Zur Bedeutung von β-hCG im serum als tumormarker fur das magenkarzinom

Zusammenfassung Einleitung: Nach neueren Untersuchungen ist davon auszugehen, daß bei des Hälfte von Patienten mit einem Magenkarzinom -hCG-positive Zellen im Tumor immunhistochemisch gefunden werden können. Ziel war daher, systematisch zu untersuchen, inwieweit -hCG-immunreaktive Magenkarzinome von einem Anstieg des Serum--hCG begleitet werden and dieses damit als Verlaufsparameter zur Verfügung steht. Methode: Bei 54 Patienten mit einem Magenkarzinom wurde zur immunhistochemischen Darstellung ein gegen -hCG gerichteter monoklonaler Antikörper (Fa. Sigma, 1:100) im APAAP-System verwendet. Die Auswertung wurde nach positiver and negatives Reaktion graduiert. Parallel wurde im Serum des Patienten -hCG präoperativ mit einem Enzymimmunoassay (MEIA, Fa. Abbot) bestimmt. Tumor-stadium, Grading and Tumor-lokalisation werden in die Auswertung mit einbezogen. Ergebnisse: Es wird bestätigt, daß 41% (22 von 54) des Karzinome, unabhängig von ihrer Lokalisation im Magen, eine positive immunhistochemische Reaktion gegen -hCG auslösen. Es zeigte sich in Abhängigkeit vom Tumorstadium eine positive -hCG-Immunreaktivität in 27% (6 von 22) des Tumoren ohne Lymphknoten- and Fernmetastasierung (T_1–4 N₀ M₀), in 54% (7 von 13) des Tumoren mit Lymphknotenaber ohne Fernmetastasen (T_1–4 N₁ M₀) und in 47% (9 von 35) des Tumoren mit Fernmetastasierung. Schlecht differenzierte Tumoren (G3–4) waren zu 42% (15 von 36) und gut differenzierte Tumoren (G_1–2) nur zu 39% (7 von 18) positiv. Aber lediglich bei einer Patientin war der -hCG-Spiegel im Serum erhöht. Zusammenfassung: Immunhistochemisch -hCG-positive Magenkarzinome werden vermehrt bei fortgeschrittenem Tumorstadium und Schlecht differenzierten Karzinomen gefunden. Diese Kar zinome scheinen aber nicht in ausreichender Menge -hCG ins Serum abzugeben, was zu serologisch meßbar erhöh-ten Werten führt. -hCG im Serum kann daher nicht als Prognosefaktor bzw. zur Verlaufskontrolle herangezogen werden. Abzuwarten bleibt, inwieweit die -hCG-Expression von Tumorzellen u. U. Einfluß auf die Propose der Patienten besitzt.

---

Significance of -hCG in the serum as a tumour marker for gastric cancer

Introduction: Recent investigations indicate that in 50% of patients with gastric cancer, -hCG-posiitive cells can be found in the tumour by immunohistochemical investigations. The objective of this study was to investigate how often -hCG-immunoreactive gastric carcinomas were accompanied by an elevation in serum -hCG, that could have been used as a course control variable. Methods: In 54 patients with gastric carcinoma a monoclonal antibody directed against -hCG was used for immunohistochemical marking in the APAAP system. The evaluation was graded positive or negative. In parallel, serum -hCG was determined preoperatively using an enzyme immunoassay (MEIA). Tumour stage, grading and tumour locallization were determinants in the evaluation. Results: We found that 41% (22 of 54) of the carcinomas induced a :positive immunohistochemical response to -hCG, regardless of their location in the stomach. In relation to tumour stage, a positive -hCG immunoreactivity was apparent in 27% (6/22) of tumours without lymph node or distant metastases (TI -4N0M0), in 54% (7/13) of tumours with lymph node and without distant metastases (T1–4N1 M0) and in 47% (9/35) of tumours with distant metastases. Poorly differentiated tumours (G3–4) were positive in 42% (15/36) and well-differentiated tumors (G1–2) in 39% (7/18) of cases. In only 1 patient was the -hCG, level in serum elevated, however. Conclusions: -hCG-Positive gastric carcinomas are found more frequently in advanced tumour stages and poorly differentiated carcinomas. These carcinomas, however, seem not to excrete -hCG in sufficient amounts to produce measurable serum values. Therefore, -hCG cannot be used a prognostic factor or for course control. The relevance of -hCG expression of tumour cells to the patients' prognosis remains obscure.

