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

Conceptual Model:

Puberty Smoking Depressive Sx Bone Accrual Age 11-19

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 Smoking Depressive Sx Bone Accrual Age 11-19

Hypotheses

 A) Greater smoking behavior and B)

higher depressive symptoms would negatively predict bone accrual across adolescence in girls.

• -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 < 1st % 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/m2

– > 85th %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

• steoporosis 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., E2)

 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

Smoking Status/ Depressive Sx/ Anxiety Bone Health

(Bone mineral accrual)

Conceptual Model for R21

Stress System Cytokines Alcohol Use

Next steps . . .

 R21 (submit 8/5): stress as mechanism

– Discuss content

 Developing R01–

– Discuss content

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