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