Intermittent administration of human parathyroid hormone enhances bone formation and union at the site of cancellous bone osteotomy in normal and ovariectomized rats

Nozaka, Koji; Miyakoshi, Naohisa; Kasukawa, Yuji; Maekawa, Shigeto; Noguchi, Hideaki; Shimada, Yasuhiro

doi:10.1016/j.bone.2007.08.041

Cited by 92 publications

(53 citation statements)

References 48 publications

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“…We may assume the deterioration of bone quality when we think about suppressed bone absorption. However, bone absorption was not suppressed more in the PTH treated OVX rat than that in the non-PTH treated non-OVX rat (Nozaka et al 2008). Therefore, we can consider that intermittent administration of PTH for OVX rats suppresses the redundant osteoclasts induced by OVX.…”

Section: Discussionmentioning

confidence: 88%

“…In this study, our PTH administration protocol increased bone formation and suppressed bone absorption. In recent years, some animal or human studies have reported that bone absorption was suppressed by intermittent administration of PTH (Nozaka et al 2008). We may assume the deterioration of bone quality when we think about suppressed bone absorption.…”

Section: Discussionmentioning

confidence: 99%

“…A cancellous bone osteotomy of the right proximal tibia was performed, as previously described (Nozaka et al 2008;Tsuchie et al 2011), 4 weeks after a bilateral OVX, a time period that ensures sufficient osteopenia (Nitta et al 1999). A median parapatellar incision from the knee joint through the proximal half of the tibia was made in the right hind limb, and a complete mid-sagittal osteotomy from the joint surface to the outer tibial diaphysis was performed using an electrically powered bone saw under general anesthesia with ketamine (Sankyo, Tokyo, Japan) and xylazine (Zenoaq, Fukushima, Japan) (Fig.…”

Section: Cancellous Bone Osteotomy At the Proximal Tibiamentioning

confidence: 99%

“…The percentage of bone union (rate of the length of bone union to the total length of the osteotomy) was calculated with a semiautomatic graphic system (Histometry RT Camera, System Supply Co., Nagano, Japan) at a magnification of 100 ×. Complete bone union (bone-to-bone binding at the osteotomy site) was defined as bone union, whereas fibrous union (fibrous binding) was defined as non-union (Nozaka et al 2008).…”

Section: Evaluation Of Bone Union After the Osteotomymentioning

confidence: 99%

“…Therefore, a cancellous bone fracture model was created and an osteotomy of the proximal tibia was performed. The effects of intermittent admin-istration of PTH on fracture healing were evaluated in this model based on a previous study (Nozaka et al 2008). However, surgical treatment is occasionally delayed in elderly patients because of medical complications that need to be monitored and the cessation of anticoagulants.…”

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confidence: 99%

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Intermittent Administration of Human Parathyroid Hormone before Osteosynthesis Stimulates Cancellous Bone Union in Ovariectomized Rats

Tsuchie

Miyakoshi

Kasukawa

et al. 2013

Tohoku J. Exp. Med.

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It has been reported that intermittent administration of human parathyroid hormone (h-PTH) promotes bone healing after surgery for osteoporotic fractures. If bone healing is promoted by the administration of h-PTH during pre-operative waiting period, we can prevent prolonged bed rest. Therefore, we evaluated the effects of pre-operative h-PTH treatment on cancellous bone union and its mechanism for fracture healing in ovariectomized rats as a model for osteoporosis. Ovariectomized 7-month-old female Sprague-Dawley rats underwent an osteotomy of the proximal tibia as a fracture model, and h-PTH (30 µg/kg body weight) or vehicle was administered as a pre-operative treatment for one week. After the one-week treatment, tibiae were fixed with wire for osteosynthesis, and h-PTH or vehicle was administered for 1 or 3 weeks following wire fixation. In addition to bone histomorphometry, we used alcian blue/hematoxylin stained sections for evaluating cartilage volume and immunostained sections for analyzing the expression of proliferating cell nuclear antigen (PCNA) for cell proliferation and that of Sox9 and Runx2, differentiation markers for cartilage cells and osteoblasts, respectively. Pre-operative treatment with PTH significantly increased bone volume. Pre-operative and pre-to post-operative treatment with PTH for 2 weeks significantly promoted bone union. Pre-operative treatment with PTH significantly increased cartilage volume, and pre-to post-operative treatment with PTH for 2 weeks significantly increased the percentage of cells positive for Runx2 (p < 0.01), but not PCNA or Sox9. Pre-operative administration of h-PTH enhances bone union by promoting cartilage formation and cell differentiation to osteoblasts, but not by promoting cell proliferation.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Cancellous Bone Osteotomy At the Proximal Tibiamentioning

confidence: 99%

Section: Evaluation Of Bone Union After the Osteotomymentioning

confidence: 99%

mentioning

confidence: 99%

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Intermittent Administration of Human Parathyroid Hormone before Osteosynthesis Stimulates Cancellous Bone Union in Ovariectomized Rats

Tsuchie

Miyakoshi

Kasukawa

et al. 2013

Tohoku J. Exp. Med.

