Daily subcutaneous Teriparatide injection increased bone mineral density of newly formed bone after tibia distraction osteogenesis,a randomized study

Long bone defects are often treated by bone segment transport with the Ilizarov method requiring months spent with fixator mounted until bony consolidation of the newly formed bone. Shortening of consolidation would allow earlier fixator removal and earlier return to work. In pre-clinical studies parathyroid hormone, increased bone mineral density and mechanical properties of regenerate bone formed during distraction osteogenesis. Clinical studies showed that Teriparatide accelerated fracture healing in patients with osteoporotic fracture of the pelvis, hip, wrist and shoulder. We hypothesized that rhPTH(1-34) (Teriparatide) administered to patients who had undergone distraction osteogenesis, would increase mineralization of the regenerate formed during the consolidation phase.Sixteen patients with tibial defects after infection, underwent bone segment transport and at the time of docking the transport segment, were randomized to 8 weeks treatment with daily subcutaneous 0.20-μg Teriparatide injection followed by 8 weeks with no treatment, or to 8 weeks with no treatment followed by 8 weeks with daily subcutaneous 0.20 μg Teriparatide injection. Bone mineral density (BMD) of the regenerate was measured at the time of docking, 8 weeks after docking and 16 weeks after docking with DEXA. Functional evaluation was performed after one year. The design was a cross-over study.Overall BMD increased 0.14 g/cm² in 8 weeks without treatment and 0.33 g/cm² under Teriparatide treatment. After adjustment for a potential phase difference, 8 weeks of Teriparatide treatment led to an additional 0.19 g/cm² BMD increase (95%-CI:[0.11,0.28], p < 0.001). The ratio of the BMD increase between the two treatments was 0.33/0.14 = 2.43 (CI: [1.21,3.65]).Teriparatide treatment during the consolidation phase of distraction osteogenesis doubled the mineralization rate of the regenerate when compared to no treatment.     

The effect of monocyclic and bicyclic analogs of human parathyroid hormone (hPTH)-(1-31)NH2 on bone formation and mechanical strength in ovariectomized rats

The [Leu²⁷]cyclo(Glu²²-Lys²⁶)-hPTH-(1-31)NH₂ lactam is a stronger stimulator of adenylyl cyclase activity and a better stimulator of trabecular bone in the ovariectomized (OVX) rat model of osteopenia than hPTH-(1-31)NH₂. This enhanced activity is due in large part to the stabilization of the amphiphilic receptor-binding α-helix in the Ser¹⁷-Gln²⁹ region. The goal of the present study was to determine whether further cyclization could produce a more active hPTH analog. To this end, we compared the relative bioactivities of the bicyclic hPTH analog [Glu¹⁷,Leu²⁷]cyclo(Lys¹³-Glu¹⁷,Glu²²-Lys²⁶)-hPTH-(1-31)NH₂, made by replacing Ser¹⁷ with Glu¹⁷ and introducing a second lactam linkage between Lys¹³ and Glu¹⁷. The relative EC₅₀ for adenylyl cyclase stimulation by the bicyclic hPTH analog was similar to the EC₅₀ of the monocyclic [Leu²⁷]cyclo(Glu²²-Lys²⁶)-hPTH-(1-31)NH₂, but the bicyclic analog was still more active than hPTH-(1-31)NH₂. As expected from adenylyl cyclase stimulation being responsible for PTH’s anabolic action, the bicyclic hPTH analog [Glu¹⁷, Leu²⁷]cyclo(Lys¹³-Glu¹⁷, Glu²²-Lys²⁶)-hPTH-(1-31)NH₂ was able to increase femoral trabecular volume and thickness and mechanical strength in OVX rats, but it was no more effective than [Leu²⁷]cyclo(Glu²²-Lys²⁶)-hPTH-(1-31)NH₂ when injected once daily in a dose of 0.8 nmol/100 g body weight. Thus, further constraint of the conformation of hPTH-(1-31)NH₂ by introducing two lactam linkages between Lys¹³-Glu¹⁷ and Glu²²-Lys²⁶ did not raise the osteogenicity above that of the monocyclic analog.     

