Hip Fracture & Vitamin D Update November 2007 Gregory Gahm, MD

Informational Tidbits 60-90% of NH residents fall annually 20-50% of LTC pts who fall DIE the following year 33% who have a hip fracture never walk again From start (ambulance) to finish (therapy ends), the average direct cost of treating a hip fracture in Colorado is about $30,000 (Taxpayers pay most of it…) Falls and hip fractures account for a significant percentage of malpractice suits and formal complaints against NHs Evercare Colorado

Statistics Review RR = Relative Risk CI = Confidence Interval RR is reported with a Confidence Interval statistically calculated based on magnitude of measured difference, # of study subjects, time… RRs w/ CIs: < 1.0: Result less likely to happen w/ Intervention > 1.0: Result more likely to happen w/ Intervention When CI includes 1.0: Can’t tell If CI does not include 1.0, there is a 95% chance the same result would occur no matter how many times you repeat the study Evercare Colorado

Falls and Fractures Interventions shown to decrease falls in community-dwelling elderly: Muscle strengthening / balance retraining [RR 0.80*; CI* 0.66-0.98] 15 Week Tai Chi group exercise [RR 0.51; CI 0.36-0.73] - only for active participants; benefits disappeared when exercise stopped Withdrawal of psychotropic medication [RR 0.34; CI 0.16-0.74] Multidisciplinary, multifactorial, health/environment RF screening /intervention trials {No Rx changes} [RR 0.79; CI 0.67-0.94] Same interventions in LTCFs are markedly less effective Evercare Colorado

Hip Fractures and PPIs Pts >50 yo on Proton Pump Inhibitors (eg, Prilosec, Prevacid, Aciphex, Nexium, Omeprazole, Protonix) 13,556 hip fracture cases compared to 135,000 matched controls in the UK RR of hip fracture increased with dose, duration and age >1 year: RR = 1.44 [CI = 1.3-1.6] High Dose*: RR = 2.65 [CI = 1.8-3.9] *(>1.75x avg qd dose) JAMA, Dec 27, 06; Vol 296: 2947-53 Evercare Colorado

Clinical Trials of External Hip Protectors Early studies with < 50% compliance: Lauritzen (Lancet, 1993) 31 hip fxs in 418 controls [7.5%] vs 8 in 247 [3.2%] in treatment group. NONE on a pad protected hip. Kannus (NEJM, 2000) 21 hip fxs / 1000 pt-yrs [protected] vs 46 in the control group. 4 fxs on a pad protected hip. Ekman (Lancet, 1997) 21 hip fxs during study period Evercare Colorado

Clinical Trials of EHPs Wiener & Birge (02): 19 fractures / 310 patient-years on unprotected hips - vs - 1 fracture / 320 patient-years on protected hips Pooled data from 6 major trials: 3553 subjects Hip fxs in 2.2% of those with EHPs vs 6.2% of control group Average compliance rates estimated to be about 40% NNT to prevent 1 fracture / year is  25-40 with 40% compliance or  10-12 with 85% compliance Evercare Colorado

NH Chain National Hip Protector Study 14,000 patients in facilities were given the opportunity to wear hip protectors - 7000 chose NOT to wear them. - 7000 chose to wear hip protectors Compliance was estimated to be 55-70% Evercare Colorado

NH Chain National Hip Protector Study At the end of 1 year / 3500 pt-years: In those NOT wearing Hip Protectors…  115 Fractures (= 33 Fractures per 1000 residents annually) In the Hip Protector Intention to Treat group…  45 Fractures (= 13 Fractures per 1000 residents annually) Only 3 were in patients wearing EHPs Comparing ‘Wearers’ to ‘NON-wearers’ –> 3 vs 42 Fxs or 0.8 vs 12 Fractures / 1000 Patient-Years Evercare Colorado

The HIP PRO RCT Efficacy of a Hip Protector to Prevent Hip Fracture in NH Residents 1042 NH Residents, Mean age 85 Left or Right Pad Only 8 month avg participation Compliance checked 3x/wk: 60-80% avg Results: Same incidence of fractures on padded vs unpadded hips JAMA; July 25, 2007; Vol 298: 413-22 Evercare Colorado

The Rebuttal The JAMA article used a Hip Protector that has not been available since 2003! The study pad and the one that replaced it were tested using a drop weight system in 2004. The study pad absorbed 30% of peak force, the replacement 75-90% Most brands currently available still absorb only 25-35% of peak force, which may not be adequate to prevent a fracture Human volunteer fallers using the new pad in 2004 did > 400 falls without pain or hip injury Fall reflex characteristics (the baby / ice argument) Evercare Colorado

So, are the major brands of EHPs available equivalent? No. Brand makes a difference. Some brands tested in RCTs have shown dramatic reductions in hip fractures (FallGard) or at least statistically significant decreases (HipSavers) Some have shown NO difference or even MORE fractures (usu due to poor design, inadequate pad, or pad placement) Many have never been studied in RCTs Evercare Colorado

