Obesity and Bone health cancer survivors. Kate Wolin, ScD, FACSM Loyola University Chicago, Stritch School of Medicine

Transcription

1 Obesity and Bone health cancer survivors Kate Wolin, ScD, FACSM Loyola University Chicago, Stritch School of Medicine

2 conflict of interest disclosure: Theraband research support Up to Date publishing royalty Dr. Oz Show travel expenses AICR travel expenses

3 Irwin ML. Exerc. Sport Sci. Rev. 2006; 34(4): Dietary- Weight Loss and Physical

4 Post diagnosis health in cancer survivors Increased risk of diabetes Increased risk of heart disease Diminished quality of life Fatigue Lymphedema Diminished bone density Functional limitations Cognitive function Sleep (quality and quantity) Recurrence and Survival

5 Bone health in women Age Ethnicity Vitamin D Calcium Family history Sex hormones Other medications (e.g., steroids) Weight Exercise Smoking Alcohol

6 Bone health in women Age Ethnicity Vitamin D Calcium Weight Exercise Smoking Family history Sex hormones Other medications (e.g., steroids) Chemotherapy Radiation therapy Aromatase inhibitors Alcohol

7 Obesity & Fracture de Laet et al

8 Bones & Hormones G 2 S M Factors that trigger proliferation: GH, IGF-1, leptin, afgf, TGF β Factors that inhibit: estradiol, cortisol Pro-apoptotic factors: estradiol G 1 G 0 Apoptosis Factors that trigger differentiation: GH, IGF-1, bfgf, BMPs, leptin, PTH, T 3, cortisol Anti-apoptotic factors: PTH, cortisol Fig. 10. Hormonal control of bone growth. The proliferative component of cell growth cycle [157] includes DNA replication (S phase), preparation for mitosis (G 2 phase) and mitosis (M phase). Initiation factors mediate transition from the quiescent G 0 state to S phase. Progression factors mediate terminal differentiation and transition from M phase to the hypertrophic G 1 phase of the cell cycle. Cells can also enter the quiescent G 0 phase and, under the influence of pro-apoptotic factors, undergo cell death (reproduced from Borer, [158] with permission. Copyright John Wiley and Sons Limited). afgf = acidic fibroblast growth factor; bfgf = basic fibroblast growth factor; BMPs = bone morphogenetic proteins; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTH = parathyroid hormone; T 3 = liothyronine; TGF β = transforming growth factor β. Borer 2005 Sports Med

9 Mechanisms linking Fat and Bone Fig. 2 Summary of the principal mechanisms by which the hyper- Reid 2008

10 exercise and bone in women 11 Exercise No exercise 8 Change/y in spine BMD (%) Calcium intake (mg/d) Specker, Am Soc Bone Min Research

11 Exercise and bone Swimming 1.0 BMD (g/cm 2 ) b Reference Basketball/volleyball Running/speed skating Soccer/track Tennis/squash Triathlon Weightlifting Cycling Gymnastics Cross-country skiing/orienteering Swimming Age (y) Fig. 15. The effects of different sports on the bone mineral density (BMD) of the spine and the femoral neck in young female athletes. Borer 2005 Sports Med

12 Weight loss & Bone Density Riedt et al 2005

13 weight loss & bone loss TABLE 3 -- Regression Coefficients for Predicting Weight Loss from Six-Month Changes in BMD and Bone Markers: A Positive Relationship Indicates that Weight Loss was Associated with Decreases in BMD or the Bone Markers Fitted Regression Coefficients ± SE ( P value) Covariate Adjustment Baseline bone measure Baseline bone measure and intervention assignment * Panel of baseline BMD total gm/cm 2 /lb ( 10-4 ) BMD spine gm/cm 2 /lb ( 10-4 ) BMD hip gm/cm 2 /lb ( 10-4 ) NTx nm/mmcreat/lb Alk. Phosphatase u/l/lb ( 10-2 ) Osteocalcin ns/ml/lb ( 10-2 ) 6.25 ± ± ± ± ± ± 2.04 P =.003 P =.22 P =.44 P =.09 P =.68 P = ± ± ± ± ± ± 2.08 P =.004 P =.13 P =.66 P =.03 P =.80 P = ± ± ± ± ± ± 2.09 Chao et al 2000

