Anne Sølling, MD, PhD

Aarhus University Hospital, Dept. of Endocrinology and Internal Medicine

Title of project

Denosumab for the treatment of osteoporosis – DENOPOS


Denosumab is an important treatment modality in the management of osteoporosis and fracture risk. Of the antiresorptive treatments approved, denosumab provides the best bone mineral density (BMD) improvement on treatment and a strong protection against fractures. However, the treatment effect on bone turnover and BMD has been demonstrated to be reversible and it is therefore important to investigate what the underlying mechanisms for this rebound are, as they may be key to optimizing and individualizing the management of discontinuation of denosumab in the clinic. In addition, it will be equally important to understand the long-term consequences and possible measures to counteract these consequences of discontinuation of denosumab. In ZOLARMAB 2 we
will investigate the underlying pathophysiological mechanisms occurring when discontinuing deno-sumab. We will investigate, if multiple infusions of zoledronate can prevent the rebound activation of bone turnover and the subsequent bone loss in patients previously treated with denosumab and if there is difference between infusing zoledronate at fixed time-points after the last injection of denosumab or when bone turnover is increased. The 3-year outcome of the ZOLARMAB 2 study will be included in the DENOPOS.

Preclinical studies and small, observational studies have indicated that denosumab may have beneficial effects on muscle strength and insulin sensitivity. Muscle mass and strength as well as diabetes are important risk factors for both falls and fractures and therefore of great importance for patients with osteoporosis. In DENMUSIN, we will investigate the effect of denosumab on muscle mass and muscle strength and insulin sensitivity. The results of this study will provide information about additional potential benefits of denosumab will help qualify the choice of treatment in the individual patients.

Improvement of the understanding of the use of denosumab in clinical practice and the consequence of poor adherence and compliance as well as discontinuation of denosumab will be important for optimizing the use of denosumab in the long-term management of osteoporosis. In DENEPI, we will evaluate the duration of treatment, adherence and compliance, and fracture risk during denosumab treatment and after discontinuation of denosumab using Danish registries.

Anne Sølling, MD, PhD

20%-financed clinical postdoctoral fellowship

Principal investigator

Bente Langdahl, Aarhus University Hospital, Dept. of Endocrinology and Internal Medicine

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