Post on 08-Jan-2017
Factors influencing peak bone mass
Nicholas HarveyMA MB BChir PhD FRCP
Professor of Rheumatology and Clinical EpidemiologyMRC Lifecourse Epidemiology Unit, University of Southampton
Outline
MRC Lifecourse Epidemiology Unit, University of SouthamptonDirector: Professor Cyrus Cooper
• Overview
• Relevance of PBM
• Determinants of PBM
• Conclusions
Bone mass(g/Ca)
Age (yr)
1500 -
1000 -
500 -
0 -0 20 40 60 80 100
Peak bone mass predicts risk of osteoporosisHernandez et al., OI 2003
Maternal lifestyle, body build, 25(OH)D during pregnancyGodfrey et al., JBMR 2001Javaid et al., Lancet 2006Harvey et al., JDOHAD 2012
Postnatal nutrition, body composition and PAHarvey et al., BJN 2009Cole et al., Bone 2012Harvey et al., OI 2012
Developmental origins of osteoporotic fracture
Poor early growth, reduced adult BMC, increased risk hip fractureCooper et al., JBMR 1995Cooper et al., OI 2001Javaid et al., OI 2011
Harvey, Dennison, Cooper JBMR 2014; 29(9):1917-25
Maximize peak Reduce fracture risk
Risk factors for low PBM
• Population level– Nutrition, physical activity, smoking, alcohol
• Chronic disease– Malabsorption, Inflammation, Endocrine,
Musculoskeletal, any!– Malignancy– Genetic– Medications
Growth, timing of exposure and PBM
• Long-term trajectory vs transient deviation?
• Linear growth or BMD
Miss B.P.
• 25 year old lab technician, Porton Down• GP referral after 2 wrist fractures• Crohn’s disease since age 8 years
– Prednisolone, azathrioprine– CRP 54, ESR 71– DXA Z-score: LS -3.2; LFN -2.3– Vegan, elite cycle training, smoker, no
alcohol
Childhood calcium, vitamin D and BMD
Modest effect on LS BMD and TBMD when 25(OH)D<35nmol/l
Winzenberg et al., BMJ 2011;342:c7254Winzenberg et al., BMJ 2006: doi:10.1136/bmj.38950.561400.55
Vitamin D
Calcium
WB BMC
Childhood physical activity, BMD and fracture
4 yr BMC and habitual PA
Harvey et al., Osteoporos Int. 2012;23:121-30
Clark et al., J Bone Miner Res. 2008;23:1012-1022
Greater physical activity (impact) associated with greater BMDBut… also with more fractures
Miss B.P., continued
• Mentions has had weight issues since childhood acute lymphoblastic leukaemia
• Amenorrhea
• BMI 16kg/m2
• Keen to start a family
pQCT volumetric BMD in ALL
p=0.03
p=0.002
RADI
IUS
TIBI
A
p=0.09
p=0.71
TRABECULAR CORTICAL
Kohler, Moon et al., Bone. 2012 Oct;51(4):765-70
Anorexia Nervosa and BMDMean difference LS BMD eating disorder vs control
Robinson et al., Osteoporos Int. 2016; 27:1953-1966
Adolescent AN:Reduced trabecular vBMDIncreased cortical vBMDReduced muscle CSADiVasta et al., Osteoporos Int. 2016 ePub
MalnutritionLow oestrogen? Excessive PA
Miss B.P., continued
• Volunteers further information– Deprived intra-uterine life
– Parents smoked and “never went outdoors”
– “always on bottom centile”
Late pregnancy maternal 25(OH)-vitamin D, venous umbilical cord calcium and nine year WBBMC
Mean (95% CI)Pearson r (p) continuous data
Maternal 25 (OH)-Vit D (ng/ml)
r=0.20p=0.008
<11 -20 >200
0.9
1.0
1.1
1.2
1.3
Child
hood
who
le b
ody
BMC
(kg)
Child
hood
who
le b
ody
BMC
(kg)
r=0.19p=0.02
Umbilical cord Ca2+
corrected for albumin (mmol/L)
<2.7 -2.8 >2.80.00.9
1.0
1.1
1.2
1.3
1.4
Javaid et al, Lancet 2006
875
880
885
890
895
900
905
910
915
Bone
are
a (c
m2)
0.505
0.51
0.515
0.52
0.525
0.53
0.535
0.54
0.545
0.55
0.555
Bone
min
eral
con
tent
(kg)
0.576
0.582
0.588
0.594
0.600
0.606
Bone
min
eral
den
sity
(g/c
m2)
<25 ≥25 <25 ≥25 <25 ≥25
Maternal 25(OH)D (nmol/l)
P=0.016 P=0.015 P=0.046
Maternal late pregnancy 25(OH)D status and offspring whole body less head bone mineral at 6-7 years
Southampton Women’s Survey
Moon et al, Osteoporosis International 2015, 26(4):1449-51
N=1004, shown as mean±95% CI
Expected differences in whole body bone mineralisation at age 20 years for every 10nmol/l maternal 25(OH)D
Western Australia Pregnancy (Raine) Cohort
Model 1: adjusted for season of blood sampling, sex and age at DXAModel 2: Model 1 + maternal education, parity, ethnicity, maternal height and pre-pregnancy weight
Model 3: Model 2 + offspring height, lean mass and fat mass at 20 years
Zhu et al, J Bone Miner Res. 2014;29(5):1088-95
N=341, shown as mean±95% CI
BMC BA BMD
Antenatal vitamin D supplementation increases offspring BMC in winter births
p=0.004
5060
70W
hole
bod
y BM
C (g
)
Placebo 1000 IU/d
Winter
p=0.44
5060
70
Placebo 1000 IU/d
Spring
p=0.73
5060
70
Placebo 1000 IU/d
Summer
p=0.2150
6070
Placebo 1000 IU/d
Autumn
Mean (95% CI) p interaction=0.04
p interaction = 0.04
Cooper, Harvey et al., Lancet DE 2016
6 year follow-up now funded by Arthritis Research UK
Determinants of 25(OH)D response to cholecalciferol supplementationMoon, Harvey, Cooper et al., JCEM 2016 (in press)
Tracking of 25(OH)D across gestationMoon et al., AJCN 2015; 102:1081-7
Genetic determinants of 25(OH)D response
Neonatal BMC (g)
Conclusions
• Determinants of PBM many and varied– From conception onwards
• Considerations– Chronic vs transient– Lifestyle vs morbidity– Size vs BMD
• In younger adults with OP, consider low PBM vs loss
Acknowledgements• MRC LEU Cyrus Cooper (Director and Professor
of Rheumatology),Elaine Dennison, Avan Aihie Sayer, Chris Holroyd, Mark Edwards, Becca Moon, Beth Curtis, Janis Baird, Caroline Fall, Clive Osmond, Sian Robinson, Keith Godfrey, Hazel Inskip
• Osteoporosis Centre, SGH Pat Taylor, Gill Pearson
• Bone & Joint Laboratories Richard Oreffo, Stuart Lanham
• Institute of Developmental Sciences/ EpiGenMark Hanson, Peter Gluckman,
Graham Burdge, Karen Lillycrop, Jane Cleal, Jo Slater-Jefferies
• Botnar Research Centre, Oxford Nigel Arden, Kassim Javaid,
Richie Gill, Andy Price, Andy Carr