Article Figures & Data
Figures
- Figure 1.
Forest plot of denosumab versus bisphosphonates for clinical and osteoporotic fractures. A: Clinical fracture data. B: Osteoporotic fracture data. The forest plot represents the odds ratio for fracture events among participants randomized to denosumab versus bisphosphonates.
- Figure 2.
A: Regression of log odds ratio of denosumab’s treatment effect on osteoporotic fracture on percent difference in BMD between denosumab and bisphosphonates. B: Regression of log odds ratio of denosumab’s treatment effect on clinical facture on percent difference in total hip BMD between the denosumab and bisphosphonate arms. Fixed effects meta-regression. The x-axis is the percent change in total hip bone mineral density (BMD) between denosumab and bisphosphonates. The y-axis represents the treatment effect of denosumab (log odds ratio) on osteoporotic fracture (A) and clinical fracture (B). Each circle represents an included randomized controlled trial, and the size of the circle represents the weight of the study in the regression model. The dark center line is the regression line and the lighter outer lines are the 95% CI.
- Appendix Figure 1.
PRISMA diagram of trials comparing denosumab to bisphosphonates. RCTs, randomized controlled trials.
- Appendix Figure 2.
Risk of bias graph for trials comparing denosumab and bisphosphonates.
- Appendix Figure 3.
Risk of bias summary for trials comparing denosumab and bisphosphonates.
- Appendix Figure 4.
Funnel plot of denosumab versus bisphosphonates trials for clinical fractures.
- Appendix Figure 5. Funnel plot of denosumab versus bisphosphonates trials for osteoporotic
fractures.
Tables
Intervention Arm Control Arm Trial Year Length of Study (in months) Primary Endpoint of Trial Patient Baseline Characteristics Intervention Arm Control Arm n # of Clinical Fractures # of Osteoporotic Fractures n # of Clinical Fractures # of Osteoporotic Fractures Location Miller 2008 48 BMD at total hip, lumbar spine, total hip, distal one-third radius, total body; bone turnover markers (sCTX1 and uNTX), safety Postmenopausal women up to 80 years (mean age not reported) with T-scores between −1.8 and −4.0 at the lumbar spine or −1.8 and −3.5 at the femoral neck or total hip. Denosumab 6 mg, 14 mg, or 30 mg Q3 mol/L subcutaneously or denosumab 14 mg, 60 mg, 100 mg, or 210 mg Q6M Alendronate 70 mg Q1W PO 319 33 22 47 3 2 United States Brown 2009 12 BMD at total hip, femoral neck, trochanter, lumbar spine, one-third radius; bone turnover markers (sCTX1 and P1NP) Postmenopausal women (mean age not reported); T‐score ≤ −2.0 at the lumbar spine or total hip Denosumab 60 mg Q6 mol/L SC Alendronate 70 mg Q1W PO 594 6 18 595 6 13 International Kendler 2010 12 Percent change in total hip BMD from baseline to month 12 Postmenopausal women ≥ 55 years (mean age not reported) with a T‐score between −4 and −2 at lumbar spine or total hip and who had been receiving alendronate treatment equivalent to 70 mg/week ≥ 6 months Denosumab 60 mg Q6 mol/L SC Alendronate 70 mg Q1W PO 253 8 2 249 4 0 International Freemantle 2012 12 Medication adherence (compliance and persistence) Postmenopausal women aged ≥ 55 years (mean age not reported) with T-scores between −4 and −2 at femoral neck, lumbar spine, or total hip Denosumab 60 mg Q6 mol/L SC Alendronate 70 mg Q1W PO 126 1 0 124 1 0 International Recknor 2013 12 Percentage change from baseline in BMD at total hip, femoral neck, lumbar spine; percentage change from baseline in sCTX1 Postmenopausal women aged ≥55 years (mean age not reported) who were previously prescribed bisphosphonate therapy but had either stopped taking it by the time of the study screening visit or were still taking it with low adherence; T-score of −2 or less and −4 or greater at the total hip or lumbar spine determined at the local site and had one or more proximal femur (hip) and two or more vertebrae between L1 and L4 Denosumab 60 mg Q6 mol/L SC Ibandronate 150 mg Q1 mol/L PO 417 13 2 416 10 3 International Roux 2014 12 Percentage change from baseline in BMD at total hip, femoral neck, lumbar spine; percentage change from baseline in sCTX1 Postmenopausal women aged ≥55 years (mean age not reported) who were previously prescribed alendronate therapy but had either stopped taking it by the time of the study screening visit or were still taking it with low adherence Denosumab 60 mg Q6 mol/L SC Risedronate 150 mg Q1 mol/L PO 435 19 6 435 15 2 International Miller 2016 24 Mean percentage change from baseline in lumbar spine BMD Postmenopausal women ≥ 55 years (mean age not reported) who received oral bisphosphonate therapy for ≥2 years immediately before screening; T-score of ≤ −2.5 at the lumbar spine, total hip, or femoral neck Denosumab 60 mg Q6 mol/L SC Zoledronic acid 5 mg Q12 mol/L IV 313 11 7 312 18 15 International P1NP = N-terminal propeptide of type 1 collagen; sCTX1, serum carboxy-terminal collagen crosslinks; uNTX, urinary N-telopeptide cross-links.
Denosumab vs Bisphosphonates Outcomes Illustrative Comparative Risks* (95% CI) Odds Ratio (OR)
(95% CI)Number of Participants
(Studies)Quality of the Evidence
(GRADE)Assumed Risk
[Bisphosphonate]Corresponding Risk
[Denosumab]Clinical fractures [26] per 1000 [29] per 1000 (21 to 42) OR [1.12] (0.79 to 1.61) [4635] (7) ⊕⊕⊕⊝ moderate Osteoporotic fractures [17] per 1000 [19] per 1000 (12 to 29) OR [1.11] (0.71 to 1.73) [4635] (7) ⊕⊕⊕⊝ moderate ↵*The basis for the assumed risk is the rate of events in the bisphosphonate group. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the odds ratio of the intervention (and its 95% CI).
GRADE, Working Group grades of evidence: high quality—further research is very unlikely to change our confidence in the estimate of effect; moderate quality—further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate: low quality—further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very low quality—we are very uncertain about the estimate.
