骨康胶囊联合鹿瓜多肽注射液治疗椎体压缩性骨折的临床研究

目的探讨骨康胶囊联合鹿瓜多肽注射液治疗椎体压缩骨折的临床疗效。方法选取2017年5月—2018年5月在成都医学院第一附属医院治疗的椎体压缩骨折患者88例,根据用药差别分为对照组(44例)和治疗组(44例)。对照组静脉滴注鹿瓜多肽注射液,8 mL/次加入生理盐水250 mL,1次/d;治疗组在对照组基础上口服骨康胶囊,4粒/次,3次/d。两组患者均治疗2周。观察两组患者临床疗效,同时比较治疗前后两组患者VAS评分、ODI评分、血清学指标、骨密度和Cobb角。结果治疗后,对照和治疗组临床有效率分别为81.82%和97.73%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者VAS评分、ODI评分均明显降低(P0.05),且治疗组患者VAS和ODI评分均明显低于对照组(P0.05)。治疗后,两组患者血清骨钙素(BGP)、尿脱氧吡啶啉(DPD)、抗酒石酸酸性磷酸酶5b(TRACP5b)、Ⅰ型胶原交联羧基端肽(CTXI)、Ⅰ型胶原氨基肽前肽(PINP)水平均显著降低(P0.05),25羟维生素D [25-(OH)D]水平均显著升高(P0.05),且治疗组患者这些血清学指标均明显好于对照组(P0.05)。治疗后,两组患者腰椎L1-4和股骨大粗隆骨密度均显著升高(P0.05),Cobb角明显减小(P0.05),且治疗组患者骨密度及Cobb角均明显好于对照组(P0.05)。结论椎体压缩骨折患者采用骨康胶囊联合鹿瓜多肽注射液治疗可有效改善骨密度和骨代谢指标,促进骨折愈合。     

六味地黄丸联合唑来膦酸治疗妇女绝经后骨质疏松的临床研究

目的探讨六味地黄丸联合唑来膦酸治疗妇女绝经后骨质疏松的临床效果。方法选取2015年6月—2017年1月广东医科大学附属医院收治的86例绝经后骨质疏松患者,随机分为对照组和治疗组,每组各43例。对照组静脉滴注唑来膦酸注射液,5 mg/次,1次/年。治疗组在此基础上口服六味地黄丸,8丸/次,3次/d。所有患者均连续治疗12个月。观察两组的临床疗效,比较两组治疗前后视觉模拟(VAS)评分、简明健康状况调查量表(SF-36)评分、腰椎1~4骨质密度(BMD)、全髋关节骨BMD、左侧股骨颈BMD、Ⅰ型原胶原氨基端前肽(PINP)、β-胶原降解产物(β-CTX)、碱性磷酸酶(ALP)、骨钙素(BGP)的变化情况。结果治疗后,对照组和治疗组的总有效率分别为79.07%、95.35%,两组比较差异有统计学意义(P0.05)。治疗后,两组VAS评分、血清PINP、β-CTX、ALP及BGP水平显著降低,SF-36评分、腰椎1~4 BMD值、全髋关节骨BMD值、左侧股骨颈BMD值显著升高,同组治疗前后比较差异有统计学意义(P0.05);治疗后,治疗组VAS评分、血清PINP、β-CTX、ALP及BGP水平低于对照组,SF-36评分、腰椎1~4 BMD值、全髋关节骨BMD值、左侧股骨颈BMD值高于对照组,两组比较差异有统计学意义(P0.05)。结论六味地黄丸联合唑来膦酸治疗妇女绝经后骨质疏松具有较好的临床疗效,可有效缓解患者疼痛症状,增加骨密度,提高生活质量,具有一定的临床推广应用价值。     

绝经后女性外周骨超声速率与PINP的相关性研究

目的 观察绝经后女性指骨、桡骨、胫骨超声速率(SOS)随年龄变化的规律及其与骨代谢指标血清Ⅰ型前胶原氨基端前肽(PINP)、骨钙素(BGP)和甲状旁腺激素(PTH)的关系.方法 入选绝经后女性84例(42～85岁),其骨代谢生化指标血清PINP和PTH采用酶联免疫法测定,BGP采用放射免疫法测定;应用sunlight omnisense 7000TM型超声骨量测定系统测量研究对象的SOS.结果 绝经后女性桡骨、指骨和胫骨SOS指标值随年龄段递增而下降,但只有桡骨SOS在各年龄段之间差异存在统计学意义(P＜0.05);PINP、BGP和PTH随年龄段递增有变化但(P＞0.05),且与各部位超声骨量SOS的直线相关分析及多元线性回归均无统计学意义.结论 绝经后女性桡骨SOS能够反映绝经后女性骨密度随年龄的衰减,可能是超声骨量测定反映绝经后女性骨量变化的最佳部位.     

