Watts NB, Chines A, Olszynski WP, et al. Fracture risk remains reduced one year after discontinuation of risedronate. Osteoporosis International 2008;19:365–72-65–72
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/17938986
Full text article: https://link.springer.com/article/10.1007%2Fs00198-007-0460-7
| Methods | Study design: Open-label non-randomized trial as an extension to a randomized,double-blind placebo-controlled trial with a parallel-design
Number of groups: Two groups |
| Participants | Number of participants: 759 enrolled, 599 completed
· Intervention group: 361 enrolled, 290 completed · Control group: 398 enrolled, 309 completed Age: 68.5 ± 7.5 years Sex: 759 female, 0 male Participants with dementia: No Inclusion criteria: · Female · At least 5 years post-menopausal · Under 85 years · Had either two or more vertebral fractures or one vertebral fracture and low spinal bone mineral density (T-score ≤−2) Exclusion criteria: · Not described Concomitant medicines: 1000 mg of calcium daily and, if baseline serum 25-hydroxyvitamin D levels were low, received vitamin D supplementation Country: United States of America Setting: Community |
| Interventions | Medicine: Risedronate 5mg daily for three years
Withdrawal schedule: Not described Comparator: Placebo risedronate 5mg daily for three years then deprescribed |
| Outcomes | Bone Mass Density of the femoral neck
Bone Mass Density of the lumbar spine Urine NTX Serum bone-specific alkaline phosphatase New vertebral fractures New non-vertebral fractures |
| Dates | Dates: Not described
Follow-up duration: Four years total – three years treatment and one year deprescribing |
| Funding sources | Grants from Procter & Gamble Pharmaceuticals, Cincinnati, Ohio, and Sanofi-Aventis Pharma, Bridgewater, New Jersey. |
| Notes | Authors stated: “Dr. Watts receives honoraria for lectures from Amgen, Novartis, Procter & Gamble and Sanofi-Aventis; consulting fees from Amgen, Eli Lilly, Kyphon, Novartis, Procter & Gamble, Roche and Sanofi-Aventis; and research support through Amgen, Eli Lilly, Novartis, Procter & Gamble and Solvay. Dr. Chines is a former employee of Procter & Gamble and owns Procter & Gamble shares. He is currently an employee of Wyeth. Dr. McKeever is a consultant for Procter & Gamble, Merckand Roche and receives research grants from Procter & Gamble, Merck, Lilly and Roche. Dr. McClung receives research grants from Amgen, Eli Lilly, Merck, Novartis, Procter & Gamble, and Roche. He receives consulting fees from Amgen, Eli Lilly, Merck, Novartis, Procter & Gamble, Rocheand Sanofi-Aventis. He is a member of speaker’s bureaus for Eli Lilly, Merck, Procter & Gamble, and Sanofi-Aventis. Dr. Zhou and Dr. Grauer are full-time employees of Procter & Gamble and own stocks of the company.”Additional information sought, but not received. |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Unclear risk | Allocation based on group assignment from the parent study.
Patients were randomly assigned in the original study. all women who completed the 3-year treatment period were given the option of remaining in the study for the fourth year, where active treatment and placebo were discontinued but calcium and vitamin D supplementation was continued as before. No method of randomization was given therefore bias marked as unclear. |
| Allocation concealment (selection bias) | Unclear risk | Allocation based on group from parent study.
“Except for 121 women who had bone biopsies at the end of year three, all women who completed the 3-year treatment period were given the option of remaining in the study for the fourth year, where active treatment and placebo were discontinued but calcium and vitamin D supplementation was continued as before.” “Patients and clinical personnel remained blinded to the original treatment assignments throughout the 4 years of observation.” It appears that all women were treated identically who remained in the study for the fourth year. Therefore, allocation remained blinded. |
| Blinding of participants and personnel (performance bias) | 1 out of 5 | They knew they had been deprescribed, but remained blinded as to whether they had previously used the active treatment or not.
“Patients and clinical personnel remained blinded to the original treatment assignments throughout the 4 years of observation.” |
| Blinding of outcome assessment (detection bias) | 1 out of 5 | As above. |
| Incomplete outcome data (attrition bias) | 1 out of 5 | Intention-to-treat analysis. |
| Selective reporting (reporting bias) | 5 out of 5 | Adverse event data were collected but not reported.
It appears that the researchers had a pre-specified protocol and analysis plan. Outcomes were not pre-specified for the one year extension study. Events and measurements were reported. |
| Confounding (non-randomized) | 2 out of 5 | Concurrent control for placebo treatment.
It appears that groups were balanced at baseline. |
| Other bias | High risk | Would have been useful to see comparison between those who remained on risedronate compared to those who withdrew.
This study was funded by grants from Procter & Gamble Pharmaceuticals, Cincinnati, Ohio, and Sanofi-Aventis Pharma, Bridgewater, New Jersey. |
| Newcastle-Ottawa scale | ||
| Selection bias | Representativeness of the exposed cohort | Appears representative sample of post-menopausal women with osteoporosis. |
| Selection of the non-exposed cohort | The concurrent control group was drawn from the same population at the baseline of the parent study.
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| Ascertainment of exposure | Ascertainment of exposure was by secure record.
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| Demonstration that outcome of interest was not present at start of study | Demonstrated that outcome of interest was not present at start of study. | |
| Comparability bias | Comparability of cohorts on the basis of the design or analysis | Study controlled for bisphosphonate/placebo deprescribing. |
| Outcome bias | Assessment of outcome | Outcome assessment by independent blind assessment. |
| Was follow-up long enough for outcomes to occur | Follow-up probably not long enough for outcomes to occur.
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| Adequacy of follow-up of cohorts | Complete follow-up – all subjects accounted for. | |
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