     

Mechanism of action of β-glycerophosphate on bone cell mineralization

Summary Experiments were performed to determine whether -glycerophosphate (-GP) promoted mineralization in vitro by modulating bone cell metabolic activity and/or serving as a local source of inorganic phosphate ions (Pi). Using MC3T3-E1, ROS 17/2.8, and chick osteoblast-like cells in the presence of -GP or Pi, we examined mineral formation, lactate generation, alkaline phosphatase (AP) activity, and protein and phospholipid synthesis. Neither -GP nor Pi modulated any of the major biosynthetic activities of the bone cells. Thus, we found no change in the levels of phospholipids, and the total protein concentration remained constant. Measurement of lactate synthesis showed that -GP did not effect the rate of anaerobic glycolysis. Evaluation of medium Pi levels clearly indicated that -GP was hydrolyzed by bone cells; within 24 hours, almost 80% of 10 mM -GP was hydrolyzed. It is likely that this local increase in medium Pi concentration promoted rapid mineral deposition. Chemical, energy dispersive X-ray, and Fourier transform infrared analysis of the mineral formed in the presence of -GP showed that it was nonapatitic; moreover, mineral particles were also seen in the culture medium itself. Experiments performed with a cell-free system indicated that mineral particles formed spontaneously in the presence of AP and -GP and were deposited into a collagen matrix. We conclude that medium supplementation with -GP or Pi should not exceed 2 mM. If this value is exceeded, then there will be nonphysiological mineral deposition in the bone cell culture.     

ACE inhibition modulates transforming growth factor-β receptors in the young rat

The renin-angiotensin system plays an important role in renal growth and development. Exposure of the neonate to angiotensin converting enzyme (ACE) inhibitors increases mortality and results in growth retardation and abnormal renal development. It has been demonstrated that ACE inhibition in the developing kidney reduces the renal expression of growth factors, which may account for renal growth impairment. This study was designed to investigate the relationship between renal growth impairment and the expression of transforming growth factor-1 (TGF-1), TGF- receptor I [TRI, activin-like kinase (ALK)-1 and ALK-5], and TGF- receptor II (TRII). Newborn rat pups were treated with enalapril (30 mg/kg per day) or vehicle for 7 days, and kidneys were removed for Western blotting of TGF-1, ALK-1, ALK-5, and TRII, and for RT-PCR of ALK-5 and TRII. TGF-1, ALK-1, ALK-5, and TRII were also detected by immunohistochemistry. Enalapril treatment resulted in an increased mortality (30.4%) by day 7, and reduced body weight and kidney weight (P<0.05 versus vehicle). Enalapril decreased renal TGF-1, ALK-1, and ALK-5 protein expression (P<0.05). Also, enalapril decreased ALK-5 mRNA expression (P<0.05). TRII expression was not changed by enalapril treatment. These results indicate that ACE inhibition in the developing kidney decreases TGF-1, ALK-1, and ALK-5 expression, which may account for renal growth impairment. TRII may not be modulated by ACE inhibition in the developing kidney.     

Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate

We have quantified and characterized ₁-, ₂-and -adrenoceptor subtypes in porcine bladder detrusor and bladder neck, human bladder detrusor, and porcine and human prostate. ₁-, ₂- and -adrenoceptor were identified in radioligand binding studies using [³H]prazosin, [³H]RX 821002 and [¹²⁵I]iodocyanopindolol, respectively, as the radioligands. In porcine male and female detrusor and bladder neck and male prostate, adrenoceptors were detected in the order of abundance > _{2 1} (not detectable), with no major differences between the sexes or between detrusor and bladder neck. In human detrusor and prostate the order of abundance was > _{2 1} (not detectable) and ₁ > ₂. respectively. The ₂-adrenoceptors in all tissues were homogeneously of the _2A-subtype as evidenced by competition binding studies with yohimbine, prazosin, ARC 239 and oxymetazoline. The -adrenoceptors represented a mixed population with a dominance of the ₂-subtype in all tissues as demonstrated by competition binding with ICI 118,551 and CGP 20,712A. We conclude that pigs may be a suitable model for studies of detrusor function with respect to adrenoceptor expression. They may be less suitable for studies of bladder neck or prostate function.     

Dexamethasone regulates IL-1β and TNF-α-induced interleukin-8 production in human bone marrow stromal and osteoblast-like cells

We have investigated both constitutive- and cytokine-induced secretion of interleukin-8 (IL-8) and its regulation by dexamethasone and 17-estradiol in normal human bone marrow stromal (HBMS), osteoblast-like cells (hOB), and osteosarcoma MG-63 cells. Although HBMS cells secrete low levels of IL-8 constitutively, treatment with IL-1 and tumor necrosis factor- (TNF-) induced IL-8 secretion. Their effects were synergistic but IL-8 production was not affected by 17-estradiol. Human osteosarcoma MG-63 cells also secreted low levels of IL-8 constitutively; the production was induced by IL-1 and TNF- and was also not affected by 17-estradiol. The magnitude of the response to cytokine stimulation of IL-8 in MG-63 cells was much lower than that of HBMS and hOB cells, indicating differences in response in normal and osteoblastic osteosarcoma cells. Dexamethasone (10^-7 M) significantly inhibited IL-1 plus TNF- stimulated IL-8 production in HBMS, MG-63, and hOB cells. The accumulated results demonstrate that IL-8 is secreted by HBMS, MG-63, and hOB cells, suggesting that IL-8 may play a role in the regulation of bone cell function. These data also emphasize the importance of glucocorticoids in controlling cytokine secretion in HBMS, hOB, and MG-63 cells.     

Methylated β-cyclodextrins are able to improve the nasal absorption of salmon calcitonin

The absorption enhancing effect of methylated -cyclodextrins on the nasal absorption of salmon calcitonin (sCT) was studied in rats and rabbits. The nasal absorption of sCT following administration without additives was low in both species. The absorption in rats could be largely improved by coadministration of cyclodextrins as apparent from the effect on serum calcium concentrations. Trimethyl--cyclodextrin (TMCD), at a concentration of 5% (w/v), was the least potent enhancer. Randomly methylated--cyclodextrin (RMCD) and dimethyl--cyclodextrin (DMCD), all at a concentration of 5% (w/v), were almost equally effective in decreasing serum calcium levels, and the hypocalcemic responses were similar to those of i.v. and s.c. injected sCT. Absorption enhancement was already achieved with 1% DMCD added to the nasal formulations. In rabbits, only the effect of DMCD on the nasal sCT absorption was investigated. A total serum calcium decrement in 4 hours of 9.4±3.9% (mean±SD) was observed following nasal administration of 12.6 IU/kg sCT with 5% DMCD, comparable to that of i.v.-injected sCT. In conclusion, the methylated cyclodextrins DMCD and RMCD are suitable absorption enhancers for nasal sCT administration, which is expected to have a clinical impact on the therapy with calcitonin.     