Effects of rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats

Objective

Distraction osteogenesis typically requires a long treatment period, which can lead to bone and soft-tissue infection and considerable patient discomfort. Use of a rapid distraction rate in craniofacial distraction osteogenesis to shorten the distraction period is possible owing to the unique characteristics of craniofacial bones, including an abundant blood supply and rapid bone healing compared with long bones. The effects of using a rapid distraction rate in the treatment of craniofacial deformities are currently unclear, however. The objective of this study was to investigate the effects of a rapid distraction rate on new bone formation during mandibular distraction osteogenesis in goats.

Methods

Sixteen goats were randomly divided into four groups consisting of four goats each. In Groups A, B, and C, the right mandible of each goat was distracted at a rate of 0.8 mm/d, 1.6 mm/d, and 2.0 mm/d, respectively; Group D was the control group and did not undergo distraction. Six weeks after the conclusion of distraction, bone densitometry and three-point bending testing were performed in all groups.

Results

The mean bone density value of goats in Group A was significantly higher than those of all the other groups (p < 0.05), and the mean bone density value of goats in Group C was significantly lower than those of all the other groups (p < 0.05). The mean curve slope, peak stress, bending modulus, and energy to failure values of Groups A, B, and C were all significantly lower than those of the control group (p < 0.05). As the distraction rate increased, the curve slope and peak stress values gradually declined (p < 0.05).

Conclusions

Use of a rapid distraction rate in mandibular distraction osteogenesis may have detrimental effects on the quality of new bone, despite the abundant blood supply of craniofacial bones.     

Application of distraction osteogenesis in managing bone cysts

Background

Despite the great amount of research concerning bone cysts, there is still no commonly accepted method of treatment. The aim of this study was to evaluate the effectiveness managing bone cyst with hybrid external fixator by distraction osteogenesis.

Materials and methods

Between 1982 and 2009, 25 patients with unicameral (20 patients) and aneurismal (five patients) bone cysts were treated using this method. Eighteen patients had a history of pathological fracture at the same location. Cysts were located in the humerus, femur, tibia, and radius. Median follow-up was 48 (range 31–91) months. Results were evaluated on plain radiographs according to the classification system of Capanna et al. Functional assessment was done using the modified system recommended by Enneking et al.

Results

In our study group of 25 bone cysts, 15 were classified as completely healed and nine as healed with residual radiolucency. Recurrence was observed in one patient. Absence of response to treatment was not observed. All patients had excellent functional outcomes, except one with recurrence who was rated poor.

Conclusions

As bone cysts are found in long bones in 90–95 % of patients, and taking into account our achieved positive results in almost all patients, we recommend this method of distraction osteogenesis as a treatment option. It is an effective, economical method of treatment, which eliminates deformity and restores bone length, especially in patients with pathologic fractures.     

Rapid new bone tissue remodeling during distraction osteogenesis is associated with apoptosis.

During the process of distraction osteogenesis new bone forms and undergoes rapid remodeling. Apoptosis may be one of the regulatory mechanisms governing the removal of the redundant callus during distraction osteogenesis. A rabbit tibial lengthening model was used and lengthened at 0.7 mm/day for 3 weeks. The regenerating tissues from the distraction gap were examined for apoptotic changes by transmission electron microscopy (TEM) and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. Osteoclastic bone resorption activities were demonstrated by tartrate resistant acid phosphatase (TRAP) staining. The apoptotic cells were mainly present in the transitional regions between the fibrous tissue and the new bone in the mineralization front, and close to or on the new bone surfaces near the center of the regenerate. The TUNEL labeling was greatly reduced in the mature bone near the osteotomied bone ends. TEM examination confirmed the presence of cells with apoptotic changes at various regions of the regenerate. TRAP staining revealed that osteoclastic bone resorption activities in the regenerate were in a similar pattern of distribution to those of the TUNEL labeling. The localization of apoptotic cells at the different regions of the regenerate, accompanied by the osteoclast activities, suggest that apoptosis is closely related to bone formation and remodeling during distraction osteogenesis.     

