小剂量化疗对老年消化系肿瘤患者机体免疫系统的影响

应用双染色一流式细胞术结合4种抗T淋巴细胞表面抗原单克隆抗体．对8例老年消化系肿瘤小剂量化疗前后外周血T淋巴细胞亚群的变化进行了检测。结果表明：Leu4、Leu3a、Leu7在化疗前后皆无明显变化，Leu2a化疗后较化疗前略有增高，Leu3a/Leu2a比例有所下降，但皆无统计学意义。本结果提示：小剂量化疗对老年消化系统肿瘤患的机体免疫系统影响不大．适合于年老体弱不能耐受大剂量化疗的患。     

肺结节病时支气管肺泡淋巴细胞和T细胞亚群的变化

作者对14名经活检证实的不同病期和不同活动程度的结节病患者和8名正常人的周围血液和支气管肺泡灌洗液中的淋巴细胞,应用直接免疫荧光单克隆抗体(Leula,Leu3a,Leu2a)分析T淋巴细胞总数(Leu1a),抑制细胞毒素T细胞(即Tsc,Leu2a~+)或辅助诱导T淋巴细胞(Thi,Leu3a~+)的分布恃况。他们未能发现患者周围血液中T淋巴细胞亚群有何变化,但支气管肺泡炎灌洗液中的Tsc细胞的比例大大超过正常人(患者为36.0%SD±17.6%,正常15%SD±5.6%     

消化道恶性肿瘤患者化疗前后外周血T淋巴细胞亚群变化及其对PG-SGA评分的影响

目的通过分析消化道肿瘤患者在化疗前后外周血T淋巴细胞亚群水平、主观全面评价法(PG-SGA)评分的变化及二者之间的相关性,探讨消化道恶性肿瘤患者经过化疗后的免疫功能变化及对患者营养状况的影响。方法对消化道肿瘤患者进行化疗,分别于化疗前和化疗后对不同疗效的患者进行外周血T淋巴细胞亚群水平检测和PG-SGA评估,同时对化疗前后患者的PG-SGA评分和T淋巴细胞亚群水平进行相关性分析。结果所有患者治疗的缓解率为43.3%,经过4个疗程化疗后,化疗后各疗效组患者外周血CD3^+和CD8^+ T细胞水平较化疗前显著升高,化疗后CD4^+/CD8^+较化疗前显著降低。化疗后患者的PG-SGA评分较化疗前显著增加。患者在化疗前和化疗后PG-SGA评分和外周血CD3^+和CD4^+T淋巴细胞亚群水平及CD4^+/CD8^+呈显著负相关。结论 T淋巴细胞亚群水平能够影响到胃肠道肿瘤患者的营养状况。     

复方抗瘤冲剂对老年胃肠道肿瘤患者免疫功能的影响

目的:评价复方抗瘤冲剂配合静脉化疗对老年胃肠道肿瘤患者免疫功能的影响.方法:老年胃肠道肿瘤患者43例随机分为两组:对照组22例,用甲酰四氢叶酸钙、5-氟尿嘧啶、丝裂霉素方案行静脉化疗;治疗组21例,在静脉化疗同时,服用复方抗瘤冲剂.化疗前及化疗2个疗程结束后(6周)分别检测外周血常规、免疫球蛋白、T淋巴细胞亚群,进行统计学分析.结果:化疗结束时治疗组患者外周血中白细胞、血小板计数、血红蛋白较化疗前无明显下降;与对照组比较,治疗组免疫球蛋白IgG、IgM及T淋巴细胞亚群CD 4、CD 4/CD 8值均有提高,两组差异均有统计学意义.结论:复方抗瘤冲剂可有效提高老年胃肠道肿瘤患者机体免疫功能,使患者平稳经受化疗.     

