Parathyroid hormone and leptin – new peptides, expanding clinical prospects

Abstract

There are three injectable and one oral bone-building (i.e., bone anabolic) parathyroid hormone (PTH) peptides. One of the four, Lilly’s injectable teriparatide (Forteo™), is currently being used, and the other three are in clinical trials. They are being used or assessed only for treating postmenopausal osteo-porosis. However, their potential clinical targets now extend far beyond osteoporosis. They can accelerate the mending of even severe non-union fractures; they will probably be used to strengthen the anchorage of pros-theses to bone; they have been shown to treat psoriasis that has resisted other treatments; they can increase the size of haematopoietic stem cell proliferation and accelerate the endogenous repopulation or repopulation by donor transplants of bone marrow depleted by chemotherapeutic drugs; and they may prevent vascular ossification. Leptin, a member of the cytokine superfamily has a PTH-like osteogenic activity and may even partly mediate PTH action. But leptin has two drawbacks that cloud its therapeutic future. First, apart from directly stimulating osteoblastic cells, it targets cells in the hypothalamic ventromedial nuclei and through them it reduces oestrogenic activity by promoting osteoblast-suppressing adrenergic activity. Second, it stimulates vascular and heart valve ossification, which leads to such events as heart failure and diabetic limb amputations.

• atherosclerosis
• bone marrow
• diabetes
• fractures
• hypothalamus
• keratinocytes
• leptin
• orthopaedic implants
• osteoporosis
• psoriasis
• PTH
• PTHrP
• PTHr1 receptor
• vascular ossification