Denosumab significantly improves lumbar spine bone mineral density more in treatment-naïve than in long-term bisphosphonate-treated patients.

The purpose of our study was to compare the skeletal responses to 3-year denosumab treatment in bisphosphonate (BP)-naïve and long-term BP-treated patients with postmenopausal osteoporosis. Female patients who were BP treatment-naïve (treatment-naïve group: 25 cases) or who received long-term BPs (BP pre-treated group: 24 cases) were compared for serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP)-5b, and urinary N-terminal telopeptide of type I collagen (NTX) at baseline and at 4, 8, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months of denosumab therapy. Lumbar 1-4 (L) spine bone mineral density (BMD), total hip (H)-BMD, and femoral neck (FN)-BMD values were measured at baseline and at 4, 8, 12, 18, 24, 30, and 36 months. The percentage changes of bone turnover markers were significantly decreased throughout the study period by a larger margin in the treatment-naïve group than in the BP pre-treated group. L-BMD, H-BMD, and FN-BMD were all significantly increased in the treatment-naïve and BP pre-treated groups at 36 months (12.9% and 7.5%, 5.9% and 6.0%, and 7.6% and 4.5%, respectively), compared with pre-treatment levels. There were significant differences for L-BMD at 12, 24, 30, and 36 months between the groups. Our findings suggest that the BMD response to denosumab, especially that of L-BMD, was diminished following BP therapy relative to treatment-naïve patients, thus providing evidence supporting the use of denosumab as a first-line therapy.