The Impact of Depressive Symptoms and Smoking on Bone Health in - PowerPoint PPT Presentation

The Impact of Depressive Symptoms and Smoking on Bone Health in Adolescent Girls: Recent Findings and New Directions in Research

Goals for Today  Overview of recent collaborative paper – has overlap with expertise in multiple HHD departments  Implications for prevention  Current plans for my “next steps”  Potential new collaborations?

Overall Questions in Program of Research  In the transition of puberty . . . – What makes some adolescents more vulnerable than others to negative behavioral and physical health outcomes? – Does the stress system (or other hormones) play a role in this vulnerability?

Recent research findings  Smoking & Metabolic Consequences in Adolescent Girls – aka “Health Behavior” study

Acknowledgements  R01 & R21 funding from NIDA  CTRC: nursing, DXA, core labs  Co-I’s: Elizabeth Susman, PhD, Heidi Kalkwarf, PhD; Sarah Berga, MD  Project Director: Stephanie Pabst, MEd, CCRP  Post-doc: Sarah Beal, PhD

Health Behavior Study  Opportunity: – Examine impact of puberty, smoking and depressive symptoms on bone accrual – Stress system mediators

Puberty (Timing) Reproductive Health (gonadal and adrenal hormones, menstrual = Unknown Smoking cycle) effect = Positive Status effect = Negative Bone Health effect Depression/ (Bone mineral accretion) Anxiety Figure 1 – Conceptual Model

Conceptual Model: Puberty Bone Accrual Smoking Age 11-19 Depressive Sx

Bone Health  Osteoporosis costly public health problem – affecting > 10 million adults (NIH consensus 2000); particularly elderly women – > 30 mil others have low bone mass – $25 billion expected costs for 3 mil fractures by 2025 (NOF, 2011)

Bone Health  Non-modifiable factors account for large component of bone mass – Race, gender, genetic background – 75% variance in peak mass due to inherited factors (Mora & Gilsanz, 2003)

Bone Health– modifiable factors  Lifestyle: – Exercise, nutrition » Activity accounts for 2% variance in bone mass (Janz et al., 2006) » Exercise intervention: -0.7 to 3.22% change in postmenopausal women ( Review ; Cheung & Giangregorio, 2012)  Endocrine: » Post-menopausal loss (2-5%/yr) » Teen DEPO group decreased BMD 1.5-5.2%; control increased 4.2-9.3% (Cromer et al., 2000; 2008)  BMD likely returns post DEPO (Harel et al., 2010)

Bone Accrual in Adolescence  ~50% of bone mass in girls is accrued in adolescence – Primarily 2 yrs around menarche – As much bone is accrued in 2 yrs of puberty as is lost in last 4 decades of life (Bailey et al., 2000; McKay et al., 2000; Seeman et al., 1993)

Maximize the “bone bank”  Attaining optimum bone mass in adolescence is best protection against later osteoporosis & potential fracture.

Depression and Smoking Statistics in Adolescence  Familiar to most in this group

Smoking & adult bone health  BMD lower by 1-2% each 10 pk yrs – When > 20 pk yrs; changes to 6-9% lower – With these smoking rates , fracture rates increase 13% in spine; 31% hip across lifetime (Ward & Klegyes, 2001; Hopper & Seemen, 1994)  Rat model: exposure inhibited adolescent bone (Fung et al., 1999; Akhter et al., 2005)

Depression & adult bone health  Multiple studies show adults with depression are more likely to be osteoporotic – Supported by meta-analyses » ( Cizza et al., 2010; Wu et al., 2009; Yirmiya & Bab, 2009) – Primarily » Elderly » Women – Primarily cross sectional studies

Conceptual Model: Puberty Bone Accrual Smoking Age 11-19 Depressive Sx

Hypotheses  A) Greater smoking behavior and B) higher depressive symptoms would negatively predict bone accrual across adolescence in girls.

13 yr 13 yr 13 yr 15 yr 15 yr 15 yr 17 yr 17 yr 17 yr 19 yr 19 yr 19 yr T 3 T 3 12 yr 12 yr 12 yr 14 yr 14 yr 14 yr 16 yr 16 yr 16 yr 18 yr 18 yr 18 yr T 2 T 2 T 1 T 1 11 yr 11 yr 11 yr 13 yr 13 yr 13 yr 15 yr 15 yr 15 yr 17 yr 17 yr 17 yr --Cross sequential design N = 262 --Statistical options

Inclusion Criteria  Girls age 11, 13, 15, or 17  One of 5 designated lifetime smoking categories (Mayhew, Flay, & Mott 2001) – Never (not even a puff) – A puff or two – < 100 cigarettes – > 100 cigarettes; < 15 in last 30 days – > 100 cigarettes; 15-30 last 30 days

