Osteoporotic fracture and parathyroid hormone

Abstract

Osteoporosis and age-related bone loss is associated with changes in bone remodeling characterized by decreased bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Stimulating the function of bone-forming osteoblasts, is the preferred pharmacological intervention for osteoporosis. Recombinant parathyroid hormone (PTH), PTH(1-34), is an anabolic agent with proven benefits to bone strength and has been characterized as a potential therapy for skeletal repair. In spite of PTH's clinical use, safety is a major consideration for long-term treatment. Studies have demonstrated that intermittent PTH treatment enhances and accelerates the skeletal repair process via a number of mechanisms. Recent research into the molecular mechanism of PTH action on bone tissue has led to the development of PTH analogs to control osteoporotic fractures. This review summarizes a number of advances made in the field of PTH and bone fracture to combat these injuries in humans and in animal models. The ultimate goal of providing an alternative to PTH, currently the sole anabolic therapy in clinical use, to promote bone formation and improve bone strength in the aging population is yet to be achieved.

Keywords: Emerging therapies; Fracture repair; Osteoporosis; Parathyroid hormone; Parathyroid hormone-1 receptor.

Figure 1

Current and future therapies for osteoporotic fractures[107-109]. SERMs: Selective estrogen receptor modulators; RANKL: Ab-receptor activator of nuclear factor ЌB antibody; Wnt: Wingless signaling pathway; CAM: Cell adhesion molecules; IGF: Insulin growth factor, LC: L-carnitine; Iso-V-LC: Isovaleryl-L-carnitine; MMP: Matrix metalloproteinase; PTH: Parathyroid hormone; LRP: LDL receptor related protein receptor; SARM: Selective androgen receptor modulators.

Figure 2

Effect of parathyroid hormone on bone cells.