Evercare Colorado Hip Protector Study 3 Facilities chosen that historically [98-2001] had the highest number of hip fractures. There were 16 hip fractures among 200 patients in the previous 7 months (Annually, 27.5 hip fractures would be expected to occur in this group, a number that was consistent from 1998-2001) 180 of these patients were identified as being at highest risk and given Hip Protectors (FallGard) The 20 patients deemed to be at lowest risk for falls were excluded from the study Evercare Colorado

Evercare Hip Protector Study There were 3 hip fractures among these 180 pts the following year… …none of them were wearing their hip protectors at the time of their fall / fracture PS. There were also 3 fractures among the 20 persons excluded from the study… Evercare Colorado

Implementation Issues Lost Briefs Mark them well / Inservice Staff Acceptance by Facilities Significant financial savings from keeping census up and patients alive Fewer Complaint Surveys / Law suits Improved MDS data (better surveys?) No F Tags for ‘acceptable’ noncompliance rates SIGNIFICANT findings studies all had only 35-60% compliance Acceptance by Patients & Familes Nonpharmacologic treatment that works Families / patients appreciate the risk reduction in death, permanent disability, hospitalization / surgery, loss of Ambulation & Independent skills… Noncompliance Takes about 2-6 weeks for patients to get used to them Routine Checks + immediate feedback to nursing & CNAs Assistance from families – use information sheets Evercare Colorado

Ordering FallGard Hip Protectors 631 Alexandria Dr Naperville, IL 60565 800-828-0702 Fax 630-369-5219 www.fallgard.com Sizes: XS, S, M, L, XL, XXL, XXXL Order the “Sewn-In Pad” version Evercare Colorado

Vitamin D: The Basics Essential for adequate intestinal absorption of Ca++ Vitamin D insufficiency: Can compromise muscle strength & impair lower extremity function Associated with Increased Arterial Calcification Occurs in 75-85% of patients with Chronic Kidney Disease (Prevalence of CKD in NHs is likely >60-75%) Leads to Increased PTH -–> Higher Bone Turnover Evercare Colorado

Vitamin D: The Problem Most LTC residents have insufficient / deficient levels of Vitamin D –> 70-98% in recently published studies Evercare Colorado

Vitamin D and Falls Meta-analysis of RCTs in elderly (n=1237) -> 700 IU D2 = Avg Dose Vitamin D reduced risk of falling by 22% (OR 0.78; 95% CI (0.64-0.92) compared to Ca++ or placebo JAMA, April 28, 2004; Vol 291: 1999-2005 Evercare Colorado

Dosage of Vitamin D Needed to Reduce Falls N=125 LTC residents 5 months of D2 supplements 200, 400, 600 or 800 IU qd 800 IU supplement was not enough to achieve “sufficient” Serum 25(OH) levels in 50% of those treated Units / day 25 (OH) Vit D ng/ml RR falls 0 24 +13 1.0 200 24+8 1.10 400 22+9 1.05 600 24+9 1.21 800 30+6 0.28* (.10-.75) JAGS 2007; 55:234 Evercare Colorado

Vitamin D2 vs D3 Most standard Ca++ combinations contain 200 IU of Vit D2 -> Available as 400 IU Caps & usu given 3 qd -> D2 is only  2/3 as effective in raising Vit D levels as D3 -> 200 U Vitamin D2 =~ 140 U D3 -> Daily rec for Vit D2 would be 1500 IU qd Vitamin D3 Caps of 50,000 & 5,000 units are available and can be given monthly (always with a meal) -> Give with meals that contain fats or oils to stimulate bile acids & improve absorption Evercare Colorado

Vitamin D3 Supplementation with 800-1200 IU qd of Vit D3 in seniors reduces both falls and fractures by 20-30% Alternatively, give 50,000 IU q month of Vitamin D3 Lower doses have much less effect & do not correlate with decreased fracture rates with or without Ca++ supplementation 800 IU of Vitamin D3 qd undertreats 50% of pts Current AMDA guideline: 1000 IU of Vitamin D3 qd Evercare Colorado

Vitamin D: Resident Safety Residents with Stage IV Kidney disease (GFR <15) may not benefit from getting Vitamin D3 History of Kidney Stones is generally not a contraindication, but history must be reviewed carefully Recent studies show that doses of 100,000 - 130,000 IU / mo did not lead to adverse effects No need to test Vit D-25(OH) routinely! Lab test is MUCH more expensive (circa $50) than years of treatment Prevalence is high enough to assume >4 of 5 elderly patients are deficient Treating pts who aren’t deficient is very unlikely to cause harm & may have benefits Malabsorption syndromes may require higher doses & measurement of 25 (OH) Vit D levels to find effective dose Evercare Colorado

