国产注射用特立帕肽的过敏性及免疫原性研究

目的 考察国产注射用特立帕肽在动物中的过敏性及免疫原性.方法 对豚鼠和家兔分别于0d和14 d注射一定浓度的特立帕肽,观察豚鼠全身变态反应及对家兔的免疫原性,并采用ELISA分析家兔血清抗体的变化规律.结果 给药后豚鼠未见明显全身变态反应.家兔免疫原性实验结果表明,低剂量组（1 μg/kg）血清中的IgE含量经免疫后无明显上升;中剂量组（5μg/kg）和高剂量组（10 μg/kg）血清中IgE含量在首次免疫后略有快速上升,但随后中剂量组恢复正常,而高剂量组在加强免疫后IgE含量仍有一定上升.结论 国产注射用特立帕肽在拟定的人用剂量范围内具有很好的安全性,可供皮下注射给药.     

Systemic administration of pharmacological agents and bone repair: what can we expect

Pharmacologic agents that modulate bone formation and bone remodelling are in broad use and development for the treatment of osteoporosis and other disorders of bone fragility. There is significant interest into the effect these agents may have on bone repair and fracture healing and whether these agents may be beneficial or detrimental to bone repair. Bisphosphonates delay callus remodelling, but increased callus volume seen during endochondral bone repair with bisphosphonate use allows for equivalent biomechanical properties for the fractured bone. Teripartide stimulates bone formation and in bone repair appears to have the potential to accelerate fracture callus formation and remodelling, potentially accelerating fracture healing. Animal models of fracture healing have demonstrated accelerated healing with larger callus volume, more rapid remodelling to mature bone, and improved biomechanical properties of the fractured bone. Clinical data with teriparatide has shown mixed results for its ability to stimulate fracture healing. Wnt signalling is one of the major pathways through which cartilage and bone formation is regulated during development. This same pathway has been identified as one of the ways that teriparatide stimulates bone formation. Antibodies to downstream proteins in this pathway, Dkk-1 and sclerostin, show significant promise of accelerating even normal fracture healing in preclinical animal models.     

Osteogénesis imperfecta. Descripción de 15 casos

Osteogenesis imperfecta (OI) is an inherited connective tissue disease. The disease has been linked to mutations in one of the type I collagen genes. The diagnosis is based on clinical and radiologic findings. The management of OI in adults is not well-established and includes physical rehabilitation, surgical procedures, the use of antiresorptive therapy and anabolic agents. The aim of the present work was to analyze the clinical and analytical characteristics of these patients in adulthood, as well as to evaluate the different treatments administered. We reviewed the cases of OI diagnosed in our center over the last 12 years (2005-2017). We describe 15 adult patients with OI.     

骨质疏松性骨折的药物治疗策略与选择

随着老龄化社会的到来,低暴力脆性骨折的发病率逐年提高。而锁定钢板和骨水泥加强技术在临床中的应用,使得手术治疗骨质疏松性骨折已不再困难,但骨质疏松再骨折已成为另一治疗难点和热点。各种新型抗骨质疏松药物的问世,使得医务工作者在使用抗骨质疏松药物时,面临更多的选择难题。本文通过对既往临床文献的阅读和结果的总结,旨在为广大医务工作者在抗骨质疏松药物治疗骨质疏松性骨折的使用方面提供参考。     

特立帕肽联合阿仑膦酸钠治疗绝经后骨质疏松症的临床研究

目的探讨特立帕肽联合阿仑膦酸钠治疗绝经后骨质疏松症的临床疗效。方法选取2014年1月—2015年6月天津中医药大学第一附属医院收治的绝经后骨质疏松症患者140例,随机分为对照组和治疗组,每组各70例。对照组患者口服阿仑膦酸钠片,1片/次,1次/d。治疗组在对照组治疗基础上皮下注射特立帕肽注射液,20μg/次,1次/d。两组患者均连续治疗6个月。观察两组患者治疗前后骨密度和骨代谢指标的变化情况。结果治疗组治疗3个月时腰椎骨密度相对于治疗前有明显上升,全髋与股骨颈骨密度则无明显变化,治疗组治疗6个月时腰椎、全髋、股骨颈骨密度均明显上升,同组治疗前后差异具有统计学意义(P0.05);对照组治疗3个月各部位骨密度均未出现明显上升,治疗6个月腰椎骨密度较治疗前有明显上升(P0.05)。治疗组治疗6个月时腰椎、全髋、股骨颈骨密度改善情况明显优于对照组,两组比较差异有统计学意义(P0.05)。治疗组治疗3、6个月血清骨钙素(OC)水平逐渐上升,均明显高于治疗前,同组治疗前后差异具有统计学意义(P0.05);对照组则逐渐下降,均明显低于治疗前(P0.05);治疗组治疗3、6个月血清Ⅰ型胶原羧基端肽交联(β-CTX)水平逐渐下降,对照组也逐渐下降,对照组下降幅度则明显大于治疗组(P0.05)。结论特立帕肽联合阿仑膦酸钠治疗绝经后骨质疏松症具有较好的临床疗效,可增加患者的骨密度,可有效改善骨代谢,具有一定的临床推广应用价值。     

Effective ancillary role and long-term course of daily or weekly teriparatide treatment on refractory medication-related osteonecrosis of the jaw: a clinical case series

