Parathyroid hormone 1-34 and skeletal anabolic action

Abstract

Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1.

Intermittent Administration of Parathyroid Hormone 1–34 Enhances Osteogenesis of Human Mesenchymal Stem Cells by Regulating Protein Kinase Cδ

“…The most common treatment for osteoporosis is anti-resorptive agents that inhibit osteoclast activity. Another therapeutic option, especially for severe cases, is teriparatide, a synthetic and active fragment of parathyroid hormone (PTH), comprising the N-terminal 1–34 amino acids (PTH (1–34)) [ 1 , 2 ]. Currently, PTH is a more effective treatment option reported to have catabolic effects on bone.…”

“…Synthetic recombinant human PTH (1–34) has been shown to promote bone mineral density and has been applied to treat severe osteoporosis. However, intermittent and continuous PTH administration has disparate effects [ 1 , 2 , 3 , 4 , 5 , 6 ]. It is well known that intermittent daily subcutaneous PTH injection can increase osteoblast activity, whereas continuous treatment generates osteoclasts that exhibit high resorptive ability, inhibits osteoblast precursor cells, and is more active in osteoclastogenesis.…”

The Influence of PTH 1-34 on the Osteogenic Characteristics of Adipose and Bone Marrow Derived Stem Cells from Juvenile and Ovarectomized Rats

“…The stimulation, proliferation and differentiation of bone marrow derived osteoprogenitor cells by PTH 1-34 has been well documented in the literature (31). The anabolic window is based on findings of intermittent dosing regimens, Contrary to the larger body of literature we did not find an increase in proliferation of cells from any group after PTH dosing, this is contrary to work where proliferative increases with shorter exposure cycles to PTH (30minutes-1hour), thought to be due to selective upregulation of the cAMP/PKA pathways (32).…”

Hypocalcemia in the Critically Ill: A Mini-Review

“…However teriparitide was not superior to alendronate in reducing fracture risk [54]. Both these analogues have anabolic properties and effects [52][53][54][55][56][57] Studies about their efficacy in the hypocalcemia of the critically ill patient are awaiting as they could reverse or improve bone hyperresorption in the critically ill patient [27].…”