OBJECTIVE To emphasize the potential for Roux-en-Y gastric bypass treatment of morbid obesity to result in late development of metabolic bone disease and to illustrate the error of treating a low bone mineral density with bisphosphonates in the presence of unrecognized osteomalacia. METHODS We conducted a retrospective case review of clinical, laboratory, and radiologic details in a patient who underwent Roux-en-Y gastric bypass as well as a review of the literature relative to metabolic bone disease associated with bariatric surgical procedures. RESULTS A 42-year-old woman was diagnosed with high bone turnover osteoporosis and failed to respond to bisphosphonate (alendronate) therapy. Her past medical history included corticosteroid-dependent asthma and a Roux-en-Y gastric bypass surgical procedure for obesity approximately 6 1/2 years before the current assessment. Evaluation revealed vitamin D deficiency in conjunction with pronounced secondary hyperparathyroidism and biochemical evidence of osteomalacia. Aggressive calcium and vitamin D supplementation corrected the vitamin D-deficient state and was accompanied by rapid improvement in clinical symptoms, biochemical variables, and bone mineral density. CONCLUSIONS This case exemplifies two principles: (1) the potential for a Roux-en-Y gastric bypass surgical procedure to lead to the development of metabolic bone disease and (2) the importance of recognizing mineralization defects as a cause for low bone mineral density, before initiation of therapy with bisphosphonates.