BSR MUSCULOSKELEAL MEDICINE AND PREGNANCY
Metabolic Bone Disease, Vitamin D Deficiency and Bisphosphonates in Pregnancy M Kassim Javaid Norman Collisson Senior Research Fellow, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford Oxfordshire Osteoporosis Metabolic Bone Disease Service Nuffield Orthopaedic Centre, Oxford
Aims Bone metabolism Pregnancy induced osteoporosis Parathyroid disorders Bisphosphonates in pregnancy
Vitamin D in pregnancy
Bone cells Osteoclasts cut bone Osteoblasts build bone
Osteocytes 95% cells in skeleton dense neural network
Bone cells Osteoclasts cut bone Osteoblasts build bone RANKL
OPG
RANKL
wnt Sclerostin/ DKK1
Osteocytes 95% cells in skeleton dense neural network
Investigations
BLOOD ◦ ◦ ◦ ◦ ◦ ◦ ◦
Ca2+, phosphate, ALP, 25-Vit D, PTH Sodium, potassium, urea, creatinine, eGFR AST/ ALT, TSH T4 T3 ESR, EP strip Testosterone/SHBG (ratio >0.3), E2, LH FSH Coeliac screen Bone markers (formation/resorption)
URINE ◦ Calcium creatinine ratio ◦ Cortisol
DXA results
Absolute areal density (g/cm2)
T score
Z score
Lumbar spine Total hip – Neck + troch + shaft
SD = standard deviation= -2.5SD
DXA
DXA
The T score
Compares BMD with young adult mean
Normal T >= -1
Osteopenia -1 to -2.5
Osteoporosis 100 nM
Vitamin D deficiency in pregnancy
Prevalence ◦ Iran: 86% < 25 nM in winter ◦ Belfast: 12,20, 35 wk 16 – 35% < 25 nM 75 – 96% < 50 nM
◦ Pakistan/ Turkish/ Somalian immigrants 57% < 25nM; 26% secondary HPTH Infants: 47% < 25nM
Can so many of us be functionally deficient?
Prentice Nut Rev 2008
Risk of osteoporosis from cradle to grave
Maternal effects on offspring’s bone mass
Pre -pregnancy
Pregnancy
Lifestyle & nutrient status
‘Cradle’ Neonatal Bone mass Childhood Bone mass
Developmental origins of adult disease “Developmental plasticity”
Intrauterine Environment
~single genotype ~multiple phenotypes
Multiple pathways to chronic disease
Adaptation vs constraint
Gene/ Environment Interactions ‘epigenetic’
Child/ Adult phenotype
Barker DJP et al Eur J Clin Inv. 1995 Gluckman PD et al Science 2004;305:1733-6
Late pregnancy maternal 25(OH) vitamin D and Nine year WBBMC Childhood 0.95 WBBMC/BA (g/cm2)
p = 0.004
0.90
0.85
0.8 0.0
20 Maternal 25 (OH) Vit D (late pregnancy) (ng/ml)
Maternal Vitamin D in Osteoporosis Study Chief Investigator: C Cooper, Norman Collisson Chair of Musculoskeletal Sciences The Botnar Research Centre Principal Investigators: N Harvey, University of Southampton S Kennedy, University of Oxford N Bishop, University of Sheffield
Maternal vitamin D supplementation in pregnancy (n=600) Down’s Screenin g (12/40)
Mothers recruited Check 25D, PTH,ALP, Ca, Albumin
Randomisation D3 1000 iu/day
19/40 34/40 Birth
25D 100 nmol/l
25nmol/l< 25D 100 nmol/L at baseline 40% white, 30% Hispanic, 30% black 28% BMI >30kg/m2
350 completed study
Maternal outcomes (mode delivery) not different Neonatal outcomes (GA/ birthweight) not different
Hollis 2011 JBMR
Which dose
Hollis 2011 JBMR
Which dose
Hollis 2011 JBMR
Summary
PIO
Bisphosphonates in pregnancy
Vitamin D deficiency treatment is changing
Kerri Rance Sally Hope Sarah James Terri Morgan Carol Weeks Lynda Lyzba Rachael Knight Abigail Koelewyn Tracy Dobbin Leonora Langstaff Rhea Zambellas Suzanne Jones/ Sylvie Thorn Adam Dawroski / Antoinette Broad
Professors
Cooper Wass Willett Arden Carr D Prieto Alhambra, A Judge, R Batra, G Round, A Kiran, K Leyland, A Soni, R Warne A Papageorghiou , C Ioannou, M Yaqub,A Noble, S Kennedy ….… and all the FRiSCy team! Stephen, Colin, Annie, Gill, Mark…
