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Lorenz C Hofbauer, Christine Hamann and Peter R Ebeling

Abstract

Secondary osteoporosis is characterized by low bone mass with microarchitectural alterations in bone leading to fragility fractures in the presence of an underlying disease or medication. Scenarios that are highly suspicious for secondary osteoporosis include fragility fractures in younger men or premenopausal women, very low bone mineral density (BMD) values, and fractures despite anti-osteoporotic therapy. An open-minded approach with a detailed history and physical examination combined with first-line laboratory tests are aimed at identifying clinical risk factors for fractures, osteoporosis-inducing drugs, and underlying endocrine, gastrointestinal, hematologic, or rheumatic diseases, which then need to be confirmed by specific and/or more invasive tests. BMD should be assessed with bone densitometry at the hip and spine. Lateral X-rays of the thoracic and lumbar spine should be performed to identify or exclude prevalent vertebral fractures which may be clinically silent. Management of secondary osteoporosis includes treatment of the underlying disease, modification of medications known to affect the skeleton, and specific anti-osteoporotic therapy. Calcium and vitamin D supplementation should be initiated with doses that result in normocalcemia and serum 25-hydroxyvitamin D concentrations of at least 30 ng/ml. Oral and i.v. bisphosphonates are effective and safe drugs for most forms of secondary osteoporosis. Severe osteoporosis may require the use of teriparatide.

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Elena Tsourdi, Tilman D Rachner, Martina Rauner, Christine Hamann and Lorenz C Hofbauer

Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

Free access

Elena Tsourdi, Tilman D Rachner, Martina Rauner, Christine Hamann and Lorenz C Hofbauer