Bisphosphonate drug holidays in osteoporosis according to fracture risk profile.

We analyzed the incidence of fractures and changes in bone mineral density and bone turnover markers in 264 patients who discontinued bisphosphonates. Fractures were recorded in 12.3%. Half were clinical vertebral fractures. We identified patients with a high-risk profile who should not discontinue treatment.

Objective: The optimal length of bisphosphonate discontinuation is unknown, as is the type of patient who could benefit from this approach. The objectives of the study were to analyze, in clinical practice, the incidence of fractures and associated risk factors, changes in bone mineral density (BMD) and bone turnover markers (BTMs) after discontinuation of bisphosphonates.

Methods: This observational retrospective study included 264 patients from 14 Spanish rheumatology departments. Postmenopausal women or men with osteoporosis received alendronate or risedronate for ≥ 5 years or zoledronate for ≥ 3 years and had discontinued treatment for ≥ 1 year or ≥ 2 years, respectively. Spinal X-rays were obtained before discontinuation and in suspected clinical vertebral fracture during follow-up. BMD and BTMs were determined before discontinuation and at different time points.

Results: The mean discontinuation time was 2.7 (± 6.7) years. Thirty-two patients (12.3%) had 36 fractures, mainly clinical vertebral fractures. The main risk factor for fracture was a high-risk profile (femoral neck T-score ≤ -2.5 and/or a history of fracture and/or multiple fractures [≥ 5 years]) before discontinuation. At 12 months, 10.41% of patients with high-risk profile experienced a fracture, being 0.8% and 1.08% in moderate- and low-risk patients, respectively. Significant BMD loss at the femoral neck and total hip was detected, with duration of discontinuation being the key factor. PINP was the marker with the greatest changes.

Conclusions: We identified a profile of patients with osteoporosis who should not discontinue bisphosphonates, owing to the possibility of fractures, especially vertebral, which are already evident the first year after discontinuation.