 micrograms/kg of hPTH(1-34) three times a week beginning 4 weeks after surgery, then PTH treatment was withdrawn and YM175 (10 micrograms/kg) was injected subcutaneously three times a week for 4 weeks. YM175 treatment was withdrawn for the last 8 weeks of the protocol. The results of microstructural assessment in proximal tibial metaphysis and bone mineral density in distal and proximal femur demonstrated that PTH treatment for 8 weeks restored bone mass to the sham control level. However, after cessation of PTH treatment, the PTH-induced tibial cancellous bone mass showed a decrease at 4 weeks and almost totally disappeared after 12 weeks. Conversely, YM175 treatment maintained the PTH-induced tibial cancellous bone mass, and the bone continued to be maintained after 8 weeks of withdrawal of the YM175. Cortical bone was not lost during PTH treatment. YM175 maintained the PTH-induced new tibial cancellous bone in OVX rats by suppressing remodeling.

Changes in biological activity of bone cells in ovariectomized rats revealed by in situ hybridization.

Twelve-week-old female rats were ovariectomized (OVX) and compared with sham-operated control rats at 3, 5, 7, 10, 14, 30, and 60 days postoperation with respect to the expression of type I collagen and osteopontin mRNAs, as well as bone structure and the number of osteoclasts. The trabecular number and separation were significantly decreased and increased, respectively, in the metaphyseal trabecular bones of OVX rat femurs. The number of osteoclasts was significantly increased in the same region of OVX rats at 3 and 5 days postoperation. Type I collagen mRNA was expressed in osteoblasts, and osteopontin mRNA was expressed in some osteoclasts, in mononuclear cells on the bone resorption surface, and in osteocytes near the resorption surface. In the metaphyseal trabecular bone, type I collagen and osteopontin mRNA expression levels in individual cells was initially increased in OVX rats from 7 to 10 days postoperation, and this was sustained for 60 days. The number of osteopontin mRNA-expressing osteocytes was also significantly increased at 10 days postoperation, which lasted until 60 days. In the epiphysis, an increase in type I collagen mRNA expression was initially observed in OVX rats at 14 days postoperation, which lasted until 60 days. The number of osteopontin mRNA-expressing osteocytes was virtually identical until 30 days postoperation in the epiphysis. These findings indicated that the biological activities of osteoblasts and osteocytes are stimulated in bones of the OVX rat and that the response for OVX differs between the metaphysis and epiphysis. Furthermore, the number of osteopontin mRNA-expressing osteocytes was increased only in bones that tended to be resorbed after OVX. This indicates that some osteocytes were stimulated to express osteopontin mRNA by estrogen deficiency and suggests that these osteopontin mRNA-expressing osteocytes may be involved in regulation of bone metabolism.

Changes in cortical width with bone turnover in the three different endosteal envelopes of the ilium in postmenopausal osteoporosis.

Histological indicators of bone turnover were compared in the three endosteal envelopes (cancellous, endocortical, and intracortical) of iliac bone specimens obtained from 82 osteoporotic women, to assess the correlation between bone turnover and bone volume in different remodeling sites. Although there was a significant but weak correlation between the mineral apposition rate (MAR), a histological indicator of bone formation at the basic multicellular unit (BMU) level, and the three endosteal envelopes, the bone formation rate corrected for bone surface (BFR/BS) and mineralizing surface (MS/BS), indicators of the rate of bone formation reflecting activation frequency, in the cancellous and endocortical envelopes was more closely related to the rate in the intracortical envelope. The endocortical BFR/BS and MS/BS were higher than the rate in the cancellous envelope (1.6-2.1 times and 2.0-2.4 times, respectively), indicating a higher turnover rate in the endocortical envelope. According to stepwise regression analysis of the significant determinants contributing to bone mass, several histological determinants relating to bone turnover were identified: (1) trabecular thickness (Tb.Th) was a positive determinant, whereas age and cancellous bone volume referent BFR (BFR/BV) were negatively correlated determinants of the cancellous bone volume (BV/TV) (R2 = 0.50, p < 0.001); and (2) the endocortical wall thickness (W.Th) of the given side and the cortical width (Ct.Wi) of the opposite side were positive determinants, whereas the cancellous osteoid surface (OS/BS), cancellous MAR, and endocortical eroded surface (ES/BS) of the given side were the negatively correlated determinants of the Ct.Wi of the thicker cortex (R2 = 0.62, p < 0.001). In the thinner cortex, the endocortical W.Th of the given side and Ct.Wi of the opposite side were only used as the positive determinants of the Ct.Wi of the given side (R2 = 0.55, p < 0.001). In addition: (3) a significant but weak correlation was found using the intracortical BFR/BV as a positively correlated determinant of the cortical porosity (Ct.Po) in the thicker cortex (R2 = 0.17, p < 0.01). Although these histological determinants do not fully explain the mechanisms of bone loss, an increased rate of bone turnover contributes to bone loss not only in the cancellous and intracortical envelopes, but also in the endocortical envelope, indicating increased endocortical bone resorption in osteoporosis.

