Effect of partially purified bone morphogenetic protein on DNA synthesis and cell replication in calvarial and fibroblast cultures

The effects of bone morphogenetic protein (BMP), a molecule extracted from demineralized bone, were observed in organ cultures of 21-day fetal rat calvariae. The effects of BMP on cell replication in cultures of normal rat kidney (NRK) fibroblasts were studied for comparison. At concentrations of 0.1-10 micrograms/ml for periods of 24-96 hours, BMP stimulated the incorporation of 3H-thymidine into acid-insoluble residues (DNA) in calvariae by 25%-159%, and at 1-10 micrograms/ml it increased bone DNA content by 20%-23%. BMP at 1 micrograms/ml also increased the number of calvarial mitoses after colcemid arrest by 1.5-1.8-fold. The effect of BMP on calvarial DNA synthesis was observed in the periosteal bone. In contrast to its effects on DNA synthesis, BMP did not stimulate the incorporation of 3H-proline into collagenase-digestible and noncollagen protein and did not alter calvarial alkaline phosphatase activity. BMP at 1-10 micrograms/ml caused a marked increase in 3H-thymidine incorporation into DNA in cultured NRK fibroblasts and increased DNA content and cell number by 1.5-2-fold. These studies indicate that BMP stimulates DNA synthesis and cell replication in calvarial and fibroblast cultures but does not stimulate postdifferentiated bone cells in incubated calvariae.     

Effect of simvastatin on bone morphogenetic protein-2 expression and alkaline phosphatase activity of bone marrow stromal cell]

OBJECTIVE: To study the effect of simvastatin on the expression of bone morphogenetic protein-2 (BMP-2) and alkaline phosphates (ALP) activity in the primary cultured bone marrow stromal cells, and to elucidate the mechanism of the anabolic osteogenetic effect of simvastatin. METHODS: Bone marrow stromal cells in femur and tibia of adult mouse were cultured in vitro. after treated with different concentrations of simvastatin (0, 0.1, 0.2, 0.5 and 1.0 mumol/L) or recombinant human BMP-2 for 72 hours, ALP activity of bone marrow stromal cells was determined. BMP-2 expression of bone marrow stromal cells was analyzed by using immunocytochemistry and Western blotting. RESULTS: After treated with simvastatin for 72 hours, BMP-2 expression increased, while little BMP-2 expression could be observed in the control group. ALP activity also increased in a dose-dependent manner; t-test showed that ALP activity in the group which concentrations of simvastatin were 0.5 mumol/L (t = 2.35, P = 0.041), 1.0 mumol/L (t = 2.348, P = 0.041) had significant difference when compared with control group. CONCLUSION: Simvastatin lead to high expression of BMP-2 in bone marrow stromal cells, via the increased auto- or para-crine of BMP-2, and ALP activity increased. These may be parts of the mechanism on the anabolic osteogenetic effect of simvastatin.     

Expression of collagen,osteocalcin, and bone alkaline phosphatase in a mineralizing rat osteoblastic cell culture

Summary Rat calvaria bone cells isolated by collagenase digestion form a bone-like matrix which mineralizes in vitro in the presence of -glycerophosphate, in less than 2 weeks. The purpose of this work was to investigate, in this mineralizing rat osteoblastic cell culture, the synthesis of collagen, osteocalcin, and bone alkaline phosphatase (ALP). The results obtained indicate (1) After 15 days in culture, the extracellular-matrix contains collagen type I, V, and to some extent type III. Metabolic labeling at day 14, during the phase of nodules mineralization as well as new nodules formation, shows that collagen types I and type V are synthesized; (2) During the phase of cell growth, no osteocalcin could be detected in the medium, however, at the point of nodule formation, the osteocalcin level reached values of 3.55±1.39 ng/ml, followed by a 30-fold increase after nodules became mineralized. At day 14, after metabolic labeling, de novo synthesized osteocalcin was chromatographed on an immunoadsorbing column. With urea-SDS PAGE the apparent molecular weight was determined to be 9,000 daltons. (3) Specific activity of ALP was found to be 10 nmol/min/mg of proteins at cell confluence. At day 15, when nodules are mineralized, this activity was increased by 40-fold. The Michaelis constant was 1.58 10^-3 M/L. ALP was inhibited by L-homoarginine and levamisole but not by L-phenylalanine. ALP was shown to be heat sensitive at 56°C with two slopes of inhibition. On SDS-PAGE, apparent molecular weight of ALP showed one band at 116,000 daltons (d) when extracted at cell confluence and two bands at 116,000 and 140,000 d when extracted at the 15th day of culture. ³²P-labeled subunit of the enzyme migrated as one band at 75,000 d. Sialic acid content was demonstrated by neuraminidase treatment either on the dimeric form or on the ³²P-labeled subunit. These data indicate that ALP expressed in this culture is bone specific. The results of the present study show that this mineralizing rat osteoblastic cell culture system synthesizes collagen type I, V, and traces of type III, osteocalcin, and bone ALP isoenzyme. Medium osteocalcin was detected during nodule formation and increased during mineralization. Increase in ALP activity as well as the presence of an additional form of ALP occurred in the mineralization phase. Therefore, this culture may be a useful model for studying the functions of bone-specific proteins during the process of mineralization.     

