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

Junro Yamashita,Laurie K McCauley

doi:10.1002/jbm4.10250

Junro Yamashita, Laurie K McCauley

Open Access

https://doi.org/10.1002/jbm4.10250

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Abstract

ABSTRACTIntermittent 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.

Highlights

The fracture healing process begins with hematoma formation followed by an inflammatory phase, a proliferative phase with soft callus formation, callus ossification, and the bone remodeling phase
Beneficial effects of daily parathyroid hormone (PTH) therapy on fracture healing was reported by Holzer et al where they induced closed femoral shaft fractures in 3-month-old female rats and administered 80 μg/kg PTH daily for 21 days.[17]. Significantly higher callus area and strength were found in the PTH-treated fractures compared to controls
The results of animal studies clearly indicate that intermittent PTH administration promotes fracture healing by accelerating callus formation and ossification

Summary

Introduction

The fracture healing process begins with hematoma formation followed by an inflammatory phase, a proliferative phase with soft callus formation, callus ossification, and the bone remodeling phase. Pathological conditions which have negative influences on progenitor cell recruitment, angiogenesis, or extracellular matrix formation could result in impaired or delayed healing Such conditions include but are not limited to radiation therapy, osteoporosis, diabetes mellitus (DM), antiangiogenic therapy, advanced age, steroid therapy, and infection.[1] In long bones, nearly 10% of fractures are associated with impaired healing.[2,3] Bone grafting procedures or local applications of osteoinductive cytokines, such as bone morphogenetic protein-2 and -7, are applied to promote repair of fractures with compromised healing.[4] these procedures generally involve surgical intervention and have a risk of potential infection and morbidity. Systemic anabolic agents including parathyroid hormone (PTH) and PTH-related protein (PTHrP) have demonstrated potential as candidates which could augment localized osseous healing

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