Patients with cystic fibrosis (CF) have low bone mineral density (BMD). The clinical relevance of this is not clearly established. The aim of this study was to determine the prevalence of low BMD and vertebral deformities in CF adults with varied disease severity. One hundred and seven patients (58 men) aged 18-60 years underwent dual-energy X-ray absorptiometry scanning of the lumbar spine and hip, radiology of the spine and biochemical studies. Thirty-eight percent had a Z-score of < -1, with 13% having Z-scores < -2. Seventeen percent had evidence of vertebral deformity on radiography, mostly in the thoracic spine. Thirty-five percent reported past fractures, of which 9% were rib fractures. Percent predicted forced expiratory volume in 1 second (FEV1) and the amount of daily physical activity were positively related to BMD. The number of intravenous antibiotic courses in the previous 5 years was negatively related to BMD. Patients with a history of rib fracture and CF-related diabetes had significantly lower femoral neck BMD (p < 0.02). The median serum 25-hydroxyvitamin D was 28 nmol/l, with 36% of patients having levels below 25 nmol/l despite vitamin D supplementation. Forty-four percent had raised levels of urinary pyridinium crosslinks (NTx). In conclusion, fragility fractures and hypovitaminosis D occur commonly in adult patients with CF. Low BMD occurs in patients with more severe disease and significantly relates to FEV1, infective exacerbations and daily energy expended in physical activity.