Ectopic bone induction on and in porous hydroxyapatite combined with collagen and bone morphogenetic protein

Porous hydroxyapatite (HA-P) discs (5 mm in diameter; 1.5 mm thick; porosity, 80%; mean pore size, 200 micron) were impregnated with purified bovine skin collagen (1 mg/disc) and a small amount of semipurified bone morphogenetic protein (BMP) of sarcoma origin (100 micrograms/disc) and implanted into dorsal muscles of ddY mice. Within one week new ectopic cartilagenous tissue was consistently formed on the surface of the discs adjacent to the host tissue. The cartilage was resorbed and replaced by normal bone containing hematopoietic bone marrow four weeks after implantation and the discs became encased in the newly formed bone. HA-P discs impregnated with only collagen (HA-P/collagen) or only BMP (100 micrograms/disc; HA-P/BMP) did not evoke formation of new cartilage or bone. These results indicate that collagen is effective as a carrier of BMP for expression of the biologic activity of the latter in vivo and that it may be of practical use as a carrier of BMP with synthetic biomaterials.     

Profile of placental alkaline phosphatase expression in human malignancies: effect of tumour cell activation on alkaline phosphatase expression

Cellular alkaline phosphatases (ALP) are increasingly recognised as important markers for monitoring tumour cell behaviour in human malignancies. Colorimetric, flow-cytometric, and immunocytochemical assays were employed to assess the influence of activation on expression of cellular ALP in human tumour cell lines. The results showed the following: (1) Testis tumour biopsies (16/16) unlike bladder (0/14) and head and neck (0/16) tumours showed positive staining for ALP, particularly the placental type, i.e. PLAP, although this was not always present on all the cells of non-seminoma biopsies. (2) The intensity of ALP expression differed widely in tumour cell lines. Based on biochemical analysis, the profile of ALP fell into two categories: (a) low expressing (MW 70 kD, placental type ALP) like Hep2 and KB lines, and (b) those expressing both low and high molecular (MW 95 kD) bands like testis lines Tera II and Ep2102. In all cases treatment of tumour cell lysates with heat prior to biochemical analysis showed the disappearance of the higher and sharpening of the lower molecular weight ALP band. (3) Exposure of tumour cells to epidermal growth factor (EGF) expressing EGF receptor led to a decreased ALP expression by as much as 54% as assessed by biochemical or flow-cytometric techniques. These data demonstrated that testis tumour tissues and cell lines expressed ALP which were different from others. The data also showed that exposure of tumour cell lines expressing EGFr to EGF resulted in suppression of ALP expression. These observations are consistent with the notion that EGFr and PLAP expression may be taken as a marker of proliferation and differentiation in human malignancies, respectively.     

血液透析对患者血清碱性磷酸酶、骨硬化蛋白与骨代谢的影响

目的血液透析对患者血清碱性磷酸酶(ALP)、骨硬化蛋白(SOST)与骨代谢等指标的影响。方法选取本院2016年1月至2019年1月期间收治的血液透析患者116例为研究对象纳入观察组,另选同期在本院进行体检的50例健康受试者为对照组。采用酶联免疫吸附试验法对两组患者入院时的ALP、SOST、骨代谢指标:血清骨钙素(OC)、β胶原蛋白(β-CTX)、I型前胶原氨基末端前肽(PINP)指标水平,并进行组间对比。对观察组患者进行维持性的血液透析治疗,并检测比较在患者透析治疗前、透析治疗1、6、12个月的各项指标水平。采用Pearson检验对观察组患者的ALP、SOST与骨代谢指标的相关性进行分析。结果与对照组比较,观察组患者血液透析治疗前ALP、SOST、OC、β-CTX、PINP等指标均低于对照组受试者各项指标水平,组间比较差异有统计学意义(P<0.05)。观察组患者中随着透析治疗时间的延长,患者的ALP、SOST、OC、β-CTX、PINP等指标水平均明显上升,各时间点间比较差异有统计学意义(P<0.05)。经Pearson检验分析,血液透析患者的ALP、SOST与骨代谢指标OC、β-CTX、PINP呈正相关性。结论血液透析患体内的ALP、SOST、骨代谢指标均呈现异常降低,经持续性血液透析治疗患者的ALP、SOST、骨代谢指标均有改善,且ALP、SOST与骨代谢指标OC、β-CTX、PINP呈正相关性。     