Exclusion Criteria  Pregnant or breast feeding w/in 6 mo  Primary amenorrhea (> 16 yrs)  Secondary amenorrhea (< 6 cycles/yr)  BMI < 1 st % or > 300 lbs  Meds or disorder influencing bone – Hormone contraceptives ok  Psych or developmental disorder impairing comprehension/compliance

Recruitment  Community recruitment – Cincinnati Children’s Hospital Teen Health Center (THC) – Presentations at Public & Private Schools – Directed mailing – Emails to CCHMC employees – Flyers

Sample  262 healthy girls  Caucasian (61.8%), African- American (32.3%)  Tanner 1-5 – 79.8% post-menarcheal  BMI 24.0 + 6.3 kg/m 2 – > 85 th %tile: n = 106 (~40.5%)

Protocol  Annual 3-4 hr CTRC visit (Year 1-3) – Physical measures (e.g., ht, wt, pubertal stage) – Labs (e.g., gonadal & adrenal hormones) – DXA – Questionnaires & Interviews » e.g., CDI, menstrual hx, smoking, health, etc. » Repeat questionnaires 3, 6, 9 mo by phone

Findings from:  LD Dorn, SJ Beal, H Kalkwarf, S Pabst, JG Noll, & EJ Susman. (2013). Longitudinal impact of substance use and depressive symptoms on bone accrual among girls age 11-19. J Adol Health 52(4):393-399

Measures in these analyses  Dual Energy X-Ray Absorptiometry (DXA) – Total Body Bone Mineral Content (TB BMC) – Region Bone Mineral Density (BMD): » total hip » spine

Measures (contd.)  Depressive Symptoms – Children’s Depression Inventory (CDI)  Smoking history questionnaire – Graded lifetime: never, 1puff -2 cigs, 3-99, > 100 – Past 30 days

Covariates  Age*  Race  Height*  Weight*  Tanner breast  Duration DEPO & OCP, physical activity*, menarcheal age, 25- (OH)D, Ca intake – * time-varying

Analyses  Hierarchical linear modeling (HLM) was used to estimate BMC and BMD trajectories over the ages of 11-19 years – Contribution of independent predictors evaluated – Maximum likelihood estimation for MD

Results  Trajectories of bone accrual equivalent to expected normal development (Kalkwarf et al., 2007) – TB BMC: linear; quadratic (p < .01) – Hip & Spine BMD: linear (p < .01)

Effect of Smoking on BMD • Smoking X Age B = -.001, SE = .001 p < .05 • Smoking X Age B = -.002, SE = .000 p < .01

Effect of Depressive Symptoms on BMD • Depressive Symptoms B = -.001, SE = .001 p < .05 • Depressive Symptoms B = -.001, SE = .000 p > .05 Interactions with age n.s.

Limitations  Enrollment in smoking categories limited because trajectories of use just beginning – Small sample in some categories  Smoking may be marker for something else that may influence bone  Depressive sx; not diagnosis  Self-report (activity, Ca intake)  Needs replication

Implications for Prevention  Vigilance towards potential impact of depressive sx on bone – Meta analysis in adult lit recommends depression be labeled as risk for osteoporosis and for clinicians to monitor bone mass  Recognition that smoking/depressive symptoms may also influence bone health even at young ages

Future Research Considerations:

What is the mechanism for depression impacting bone?  Increased cortisol? – Cort may directly impact bone – Cort higher in adult depression – Cort inhibits gonadal hormones (e.g., E 2 )  Change in immune markers (cytokines)? – Stress inhibits immune function

What is the mechanism of smoking on bone health?  Could be local/toxic effect or  May not be smoking per se – Most girls not heavy smokers – Our measure of smoking may be tapping another variable that impacts bone health in a negative way.

Alcohol & adult bone health  Chronic, excessive alcohol: often detrimental  Moderate use adult males & post-menopausal women: – sometimes advantageous (Feskanich et al., 1999;Laitinen et al., 1991) » Via reducing bone turnover markers in 40 post-menop.  Iwaniec et al., 2012  Animal model: chronic exposure in adolescence had negative effect (Sampson et al., 1999) – Cessation didn’t change effect – Binge drinking particularly detrimental

Conceptual Model for R21 Smoking Status/ Alcohol Use Bone Health Stress (Bone mineral accrual) System Depressive Sx/ Anxiety Cytokines

Next steps . . .  R21 (submit 8/5): stress as mechanism – Discuss content  Developing R01– – Discuss content

Questions . . . Comments . . . Ideas . . . ?