CD4~+、CD8~+细胞水平变化与恶性肿瘤疗效的关系

目的探讨观察T淋巴细胞亚群水平变化与恶性肿瘤疗效之间的相关性和化疗对恶性肿瘤患者细胞免疫功能的影响及免疫支持治疗的临床意义。方法通过流式细胞检测技术检测外周血T淋巴细胞亚群CD3+CD4+、CD3+CD8+、CD4+/CD8+水平;应用蛋白芯片技术检测相关肿瘤标志物水平。结果与健康人群相比,恶性肿瘤患者存在细胞免疫功能低下;9例化疗有效的肺癌病人化疗后T淋巴细胞亚群CD3+CD4+、CD4+/CD8+水平明显高于化疗前;22例卵巢癌病人化疗前后T淋巴细胞亚群水平变化不明显,但化疗后肿瘤标志物(CA125)水平较化疗前有明显降低;经过免疫治疗后的肾癌病人T淋巴细胞亚群水平与治疗前比较均有明显好转。结论化疗并不损害恶性肿瘤患者的细胞免疫功能;免疫治疗有助于提高恶性肿瘤患者的细胞免疫功能。     

胸腺肽α1联合LV／5-Fu持续灌注预防老年结直肠癌术后复发

目的观察胸腺肽α1联合亚叶酸钙（LV）／5-氟尿嘧啶（5-Fu）化疗对老年结直肠癌术后患者治疗前后T淋巴细胞亚群变化,探讨该疗法预防老年结直肠癌术后复发的作用。方法将42例结直肠癌根治术后患者随机分为两组,对照组术后4—8周用LV／5-Fu方案持续灌注化疗6个周期;在此基础上,治疗组加用胸腺肽α1皮下注射,连续3a。治疗期间检测T淋巴细胞亚群变化。结果与对照组比较,治疗后1、2、38,治疗组CD3^＋、CD4^＋和CD4^＋／CD8^＋比值明显升高（P均〈0．05）;治疗后3a对照组复发率明显高于治疗组（P〈0．05）。结论老年结直肠癌患者术后化疗后定期给予胸腺肽α1治疗,可改善细胞免疫功能,对预防术后复发、转移有一定作用。     

20( R)-人参皂甙Rg3对老年肿瘤患者放、化疗后的辅助治疗效果

老年肿瘤患者免疫功能明显降低,放、化疗对机体免疫功能又进一步影响[1～3],因此在老年中晚期肿瘤患者放、化疗常规治疗后,提高其机体的免疫功能,加快疾病恢复,改善其生存质量更为重要.20(R)-人参皂甙Rg3被证明具有显著的抗肿瘤效应[4],且有调节免疫的作用[5,6],可增强放、化疗患者的外周血淋巴细胞免疫功能.本文以放、化疗后中晚期老年肿瘤患者为对象,检测了应用20(R)-人参皂甙Rg3前后其外周血淋巴细胞亚群水平变化及Karnofsky评分(KPS)状态.     

老年结肠癌患者树突细胞免疫治疗后免疫功能的变化及其疗效

目的观察老年结肠癌患者树突细胞(DC)免疫治疗后免疫功能的变化及其治疗效果。方法选取该院收治的96例老年结肠癌患者为研究对象,按照入院顺序随机均分为观察组和对照组,观察组患者在手术治疗和化疗基础上给予DC免疫治疗,对照组患者给予手术治疗和化疗,比较两组患者免疫功能的变化和临床疗效。结果对照组患者治疗后CD3+、CD4+、CD8+、CD4+/CD8+T淋巴细胞亚群比例与治疗前比较无明显差别(P>0.05)。观察组治疗后CD3+、CD4+、CD8+、CD4+/CD8+T淋巴细胞亚群比例与治疗前比较均增加(均P<0.05);且高于对照组治疗后(均P<0.05)。观察组患者治疗有效率为60.42%高于对照组有效率(χ2=7.07,P<0.05)。结论结肠癌患者的DC免疫治疗可明显提高患者免疫功能和肿瘤清除效果,术后化疗联合细胞免疫治疗可获得较单纯术后化疗更为满意的治疗效果。     

老年肺炎患者免疫状态初探

目的 观察老年社区获得性肺炎（CAP）患者免疫功能的改变.方法 以58例老年社区获得性肺炎患者为研究对象,以60例无肺炎体检老年人作为对照组,检测外周血淋巴细胞计数及各淋巴细胞亚群计数,放射免疫法测定外周血肿瘤坏死因子-α（TNF-α）、外周血白细胞介素-2（Interleukin-2,IL-2）等指标,观察老年肺炎患者机体免疫功能变化.结果 肺炎组老年患者与无肺炎组老年人比较,外周血淋巴细胞计数、T淋巴细胞计数（CD＋3）、CD4T淋巴细胞计数（CD＋3CD＋4）、CD＋4/CD＋8比值均明显低（P≤0.001）,NK细胞计数（CD＋16CD＋56）也偏低（P＜0.05）,而CD8T淋巴细胞细胞（CD＋3CD＋8）、B细胞计数（CD＋19）无明显差别（P＞0.05）.肺炎组老年患者与无肺炎组老年人比较外周血TNF-α明显升高（P〈0.001）,外周血IL-2明显偏低（P〈0.001）.结论 老年人免疫功能的减退改变与老年人CAP有着密切的关系.     

