Vescini Fabio, Grimaldi Franco
Endocrinology and Metabolism Unit, University-Hospital "Santa Maria della Misericordia", Udine, Italy.
Clin Cases Miner Bone Metab. 2012 Jan;9(1):31-6. Epub 2012 May 29.
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.
骨质疏松性骨折，尤其是在老年人中，是一个健康问题，因为它们与发病率和死亡率增加以及社会经济负担加重相关。在过去20年里，人们为降低骨折风险付出了巨大努力，现在有许多药物可用于此目的，但骨质疏松症仍被视为衰老过程中不可避免的后果。骨质疏松性骨折最常发生在脊柱和髋部，腕部、骨盆和上臂的发生率较低。它们与显著的发病率相关，髋部和脊柱的骨折还与额外的死亡率相关。骨质疏松症的正确诊断和适当治疗可以降低骨折风险。在过去几年里，除了众所周知的抗吸收剂（如双膦酸盐、雌激素和选择性雌激素受体调节剂）外，甲状旁腺激素（PTH）的合成代谢疗法已可用于治疗严重骨质疏松症。人重组完整甲状旁腺激素（PTH 1-84）和人重组PTH肽1-34（特立帕肽）属于这类药物。本文将综述PTH的作用以及PTH 1-84在降低骨折风险和促进骨折愈合方面的合成代谢作用。尽管在原发性甲状旁腺功能亢进中骨分解代谢强于骨合成代谢，但PTH仍然是成骨细胞的有效刺激剂，当以低剂量和间歇性给药时，其合成代谢特性可见。间歇性PTH比骨吸收能更早、更大程度地刺激骨形成，从而形成所谓的“合成代谢窗口”。TOP研究表明，PTH 1-84能够降低患有椎体骨折患者发生新骨折的风险，但在基线时无骨折的女性中，对首次骨折的发生率也有同样的效果。此外，PTH使骨矿物质密度持续增加，尤其是在松质骨中。PTH对骨折愈合也有积极作用，包括缩短骨折修复时间以及改善骨痂形成和发育的所有参数。尽管大多数证据是在动物身上获得的，但最近一些人体研究至少部分证实了这些发现。在患有骨质疏松症和骨折的老年患者中，PTH治疗可能会缩短愈合时间，改善临床结果，减少固定时间以及并发症风险。
