Inadequate responders to osteoporosis treatment: proposal for an operational definition

Abstract

The concept of inadequate response to osteoporosis treatment is not clear. In the literature several criteria have been used. We propose an operational definition of an inadequate responder based on the changes observed in bone mineral density and incident fractures while on therapy.

Introduction: Fractures may occur in compliant patients even while on active treatment. These cases have been defined as inadequate responders (IR).

Methods: We reviewed the basis for this concept and propose an operational definition for IR.

Results: Good compliance and adequate calcium and vitamin D supplementation are the first requirement. The second requirement is a treatment period of at least 1 year, since before that time treatment may not have been fully effective. Fractures are the gold standard for measuring efficacy and changes in bone density and turnover markers may be surrogates. We propose classifying patient response as: Inadequate--incident fracture and a decrease in BMD greater than a significant change (Trend Assessment Margin or TAM); Possibly inadequate--incident fracture or a decrease in BMD greater than a significant change (TAM); and Appropriate--no fracture and no decrease in BMD greater than a significant change (TAM). Additional criteria (biochemical markers, bone quality parameters) may be taken into account.

Conclusion: A wide consensus on the IR concept is required given its clinical, regulatory, and reimbursement implications.