Endocrine Abstracts

Over past years various treatment options for osteoporosis have become available and withdrawn due to side effects or insufficient efficacy. This summary reviews sequential and combination therapy for osteoporosis with the currently approved first line treatments such as potent antiresorbtive (nitrogen-containing bisphosphonates (BP), denosumab (DM)) or anabolic agents (teriparatide, abaloparatide). We assume that all medications are taken with vitamin D and calcium supplements. The differences in mechanisms of action between BP and DM provide explanations in clinical outcome and opportunities in sequential therapy. BP attach to hydroxyapatite preferably on metabolically active bone surfaces, where they are ‘ingested’ by osteoclasts and promote osteoclast apoptosis. BP can remain in bone tissue for up to 10 years. DM acts by binding to and inhibiting RANKL in circulation, leading to the loss of mature osteoclast formation. DM accesses every bone remodeling unit within circulation and its distribution does not depend on the activity of bone remodeling. In clinical trials, DM given after BP continued to increase bone mineral density (BMD) and produced significantly greater gains in BMD at all measured sites when compared to all BP. Consequently, DM can be given after BP when the treatment goal in BMD gain is not achieved. However, BP also should be given after DM discontinuation to prevent BMD loss. Both VERO and ARCH studies proved that anabolic treatment for osteoporosis is more effective than BP at preventing vertebral fractures in a high risk population (with previous vertebral fractures) in both treatment-naïve or BP treated patients. Consequently, anabolic treatment should be considered either as a first-line treatment in patients with previous vertebral fractures or in case a low-traumatic fracture occurs while on BP treatment. However, the duration of anabolic treatment is limited and requires antiresorbtive medication after discontinuation. The sequential treatment approach in osteoporosis is slightly limited with the result of DATA study, which showed that switching to teriparatide after DM lead to BMD loss and should be considered with caution. According to the DATA study, teriparatide combined with DM gives better BMD gain than both treatments alone. This is the only currently recommended approach using combined treatment in osteoporosis which remains controversial because of the high cost and lack of evidence regarding antifracture benefit.