BACKGROUND: Bisphosphonates, antiresorptive drugs, are widely used to treat osteoporosis patients. However, recent reports indicated that several osteoporosis patients who underwent long-term bisphosphonate therapy subsequently developed severe suppression of bone turnover. We investigated whether urinary crosslinked N-telopeptide of type I collagen (NTX), a bone resorption marker, in osteoporosis patients was highly suppressed during long-term treatment with alendronate or risedronate. METHODS: We investigated 87 primary osteoporosis outpatients who were treated with alendronate or risedronate for more than 2 years. All patients were women, with an average age of 72.6 years. Altogether, 49 patients were treated with alendronate and 38 with risedronate, and the average administration period was 3.5 years. We defined high suppression as NTX being reduced <9.3 nmol bone collagen equivalent/mmol.Cr and a 35% decrease from baseline. RESULTS: In total, 11 of 87 patients (12.6%) had high NTX suppression based on the above criteria. The incidences of high suppression of NTX at 1,2,3,and 4 years after starting the treatment were 0%, 1.1%, 11.9%, and 4.7%, respectively. The average age, bone mineral density, and NTX values at baseline and the administration period were not associated with high suppression of NTX during alendronate or risedronate treatment. Regarding suppression of NTX during long-term treatment, there was no significant difference between alendronate and risedronate. CONCLUSIONS: The results suggested that long-term treatment with bisphosphonates necessitates careful follow-up of the patients.