Vit D Deficiency & Prostate Cancer 14,916 men in Physicians' Health Study initially cancer-free After 18 yrs of F/U, 1,066 subjects were identified with incident Prostate CA & compared their Vit D status with that of 1,618 cancer- free, age- and smoking-matched controls Men with below-median levels of Vit D had a significantly higher risk of aggressive Prostate CA (OR 2.1) Men with below-median levels of Vit D & the Vit D receptor polymorphism FokI ff had a higher risk of total and aggressive Prostate CA than those with above-median levels and the Ff or FF genotype (OR 1.9 & 2.5, respectively). 
 Overall, 13-51% of the physicians in the study were Vit D deficient in the summer/fall & 36-77% were deficient in the winter/spring Li H, Stampfer MJ, Hollis JBW, Mucci LA, Gaziano JM, et al. (2007) A Prospective Study of Plasma Vitamin D Metabolites, Vitamin D Receptor Polymorphisms, and Prostate Cancer. PLoS Med 4(3): e103 doi:10.1371/journal.pmed.0040103 Evercare Colorado

Link Between Serum Vit D & Heart Disease Risk Levels of serum 25-OH D & CVD risk examined in 15,088 individuals age >20 7,186 men / 7,902 women versampling of blacks, Hispanics & individuals aged > 60 Mean 25-OH D level = 30 ng/mL. Levels lower in women, older individuals, ethnic minorities, obese subjects & those with HTN or DM OR of CVD comparing those w/ serum OH 25 D in lowest (<21) vs highest (>37) quartiles: – HTN: 1.30 – DM: 1.98 – Obesity: 2.28 – High serum triglyceride: 1.47 Good safety at doses of 2000-3000 IU per day Vit D level < 21 assoc w/ immunological abnormalities, HTN & CHF Author emphasized that 2000 IU/day is more likely to achieve adequate blood levels of Vit D for prevention of CVD & that there is compelling evidence that it reduces inflammation, lowers renin & angiotensin, may lower BP or blood vessel proliferation and may improve insulin sensitivity! Norris, et al. Archives of Internal Medicine; June 11, 2007 Evercare Colorado

Calcium Ca++ should still be given at doses of 1000-1500 mg qd as multiple doses –> never more than 500-600 mg at a time because people can’t absorb more from a single dose May give Ca++ with or without Vit D, as safety profile shows that the additional D2 will not cause harm (Norris study recommended 2000 IU / d or 60,000 IU q mo) Evercare Colorado

Conclusions Falls are bad Hip Fractures are worse We can have an immediate & long term impact with very little cost or effort Every patient should be on the equivalent of ±1000-1500 IU of Vitamin D3 daily, given most easily as: 50,000 units monthly, or 10,000 units (2 x 5000 u caps) weekly Every patient possible should be in GOOD Hip Protectors (eg, FallGard) Continue Ca++ supplements at 500 mg bid - tid Evercare Colorado

Obtaining Vitamin D3 Biotech-Pharmacal 50,000 IU capsule OTC? I’m still researching this… Biotech-Pharmacal 50,000 IU capsule NDC # 53191-362-01 (Product ID 362A) Bottles of 100 by prescription only for $15 5000 IU capsule NDC # 53191-244-50 (Product ID 2445000A) Bottles of 250 by prescription only for $7.85 Contact Brad Smith 1-800-345-1199 Fax: 479-443-5643 Brad@bio-tech-pharm.com Cardinal will drop ship the item, but you'll have to speak with a representative and tell them you need to have it "drop shipped from “Biotech-Pharmacal" Evercare Colorado

Vitamin D3 to reduce falls and Fractures References Bischoff-Ferrari HA. Effect of vitamin D on falls: a meta-analysis. JAMA. 2004;291:1999-2006. Bischoff-Ferrari HA. Fracture Prevention With Vitamin D,A Meta-analysis JAMA. 2005;293:2257-2264. Sambrook PN, et al. Vitamin D deficiency is common in frail institutionalised older people in northern Sydney. Med J Aust 2002; 176:560 Le Boff MS. Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA 1999; 281:1505–11. Harwood RH, et al. A randomized, controlled comparison of different calcium & vitamin D supplementation regimens in elderly women after hip fracture: the Nottingham Neck of Femur Study (NoNOF). Age Ageing 2004; 33:45–51. Semba RD. Vitamin D deficiency among older women with and without disability. Am J Clin Nutr 2000; 72:1529–34. Flicker L. Serum vitamin D & falls in older women in residential care in Australia. J Am Geriatr Soc 2003; 51:1533–8. Sahota O, Masud T, San P, Hosking DJ. Vitamin D insufficiency increases bone turnover markers and enhances bone loss at the hip in patients with established vertebral osteoporosis. Clin Endocrinol (Oxf ) 1999; 51:217–21. Morris A, Nordin BEC. Relationship between serum hydroxyvitamin D and bone resorption markers in vitamin D insufficiency. Bone 2002; 31:626–30. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999;69:842–56 Heaney R Symposium: Optimizing Vitamin D Intake for Populations with Special Needs: Barriers to Effective Food Fortification & Supplementation Barriers to Optimizing Vitamin D3 Intake for the Elderly; J. Nutr. 136:1123-1125, April 2006 Bischoff-Ferrar HA. Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged 60 y. Am J Clin Nutr 2004;80:752–8. NIH Web Site for Vitamin D recommendations : http://ods.od.nih.gov/factsheets/vitamind.asp Bio-Tech Pharmacal Web site www.bio-tech-pharm.com/products/d35.html Evercare Colorado