1. Division of Geriatrics and Nutritional Science
Pharmacological and Non-Pharmacological Interventions after Hip Fracture
Ellen F. Binder, MD
Division of Geriatrics and Nutritional Science

2. Disclosures of Interest
Research Support:
National Institute on Aging
Eli Lilly, USA
Consulting
Regeneron Pharmaceuticals, Inc.

3. Percentage New Impairment at 12 Months
Lower Extremity Activities of Daily Living Percentage of those Unimpaired Pre-Fracture With Impairment at 12 months Post-Fracture 10 20 30 40 50 60 70 80 90
100
Put on
Pants
In/Out
Bed
Walk
10 Feet
Rise
From
Chair
Walk 1
Block
On/Off
toilet
Bath
Climb 5
Stairs
Percentage New Impairment at 12 Months
Magaziner, J., Hawkes, W., Hebel, J.R., Zimmerman, S.I., Fox, K.M., Dolan, M., Felsenthal, G., Kenzora, J. Recovery from hip fracture in eight areas of function. J Gerontol A Biol Sci Med Sci, 55A, (9), 2000, M498-M507.
Magaziner J, et al. J Gerontol A Biol Sci Med Sci. 2000;55A:M498-M507.

4. Other Functional Consequences of Hip Fracture
Loss of Neuromuscular Function
gait/balance
More Difficulties with Instrumental Tasks
Shopping/housework
Increase in Cognitive Deficits
50% in hospital; 25% at 2 months
Increase in Depressive Symptoms
Changes in Social Function
visiting with others/participating in activities
Magaziner, J., Hawkes, W., Hebel, J.R., Zimmerman, S.I., Fox, K.M., Dolan, M., Felsenthal, G., Kenzora, J. Recovery from hip fracture in eight areas of function. J Gerontol A Biol Sci Med Sci, 55A, (9), 2000, M498-M507.
Magaziner, J., Simonsick, E.M., Kashner, T.M., Hebel, J.R., Kenzora, J.E. Predictors of functional recovery one year following hospital discharge for hip fracture: a prospective study. J Gerontol, 45, (3), 1990, M101-M107.
Magaziner J, et al. J Gerontol A Biol Sci Med Sci. 2000;55A:M498-M507.
Magaziner J, et al. J Gerontol. 1990;45:M101-M107.

5. Recovery In Lower Extremity ADLs10 20 30 40 50 60 70 80 2 6 12 18 24
Get In/Out of Bed
Walk 10 Feet
Rise From Chair
Walk 1 Block
Months
Unpublished data from Baltimore Hip Studies Cohort 2

6. Dependency in Walking 10 Feet Following Hip Fracture
100 90 80 70 60
% Dependent 50 40
Magaziner, J., Hawkes, W., Hebel, J.R., Zimmerman, S.I., Fox, K.M., Dolan, M., Felsenthal, G., Kenzora, J. Recovery from hip fracture in eight areas of function. J Gerontol A Biol Sci Med Sci, 55A, (9), 2000, M498-M507. 30
Observed % Dependent 20
Predicted % Dependent 10 2 6 12 18 24
Time (Month)
Magaziner J, et al. J Gerontol A Biol Sci Med Sci. 2000;55A:M498-M507.

7. Risk Factors for Poor Functional Recovery after Hip Fracture
Older age
Pre-fracture functional status
Multiple co-morbidities
Cognitive impairment
Poor social support
Depression
Delayed mobility after surgery
Hip pain at 2 months after surgery
Decline in muscle strength (& mass?)

8. Falls and Injury after Hip Fracture
~50% of hip fracture patients fall within 12 mo
~30% have recurrent falls within a year
~30% sustain a fall-related injury
~12% sustain a fall-related fracture
Lloyd BD et al. J Gerontol Med Sci 2009; 64A: 599-=609

9. Risk Factors for Falls and Injury 12 months after Hip Fracture
Recurrent Falls
Number of co-morbidities & medications
Congestive Heart Failure*
Post-fracture vitamin D levels
Pre-fracture disability
Handgrip strength
SF-36 Quality of life*
* Independent risk factor in multivariate model
Lloyd BD et al. J Gerontol Med Sci 2009; 64A: 599-=609

10. Risk Factors for Falls and Injury 12 months after Hip Fracture
Injurious Falls
Number of co-morbidities & medications
Post-fracture vitamin D levels
Pre-fracture disability
Multiple strength measures
Static balance
Habitual physical activity
Depth perception
SF-36 Quality of life
Lloyd BD et al. J Gerontol Med Sci 2009; 64A: 599-=609

11. Risk Factors for Falls and Injury 12 months after Hip Fracture
Fractures
Age*
Osteoarthritis
Nutritional status (MNA score)*
Pre-fracture disability
SF-36 Quality of life
Lloyd BD et al. J Gerontol Med Sci 2009; 64A: 599-=609

