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Osteologie 2010; 19(02): 149-156
DOI: 10.1055/s-0037-1619936
Sexualhormone und Knochenstoffwechsel
Schattauer GmbH

Stellenwert der SERMs in der Osteoporosetherapie

The role of SERMs in the treatment of osteoporosis
V. Ziller
1   Schwerpunkt gynäkologische Endokrinologie, Reproduktionsmedizin und Osteologie, Klinik für Gynäkologie, gynäkologische Endokrinologie und Onkologie, Philipps-Universität Marburg
,
P. Hadji
1   Schwerpunkt gynäkologische Endokrinologie, Reproduktionsmedizin und Osteologie, Klinik für Gynäkologie, gynäkologische Endokrinologie und Onkologie, Philipps-Universität Marburg
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Further Information

Publication History

eingereicht: 08 January 2010

angenommen: 11 January 2010

Publication Date:
30 December 2017 (online)

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Zusammenfassung

Das Steroidhormom Östrogen ist ein intrazellulärer Schlüsselmediator verschiedenster Prozesse skelettaler, muskulärer, kardiovaskulärer, neuronaler und reproduktiver Funktionen. Ziel der Entwicklung der “Selektiven Estrogenrezeptormodulatoren” (SERM) war es, über die physiologische Signalkette des Östrogenrezeptors gewebsspezifische erwünschte Östrogen-agonistische Wirkungen am Knochenstoffwechsel sowie Östrogen-antagonistische Wirkungen am Uterus und an der Brustdrüse zu erzielen. Der erste selektive Östrogenrezeptormodulator, der im Rahmen der adjuvanten Therapie des rezeptorpositiven Mammakarzinoms in die klinische Praxis eingeführt wurde, war Tamoxifen. Neben der positiven Wirkung auf die Rezidivrate beim Mammakarzinom zeigt das Profil von Tamoxifen einen ebenfalls protektiven Effekt auf den Knochenstoffwechsel und die Knochenmineraldichte sowie auf den Fettstoffwechsel postmenopausaler Frauen. Bei Raloxifen handelt es sich um die erste, seit 1998 für die Prävention und Therapie der postmenopausalen Osteoporose zugelassene Substanz aus der Gruppe der SERM. Am Knochen führt Raloxifen über eine Hemmung der Osteoklasten zu einer Umkehrung des progredienten, postmenopausalen Knochenmasseverlustes, was sich an der Reduktion der Serumspiegel der Resorptionsmarker des Knochenstoffwechsels (CTX und NTX) in den physiologischen, präme- nopausalen Bereich ablesen lässt. Die Knochenmineraldichte an Lendenwirbelsäule und Oberschenkelhals nimmt zu, das Risiko vertebraler Frakturen wird signifikant gesenkt. Die partiell Östrogen-antagonistische Wirkung des Raloxifen am Brustdrüsengewebe zeigt sich in einer signifikanten Senkung des Brustkrebsrisikos bei Osteoporosepatientinnen und bei Frauen mit erhöhtem Brustkrebsrisiko ohne eine relevante Wirkung auf das Endometrium. Die häufigsten, für die Praxis relevanten Nebenwirkungen sind die leicht erhöhte Rate von Hitzewallungen sowie Thrombosen. Zusammenfassend zeigt sich ein eindeutig positives Nutzen-Risiko-Verhältnis, so dass mit Raloxifen ein effektives Mittel zur Therapie der postmenopausalen Osteoporose zur Verfügung steht. Weitere SERM der dritten Generation wie Lasofoxifen, Bazedoxifen, Arzoxifen etc. befinden sich derzeit in klinischer Erprobung. Lasofoxifen ist seit Februar 2009, Bazedoxifen seit April 2009 zur Therapie der postmenopausalen Osteoporose zugelassen, beide sind derzeit noch nicht im Handel. Ein weiterer neuer Ansatz ist die Kombination aus Basedoxifen mit konjugiertem Östrogen, die gegebenenfalls weitere Therapieoptionen zur Prävention und Therapie der Osteoporose und anderer menopausaler Erkrankungen eröffnet.

Summary

The steroidal hormone estrogen is an intracellular key mediator of diverse processes regulating skeletal, muscular, cardiovascular, neuronal and reproductive functions. The aim of developing selective estrogen receptor modulators (SERM) was to use the physiological estrogen pathway to obtain tissue specific estrogen agonist effects on bone and estrogen antagonist effects on the breast and uterus. The first selective estrogen receptor modulator that was introduced in the adjuvant treatment of hormone receptor positive breast cancer was tamoxifen. In addition to the positive effects on the recurrence rates of breast cancer, tamoxifen also showed positive effects on bone metabolism and bone mineral density as well as on lipid profiles in postmenopausal women. Raloxifene was the first SERM, which was introduced in 1998, for the therapy and the prevention of postmenopausal osteoporosis. In bone, raloxifene leads to an inhibition of osteoclast function, which is reflected in a reduction of bone resorption markers (CTX and NTX) to the pre-menopausal range. Bone mineral density at the lumbar spine and the hip increases and the risk of vertebral fracture is significantly reduced. In breast tissue, the estrogen antagonistic effects lead to a significant reduction in the risk of breast cancer in osteoporotic patients and women at a high risk of breast cancer, without having any relevant effects on the endometrium. The two major clinically relevant side effects are the increased risk for hot flushes and thromboembolic events. In summary, raloxifene comprises a positive risk benefit ratio and is therefore an effective treatment for postmenopausal osteoporosis. Further third generation SERM, such as lasofoxifene and arzoxifene etc. are currently being investigated in large clinical trials. Recently, lasofoxifene and bazedoxifene received approval for the treatment of postmenopausal osteoporosis (February and April 2009, respectively) but are not yet available. A new, promising approach using the combination of bazedoxifene and conjugated estrogen for the treatment of hot flushes as well as postmenopausal osteoporosis is currently being investigated.

Schlüsselwörter

SERM - Osteoporose - Östrogen-Rezeptor - Mammakarzinom

Keywords

SERM - osteoporosis - estrogen receptor - breast cancer
 

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