Comparison of the effects of a potent synthetic analog of bovine parathyroid hormone with native bPTH-(1-84) and synthetic bPTH-(1-34) on bone resorption and collagen synthesis

Summary An analog of bovine PTH [nle-8, nle-18, tyr-34 bPTH-(1-34) amide, (PTH-Ana)] which is a potent stimulator of renal adenylate cyclase has been compared with the native hormone bPTH-(1-84) and the biologically active amino terminal portion, bPTH-(1-34), for its effects on bone resorption and bone collagen synthesis in organ culture. All three compounds stimulated the release of previously incorporated⁴⁵Ca from cultured fetal rat long bone shafts with similar dose-response curves at 10⁻⁹ to 3 × 10⁻⁸ M. All three compounds inhibited bone collagen synthesis as measured by incorporation of proline into collagenase digestible protein, whereas incorporation into noncollagen protein was not inhibited. The effects were dose related and decreases in percent collagen synthesis were significant at 10⁻⁹ M. Thus PTH-Ana appears to have the same effects on bone resorption and collagen synthesis as bPTH-(1-84) and (1-34) and is likely to be a valid probe for investigating PTH receptors in bone as well as in kidney.     

Combined effects of recombinant human BMP-2 and Nell-1 on bone regeneration in rapid distraction osteogenesis of rabbit tibia

Distraction osteogenesis (DO) has been accepted as an effective technique for bone lengthening. However, the long treatment period and possible fibrous union or nonunion hampers its further clinical application. Bone regeneration in DO involves multiple stages of repair and coordinated action of multiple cell types. Consequently, it may be possible to enhance bone regeneration through treatment strategies that target more than one repair process or cell types. The goal of this study was to determine the combined effects of recombinant human bone morephogenetic protein 2 (rhBMP-2) and NEL-like molecule-1 (NELL-1) on bone formation in DO. Unilateral tibiae in 48 rabbits were lengthened for 7 days at a rate of 2 mm/day after 3-day lag. At the end of distraction, the animals were randomly divided into four groups (n = 12) and received phosphate-buffered saline, 50 μg rhNell-1 or 50 μg rhBMP-2, or both 25 μg rhBMP-2 and 25 μg rhNell-1 at the lengthened segment, respectively. After 4-week consolidation bony healing was assessed using histology, radiography, dual energy X-ray absorptiometry, micro-CT, and three-point bend testing. Treatment with rhNell-1 and/or rhBMP-2 resulted in better bone formation and higher BMD and BMC than the saline group, whilst excellent bone formation and the highest BMD and BMC was observed in the combined treatment group. Both rhNell-1 and rhBMP-2 groups presented more mature characteristics in the micro-architecture than the saline group, whereas the combined treatment group presented the highest BV/TV, Tb.Th and Tb.N as well as the lowest Tb.Sp. The peak load of the lengthened tibia increased by 71% in the combined treatment group, 54% in the rhBMP-2 group, and 25% in the rhNell-1 group compared to the control group, respectively. This work suggests that BMP-2 and Nell-1 enhance each other's ability and dual delivery of two agents can significantly improve bony healing in tibial DO.     

Mechanical loading enhances the anabolic effects of intermittent parathyroid hormone (1-34) on trabecular and cortical bone in mice

The separate and combined effects of intermittent parathyroid hormone (iPTH) (1-34) and mechanical loading were assessed at trabecular and cortical sites of mouse long bones. Female C57BL/6 mice from 13 to 19 weeks of age were given daily injections of vehicle or PTH (1-34) at low (20 microg/kg/day), medium (40 microg/kg/day) or high (80 microg/kg/day) dose. For three alternate days per week during the last two weeks of this treatment, the tibiae and ulnae on one side were subjected to a single period of non-invasive, dynamic axial loading (40 cycles at 10 Hz with 10-second intervals between each cycle). Two levels of peak load were used; one sufficient to engender an osteogenic response, and the other insufficient to do so. The whole tibiae and ulnae were analyzed post-mortem by micro-computed tomography with a resolution of 5 microm. Treatment with iPTH (1-34) modified bone structure in a dose- and time-dependent manner, which was particularly evident in the trabecular region of the proximal tibia. In the tibia, loading at a level sufficient by itself to stimulate osteogenesis produced an osteogenic response in the low-dose iPTH (1-34)-treated trabecular bone and in the proximal and middle cortical bone treated with all doses of iPTH (1-34). In the ulna, loading at a level that did not by itself stimulate osteogenesis was osteogenic at the distal site when combined with high-dose iPTH (1-34). At both levels of loading, there were synergistic effects in cortical bone volume of the proximal tibia and distal ulna between loading and high-dose iPTH (1-34). Images of fluorescently labelled bones confirmed that such synergism resulted from increases in both endosteal and periosteal bone formation. No woven bone was induced by iPTH (1-34) or either level of loading alone, whereas the combination of iPTH (1-34) and the "sufficient" level of loading stimulated woven bone formation on endosteal and periosteal surfaces of the proximal cortex in the tibiae. Together, these data suggest that in female C57BL/6 mice, under some but not all circumstances, mechanical loading exerts an osteogenic response with iPTH (1-34) in trabecular and cortical bone.     

