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
Smoking
(gonadal and adrenal
hormones, menstrual
cycle)
Bone Health
Depression/
= Unknown
effect
= Positive
effect
Status
(Bone mineral
accretion)
Anxiety
Figure 1 – Conceptual Model
= Negative
effect
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.
T3
13 yr
15 yr
17 yr
19 yr
T2
12 yr
14 yr
16 yr
18 yr
T1
11 yr
13 yr
15 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 < 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
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., 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
Conceptual Model for R21
Smoking Status/
Alcohol Use
Bone Health
Stress
System
Depressive Sx/
Anxiety
Cytokines
(Bone mineral accrual)
Next steps . . .

R21 (submit 8/5): stress as mechanism
– Discuss content

Developing R01–
– Discuss content
Questions . . . Comments . . .
Ideas . . . ?