甲状旁腺素与二磷酸盐治疗绝经妇女骨质疏松症有效性及安全性评价——Meta分析

目的 评价甲状旁腺素与二磷酸盐治疗绝经妇女骨质疏松症有效性及安全性差异.方法 通过检索Pubmed、Cochrane图书馆、EMbase、Highwire、中国生物医学文献数据库CBM、CNKI等中外生物医学数据库,收集有关应用甲状旁腺素与二磷酸盐治疗绝经妇女骨质疏松症的临床随机对照试验,检索文献日期从2002年1月至2012年9月.采用Cochrane系统评价方法,按照纳入和排除标准限定研究对象,评估所纳入研究的文献质量,并提取有效数据后采用RevMan5.0软件进行Meta分析.结果 共纳入应用甲状旁腺素与二磷酸盐对比治疗绝经妇女骨质疏松症的临床对照研究9项(共1287例).结果 显示:在有效性方面,甲状旁腺素组比二磷酸盐组能提高绝经妇女骨质疏松症者腰椎BMD[WMD=3.96,95%CI(3.10,4.82)]和股骨颈BMD[WMD=2.05,95%CI(0.27,3.83)],而后者比前者更能提高髋BMD[WMD=-1.07,95%CI(-1.72,-0.41)];在安全性方面,甲状旁腺素组不良事件总发生率低于二磷酸盐组[WMD=0.87,95%CI(0.59,1.30)].二者背痛与非椎体骨折发生率无显著差异,但前者血钙、尿钙超出正常水平发生率显著高于后者{血钙:[WMD=13.68,95%CI(6.12,30.59)];尿钙:[WMD=2.21,95%CI(1.14,4.26)]}.结论 甲状旁腺素类药物比二磷酸盐类药物更能提高绝经妇女骨质疏松症病人腰椎、股骨颈BMD,改善骨质量的疗效肯定,且安全性较高.但在临床使用中,要定时监测患者血钙、尿钙水平,进一步提高用药安全性.     

Alteration of the circadian rhythm of intact parathyroid hormone and serum phosphate in women with established postmenopausal osteoporosis

Several studies have established that the circulating concentration of intact parathyroid hormone, PTH (1–84), over 24 h follows a circadian rhythm. The importance of this circadian rhythm is not known although some authors have detected alterations in the rhythm in metabolic bone disease and following dietary manipulation. We have studied the circadian rhythm of PTH (1–84) in 8 premenopausal women, 8 postmenopausal women with established osteoporosis and 8 postmenopausal women with no evidence of osteoporosis. Blood samples were obtained at 30-min intervals over a 24-h period and significant differences were found in the profiles of PTH (1–84) and serum phosphate in the three groups studied. Premenopausal women possessed a nocturnal/early morning increase in PTH (1–84) and phosphate (between 2200 and 0700 hours), as did postmenopausal women without osteoporosis. In postmenopausal women with osteoporosis the nocturnal increase in PTH (1–84) and serum phosphate was absent and PTH (1–84) decreased during the period 2200-0700 hours. A shift in acrophase is observed between premenopausal and postmenopausal women without osteoporosis. No acrophase was found in postmenopausal women with osteoporosis for either PTH (1–84) or serum phosphate. No circadian rhythm, acrophase or significant amplitude was observed in serum adjusted calcium or ionized calcium in any group studied. Alterations in the circadian rhythms for PTH (1–84) and serum phosphate occur in patients with postmenopausal osteoporosis that suggest the normal dynamics of PTH (1–84) secretion may play a role in both calcium and phosphate metabolism and the bone remodelling process. Whether these changes are causative or a response to the pathology will require further investigation.     

甲状旁腺激素（1-34）与唑来膦酸联合治疗对骨质疏松大鼠骨折愈合的影响

目的探讨唑来膦酸(ZA)与甲状旁腺激素(PTH)的联合应用对去势大鼠骨折愈合的影响。方法对双侧卵巢摘除术12周后的大鼠行单侧胫骨水平骨切开术,并以髓内钉进行固定。所有大鼠在行骨折造模术后,随机接受赋形剂、ZA、PTH与ZA+PTH治疗。在治疗4或8周后,收集胫骨标本进行micro-CT、组织学及生物力学测试。结果与对照组相比,所有药物干预方法都促进了骨痂形成、增加了骨痂强度;ZA+PTH组在相对骨体积(BV/TV)、骨小梁粗度和生物力学上表现出了最强的促进作用。结论 ZA与PTH联合应用对去势大鼠的骨折愈合有累加作用。     