T细胞核仁组成区嗜银蛋白对老年人肿瘤诊断的价值

目的　探讨老年肿瘤患者外周血T淋巴细胞核仁组成区嗜银蛋白的变化 ,及其与机体免疫关系。　方法　利用KL型肿瘤免疫图像分析系统检测 4 5例健康老年人 (对照组 )、36例老年炎症患者 (炎症疾病组 )、97例老年肿瘤患者 (肿瘤组 )和 30例老年肿瘤治愈患者 (肿瘤治愈组 )的外周血T淋巴细胞核仁组成区嗜银蛋白 ;应用流式细胞仪检测老年肿瘤组患者外周血T淋巴细胞表面分化抗原 (CD3、CD4、CD8)及自然杀伤细胞。　结果　与老年对照组〔(7 36± 0 76 )IS %〕及炎症疾病组〔(7 16± 1 0 4 )IS %〕相比 ,老年肿瘤组〔(5 39± 1 70 )IS %〕外周血T细胞嗜银蛋白降低 ,且差异有显著性 (P <0 0 1) ;转移性肿瘤患者嗜银蛋白下降更明显。　结论　外周血T淋巴细胞嗜银蛋白可作为老年人肿瘤的诊断和治疗监测指标。     

T4 lymphopenia in human tuberculosis

Lymphocyte subpopulations in vitro in 13 patients with bacteriologically-proven tuberculosis and 12 matched controls, by immunofluorescence using monoclonal antibodies have been studied. Active tuberculosis was associated with significant reductions in absolute numbers of total T (Leu 4 or 1+), T4 (Leu 3a+) and B (Leu 12+) lymphocytes, but there were no significant differences in total T8 (Leu 2a+) counts. In two patients, T4-lymphopenia was sufficiently profound to cause reversal of T4: T8 ratio (less than 1.2). These changes were not related to the radiological extent of the disease or size of the Mantoux reaction. Normal ranges for the different classes of lymphocytes were readily restored by chemotherapy.     

High dose intravenous methotrexate with leucovorin rescue in rheumatoid arthritis

Five patients with severe, treatment refractory rheumatoid arthritis were treated with high dose intravenous methotrexate (500 mg/m2) followed by leucovorin (50 mg/m2). Four courses of chemotherapy were given over a 2-month interval. At the end of the final course, there was a 50% or greater improvement in joint swelling and pain indices and morning stiffness in all patients. Clinical responses persisted for 6-14 weeks posttherapy. High dose methotrexate-leucovorin was associated with a significant reduction in DR antigen expression on peripheral Leu 2, Leu 3 and Leu 4 lymphocytes.     

Flowcytometric analysis of lymphocytes proliferated in vitro by PPD

The present study was undertaken to do phenotype determination of in vitro proliferating lymphocytes by PPD stimulation using combination of monoclonal antibodies and flow-cytometry. The results obtained were as follows: 1) PPD induced a significant proliferation of activated T cell subsets (Leu4+DR+ cells, IL2-R+Leu3+ cells). 2) PPD also induced a significant increase in Pan T cells (Leu4+) and helper T cells (Leu3+8-). Taken together, these results indicated that PPD induced proliferating lymphocytes belong predominantly to helper T cell subset. 3) The numbers of inducer T cells (Leu3+8+), suppressor T cells (Leu2+15+) and cytotoxic T cells (Leu2+15-) were not influenced by PPD-stimulation. 4) However, PPD induced a smaller, but significant proliferation of IL2-R+Leu2+ cells. 5) The number of B cells (Leu4-DR+) tended to increase slightly after PPD-stimulation.     