Discrepancy of response of hPTH administration and its withdrawal between trabecular and cortical bone sites in OVX rats.

We demonstrated the differences of response between trabecular and cortical bone sites in the rat induced by OVX and hPTH(1-34) administration [subcutaneous injection, 30 micrograms/kg, 3 times/week, for 12 weeks] and its withdrawal [for 8 weeks]. We observed that hPTH(1-34) administration in OVX rats partially prevented OVX-induced cancellous bone loss in the proximal tiabial metaphysis and added cortical bone in the tibial shaft. After cessation of hPTH treatment, bone loss was observed both in trabecular and cortical bone; however, it was more dramatic on endocortical surfaces.

A histomorphometric study on effects of single and concurrent intermittent administration of human PTH (1-34) and bisphosphonate cimadronate on tibial metaphysis in ovariectomized rats.

This study compared the single administration of hPTH(1-34), bisphosphonate cimadronate (YM-175), and concurrent therapy of these two for restoration of lost bone mass in ovariectomized (OVX) rats. Animals were untreated for 4 weeks after surgery, and then injected s.c. with vehicle (OVX+V), hPTH(1-34) (30 micrograms/kg) (OVX+P), YM-175 (5 micrograms/kg) (OVX+Y), or a combination of these two (OVX+P+Y), 3 days a week, for 8 weeks, and sacrificed. Their proximal tibia were processed undecalcified for quantitative bone histomorphometry. Although OVX+Y showed a reduction of bone turnover compared to OVX+V, it failed to restore lost bone mass in OVX rats. In contrast, OVX+P exhibited a stimulation of bone formation and restored cancellous osteopenia due to OVX. OVX+P+Y also resulted a recovery of osteopenia, however, stimulation of bone formation by PTH was suppressed by YM-175.

Bone particles disturb new bone formation on the interface of the titanium implant after reaming of the marrow cavity.

Histomorphometric studies were conducted in rats to determine whether bone particles would disturb new bone formation on the interface of titanium implants inserted after reaming of the marrow cavity. In eighty 10-week-old female Wistar rats, smooth-surfaced titanium alloy implants were inserted bilaterally into the marrow cavity after reaming in the distal femur. There were three experimental groups: in the irrigated femora, sterile saline was flushed through the medullary canal; in the particle femora, autologous bone particles were inserted into the intramedullary cavity; and in the reamed femora, the implant was inserted without procedures after reaming. The rats were sacrificed at one, two, four or eight weeks postoperatively, and Villanueva bone staining was applied for histomorphometric studies. The bone volume of new bone on the interface of the implant in the irrigated femora was greater than that in the particle or the reamed femora throughout the study period. The results suggest that clearance of bone particles by irrigation after reaming of the marrow cavity significantly facilitates new bone formation on the interface of implants by one week. The findings also suggest the potential clinical application of total canal irrigation prior to insertion of cementless femoral components as well as cemented prosthesis.

Three-dimensional microstructural analysis of human trabecular bone in relation to its mechanical properties.

The purpose of this preliminary study is to explore the relationship between elastic modulus, bone mineral density (BMD), and trabecular microstructure in three dimensions. Twenty cubes of trabecular bone were processed from two lumbar vertebrae obtained from one individual. The BMD of each cube was measured by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Each cube was serially scanned by microcomputed tomography to produce three-dimensional data sets. By analyzing these data sets, three-dimensional trabecular microstructural indices of connectivity density and fractal dimension were calculated as well as histomorphometric parameters. The cubes were tested mechanically in a nondestructive manner for measurement of their elastic modulus. This preliminary study showed that: (1) bone mass index is correlated with mechanical properties, with coefficients of correlation ranging from 0.552 to 0.601; and (2) when controlling for BMD, no association could be detected between measures of structural complexity (connectivity density and fractal dimension) and elastic modulus in the craniocaudal direction of human vertebral bodies.

Effects of intermittent administration of low dose human PTH(1-34) on cancellous and cortical bone of lumbar vertebral bodies in adult beagles.