Protein tyrosine kinase inhibitors block the stimulatory actions of phosphotyrosine phosphatase inhibitors to increase cell proliferation, alkaline phosphatase activity, and collagen synthesis in normal human bone cells

The present study sought to test whether inhibition of phosphotyrosine phosphatases (PTPs) would stimulate proliferation and differentiation of normal bone cells, and whether the PTP inhibitor-mediated effects would be blocked by protein tyrosine kinase (PTK) inhibitors. Three inhibitors [phenylarsine oxide (PAO), orthovanadate (VO(4)), and molybdate (MoO(4))] and two normal human bone cells with different basal differentiation status (i.e., mandible- and vertebra-derived bone cells) were used. Cell proliferation was determined with [(3)H]thymidine incorporation, and confirmed by cell counting. Bone cell differentiation was assessed by increases in alkaline phosphatase (ALP) specific activity and collagen synthesis. The three test PTP inhibitors each stimulated [(3)H]thymidine incorporation in both human bone cell types in a biphasic, dose-dependent manner with optimal doses of 20 nM PAO, 1 microM VO(4) and 2 microM MoO(4), respectively. These PTP inhibitors at mitogenic doses each significantly and reproducibly increased ALP specific activity and collagen synthesis. To determine whether the stimulatory effects of PTP inhibitors could be blocked by PTK inhibitors, the effects of tyrphostin A51 and erbstatin, two potent PTK inhibitors, on the actions of PTK inhibitors on [(3)H]thymidine incorporation and ALP specific activity were evaluated. Both tyrphostin A51 and erbstatin, which by themselves alone significantly inhibited human bone cell proliferation and increased ALP specific activity, completely abolished the stimulatory effects of each of the three test PTP inhibitors on bone cell proliferation and ALP specific activity. In conclusion, these findings confirm the premise that inhibition of PTP activities in normal human bone cells could lead to increases in cell proliferation and differentiation, effects that are independent of basal differentiation status of the cells. More importantly, this study demonstrates for the first time that the stimulatory actions of the PTP inhibitor on bone cell proliferation and ALP could be blocked by a PTK inhibitor, suggesting that the osteogenic effects of PTP inhibitors may depend on PTK activities, presumably to increase basal tyrosyl phosphorylation level. Accordingly, one should interpret results of studies using PTK inhibitors with caution in that an inhibition by a PTK inhibitor does not necessarily indicate the requirement of PTK activities, as it could also suggest involvement of an inhibition of PTPs.     

Distal metaphyseal tibial nonunion. Deformity and bone loss treated by open reduction, internal fixation, and human bone morphogenetic protein (hBMP)

Four patients with severely deformed nonunions of the distal end of the tibia failed to respond to standard surgical methods and were successfully treated as follows: debridement of fibrous tissue, sequestrectomy, correction of angulatory deformities, internal stabilization, and implantation of human bone morphogenetic protein (hBMP). After resection of the sequestra, all four patients had significant bone defects of the anterior tibial cortex extending to the ankle joint. The average number of failed previous surgical procedures was 5.8. The average patient age was 35.3 years. The intervals of nonunion averaged 24.8 months. In two patients, the hBMP, including other low molecular weight bone matrix noncollagenous proteins (hBMP/NCP), was implanted across the fracture site in polylactic-polyglycollic acid strips (1 X 13 cm) as an onlay graft. In one patient, the BMP was implanted in the fracture gap in absorbable gelatin (No. 5 capsules). In another patient, the BMP/NCP was also implanted in the form of a composite of cortical allogeneic bone in addition to a capsule of BMP/NCP. In all four cases, alignment was restored and the bone ends were stabilized with internal fixation. Preoperatively, the ankle joints were ankylosed and painful. Healed fractures and functional ankle joints were observed in three of four patients at an average of 4.4 months. In one patient, the fracture healed but the joint remained ankylosed. Although a randomized double-blind consecutive series of matched cases is necessary to prove the efficacy of hBMP, implants of hBMP combined with skillful surgical treatment are under investigation in the interim as an alternative to amputation.     

