Osteoporosis Screening and Treatment in Type 2 Diabetes

Transcription

1 Osteoporosis Screening and Treatment in Type 2 Diabetes Ann Schwartz, PhD! Dept. of Epidemiology and Biostatistics! University of California San Francisco! October 2011! Presenter Disclosure Information ANN V. SCHWARTZ Research support: GlaxoSmithKline, Merck 1

2 Outline Increased fracture risk with type 2 diabetes (T2D) Prediction of fracture risk Risk factors for fracture Osteoporosis treatments Type 1 Diabetes Modest reduction in BMD Higher fracture risk Meta-analysis: Hip RR = 6.9 ( ) Not entirely accounted for by lower BMD RR expected from BMD = 1.4 Vestergaard

3 Type 2 Diabetes Average or higher BMD Overweight Higher risk of fractures T2 Diabetes and Hip Fracture Risk Meta-analysis Hip RR = 1.38 ( ) Meta-analysis. Age-adjusted. Vestergaard

4 T2D and Fracture Risk WHI Skeletal site RR (95% CI) Hip 1.41 (1.17, 1.70) Proximal humerus 1.30 (1.07, 1.56) Foot 1.44 (1.21, 1.71) Ankle 1.34 (1.16, 1.55) Clinical spine 1.28 (1.04, 1.56) Forearm 0.98 (0.84, 1.15) Bonds, et al Higher BMD in T2D Older Women 0.7" 0.6" 0.5" 0.4" 0.3" Femoral Neck" Calcaneal" Adjusted for age, BMI" All p <0.01 for Non-ins tx vs. not DM. Distal Radius" Insulin Tx" Non-Insulin Tx" Non-Diabetic" All NS for Insulin tx vs. non-insulin-tx." Schwartz et al. 2001" 4

5 Predicting fracture risk in T2D T2D have increased fracture risk but higher BMD. Or, diabetic patients fracture at a higher BMD. Can we use BMD to predict fracture risk? T-score predicts fracture in older adults with and without diabetes Femoral Neck BMD T-score Gender Fracture site Without diabetes HR (95% CI) C- index With diabetes HR (95%CI) C- index Women Hip 2.23 (2.06, 2.41) (1.43, 2.48) 0.72 Non-Spine 1.53 (1.47, 1.60) (1.31, 1.75) 0.64 Men Hip 3.53 (2.84, 4.38) (3.42, 9.53) 0.85 Non-Spine 1.62 (1.47, 1.77) (1.75, 2.69) 0.66 Data from three cohorts: Health ABC, SOF, and MrOS Femoral neck BMD T-score models adjusted for age. HR per 1 unit decrease in T-score. Schwartz et al

6 FN BMD T-score and Hip Fracture T-score difference of 0.6 for same fracture risk. FN BMD T-score FN BMD T-score and Hip Fracture FN BMD T-score 6

7 FRAX Score BMD (Femoral neck t-score) Age Gender Race BMI Fracture history Parental history of hip fracture Current smoker Recent corticosteroid use Rheumatoid arthritis 3+ alcohol drinks/day FRAX score predicts fracture in older adults with and without diabetes FRAX score Without diabetes With diabetes Gender Fracture site HR (95% CI) C- index HR (95%CI) C- index Women Hip 1.06 (1.05, 1.06) (1.03, 1.07) 0.70 Non-Spine 1.04 (1.03, 1.04) (1.02, 1.05) 0.64 Men Hip 1.10 (1.08, 1.13) (1.07, 1.27) 0.83 Non-Spine 1.07 (1.06, 1.08) (1.04, 1.14) 0.63 Data from two cohorts: SOF and MrOS FRAX score models are not adjusted for other variables. HR per 1 unit increase in FRAX score. 7

8 FRAX and Hip Fracture FRAX underestimates risk in DM FRAX and Hip Fracture 8

9 Fracture Prediction in T2DM Lower BMD predicts fractures, but at higher threshold for similar fracture risk FRAX predicts fractures, but current algorithm under-estimates risk in T2DM Add T2D to FRAX Risk Factors for Fracture in T2D Older age, female, previous fracture Lower BMD More frequent falls Reduced balance, gait, strength History of stroke Steroid use Peripheral neuropathy Insulin use TZD use Strotmeyer et al. 2001; Strotmeyer et al. 2005; Melton et al. 2008; Vestergaard et al. 2009; Kim et al

10 RSG: Increased fracture risk in women compared with metformin or glyburide Kahn et al ADOPT No Increased Fracture Risk in Men 10

11 More Frequent Falls in T2D (Health, Aging and Body Composition Study) OR* (95% CI) Normal glucose 1.00 Reference Impaired glucose 0.95 (0.82, 1.11) metabolism T2D 1.42 (1.20, 1.68) Falls: 0, 1, 2-3, 4-5, 6+ in past year! * Adjusted for age, race, gender Schwartz et al Osteoporosis therapy in T2D Lower BMD predicts fracture so therapy targeting BMD logical in T2D Little direct evidence of efficacy Are anti-resorptive therapies effective and safe in T2D at high risk of fracture? Lower bone turnover in T2D. Will further suppression of turnover have a negative effect on bone strength? Mechanism of reduced bone strength for a given BMD is not known. 11

12 Effect of Alendronate on BMD in Diabetic Women! Fracture Intervention Trial! Change in BMD (%)" 4" 3" 2" 1" 0" -1" Total Hip! ALN -2" PBO -3" 0" 12" 24" 36" Month" Keegan et al Change in BMD (%)" 8" 7" 6" 5" 4" 3" 2" 1" 0" Lumbar Spine! ALN 0" 12" 24" 36" Month" Nondiabetic ALN" Diabetic ALN" Nondiabetic placebo" Diabetic placebo" PBO Raloxifene and Vertebral Fracture MORE Trial (p for interaction = 0.04)" (60 and 120mg/d combined)! 0.13 (0.03, 0.55)! Diabetes! No diabetes! 0.59 (0.49, 0.71)! Overall, 60 mg/day! 0.70 (0.50, 0.80)! Overall, 120 mg/day! 0.50 (0.40, 0.70)! Johnell et al. 2004" RR (95% CI)! 12

13 Osteoporosis Therapy in T2D Limited data suggest that bisphosphonates are effective in preventing bone loss. Fracture efficacy? Raloxifene prevents vertebral fracture in T2D patients, as in other postmenopausal women. Summary In T2D, T-score and FRAX score predict fracture but under-estimate risk compared to non-dm Standard guidelines for fracture prevention: Fall prevention, particularly important Lifestyle modifications Diet Exercise Consider pharmacological therapy if fracture risk is high. Limited data on efficacy and safety of currently available osteoporosis therapies in T2D. 13

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