Bisphosphonates in multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder - an alternative therapeutic approach

Karin Pichler; Daniela Karall; Dieter Kotzot; Elisabeth Steichen-Gersdorf; Alexandra Rümmele-Waibel; Laureane Mittaz-Crettol; Julia Wanschitz; Luisa Bonafé; Kathrin Maurer; Andrea Superti-Furga; Sabine Scholl-Bürgi

doi:10.1038/srep34017

Bisphosphonates in multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder - an alternative therapeutic approach

Sci Rep. 2016 Sep 30:6:34017. doi: 10.1038/srep34017.

Affiliations

¹ Clinic for Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
² Department of Pediatrics, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
³ Department of Human Genetics, Medical University of Innsbruck, Peter-Mayr-Strasse 1/1, A-6020 Innsbruck, Austria.
⁴ Department of Pediatrics, Dornbirn General Hospital, Lustenauerstrasse 4, A-6850 Dornbirn, Austria.
⁵ Center for Molecular Diseases, Lausanne University Hospital, Av. P. Decker 2, CH-1011 Lausanne, Switzerland.
⁶ Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
⁷ Department of Radiology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
⁸ Department of Pediatrics, University of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland.

Abstract

Multicentric osteolysis, nodulosis and arthropathy (MONA) spectrum disorder is a rare inherited progressive skeletal disorder caused by mutations in the matrix metalloproteinase 2 (MMP2) gene. Treatment options are limited. Herein we present successful bisphosphonate therapy in three affected patients. Patients were treated with bisphosphonates (either pamidronate or zoledronate) for different time periods. The following outcome variables were assessed: skeletal pain, range of motion, bone densitometry, internal medical problems as well as neurocognitive function. Skeletal pain was dramatically reduced in all patients soon after initiation of therapy and bone mineral density increased. Range of motion did not significantly improve. One patient is still able to walk with aids at the age of 14 years. Neurocognitive development was normal in all patients. Bisphosphonate therapy was effective especially in controlling skeletal pain in MONA spectrum disorder. Early initiation of treatment seems to be particularly important in order to achieve the best possible outcome.