Preservation of bone morphogenetic protein in heat-treated bone.

In operations of bone tumors, reimplantation of resected bone after boiling or autoclaving is a simple means of obtaining both tumor necrosis and skeletal reconstruction. However, such reimplants lose their osteogenesity. We investigated whether bone inductive ability could be maintained in heat-treated bone. Bone morphogenetic protein (BMP) extracted from rabbit bone after heating for various periods at different temperatures was implanted into the muscles of mice to evaluate osteogenetic activity. The maximum new bone formation was observed in specimens treated at 70 degrees C for 10 minutes, followed by those treated at 70 degrees C for 15 minutes. We then measured the temperature in the center of a cortical bone heated in 0.15 N NaCl solution at 50 degrees, 60 degrees, 70 degrees, 80 degrees, and 90 degrees C. Cortical bone center temperature reached that of the surrounding solution within 2.5 minutes. These results indicated that heating at 70 degrees for 10 to 15 minutes was suitable for heat treated-bone to maintain bone inductive ability.     

骨形态发生蛋白复合物联合自体骨髓移植治疗四肢长管状骨骨不连

目的:观察骨形态发生蛋白复合物联合自体红骨髓移植治疗四肢长管状骨骨不连的临床疗效.方法:自2004年1月至2010年12月,采用骨形态发生蛋白复合物联合自体红骨髓移植法治疗四肢长管状骨骨不连患者36例,男22例,女14例;年龄22～68岁,平均36.8岁.骨不连部位:肱骨6例,尺骨4例,桡骨3例,股骨10例,胫骨13例.伤后距治疗时间8～24个月,平均13.7个月.增生性骨不连22例,萎缩性骨不连14例 患者主要临床症状为骨折部位负重时疼痛,肢体肿胀X线片提示骨折线清晰伴骨缺损.术后通过观察手术切口愈合、植骨区及骨髓穿刺区反应、骨折愈合、邻近的关节功能恢复等情况评估手术疗效.结果:术后患者切口均甲级愈合,未发现过敏和免疫排斥反应.骨髓穿刺区无感染及血肿形成.36例患者均获随访,时间3～28个月,平均16.2个月.无骨髓穿刺区慢性疼痛、植骨区骨质感染、切口周围皮肤红肿或窦道形成.骨不连均获得骨性愈合,愈合时间3～12个月,平均6.2个月,无畸形愈合.骨不连愈合后骨折部位负重时疼痛消失、肢体肿胀消退.5例患者遗留邻近关节功能部分受限,其余患者均完全恢复.结论:骨形态发生蛋白复合物联合自体红骨髓移植在治疗四肢长管状骨骨不连中具有来源广泛、安全可靠、加速骨愈合等优点,是其理想的植骨材料之一.     

自体骨移植与骨形成蛋白治疗成人长骨骨折不愈合的Meta分析

目的：系统评价自体骨移植与骨形成蛋白治疗成人长骨骨折不愈合相关指标,为成人长骨骨折不愈合治疗提供参考依据。方法：计算机检索PuMed、Embase、Cochrane图书馆、中国知网（CNKI）、万方数据期刊全文数据库及中国生物医学文献数据库（CBM）发表的对于自体骨移植与骨形成蛋白治疗成人长骨骨折不愈合的随机对照试验,检索时间从建库至2019年3月。由2名研究者按照纳入和排除标准独立进行筛选文献,提取资料,并采用Jadad评价量表对纳入的文献进行质量评价。采用RevMan 5.3统计学软件对两种方法的感染发生率、成功愈合率、二次手术率、住院时间及术中失血量进行Meta分析。结果：共纳入7个随机对照试验研究,共652例患者,自体骨移植组有410例,骨形成蛋白组有242例。Meta分析结果显示：自体骨移植组与骨形成蛋白组在感染发生率［RR=1.32,95%CI（0.90,1.93）,P=0.16］,成功愈合率［RR=0.95,95%CI（0.84,1.08）,P=0.43］,二次手术率［RR=1.16,95%CI（0.43,3.12）,P=0.76］及住院时间［MD=0.69,95%CI（-0.38,1.75）,P=0.21］方面比较差异无统计学意义。自体骨移植组术中失血量明显高于骨形成蛋白组［MD=223.00,95%CI（32.72,413.28）,P=0.02］。结论：对于成人长骨骨折不愈合的治疗,骨形成蛋白可以获得和自体骨移植一样的骨折愈合率,同时可以明显减少术中失血量。骨形成蛋白可能更适合成人长骨骨折不愈合的治疗。     

