Use of peptides derived from parathyroid hormone-related protein for increasing bone formation and bone regeneration

Abstract

Osteoporosis, the most prevalent pathology affecting the skeleton, currently represents a challenge for Western societies. Bone mass loss with age, mainly but not exclusively related to estrogen deficiency, increases fracture risk. Fracture repair is frequently impaired due to metabolic alterations and/or the extention of bone damage. Thus, strategies like use of osteogenic factors that help regenerate damaged bone tissue are highly needed. In this regard, systemic administration of parathormone (PTH) represents the first anabolic treatment in osteoporosis by predominantly increasing bone formation over bone resorption during bone remodeling. Recently, there is a pharmacological alternative to PTH based on a peptide analogue derived from the N-terminal sequence of PTH-related protein (PTHrP) (named abaloparatide). This peptide exhibits great affinity for PTH type 1 receptor, and presents pharmacokinetic advantages (decreasing the risk of hipercalcemia), compared to PTH in the treatment of osteoporosis. N-terminal peptides of both PTH and PTHrP promote the formation of fracture callus and bone healing in animal models of bone injury. In addition, osteostatin peptide derived from the C-terminal tail of PTHrP -unrelated to PTH- displays osteogenic features in vitro and in vivo in osteoporosis models. In recent years, osteostatin loading into various types of implants (including mesoporous bioceramics based on SiO and Zn-doped bioglasses) improves the capacity of the biomaterial to increase bone regeneration. Current data support the notion that PTHrP-derived peptides are a promising strategy for bone tissue engineering applications.