Plain vitamin D or alfacalcidol as follow-up treatment of postmenopausal osteoporosis after continuous long-term once weekly bisphosphonate intake

Zusammenfassung

Eine langjährige orale Bisphosphonat (BP)– Behandlung der Osteoporose kann durch übermäßige Suppression des Knochenumbaues negative Effekte auf die Knochenqualität haben. Es gibt bislang keine verbindlichen Empfehlungen zur Anwendungsdauer der BP, aber eine Therapieunterbrechung nach etwa fünf Jahren wird heute überwiegend angeraten. Bezüglich anschließenden Folgebehandlung gibt es allerdings auch kaum publizierte wissenschaftliche Daten. Wir haben in einer zweijährigen Studie an 85 Frauen mit postmenopausaler Osteoporose nach einer mittleren BP-Einnahmedauer von 4,2 Jahren zwei verschiedene Folge behandlungen vergleichend untersucht: Gruppe A (n = 42) erhielt 800 IE natürliches Vitamin D + 1200 mg Kalzium pro Tag, Gruppe B (n = 43) 1 µg Alfacalcidol + 500 mg Kalzium pro Tag. Primärer Endpunkt war die Änderung der Knochenmineraldichte (BMD) nach 12 und 24 Monaten. Weitere Endpunkte waren neu auftretende Stürze und Frakturen, Rückenschmerz (VAS 0–10) und unerwünschte Therapieeffekte. Zwischen den beiden Gruppen bestanden keine Unterschiede in den Ausgangscharakteristika Alter, Body-Mass-Index, Größenverlust, BMD, Rückenschmerz-Score und der Anzahl vorbestehender Stürze und Frakturen. In Gruppe A änderten sich die BMD-Werte an der LWS nicht signifikant während der zwei Jahre Follow-up nach Absetzen der BPEinnahme. Dagegen zeigte sich in Gruppe B für die LWS ein signifikanter Anstieg von 2,1 % (B vs. A p < 0,01). An den zwei Femurmessorten fanden wir leichte Abnahmen in der Vitamin-D-Gruppe und einen signifikanten Anstieg unter Alfacalcidol. Die mittlere Anzahl von Stürzen pro Patient blieb unverändert in Gruppe A und nahm signifikant ab in Gruppe B (p < 0,05). Die Anzahl der Patienten mit neuen Wirbelfrakturen unterschied sich nach zwei Jahren nicht zwischen beiden Therapiegruppen, während die Inzidenz von nichtvertebralen Frakturen in der Alfacalcidol-Gruppe signifikant niedriger ausfiel (p < 0,05). Des Weiteren fand sich eine signifikant stärkere Verminderung der Rückenschmerzen bei den Patienten unter Alfacalcidol- Behandlung. Bezüglich der Häufigkeit unerwünschter Wirkungen fand sich kein Unterschied zwischen den beiden Gruppen. Die Ergebnisse zeigen, dass eine Therapieumstellung nach langzeitiger BP-Anwendung bei postmenopausaler Osteoporose auf Alfacalcidol der Nachbehandlung mit natürlichem Vitamin D überlegen ist.

Summary

Long-term oral bisphosphonate (BP) therapy of osteoporosis may be associated with negative effects on bone quality due to oversuppression of bone turnover. Although clear recommendations regarding the duration of the use of bisphosphonates are not available, a “drug holiday” after about five years of treatment is today generally recommended. There is however very limited experience with follow-up treatments after BP-therapy. We performed a two year study comparing two different follow-up treatments in 85 women with postmenopausal osteoporosis after an average oral BP intake of 4.2 years. Group A (n = 42) received plain vitamin D 800 IU + calcium 1200 mg/d, group B (n = 43) alfacalcidol 1 µg + calcium 500 mg/d. Primary endpoint were changes of bone mineral density (BMD) after 12 and 24 months. Further endpoints were incident falls and fractures, back pain (VAS 0–10) and adverse events. The two groups were well matched concerning mean age, mean body mass index, loss of height versus young adulthood and there were no significant differences in average BMD values, numbers of prevalent falls or fractures and mean back pain score. BMD at the lumbar spine did not change significantly during the two years of follow-up after cessation of BP-therapy in group A, but increased significantly in group B by +2.1 % (B vs. A p < 0.01). At the two femur sites we found a slight decrease with plain vitamin D and a significant increase in the alfacalcidol group. The number of falls per patient year remained unchanged in group A but was reduced significantly in the patients of group B treated with the active analogue alfacalcidol (p < 0.05). The number of patients with new vertebral fractures was not different between A and B after two years but there was a significantly lower rate of non-vertebral fractures in the alfacalcidol group (p < 0.05). Furthermore there was a significantly stronger decrease in average back pain in patients receiving alfacalcidol. The numbers of adverse events did not differ between the two follow-up groups. The data show that switching long term bis phosponates treatment of postmenopausal osteoporosis to alfacalcidol is superior to a subsequent treatment with plain vitamin D.

Schlüsselwörter

Osteoporose - Bisphosphonate - Therapiepause - Folgetherapie - Vitamin D - Alfacalcidol

Keywords

Osteoporosis - bisphosphonates - drug holiday - follow-up-treatment - vitamin D - Alfacalcidol

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