The Optimised Use of Romozosumab Study

OPTIMIST is a two-year, randomised, active controlled, open-label, multicentre intervention trial. OPTIMIST includes 3 treatment groups each comprising combinations of romosozumab (ROMO) and zoledronate (ZOL) treatment used in standard doses (210 mg monthly (sc) and 5 mg yearly (iv), respectively). The study will investigate if it is possible to maximize the effect of romosozumab by giving it in 2 periods of 6 months interrupted by zoledronate for 12 months compared to romosozumab for 12 months uninterrupted followed by zoledronate for 12 months. The investigators will also evaluate if 6 months of romosozumab followed by 18 months of zoledronate is non-inferior to the standard regimen of romosozumab for 12 months followed by zoledronate for 12 months.

Inclusion Criteria: * Postmenopausal women (postmenopausal for at least two years) * BMD T-score \< -2.5 at lumbar spine, total hip, or femoral neck * Osteoporotic fracture within the last 3 years at the spine, hip, pelvis, humerus or forearm after the age of 50 years. Exclusion Criteria: * Osteoporosis treatment including hormone replacement therapy within the last 5 years * Metabolic bone disease * Known disorders affecting bone metabolism, e.g., uncontrolled thyrotoxicosis, liver dysfunction (baseline phosphatase higher than twice upper limit), rheumatism, severe COPD (chronic obstructive pulmonary disease), hypopituitarism, Cushing's disease * Ongoing treatment with glucocorticoids (systemic) * Estimated glomerular filtration rate (eGFR) \< 35 mL/min * Contraindications for zoledronate according to the Supplementary protection certificates (SPC) * Contraindications for romosozumab according to the SPC * For the subgroup with Jamshidi biopsies contraindications for local anaesthetics according to the SPC * For the subgroup with Jamshidi biopsies contraindications for tetracycline or doxycykline according to the SPC