PTH 1-84: bone rebuilding as a target for the therapy of severe osteoporosis

Osteoporotic fractures, especially in elderly people, represent a health concern as they are associated with increased morbidity and mortality together with an increased economic burden for the society. During the past 20 years a great effort has been done in order to reduce the risk of fracture and many drugs are now available for this purpose, but osteoporosis is still regarded as an inevitable consequences of the aging process. Osteoporotic fractures occur most frequently in the spine and hip and with lower frequency in the wrist, pelvis, and upper arm. They are associated with significant morbidity and those of the hip and spine are also associated with excess mortality. The correct diagnosis and the adequate treatment of osteoporosis can reduce fracture risk. Together with well known anti-resorptive agents (like bisphosphonates, oestrogen and selective oestrogen receptor modulators) in the past few years anabolic therapy with parathyroid hormone (PTH) has become available for the treatment of severe osteoporosis. Human recombinant intact parathyroid hormone (PTH 1-84) and human recombinant PTH peptide 1-34 (Teriparatide) belong to this group of agents. This paper will review PTH actions together with the anabolic effect of PTH 1-84 both in reducing fracture risk and in promoting fracture healing. Although in primary hyperparathyroidism bone catabolism prevails on bone anabolism, PTH remains a potent stimulator of osteoblasts and its anabolic properties can be seen when it is given at a low dosage and intermittently. Intermittent PTH can stimulate bone formation to a greater extent and earlier than bone resorption, thus creating the so called "anabolic window". The TOP study demonstrated that PTH 1-84 is able to reduce the risk of a new fracture in patients with prevalent vertebral fractures, but the same effect was also seen on the incidence of the first fracture in women without fractures at baseline. Moreover PTH produced a continuous increase of bone mineral density, particularly in the cancellous bone. A positive effect of PTH has been described also on fracture healing, consisting both by a shortened time for fracture repair and by an improving of all the parameters of callus formation and development. Although most of the evidence has been obtained in animals some recent studies in humans confirmed, at least in part, these findings. In elderly patients with osteoporosis and fractures PTH treatment may reduce the healing time, improve clinical outcomes and reduce the time of immobilization together with the risk of complications.