New approaches to the treatment of osteoporosis.
Under physiological conditions, maintenance of skeletal mass is the result of a tightly coupled process of bone formation and bone resorption. Disease states, osteoporosis included, arise when this delicate balance is disrupted such as in menopause, when estrogen levels decrease dramatically corresponding with the cessation of ovarian function. Current therapies for the treatment of osteoporosis, including estrogen replacement therapy, selective estrogen receptor modulators and bisphosphonates, are primarily based on blunting the resorption component of bone homeostasis. Although selective estrogen receptor modulators offer bone protection without the side effects of estrogen replacement therapy, there are some areas of improvement for the current generation of selective estrogen receptor modulators; particularly in reducing their antagonistic properties in the central nervous system that lead to vasomotor symptoms. There are few therapies that are focused on increasing bone formation, but they offer promising avenues in which to expand the repertoire of drugs to restore bone mass. Selective androgen receptor modulators, parathyroid hormone analogs, oxytocin analogs and statins, all with improved pharmacological properties in bone, are among the potential approaches to eliciting anabolic effects in the skeleton.
López
F J
FJ
Ligand Pharmaceuticals Inc, San Diego, CA 92121, USA. FLopez@ligand.com
D000728:Androgens / Q000627:therapeutic use; D002117:Calcitriol / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000627:therapeutic use; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D005260:Female; D006023:Glycoproteins / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D015394:Molecular Structure; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D053244:Osteoprotegerin; D010121:Oxytocin / Q000627:therapeutic use; D018160:Receptors, Cytoplasmic and Nuclear / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor
D000728:Androgens; D004164:Diphosphonates; D020847:Estrogen Receptor Modulators; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D010121:Oxytocin; D002117:Calcitriol