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A biomimetic and bioactive scaffold with intelligently pulsatile teriparatide delivery for local and systemic osteoporosis regeneration

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Bioactive Materials 2023年第1期19卷 75-87页

作者： Lingbin Che Ying Wang Dongyong Sha Guangyi Li Ziheng Wei Changsheng Liu Yuan Yuan Dianwen Song Department of Orthopedics Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200080PR China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry and School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237PR China Shanghai Advanced Research Institute Chinese Academy of SciencesShanghai201210PR China

Osteoporosis is one of the most disabling consequences of aging,osteoporotic fractures and higher risk of the subsequent fractures leading to substantial disability and deaths,indicating both local fractures healing and the early anti-osteoporosis therapy are of great *** is strong bone formation promoter effective in treating osteoporosis,while side effects limit clinical *** drug delivery is lack of sensitive and short-term release,finding a new non-invasive and easily controllable drug delivery to not only repair the local fractures but also improve total bone mass has remained a great ***,bioinspired by the natural bone components,we develop appropriate interactions between inorganic biological scaffolds and organic drug molecules,achieving both loaded with the teriparatide in the scaffold and capable of releasing on ***,biomimetic bone microstructure of mesoporous bioglass,a near-infrared ray triggered switch,thermosensitive liposomes based on a valve,and polydopamine coated as a heater is developed rationally for osteoporotic bone *** is pulsatile released from intelligent delivery,not only rejuvenating osteoporotic bone defect,but also presenting strong systemic anti-osteoporosis *** biomimetic bone carrying novel drug delivery platform is well worth expecting to be a new promising strategy and clinically commercialized to help patients survive from the osteoporotic fracture.

关键词： Precise pulsatile release teriparatide Smart delivery Osteoporotic bone regeneration

Two-year clinical outcome of denosumab treatment alone and in combination with teriparatide in Japanese treatment-naive postmenopausal osteoporotic women

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Bone Research 2017年第2期5卷 152-158页

作者： Yukio Nakamura Takako Suzuki Mikio Kamimura Shota Ikegami Kohei Murakami Shigeharu Uchiyama Akira Taguchi Hiroyuki Kato Department of Orthopedic Surgery Shinshu University School of Medicine Matsumoto Japan Department of Orthopedic Surgery Showa-Inan General Hospital Komagane Japan Center of Osteoporosis and Spinal Disorders Kamimura Orthopaedic Clinic Matsumoto Japan and Department of Oral and Maxillofacial Radiology Matsumoto Dental University Shiojiri Japan

This randomized prospective study aimed to evaluate the clinical outcome of denosumab treatment alone and in combination with teriparatide in treatment-naive postmenopausal Japanese female patients with osteoporosis. Thirty patients were randomly assigned to two groups:(1) denosumab group(denosumab alone, n=13); and(2) combination group(denosumab+teriparatide, n=17). Serum bone-specific alkaline phosphatase(BAP), serum tartrate-resistant acid phosphatase(TRACP)-5b, urinary cross-linked N-terminal telopeptides of type I collagen(NTX), and bone mineral density(BMD) of L1–4 lumbar vertebrae(L-BMD)and bilateral total hips(H-BMD) were determined at the first visit and at various time points up to 24 months post-treatment to determine percentage changes. Serum TRACP-5b and urinary NTX were equally suppressed in both groups and maintained at low levels, with slight increases at 12, 18 and 24 months. BAP was significantly decreased in both groups from 4 to 24 months, with significant differences between the groups at 4, 8 and 15 months(Pteriparatide combination therapy may represent an important treatment for primary osteoporotic patients at high risk of vertebral fracture.

关键词： teriparatide denosumab treatment

teriparatide anabolic therapy as potential treatment of type Ⅱ dens non-union fractures

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World Journal of Orthopedics 2017年第1期8卷 82-86页

作者： Enrico Pola Virginia Pambianco Debora Colangelo Virginia M Formica Giovanni Autore Luigi A Nasto Spinal Unit Department of Orthopaedics and Traumatology"A.Gemelli" University HospitalCatholic University of Rome Centre for Spine Studies and Surgery Queen’sMedical CentreNottingham University Hospitals NHS Trust

Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type Ⅱ fractures are the most common fracture pattern in elderly patients. Treatment(rigid and non-rigid immobilization, anterior screw fixation of the odontoid and posterior C1-C2 fusion) remains controversial and represents a unique challenge for the treating surgeon. The aims of treatment in the elderly is to quickly restore pre-injury function while decreasing morbidity and mortality associated with inactivity, immobilization with rigid collar and prolonged hospitalization. Conservative treatment of type Ⅱ odontoid fractures is associated with relatively high rates of non-union and in a few cases delayed instability. Options for treatment of symptomatic non-unions include surgical fixation or prolonged rigid immobilization. In this report we present the case of a 73-year-old woman with post-traumatic odontoid nonunion successfully treated with teriparatide systemic anabolic therapy. Complete fusion and resolution of the symptoms was achieved 12 wk after the onset of the treatment. Several animal and clinical studies have confirmed the potential role of teriparatide in enhancing fracture healing. Our case suggests that teriparatide may have a role in improving fusion rates of C2 fractures in elderly patients.