This study assessed the effect of low dose human parathyroid hormone [hPTH(1-34)] administration on cancellous and cortical bone of lumbar vertebrae in intact male beagles. 16 19-20-month-old beagle dogs were randomized into four groups: in group 1, the vehicle control group, saline was injected daily; in group 2, the sequential group, 0.375 microg/kg of PTH was injected daily for 4 weeks, then off 8 weeks, and this sequence was once repeated for another 4 and 8 weeks; in group 3, the same dose of PTH was injected once per week for 24 weeks; and, in group 4, PTH was injected three times per week for 24 weeks. Histomorphometric assessment on cancelllous and cortical bone (both ventral and dorsal shell) and two-dimensional node-strut analysis were done on the fifth lumbar vertebral bodies after calcein double bone labeling. In intact adult beagles, on the group treated with 0.375 microg/kg per day three times per week (group 4): (1) had a higher mean value in cancellous bone formation parameters [osteoid surface (+74%), osteoid volume (twofold), mineral apposition rate (+21%), and bone formation rate (twofold)]; (2) exhibited no effect on cortical thickness and porosity in both the ventral and dorsal shell; and (3) showed a lower mean value of node to termini (0.11 +/- 0.02 vs. 0.22 +/- 0.09) and a higher mean value of cortex to node (0.18 +/- 0.06 vs. 0.08 +/- 0.02), but not in trabeculae to trabeculae node, than age-related controls. In conclusion, we found that a low dose of PTH administration: (1) stimulated cancellous bone formation; (2) improved connectivity of trabeculae joined to the cortex; (3) did not decrease cortical thickness; and (4) did not increase cortical porosity in both ventral and dorsal cortexal shell of the lumbar vertebrae during this dosage and period in intact male beagles.

Reduction in bone formation and elevated bone resorption in ovariectomized rats with special reference to acute inflammation.

Changes in bone modeling and remodeling in the tibia of growing rats within 30 days of ovariectomy (ovx) were evaluated by histomorphometric, mechanical; and biochemical means. Three days after ovx, suppressed bone formation was seen. This was shown by reduced osteoid volume, osteoblast surface, and bone formation rate in the secondary spongiosa, and a reduced longitudinal growth rate in the growth plate. In addition, the alkaline phosphatase and tartrate-resistant acid phosphatase activity in bone marrow supernatants was suppressed in conjunction with elevated serum sialic acid levels, indicating inflammation. Although estrogen deprivation itself may provoke the inflammatory process, the serum sialic acid level in the ovx group returned to the baseline level within 5 days after surgery, while that of estradiol in the ovx group remained consistently lower. This suggests that surgical stress, not estrogen deprivation, is the primary cause of the inflammatory response shortly after ovx. A significant difference (p < 0.01) between the ovx and sham rats was seen in the osteoclast surface, which peaked on day 7 in the ovx rats. On day 14 postovariectomy, the bone formation rate peaked and remained constant until day 30. In the ovx rats, there was a sustained reduction in the serum albumin level until day 30. Estrogen deprivation may be the primary cause of these changes, because both surgical ovx and medical oophorectomy with gonadotropin-releasing hormone agonist (G(nRHa) reduce the serum albumin level. In numerous studies dealing with changes after ovx in rats, we have observed: 1) a transient reduction in bone formation in relation to inflammatory changes evoked by ovx surgery, and 2) a sustained reduction in the serum albumin level for at least 30 days after ovx that is possibly due to estrogen deprivation.

Increased bone formation by intermittent parathyroid hormone administration is due to the stimulation of proliferation and differentiation of osteoprogenitor cells in bone marrow.

In order to examine the mechanism of the anabolic effect of parathyroid hormone (PTH) on bone formation, human PTH(1-34) [hPTH(1-34)] (30 micrograms/kg) was injected subcutaneously to 9-week-old rats 5 times a week for 1 or 3 weeks. Trabecular bone volume (BV/TV) in the tibial metaphysis was not significantly different between the PTH- and vehicle-treated groups, but the parameters related to bone formation, including osteoid surface (OS/BS), mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS), were significantly increased as early as 1 week after PTH treatment. And the parameters related to bone resorption including eroded surface (ES/BS) and osteoclast number (N.Oc/BS) were also significantly increased as early as 1 week after PTH treatment. Treatment with PTH for 1 week induced no significant increase in bone mineral density at the femoral metaphysis, whereas the same treatment for 3 weeks induced a significant increase. When bone marrow cells isolated from femora and tibiae of either PTH- or vehicle-treated rats were cultured at a high density (2 x 10(7) cells/one well of 24-multiwell plate), cellular alkaline phosphatase (ALP) activity was significantly increased in the cells isolated from PTH-treated rats compared with vehicle-treated rats. When bone marrow cells were cultured at a low density (4 x 10(6) cells/a one well of 6-multiwell plate) to generate colonies (colony forming unit-fibroblastic, CFU-F), PTH induced apparent increases in both the total number of CFU-F and the number of ALP-positive CFU-F.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunolocalization of platelet-derived growth factor, transforming growth factor-beta, and fibronectin in acute megakaryoblastic leukemia manifesting tumor formation.