14 Breast Cancer Treatment & Bone Loss

15 Bone health in breast cancer Crude Model 1 Model 2 Spine P crude P adjusted P adjusted Total hip P crude P adjusted P adjusted Total body P crude P adjusted P adjusted Any site P crude P adjusted P adjusted Model 1 is adjusted for age, race/ethnicity, clinical center, and years since menopause. Model 2 is adjusted for age, race/ethnicity, clinical center, years since menopause, and hormone therapy use. FIGURE 1. Comparison of prevalence of osteoporosis based on DXA measurements at baseline. Osteoporosis is defined by a T score 2.5 from Chen 2005 Cancer

16 Treatment and Bone in Breast Cancer Table 4. Effects of Adjuvant Chemotherapy on Bone Density for Age (Z Scores) at Selected Sites* Site Site of Chemotherapy (95% Confidence Interval) P Value Total hip 0.65 ( 0.32 to 0.98) Femoral neck 0.47 ( 0.12 to 0.82) Trochanter 0.55 ( 0.20 to 0.90) Anteroposterior spine 0.60 ( 0.01 to 1.19) 0.05 Lateral spine 0.84 ( 0.23 to 1.45) * Adjusted for body mass index, family history of osteoporosis, and ever use of hormone replacement therapy, alcohol, and tamoxifen. A negative number indicates lower bone density in women who received adjuvant chemotherapy. Greep 2003 Eastell 2006 FIG. 2. Unadjusted median percentage change in (A) lumbar spine and (B) total hip BMD after 1- and 2-year treatment. Bars represent 95% CIs.

17 Lean & Fat Mass in BrCa 1.2" 1.16" BMD 1.12" Lean"Mass" Fat"Mass" 1.08" 1.04" 1" Q1" Q2" Q3" Q4" Body composition George et al 2013

18 Gynecologic Cancer Stavraka et al 2013 Oncologist

19 Role of BMI

20 Irwin 2009 Postmenopausal survivors in an exercise intervention Treatment (%) None 5 14 Radiation only Chemotherapy only Radiation and chemotherapy Hormone therapy (%) None Tamoxifen Aromatase Inhibitors Current use of calcium supplements Current use of vitamin D supplements EX UC Current use of bisphosphonates 13 3

21 Schmitz 2010 MSSE; Wolin 2012 J Support Oncol Exercise & Survivors Evidence-Base Breast (during) Breast (after) Prostate Hem (no HSCT) Hem (during or after HSCT) Safety A A A A Fitness A A A B C Strength A A A C Body composition B B B QOL B B B C Fatigue B B A B C Anxiety B B Flexibility A Physical function A B Lymphedema A (is safe) Body image B

22 Fracture Risk NCCN Guidelines in Prostate: FRAX algorithm Treat those with 10 yr hip fracture risk >3% or 10 yr major fracture risk >20% NCCN Breast Use of DXA to evaluate fracture risk FRAX algorithm USPSTF Screen all women over 65 and those at high risk ASCO Bone density screening for breast cancer survivors with high risk family history, AI use, ovarian failure, prior fracture, weight< 70kg Wolin et al 2011 J Supp Oncol

23 Fracture Risk At what fracture risk level is exercise unsafe? Wolin et al 2011 J Supp Oncol

24 Exercise and Nutrition to Enhance Recovery and Good Health for You NCI RO1CA148791

25 Who is eligible? Women 21 or older 25 BMI<45 Diagnosed with stage I-III breast cancer within the last 5 years Completed treatment Willing to attend group meetings and stay in contact for 2 years Able to be physically active NOT currently enrolled in another weight loss or nutrition study

26 Bone Ancillary Study Establish the relations between weight loss, exercise and bone loss in postmenopausal breast cancer survivors Evaluate whether exercise offsets weight-loss associated bone loss in breast cancer survivors NCI R21CA161105

27 Eligibility Postmenopausal Accelerometer at baseline, 6, 12 mo DXA at baseline and 12 months

28 Participant Data StL N= screened, 135 eligible N=81 consented Mean age: 56 Mean BMI: 32 86% currently taking osteoporosis medications Stage: 31% stage I 53% stage II 16% stage III Mean DXA T-score Lumbar: 1.08 Spine: 1.21

29 Key energy measures Medical history oophorectomy amenorrheic at least 12 mos Supplements (calcium, vitamin D) Medication use (bisphosphonates, hormone therapies, SERMS, AIs) Physical activity (Godin) BMI

30 Additional Measures Bone density via DXA Lean mass via DXA Weight bearing/bone loading exercises via self report Accelerometer measured physical activity Bone turnover assays

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32 Acknowledgements Wolin WUSTL Team: Casey Fagin, Sonya Izadi, Shelley Forbes, Georgina Hartzell ENERGY Team Funders