Understanding Patterns and Estimating Relative Effects of Long-term Bisphosphonate Therapy and Drug Holidays
Bibliographic record
Abstract
Osteoporosis is a disease of low bone mass that causes debilitating fractures. Oral bisphosphonates (alendronate, risedronate, and etidronate) are first-line therapy for osteoporosis. Guidelines recommend at least three to five years of initial bisphosphonate therapy. Thereafter, most patients can undergo a bisphosphonate drug holiday for up to 3 years, as bisphosphonates have extended half-lives and continue to provide fracture protection after therapy discontinuation. However, the relative anti-fracture benefit of different bisphosphonates during drug holidays is uncertain. Risedronate has a shorter half-life in bone than alendronate, and thus fracture protection during risedronate drug holidays may be shorter. This research aimed to provide evidence on long-term oral bisphosphonate therapy and drug holidays using a series of population-based studies. First, Study 1 described time trends in oral bisphosphonate initiation and characteristics of older adults starting therapy in Ontario, Canada over 20 years. Then, Study 2 identified patterns of long-term oral bisphosphonate exposure (≥3 years with ≥80% adherence) using a cohort study design. Lastly, Study 3 examined the comparative anti-fracture benefits of risedronate versus alendronate therapy during drug holidays. Study 1 showed that alendronate and risedronate have largely replaced etidronate and found important changes in patient characteristics over time. Study 2 identified that 60% of patients initiating alendronate or risedronate had a period of long-term exposure. Finally, long-term therapy with risedronate was associated with a modestly increased hip fracture risk compared to alendronate during drug holidays longer than 2 years (HR=1.18 [95% CI 1.04 to 1.34]) in Study 3. The findings from this thesis highlight oral bisphosphonates as a mainstay of osteoporosis therapy, demonstrate that most patients starting oral bisphosphonates have long-term use, and suggest that drug holidays after risedronate therapy should be limited to 2 years. Further research is required to examine the comparative benefits and harms of long-term oral bisphosphonate therapy versus other osteoporosis treatments.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.019 | 0.064 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.003 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".