The purpose of this study was to determine whether a marker of bone resorption could be used noninvasively to diagnose and assess treatment of periprosthetic osteolysis. The crosslinked N-telopeptide marker of osteoclast-mediated bone resorption potentially has the sensitivity to detect periprosthetic osteolysis. Second-morning urine specimens were obtained from (a) seven age-matched controls, (b) eight patients who had a hip arthroplasty, hybrid implants at least 1 year after surgery, and no osteolysis, (c) 11 patients who had a hip arthroplasty and osteolysis, and (d) 10 patients who had a hip arthroplasty and with osteolysis before and after 6 weeks of oral Fosamax (alendronate) treatment. The Fosamax treatment consisted of one 10-mg dose per day for 6 weeks. Men and young women (less than 40 years old) were chosen for this study to avoid bone resorption enhanced after menopause as a possible confounder. An enzyme-linked immunosorbent assay technique for quantifying crosslinked N-telopeptides of type-I collagen was performed on all specimens. The patients with osteolysis had significantly elevated levels of N-telopeptide compared with the implant control group. In addition, levels of N-telopeptide were significantly lowered after Fosamax treatment. These findings indicate that a systemic bone-resorption marker (N-telopeptide) can be used to evaluate local particulate-induced osteolysis and its treatment. The study also provides clinical evidence that osteolysis is associated with increased osteoclast-mediated bone resorption and that this locally induced bone resorption can be suppressed by certain bisphosphonates (Fosamax). These insights have potential value in the understanding and clinical management of aseptic loosening.