Anabolic effect of parathyroid hormone on cancellous and cortical bone histology

Gunness, M.; Hock, Janet M.

doi:10.1016/8756-3282(93)90152-z

Cited by 26 publications

(19 citation statements)

References 20 publications

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“…Intermittent dosing of PTH results in a net increase in bone mass while continuous infusion of PTH results in a net loss of bone mass [7] as the anabolic and catabolic effects of PTH are determined primarily by the duration of time that serum concentrations of PTH remain elevated [8]. The anabolic effect of intermittent PTH on bone formation is largely attributed to an increase in the number of matrix-synthesizing osteoblasts [9-15].…”

Section: Introductionmentioning

confidence: 99%

Parathyroid hormone reverses radiation induced hypovascularity in a murine model of distraction osteogenesis

Kang

Deshpande

Donneys

et al. 2013

Bone

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Background Radiation treatment results in a severe diminution of osseous vascularity. Intermittent parathyroid hormone (PTH) has been shown to have an anabolic effect on osteogenesis, though its impact on angiogenesis remains unknown. In this murine model of distraction osteogenesis, we hypothesize that radiation treatment will result in a diminution of vascularity in the distracted regenerate and that delivery of intermittent systemic PTH will promote angiogenesis and reverse radiation induced hypovascularity. Materials and methods Nineteen Lewis rats were divided into three groups. All groups underwent distraction of the left mandible. Two groups received radiation treatment to the left mandible prior to distraction, and one of these groups was treated with intermittent subcutaneous PTH (60 μg/kg, once daily) beginning on the first day of distraction for a total duration of 21 days. One group underwent mandibular distraction alone, without radiation. After consolidation, the rats were perfused and imaged with micro-CT angiography and quantitative vascular analysis was performed. Results Radiation treatment resulted in a severe diminution of osseous vascularity in the distracted regenerate. In irradiated mandibles undergoing distraction osteogenesis, treatment with intermittent PTH resulted in significant increases in vessel volume fraction, vessel thickness, vessel number, degree of anisotropy, and a significant decrease in vessel separation (p < 0.05). No significant difference in quantitative vascularity existed between the group that was irradiated, distracted and treated with PTH and the group that underwent distraction osteogenesis without radiation treatment. Conclusions We quantitatively demonstrate that radiation treatment results in a significant depletion of osseous vascularity, and that intermittent administration of PTH reverses radiation induced hypovascularity in the murine mandible undergoing distraction osteogenesis. While the precise mechanism of PTH-induced angiogenesis remains to be elucidated, this report adds a key component to the pleotropic effect of intermittent PTH on bone formation and further supports the potential use of PTH to enhance osseous regeneration in the irradiated mandible.

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Section: Introductionmentioning

confidence: 99%

Parathyroid hormone reverses radiation induced hypovascularity in a murine model of distraction osteogenesis

Kang

Deshpande

Donneys

et al. 2013

Bone

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“…Continuous infusions of the hormone (or its active portion, amino acids 1 to 34) lead to greater bone resorption, whereas intermittent daily dosing has an anabolic effect and leads to increased bone mass, osteoblast generation and mobilization, and improved fracture healing. 8 …”

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confidence: 99%

Parathyroid Hormone Therapy Mollifies Radiation-Induced Biomechanical Degradation in Murine Distraction Osteogenesis

Deshpande

Gallagher

Donneys³

et al. 2013

Plastic and Reconstructive Surgery

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Objective Descriptions of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis have been limited. Previous work demonstrated radiation decreases union formation, cellularity and mineral density in mandibular distraction osteogenesis. The authors posit that intermittent systemic administration of parathyroid hormone will serve as a stimulant to cellular function, reversing radiation-induced damage and enhancing bone regeneration. Methods Twenty male Lewis rats were randomly assigned to three groups: group 1 (radiation and distraction osteogenesis, n = 7) and group 2 (radiation, distraction osteogenesis, and parathyroid hormone, n = 5) received a human-equivalent dose of 35 Gy of radiation (human bioequivalent, 70 Gy) fractionated over 5 days. All groups, including group 3 (distraction osteogenesis, n = 8), underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Distraction osteogenesis was performed at a rate of 0.3 mm every 12 hours to reach a gap of 5.1 mm. Group 2 was injected with parathyroid hormone (60 μg/kg) subcutaneously daily for 3 weeks after the start of distraction osteogenesis. On postoperative day 40, all left hemimandibles were harvested. Biomechanical response parameters were generated. Statistical significance was considered at p ≤ 0.05. Results Parathyroid hormone–treated mandibles had significantly higher failure load and higher yield than did untreated mandibles. However, these values were still significantly lower than those of nonirradiated mandibles. Conclusions The authors have successfully demonstrated the therapeutic efficacy of parathyroid hormone to stimulate and enhance bone regeneration in their irradiated murine mandibular model of distraction osteogenesis. Anabolic regimens of parathyroid hormone, a U.S. Food and Drug Administration–approved drug on formulary, significantly improve outcomes in a model of postoncologic craniofacial reconstruction.

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“…Experimental studies in rats have shown that intermittent hPTH-(1-34) treatment can exert a potent dosedependent anabolic response in cortical and trabecular bone (Dempster et al, 1993;Gunness and Hock, 1993;Kimmel et al, 1993;Riond, 1993;Dobnig and Turner, 1997;Cosman and Lindsay, 1998) with concomitant increases in stiffness and bending strength (Ejersted et al, 1993;Mosekilde et al, 1995;Sato et al, 1997). The beneficial effects of hPTH-(1-34) treatment are also reported to be synergistically enhanced by concurrent mechanical stimulation (Chow et al, 1998;Ma et al, 1999;Hagino et al, 2001;Kim et al, 2003;Li et al, 2003).…”

Section: Introductionmentioning

confidence: 90%

Local bone formation due to combined mechanical loading and intermittent hPTH-(1-34) treatment and its correlation to mechanical signal distributions

Roberts

Santner

Hart

2009

Journal of Biomechanics

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Anabolic effect of parathyroid hormone on cancellous and cortical bone histology

Cited by 26 publications

References 20 publications

Parathyroid hormone reverses radiation induced hypovascularity in a murine model of distraction osteogenesis

Parathyroid hormone reverses radiation induced hypovascularity in a murine model of distraction osteogenesis

Parathyroid Hormone Therapy Mollifies Radiation-Induced Biomechanical Degradation in Murine Distraction Osteogenesis

Local bone formation due to combined mechanical loading and intermittent hPTH-(1-34) treatment and its correlation to mechanical signal distributions

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