Anabolic agents and bone quality.
BACKGROUND
The definition of bone quality is evolving particularly from the perspective of anabolic agents that can enhance not only bone mineral density but also bone microarchitecture, composition, morphology, amount of microdamage, and remodeling dynamics.


OBJECTIVE
This review summarizes the molecular pathways and physiologic effects of current and potential anabolic drugs.


METHODS
From a MEDLINE search (1996-2010), articles were identified by the search terms "bone quality" (1851 articles), "anabolic agent" (5044 articles), "PTH or parathyroid hormone" (32,229 articles), "strontium" or "strontium ranelate" (283 articles), "prostaglandin" (77,539 articles), and "statin" or "statins" (14,233 articles). The search strategy included combining each with the phrase "bone quality." Another more limited search aimed at finding more novel potential agents.


RESULTS
Parathyroid hormone is the only US Food and Drug Administration-approved bone anabolic agent in the United States and has been the most extensively studied in in vitro animal and human trials. Strontium ranelate is approved in Europe but has not undergone Food and Drug Administration trials in the United States. All the studies on prostaglandin agonists have used in vivo animal models and there are no human trials examining prostaglandin agonist effects. The advantages of statins include the long-established advantages and safety profile, but they are limited by their bioavailability in bone. Other potential pathways include proline-rich tyrosine kinase 2 (PYK2) and sclerostin (SOST) inhibition, among others.


CONCLUSIONS
The ongoing research to enhance the anabolic potential of current agents, identify new agents, and develop better delivery systems will greatly enhance the management of bone quality-related injuries and diseases in the future.
Department of Orthopaedic Surgery, Boston University Medical Center, 720 Harrison Avenue, Suite 808, Boston, MA 02118, USA.
Tarek
T
Sibai
Elise F
EF
Morgan
Thomas A
TA
Einhorn
D048868:Adaptor Proteins, Signal Transducing; D045930:Anabolic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology*; D051418:Focal Adhesion Kinase 2 / Q000502:physiology; D017102:Fracture Healing / Q000187:drug effects; D005819:Genetic Markers / Q000502:physiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000494:pharmacology; D010024:Osteoporosis / Q000188:drug therapy; D010281:Parathyroid Hormone / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage; D011453:Prostaglandins / Q000819:agonists; D019379:Teriparatide / Q000008:administration & dosage / Q000031:analogs & derivatives; D013876:Thiophenes / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D045930:Anabolic Agents; D050071:Bone Density Conservation Agents; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009942:Organometallic Compounds; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011453:Prostaglandins; C422903:SOST protein, human; D013876:Thiophenes; C081587:strontium ranelate; D019379:Teriparatide; D007334:Insulin-Like Growth Factor I; D051418:Focal Adhesion Kinase 2; C035748:parathyroid hormone (1-34)amide