Transforming Growth Factor-β1 Gene Polymorphisms and Bone Turnover,Bone Mineral Density and Fracture Risk in Southern Chinese Women

Genetic contributions play an important role in determining bone mineral density (BMD) and bone turnover. Transforming growth factor- (TGF-) is abundant in bone and has been implicated as an important regulator of both bone formation and resorption. Several polymorphisms of the TGF-1 gene have recently been suggested to be associated with BMD and susceptibility to osteoporotic spine fractures. To determine the relationship between TGF-1 polymorphisms and BMD in southern Chinese women, three SNPs at C^–1348-T, T²⁹-C, and T^861-20-C of TGF-1 gene were analyzed in 237 postmenopausal southern Chinese women by RFLP and direct sequencing. BMD at the lumbar spine and hip region, biochemical markers of bone turnover, as well as serum levels of TGF-1 were measured. Only the T²⁹-C polymorphism of TGF-1 gene was associated with BMD and fracture risk. The prevalence of fragility fractures was significantly higher in individuals with TC genotype (P < 0.05). Serum alkaline phosphatase and osteocalcin levels as well as urinary N-telopeptide excretion were significantly higher in women with TC than with TT or CC genotypes, and the difference remained significant after adjusting for age and BMI (all P < 0.05). Women with TC genotype had lower BMD at the trochanteric (P < 0.03) and total hip region (P = 0.05). No difference was observed in the serum TGF-1 levels among the three genotypes. In conclusion, an association between T²⁹-C polymorphisms of TGF-1 gene and BMD, bone turnover as well as fragility fractures were demonstrated in postmenopausal southern Chinese women.     

Role of TGFβ in the anti-estrogen response/resistance of human breast cancer

Transforming growth factor (TGF) has potent inhibitory effects upon epithelial proliferation and malignant progression may be associated with breakdown of the autocrine and paracrine inhibitory loops in which TGF participates. The therapeutic effects of anti-estrogens may be partially attributable to boosting of local endogenous levels of TGF. This article reviews the evidence in support of TGF being a proximate effector in mediation of the anti-neoplastic effects of anti-estrogens. Both the conventional estrogen receptor (ER)³ dependent and ER independent mechanisms of action are likely to be involved. Evidence for preferential stromal induction of TGF by anti-estrogens is emphasized, together with the therapeutic potential of this strategy for improving outcome in early breast cancer irrespective of ER status.     

Association of IL-1β, IL-1ra, and TNF-α gene polymorphisms in childhood nephrotic syndrome

We investigated the association between IL-1, IL-1ra, and TNF- gene polymorphisms and childhood nephrotic syndrome (NS). We analyzed the genetic polymorphism of IL-1, IL-1ra, and TNF- genes in 152 patients with childhood NS and 292 healthy adult controls. The C to T exchange at position –511 of IL-1 and the G to A at –308 of the TNF- gene were genotyped. Five alleles of the IL-1ra gene were identified and designated as IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5, according to the variable number of tandem repeats in intron 2. The allele frequencies of IL-11 (-511C), IL-12 (-511T), TNF1 (-308G), and TNF2 (-308A) were 53.0, 47.0, 92.1, and 7.9%, respectively, in the childhood NS group. This was not significantly different from normal controls. In the childhood NS group, the allele frequencies of IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5 were 90.8, 7.6, 1.6, 0, and 0% [IL1RN*1 odds ratio (OR)=0.296, P=0.0001, IL1RN*2 OR=3.902, P=0.0002]. A high allele frequency of IL1RN*2 and a lower allele frequency of IL1RN*1 were found in childhood NS, although there was no association with IL-1 and TNF-. A high allele frequency of the IL1RN*2 allele may affect disease susceptibility in childhood NS.     

