Dr. Michael McClung addressed anabolic therapy in osteoporosis, with a focus on 3 options: teriparatide, abaloparatide and romosozumab.
We know that osteoporosis is a condition of low bone mass, deterioration and impaired bone strength, resulting in increased risk of fracture. Anabolic medications such as teriparatide stimulate bone formation but also increase bone resorption. Teriparatide up-regulates RANK ligand, making it a remodeling stimulator. It has been shown to increase bone mass at the spine and femoral neck, but only has modest effects at the hip. Sequencing of therapy is important: using denosumab after teriparatide has been shown to improve BMD, whereas teriparatide after denosumamb results in decreased BMD. Therefore, denosumab should be combined with teriparatide instead of stopping denosumab or switching to teriparatide.
Abaloparatide is a novel synthetic analog of human parathyroid related protein that holds promise as a new osteoporosis therapy. It can stimulate bone formation with less of the accompanying bone resorption and hypercalcemic effects that can occur with PTH. In the ACTIVE trial, abaloparatide showed a slight advantage over teriparatide. Abaloparatide was well tolerated and was associated with less hypercalcemia. It is administered as a daily SC injection for 18 months.
Romosozumab is a sclerostin inhibitor. Sclerostin is produced by osteocytes and has anti-anabolic effects on bone formation.The FRAME study reported a 73% reduction in vertebral fracture risk and a 35% reduction in clinical fracture risk with romosozumab versus placebo at 12 months. In the second year of the study, there were 25 vertebral fractures in patients who transitioned from placebo to denosumab versus 5 in those who transitioned from romosozumab to denosumab. This suggests that romosozumab does not need to be used long-term but may be used short-term to increase the benefits of other therapies.
Other possible uses for romosozumab include for states of impaired bone formation such as: glucocorticoid-induced osteoporosis, adynamic renal osteodystrophy, eating disorders such as anorexia, chronic immobilization, multiple myeloma, osteogenesis imperfecta, or in fracture healing. However, in preclinical studies, the effectiveness was not established because clinical development was abandoned due to regulatory hurdles.
In summary, anabolic treatment options are promising and may bring in an era of sequential therapy for many patients especially those in need of skeletal reconstruction or at imminent risk of fracture.