Clarifying clinically treatment-naive status for osteoporosis patients

David L Kendler; Jeffrey Habert; Aliya A Khan; Raheem B Kherani; Sandra Kim; Christopher S Kovacs; Jooho Lee; Jane Purvis; Jodie Reis; Lubomira Slatkovska; Jenny Thain; Jonathan D Adachi

doi:10.1007/s00198-026-07864-3

Clarifying clinically treatment-naive status for osteoporosis patients

Osteoporos Int. 2026 Feb 17. doi: 10.1007/s00198-026-07864-3. Online ahead of print.

Authors

Affiliations

¹ Department of Medicine, University of British Columbia, 150-943 West Broadway, Vancouver, BC, V5Z 4E1, Canada. davidkendler@gmail.com.
² University of Toronto, Toronto, ON, Canada.
³ McMaster University, Hamilton, ON, Canada.
⁴ Department of Medicine, University of British Columbia, 150-943 West Broadway, Vancouver, BC, V5Z 4E1, Canada.
⁵ Memorial University of Newfoundland, St. John's, NL, Canada.
⁶ University of Calgary, Calgary, AB, Canada.
⁷ Queen's University, Kingston, ON, Canada.
⁸ University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
⁹ Independent Researcher, Haliburton, ON, Canada.
¹⁰ Western University, London, ON, Canada.

PMID: 41701231
DOI: 10.1007/s00198-026-07864-3

Abstract

Clinical relevance: Although patients with remote or brief prior exposure to osteoporosis treatments are strictly not "treatment naive," osteoporosis treatment effects on bone mineral density and bone turnover resolve over time. It would therefore be useful to categorize patients with remote or brief prior exposure to osteoporosis treatment as "clinically treatment naive." This lack of clarity of who can be categorized as clinically treatment naive may disadvantage patients at very high fracture risk with brief or remote prior exposure who may face barriers to bone-building therapies. Access may be restricted to those who have never received treatment, based on the mistaken assumption that brief or remote prior exposure significantly impairs treatment response. Here, we summarize how clinically treatment-naive has been defined in protocols for pivotal trials of approved osteoporosis therapies and recent practice guidelines in North America. Consistent definitions are proposed for initial therapies for patients at high-to-very-high fracture risk. Bisphosphonates are discussed in greater detail owing to their unique bone-binding properties, leading to more persistent, albeit finite, antiresorptive activity after discontinuation. A discussion of possible lingering effects of long-term bisphosphonates on bone strength and predisposition to atypical femoral fractures was beyond the scope of this report. In contrast, non-bisphosphonate therapies resolve relatively rapidly after discontinuation, necessitating timely transition to another agent to prevent reversal of anti-fracture efficacy.

Observations: Proposed definitions of treatment-naive for the therapies discussed here are treated with oral bisphosphonate for ≥ 1 year or received ≥ 1 annual IV bisphosphonate dose and discontinued ≥ 2 years ago; treated with oral bisphosphonate for > 3 months and < 1 year and discontinued 1-2 years ago; discontinued oral bisphosphonate after ≤ 3 months; received last denosumab injection ≥ 12 months ago; and discontinued abaloparatide, romosozumab, or teriparatide ≥ 12 months ago.

Conclusions: In conclusion, a unified definition could aid multidisciplinary care teams and healthcare decision-makers in making treatment sequencing decisions.

Keywords: Abaloparatide; Bisphosphonate; Denosumab; Romosozumab; Teriparatide; Treatment naive.