Update on Fracture Risk and Osteoporosis in Type 2 Diabetes Steven Ing, MD, MSCE 3/29/2014
Fracture Risk in Diabetes Mellitus
Diabete s Type
# Studies
Spine Zscore
Hip Z-score
Expected Hip Fracture Risk
Observed Hip Fracture Risk
T1DM
5
-0.22 ± 0.01
-0.37 ± 0.16
1.42
6.94 (3.25-14.78)
T2DM
8
+0.41 ± 0.01
+0.27 ± 0.01
0.77
1.38 (1.25-1.53)
Vestergaard 2007 Osteoporos Int 2007;18(4):427-444
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Objectives Discuss Fracture risk in DM BMD and FRAX as predictors of fracture in DM Glycemic control as a fracture risk DM medications and fracture risk Bisphosphonate effects in DM
Case 60 year old woman comes for osteoporosis evaluation. 2012: walking dog, slipped on ice down stairs, T12 compression fracture fracture, s/p vertebroplasty 2013: fell down stairs, first metatarsal, midfoot fracture T2DM: metformin, HbA1c 6.5% HLD: simvastatin Hypothyroidism: levothyroxine Seizure disorder: depakote Mother had fragility pelvic fracture 139 lb, 5’6” (63 kg, 167.6 cm) DXA: Femoral neck T-score -2.2
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Fracture Risk in T2DM WHI-OS, n=93,676, follow up 7 years 5,285 with T2DM at baseline BMD subset n=6,384 Site
Multivariate Adjusted RR (95% CI)
Multivariate & BMD Adjusted RR (95% CI)
Any fracture
1.20 (1.11-1.30)
1.24 (0.96-1.63)
Hip/pelvis/upper leg
1.46 (1.17-1.83)
1.82 (0.90-3.64)
Lower leg/ankle/knee
1.13 (0.95-1.34)
1.31 (0.76-2.24)
F t Foot
1 32 (1 1.32 (1.07-1.62) 07 1 62)
1 27 (0.61-2.64) 1.27 (0 61 2 64)
Upper arm/shoulder/elbow
1.13 (0.90-1.41)
0.90 (0.39-2.07)
Lower arm/wrist/hand
1.02 (0.85-1.22)
1.27 (0.71-2.25)
Spine
1.27 (1.00-1.61)
1.57 (0.72-3.44)
Bonds JCEM 2006;91(9):3404-10
Does BMD Predict Fractures in T2DM?
Schwartz JAMA 2011;305(21):2184-2192
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FRAX Underestimates Fractures in T2DM Adjustment for:
Major Osteoporotic Fracture
Hip Fracture < 65 Years
Hip Fracture ≥ 65 Years
FRAX Risk Factors
1.61 (1.42-1.83)
6.27 (3.62-10.87)
2.22 (1.71-2.90)
FRAX Probability (Continuous)
1.59 (1.40-1.79)
5.34 (3.14-9.08)
2.06 (1.59-2.66)
Giangregorio JBMR 2012;27(2):301-308
FRAX Underestimates Fractures in T2DM
Giangregorio JBMR 2012;27(2):301-308
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FRAX Underestimates Fractures in T2DM
Adding T2DM to FRAX is desirable but requires additional data and modeling Giangregorio JBMR 2012;27(2):301-308
Possible Mechanisms for Increased Fracture Risk in T2DM Increased falls (hypoglycemia, neuropathy, retinopathy) Bone Turnover: Low bone formation Microarchitecture: increased cortical porosity Material properties: AGE accumulation in bone collagen Longitudinal Changes in BMD
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DM increases risk of fracture-related hospitalization ARIC Study N=15 140 N=15,140 DM dx: 1,195 DM undx: 605 No DM: 13,340 HbA1c measured 1990-1992 Median follow up 20 years 1,078 incident fracturerelated hospitalizations +DM: 6.6/1000 PY -DM: 3.9/1000 PY HR 1.74 (1.42-2.14)
Schneider, Diabetes Care 2013;36:1153-1158
Poor glycemic control ↑ fracture risk
Schneider, Diabetes Care 2013;36:1153-1158
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Poor glycemic control ↑ fracture risk Rotterdam Study N=4,135 HbA1c>7.5% vs 7.5% vs No DM
HbA1c