甲状旁腺素促成骨作用的研究进展

甲状旁腺素(Parathyroid hormone,PTH)能够调节骨骼的合成代谢和分解代谢过程,通过影响包括成骨细胞、破骨细胞、骨骼内衬细胞、骨细胞等众多种类的细胞系,并激活多种信号途径,从而达到促进骨形成的作用.这取决于低剂量及间断性的给药方式.大量动物试验和临床研究,显示甲状旁腺素可有效的治疗骨质疏松.近年来动物实验发现甲状旁腺素也可有效的促进骨折愈合.甲状旁腺素作为骨形成促进剂,将广泛应用于临床治疗.     

联合使用甲状旁腺激素和钙剂对骨质疏松的防治有叠加作用

目的探索联合使用甲状旁腺激素和钙剂对去势大鼠诱导骨质疏松的防治作用。方法 50只健康雌性SD大鼠随机行假手术(Sham,N=10)和切除双侧卵巢(OVX,N=40)手术后,OVX大鼠随机的分成4组:OVX组、CA组、PTH组、PTH+CA组。术后第一天PTH组及PTH+CA开始给予药物治疗:PTH皮下注射(剂量60μg/kg,每周3次)。术后CA组及PTH+CA组大鼠饮食中加入钙剂,其余组大鼠普通饮食,直至手术后12周为止,12时所有大鼠处死取胫骨行Micro-CT、硬组织切片检测。结果 CA组、PTH组、PTH+CA组和OVX组相比,胫骨近端都有较高的BMD、BV/TV、Tb.Th、Tb.N、Conn.D、骨矿化沉积率(MAR)和较低的Tb.Sp,其中PTH+CA组大鼠胫骨有最高的BMD、BV/TV、Tb.Th、Tb.N、Conn.D、MAR和最低Tb.Sp。钙剂和PTH单独使用的效果明显低于他们联合使用对去卵巢大鼠骨质疏松的防治作用。结论联合使用甲状旁腺激素和钙剂对去势大鼠骨质疏松的防治有叠加作用     

Intermittent treatment with parathyroid hormone (PTH) as well as a non-peptide small molecule agonist of the PTH1 receptor inhibits adipocyte differentiation in human bone marrow stromal cells

Whereas continuous PTH infusion increases bone resorption and bone loss, intermittent PTH treatment stimulates bone formation, in part, via reactivation of quiescent bone surfaces and reducing osteoblast apoptosis. We investigated the possibility that intermittent and continuous PTH treatment also differentially regulates osteogenic and adipocytic lineage commitment of bone marrow stromal progenitor/mesenchymal stem cells (MSC). The MSC were cultured under mildly adipogenic conditions in medium supplemented with dexamethasone, insulin, isobutyl-methylxanthine and troglitazone (DIIT), and treated with 50 nM human PTH(1–34) for either 1 h/day or continuously (PTH replenished every 48 h). After 6 days, cells treated with PTH for 1 h/day retained their normal fibroblastic appearance whereas those treated continuously adopted a polygonal, irregular morphology. After 12–18 days numerous lipid vacuole and oil red O-positive adipocytes had developed in cultures treated with DIIT alone, or with DIIT and continuous PTH. In contrast, adipocyte number was reduced and alkaline phosphatase staining increased in the cultures treated with DIIT and 1 h/day PTH, indicating suppression of adipogenesis and possible promotion of early osteoblastic differentiation. Furthermore, intermittent but not continuous PTH treatment suppressed markers of differentiated adipocytes such as mRNA expression of lipoprotein lipase and PPARγ as well as glycerol 3-phosphate dehydrogenase activity. All of these effects of intermittent PTH were also produced by a 1 h/day treatment with AH3960 (30 μM), a small molecule, non-peptide agonist of the PTH1 receptor. AH3960, like PTH, activates both the cAMP and calcium signaling pathways. Treatment with the adenylyl cyclase activator forskolin for 1 h/day, mimicked the anti-adipogenic effect of intermittent PTH, whereas pretreatment with the protein kinase-A inhibitor H89 prior to intermittent PTH resulted in almost complete conversion to adipocytes. In contrast, the MAP kinase inhibitor PD 98059 failed to prevent the anti-adipocytic effect of intermittent PTH, suggesting that the inhibitory effect of PTH on adipocyte differentiation is predominantly cAMP-dependent. These results demonstrate a differential effect of PTH1 receptor agonists on the adipocytic commitment and differentiation of adult human bone marrow mesenchymal stem cells. This response may represent an additional mechanism that contributes to the overall bone anabolic action of intermittent PTH.     

