Background

Failure of antiresorptive therapy in severe osteoporosis should prompt evaluation for secondary contributors to impaired bone quality. In surgical populations—particularly spinal fusion and orthopaedic cohorts—unrecognised metabolic factors may significantly compromise outcomes. This represents a common but under-recognised clinical scenario in patients presenting for major orthopaedic and spinal procedures. We present a case illustrating the interaction between malabsorption and skeletal fragility, with implications for perioperative bone optimisation pathways.

Case Presentation

A female patient with severe osteoporosis presented with progressive vertebral fractures despite denosumab therapy, involving thoracic (T1–T5, T11–T12) and lumbar levels, alongside a prior humeral fracture. She reported significant height loss (3–4 inches) and severe functional limitation.

Her history was notable for longstanding gastrointestinal dysfunction, requiring bowel surgery and prolonged parenteral nutrition, with a predominantly liquid diet due to impaired gastrointestinal transit.

Bone densitometry confirmed severe osteoporosis (forearm T-score −3.8; hip −2.8).

Further evaluation identified:

• Exocrine pancreatic insufficiency (faecal elastase 188 µg/g)
• Zinc deficiency (8.4 µmol/L)
• Negative coeliac serology and mast cell markers
• Incidental thyroid nodules (TI-RADS 3)

Management and Outcome

Given ongoing fractures on denosumab, therapy was transitioned to romosozumab, with concurrent correction of underlying metabolic abnormalities:

• Pancreatic enzyme replacement (Creon)
• Micronutrient repletion (zinc and targeted mineral assessment)

At 6-month follow-up, no new fractures were observed, suggesting improved skeletal stability following combined anabolic therapy and correction of malabsorption.

Discussion

This case highlights key clinical principles:

• Antiresorptive failure is a red flag
Continued fractures on denosumab should trigger systematic reassessment for secondary causes.
• Malabsorption is an under-recognised driver of skeletal fragility
Subclinical deficiencies may impair bone remodelling and therapeutic response.
• Bone therapy in isolation is insufficient
Effective management requires correction of the metabolic substrate.
• Relevance to perioperative care
Patients with untreated metabolic bone disease undergoing spinal or major orthopaedic procedures are at increased risk of fixation failure, non-union, and adjacent fractures.

Conclusion

In severe osteoporosis with treatment failure, systematic evaluation for malabsorption and metabolic contributors is essential. These findings support the integration of structured metabolic assessment and anabolic sequencing into perioperative bone optimisation pathways for high-risk surgical patients.

Keywords

Osteoporosis; Romosozumab; Malabsorption; Secondary osteoporosis; Bone optimisation