Classification
| Agent | Mechanism | Notes |
|---|---|---|
| Bisphosphonates | Bind hydroxyapatite and cause osteoclast apoptosis | First line. See Bisphosphonates |
| Denosumab | Monoclonal antibody against RANKL | 60 mg every 6 months. Stopping causes rebound vertebral fractures unless followed by a bisphosphonate |
| Raloxifene | Selective oestrogen receptor modulator | Reduces vertebral fractures. Increases VTE risk |
| Oestrogen | Hormone replacement | Fracture benefit balanced against breast cancer and VTE risk |
| Calcitonin | Inhibits osteoclasts directly | Short term analgesia after vertebral fracture |
Complications
- Osteonecrosis of the jaw, higher with high dose cancer regimens
- Atypical femoral fractures with long term use
- Hypocalcaemia, check vitamin D before starting
- Atypical femoral fractures are transverse, lateral cortex fractures of the subtrochanteric or diaphyseal femur, often with prodromal thigh pain
- Image both femurs and stop the bisphosphonate after an atypical fracture
- Acute phase reaction with fever and myalgia after the first zoledronic acid infusion
- Oesophagitis with oral bisphosphonates, taken fasting and upright
Clinical Use
- Start treatment after a minimal trauma fracture, as most patients go untreated
- PBS listing in Australia covers a minimal trauma fracture or a T score of minus 2.5 or less in older patients
- Zoledronic acid given after hip fracture surgery reduced new fractures and mortality (HORIZON Recurrent Fracture Trial)
- Consider a drug holiday after 5 years of oral or 3 years of intravenous bisphosphonate in lower risk patients
- Dental review before starting in patients with poor dentition
Anabolic Agents
- Teriparatide, intermittent PTH analogue that stimulates formation
- Romosozumab, anti-sclerostin antibody that increases formation and reduces resorption
Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 10 October 2026.