M2A胶囊内镜在消化病诊断中的应用研究

目的 探讨胶囊内镜在消化道疾病诊断中的应用价值。方法 对不明原因消化道出血等症状的45例患者(男26例，女19例，平均年龄47．8岁)，采用Given M2A胶囊内镜检查。其中3l例在胶囊内镜检查前后行传统检查(包括胃镜、小肠镜、结肠镜、小肠X线检查、肠系膜动脉造影等)，与胶囊内镜的检查结果作比较。结果 胶囊内镜检查中均无任何不适或并发症，所得图像质量优良。44例完成检查，其中37例发现有消化道病变，检出率为84．1％，包括食管、胃病变5例，小肠病变29例，结肠病变3例。3l例在胶囊内镜检查前后行传统检查，其中消化道出血2l例，胶囊内镜检出出血病变17例，而传统检查检出4例；腹痛5例，胶囊内镜检出病变5例，传统检查检出2例；慢性腹泻4例，胶囊内镜检出病变4例，传统检查检出l例；转移性肿瘤者l例，胶囊内镜和传统检查均发现病变。病变定位与l临床基本相符。结论 胶囊内镜检查方法安全，检查质量优良，病变定位正确，尤其适宜于小肠疾病的检查。以其无痛、无损伤为特点，易为患者所接受。     

胸腺肽α1对高龄患者消化系统肿瘤的临床效果研究

目的 研究胸腺肽α1对高龄消化系统恶性肿瘤患者的临床疗效.方法 选取湖北省黄岗市中心医院2010年2月-2012年6月收治的192例临床资料较为完整的老年消化系统肿瘤患者作为研究对象,随机分为对照组和治疗组,每组96例.对对照组进行化疗,同时皮下注射生理盐水,116 mg/次,每2d一次,连续治疗8周;对治疗组进行化疗,同时皮下注射胸腺肽α1,116mg/次,每2d一次,连续治疗8周.对所有患者进行T细胞亚群和NK淋巴细胞活性监测,监测时间为治疗前1周和治疗第2、4、8周,同时对比治疗前后两组患者的体力情况,进行Karnofsky评分比较.结果 治疗前,治疗组与对照组各免疫指标差异均无统计学意义（P＞0.05）.治疗后,治疗组CD4＋、CD4＋/CD8＋和NK淋巴细胞指标明显高于对照组,差异均有统计学意义（P均＜0.05）;CD3＋ 、CD8＋指标差异均无统计学意义（P均＞0.05）.治疗组治疗后CD4＋、CD4＋/CD8＋和NK淋巴细胞指标明显高于治疗前,差异有统计学意义（P＜0.05）.治疗前后对所有患者进行Karnofsky评分比较,治疗后治疗组平均评分明显高于对照组,差异有统计学意义（P＜0.05）;所有患者体力情况随治疗时间延长均有所下降,对照组患者治疗前后评分比较差异有显著统计学意义（P＜0.01）.结论 胸腺肽α1对提高患者的免疫指数具有显著效果,对患者体力下降的情况具有明显的抑制作用,对高龄患者消化系统肿瘤的临床效果显著.     