关键词： Type Ⅱ odontoid fractures Non-union Anabolic therapy teriparatide Fracture healing

Use of teriparatide to improve fracture healing: What is the evidence?

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World Journal of Orthopedics 2015年第6期6卷 457-461页

作者： Satish Babu Nemandra A Sandiford Mark Vrahas Core Surgical Trainee St. George’s Hospital Lower Limb and Tumor Reconstruction Fellow University of British Columbia Orthopaedic Trauma Service Massachusetts General Hospital

teriparatide is a recombinant form of the biologicallyactive component of Parathyroid hormone. It has been shown to increase bone mass and prevent fractures in osteoporotic bone. It is licensed by the Food and Drug Administration for the treatment of Osteoporosis. Over the last decade, a growing body of evidence has accumulated suggesting a role for teriparatide in the management of fractures. Studies in both normal and delayed healing models have shown improvement in callus volume and mineralisation, bone mineral content, rate of successful union and strength at fracture sites. However most of these results have been derived from animal studies. The majority of this research on humans has comprised low level evidence, with few randomised controlled trials, many case reports and case series. Nevertheless, the results from these studies seem to support research from animal models. This has led to a growing number of clinicians using teriparatide "off license" to treat fractures and non-unions in their patients. This review presents a critical appraisal of the current evidence supporting the use of teriparatide for fracture healing, delayed unions and non unions and in the setting of osteoporotic fractures, the studies producing this evidence and their transferability to human beings.

关键词： teriparatide Fractures Healing Bone Osteoporosis

Successful Treatment with a Weekly Injection of teriparatide for the Nonunion of a Distal Humerus Fracture

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Open Journal of Orthopedics 2017年第7期7卷 173-179页

作者： Hiroshi Yonezu Hiroshi Mikami Koichi Oba Katsutoshi Miyatake Michihiro Takai Akihiro Nitta Department of Orthopedics Yoshinogawa Medical Center Yoshinogawa Tokushima Japan

A distal humerus fracture nonunion is one of the complications with which we should be vigilant. It requires an open reduction and rigid internal fixation. However, treatment with an operative procedure is difficult because the small bones involved in distal humerus fracture nonunion or if osteoporosis is present. And an improvement in the function of the elbow joint is not satisfied because of a postoperative elbow joint contracture. Furthermore, the risk of anesthesia to elderly patients restricts the use of an operation for treatment. A weekly injection of teriparatide has the ability to stimulate bone formation. We present a case of an 87-year-old woman treated with a weekly injection of teriparatide for the nonunion of a distal humerus fracture.

关键词： Distal Humerus Fracture Nonunion teriparatide

The Clinical Effect of Zoledronic Acid Combined with teriparatide in Perverting Recurrent Fracture of Osteoporotic Vertebral Compressive Fractures in the Elderly after Percutaneous Kyphoplasty

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Surgical Science 2021年第6期12卷 161-173页

作者： Le Zhao Xinming Yang Ying Zhang Department of Surgery Graduate School of Hebei North University Zhangjiakou China Department of Orthopaedics The First Affiliated Hospital of Hebei North University Zhangjiakou China

Background: Zoledronic acid and teriparatide have been proved to be effective in improving bone metabolism and preventing fractures, but there is no clear clinical report on the efficacy of their combined application. Purpose: To discuss the clinical effect of zoledronic acid combined with teriparatide in perverting recurrent fracture of osteoporotic vertebral compressive fractures (OVCF) in the elderly after percutaneous kyphoplasty (PKP). Method: A randomized clinical trial was conducted at the First Affiliated Hospital of Hebei North University in China from September 2018 and September 2019. A total of 60 patients with OVCF were enrolled in the study (zoledronic acid: 20 cases;teriparatide: 20 cases;zoledronic acid + teriparatide: 20 cases). Observe and compare the changes of bone mineral density (BMD), pro-collagen type I N-terminal propeptide (PINP) and cross-linked C-terminal telopeptide of type I collagen (β-CTX) before surgery, 6 months and 1 year after surgery. At the same time, secondary fracture events and adverse reaction events were recorded during the follow-up period. Results: After normalized treatment, the bone metabolism indexes of PINP and β-CTX were improved and BMD was increased in three groups. Adverse Reactions: There was no statistical significance in the incidence of fever, gastrointestinal reactions and myalgia among the three groups (P > 0.05). The incidence of recurrent fractures in group A was higher than that in group C (P 0.05). Conclusion: Zoledronic acid combined with teriparatide is superior to Zoledronic acid in preventing the risk of recurrent fracture after PKP for old patients with OVCF, but it has no significant advantage over teriparatide.