Parathyroid hormone (1–34) increases vertebral bone mass, compressive strength, and quality in old rats

Human parathyroid hormone 1–34 (PITH) exerts an anabolic effect on bone in younger rats. The aim of the present study was to examine the effect of PTH on vertebral bone in 2-year-old male rats. The rats were treated with daily injections of 15 nmol/kg PTH or vehicle (V) for 56 days. Tetracycline and calcein were injected on day 15 and day 40 of the treatment period, respectively. The PTH treatment did not influence the body weights of the rats, the volumes of whole vertebra, or the vertebral body heights. However, the PTH treatment induced profound changes in the bone structure. Histomorphometric analyses of the vertebral bodies (L-6) revealed an approximate doubling of the cancellous bone volume after PTH treatment from 24.6 ± 1.3% to 54.9 ± 2.0% (p < 0.001) as well as a doubling of the trabecular thickness while the bone surface/bone volume decreased by 60%. PTH treatment also increased bone formation as indicated by an increase in mineral apposition rate (from 0.42 ± 0.01 to 0.89 ± 0.01 μm/day, p < 0.01), increased mineralizing surface (from 7.8 ± 1.4 to 43.8 ± 1.9%, p < 0.01) and an increase in both volume-related and surface-related bone formation rates (5 and 11 times, respectively). The biomechanical properties were analyzed using standardized bone specimens from the vertebral bodies of L-4 by applying cranial-caudal compression in a materials testing machine. The PTH treatment induced a substantial increase in the strength of the vertebral body: ultimate load increased by 66%, ultimate stiffness by 47%, and energy absorption by 98%. The increase in vertebral body strength was also evident after normalizing the parameters to the cross sectional area and the ash content of the vertebral body specimens. PTH treatment increased ultimate stress from 26 ± 3 to 44 ± 3 N per mm² (p < 0.01) and increased ultimate load normalized to ash content per mm specimen height from 59 ± 4 to 72 ± 4 N (mm/mg) (p < 0.05). The PTH treatment induced an increase in dry defatted bone density and ash density of both the vertebral body specimen (L-4) and the whole vertebra (L-5). In conclusion, PTH showed a remarkable ability to stimulate bone formation in the vertebral body of old rats. Furthermore, the biomechanical analysis revealed an enhanced compressive bone strength, even after correction for the increased bone mass, indicating an improved bone quality after the PTH treatment.     

老年男性甲状旁腺激素与骨密度的关系

本文的目的在于探讨在健康老年人中，甲状旁腺素（ＰＴＨ），钙（Ｃａ）、磷（Ｐ）、镁（Ｍｇ）、碱性磷酸酶（ＡＫＰ）、肌酐（Ｃｒ）与骨密度（ＢＭＤ）之间的关系。选择７０名健康老人，抽血查Ｃ－ＰＴＨ、Ｃａ、Ｐ、Ｍｇ、ＡＫＰ和Ｃｒ的水平。并在左侧桡骨远端１／３处，用单能光子骨密度测定仪测定ＢＭＤ。以正常参考值为标准（０．６２９７～０．７６９５ｇ／ｃｍ２），将对象分为ＢＭＤ降低组和ＢＭＤ正常组。结果显示：（１）在ＢＭＤ正常组（ＢＭＤ值为０．７３±０．０７ｇ／ｃｍ２）中，ＰＴＨ的水平为１５５．３６±９３．４５（ｎｇ／Ｌ），在ＢＭＤ降低组（ＢＭＤ值为０．５７±０．０４ｇ／ｃｍ２）中，ＰＴＨ的水平为２１４．１１±９１．９３（ｎｇ／Ｌ）。二组间差异有统计学意义。（２）在ＢＭＤ正常组中，血清钙的水平为２．１２±０．２２（ｍｍｏｌ／Ｌ），在ＢＭＤ降低组中，血清钙的水平为２．２３±０．１９（ｍｍｏｌ／Ｌ）。两组相比，差别有统计学意义（Ｐ＜０．０５）。实验结果提示：在老年男性与年龄有关的骨密度降低中，ＰＴＨ的分泌起到重要作用。     

