Endocrine Abstracts

Bisphosphonates, because of their efficacy, safety and ease of administration, are accepted as first-line therapy for osteoporosis worldwide. They decrease the rate of bone resorption but have also distinct pharmacological properties including preferential uptake in the skeleton, primarily at sites with increased bone remodeling, and long-term retention in bone. There are differences among bisphosphonates both in their affinity for bone as well as in their antiresorptive poten...

Sclerostin is an osteocyte-expressed, extracellular cystine-knot protein that is lacking in patients with sclerosteosis, a rare condition characterized by excessive bone formation. Sclerosteosis patients exhibit very high bone mass (lumbar spine Z scores up to +14) and are anecdotally resistant to bone fracture. Homozygous patients commonly develop symptoms associated with cranial nerve entrapment from excessive bone formation but do not show signs of heterotopic bone formatio...

Current osteoporosis therapy is predominantly ‘anti-resorptive’. Oestrogen antagonises the action of RANK-Ligand, a potent cytokine for osteoclast differentiation. Amino-bisphosphonates inhibit the HMG CoA reductase pathway, reducing osteoclast activity and viability, while denosumab is a human monoclonal antibody that binds to RANKL. Denosumab treatment reduces fractures. In a study of 7868 women with postmenopausal osteoporosis, denosumab reduced new radiographic v...