关键词： Zoledronic Acid teriparatide Percutaneous Kyphoplasty (PKP) Osteoporotic Vertebral Compressive Fractures (OVCF)

Effects of teriparatide and Aerobic Exercise on Lumbar Spine Microstructure in Ovariectomized and Tail-Suspended Rats

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Open Journal of Orthopedics 2021年第1期11卷 1-11页

作者： Chiaki Sato Naohisa Miyakoshi Yuji Kasukawa Koji Nozaka Hiroyuki Tsuchie Itsuki Nagahata Yusuke Yuasa Kazunobu Abe Hikaru Saito Ryo Shoji Yoichi Shimada Department of Orthopedic Surgery Akita University Graduate School of Medicine Akita Japan

Osteoporosis is an increasingly prevalent malady of the elderly that is associated with bone fragility and increased risk of fractures. Osteoporosis treatments focus on restoring bone strength and quality. Teriparatide (TPTD) is a therapeutic agent that has been shown to increase bone strength by improving the volume and connectivity of trabecular bone. Exercise is also known to have pro-osteogenic effects. Here we used a rat model of severe osteoporosis (ovariectomized and tail-suspension) to evaluate the effects of TPTD, exercise and a combination of TPTD and exercise on the microstructure of trabecular bone. TPTD mono-therapy and TPTD combined with exercise treatment significantly increased bone mineral density (BMD) in the whole body. Micro-computed tomography analysis revealed that a combination of exercise and TPTD treatment significantly decreased bone surface to volume and trabecular separation compared with those of the control and exercise groups. Node-strut analysis indicated that exercise or TPTD alone did not affect trabecular bone connectivity. However, the combination of exercise and TPTD treatment significantly decreased measures of trabecular bone connectivity (node number) that are consistent with a transition from rod-like to plate-like of trabecular bone microstructures. The combination treatment with exercise and TPTD improved microstructure of trabecular bone in the OVX and tail-suspended rats. These results indicate that combining exercise with TPTD represents a viable means to improve cancellous bone strength in osteoporosis populations.

关键词： teriparatide Aerobic Exercise Micro Structure Cancellous Bone

Successful Treatment of Spine Fracture for Diffuse Idiopathic Skeletal Hyperostosis with teriparatide—A Report of Two Cases

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Open Journal of Orthopedics 2013年第6期3卷 278-282页

作者： Yasuaki Iida Hiroshi Takahashi Yuichiro Yokoyama Yasuhiro Inoue Daisuke Suzuki Keiji Hasegawa Shintaro Tsuge Wataru Shishikura Katsunori Fukutake Ryo Takamatsu Kazumasa Nakamura Masayuki Sekiguchi Akihito Wada Department of Orthopaedic Surgery Toho University School of Medicine Tokyo Japan Department of Orthopaedic Surgery Toho University School of Medicine Tokyo Japan.

We experienced 2 cases of spinal fracture in patients aged 80 years or older with diffuse idiopathic skeletal hyperostosis (DISH). Since they decided not to undergo surgical treatment, we provided conservative treatment with teriparatide. There has been no previous study on teriparatide for spine fracture in DISH. This is the first report of the successful use of teriparatide to treat spine fracture in DISH without surgical intervention. Our patients were treated with teriparatide for 8-9 months after diagnosis of the fracture. Union was obtained in two cases and no adverse events were observed during treatment. Our report showed that teriparatide could be an alternative to conventional intervention in spinal fracture of DISH.

关键词： Diffuse Idiopathic Skeletal Hyperostosis teriparatide Spine Fracture

Nonunion of the humeral shaft successfully treated with teriparatide [rh (1-34) PTH]

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Case Reports in Clinical Medicine 2013年第1期2卷 11-15页

作者： ángel Oteo-álvaro María T. Marín Fragility Fracture Treatment Unit Hospital Universitario de Madrid Madrid Spain Primary Care C. S. General Ricardos Madrid Spain

We reported a case of atrophic nonunion after humeral shaft fracture in a patient with severe psychiatric disorders that advised against hospital admission and surgery. He was treated with teriparatide (recombinant human 1-34 parathyroid hormon) [rh (1-34) PTH] in daily subcutaneous injections. After 4 months of treatment, healing of nonunion, associated to clinical improvement and functional recovery of the patient, was observed. No other intervention was required, and no side effects attributable to the drug occurred.

关键词： Atrophic Nonunion Delayed Healing Humeral Shaft Nonunions Nonunion teriparatide