中晚期非小细胞肺癌患者化疗前后T淋巴细胞亚群表达差异分析及临床意义

目的回顾性分析中晚期非小细胞肺癌患者化疗前后淋巴细胞亚群表达差异,以及与化疗疗效的相关性。 方法选择2014年1月至2018年6月在我院进行化疗治疗的中晚期非小细胞肺癌患者122例作为病例组,同期在我院进行健康体检64例作为对照组,对比分析各组T淋巴细胞亚群CD3⁺(%)、CD8⁺(%)、CD4⁺(%)、CD4⁺/CD8⁺细胞比值差异。 结果病例组化疗前及后的CD3⁺(%)、CD4⁺(%)、CD4⁺/CD8⁺细胞比值均显著低于对照组(P<0.05);化疗后CD3⁺(%)、CD4⁺(%)、CD4⁺/CD8⁺细胞比值均较化疗前有显著升高(P<0.05);化疗前后病例组患者CD8⁺(%)略高于对照组,但差异未发现统计学意义(P>0.05),且化疗前后CD8⁺(%)对比,差异未发现统计学意义(P>0.05)。化疗治疗后,将病例组分为疾病控制组共90例(73.77%),其中完全缓解(CR)0例,部分缓解(PR)25例(20.49%),疾病稳定(SD)65例(53.28%);疾病进展(PD)32例(26.23%)。疾病控制组的年龄、性别与疾病进展组对比,差异无统计学意义(P>0.05)。疾病控制组治疗前CD3⁺(%)、CD4⁺(%)、CD8⁺(%)、CD4⁺/CD8⁺与疾病进展组对比,差异均无统计学差异(P>0.05),疾病控制组治疗后CD3⁺(%)、CD4⁺(%)、CD4⁺/CD8⁺显著高于疾病进展组,差异均具有统计学意义(P<0.05)。DCR和PD两组治疗后CD3⁺(%)、CD4⁺(%)、CD4⁺/CD8⁺细胞比值均显著高于治疗前。两组治疗后CD8⁺(%)对比,差异无统计学意义(P>0.05)。治疗后CD3⁺(%)、CD4⁺(%)、CD4⁺/CD8⁺水平在预测非小细胞肺癌患者化疗效果的AUC面积分别为：0.789、0.823、0.758。通过最大约登指数计算得出CD3⁺(%)、CD4⁺(%)、CD4⁺/CD8⁺指标的最大AUC面积相应参数截止值,其中CD3⁺(%)截止值为65.95(%)(敏感度＝83.30%,特异性＝78.60%,P＝0.021),CD4⁺(%)截止值为39.81(%)(敏感度＝87.30%,特异性＝85.20%,P＝0.034),CD4⁺/CD8⁺截止值为1.250(敏感度＝81.20%,特异性＝76.70%,P＝0.017)。 结论中晚期非小细胞肺癌患者的T淋巴细胞比例显著降低,细胞免疫功能呈现紊乱状态。化疗治疗的效果可能与机体外周血T淋巴细胞表达状态有关,提示肺癌患者的外周血T淋巴细胞亚群表达状态可能成为预测化疗临床效果的一种标记物。     

Lymphocyte phenotypes in bronchoalveolar lavage and lung tissue in sarcoidosis and idiopathic pulmonary fibrosis

To determine whether the lymphocytes recovered by bronchoalveolar lavage (BAL) are representative of the cells found in lung tissue, we identified and enumerated lymphocyte phenotypes directly in lung tissue and lavage fluid with monoclonal antibodies (Leu 4-total T, Leu 3-helper T, Leu 2-suppressor/cytotoxic T cells) and an avidin-biotin peroxidase method in 6 patients with sarcoidosis and 6 patients with idiopathic pulmonary fibrosis (IPF). We found that the absolute numbers of each phenotype and the ratios of Leu 3/Leu 4, Leu 2/Leu 4, and Leu 3/Leu 2 in lavage fluid and tissue correlated well for both groups of patients. This supports the notion that the lymphocytes recovered by BAL are representative of the cells present in the lung. However, when cell recovery was expressed as the number per milliliter of recovered lavage fluid, there were no significant correlations between lavage fluid and tissue for any phenotype in the IPF group. The degree of restrictive impairment was significantly greater and the lavage fluid recovery was significantly lower in this group than in the sarcoid group. Thus, the lymphocytes recovered by BAL appear to mirror the types of cells found in lung tissue in these 2 forms of diffuse interstitial disease, but this relationship may not hold when there is a severe restrictive impairment and a low recovery of lavage fluid.     

Evaluation of lymphocyte subsets after autologous bone marrow transplantation with marrow treated by ASTA Z 7557 in acute leukemia: incidence of the in vitro treatment

The lymphocyte subset reconstitution after high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation (ABMT) has been studied in ten patients with acute leukemia (AL) (6 ALL and 4 ANLL) in complete remission (CR). Bone marrow was treated in vitro with high-dose ASTA Z 7557, individually determined according to CFU-GM sensitivity. The different peripheral blood lymphocyte subsets were characterized by means of monoclonal antibodies (indirect immunofluorescence assay) belonging to the following classes of differentiation: OKT11-T11 (CD2), OKT3-T3 (CD3), OKT4-T4 (CD4), OKT8-T8 (CD8), OKIal-I2 (HLA-DR), Leu7 (natural killer/killer) and by means of polyspecific antiimmunoglobulin sera (direct immunofluorescence assay). Data in these ten patients were compared with those of a control group of 21 normal donors and with a control group of 14 patients in CR without ABMT. Our results showed a marked depression of the T4:T8 ratio in patients with AL before ABMT, compared with normal donors who had respective values of 1.02 and 1.33 (p less than 0.01). This depression was increased and prolonged up to day 515 after ABMT, with a value of 0.32 (p less than 0.01 compared with the pregraft situation; p less than 0.001 compared with normal donors). This T4:T8 ratio imbalance was related to the depletion of the T4+ population and to the increase of the T8+ subset. This imbalance was emphasized after ABMT. The Leu 7+ population was also increased in grafted patients compared with normal donors (p less than 0.01). The B-cell population remained unchanged throughout the study. We conclude that patients autografted with marrow treated in vitro by high-dose ASTA Z 7557 may experience a long-term T-cell subset imbalance.     

