Three-Times-Weekly Administration of Teriparatide Improves Vertebral and Peripheral Bone Density, Microarchitecture, and Mechanical Properties Without Accelerating Bone Resorption in Ovariectomized Rats

Takao-Kawabata, Ryoko; Isogai, Yukihiro; Takakura, Aya; Shimazu, Yukari; Sugimoto, Emika; Nakazono, Osamu; Ikegaki, Ichiro; Kuriyama, Hiroshi; Tanaka, Shinya; Oda, Hiromi; Ishizuya, Toshinori

doi:10.1007/s00223-015-9998-0

Cited by 27 publications

(28 citation statements)

References 33 publications

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“…23–25 In this model, a significant reduction in the BMD in the OVX group compared with that in the sham group is observed starting from 3 months after the surgery. 23,36–39 This study monitored blood and urine samples until 7 weeks after surgery (4 weeks after the initial TPTD treatment), and dissected specimens at 7 weeks after the surgery for morphological evaluations to observe the early pharmacological actions of TPTD, especially on changes in the microarchitecture. In fact, we did not observe significant differences in the BMD, mechanical properties, average serum OC, or average cortical porosity between the sham group and OVX vehicle group, which is consistent with our previous report.…”

Section: Discussionmentioning

confidence: 99%

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Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariectomized rats

et al. 2017

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To investigate whether the administration frequency of parathyroid hormone (PTH) is associated with the development of cortical porosity, this study established 15 dosage regimens of teriparatide [human PTH(1–34), TPTD] with four distinct concentrations and four distinct administration frequencies of TPTD to 16-week-old ovariectomized rats. Our analyses demonstrated that the bone mineral density, mechanical properties, and bone turnover were associated with the total amount of TPTD administered. Our observations further revealed that the cortical porosity was markedly developed as a result of an increased administration frequency with a lower concentration of total TPTD administration in our setting, although the highest concentration also induced cortical porosity. Deconvolution fluorescence tiling imaging on calcein-labeled undecalcified bone sections also demonstrated the development of cortical porosity to be closely associated with the bone site where periosteal bone formation took place. This site-specific cortical porosity involved intracortical bone resorption and an increased number and proximity of osteocytic lacunae, occasionally causing fused lacunae. Taken together, these findings suggested the involvement of local distinctions in the rate of bone growth that may be related to the site-specific mechanical properties in the development of cortical porosity induced by frequent and/or high doses of TPTD.

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Section: Discussionmentioning

confidence: 99%

“…23,26 For the sham surgery, ~10-mm-long incisions were made on the back of each rat, as in the ovariectomy, and the ovaries were exposed and then replaced.…”

Section: Methodsmentioning

confidence: 99%

Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariectomized rats

et al. 2017

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“…; Takao‐Kawabata et al. ). Under some conditions, PTH(1‐34) can be used to improve fracture healing (Chiang et al.…”

Section: Introductionmentioning

confidence: 99%

“…PTH(1-34), also known as Teriparatide, is an FDA-approved anabolic drug for osteoporosis, increasing bone deposition. It has also been demonstrated that, although PTH(1-34) can also stimulate bone resorption, the net effect of intermittent daily administration is the increase in bone mass (Hock & Gera, 1992;Burr et al 2001;Oswald et al 2014;Saidak et al 2014;Takao-Kawabata et al 2015). Under some conditions, PTH(1-34) can be used to improve fracture healing (Chiang et al 2013), although this may be dependent on the severity and location of bone injury as well as on an individual's overall bone health.…”