Experimental determination of “the law of bone remodeling” and effect of rat parathyroid hormone (1–34) infusion on derived parameters

Summary The dependence of bone remodeling probability on bone age was investigated by fitting a previously described mathematical model [1] to data describing the decline of radioactivity in the femurs of growing rats prelabeled with [³H]tetracycline. The remodeling probability declined with increasing bone age, but because the data were obtained at the whole bone level, several explanations for this finding are possible, and the results cannot be extrapolated beyond the duration of the experiment. A simpler exponential model that assumes remodeling probability is constant can be used to calculate bone resorption rate within a limited time period. A significantly increased bone resorption rate in PTH-infused rats could readily be demonstrated using the exponential model. A more sophisticated statistical analysis was required to discriminate between control and PTH-infused rats using the more complex model in which resorption rate was not constant.     

Effect of chemotherapeutic agents on distraction osteogenesis. An experimental investigation in rabbits

Limb-salvage operations such as vascularised or non-vascularised osseous grafts and allograft and callus distraction methods have replaced amputations because of the increase in the life expectancy of patients with malignant tumours. In this study we aimed to evaluate the effects of chemotherapeutic agents on distraction osteogenesis. For this purpose, 23 rabbits randomly divided into two groups were included in the study. The experimental group and the control group consisted of 12 rabbits and 11 rabbits, respectively. The experimental group were administered chemotherapeutic agents with the protocol identified in the osteogenic sarcoma regimen. All the subjects were corticotomised in the metaphyseal-diaphyseal region, and both groups underwent distraction with a circular ring fixator. X-ray films, bone scintigraphy and histopathological examination were performed three times during the study. No difference between the two groups was observed in radiological, scintigraphical and histopathological studies carried out before the distraction period and following the end of the distraction period. In this study, it was shown that the use of antineoplastic drugs has no significant negative effect on distraction osteogenesis applied for reconstruction in rabbits. We think that it can be an alternative treatment method in humans as well. Received: 20 February 2000     

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。     

Temporal and spatial expression of bone morphogenetic protein-2, -4, and -7 during distraction osteogenesis in rabbits

The Ilizarov method of limb lengthening makes use of the fact that osteogenesis is induced at an osteotomy site when distraction is applied. It is unknown at present how the mechanical forces created by distraction are translated into biological signals. Because bone morphogenetic proteins (BMPs) are potent inducers of osteogenesis in many experimental systems, they are obvious candidates for playing a role in this process. In this study, we investigated the temporal and spatial expression of BMP-2, -4, and -7 proteins during distraction osteogenesis using immunohistochemistry. An osteotomy was performed on the right tibiae of white New Zealand rabbits. After a delay of 7 days, distraction was started at a rate of 0.25 mm/12 h for 3 weeks, followed by a 3 week consolidation phase. Each week after osteotomy one rabbit was killed for immunohistochemical studies. Staining for BMP-2, -4, and -7 was evident before distraction was applied and was mainly localized to mesenchymal cells and osteoblastic cells in the periosteal region. After distraction was started, the typical fibrous interzone developed between the osteotomy fragments, where both intramembranous and endochondral ossification were noted. In this area, cells resembling fibroblasts and chondrocytes, but not mature osteoblasts, showed intense staining for all three BMPs. This high level of expression was maintained during the entire distraction phase and then gradually disappeared during the consolidation phase. These results are compatible with the hypothesis that BMPs play an important role in the signaling pathways that link the mechanical forces created by distraction to biological responses.     

