Endocrine Abstracts

Osteoporosis is a common condition characterised by reduced bone mass and deteriorated bone architecture. Osteoporosis is by WHO defined as bone mineral density (BMD) T-score < -2.5 at the spine or hip. Osteoporosis is a very heterogeneous condition, ranging from asymptomatic to severe in patients with fractures, especially vertebral and hip fractures, but also other central fractures are associated with morbidity and increased mortality. Management of osteoporosis is challenging as seen by the very large diagnosis and treatment gap seen in most countries across the world. Identification of patients with osteoporosis is driven by attention to clinical risk factors, most importantly fragility fractures, family history, early menopause, smoking and other diseases or treatments that increases the risk of osteoporosis. This should be easy, however, it has proven to be difficult as many other conditions demand attention from the health care systems. Treatment of osteoporosis includes a bone healthy lifestyle (sufficient intake of calcium and vitamin D, physical activity, no smoking and limited alcohol intake) and medical treatment. Implementation of bone healthy lifestyle requires patient education. Medical treatment of osteoporosis includes antiresorptive, bone forming and dual action treatments. The antiresorptives include bisphosphonates and denosumab, the bone forming treatments includes teriparatide and abaloparatide, and the dual action treatment includes romosozumab. All of the approved treatments improve BMD and reduce fracture risk, but it has been shown in head-to-head studies that bone forming and dual action treatments improve BMD and reduce fracture risk more than antiresorptive treatments in patients with severe osteoporosis. These treatments should therefore be considered in patients at high risk of fracture. All treatments with the exception of bisphosphonates are reversible and with osteoporosis being a chronic condition most patients will need sequential treatment with these medications. Recently, the FNIH-SABRE project has demonstrated that increase in total hip BMD during treatment is a very strong predictor of the anti-fracture efficacy of any treatment. That has led to a discussion with the FDA and other regulatory authorities about possible changing the conditions for getting new treatments for osteoporosis approved, focussing more on BMD changes – this process is still ongoing. The same data, but also the clinical head-to-head trials clearly demonstrating that not all treatments are the same and bone forming and dual action treatments reduce fracture risk more rapidly and more prominently have challenged the step-wise treatment approach: all patients start with an oral bisphosphonate and are only shifted to a more potent treatment if there are indications of treatment failure. A more aggressive approach, the treat-to-target or goal-directed approach has been proposed. This approach takes the severity of osteoporosis and the actual fracture risk into consideration and suggests that patients with severe osteoporosis at high and/or imminent risk of osteoporosis should be initiated on bone forming og dual-action treatment (1).

1. Cosman F, Lewiecki EM, Eastell R, Ebeling PR, De Beur SJ, Langdahl B, Rhee Y, Fuleihan GE, Kiel DP, Schousboe JT, Borges JL, Cheung AM, Diez-Perez A, Hadji P, Tanaka S, Thomasius F, Xia W, Cummings SR. Goal-Directed Osteoporosis Treatment: ASBMR/BHOF Task Force Position Statement 2024. J Bone Miner Res. 2024 Epub.