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Effects of Intermittent Administration of Parathyroid Hormone and Parathyroid Hormone‐Related Protein on Fracture Healing: A Narrative Review of Animal and Human Studies

Yamashita

McCauley

2019

JBMR Plus

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Intermittent administration of parathyroid hormone (PTH) stimulates skeletal remodeling and is a potent anabolic agent in bone. PTH‐related protein (PTHrP) is anabolic acting on the same PTH1 receptor and is in therapeutic use for osteoporosis. The body of literature for PTH actions in fracture healing is emerging with promising yet not entirely consistent results. The objective of this review was to perform a literature analysis to extract up‐to‐date knowledge on the effects of intermittent PTH and PTHrP therapy in bone fracture healing. A literature search of the PubMed database was performed. Clinical case studies and articles related to “regeneration,” “implant,” and “distraction osteogenesis” were excluded. A narrative review was performed to deliberate the therapeutic potential of intermittent PTH administration on fracture healing. A smaller number of studies centered on the use of PTHrP or a PTHrP analog were also reviewed. Animal studies clearly show that intermittent PTH therapy promotes fracture healing and revealed the strong therapeutic potential of PTH. Human subject studies were fewer and not as consistent as the animal studies yet provide insight into the potential of intermittent PTH administration on fracture healing. Differences in outcomes for animal and human studies appear to be attributed partly to variable doses, fracture sites, age, remodeling patterns, and bone architectures, although other factors are involved. Future studies to examine the dose, timing, and duration of PTH administration will be necessary to further delineate the therapeutic potential of PTH for fracture healing in humans. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Comparison of the effects of once‐weekly and once‐daily rhPTH (1–34) injections on promoting fracture healing in rodents

Wen

Zhu

et al. 2017

Journal Orthopaedic Research

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To compare the efficacy of once-weekly and once-daily subcutaneous injections of teriparatide (recombinant human parathyroid hormone 1-34) on fracture healing, 50 adult male Sprague-Dawley rats were subjected to a unilateral tibia fracture and received internal fixation with a Kirschner needle. Based on the injection dose and frequency, the rats were randomly divided into five groups (n = 10 each): subcutaneous injections of saline or 10 µg/kg/w, 20 µg/kg/w, 10 µg/kg/d, and 20 µg/kg/d teriparatide. Four weeks later, the rats were euthanatized, and the fractured tibiae were assessed using X-rays, dual-energy X-ray absorptiometry, micro-computed tomography, the three-point bending biomechanics test, and histology. Compared to the saline control group, either daily or weekly subcutaneous injections of teriparatide significantly increased bone mass, improved the bone microarchitecture, and promoted fracture healing (p < 0.05). There were no significant differences in bone mineral density (BMD), bone microstructure or bone strength between the 20 µg/kg/w and 10 µg/kg/d groups (p > 0.05). Teriparatide 20 µg weekly injections promoted bone fracture healing to the same extent as teriparatide 10 µg daily injections, which can dramatically decrease the cumulative dosage of teriparatide injections. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1145-1152, 2018.

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Intermittent administration of human parathyroid hormone enhances bone formation and union at the site of cancellous bone osteotomy in normal and ovariectomized rats

Cited by 92 publications

References 48 publications

Intermittent Administration of Human Parathyroid Hormone before Osteosynthesis Stimulates Cancellous Bone Union in Ovariectomized Rats

Intermittent Administration of Human Parathyroid Hormone before Osteosynthesis Stimulates Cancellous Bone Union in Ovariectomized Rats

Effects of Intermittent Administration of Parathyroid Hormone and Parathyroid Hormone‐Related Protein on Fracture Healing: A Narrative Review of Animal and Human Studies

Comparison of the effects of once‐weekly and once‐daily rhPTH (1–34) injections on promoting fracture healing in rodents

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