Table 1.

Examples of Current and Emerging Agents Investigated for Osteoporosis^*

Classification	Compound	Mechanism	Type	Status
Current Treatments
Hormones	Estrogen Calcitonin	Activate estrogen or calcitonin receptors mediating cytokine responses and adenosine monophosphate (cAMP) kinase signaling, respectively, involved in osteoblast/clast function	Antiresorptive Antiresorptive	Marketed
	PTH (teriparatide)	Activate PTH-receptors in mediating kinase signaling involved in osteoblast/clast function	Anabolic
SERMs	Raloxifene Bazedoxifene	Activate or inhibit estrogen-specific receptor mediation of cytokine responses	Antiresorptive	Marketed
Bisphosphonates	Alendronate Ibandronate Residronate Zoledronate	Inhibitor of farnesyl pyrophosphate synthase, involved in osteoclast function	Antiresorptive	Marketed
AMARTs	Denosumab	Inhibitor of RANKL, ligand involved with osteoclast formation and activity	Antiresorptive	Marketed
Dietary Supplements	Calcium Vitamin D Calcitriol	Intracellular receptor-mediated signaling	Aid in anabolic process	Marketed
Other	Strontium ranelate	Inhibitor of RANKL, upregulates OPG, activates calcium receptors	Anabolic and antiresorptive	Marketed (in Europe)
	Sodium fluoride	Activate Wnt signaling	Anabolic
Emerging Treatments
Cathepsin K inhibitor	Odanacatib	Inhibitor of cathepsin K, which degrades type I collagen in bone	Antiresorptive	Phase III, ended early, good results
SERMs	Lasofoxifene Ospemifene Arzoxifene	Activate or inhibit estrogen-receptor mediated cytokine responses	Antiresorptive	Phase III
AMARTs	Romosozumab Blosozumab BPS804	Inhibitor of sclerostin, a Wnt inhibitor	Anabolic	Phase III Phase III Phase II
PTHrP analogs	Abaloparatide	Mediate endochondral bone formation through paracrine signaling	Anabolic	Phase III
β-arrestin analogs	PTH-barr	Activate transmembrane proteins in PTH signaling	Anabolic	Preclinical
(Src) tyrosine kinase inhibitors	Saracatinib (AZD0530) AZD0424	Inhibit Src, expressed by osteoclasts, required for ruffled border development	Antiresorptive	Phase I Phase I
Dickkopf-1 receptor antagonists	RN564 RH2-18 PF-04840082 BHQ880	Inhibit function of dickkopf-1, a Wnt inhibitor	Anabolic	Phase I Preclinical Preclinical Phase I
Activin A receptor antagonists	Sotatercept (ACE-011)	Inhibit binding of activin A to Act RIIA receptor involved in osteoblast/clast formation	Anabolic and antiresorptive	Phase I
Calcium-sensing receptor antagonists (calcylitics)	Ronacaleret (SB-751689) MK-5442	Alter calcium/PTH homeostasis by stimulating PTH secretion despite calcium serum levels	Anabolic	Phase II, discontinued phase II
Statins	Simvastatin Lovastatin Rosuvastatin Fluvastatin	3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitors	Anabolic	Preclinical Preclinical Phase III Preclinical

^*Table information was compiled from [11, 16, 17, 19, 22, 26, 29, 31, 36, 37, 39, 42, 44, 50, 53–66]