Biological agents in management of osteoporosis

Research output: Contribution to journalReview article

33 Citations (Scopus)

Abstract

Osteoporosis is a skeletal disease associated with an imbalance between formation and resorption, leading to net loss of bone mass, loss of bone microarchitecture, and development of fractures. Bone resorption is primarily due to an activation of osteoclastogenesis and an increase in receptor activator of nuclear factor kappa-B ligand (RANKL) expression, a cytokine involved in the final pathway of the osteoclast cycle. Recent studies of genetic diseases led to the discovery of the wingless-type (Wnt) signaling pathway that plays a major role in bone formation. Further work showed that sclerostin produced by osteocytes and the Dickkopf (DKK1) protein secreted in bone were negative regulators of the Wnt signaling bone formation pathway that act directly by binding to the co-receptors LRP5 and LRP6 of WnT and thereby inhibiting the anabolic Wnt pathway. This understanding of the bone remodeling led to the discovery of new biological drugs that target these pathways and have been evaluated in clinical trials. The current article discusses the role of these newer "biological" agents in management of osteoporosis. Denosumab, a human monoclonal antibody that specifically binds RANKL, blocks the binding of RANK to its ligand markedly reducing bone resorption, increases bone density, and reduces fractures and is approved for osteoporosis. Parathyroid hormone PTH 1-34 (teriparatide) stimulates bone formation through inhibition of sclerostin, DKK1, and frizzled protein; increases BMD; improves microarchitecture; and decreases fractures and is approved for osteoporosis. The anti-sclerostin antibodies (romosozumab, blosozumab) increase bone mass by neutralizing the negative effects of sclerostin on the Wnt signaling pathway. These biologics are being evaluated now in a clinical trial and early data looks promising. Cathepsin K is a proteolytic enzyme that degrades bone matrix and inhibitors such as odanacatib show increasing bone density and perhaps decreased fractures. The potential power of combining these newer antiresorptives with the newer anabolic agents could theoretically increase bone mass rapidly to normal within 1 year and reduce fractures. These newer treatments are revolutionizing the management of osteoporosis.

Original languageEnglish
Pages (from-to)1291-1301
Number of pages11
JournalEuropean Journal of Clinical Pharmacology
Volume70
Issue number11
DOIs
StatePublished - 2014

Fingerprint

Biological Factors
Osteoporosis
Osteogenesis
RANK Ligand
Bone and Bones
Bone Resorption
Parathyroid Hormone
Bone Density
Frizzled Receptors
Clinical Trials
Cathepsin K
Teriparatide
Anabolic Agents
Osteocytes
Inborn Genetic Diseases
Bone Matrix
Bone Remodeling
Bone Development
Osteoclasts
Biological Products

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Pharmacology
  • Medicine(all)

Cite this

Biological agents in management of osteoporosis. / Tella, Sri Harsha; Gallagher, John Christopher G.

In: European Journal of Clinical Pharmacology, Vol. 70, No. 11, 2014, p. 1291-1301.

Research output: Contribution to journalReview article

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