Osteoporotic fracture and parathyroid hormone

Osteoporosis and age-related bone loss is associated with changes in bone remodeling characterized by decreased bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Stimulating the function of bone-forming osteoblasts, is the preferred pharmacological intervention for osteoporosis. Recombinant parathyroid hormone (PTH), PTH(1-34), is an anabolic agent with proven benefits to bone strength and has been characterized as a potential therapy for skeletal repair. In spite of PTH's clinical use, safety is a major consideration for long-term treatment. Studies have demonstrated that intermittent PTH treatment enhances and accelerates the skeletal repair process via a number of mechanisms. Recent research into the molecular mechanism of PTH action on bone tissue has led to the development of PTH analogs to control osteoporotic fractures. This review summarizes a number of advances made in the field of PTH and bone fracture to combat these injuries in humans and in animal models. The ultimate goal of providing an alternative to PTH, currently the sole anabolic therapy in clinical use, to promote bone formation and improve bone strength in the aging population is yet to be achieved.     

甲状旁腺激素(1-34)联合维生素K2对绝经后骨质疏松患者疗效的临床研究

目的观察甲状旁腺激素(1-34)(parathyroid hormone,PTH)联合维生素K_2(VK_2)对绝经后骨质疏松患者的临床疗效。方法选取2014年5月至2016年2月于我院治疗的120例绝经后骨质疏松患者进行研究,按照1∶1∶1比例随机分为3组:VK_2组、PTH组、联合治疗组。PTH组40例患者给予特立帕肽20μg皮下注射,每日1次,治疗6个月;VK_2组40例患者口服四烯甲萘醌软胶囊45 mg/d,每日3次,治疗12个月。联合治疗组40例给予特立帕肽联合四烯甲萘醌软胶囊治疗。药物治疗后,将3组患者的腰椎及髋部骨密度、血钙、血磷、血清骨转换指标骨碱性磷酸酶(BALP)、I型胶原N末端肽/肌酐(NTX/Cr)变化情况进行对比,同时对患者服药后的不良反应发生率进行比较。结果治疗6个月和12个月后,3组患者骨密度较治疗前都显著改善(P0.05),且相同时间点联合治疗组均明显优于VK_2组及PTH组(P0.05)。药物治疗12个月后,3组患者血清BALP和NTX/Cr水平较治疗前有显著改变(P0.05),且相同时间点联合治疗组均明显优于VK_2组和PTH组(P0.05)。3组药品不良反应发生率比较,差异无统计学意义(P0.05)。结论甲状旁腺激素和维生素K2均对绝经后骨质疏松患者疗效显著,且联合使用效果更佳。     

The effect of an oral calcium load on plasma ionized calcium and parathyroid hormone concentrations in osteoporotic postmenopausal women

Summary Plasma ionized calcium (IC) and parathyroid hormone (PTH) concentrations were measured in 31 osteoporotic postmenopausal women at hourly intervals for 5 hours after a 1 g oral calcium load. Fifteen subjects had normal radiocalcium absorption and 16 subjects were malabsorbers of calcium. IC rose and PTH fell after the calcium load in both groups with a plateau at 3–4 hours, and the rise in IC was greater (P<0.01) in the normal absorbers. There was a nonsignificant trend for the fall in PTH to be greater in the normal absorbers. In the group as a whole the mean increase in IC (above baseline) at 4 hours was directly related to calcium absorption (P<0.025) and the mean change in PTH was inversely related to calcium absorption (P<0.05). These results demonstrate that in subjects with postmenopausal osteoporosis the responses of IC and PTH to an oral calcium load are a function of calcium absorptive status.     