Hypophosphatemic osteomalacia: a report of five cases and evaluation of bone markers

In this study, we analyzed the changes in biochemical markers of bone turnover in five patients with hypophosphatemic osteomalacia. The following bone markers were evaluated: among bone formation markers, total alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), osteocalcin (bone Gla protein, BGP) and procollagen type I N propeptide (PINP); among bone resorption markers, serum C-terminal cross-linked telopeptide of type I collagen (s-CTx), urinary hydroxyproline (HYP), and N-terminal and and C-terminal cross-linked telopeptides of collagen (NTx and - and -CTx). In addition, the /-CTx ratio was evaluated. TAP and BAP were the markers with the highest increase in both frequency and magnitude. Conversely, BGP values were low in all patients. Collagen-related markers were slightly increased in nearly half of the patients. Among them, PINP showed the highest proportion of increased values. The /-CTx ratio was within normal values in all patients. In conclusion, TAP and BAP seem to be the best bone markers in the diagnostic evaluation of hypophosphatemic osteomalacia. In addition, their high values associated with low levels of BGP provide an even more reliable biochemical profile of this disorder, when associated with the classic mineral and skeletal homeostasis abnormalities.     

Tocilizumab controls bone turnover in early polymyalgia rheumatica

ObjectivesThis study explores changes in the bone homeostasis by testing the N-terminal collagen type I extension propeptide (PINP) marker for osteo-formation and the carboxy-terminal region of collagen type I (CTX-I) marker for osteo-resorption in patients taking tocilizumab for polymyalgia rheumatica (PMR).MethodsTwenty patients were included in the prospective open-label TENOR study (Clinicaltrials.gov NCT01713842) and received three monthly tocilizumab infusions, followed by corticosteroids starting at week (W) 12. PINP and CTX-I were tested at inclusion (W0), after tocilizumab but before steroid initiation (W12), at the end of the protocol (W24) and were compared to healthy controls. Information regarding disease activity, bone mineral density using scanographic bone attenuation correlation (SBAC), inflammatory parameters and interleukin (IL)-6 levels were collected during the follow-up of the patients.ResultsPMR patients were characterised by a reduction in bone mineral density and a higher level of CTX-I relative to healthy controls matched in age and sex at baseline. PINP levels increased at W12 (P < 0.001, versus W0) following tocilizumab introduction and CTX-I levels decreased at W24 and after steroid initiation (P = 0.001, versus W0). Such modifications explain the altered correlation observed between PINP and CTX-I at W0 (r = 0.255 at W0 versus r = 0.641 in healthy controls) and its correction after treatment (r = 0.760 at W12 and r = 0.767 at W24). Finally, greater changes in PINP were observed in patients whose circulating IL-6 levels decreased after tocilizumab therapy.ConclusionsControl of bone turnover, in part through the inhibition of the IL-6 axis, is observed during tocilizumab and subsequent steroid treatment of PMR.     

Effects of low- and conventional-dose transcutaneous HRT over 2 years on bone metabolism in younger and older postmenopausal women

The minimum dosage of transcutaneous hormone replacement therapy (HRT) able to exert protective effects on postmenopausal bone mass, especially in older women, is uncertain. This study investigates the effects of transcutaneous HRT at two different doses of oestradiol [Estraderm 25 and 50 (E25, E50)] over 2 years in 44 postmenopausal women younger than 67 years and 27 of 67 years and older. Circulating biochemical markers of bone and connective tissue turnover, collagen type I (intact PINP, PICP) and type III (PIIINP) propeptides and type I telopeptide (ICTP), osteocalcin (OC) and alkaline phosphatase (AP) were measured. The responses of the biochemical markers in all the groups were very similar, and most of the observed changes occurred within the first year of treatment. E25 had an effect on the bone markers similar to that of E50, and there was little difference in response according to the patient's age. PINP fell markedly after 1 year in all groups to about half the pretreatment level, with a smaller drop in the second year. PICP responded more variably, and mean values were little changed. There was a slight fall at the higher dose in the younger women, and also in the older women (whose baseline level was higher) on the lower dose. The correlation between PINP and PICP was 0.52 at pretreatment and 0.84 after 2 years of treatment. PIIINP showed no changes. OC and AP both fell in all groups by the first year, but less markedly than PINP. Their response was slightly less pronounced in the older women. ICTP fell marginally in the younger women, and only after 2 years, regardless of dose. Postmenopausal serum oestradiol levels increased after HRT and were associated with decreased binding globulin (SHBG) levels in all groups. After E25 patch application individual serum oestradiol levels were variable and peaked between 13 and 36 h with a median value of 83.8 pmol L^–1. Our data suggest that low-dose transcutaneous HRT restores circulating oestradiol levels in postmenopausal osteopenic women of all ages as effectively as conventional-dose HRT and is associated with decreased circulating markers of bone and connective tissue turnover.     