Transforming growth factor-β pathway is activated in cholecystolithiasis

Background The etiopathogenesis of cholecystolithiasis is not well defined. Primary dysmotility of the organ, due to fibrosis of the gallbladder wall or muscular dysfunction, is suggested as a crucial factor. Transforming growth factor-beta (TGF-) and connective tissue growth factor (CTGF) are involved in several fibrotic disorders and play a critical role in fibrogenesis, thereby changing the physiological function of the organs. In the present study we analyzed the role of TGF- and its downstream target CTGF in patients with cholecystolithiasis.Methods Gallbladders were obtained from 16 individuals undergoing surgery for symptomatic cholecystolithiasis. Normal human gallbladder tissue samples from five individuals without any history of gallbladder disease were obtained through an organ donor transplantation program. Northern blot analysis, in situ hybridization, and immunohistochemistry were used to analyze the expression of TGF-1 and CTGF in the gallbladder tissue samples.Results By northern blot analysis there was an enhanced TGF-1 mRNA expression (eightfold increase; P<0.04) in the cholecystolithiasis tissue samples in comparison with normal controls. There was also a concomitant increase in CTGF (41-fold increase; P<0.01). By in situ hybridization and immunohistochemistry, CTGF mRNA was localized mainly in the mucosa layer, while intensive staining of the smooth muscle cells with TGF-1 and CTGF was observed. In addition, TGF-1 immunoreactivity was also localized in the fibroblasts and inflammatory cells. TGF-1 m-RNA levels showed a significant relationship with the degree of fibrosis in the tissue samples (P<0.04, r=0.5).Conclusion Our data indicate that TGF- and CTGF are involved in ultrastructural tissue changes in patients with cholecystolithiasis. Activation of the TGF- pathway, predominantly in the remaining mucosa and submucosal layer, indicates that extracellular matrix (ECM) synthesis with subsequent gallbladder wall fibrosis is an important step in gallbladder dysfunction in this disorder.     

The association between transforming growth factor-β gene promoter C-509T polymorphism and Chinese children with Henoch-Schönlein purpura

Many cytokines, including transforming growth factor- (TGF-) and tumor necrosis factor- (TNF-), are involved in the inflammatory process of Henoch-Schönlein purpura (HSP). The objective of this study was to investigate whether TGF- C-509T and TNF- G-308A polymorphisms are associated with childhood HSP. The loci of interest were amplified from genomic DNA using specific primers and polymerase chain reaction, and these two polymorphisms were compared between Chinese children with HSP and healthy controls. The disease severities evaluated and expressed as symptom score of patients with different genotypes were also compared. The TGF- -509 TT genotype was more common in children with HSP than controls (31% vs. 8%, P =0.03, odds ratio=4.95). The allelic frequencies of TGF- -509, genotypic and allelic frequencies of TNF- -308 were not significantly different. Patients with the TT genotype had more severe clinical presentations than non-TT (TC+CC) patients (4.1±0.42 vs. 2.7±0.31, P =0.018). These results suggest that the TT genotype of the C-509T polymorphism of the TGF- gene might be related to the susceptibility of Chinese children to HSP and to the severity of this disease.     

Effects of cyclosporins and transforming growth factor β1 on thyroid hormone action in cultured fetal rat limb bones

Summary To study the mechanism of action of thyroid hormones on bone, we examined the effects of immunosuppresive and nonimmunosuppressive cyclosporins, as well as of transforming growth factor ₁ (TGF₁), 17-estradiol (E₂), and dihydroxytestosterone (DHT) on thyroxine (T₄)-and triiodothyronine (T₃)-stimulated bone resorption in fetal rat limb bones. The immunosuppressive cyclosporins A (CsA) and G (CsG) inhibited thyroid hormone (T₄+T₃)-stimulated resorption and -glucuronidase release into the culture medium, whereas the weak or nonimmunosuppressive cyclosporins D (CsD) and H (CsH) did not show this effect. Increasing the medium calcium concentration reduced the ability of T₄ to stimulate ⁴⁵Ca release, while not significantly affecting the response to CsA. TGF₁ elicited a biphasic effect when administered together with T₄. During the first 3 days of culture, TGF₁ elicited a small, nonsignificant decrease in released ⁴⁵Ca; during a subsequent 3 days of culture, it enhanced T₄-stimulated bone resorption significantly. These effects differed from those of TGF₁ on parathormone-stimulated resorption. E₂ and DHT did not influence the action of T₄ on bone tissue. These results suggest that the mechanism of action of thyroid hormones on bone may involve immune factors, as well.     