12. Challenges to Designing & Comparing Interventions for Hip Fracture Recovery
Heterogeneous patient characteristics
Timing and duration of interventions
Intensity of interventions
Location of intervention delivery
Adherence to interventions
Multi-component intervention design
Variation in global health care systems
Outcome measurement

13. Potential Interventions for Hip Fracture Recovery and Injury Prevention
Non-Pharmacologic Interventions - Interdisciplinary team management - Post-discharge GRN case management - Nutritional interventions - Exercise training/physical therapy Pharmacologic Interventions - Anabolic steroids - Vitamin D - Antidepressants

14. Nutritional Interventions (RCT n=24 trials)
Oral Nutritional Supplements (n=10 trials) - Trend toward decrease in acute complications - Variable effects on LOS - Variable mostly NS effects on FXN & QOL - No effects on mortality Nasogastric Feedings - No beneficial effects Limitations Small samples, no ITT analysis Lack of blinding Variable assessment of nutritional status

15. Pooled Outcomes From RCTs (n=11) of Extended Rehabilitation after Hip Fracture
From Auais MA et al Phy Ther 2012; 92:

16. Pooled Outcomes from RCTs of Extended Rehabilitation after Hip Fracture
From Auais MA et al Phy Ther 2012; 92:

17. Pooled Outcomes from RCTs of
Extended Rehabilitation after Hip Fracture
From Auais MA et al Phy Ther 2012; 92:

18. Effects of High-Intensity PRT and Targeted Multidisciplinary Treatment after Hip Fracture Singh NA et al. JAMDA : 24-30
12 months of PRT + targeted geriatrician supervised multi-component TX vs. UC
81% reduction in mortality
84% reduction in NH admissions
Improvements in physical impairments and depression correlated with ADL improvements
Improvements in BADL, vision, walking endurance correlated with NH use

19. Key Characteristics of Successful Exercise/Rehab Interventions
Progressive resistance exercises
≥ 12 weeks of resistance training
Cognitively intact or MCI level
Attention to nutrition
Multi-component approach

20. Other Considerations Cost-effectiveness
Cognitive-behavioral strategies
Appropriate patient targeting
Integration in existing health care programs

21. Why Consider Anabolic Agents to Enhance Hip Fracture Recovery?

22. Potential Pharmacological Agents
Anabolic steroids
-Growth Hormone (n=161, 6 mo tx)
-Nandrolone & Testosterone
Myostatin Antagonists
GDF8 is a negative regulator of muscle growth.
When inhibited it can induce skeletal muscle hypertrophy.
Antidepressant medications

23. Testosterone Replacement in Female Hip Fracture patients Baseline Sample Characteristics

24. Testosterone Replacement in Female Hip Fracture patients Effects on Body Composition
Variable
Time
Placebo
(n=5)
Testosterone
(n = 9)
p-value
Total Fat-Free Mass
by DXA (kg)
Baseline
38.6 ± 2.2
38.0 ± 6.3
Final
38.5 ± 2.0
39.6 ± 7.8
change
-0.01 ± 0.9
1.6 ± 1.8*
0.03
Total Fat Mass
DEXA (kg)
17.2 ± 6.6
20.9 ± 8.8
18.7 ± 6.8
20.6 ± 8.6
1.5 ± 1.4
-0.3 ± 2.3
0.20
Thigh Muscle Area (cm2)
FX’d side
56.2 ± 7.1
50.1 ± 10.8
63.2 ± 8.3
58.6 ± 11.2
6.9 ± 5.7
8.5 ± 6.5*
0.88

25. Testosterone Replacement in Female Hip Fracture patients Effects on Physical Performance
Variable
Time
Placebo
(n=5)
Testosterone
(n = 9)
p-value
Total Modified PPT Score
Baseline
24.5 ± 4.1
23.0 ± 4.8
Final
29.0 ± 2.9
26.4 ± 4.8
Change
4.5 ± 4.6
3.4 ± 3.5*
0.46
Knee Extension
1-RM (lbs)
63.1 ± 16.3
61.4 ± 22.0
68.4 ± 23.4
74.2 ± 26.8
6.3 ± 9.2
12.8 ± 8.6*
0.20

26. Vitamin D Replacement in Hip Fracture Patients
8 ng/dl
Mak JCS et al. JAGS 58: , 2010

27. Vitamin D Replacement After Fracture
Papaioannou A et al.
BMC Musculoskeletal
Disorders 2011; 12: 135

28. Summary
Optimal management strategies for hip fracture recovery require further study. A multi-disciplinary, multi-component approach may have greatest effectiveness.
Extended physical rehabilitation/exercise with PRT for several months after fracture can improve physical performance, ADL performance, and QOL at 12 mo after fracture.
Pharmacologic approaches have not been adequately tested, but have the potential to enhance recovery.
Cost effectiveness of most interventions has not been adequately evaluated.

29. Questions???