Acute megakaryoblastic leukemia (AMKL) manifesting myelofibrosis and tumor formation in the liver with marked increase of reticulin is described. The megakaryoblastic nature of the leukemic cells of the bone marrow and the hepatic tumor nodule was established by positive immunohistochemical stains for CD41a and CD41b on frozen tissue sections. Immunolocalization of the platelet-derived growth factor (PDGF) protein and transforming growth factor (TGF)-beta protein also was demonstrated in the leukemic cells of the bone marrow and the hepatic tumor. Further, the deposition of fibronectin that has been known as the ligand of CD41a molecule and collagen types I and IV were recognized in the extracellular matrix of the bone marrow and the hepatic tumor. These results suggest that specific expression of growth factor proteins by the leukemic cells may selectively regulate the fibrosis of the bone marrow as well as the tumor formation of AMKL. The expression of adhesion molecules and growth factor proteins by the leukemic cells and the deposition of extracellular matrix are discussed in relation to the myelofibrosis as well as the tumor-forming nature of AMKL.

Glomerulonephritis with focal and segmental distribution of glomerular basement membrane antigen(s).

In this report, the authors describe a case of a 2-year, 11-month-old girl with glomerulonephritis and no family history of renal diseases and deafness. Immunofluorescent studies in the renal biopsy specimens with the use of anti-sera against human glomerular basement membrane (GBM) and P3 antigen (prepared from bovine GBM and inducible of Steblay's type nephritis in rats) demonstrated focal and segmental distribution of the GBM antigen(s). Electron microscopic examination revealed splitting and thinning of the GBM. Indirect immunofluorescence showed that there was no binding of Goodpasture's anti-GBM antibodies to the glomeruli. These findings are similar to those in patients with hereditary nephritis. The immunofluorescent examination of the fixation of the various anti-sera, including anti-types IV and V collagens, laminin, fibronectin, and actomyosin sera on the GBM, revealed normal reactivity. The abnormalities observed in this case may be a part of the spectrum of primary GBM defects.

Effects of human PTH(1-34) and bisphosphonate on the osteopenic rat model.

It has been demonstrated that the intermittent administration of human parathyroid hormone (hPTH) is beneficial for restoration of bone mass in osteoporotic patients. The mechanisms of anabolic effects of hPTH have been determined by ovariectomized rat models and other larger remodeling animals. However, treatment with hPTH may increase the cancellous bone mass at the expense of cortical bone mass and cessation of the treatment results in rapid bone loss. Efforts have been made to maintain newly formed bone mass after withdrawal of the hPTH treatment. These issues are not well understood. In this article, the authors would like to represent previous studies of their own and others concerning these issues.

Silent and progressing accumulation of aluminum in bone without definite histological osteomalacic aspects in chronic hemodialysis patients.

The aluminum (Al) contents of the tap water and the dialysis fluid in our center had proven to be less than 10 micrograms/l during more than 10 years. We evaluated the Al content, stainable Al, and the histomorphometry of the bone biopsy specimens from the 23 chronic renal failure patients on dialysis. The plasma Ca, P, Mg, ALP, C-PTH, and Al levels except calcitonin (CT, r = 0.442, p < 0.05) had no significant relationship to the hemodialysis (HD) duration. Their bone histologies were classified as osteitis fibrosa (OF) in 9, mild type (MILD) in 11, mixed type (MIXED) in 2, and osteomalacia (OM) in 1. The stainable Al% on the trabecular bone surface showed a positive correlation with HD duration (r = 0.569, p < 0.001), with the bone Al content (r = 0.455, p < 0.05), and with the bone Al/Ca ratio (r = 0.668, p < 0.01), respectively. The bone Al, Ca and Mg content did not correlated with HD duration and with plasma Al levels, although the bone Al/Ca ratio showed a strong correlation with HD duration (r = 0.675, p < 0.01) and with plasma Al levels (r = 0.719, p < 0.001). In the histomorphometric parameters, plasma Al levels, stainable Al, bone Al content, as well as bone Al/Ca ratio had no significant correlation with the osteomalacic aspects. Thus, our observations revealed that the Al accumulation in the bones was latent and progressing without definite osteomalacic changes, even though the dialysate Al concentration was under the critical level. Other Al invasion roots besides dialysis fluid should be regarded, including oral intake of Al-containing phosphate binders or other gastrointestinal medicines, as well as food content.