Complex role of tumor cell transforming growth factor (TGF)-βs on breast carcinoma progression

Growth inhibition by the TGF-s has been extensively studied in both normal and transformed mammary epithelial cells. It has been proposed that loss of autocrine TGF- mediated growth regulation is a critical event in breast tumorigenesis and several lines ofin vitro andin vivo data support this hypothesis. However, a positive association between the expression of TGF-s by tumor cells and the progression or maintenance of breast cancinoma cells has been observed in many studies inin vivo tumor models. Possible mechanisms for these growth enhancing effects of TGF- include immunosuppression mediated by tumor TGF-s, enhanced angiogenesis, increased peritumoral stroma formation, and cell adhesion. The net effect of tumor cell TGF- on the biology of breast carcinogenesis would depend on the balance between autocrine growth inhibition of mammary epithelial cells and these growth enhancing effects.     

Demonstration of TGF-β1 mRNA by in situ hybridization in normal human fracture healing

Summary The role of transforming growth factor (TGF-) in fracture healing has previously been investigated in a rodent model, but not in human material. We investigated TGF-1 gene expression in specimens of callus from normally healing human fractures, using in situ hybridization to a cDNA TGF-1 probe and an autoradiographic disclosure system. TGF-1 mRNA was present in areas of proliferation of mesenchymal tissue, bone, and cartilage. Levels of expression were lower in cells in the fracture hematoma and in differentiated (hypertrophic) chondrocytes. These results are compatible with those found in various animal models using immunohistochemistry and support the view that locally produced TGF-1 is a regulator of fracture repair in humans from the early (mesenchymal proliferation) stage to the stage of remodeling of woven bone. They also indicate that, for TGF-1, animal models accurately reflect human bone repair.     

Effects of oral atenolol on volatile anesthetic induction with sevoflurane in adults

Purpose To determine whether premedication with a -blocker can bring about a more rapid and smooth induction of anesthesia, we investigated the effect of oral premedication with atenolol on volatile anesthetic induction with sevoflurane by monitoring the cardiac output (CO) and bispectral (BIS) index.Methods Twenty-four patients undergoing general anesthesia with endotracheal intubation were randomly divided into two groups: a control group (n = 12) and a -blocker group (n = 12). Each patient in the -blocker group was premedicated with oral atenolol 25mg 1h before the induction of anesthesia. Anesthesia was induced by the repeated vital capacity technique with 5% sevoflurane and 66% nitrous oxide. The trachea was intubated 5min after sevoflurane exposure. The CO and BIS index, as well as the induction time and specific side effects of induction (e.g., movement of limbs), were recorded.Results There were no significant differences in induction time and specific side effects between the groups. The downward-sloping part of the BIS index curve in the -blocker group (mean, 2.9 ± 0.2) was significantly sharper than that in the control group (2.5 ± 0.2), and the BIS index after induction of anesthesia was significantly lower in the -blocker group (21.0 ± 2.2) than in the control group (24.2 ± 2.0). CO in the -blocker group was significantly lower than in the control group during the study period. The hemodynamic changes caused by endotracheal intubation were inhibited in the -blocker group but not in the control group.Conclusion Oral premedication with 25mg of atenolol provides a more rapid decrease in BIS index and is recommended for use in stable volatile anesthetic induction with sevoflurane.     

The Normal and Malignant Mammary Gland: A Fresh Look with ERβ Onboard

Estrogens are important for the development and function of the normal mammary gland as well as for development of mammary cancer. The frontline therapy for treatment of estrogen receptor (ER)⁴ positive breast cancer is antiestrogens. A second estrogen receptor (ER) is also expressed in the breast but it has not been measured because it is not detected by the immunoassays used to detect ER. In many cell systems ER has actions which are opposite to those of ER and this finding has raised questions about the role of ER in the development and treatment of breast cancer.     

