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

    Resumé

    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
    Aslan, Derya ; Dahl Andersen, Mille ; Gede, Lene Bjerring ; de Franca, Tine Kellemann ; Rubek Jørgensen, Sara ; Schwarz, Peter ; Jørgensen, Niklas Rye. / Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans. I: Scandinavian Journal of Clinical & Laboratory Investigation. 2012 ; Bind 72, Nr. 1. s. 14-22.
    @article{6750227191724161b4a3f3defad35c8c,
    title = "Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans",
    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.",
    author = "Derya Aslan and {Dahl Andersen}, Mille and Gede, {Lene Bjerring} and {de Franca}, {Tine Kellemann} and {Rubek J{\o}rgensen}, Sara and Peter Schwarz and J{\o}rgensen, {Niklas Rye}",
    year = "2012",
    doi = "10.3109/00365513.2011.624631",
    language = "English",
    volume = "72",
    pages = "14--22",
    journal = "Scandinavian Journal of Clinical & Laboratory Investigation",
    issn = "0036-5513",
    publisher = "Taylor & Francis",
    number = "1",

    }

    Aslan, D, Dahl Andersen, M, Gede, LB, de Franca, TK, Rubek Jørgensen, S, Schwarz, P & Jørgensen, NR 2012, 'Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans' Scandinavian Journal of Clinical & Laboratory Investigation, bind 72, nr. 1, s. 14-22. https://doi.org/10.3109/00365513.2011.624631

    Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans. / Aslan, Derya; Dahl Andersen, Mille ; Gede, Lene Bjerring; de Franca, Tine Kellemann; Rubek Jørgensen, Sara ; Schwarz, Peter; Jørgensen, Niklas Rye.

    I: Scandinavian Journal of Clinical & Laboratory Investigation, Bind 72, Nr. 1, 2012, s. 14-22.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans

    AU - Aslan, Derya

    AU - Dahl Andersen, Mille

    AU - Gede, Lene Bjerring

    AU - de Franca, Tine Kellemann

    AU - Rubek Jørgensen, Sara

    AU - Schwarz, Peter

    AU - Jørgensen, Niklas Rye

    PY - 2012

    Y1 - 2012

    N2 - 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.

    AB - 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.

    U2 - 10.3109/00365513.2011.624631

    DO - 10.3109/00365513.2011.624631

    M3 - Journal article

    VL - 72

    SP - 14

    EP - 22

    JO - Scandinavian Journal of Clinical & Laboratory Investigation

    JF - Scandinavian Journal of Clinical & Laboratory Investigation

    SN - 0036-5513

    IS - 1

    ER -