Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis
2007 · paper · Clinical trials
A three-year placebo-controlled trial of yearly zoledronic acid infusions in about 7,700 postmenopausal women with osteoporosis. Treatment cut vertebral fractures by 70% and hip fractures by 41%; serious atrial fibrillation was more frequent with the drug.
4 findings
Substance Results: "1.3% of patients in the zoledronic-acid group had an increase of more than 0.5 mg per deciliter". Table 3 gives 31 (1.2), with denominator 2521 in footnote †.
- p. 7 Results, Adverse Events, left column
1.3% of patients in the zoledronic-acid group had an increase of more than 0.5 mg per deciliter
- p. 11 Table 3, Renal events
31 (1.2)
- p. 7 Results, Adverse Events
1.3% of patients in the zoledronic-acid group
Only the authors can say what is right here.
Judge's note: Both places describe the same measure: an increase >0.5 mg/dl at 9–11 days in the renal subgroup. 31/2521 = 1.23%, which matches the table's 1.2% but not the text's 1.3%. The placebo value of 0.4% (10/2514) agrees in both places. The paper states no other denominator.
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Reference or label Table 2 footnote: "(3875 patients with clinical fractures in the placebo group and 3861 in the zoledronic-acid group)". The group sizes are swapped: placebo is 3861 and zoledronic acid is 3875. These are also the whole analysis sets, not patients with clinical fractures.
- p. 7 Table 2, footnote *
3875 patients with clinical fractures in the placebo group and 3861 in the zoledronic-acid group
- p. 4 Table 1 header
Placebo (N = 3861)
- p. 9 Figure 2, No. at Risk at month 0
3875
- p. 7 Table 2, footnote *
(3875 patients with clinical fractures in the placebo group and 3861 in the zoledronic-acid group)
Judge's note: On p.7 the footnote image reads as quoted. Table 1 (p.4/5) gives Placebo N=3861 and Zoledronic Acid N=3875. Figure 1 (p.3) gives efficacy analysis counts of 3875 (zoledronic acid) and 3861 (placebo). The Figure 2 (p.9) month-0 at-risk rows give Zoledronic acid 3875 and Placebo 3861. Only 456 and 308 patients had clinical fractures (Table 2).
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Wording Abstract: "Adverse events, including change in renal function, were similar in the two study groups". But the Results (p.7) say any adverse event was "significantly higher in the zoledronic-acid group (95.5% vs. 93.9%)", and Table 3 gives P=0.002 for any adverse event and P=0.001 for serum creatinine increase >0.5 mg/dl (31 [1.2%] vs 10 [0.4%]).
- p. 1 Abstract, Results
Adverse events, including change in renal function, were similar in the two study groups.
- p. 11 Table 3
3616 (93.9)
- p. 7 Results, Adverse Events
was signifi-cantly higher in the zoledronic-acid group (95.5%
- p. 11 Table 3, General and Renal events rows
3616 (93.9) 3688 (95.5) 0.002
Only the authors can say what is right here.
Judge's note: I checked the abstract (p.1), the Results text (p.7) and Table 3 (p.11). Serious adverse events (P=0.40) and creatinine clearance at 3 years did not differ. The abstract, however, says 'adverse events' and 'change in renal function' without narrowing to those, and the paper's own text calls the overall adverse-event difference significant. The abstract wording does not match the reported data. Only the authors can say which measures 'similar' was meant to cover.
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Wording Discussion: "intermittent arrhythmia might not have been captured on the short echocardiogram in this subgroup". The substudy used 12-lead electrocardiography.
- p. 12 Discussion, first column
been captured on the short echocardiogram in this
- p. 12 Discussion, left column
been captured on the short echocardiogram in this subgroup
- p. 5 Methods, Adverse Events
went 12-lead electrocardiography before and 9 to 11 days after the third infusion
- p. 12 Discussion, atrial fibrillation paragraph
might not have been captured on the short echocardiogram in this subgroup
Judge's note: On p.12 the preceding sentence refers to 'Electrocardiography that was performed before and 9 to 11 days after the third infusion in 559 patients'. The Methods (p.5) describe 12-lead electrocardiography, and the paper describes no echocardiography anywhere. The word should be electrocardiogram.
