Table 3.
Sensitivity and Stratified Analyses for the Risk of Any, Nonvertebral, and Vertebral Fractures Per One SD Increase in FT4
| Any Fracturea | Nonvertebral Fractureb | Vertebral Fracturec | ||||
|---|---|---|---|---|---|---|
| No. of Events/ Participants | HR (95% CI) | No. of Events/ Participants | HR (95% CI) | No. of Events/ Participants | HR (95% CI) | |
| Main analysis | 1629/22,977 | 1.08 (1.02–1.15) | 1273/19,101 | 1.10 (1.03–1.18) | 129/17,711 | 1.06 (0.86–1.30) |
| Sensitivity analyses | ||||||
| Medication use | ||||||
| Excluding participants with thyroid medication at baselined | 1552/22,440 | 1.09 (1.02–1.16) | 1240/18,697 | 1.14 (1.06–1.23) | 125/17,309 | 1.08 (0.86–1.37) |
| Excluding participants with thyroid-altering medication at baselinee | 1537/21,976 | 1.09 (1.02–1.15) | 1200/18,256 | 1.11 (1.03–1.19) | 125/16,868 | 1.07 (0.86–1.32) |
| Excluding participants with antifracture medication at baselinef | 1622/22,927 | 1.08 (1.02–1.15) | 1263/19,038 | 1.10 (1.03–1.18) | 127/17,666 | 1.05 (0.85–1.29) |
| Definition of fracture | ||||||
| Including only studies with formal fracture adjudicationg | 1026/15,805 | 1.11 (1.02–1.19) | 1111/17,208 | 1.11 (1.03–1.19) | 113/15,806 | 1.07 (0.86–1.32) |
| Including only studies with most uniform definition of fractureh | 1155/19,728 | 1.06 (0.99–1.14) | 685/14,461 | 1.08 (0.98–1.19) | 65/14,462 | 1.10 (0.83–1.47) |
| Other | ||||||
| Further adjusting for BMI, smoking status, and diabetes mellitus | 1591/22,536 | 1.21 (1.00–1.46) | 1140/17,562 | 1.09 (1.01–1.18) | 126/17,290 | 1.03 (0.83–1.27) |
| Excluding studies with loss of follow-up rate >5% | NA | NA | 1174/17,981 | 1.13 (1.04–1.22) | NA | NA |
| BMD | ||||||
| Further adjusting for lumbar spine BMD at baselinei | NA | NA | NA | NA | 39/1399 | 0.96 (0.68–1.36) |
| Further adjusting for whole-body BMD at baselinej | 183/1399 | 0.89 (0.75–1.04) | NA | NA | NA | NA |
| Stratified analyses | ||||||
| Stratified for sex | ||||||
| Women | 1013/11,321 | 1.11 (1.03–1.19) | 827/10,075 | 1.10 (1.01–1.20) | 62/8679 | 1.12 (0.83–1.51) |
| Men | 616/11,656 | 1.05 (0.95–1.15) | 446/9026 | 1.08 (0.96–1.22) | 67/9032 | 1.00 (0.75–1.33) |
| P value for interaction | NA | 0.39 | NA | 0.79 | NA | 0.61 |
| Stratified for age | ||||||
| <75 years at baseline | 1041/18,367 | 1.10 (1.02–1.19) | 955/17,144 | 1.10 (1.02–1.20) | 87/15,917 | 0.96 (0.74–1.25) |
| ≥75 years at baseline | 588/4610 | 1.06 (0.96–1.16) | 318/1957 | 1.10 (0.97–1.25) | 42/1794 | 1.25 (0.88–1.76) |
| P value for interaction | NA | 0.47 | NA | 0.99 | NA | 0.25 |
| Stratified for duration of follow-up | ||||||
| <5 years | 446/5920 | 1.04 (0.93–1.15) | 47/888 | 0.82 (0.59–1.14) | 7/888 | 0.60 (0.26–1.37) |
| ≥5 years | 1183/17,057 | 1.09 (1.02–1.18) | 1226/18,213 | 1.10 (1.03–1.18) | 122/16,823 | 1.07 (0.87–1.33) |
| P value for interaction | NA | 0.39 | NA | 0.07 | NA | 0.18 |
All analyses were adjusted for age (as a continuous variable) and sex; FT4 was measured in all studies but SOF and Health ABC Study (FT4 not measured in participants with TSH within the reference range). HRs are per one SD increase in FT4.
Abbreviations: EPIC, European Prospective Investigation of Cancer; Health ABC, Health, Aging, and Body Composition; InCHIANTI, Invecchiare in Chianti Study; MrOS, Osteoporotic Fractures in Men Study; NA, not appropriate; OPUS, Osteoporosis and Ultrasound Study; PROSPER, Prospective Study of Pravastatin in the Elderly at Risk; SOF, Study of Osteoporotic Fractures.
Data on any fractures were available for seven studies (MrOS, EPIC-Norfolk Study, InCHIANTI Study, Leiden 85-Plus Study, PROSPER, Rotterdam Study, and Busselton Health Study).
Data on nonvertebral fractures were available for seven studies (MrOS, EPIC-Norfolk Study, InCHIANTI Study, Rotterdam Study, Busselton Health Study, Sheffield Study, and OPUS).
Data on vertebral fractures were available for five studies (MrOS, EPIC-Norfolk Study, InCHIANTI Study, Rotterdam Study, and Busselton Health Study). Vertebral fracture was defined as a clinical symptomatic dorsal or lumbar fracture.
Thyroid medication was defined as thyroxine or antithyroid medication.
Thyroid-altering medication included oral corticosteroid, amiodarone, iodine, thyroxine, or antithyroid medication.
Antifracture medication was defined as bisphosphonate, calcitonin, selective estrogen receptor modulator, or parathyroid hormone.
EPIC-Norfolk Study, InCHIANTI Study, MrOS, OPUS, Rotterdam Study, and Sheffield Study.
EPIC-Norfolk Study, InCHIANTI Study, Leiden 85-Plus Study, MrOS, and PROSPER.
Lumbar spine BMD was available in MrOS only.
Whole-body BMD was available in MrOS only.