1.  Exercise and Vitamin D in Fall Prevention Among Older Women Journal Club, June 2016 Theresa Drallmeier and Tu Dao

2. Background  Falls are the leading cause of fracture and unintentional injury in adults  20% of falls in older adults lead to injury requiring medical attention  Prevention is key  Moderate amount of evidence exercise (particularly including balance components) prevent falls as well as injuries related to falls  Less clear evidence for vitamin D supplementation

3. Vitamin D in Fall Prevention  2010 meta-analysis: vitamin D decreased falls (RR 0.83, 95% CI 0.77-0.89)  2012: USPSTF recommended vitamin D supplementation (and exercise) for fall prevention, grade B recommendation  2012 meta-analysis: vitamin D did not reduce fall risk or rate of falls in community dwelling adults (RR 0.96, CI 95%, 0.89-1.03),but may have helped in pts with lower pretreatment vitamin D levels  2012 RCT: high dose vs low dose vit D supplementation – high dose  higher fall incidence (no placebo)  2014: American Geriatrics Society rec at least 1000 IU vit D daily

4. Study Overview  Purpose:  To investigate the separate and combined effects of exercise training and vitamin D supplementation on:  Fall reduction  Injurious falls  Improving bone density  Improving physical function … In older women at risk for falls.  Study design: RCT

5. Study Overview  Population  409 home-dwelling women, 70-80 yo, in Finland  At least 1 fall within the last year  Exclusion criteria: vitamin D use, contraindications to exercise, or >2 hours of moderate or vigorous exercise per week  Variable of interest/Comparison  4 study groups:  (1) Placebo without exercise  (2) Vitamin D (800 IU/d) without exercise  (3) Placebo and exercise  (4) Vitamin D (800 IU/d) with exercise

6. Methods  Vitamin D supplementation:  800 IU of vitamin D3 or placebo x 24 months  Pills similar in size, appearance, taste  Pill packs q6 mo, compliance confirmed by pill count  Exercise:  Supervised, progressive group training classes  Twice weekly x 1 year, then once weekly x 1 year  Led by physiotherapists  Weight machines, pulleys, free weights  Supplemental home exercise program  5-15 min daily, on all rest days

7. Measuring Outcomes  Primary outcome: monthly reported falls  Fall: “an unexpected event in which the participant comes to rest on the ground, floor, or lower level”  Secondary outcomes:  Injurious falls  Pt sought medical care, included injuries like bruises, abrasions, contusions, sprains, fractures, head injuries  Number of fallers/injured fallers  Bone density  DEXA scan to obtain BMD of lumbar spine, left proximal femur  Physical functioning  Short Physical Performance Battery: static balance, walking speed, 5 time chair stand tests, Timed Up and Go (TUG) test, backward walking

8. Methods: Critical Appraisal  Was the assignment of patients to treatments randomized?  Were the patients/clinicians kept “blind” to which treatment was being received?  Were the groups similar at the start of the trial?  Aside from the allocated treatment, were groups treated equally?  Were all patients who entered the trial accounted for, and were they analyzed in the groups to which they were randomized?

9. Methods: Critical Appraisal  Was the assignment of patients to treatments randomized?  Were the patients/clinicians kept “blind” to which treatment was being received?  Were the groups similar at the start of the trial?  Aside from the allocated treatment, were groups treated equally?  Were all patients who entered the trial accounted for, and were they analyzed in the groups to which they were randomized?

10. Randomization and Blinding  Randomization:  Validated randomization software  Simple randomization  Blinding: - Statistician blinded to characteristics of study participants during randomization - Participants and study personnel blinded to vitamin D group assignments - No way to blind exercise assignment

11. Methods: Critical Appraisal  Was the assignment of patients to treatments randomized?  Were the patients/clinicians kept “blind” to which treatment was being received?  Were the groups similar at the start of the trial?  Aside from the allocated treatment, were groups treated equally?  Were all patients who entered the trial accounted for, and were they analyzed in the groups to which they were randomized?

13. Methods: Critical Appraisal  Was the assignment of patients to treatments randomized?  Were the patients/clinicians kept “blind” to which treatment was being received?  Were the groups similar at the start of the trial?  Were all patients who entered the trial accounted for, and were they analyzed in the groups to which they were randomized?

14.  Intention-to-treat analysis = patients are analyzed in the groups to which they were randomized  Loss to follow-up should be minimal:  preferably <20%, although if few pts have outcome of interest, even smaller losses can bias the results  This study: 9.5%  Health reasons, loss of interest, spouse illness, death

15. Loss to follow-up

16. Analysis of Results  How large was the treatment effect?  How precise was the estimate of the treatment effect?

17. Measuring Treatment Effect  Injurious falls:  Placebo and exercise group: HR 0.45 (95% CI, 0.23-0.99)  Vit D and exercise group: HR 0.38 (95% CI, 0.17-0.83) Hazard ratio: HR = 1  no difference HR > 1  how many times more likely to occur HR < 1  how many times less likely Precision: does the confidence interval include 1?  if so, no statistically significant effect

18. Treatment Effect: Secondary Outcomes

19.  Femoral neck BMD declined in all groups, but the most in placebo w/o exercise group  Placebo and exercise group was only group to maintain walking speed (P = 0.007)  Both exercise groups improved in chair stand time (P=0.01)  TUG time worsened in vitamin D without exercise group compared to placebo w/o exercise (P=0.01)

20. External validity/applicability  Are my patients similar enough to those in the study?  Is the treatment feasible in my setting?

21. Take-home message  Exercise reduced injurious falls in older home- dwelling women, but did not reduce overall fall rate  Vitamin D mildly reduced bone loss per DEXA, but did not improve clinical outcomes or physical functioning

22. Limitations?

23.  High baseline vitamin D levels in population  May mask potential benefits of vitamin D  Difficult to recruit frailest women, so participants all in good health/physical condition  Cannot generalize to men, or to frail/institutionalized women  Lack of blinding for exercise  “sham” exercise routine?  Were there study crossovers that started taking vitamin D or exercising while not randomized to those groups?