甲状旁腺激素(1-34)联合伊班膦酸钠治疗严重骨质疏松症的临床研究

目的甲状旁腺激素(parathyroid hormone,PTH)(1-34)联合伊班膦酸钠治疗严重骨质疏松症效果临床观察。方法98例严重绝经后骨质疏松症合并骨骼疼痛患者随机分为治疗组和对照组,治疗组使用PTH联合伊班膦酸钠治疗,对照组单纯予以伊班膦酸钠治疗,为期12个月。分别检测两组受试者腰椎及髋部骨密度、血清骨代谢指标治疗前后的改变。结果药物治疗6个月后两组患者腰椎L1~4及股骨粗隆、左侧股骨颈、Ward三角区的骨密度明显增加,且12个月后骨密度进一步增加,显著高于对照组(P0.05);药物治疗12个月后两组血清及碱性磷酸酶(ALP)、血清Ⅰ型胶原C末端肽(s-CTX)、血清抗酒石酸酸性磷酸酶-5b(TRACP-5b)、血清骨源性碱性磷酸酶(BAP)及血清骨钙素(OC)水平均显著改变,且治疗组对ALP及s-CTX、BAP、OC及TRACP-5b影响更明显(P0.05),而两组血钙(Ca)及血磷(P)治疗前后无明显差异(P0.05)。结论PTH联合伊班膦酸钠使用能有效提高严重骨质疏松症患者髋部及腰椎骨密度,改善骨代谢。     

重组人甲状旁腺素（1-34）治疗原发性骨质疏松症疗效观察

目的 观察重组人甲状旁腺素(1-34)[PTH(1-34)]治疗前后骨密度、骨代谢指标变化,以评价该药治疗原发性骨质疏松症疗效。方法 20例原发性骨质疏松症患者皮下注射PTH(1-34) 20μg 每天1次,每日口服钙尔奇D 600mg,连续治疗6个月。所有患者于治疗前、治疗后第3月、第6月检测腰椎(L2-L4)及股骨颈骨密度、血清骨特异性碱性磷酸酶（BSAP）、血清I型胶原交基C端肽(CTX)。结果 治疗后腰椎(L2-L4)骨密度较治疗前均显著升高,差异有统计学意义（P<0.05或P<0.01）。治疗后股骨颈骨密度较治疗前无明显改善(P>0. 05)。治疗后第3月、第6月BSAP较治疗前显著升高,差异有统计学意义（P<0.01）,治疗后第6月CTX较治疗前显著升高,差异有统计学意义（P<0.01）。结论 PTH(1-34)能显著提高腰椎（L2-L4）骨密度,对原发性骨质疏松症治疗有效。     

重组人甲状旁腺激素1-34治疗绝经后骨质疏松症疗效的临床观察

绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)属于原发性骨质疏松的一种,是一种全身性骨代谢疾病,一旦发生骨折,就会给家庭和社会造成极大的负担.目前用于治疗PMOP的药物大多主要通过抑制骨吸收来提高骨密度(bone mineral density,BMD),而甲状旁腺激素(parathyroid hormone,PTH)却是通过促进骨形成来提高BMD,临床和试验研究证实,单独小剂量间断给药能提高BMD、改善骨质量、降低骨折的发生率;联合雌激素、雌激素受体调节剂、降钙素、膦酸盐同样能增加腰椎及全髋骨密度、降低骨折发生率.本文着重介绍重组人甲状旁腺激素(1-34)及其联合用药对PMOP的临床疗效.     

甲状旁腺激素(1-34)对空心钉治疗老年股骨颈骨折合并骨质疏松症的疗效影响

目的甲状旁腺激素(1-34)对空心钉治疗老年股骨颈骨折合并骨质疏松症疗效的观察及分析,为老年股骨颈骨折合并骨质疏松寻找到安全可靠,更具有良好疗效的治疗方案。方法 2010年1月至2016年1月间收治的老年股骨颈骨折合并骨质疏松患者78例,采用随机数字表法将其分为治疗组和对照组,每组39例,两组患者均接受空心钉治疗。治疗患者术后加用甲状旁腺激素治疗,比较两组患者治疗后患者视觉模拟痛疼评分(VAS)、髋关节Harris功能评分、骨折愈合时间及股骨颈及腰椎的骨密度改变。结果术后1、3、6个月两组患者VAS评分均明显降低,且治疗组患者评分明显低于对照组(P0.05);术后3、6个月两组患者的Harris评分均明显上升,且治疗组患者评分明显高于对照组(P0.05);治疗组骨折愈合的时间明显少于对照组(P0.05);术后3、6个月两组患者股骨颈及腰椎的骨密度,治疗组患者骨密度较术前显著改善(P0.05),而对照组治疗前后上述指标无明显变化(P0.05)。结论甲状旁腺激素对空心钉治疗老年股骨颈骨折合并骨质疏松症是一种安全、疗效更好的方法。     

Present and future scope of recombinant parathyroid hormone therapy in orthopaedics

Parathyroid Hormone (PTH) has a significant role in calcium metabolism. Its intermittent administration has an anabolic effect on bone mineralization. Teriparatide (PTH 1-34), a recombinant form of parathyroid hormone, is useful in the treatment of osteoporosis, fracture healing, non-union, stress fracture, augmentation of implant fixation with bone, and chondroprotection in osteoarthritis. The present review article will elaborate on the potential approved uses of recombinant PTH in orthopedics and its evolving role in the management of fracture osteosynthesis and other common challenging bone pathologies.     

