Black DM, Reid IR, Boonen S, et al. The effect of 3 versus 6 years of Zoledronic acid treatment of osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). Journal of Bone and Mineral Research 2012;27:243-54.
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/22161728
Full text article: https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbmr.1494
| Methods | Study design: Randomized double-blind controlled study (continued from the parent study HORIZON-PFT trial) with a parallel-design
Number of groups: Two groups |
| Participants | Number of participants: 1233 randomized, 921 completed
· Intervention deprescribing (zoledronic acid for 3 years/placebo for 3 years) group: 617 randomized, 470 completed · Control (zoledronic acid for 6 years) group: 616 randomized, 451 completed Age: 75.5 ± 4.9 years Sex: 1233 females, 0 males Inclusion criteria: · Post-menopausal women between the ages of 65 and 89 years · Bone mineral density T-score of: o −2.5 or less at the femoral neck with or without evidence of existing vertebral fracture; or o −1.5 or less, with radiologic evidence of at least two mild vertebral fractures or one moderate vertebral fracture · Previous use of oral bisphosphonate was allowed, with the duration of the wash-out period dependent on previous use (e.g., previous use of ≥48 weeks required 2 years of wash-out). Exclusion Criteria: · Major protocol violations during HORIZON-PFT trial · Aged 93 years and over · Specific bone-active medication use · HORIZON-PFT exclusion criteria: o Any previous use of parathyroid hormone or sodium fluoride o Use of anabolic steroids or growth hormone within 6 months before trial entry o Oral or intravenous systemic corticosteroids within 12 months o Any previous use of strontium o Patients with a serum calcium level of more than 2.75 mmol per literor less than 2.00 mmol per liter were ineligible o Calculated creatinine clearance of less than 30.0 ml per minute at either of two baseline visits o Urine dipstick results of more than 2+ for protein, without evidence of contamination of bacteriuria Country: International multi-centered trial Setting: Community |
| Interventions | Medicine: Zoledronic acid 5mg annually
Withdrawal schedule: Not described Comparator: Placebo compared to continued medicine |
| Outcomes | Bone Mass Density in femoral neck – percentage change
Bone Mass Density of spine and total hip Changes from pre-treatment levels over 6 years (baseline to 6 years) Biochemical bone turnover markers Fractures (clinical, non-vertebral, clinical spine, and morphometric vertebral) Adverse events |
| Dates | Dates: Not described
Follow-up duration: Six years total follow-up (three years treatment, three years deprescribed) |
| Funding sources | Novartis Pharma AG, Basel, Switzerland |
| Notes | The authors have included declared conflicts of interest in the original manuscript. There is insufficient room to include them here.
Additional information sought, but not received. |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Unclear risk | The method is not described:
“Women assigned to zoledronic acid in the core study were randomly assigned to receive a 15-minute intravenous infusion of zoledronic acid (Group Z6) or placebo (Group Z3P3) once per year for 3 years, in a 1:1 ratio, stratified by clinical center.” |
| Allocation concealment (selection bias) | Unclear risk | The authors refer to stratification by clinical center, but not further information is given on how allocation was concealed.
“Women assigned to zoledronic acid in the core study were randomly assigned to receive a 15-minute intravenous infusion of zoledronic acid (Group Z6) or placebo (Group Z3P3) once per year for 3 years, in a 1:1 ratio, stratified by clinical center. “ |
| Blinding of participants and personnel (performance bias) | Low risk | “To maintain blinding, patients assigned to placebo during the core study received zoledronic acid in the extension study for 2 to 3 years but will not beconsidered further in this report. To further ensure blinding, patients were randomized centrally by an interactive voice-response system to study treatment. All patients received daily oral calcium (1000 to 1500 mg) and vitamin D (400 to 1200 IU). All personnel were blinded to study medication. Study investigators, site personnel, end-point adjudicators, the Novartis clinical team, as well as the clinical research organization and Coordinating Center personnel involved in the conduct of the trial, were all blinded to treatment assignments.” |
| Blinding of outcome assessment (detection bias) | Low risk | Study investigators, site personnel, end-point adjudicators, the Novartis clinical team, as well as the clinical research organization and Coordinating Center personnel involved in the conduct of the trial, were all blinded to treatment assignments.” |
| Incomplete outcome data (attrition bias) | High risk | The study did not include the participants randomized to placebo from the original study, so this comparison was unavailable. It is unclear how/if this would have altered the comparisons.
e.g. “To maintain blinding, patients assigned to placebo during the core study received zoledronic acid in the extension study for 2 to 3 years but will not beconsidered further in this report.” |
| Selective reporting (reporting bias) | Low risk | The pre-specifiedprotocol was not published. However, the stated objectives are all reported. |
| Other bias | High risk | Industry-sponsored. |
Leave a Reply