Teriparatide

Mechanism (as reported)

A study/review reported that PTH regulates bone metabolism by binding to the PTH1 receptor (PTH1R) and that signaling pathways include Wnt, cAMP/PKA, cAMP/PKC, and RANKL/RANK/OPG. The review also describes PTH acting through effects on multiple cell types involved in bone metabolism, including mesenchymal stem cells, osteoblast-lineage cells, osteocytes, T cells, and osteoclast precursors/osteoclasts. (PMID: 34224692) A review reported that teriparatide’s effects are mediated by the G-protein-dependent parathyroid hormone receptor-1, with downstream activation of adenylate cyclase and phospholipases leading to increased intracellular cAMP and calcium; it also describes intermittent teriparatide increasing osteoblast numbers and bone formation and reducing osteoblast apoptosis. (PMID: 15228497)

Key findings (each cites a source)

• A review reported that PTH regulates bone metabolism by binding to PTH1R and described signaling pathways including Wnt, cAMP/PKA, cAMP/PKC, and RANKL/RANK/OPG, with effects across multiple bone- and immune-related cell types; the review also notes that PTH(1-34) is also known as teriparatide. (PMIDs: 34224692) [PMID 34224692]
• A review reported that teriparatide’s effects are mediated by the G-protein-dependent parathyroid hormone receptor-1, activating adenylate cyclase and phospholipases and increasing intracellular cAMP and calcium; it also described intermittent teriparatide effects on osteoblasts and bone formation and reduced osteoblast apoptosis. (PMIDs: 15228497) [PMID 15228497]
• A clinical-focused overview/review reported that PTH(1-34) (teriparatide) is discussed in the context of treatment of hypoparathyroidism and that recombinant PTH was noted as not being approved in Europe yet (with mention of FDA approval of PTH (1-84) in early 2015) and that daily subcutaneous delivery of PTH(1-84) and PTH(1-34) was described as emerging. (PMIDs: 26261924) [PMID 26261924]
• A study addressing generic teriparatide impurities reported the use of an orthogonal immunogenicity risk assessment strategy involving in silico predictions, in vitro HLA-DR binding measurements, and a PBMC T-cell assay; it reported that multiple impurities were identified as more immunogenic than teriparatide, and also reported an in silico finding of a potentially tolerogenic sequence that correlated with lower-than-expected de novo immune responses in vitro. (PMIDs: 41445733) [PMID 41445733]
• A methods validation study reported that a liquid chromatography–high-resolution mass spectrometry (LC-HRMS) method was validated to quantify six peptide-related impurities in teriparatide, describing performance characteristics (specificity, sensitivity, linearity, accuracy, repeatability, intermediate precision, robustness) and reporting lower limits of quantification below a regulatory reporting threshold; it also reported that using three isotopic peaks per peptide did not provide significant benefit over one isotopic peak. (PMIDs: 39778260) [PMID 39778260]
• A review reported that teriparatide is described as the only osteoanabolic peptide available worldwide for osteoporosis treatment and discussed research attempts for efficient delivery via non-invasive routes (oral, nasal, pulmonary, transdermal) and long-acting injectable formulations, including discussion tied to intermittent/pulsatile delivery concepts. (PMIDs: 37522550) [PMID 37522550]
• An experimental study reported development of a multifunctional thermosensitive nanodelivery system modified by a fusion peptide (LR27-a) to load and sustain PTH1-34 delivery for noise-induced hearing loss research; it reported in vitro antioxidant and anti-apoptotic assessments and in vivo findings in an NIHL mouse model. (PMIDs: 39921275) [PMID 39921275]
• A retrospective cohort study reported that, among treatment-naïve primary osteoporosis patients stratified by baseline PINP, lumbar spine BMD increases at 12 months were similar between romosozumab and teriparatide in the low PINP group, while romosozumab led to greater lumbar spine BMD increases than teriparatide in the high PINP group; it also reported that compared with denosumab, romosozumab resulted in greater increases in lumbar spine and total hip BMD in the low PINP group, with no significant differences observed in the high PINP group. (PMIDs: 40912668) [PMID 40912668]
• A review reported that teriparatide was described as approved in the EU and the USA as an anabolic treatment of osteoporosis, with effects mediated through the parathyroid hormone receptor-1 pathway; it also described clinical trial observations including reported reductions in relative risk of vertebral and appendicular fractures and increases in lumbar spine and hip bone mineral density. (PMIDs: 15228497) [PMID 15228497]