Patients treated with pharmacological agents to improve bone strength and reduce fracture risk may not achieve optimal skeletal benefit for reasons that include poor compliance and persistence, inadequate calcium and vitamin D intake, malabsorption, and medications or co-morbidities with adverse skeletal effects. Monitoring the effects of therapy can inform the patient and physician that the drug is having its expected skeletal response. Treatment is often monitored with serial bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry or bone turnover markers (BTMs). Stable or increasing BMD is associated with reduced fracture risk in clinical trials, and is considered an indication of good response to therapy in individual patients outside of clinical trials. There are many differences between subjects in clinical trials and patients being treated in clinical practice. Thus, although defining a clinical practice patient as a "nonresponder" or "suboptimal responder" to treatment is problematic, a pragmatic approach would be to consider evaluation for contributing factors and possible changes in therapy in patients who have a statistically significant decrease in BMD, do not have the expected change in BTMs, or have a fracture.