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse side effect of antiresorptive agents. However, withdrawal of such agents in patients with osteoporosis may increase the risk of fracture. The treatment of MRONJ is challenging, and standard treatment guidelines have yet to be established. In this study, the aim was to find out whether adjuvant daily or weekly teriparatide (TPTD) injections were beneficial for exposed bony MRONJ lesions compared with standard conservative management. We also studied the complications and the patients’ response to TPTD therapy. We enrolled 27 patients (January 2012 - December 2016) with chronic and refractory MRONJ. There were four men and 23 women (85% female). Nine patients who did not select TPTD therapy for several reasons formed the non-TPTD group; the remaining 18 were randomly assigned to the daily (n=9) or weekly (n=9) groups. All patients in both groups continued standard conservative therapy in addition to their daily or weekly subcutaneous injection of TPTD (20 μg or 56.5 μg, respectively). We evaluated the complications of TPTD and its benefits. Three patients in the daily group did not complete the study, resulting in six patients in the daily group, nine in the weekly group, and nine in the non-TPTD group in the final analysis. The exposed bone was completely covered with normal mucosa in all patients in the TPTD groups, and the healing period was shorter than that in the non-TPTD group. No patient had complications of atypical fractures of the femoral head. Daily and weekly TPTD treatment resulted in a shortened treatment period compared with standard conservative therapy, with no increase in the rate of complications or worsening of osteoporosis.     

特立帕肽联合利塞膦酸钠治疗骨质疏松椎体压缩骨折患者的骨代谢

背景:对于骨质疏松性椎体压缩骨折,椎体成形术后的邻近椎体再发骨折率较高,骨质疏松是导致再发骨折的一种独立危险因素,因而术后选择疗效较好的抗骨质疏松药物是临床热点问题.目的:探讨骨质疏松椎体压缩性骨折术后联合应用特立帕肽与利塞膦酸钠的效果.方法:纳入华北医疗健康集团峰峰总医院邯郸院区2018年9月至2020年10月收治的...     

Vertebral Collapse Prevented Following Teriparatide Treatment in Postmenopausal Kümmell's Disease Patients with Severe Osteoporosis

ObjectiveTo compare the preventive effects of teriparatide and alendronate on the progression of vertebral body collapse in postmenopausal single‐level Kümmell''s disease (KD).MethodsFrom March 2013 to December 2020, the medical records for 53 postmenopausal single‐level KD patients who received conservative treatment with teriparatide (25 patients, teriparatide group) or alendronate (28 patients, alendronate group) were retrospectively reviewed. Midsagittal computed tomography (CT) images were analyzed by ImageJ to assess the intravertebral bone formation (mineralized bone) by calculating the ratio of area of intravertebral mineralized bone (AIMB) to the area of fractured vertebral body (AFVB). The changes in radiological parameters of the fractured vertebral body including kyphosis angle (KA), anterior and posterior border heights (ABH and PBH) and spinal canal diameter (SCD), bone turnover biomarkers (BTMs), and bone mineral density (BMD) were analyzed to evaluate the therapeutic effect.ResultsAt month 12, the ratio of AIMB to AFVB was significantly greater in teriparatide group (54.28% ± 15.30%) than in alendronate group (35.57% ± 17.61%) (P < 0.001). Sagittal CT substantiated the formation of bone bridge in 16 patients in teriparatide group. No bone bridge was detected in alendronate group. The KA was significantly smaller and the ABH, PBH, and SCD was greater in teriparatide group than in alendronate group (all P < 0.001). The KA increments were significantly smaller in teriparatide group (3.98° ± 1.30°) than in alendronate group (11.43° ± 3.73°) (P < 0.001). The ABH and PBH decrement were significantly lower in teriparatide group (11.96% ± 1.93% and 2.80% ± 2.52%) than in alendronate group (37.04% ± 8.00% and 19.50% ± 8.22%) (both P < 0.001). The BTMs and BMD were significantly greater in the teriparatide group than in the alendronate group. In teriparatide group, KA increment was negatively correlated with the change in PINP (r = −0.781, P < 0.001) and the ratio of AIMB to AFVB (r = −0.592, P = 0.002) from baseline to month 12. The ABH decrement was negatively correlated with the change in PINP (r = −0.612, P = 0.001) and the ratio of AIMB to AFVB (r = −0.806, P < 0.001) from baseline to month 12.ConclusionsIn postmenopausal single‐level KD patients, conservative treatment with teriparatide was better than alendronate at preventing the progressive vertebral collapse.     

Bone stock reconstruction for huge bone loss using allograft-bones,bone marrow,and teriparatide in an infected total knee arthroplasty

Bone stock reconstruction using allograft-bones, bone marrow (BM), and teriparatide (TPTD) is reported. Huge and extensive bone losses occurred in the medullary cavity of the femur and tibia of a 55-year-old female rheumatoid arthritis patient with severe osteoporosis after debridement of her infected total knee arthroplasty. Because of the risks of unstable prosthetic fixation and intra-operation fracture, we first reconstructed the bone stock. Chipped allograft bones mixed with BM were implanted in the bone defects, and TPTD was administrated for the osteoporosis therapy. Good bone formation was found by computed tomography after 4 months. Bone turnover markers and bone mineral density (BMD) were increased at 6 months. We confirmed good bone formation at the re-implantation surgery. The newly formed bone harvested during the re-implantation surgery showed active osteoblast-like lining cells. TPTD is known to enhance allograft bone union, mesenchymal stem cell differentiation into osteoblasts, and BMD. This tissue engineering-based technique might be improved by the various effects of TPTD. This method without any laboratory cell culture might be a good option for bone stock reconstruction surgery in ordinary hospitals.