甲状旁腺激素经不同信号通路调节骨代谢的研究进展

甲状旁腺激素是目前广泛应用于临床中的抗骨质疏松骨形成促进剂。然而，由于其小剂量、间歇性促进骨形成以及大剂量、连续性促进骨吸收的双向调节作用，使得甲状旁腺激素在骨质疏松症的治疗中有待进一步优化。因此，立足于甲状旁腺激素调节骨代谢的分子机制，总结甲状旁腺激素主要经如下信号通路调节骨代谢：（1）Gs/cAMP/PKA信号通路，是甲状旁腺激素调节骨组织代谢引起骨形成或骨吸收效应的主要机制。（2）G_q/11/PLC/PKC信号通路，其主要功能为抑制成骨作用。（3）nonPLC/PKC信号通路，目前认为其发挥成骨效应，但具体内容尚不完全明确。（4）β-arrestin信号通路，能通过受体脱敏及内吞机制仅产生成骨作用而无破骨的激活。对甲状旁腺激素激活的上述4条主要信号通路的内容及作用进行文献综述，以期找寻更好的骨形成促进剂。其中，SOST及Dickkopf-1单克隆抗体是新颖的靶向药物，特异性激活nonPLC/PKC信号通路或β-arrestin信号通路的甲状旁腺激素相关肽值得进一步开发和应用。     

Coherence treatment of postmenopausal osteoporosis with growth hormone and calcitonin

Summary Fourteen women with postmenopausal osteoporosis, all having at least one vertebral crush fracture, were randomly assigned to two treatment arms, each lasting 24 months. The coherence treatment group (7 patients) was treated in the following sequence: human growth hormone (hGH) 7 IU subcutaneously daily for 2 months, followed by 3 months of salmon calcitonin (CT), 100 MRC units every other day. After a 3 month rest period, this sequence was repeated twice. The contrast group (7 patients) was treated intermittently with salmon CT given in the same time periods and at the same dose as in the coherence treatment group. Bone mass was measured every 4 months by neutron activation analysis for total body calcium (TBCa) and by single photon absorptiometry for bone mineral content (BMC) of the distal radius. Although there were no significant differences between the two groups (two-way ANOVA), the rate of change in TBCa in the coherence treatment group was significantly different from zero (F=3.8,P<.05) and was +2.3%/year. The increase in bone mass appeared to be sustained throughout the 2 year study, in contrast with previous studies where a plateau effect was observed with calcitonin given alone or continuously with growth hormone. No significant change was found in bone histomorphometric values measured before and after treatment in 4 patients from each group.     

Cost-effectiveness of alendronate in the treatment of postmenopausal women in 9 European countries - an economic evaluation based on the fracture intervention trial

Summary

Treatment with alendronate (Fosamax®) has been shown to significantly reduce the risk of fragility fractures. Cost-effectiveness of treatment was assessed in nine European countries in a Markov model and was generally found to be cost effective in women with a previous spine fracture.

Introduction

Treatment with alendronate (Fosamax®) reduces the risk of osteoporotic fractures at the spine, hip and wrist in women with and without prevalent vertebral fracture. Cost-effectiveness estimates in one country may not be applicable elsewhere due to differences in fracture risks, costs and drug prices. The aim of this study was to assess the cost-effectiveness of treating postmenopausal women with alendronate in nine European countries, comprising Belgium, Denmark, France, Germany, Italy, Norway, Spain, Sweden, and the UK.

Methods

A Markov model was populated with data for the nine European populations. Effect of treatment was taken from the Fracture Intervention Trial, which recruited women with low BMD alone or with a prior vertebral fracture.

Results

The cost per QALY gained of treating postmenopausal women with prior vertebral fractures ranged in the base case from “cost saving” in the Scandinavian countries to €15,000 in Italy. Corresponding estimates for women without prior vertebral fractures ranged from “cost saving” to €40,000.

