Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans

Derya Aslan, Mille Dahl Andersen, Lene Bjerring Gede, Tine Kellemann de Franca, Sara Rubek Jørgensen, Peter Schwarz, Niklas Rye Jørgensen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Abstract

    Intermittent low-dose treatment with parathyroid hormone (PTH) analogues has become widely used in the treatment of severe osteoporosis. During normal physiological conditions, PTH stimulates both bone formation and resorption, and in patients with primary hyperparathyroidism, bone loss is frequent. However, development of the biochemical measurement of PTH in the 1980s led us to understand the regulation of PTH secretion and calcium metabolism which subsequently paved the way for the use of PTH as an anabolic treatment of osteoporosis as, when given intermittently, it has strong anabolic effects in bone. This could not have taken place without the basic understanding achieved by the biochemical measurements of PTH. The stimulatory effects of PTH on bone formation have been explained by the so-called ‘anabolic window’, which means that during PTH treatment, bone formation is in excess over bone resorption during the first 6–18 months. This is due to the following: (1) PTH up-regulates c-fos expression in bone cells, (2) IGF is essential for PTH's anabolic effect, (3) bone lining cells are driven to differentiate into osteoblasts, (4) mesenchymal stem cells adhesion to bone surface is enhanced, (5) PTH has a direct antiapoptotic effect on osteoblasts and (6) when PTH interferes with remodelling, the osteoblasts over-compensate, and (7) PTH also decreases sclerostin levels, thereby removing inhibition of Wnt signalling which is required for PTH's anabolic actions. Thus, the net formative effect of PTH given in intermittent treatment emerges through a complex network of pathways. In summary, the effects of PTH on bone turnover are dependent on the mode and dose of administration and studies investigating the mechanisms underlying this effect are reviewed in this article.
    OriginalsprogEngelsk
    TidsskriftScandinavian Journal of Clinical & Laboratory Investigation
    Vol/bind72
    Udgave nummer1
    Sider (fra-til)14-22
    ISSN0036-5513
    DOI
    StatusUdgivet - 2012

    Citer dette

    Aslan, D., Dahl Andersen, M., Gede, L. B., de Franca, T. K., Rubek Jørgensen, S., Schwarz, P., & Jørgensen, N. R. (2012). Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans. Scandinavian Journal of Clinical & Laboratory Investigation, 72(1), 14-22. https://doi.org/10.3109/00365513.2011.624631