Changes in plasma thyrotrophin, thyroxine, and triiodothyronine after acute or chronic administration of iodide to iodine-deficient rats.

The effect of chronic oral or acute iv administration of small graded doses of iodide was studied in severely iodine-deficient rats. Drinking water supplemented with 0.1, 0.2, or 0.4 mug 127I-/ml was given for up to 42 days. Plasma T3, which was initially in the normal range, increased 2--3-fold on days 1 and 2 after initiation of iodide supplementation, then dropped to approximately the intial concentration at day 3. Plasma T4, initially undetectable, was calculated to increase approximately 20-fold within one day after beginning iodide supplementation, but was still climbing into the normal range at day 3. In all groups, the initially high plasma TSH fell significantly by day 1 and was in approximately the normal range for iodine-sufficient rats by day 3. At 42 days, thyroid weight and 131I uptake were significantly elevated in all groups and inversely correlated with the dose of iodide, even though the thyroidal labeled T3/T4 ratio and plasma TSH, T4, and T3 were within the normal range. Intravenous injection of 0.1 or 0.5 mug 125I-/100 g caused an approximately 2-fold increase in plasma T3 within 24 h, which was not statistically different between the 2 groups. Plasma T4 rose to the normal range 24 h after 0.5 mug and was slightly, but significantly, elevated after 0.1 mug; it then declined in both groups. Twenty-four hours after injection of 2.5 mug 125I-/100 g, there was a significant fall in plasma T3, no change in plasma TSH, and no detectable plasma T4. Thereafter, there was a dramatic increase in plasma T4 and a fall in plasma TSH. The duration and degree of suppression of plasma TSH was related to the dose of iodide injected. We conclude that, under the conditions of our experiments, plasma T3 derives primarily from thyroidal secretion rather than from extra-thyroidal conversion of T4 to T3. Severely iodine-deficient rats secrete maximum quantities of TSH which are not increased by a further transient drop in plasma thyroid hormone concentration.     

Dual-energy X-ray absorptiometry and biochemical markers of bone turnover after autologous stem cell transplantation in myeloma

Objectives: To evaluate the effect of high‐dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) on bone turnover and bone mineral density in a cohort of 39 consecutive patients with multiple myeloma (MM). Methods: Phosphorus and calcium parameters, bone turnover markers, and bone mineral density were studied. Timepoints were diagnosis (T1), just before ASCT (T2), 6 months (T3) after ASCT, and 1 yr (T4) after ASCT. Results: No bone mineral loss was shown on dual‐energy X‐ray absorptiometry (DXA) at T1 (lumbar Z‐score ?0.02, femoral neck Z‐score 0.77) or during follow‐up. Chronic vitamin D deficiency (25OHD3 11.7 ± 7.7 ng/mL at T1) and relative hyperparathyroidism from T2 to T4 were observed. In spite of this moderate hyperparathyroidism, serum C‐telopeptide of type I collagen (CTX) decreased significantly between T1 and T4. Bone alkaline phosphatase levels were low at diagnosis and showed no significant change after ASCT, unlike DKK1 levels that were high at diagnosis and decreased 6 months after ASCT in patients not previously treated with bisphosphonates. Conclusion: Bone demineralization is moderate in multiple myeloma. ASCT induces a decrease in bone resorption but no changes in bone formation, remaining low despite the decrease in DKK1. Bone mineral loss, evaluated by DXA, is moderate in multiple myeloma. High‐dose chemotherapy followed by ASCT leads to decreased bone resorption but osteoblastic bone formation remains low, in spite of reduced circulating DKK1.