Section: Introductionmentioning

confidence: 99%

PTH(1‐34) effects on repairing experimentally drilled holes in rat femur: novel aspects – qualitative vs. quantitative improvement of osteogenesis

et al. 2016

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The timetable of effects on bone repair of the active fraction-parathyroid hormone, PTH(1-34), was analytically investigated from the morphometric viewpoint in 3-month-old male Sprague-Dawley rats, whose femurs were drilled at mid-diaphyseal level (transcortical holes). The animals were divided into groups with/without PTH(1-34) administration, and sacrificed at different times (10, 28, 45 days after surgery). The observations reported here need to be framed in the context of our previous investigations regarding bone histogenesis (Ferretti et al. Anat Embryol. 2002; 206: 21-29) in which we demonstrated the occurrence of two successive bone-forming processes during both skeletal organogenesis and bone repair, i.e. static and dynamic osteogenesis: the former (due to stationary osteoblasts, haphazardly grouped in cords) producing preliminary bad quality trabecular bone, the latter (due to typical polarized osteoblasts organized in ordered movable laminae) producing mechanically valid bone tissue. The primary function of static osteogenesis is to provide a rigid scaffold containing osteocytes (i.e. mechano-sensors) for osteoblast laminae acting in dynamic osteogenesis. In the present work, histomorphometric analysis revealed that, already 10 days after drilling, despite the holes being temporarily filled by the same amount of newly formed trabecular bone by static osteogenesis independently of the treatment, the extent of the surface of movable osteoblast-laminae (covering the trabecular surface) was statistically higher in animals submitted to PTH(1-34) administration than in control ones; this datum strongly suggests the effect of PTH(1-34) alone in anticipating the occurrence of dynamic osteogenesis involved in the production of good quality bone (with more ordered collagen texture) more suitable for loading. This study could be crucial in further translational clinical research in humans for defining the best therapeutic strategies to be applied in recovering severe skeletal lesions, particularly as regards the time of PTH(1-34) administration.

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“…Common structural indices used in studies of PTH include trabecular number and thickness for cancellous bone, and cortical bone ratio and thickness for cortical bone structure . Common derived dynamic indices in clinical studies include mineralizing surface to assess the extent of surface active in mineralization at a particular time, mineral apposition rate, and bone formation rate .…”

Section: Effect Of Pth Dosing Interval On Mechanistic and Clinical Pamentioning

confidence: 99%

Influence of Dosing Interval and Administration on the Bone Metabolism, Skeletal Effects, and Clinical Efficacy of Parathyroid Hormone in Treating Osteoporosis: A Narrative Review

Kim

Lee²,

Rhee

2017

JBMR Plus

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Recombinant human parathyroid hormone (PTH) is the key anabolic agent used for preventing fracture in postmenopausal women with osteoporosis. In bone metabolism, PTH signaling is mediated through a G protein–coupled receptor that affects various post‐receptor signaling pathways. Results of preclinical and clinical studies have shown that PTH improves both the structure and strength of bone tissue. Once daily subcutaneous injection of the PTH fragment, teriparatide (PTH [1‐34]), is the most commonly recommended formulation and dosing strategy in clinical practice. However, other dosing intervals, formulations, and routes have been investigated in preclinical and clinical studies. In particular, once‐weekly and cyclical administration have been investigated mainly as a means of reducing the high direct costs of treatment. In preclinical studies, bone formation/resorption markers, bone mineral density measurements, and histomorphometric parameters improved with both once‐daily and once‐weekly administration. However, the magnitude and duration of such improvements were generally greater with once‐daily PTH administration. In clinical studies, reductions in fracture incidence were also noted with both once‐daily and once‐weekly PTH administration, although improvements in nonvertebral fractures are less evident with once‐weekly administration. This narrative review details the differences between PTH formulation and dosing strategies in relation to preclinical and clinical efficacy/safety parameters, although it should be stressed that no head‐to‐head studies allow direct comparisons. This review also seeks to outline practical considerations involved with PTH prescribing and new directions in research regarding routes of administration. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

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Three-Times-Weekly Administration of Teriparatide Improves Vertebral and Peripheral Bone Density, Microarchitecture, and Mechanical Properties Without Accelerating Bone Resorption in Ovariectomized Rats

Cited by 27 publications

References 33 publications

Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariectomized rats

Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariectomized rats

PTH(1‐34) effects on repairing experimentally drilled holes in rat femur: novel aspects – qualitative vs. quantitative improvement of osteogenesis

Influence of Dosing Interval and Administration on the Bone Metabolism, Skeletal Effects, and Clinical Efficacy of Parathyroid Hormone in Treating Osteoporosis: A Narrative Review

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