Atypical Femur Fractures Due to Drugs

Definition: an atypical femoral fracture (AFF) is a stress or insufficiency fracture of the subtrochanteric region or femoral shaft occurring with minimal or no trauma, associated with prolonged suppression of bone turnover — classically by long-term bisphosphonates, and also reported with denosumab, glucocorticoids and proton-pump inhibitors.

ASBMR major features (all five required): (i) minimal or no trauma; (ii) fracture line originates at the lateral cortex and is substantially transverse; (iii) non-comminuted or minimally comminuted; (iv) complete fractures extend through both cortices with a medial spike, incomplete fractures involve only the lateral cortex; (v) localised periosteal or endosteal thickening ("beaking" or "flaring") of the lateral cortex. Fractures of the femoral neck, intertrochanteric region with spiral extension, and pathological or periprosthetic fractures are excluded.

Minor features: generalised increase in cortical thickness of the femoral diaphysis, prodromal dull thigh or groin pain, bilaterality, delayed union, and comorbid conditions or drug exposure (bisphosphonates, denosumab, glucocorticoids, PPIs).

Pathogenesis: severe suppression of bone turnover impairs repair of micro-damage; accumulated micro-cracks, hypermineralised brittle bone and reduced collagen heterogeneity produce a fatigue fracture at the site of maximal tensile stress on the lateral femoral cortex. Bowed femora, Asian ethnicity, short stature and glucocorticoids increase risk.

Clinical presentation and diagnosis: prodromal thigh or groin pain in about two-thirds, often for weeks to months, then a fracture on trivial trauma. Investigate any patient on long-term antiresorptive therapy with new thigh pain by full-length femoral radiographs of both femora; if negative but suspicion persists, MRI or bone scintigraphy detects early stress reaction. Always image the contralateral femur, as bilateral involvement is common.

Risk in context — the crucial balance: AFF is rare (of the order of a few per 10,000 patient-years, rising with duration beyond 5 years and falling rapidly after stopping), whereas bisphosphonates prevent many times that number of typical osteoporotic fractures. The benefit clearly outweighs the risk in patients at high fracture risk. Osteonecrosis of the jaw is the other rare class effect.

Management: (a) stop the bisphosphonate or denosumab (with antiresorptive cover if denosumab is discontinued); (b) ensure calcium and vitamin D repletion; (c) prophylactic intramedullary nailing for a complete fracture, and for an incomplete fracture with a radiolucent line or persistent pain — conservative treatment with protected weight-bearing is reserved for incomplete fractures without a dreaded black line; (d) teriparatide may be used to promote healing and to continue osteoporosis treatment; (e) periodic drug holiday review at 3 years for IV and 5 years for oral bisphosphonates is the principal preventive strategy.