Parathyroid hormone pulsatility: physiological and clinical aspects

Chiavistelli, Silvia; Giustina, Andrea; Mazziotti, Gherardo

doi:10.1038/boneres.2014.49

Cited by 44 publications

(33 citation statements)

References 53 publications

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“…PTH increased trabecular bone mass in adult rats by thickening the existing trabeculae. This can be explained by significantly increased osteoblast number and surface (Supplemental Table 1), and was also suggested by previous studies [20–22, 38]. Thus, we conclude that the young and adult rat responses to PTH are not directly comparable due to their distinct bone structural development mechanisms.…”

Section: Discussionsupporting

confidence: 77%

Quantification of skeletal growth, modeling, and remodeling by in vivo micro computed tomography

Altman

Tseng

Bakker

et al. 2015

Bone

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In this study we established an image analysis scheme for the investigation of cortical and trabecular bone development during skeletal growth and tested this concept on in vivo µCT images of rats. To evaluate its efficacy, we applied the technique to young (1-month-old) and adult (3-month-old) rat tibiae with vehicle (Veh) or intermittent parathyroid hormone (PTH) treatment. By overlaying 2 sequential scans based on their distinct trabecular microarchitecure, we calculated the linear growth rate of young rats to be 0.31 mm/day at the proximal tibia. Due to rapid growth (3.7 mm in 12 days), the scanned bone region at day 12 had no overlap with the bone tissue scanned at day 0. Instead, the imaged bone region at day 12 represented newly generated bone tissue from the growth plate. The new bone of the PTH-treated rats had significantly greater trabecular bone volume fraction, number, and thickness than those of the Veh-treated rats, indicating PTH’s anabolic effect on bone modeling. In contrast, the effect of PTH on adult rat trabecular bone was found to be caused by PTH’s anabolic effect on bone remodeling. The cortical bone at the proximal tibia of young rats also thickened more in the PTH group (23%) than the Veh group (14%). This was primarily driven by endosteal bone formation and coalescence of trabecular bone into the cortex. This process can be visualized by aligning the local bone structural changes using image registration. As a result, the cortex after PTH treatment was 31% less porous, and had a 22% greater polar moment of inertia compared to the Veh group. Lastly, we monitored the longitudinal bone growth in adult rats by measuring the distance of bone flow away from the proximal tibial growth plate from 3 months to 19 months of age and discovered a total of 3.5 mm growth in 16 months. It was demonstrated that this image analysis scheme can efficiently evaluate bone growth, bone modeling, and bone remodeling, and is ready to be translated into a clinical imaging platform.

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Section: Discussionsupporting

confidence: 77%

Quantification of skeletal growth, modeling, and remodeling by in vivo micro computed tomography

Altman

Tseng

Bakker

et al. 2015

Bone

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“…Parathyroid hormone (PTH) secretion is characterized by an ultradian rhythm with tonic and pulsatile components. In healthy subjects, the majority of PTH is secreted in tonic fashion, whereas approximately 30% is secreted in low-amplitude and high-frequency bursts occurring every 10-20 min, superimposed on tonic secretion (8).…”

Section: The Role Of Pth In Bone Remodelingmentioning

confidence: 99%

Use of teriparatide off-label: our experience and review of literature

Ciurlia

Leali

Doria

2017

ccmbm

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SummaryThe aim of this paper is to report our experience and to present a review of literature about the use of teriparatide off-label in the therapy of non-unions. Teriparatide is used exclusively in treatment of osteoporosis and to prevent bone fracture because it has a positive effect on bone strength and architecture. The use of teriparatide in non-unions is described as effective in numerous case report.

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“…Normal secretion (from the parathyroid gland) is an ultradian rhythm with tonic and pulsatile components (70% tonic, 30% pulsatile), and is dependent on serum calcium and phosphorous. The half‐life of PTH in humans is approximately 2–5 min and the pulsatile component is in low amplitude high frequency bursts every 10–20 min superimposed on the tonic secretion . The pulsatile component is highly sensitive to changes in ionized calcium and calcitrol levels.…”

Section: Biological Mechanisms Of Pth Mediated Bone Formationmentioning

confidence: 99%

“…Both tonic and pulsatile secretions play a role in normal bone maintenance, though it is not fully clear what role each plays. In glucocorticoid induced osteoporosis endogenous tonic PTH levels are decreased, and the amount released in pulsatile fashion is increased . It has been proposed that the increase in pulsatile release is perhaps an attempt at compensation for the decrease in tonic release, however an osteoporotic state still develops.…”

Section: Biological Mechanisms Of Pth Mediated Bone Formationmentioning

confidence: 99%

“…Based on the success of PTH as an anabolic osteoporosis treatment, it follows that there may also be implications for its use for promoting bone regeneration in large bone defects. Though it may seem the benefits of utilizing PTH for bone regeneration are limited to intermittent administration, some of the aforementioned findings suggest continuously elevated PTH may be anabolic in certain circumstances, such as in mild PHPT and tonic PTH secretions . The ability of PTH to increase remodeling in bone gives it great potential in the realm of fracture healing .…”

Section: Efficacy Of Systemic Pth For Bone Regeneration and Defect Rementioning

confidence: 99%

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Parathyroid hormone for bone regeneration

Wojda

Donahue

2018

Journal Orthopaedic Research

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Delayed healing and/or non-union occur in approximately 5-10% of the fractures that occur annually in the United States. Segmental bone loss increases the probability of non-union. Though grafting can be an effective treatment for segmental bone loss, autografting is limited for large defects since a limited amount of bone is available for harvest. Parathyroid hormone (PTH) is a key regulator of calcium homeostasis in the body and plays an important role in bone metabolism. Presently PTH is FDA approved for use as an anabolic treatment for osteoporosis. The anabolic effect PTH has on bone has led to research on its use for bone regeneration applications. Numerous studies in animal models have indicated enhanced fracture healing as a result of once daily injections of PTH. Similarly, in a human case study, non-union persisted despite treatment attempts with internal fixation, external fixation, and autograft in combination with BMP-7, until off label use of PTH1-84 was utilized. Use of a biomaterial scaffold to locally deliver PTH to a defect site has also been shown to improve bone formation and healing around dental implants in dogs and drill defects in sheep. Thus, PTH may be used to promote bone regeneration and provide an alternative to autograft and BMP for the treatment of large segmental defects and non-unions. This review briefly summarizes the unmet clinical need for improved bone regeneration techniques and how PTH may help fill that void by both systemically and locally delivered PTH for bone regeneration applications. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2586-2594, 2018.

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Parathyroid hormone pulsatility: physiological and clinical aspects

Cited by 44 publications

References 53 publications

Quantification of skeletal growth, modeling, and remodeling by in vivo micro computed tomography

Quantification of skeletal growth, modeling, and remodeling by in vivo micro computed tomography

Use of teriparatide off-label: our experience and review of literature

Parathyroid hormone for bone regeneration

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