Health Initiative participants suggesting that long-term (10-13 years) oral bisphosphonate therapy may increase the risk of any clinical fracture more than short-term (2 years) oral bisphosphonate use and refer to several additional studies indicating that long-term oral bisphosphonate use may have no advantage over short-term use. The observed greater fracture risk during long-term oral bisphosphonate treatment was attributed to oversuppression of the bone remodeling process, which may damage bone quality and lead to greater bone fragility. I would like to suggest an alternative view.We recently showed, 2 in a cohort of women with osteoporosis deemed to be compliant with treatment with oral bisphosphonates (mainly alendronate) for a mean period of 7.2 6 3.1 years (range 2-15 years) in a realworld setup that the frequency distribution of results of a bone-resorption marker (urinary deoxypyridinoline) was clearly skewed to the right (higher values). Thus, although 62% of the women were in the normal range for premenopausal women, 31% were above the normal range for premenopausal women (exceeding 20% above the normal range in 17% and 30% above in 13%), and only 7.5% had suppressed bone resorption rates. We interpreted these results as indicating that oversuppression is uncommon during prolonged oral bisphosphonate treatment and that high bone turnover (reflecting treatment failure) is much more prevalent. We suggested that compliance or oral bisphosphonate bioavailability deteriorates with time, leading to greater bone turnover, potentially resulting in greater fracture risk, as Drieling and colleagues demonstrated. 1 Although the current paradigm, as well as Drieling and colleagues, 1 suggests putting people on prolonged bisphosphonate treatment on a drug holiday to reduce oversuppression of bone turnover, 3 our results, as well as other observations indicating a greater incidence of fractures early after initiation of a drug holiday, 4-6 suggest that a drug holiday could be risky for many people and that re-evaluation of individuals on a prolonged course of oral bisphosphonates should probably include, in addition to clinical and densitometric evaluation, an assessment of bone turnover, to exclude what could be classified as subclinical treatment failure. Individuals with high bone turnover could thus be considered for a parenteral antiresorptive drug.