Conclusions

In relation to thresholds generally used, the analysis suggests that alendronate is very cost effective in the treatment of women with previous vertebral fracture, and in women without previous vertebral fracture, cost-effectiveness depends on the country setting, discount rates, and chosen monetary thresholds.

     

Relationship between duration of teriparatide therapy and clinical outcomes in postmenopausal women with osteoporosis

Summary  The extent to which fracture protection and safety varies with increasing time on teriparatide [rhPTH(1-34)] therapy is a clinically relevant unanswered question. In postmenopausal women with osteoporosis, increased duration of teriparatide versus placebo treatment was associated with a progressive decrease in the rates of nonvertebral fragility fractures and back pain. Introduction  The impact of duration of teriparatide [rhPTH(1-34)] therapy on patient outcomes is a relevant unanswered question. Methods  Postmenopausal women with osteoporosis were randomized to once-daily subcutaneous injection with placebo (N = 544), teriparatide 20 μg (TPTD20; N = 541), or teriparatide 40 μg (TPTD40; N = 552) plus calcium and vitamin D supplementation. The time to first nonvertebral fragility fracture and new or worsening back pain following treatment initiation was analyzed using Cox partial likelihood regression treating time on therapy as a linear, time-dependent covariate. Results  Compared with placebo, the relative hazard for nonvertebral fragility fractures decreased by 7.3% for each additional month of TPTD20 [hazard ratio = 0.927, 95% CI (0.876 to 0.982), p = 0.009] and by 7.6% for each additional month of TPTD40 [hazard ratio = 0.924, 95% CI (0.871 to 0.981), p = 0.009]. Clinical vertebral fractures appeared to increase over time in the placebo group and occurred primarily in the first time interval in the teriparatide treatment groups. Compared with placebo, the relative hazard of back pain was decreased by 8.3% for each additional month of TPTD20 [hazard ratio = 0.920, 95% CI (0.902 to 0.939), p < 0.001] and 8.7% for each additional month of TPTD40 [hazard ratio = 0.917, 95% CI (0.898 to 0.935), p < 0.001]. Conclusions  These findings suggest increased nonvertebral fracture protection, reduced back pain, and reduced occurrence of side effects with longer duration of teriparatide therapy. Some of these findings were presented at the 67th Annual Scientific Meeting of the American College of Rheumatology in Orlando, Florida, October 23–28, 2003 and at the 31st European Symposium on Calcified Tissues in Nice, France, June 5–9, 2004.     

Hetereogeneity in skeletal response to full-length parathyroid hormone in the treatment of osteoporosis

Summary In the PaTH trial, among the 119 women randomized to parathyroid hormone PTH(1–84) and 60 to alendronate, we found much greater variation in BMD and markers in response to PTH(1–84) compared to alendronate. No baseline participant characteristic consistently predicted increased bone density response to PTH(1–84), although women with larger changes in 1,25 dihydroxyvitamin D during therapy had larger increases in BMD. Introduction We examined variability in BMD and markers of bone turnover in response to treatment with PTH(1–84) or alendronate in the PaTH trial. Methods Differences in SD were examined using Levine’s test for homogeneity of variance. Change in BMD across quartiles of participant characteristics was examined using ANOVA. Results We found much greater variation in response to PTH(1–84) compared to alendronate. The SD for change in cancellous spine BMD (by QCT) was 32% on PTH(1–84) compared to 13% on alendronate (p < 0.0001). The higher variability in the PTH(1–84) group was due to substantial numbers of women with large increases in BMD on PTH(1–84). Similarly, the SD of changes in markers of formation and resorption were significantly higher on PTH(1–84) than on ALN. No baseline participant characteristics predicted increased bone density response to PTH(1–84) therapy. However, change in 1,25-OH₂D explained 16% of the variance in BMD response to PTH(1–84). Conclusion There is significant variability in the skeletal response to PTH(1–84), which exceeds that observed with alendronate. Changes in 1,25-OH₂D were related to larger gains in BMD. This finding may have implications for elucidating either the pathway by which PTH affects the skeleton or traits that result in particular responsiveness to PTH therapy.     

重组甲状旁腺激素与骨质疏松关系的研究新进展

甲状旁腺激素(parathyroid,PTH)由甲状旁腺主细胞合成,是调节钙磷代谢、维持机体钙平衡的主要激素之一。本文就甲状旁腺激素与骨质疏松症间的作用加以概述。1PTH的结构与功能1.1PTH的结构PTH在体内的最初翻译产物是含115个氨基酸的前甲状腺激素原,分泌过程中其首先在粗面内质网