Parathyroid Hormone (PTH) Analogue
A synthetic compound mimicking PTH's ability to stimulate bone formation when given in intermittent pulses. Teriparatide (PTH 1-34), abaloparatide (PTHrP analogue), and palopegteriparatide (PEGylated PTH) are approved for severe osteoporosis, uniquely promoting new bone growth rather than merely preventing loss.
Technical Context
Teriparatide (PTH 1-34) contains the biologically active N-terminal fragment — the first 34 amino acids are sufficient for full PTH1R activation. Daily SC injection produces a brief pulse of PTH1R activation (hours, not continuous) that preferentially activates the Wnt/β-catenin pathway → increased osteoblast differentiation and activity → net bone formation (the anabolic window). Continuous PTH exposure shifts the balance toward RANKL upregulation → osteoclast activation → net bone resorption. Abaloparatide is an analogue of PTHrP (parathyroid hormone-related protein) 1-34, with amino acid modifications that produce more transient PTH1R signalling (preferential RG vs R0 receptor conformation binding), potentially providing similar bone formation with less bone resorption and hypercalcaemia. Palopegteriparatide uses TransCon technology — PTH linked to PEG via a cleavable linker that releases active PTH after SC injection for sustained daily exposure.