Clinical Research Directory

Inclusion Criteria: 1. The subject is a postmenopausal woman aged 60 years or older at screening. 2. The subject has provided written informed consent before any trial-specific procedure is performed. 3. The subject has osteoporosis at screening defined as a T-score of -2.5 or lower at the total hip or lumbar spine (L1-L4) on central reader confirmed bone densitometry by DXA. 4. The subject is at high fracture risk, defined by at least one of the following: a previous low-trauma fracture after age 50 years (excluding skull, face, fingers and toes); FRAX probability at or above the age-specific Swedish intervention threshold (using Nordic and Nordic borne calculations, as appropriate) in use at screening. 5. Corrected plasma calcium or ionized calcium is within the local reference range before randomization. 6. Serum 25-hydroxyvitamin D concentration ≥50 nmol/L before randomization. 7. Adequate renal function for zoledronic acid treatment, defined as creatinine clearance ≥35 mL/min calculated using the clinical trial center specified calculation procedure (e.g. the Cockcroft-Gault equation) before randomization. 8. The subject is able and willing, in the investigator's judgment, to comply with the trial procedures and attend scheduled visits. 9. For participants entering the extension, separate written extension consent is obtained before any extension-specific procedure is performed. Exclusion Criteria: 1. Severe osteoporosis, defined as total hip or lumbar spine T-score \< -3.5 and/or prevalent grade 2 or grade 3 vertebral fracture. 2. Previous myocardial infarction or stroke at any time before screening. 3. Transient ischemic attack, unstable angina, coronary or major peripheral revascularization within 12 months before screening, decompensated heart failure, uncontrolled clinically relevant arrhythmia, or any cardiovascular condition that in the investigator's judgment confers unacceptably high risk of a major adverse cardiovascular event during study participation. 4. Use of intravenous bisphosphonate therapy or teriparatide within 3 years before randomization. 5. Use of oral bisphosphonate or denosumab within 12 months before randomization. 6. Any previous use of romosozumab. 7. Use of systemic estrogen, selective estrogen receptor modulator within 3 months. 8. Use of oral glucocorticoids for more than 14 consecutive days during the 6 months before screening. 9. Known metabolic bone disease other than postmenopausal osteoporosis, including but not limited to Pagets disease, osteomalacia, untreated hyperparathyroidism, osteogenesis imperfecta, or active renal osteodystrophy. 10. Creatinine clearance below 35 mL/min, rapidly deteriorating renal function, or another renal condition that makes zoledronic acid unsafe. 11. Hypocalcaemia (ionized calcium \<1.15 mmol/l or total albumin corrected calcium of \<2.15 mmol/l) or vitamin D 25-OH-vit-D \<50nmol/l, not corrected before randomization. 12. Unexplained serum alkaline phosphatase \>2 times the local upper limit of normal. 13. Malignancy within the last 5 years, except adequately treated basal-cell carcinoma of the skin, squamous-cell carcinoma in situ of the skin, or cervical carcinoma in situ. 14. Current osteonecrosis of the jaw, unhealed oral or jaw lesions, active dental or jaw infection, or planned invasive dental extraction/implant procedure that has not been completed and healed before randomization, if considered by the investigator to represent a contraindication or unacceptable risk for treatment with romosozumab, denosumab or zoledronic acid. 15. Known hypersensitivity or contraindication to romosozumab, denosumab, zoledronic acid, calcium supplementation, or vitamin D supplementation that cannot be safely managed under the protocol. 16. Inability to undergo protocol DXA/VFA reliably, for example because of body habitus exceeding scanner limits, inability to position safely, or interfering hardware or artefacts that prevent valid endpoint assessment. 17. Current participation, or recent participation within 30 days or five half-lives (whichever is longer), in another interventional clinical trial that could affect safety or data interpretation. 18. Any other medical, psychiatric, social or logistical condition that, in the investigators opinion, makes participation unsafe or would compromise protocol adherence or data reliability.