Fluoride and bovine bone extract influence cell proliferation and phosphatase activities in human bone cell cultures

The effects of fluoride (20 mumol/L) and bovine bone extract (17 micrograms/ml) were determined on cultures of human bone cells, embryonic chick bone cells, and human skin fibroblasts. The incorporation of [3H]thymidine into DNA was measured 16 hours after the addition of factors. After three to five days treatment, Triton X-100 extracts of the cells were assayed for acid phosphatase activity, in the presence and absence of tartrate, and for alkaline phosphatase activity. Fluoride stimulated [3H]thymidine incorporation and specific activity of alkaline phosphatase in human bone cells and chick bone cells but not in human skin cells. Fluoride also stimulated the cell population doubling rate of the human bone cells with an optimum of approximately 20 mumol/L. Bovine bone extract stimulated thymidine uptake into DNA several-fold and decreased alkaline phosphatase activity in all three types of cultured cells. The specific activity of tartrate-resistant acid phosphatase was increased in bone cells but not in skin fibroblasts. These results suggest that fluoride specifically stimulates the proliferation and differentiation of osteoblasts, while the growth factors in bovine bone extract primarily stimulate proliferation of bone cells. Cultures of human bone cells respond similarly to chick calvarial cells when treated with fluoride or bovine bone extract.     

A bone replaceable artificial bone substitute: cytotoxicity, cell adhesion, proliferation, and alkaline phosphatase activity

Cellular toxicity, cell adhesion and proliferation, and alkaline phosphatase (ALP) activity were investigated for an artificial bone substitute composed of heated carbonate apatite (CAp) and Type I atelocollagen (AtCol) extracted from bovine tail skins (88/12 in %wt/wt). To enhance the intramolecular crosslinking between collagen molecules, the CAp-AtCol substitutes were irradiated by ultraviolet rays (wave length 254 nm) at 4 degrees C for 4 h or vacuum dried at 150 degrees C for 2 h. Cytotoxicity tests by a direct contact method and an extract dilution method revealed that the CAp-AtCol substitutes were cytocompatible for balb 3T3 fibroblasts. Osteoblast adhesion studies demonstrated that the substitute disks composed of 980 degrees C-heated CAp and AtCol were significantly more adhesive for osteoblasts than those of 1,200 degrees C-sintered CAp and AtCol (p < 0.05). Proliferation studies showed that the number of osteoblasts grown in the media containing substitutes of 980 degrees C-heated CAp and AtCol was statistically higher than grown in those of 1,200 degrees C-sintered CAp and AtCol after 5 days (p < 0.05). It was found that osteoblasts grown in the substitutes of 980 degrees C-heated CAp and AtCol only expressed similar ALP activity to the controls. These results suggested that the substitutes consisting of 980 degrees C-heated CAp and AtCol show more favorable interactions with osteoblasts than those of 1,200 degrees C-sintered CAp and AtCol.     

Downregulation of the expression of bone morphogenetic protein 7 in experimental pyelonephritis