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6 minor (typos and the like; most checked by the judge only)
Reference or label Discussion: "greater than the 3-year reduction previously observed for oral bisphosphonates (40 to 50%)2,4,6,18-20". Refs 19 and 20 are "1-year results from the MOBILE study" and "2 year results from the MOBILE study" (monthly ibandronate).
- p. 8 Discussion, first paragraph
previously observed for oral bisphosphonates (40 to 50%)2,4,6,18-20
- p. 13 References 19 and 20
1-year re-sults from the MOBILE study
Only the authors can say what is right here.
Judge's note: I checked the citation on p.8 and references 18–20 on p.13. Going by their titles, refs 19 and 20 are 1-year and 2-year efficacy/tolerability reports and do not plainly support a 3-year fracture-reduction figure. Ref 18 is the oral ibandronate fracture trial. This is a question for the authors about whether refs 19–20 belong in this citation.
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Wording Table 1 footnote ‡: "lumbar spine included 270 patients in the placebo group and 272 in the zoledronic-acid group". Figure 3B No. at Risk at month 0 gives Placebo 269 (zoledronic acid 272).
- p. 5 Table 1, footnote ‡
included 270 patients in the placebo group and 272 in the
- p. 10 Figure 3 Panel B, No. at Risk, month 0
269
- p. 5 Table 1 footnote ‡
270 patients in the placebo group and 272 in the zoledronic-acid group
- p. 10 Figure 3B No. at Risk
Placebo 269
Judge's note: I confirmed both values on the page images (p.5 footnote; p.10 Figure 3B). The placebo count differs by one, and the paper gives no explanation. One patient may lack a usable baseline value, but the paper does not say so. This is a minor consistency point.
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Wording Table 3 footnote † (attached to both "Increase in serum creatinine >0.5 mg/dl†" and "Urinary protein >2+†"): "The increase was based on dipstick measurements before infusion of a study drug as compared with those 9 to 11 days after infusion".
- p. 11 Table 3 footnote †
The increase was based on dipstick measurements before infusion of a study drug
Only the authors can say what is right here.
Judge's note: The Methods (p.5) say serum creatinine was measured in a subgroup of 5035 patients, so it was a serum test, not a dipstick. Dipstick applies to urinary protein. As printed, the footnote attributes a dipstick method to the serum creatinine increase. It probably means dipstick only for the protein row, but the wording is ambiguous.
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Typo Disclosures: "Rosario-Janssen (now employed by Savient Pharmaceuticals)". The byline, the Appendix and the same paragraph ('Dr. Rosario-Jansen, owning stock in Novartis') spell it 'Rosario-Jansen'.
- p. 12 Disclosures
Rosario-Janssen (now employed by Savient Pharmaceuticals)
- p. 1 Author list
Theresa Rosario-Jansen, Ph.D.
- p. 12 Disclosures
Dr. Rosario-Jansen, owning stock in Novartis
- p. 12 Disclosures
Rosario-Janssen (now
Judge's note: I confirmed on the p.12 image that the disclosure reads 'Rosario-Janssen'. In the same paragraph and in the Appendix (p.12) the name is 'Rosario-Jansen', and the byline on p.1 reads 'Theresa Rosario-Jansen'.
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Typo Appendix: "Taiwan: ... T.-S. Yang, M. Jirapinyo; Thailand: M. Jirapinyo, R. Sattaya...". The same investigator is listed under both countries.
- p. 13 Appendix, investigator list
T.-S. Yang, M. Jirapinyo; Thailand: M. Jirapinyo
Only the authors can say what is right here.
Judge's note: I confirmed on the p.13 image that the name ends the Taiwan list and begins the Thailand list. This looks like a duplicated entry at the country break, but an investigator with sites in two countries cannot be ruled out from the files, so only the authors can say.
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Typo Reference 17: "Reston, VA: Northrup Grumman, 2003.". The publisher's name is presumably 'Northrop Grumman'.
- p. 13 Reference 17
Northrup Grumman, 2003.
- p. 13 Reference 17
Reston, VA: Northrup Grumman, 2003.
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the company is spelled 'Northrop Grumman'. The p.13 image does show 'Northrup Grumman', so this is not an extraction artefact.
Second check: none (judge only)