Treatment of Osteoporosis at Very High Risk of Fracture
Patients with osteoporosis who meet one or more very-high-risk criteria represent a distinct clinical sub-population. Guidelines distinguish this group from those at high risk and recommend a specific first-line therapeutic strategy tailored to their fracture risk burden.
Very High-Risk Defining Features
- Multiple vertebral fractures
- Bone mineral density T-score ≤−3.0 to −3.5
- Fragility fracture within the previous one to two years
- High-dose glucocorticoids (>7.5 mg/day prednisolone or equivalent) sustained over three months
- FRAX 10-year major osteoporotic fracture probability >30%
- FRAX 10-year hip fracture probability >4.5%
Treatment Goals
The objective is to reach a personalised total hip T-score target. In this very-high-risk group, a higher T-score target is recommended than for patients at lower risk, with defined minimum thresholds for BMD improvement at both the total hip and lumbar spine over three years. BMD is reassessed at regular intervals during therapy.
Therapeutic Approach
All major guidelines converge on an osteoanabolic-first strategy as the preferred initial approach for patients at very high fracture risk — in contrast to the anti-resorptive first line recommended for patients at high (but not very high) risk. Calcium and vitamin D supplementation, together with structured physical activity, form part of the overall regimen.
Specific agent selection, sequencing, duration, monitoring schedule, and the full regimen are available in the structured protocol →
References
DOI: 10.1136/bmj‑2024-081250
- Features include multiple vertebral fractures, T-score ≤−3.0 to −3.5, a recent fragility fracture within the previous one to two years, high dose glucocorticoids >7.5 mg/day of prednisolone or equivalent over three months, or FRAX for MOF >30% or hip fracture >4.5% (table 2).
- All recommend anti-resorptives as first line therapy for patients at high risk and osteoanabolics for those at very high risk.
- Osteoanabolic agents preferred first line for people at very high risk: teriparatide, abaloparatide, romosozumab.
- For patients at very high risk, teriparatide, abaloparatide, or romosozumab is recommended first line in all guidelines.
- An osteoanabolic-first approach seems to be the most effective strategy in people at very high risk, rather than an osteoanabolic agent being considered as second or third line treatment after other therapies have failed.
- For postmenopausal women and older men, aim for total elemental calcium 1000–1200 mg/day and vitamin D 800–1000 IU/day.
- In people at higher risk, such as older people with history of previous fracture, a higher target of −2.0 to −1.5 might be advisable, as supported by evidence from the FREEDOM (denosumab) and ARCH (romosozumab, alendronate) trials, as well as robust meta-regression data showing continued reduction in fracture risk up to a T-score of −1.5 at the total hip.
- Experts recommend an improvement in total hip T-score of at least 0.2 units (3%) and in lumbar spine T-score of at least 0.5 units (6%), on the basis of reasonable chances of attaining such increments over three years by most therapies, including anti-resorptives.
- BMD every 1–3 years on therapy.
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