Emerging Protein and Peptide Therapeutics for Osteoporosis: Advances in Anabolic and Catabolic Treatments

Abstract

Osteoporosis is a prevalent skeletal disorder characterized by reduced bone density and increased fracture risk, primarily affecting the elderly population. The pathophysiology of osteoporosis involves an imbalance between bone resorption and bone formation, with catabolic processes (bone breakdown) counteracting anabolic processes (bone formation). Treatment strategies for osteoporosis are categorized into anabolic and catabolic approaches, each targeting different aspects of bone metabolism. Catabolic treatments focus on inhibiting bone resorption. peptides, such as Calcitonin Salmon and monoclonal antibodies like denosumab, inhibit osteoclast activity, thereby reducing bone turnover. These catabolic agents effectively stabilize bone density and reduce the incidence of fractures, especially in postmenopausal women. Anabolic treatments aim to stimulate bone formation, thereby increasing bone mass and improving bone microarchitecture. Teriparatide, a recombinant form of parathyroid hormone, and abaloparatide, a synthetic analog, and monoclonal antibody romosozumab are the primary anabolic agents. These drugs activate osteoblasts, enhancing bone formation and leading to significant improvements in bone density and reduction in fracture risk. Combining anabolic and catabolic therapies has shown promise in optimizing bone health, as it addresses both aspects of the bone remodeling process. Recent studies have shown that PEPITEM (Peptide Inhibitor of Trans-Endothelial Migration) can limit bone loss and improve bone density in animal models of menopause by acting straightly on osteoblasts, the cells responsible for formation of bone, via NCAM-1 signaling, promoting their maturation and new bone formation (anabolic). Bioactive collagen peptides have shown promise as a treatment for osteoporosis by improving bone mineral density (BMD) and supporting overall bone health.