Changes in blood perfusion and bone healing induced by nicotine during distraction osteogenesis

Nicotine is the main chemical in cigarettes responsible for the tobacco's pathological effects. The influence of nicotine on bone healing remains controversial. Distraction osteogenesis provides an ideal model to study bone healing and regeneration. The present study aims to evaluate the effects of nicotine on blood perfusion, angiogenesis and bone formation using a rabbit model of mandibular lengthening. Twenty adult New Zealand white rabbits were randomly assigned to the control group and nicotine group. The total nicotine or placebo exposure time for all animals was 7 weeks. After 2- or 4-week of consolidation following osteotomy, 3-day of latency and 11-day of active distraction, the animals were sacrificed and the mandibles were harvested. Blood perfusion and vascularization were evaluated by Laser Doppler monitoring and Collagen IV immunohistochemistry staining respectively. Bone formation was assessed by radiological, histological and immunohistochemical examination. Results showed that nicotine exposure increased microvessel density, whereas inhibited blood flow and bone formation. The expression of bone morphogenetic protein (BMP)-2 in osteoblasts was also decreased. Frequent appearance of cartilage islands suggested ischemia and low oxygen tension in the distraction regenerate. We concluded that nicotine compromises bone regeneration possibly by causing ischemia and directly inhibitory effect on osteoblastic cells. Nicotine exposure enhances angiogenesis but cannot compensate for the adverse effect of vasoconstriction.     

Comparative effects of intermittent administration of human parathyroid hormone (1-34) on cancellous and cortical bone loss in tail-suspended and sciatic neurectomized young rats

 We compared the effects of intermittent administration of human parathyroid hormone (PTH) (1-34) on tibial cancellous and cortical bone loss in tail-suspended and sciatic neurectomized young rats. Forty-eight 6-week-old male Wistar rats were randomly divided into six groups with eight animals each: age-matched controls (AMC), tail suspension (TS), sciatic neurectomy (NX), AMC + PTH, TS + PTH, and NX + PTH. Fifteen days after the start of the experiment, the proximal tibia and tibial shaft were processed for cancellous and cortical bone histomorphometric analyses, respectively. The reduction of cancellous bone volume (BV/TV) was significantly greater in the TS group than in the NX group, whereas the reduction of percent cortical area (Ct Ar) did not differ significantly between the TS and NX groups. Administration of human PTH to rats in the TS and NX groups increased BV/TV to a level significantly higher than that of the AMC group. Administration of human PTH to rats in the NX group significantly increased percent Ct Ar, but percent Ct Ar of the NX group was still significantly lower than that of the AMC group. Administration of human PTH to rats in the TS group did not significantly affect percent Ct Ar. These findings suggest that intermittent administration of human PTH (1-34) at the dose we used may completely prevent cancellous bone loss both in TS and NX young rats, and that it may not affect cortical bone loss in TS young rats but only attenuate it in NX young rats. Received: October 3, 2001 / Accepted: December 20, 2001     

间歇皮下注射人甲状旁腺激素不同片段(hFTH1-34及 hFTH1-84)对去卵巢大鼠股骨及腰椎骨量的影响

目的 比较间歇皮下注射人甲状旁腺激素不同片段（hPTH1-34)及（hPTH1-84)对完整雌性（Non-OVX)大鼠和去卵巢（OVX）大鼠股骨及腰椎1－4骨矿物含量（BMC）和骨密度（BMD）的影响。方法 Wistar雌性大鼠176只，分为hPTH1-34和hPTH1-84两大组（各80只及96只），每大组及各自分4组（每组各20只或24只），分别为：两组安慰剂组（未切卵巢及切卵巢）用安慰剂（PBS）进行皮下注射，每周3次，共2周；两组治疗组（未切卵巢及切卵巢）用hPTH1-34或hPTH1-84，皮下注射，每周3次，共2周。结果 1．卵巢切除术后3个月大鼠股骨及腰椎1－4BMC和BMD明显下降；2．两种片段的甲状旁腺激素（hPTH1-34及pPTH1-84)间歇注射均能使Non-OVX大鼠和OVX大鼠股骨及腰椎1－4BMC和BMD较相应对照组明显升高；且腰椎1－4较股骨的BMC和BMD升高更明显；3．OVX大鼠治疗后股骨与腰椎1－4BMC和BMD的升高率较Non-OVX大鼠更明显；OVX大鼠在治疗后股骨及腰椎骨量能恢复到去卵巢前水平；4．hPTH1-34较hPTH1-84更明显的使完整大鼠和OVX大鼠股骨BMC和BMD升高。结论 间歇皮下注射人甲状旁腺激素对大鼠股骨及腰椎骨量均有增高作用，尤其对腰椎的骨量以及对去卵巢大鼠骨量升高作用更明显；hPTH1-34片段对大鼠股骨骨量的增高作用强于hPTH1-84片段。     

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。     

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。