Biochemical markers in oncology. Part I: molecular basis. Part II: clinical uses

The investigation of the molecular mechanisms involved in carcinogenesis and tumor progression has led to the development of numerous biochemical markers. Biochemical markers may serve for early prediction of tumor recurrence, progression and development of metastases including bone metastases and for prediction of response to therapy. Tumor antigens have been used for more than a decade and although they have shown promising clinical results, their sensitivity and specificity remain limited. A lot of knowledge on the key molecules which control cell cycle, apoptosis and angiogenesis has been acquired during recent years, but their clinical value remains uncertain. Molecular markers which are linked to malignant transformation may provide a non-surgical therapeutic approach by targeting these molecules through gene therapy or antisense molecules. Because of the complexity of the physiopathogical processes involved in tumorogenesis and metastases, we first provide a review on the molecular basis of the various tumor markers and then discuss their potential clinical utility for the major cancers. The review of the current literature indicates that at the exception of a few examples, such as the use of Her-2 to predict response of the targeted Herceptin therapy, no single marker is sensitive and specific enough to perform an accurate diagnosis, predict disease progression or response to treatment. A combination of different biochemical and imaging markers appears to be the most promising strategy to monitor patients with cancer.     

Serum concentrations of formation (PINP) and resorption (Ctx) bone turnover markers in rheumatoid arthritis

Joint inflammation in rheumatoid arthritis (RA) induces local periarticular osteoporosis. Generalised bone mineral density (BMD) decrease concerns approximately 50% of rheumatic patients. Both types of bone mass depletion can issue from cytokine-induced (TNF-α, IL-1, IL-6) osteoclasts’ activation, osteoprotegerin and its ligand’s (RANKL) function disorders, patients’ immobilisation and glucocorticosteroid (GCS) intake, as well as from hormonal alterations in postmenopausal women, predominate among RA individuals. The aim of the study was to compare serum concentrations of marker of bone formation—serum aminoterminal propeptide of type I collagen (PINP), and bone resorption, carboxy (C) terminal telopeptide (Ctx), bone turnover markers in RA and osteoarthritis (OA) patients and in RA groups of different disease activity, different degree of joint damage and the history of GCS intake. A total of 50 RA female patients and 50 women with knee OA were included in the study. Blood for morphology and biochemistry laboratory tests was taken. Joint X-rays to establish OA and RA diagnosis and the degree of RA progression, as well as DEXA BMD measurements were performed. PINP and Ctx concentrations were assessed. In RA patients the number of swollen and painful joints, the duration of morning stiffness, visual analogue scale values and Waaler–Rose’s test activity were recorded. The Disease Activity Index (DAS 28) was counted from the appropriate formula. No differences in bone turnover markers’ concentrations were noted neither between RA and OA patients nor between the RA group when compared to the one without the history of GCS use. Bone turnover markers’ concentrations in RA were proportional to the number of swollen and painful joints. However, no correlation was found between the markers’ concentrations and RA activity assessed by DAS 28 or by laboratory means. Ctx concentrations were higher in patients at II degree joint damage according to Larsen and Dale’s than at more advanced stages. Ctx concentrations decreased with the disease duration. Serum morphogenesis and resorption markers’ concentrations change in course of RA indicating the decrease in bone metabolic activity with the disease duration and progression. High RA activity and severity correlate with increased markers’ levels—the resorption one. The influence of GCS on bone metabolism in RA requires further study.     

Fibrosis in endstage human heart failure: Severe changes in collagen metabolism and MMP/TIMP profiles

Objectives

We studied fibrosis, collagen metabolism, MMPs/TIMPs and cytokine expression in various forms of human heart failure (HF) by quantitative immunofluorescent microscopy, Western blot, zymography, RT-PCR and in situ hybridization. In explanted human hearts with HF due to either dilated (DCM, n = 6) or ischemic (ICM-BZ-borderzone, ICM-RZ-remote zone, n = 7) or inflammatory (myocarditis, MYO, n = 6) cardiomyopathy and 8 controls MMP2, 8, 9, 19, and TIMP1, 2, 3, 4 as well as procollagens I and III (PINP, PIIINP), mature collagen III (IIINTP) and the cross-linked collagen I degradation product (ICTP) were measured.

Results

In comparison with controls, MMPs and TIMPs were significantly upregulated ranging (from highest to lowest) from ICM-BZ, DCM, ICM-RZ, MYO for all MMPs with the exception of MMP9 (highest in DCM), and for TIMPs from ICM-BZ, ICM-RZ, DCM and MYO. MMP2 and 9 were activated in all groups. The TIMP/MMP ratio was 1.3 for control, 1.9 in ICM-BZ (TIMP > MMP) and lowered to 1.0 in the other groups. Collagen I/collagen III ratio correlated significantly with the decrease in LVEDP. PINP was higher than ICTP in all groups. PIIINP elevation was present in DCM and ICM-RZ and IIINTP was up to 4-fold augmented in all groups. Fibrosin mRNA was upregulated in ICM-BZ, activin A in MYO but FGF1 and FGF2 remained unchanged. ANP mRNA was increased in all groups.

Conclusions

Although different degrees of severity of collagen metabolism, MMP/TIMP imbalance and cytokine expression in diverse forms of HF are present, the end product is collagen deposition. These findings suggest multiple mechanisms acting alone or in concert in fibrosis development in HF.