Transforming growth factor-β1 in the urine of young children with urinary tract infection

Urinary tract infection (UTI) is a frequent cause of morbidity during the first years of life and may lead to renal insufficiency. Transforming growth factor-1 (TGF-) is both immunoregulatory and an important mediator of interstitial fibrosis. TGF- was detected in the urine of 52% of 48 children aged 1–24 months with a first episode of UTI (94% due to Escherichia coli) and no obstructive nephropathy compared with 0 of 20 healthy young children (P<0.001). TGF- was detected in the urine only during the early stage (<1 day) after initiation of treatment. It was detected more frequently (P=0.06) and in significantly higher concentrations (P=0.046) in children with a normal ^99m Tc-dimercaptosuccinic acid scan compared with those with abnormal scans performed 3–14 days after the diagnosis of UTI, suggesting a regulatory role in fibrogenesis and outcome of pyelonephritis in childhood.     

Urinary unconjugated 5α-androstane-3α, 17β-diol in patients with prostatic tumours

Summary A sensitive and reliable radioimmunoassay (RIA) for urinary unconjugated 5-androstane-3, 17-diol is described. The mean overall recovery of unconjugated 5-androstane-3, 17-diol was found to be 57.4%. The sensitivity of the assay was 79 fmol per assay tube and the intra and inter-assay variations ranged between 7.2% and 11.4%. The mean ± SEM for the concentration of this androgen in the urine of normal men was 339.6±66.8 nmol/24h. The corresponding values for patients with benign prostatic hypertrophy (BHP) and carcinoma of the prostate (Ca) were 297.8±44.7 and 1592.1±622.7 respectively. The mean value for Ca patients was significantly higher than either BPH (p<0.05) or normal subject (p<0.02), suggesting a differential urinary excretion pattern for unconjugated 5-androstane-3, 17-diol between BPH and Ca patients. It is concluded that the combined measurement of this androgen in the plasma and urine provides a more accurate assessment of the profile of this hormone than a single plasma estimation.     

β2-Microglobulin in postmenopausal osteoporosis

Summary The so-called bone-derived growth factor, or ₂-microglobulin, has a regulatory function in bone metabolism, stimulating osteoclastic activity. Osteoclastic activity is enhanced in postmenopausal osteoporosis, suggesting that ₂-microglobulin concentration may also be increased in this disease. ₂-microglobulin concentration was found to be raised (P < 0.001) in 30 women with postmenopausal osteoporosis as compared with 30 normal women of similar age; tartrate-resistant acid phosphatase concentration also was raised (P < 0.001), and total body bone mineral content was decreased (P < 0.001). Linear regression analysis revealed a highly negative correlation result between total body bone mineral content and ₂-microglobulin (r = 0.577,P < 0.001), and a positive correlation result between ₂-microglobulin and tartrate-resistant acid phosphatase concentration (r² = 0.806,P < 0.001). These findings, and the stimulatory effect of ₂-microglobulin on osteoclastic and osteoblastic activity, suggest that ₂-microglobulin may play an important role as a local regulatory factor in the pathogenesis of postmenopausal osteoporosis.     

β2-microglobulin in Paget's bone disease

On the basis of earlier findings of increased serum ₂-microglobulin concentration in women with postmenopausal osteoporosis, we decided to study serum ₂-microglobulin concentration in other bone diseases. In 28 patients with untreated Paget's bone disease, serum ₂-microglobulin concentration was normal (1.49±0.41 mg/liter versus 1.36±0.21 mg/liter in 42 control subjects, P= ns), a finding that contradicts reports in the literature. We found that serum ₂-microglobulin concentration was related negatively and significantly (r²=–0.154, P=0.0354) with serum total alkaline phosphatase concentration, but not with serum tartrate-resistant acid phosphatase concentration (p =ns). Urinary elimination of ₂-microglobulin was lower in the patients with Paget's disease than in the controls (34±28 versus 120±21 mg/liter, P<0.001). These findings suggest that ₂-microglobulin behaves similarly to osteocalcin (BGP) in Paget's bone disease and that its concentration remains within normal levels perhaps because of the rate of reuptake of ₂-microglobulin in bone neoformation.