Bone morphogenetic protein 7 (BMP 7) is a member of the transforming growth factor (TGF) beta superfamily and is involved in regeneration, repair, and development of specific tissues, for example kidney, gut, lens, and skeleton. BMP 7 has emerged as a renotrophic factor and experimental studies have shown its protective role against fibrotic processes. Tubulointerstitial changes are present in the pyelonephritic kidney which progresses to fibrosis. Renal fibrosis may lead to significant morbidity in the form of hypertension, proteinuria, and loss of renal function. The objective of this study was to investigate BMP 7 expression in experimental acute and chronic pyelonephritis models. Eighteen Wistar rats were injected with 0.1 mL solution containing E. coli ATCC 25922 10¹⁰ cfu mL^–1 into left renal medullae. Six rats were used as a sham group and were given 0.1 mL 0.9% NaCl. Pyelonephritic rats were sacrificed 24 h (group I, n=6), 1 week (group II, n=6), and 6 weeks (group III, n=6) after E. coli injection. Serum creatinine levels were analyzed. Renal tissues were studied histopathologically by use of hematoxylin and eosin and scored for diagnosis of pyelonephritis. BMP 7 expression was studied semiquantitatively by immunohistochemical staining. Acute (group I) and chronic (group II and group III) pyelonephritic histopathological changes were observed in experimental pyelonephritic groups. A gradual decrease in BMP 7 expression was observed in the tubulointerstitial and tubular area of the pyelonephritic kidneys, mildest in the acute pyelonephritic group and most severe in the chronic pyelonephritic 6th week group. A statistically significant difference was observed between tubulointerstitial BMP 7 expression by groups I and III (P=0.017) and by groups III and IV (P=0.000). Tubular BMP 7 expression was statistically significantly different between groups II and IV (P=0.009) and between groups III and IV (P=0.002). The data imply that BMP 7 has a major role in chronic pyelonephritis. Tubulointerstitial and tubular BMP 7 expression also had a significant negative correlation with fibrosis, tubular, atrophy, and vascular changes. Serum creatinine levels of the study group were all normal. We conclude that the decrease in renal BMP 7 expression in experimental chronic pyelonephritis is one of the factors responsible for fibrotic changes in persistent renal damage.     

Effect of chronic renal failure on bone turnover and bone alkaline phosphatase isoforms.

BACKGROUND: Biochemical markers of bone turnover are used to monitor metabolic bone disease associated with renal failure. We have applied a comprehensive panel of markers to patients with chronic renal failure (CRF), with particular focus on the isoforms of bone alkaline phosphatase (BALP). METHODS: Twenty CRF patients undergoing hemodialysis (N = 9) and peritoneal dialysis (N = 11) were measured for serum parathyroid hormone (PTH), osteocalcin, total ALP, and four BALP isoforms (B/I, B1x, B1, and B2) by high-performance liquid chromatography. These BALP isoforms were also compared with BALP measured by three commercial immunoassays (Alkphase-B, Tandem-R Ostase, and Tandem-MP Ostase). Type I collagen turnover was assessed by serum samples using the type I procollagen intact amino- and carboxy-terminal propeptides (PINP and PICP) and two fragments (ICTP and CrossLaps) derived from the carboxy-terminal telopeptide of mature matrix collagen by different degradative pathways. RESULTS: Mean levels of bone turnover markers were elevated in CRF, with marked increases in those markers, osteocalcin, ICTP, and CrossLaps, cleared by the kidney. Total ALP activities were increased corresponding to elevated B/I and B2 isoform levels. The B1 isoform level was not significantly different from healthy controls. B1x was detected in 60% of the patients but was not resolved in healthy individuals. Kendall's tau rank correlation showed that B1x correlated significantly (P < 0.05) with B1 (0.53) and PINP (0.55), and was the only marker to correlate with PTH (0.49). B1x was not significantly correlated with any of the commercial BALP immunoassays. Interestingly, the immunoassay calibrators contained high activities of the B/I peak (39 to 80%) compared with human serum (4%). CONCLUSION: There are selective differences between the BALP isoforms in CRF compared with healthy adults. The commercial BALP immunoassays are comparable with each other but are unable to distinguish the BALP isoform-specific differences in CRF patients.     

Correlation between parathyroid hormone, bone alkaline phosphatase and N-telopeptide of type 1 collagen in diabetic and non-diabetic haemodialysis patients

BACKGROUND: Haemodialysis (HD) patients with diabetes mellitus often have renal osteodystrophy (ROD) characterized by reduced bone turnover, but little is known about the correlation between bone formation and bone resorption in this population. METHODS: The authors measured serum parathyroid hormone (PTH), bone alkaline phosphatase (BAP), N-telopeptides of type 1 collagen (NTx) and fasting glucose in 48 patients with diabetic nephropathy (DN) and 80 patients with glomerulonephritis (non-DN) who had received or=5 years HD (r = 0.568) this correlation was similar to that in the non-DN group (r = 0.653), whereas there was no significant correlation in those receiving <5 years HD. Patients receiving >or=5 years HD had a comparable glucose level (111.1 +/- 19.2 mg/dL) to the non-DN group, whereas those receiving <5 years had a higher level (196.1 +/- 53.1 mg/dL). CONCLUSION: Differences in the interaction between bone cells between DN and non-DN patients are one potential cause of lower bone turnover in the former group. Research of this correlation is needed to increase understanding of the complexities of bone metabolism in DN patients.