WHAT KEEPS OUR BONES STRONG? The role of diet and lifestyle in osteoporosis prevention Thomas Walczyk PhD, Associate Professor Food Science and Technology Programme Department of Chemistry, Faculty of Science Department of Biochemistry, Yong Loo Lin School of Medicine
!!! BONE IS NO DEAD MATTER!!!
BONE REMODELLING BONE-ACCRETION Osteoblasts Ca Osteoclasts BONE RESORPTION
BONE DIET - LIFESTYLE BONE-ACCRETION Genotype Ca Vitamin D Phytoestrogenes Body Weight Physical Activity Alcohol Coffee Salt Intake Protein-Intake Acid/Base Balance Smoking BONE RESORPTION
BONE MASS AND AGE BONE MASS PEAK BONE MASS males puberty menopause females 10 20 30 0 50 60 70 80 AGE (YEARS)
BONE MASS AND AGE Lis Roskilde Lis Roskilde Vertebra young female Vertebra old female
OSTEOPOROSIS = POROUS BONE A disease characterized by low bone mass and micro-architectural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture risk. World Health Organization (WHO) 199
HIDDEN VERTEBRAE FRACTURES 5 years 75 years http://www.osteoporosezentrum.de/osteoporose/folgen.html
DANGER ZONES Solvay Pharma Vertebrae 1 in 6 women 1 in 20 men Wrist 1 in 6 women 1 in 0 men Femoral Neck 1 in 6 women 1 in 17 men Fracture Lifetime risk (western populations) 1 in 3 women and 1 in 5 man over 50 years International Osteoporosis Foundation / Kanis et al. 2000 / Melton 1992
PROJECTIONS - FOCAL POINT ASIA International Osteoporosis Foundation
CONSEQUENCES OF OSTEOPOROSIS Height loss, chronic pain affects self esteem, depression sleepless nights only 30% of osteoporotic patients fully regain their pre fracture level of independence Constipation, abdominal pain lumbar fractures may alter abdominal anatomy Limited mobility!!! REFERS BOTH TO MALES AND FEMALES!!!
SINGAPORE - FACTS AND FIGURES High prevalence among Singaporeans ca. 100,000 women suffer from osteoporosis ca. 800 to 900 osteoporotic hip fractures every year Sharp increase in hip fractures over past 3 decades in men and women (>50 years) 5 times in women from 75 cases to 02 cases per 100,000 populations 1.5 times in men from 103 cases to 152 cases per 100,000 populations High mortality and morbidity rate 1 in Singaporeans suffering an osteoporotic hip fracture die within one year after injury 1 in 3 became wheelchair bound or bedridden Source: International Osteoporosis Foundation (Country Factsheets 2007)
OSTEOPOROSIS PREVENTION BETTER CHOICE THAN THERAPY
ASSESSMENT OF CHANGES IN BONE METABOLISM Bone Mineral Density double emission X-ray absorptiometry (DEXA) computer-tomography (CT, q-ct, pq-ct, µ-ct) ultrasonic Techniques DXA measurement
ASSESSMENT OF CHANGES IN BONE METABOLISM Bone Mineral Density double emission X-ray absorptiometry (DEXA) computer-tomography (CT, q-ct, pq-ct, µ-ct) ultrasonic Techniques Biochemical Markers of Bone Metabolism degradation products of organic bone matrix in urine pyridinoline, desoxy-pyridinoline, telopeptides, sialoprotein compounds involved in bone accretion process osteocalcin, procollagen-polypeptide, alkaline phosphatase
LIMITATIONS OF AVAILABLE TECHNIQUES LIMITED SENSITIVITY = long monitoring periods STRONG INTRA-INDIVIDUAL VARIATIONS = large subject numbers
NUTRI TRACE LAB @ SCIENCE (S13) Exploration of mineral and trace element metabolism in humans by stable isotope tracer techniques for development and evaluation of strategies to improve public health through diet and lifestyle operational since 08/2008
NUTRI TRACE LAB @ SCIENCE (S13) CONTROLLED INTERVENTION STUDIES animal + men ASSESSMENT OF NUTRIENT INTAKE METABOLIC STUDIES USING ISOTOPE TECHNIQUES NUTRITIONAL STATUS
NUTRI TRACE LAB @ SCIENCE (S13) CONTROLLED INTERVENTION IRON STUDIES animal + men ASSESSMENT OF NUTRIENT INTAKE CALCIUM METABOLIC STUDIES USING ISOTOPE TECHNIQUES NUTRITIONAL STATUS
ISOTOPIC LABELING OF BONE CALCIUM SINGLE ADMINISTRATION OF CALCIUMISOTOPE
ISOTOPIC LABELING OF BONE CALCIUM SINGLE ADMINSITRATION OF CALCIUMISOTOPE INCORPORATION OF CALCIUM ISOTOPE INTO BONE MATRIX
ISOTOPIC LABELING OF BONE CALCIUM SINGLE ADMINSITRATION OF CALCIUMISOTOPE INCORPORATION OF CALCIUM ISOTOPE INTO BONE MATRIX URINARY TRACER SIGNAL = MEASURE OF BONE CALCIUM BALANCE
ISOTOPIC LABELING OF BONE CALCIUM CALCIUMISOTOPE TRACER SIGNAL IN URINE LABELING PHASE TIME
ISOTOPIC LABELING OF BONE CALCIUM TRACER SIGNAL IN URINE POSI TI VE EFFECT I NTERVENTI ON
ISOTOPIC LABELING OF BONE CALCIUM TRACER SIGNAL IN URINE NEGATI VE EFFECT I NTERVENTI ON
ISOTOPIC LABELING OF BONE CALCIUM TRACER SIGNAL IN URINE NEGATI VE EFFECT I NTERVENTI ON
WHAT ARE CALCIUM-ISOTOPES? increasing neutron number = increasing mass CALCIUM3 8 3 9 0 1 2 3 5 6 7 8 9 CALCIUM ISOTOPES = calcium atoms of different mass
STABLE VERSUS RADIOACTIVE ISOTOPES mass number abundance CALCIUM3 8 3 9 0 96.9% 1 2 0.65% STABLE ISOTOPES 3 0.1% 2.08% 5 6 0.00% 7 8 0.19% 9 Natural calcium = stable isotope mix Isotopic abundances highly constant Highly enriched stable isotopes can be used as tracers No health hazards Outrageous costs
STABLE VERSUS RADIOACTIVE ISOTOPES CALCI UM 3 8 38 0.s 3 9 39 0.9s 0 0 96.9% 1 1 1x10 5 a 2 2 0.65% 3 3 0.1% 2.08% mass number half-life 5 5 163d RADIOACTIVE ISOTOPES 6 6 0.00% 7 7.5d 8 8 0.19% 9 9 8.7m!!! HEALTH HAZARDS!!!
STABLE VERSUS RADIOACTIVE ISOTOPES effective dose < 1/1000 of standard chest x-ray CALCI UM 3 8 38 0.s 3 9 39 0.9s 0 0 96.9% 1 1 1x10 5 a 2 3 5 5 163d SEMI-STABLE RADIOACTIVE ISOTOPE 39 ISOTOPES5 38 0.s 2 0.65% 3 0.1% 2.08% 6 6 0.00% 7 7.5d 7 0.9s 1 very long 163d half-life.5d 1x10 5 a 8 8 0.19% 9 9 8.7m 9 8.7m = very slow decay (virtually stable) = very low radio-emission highly sensitive detection = low dosage
THE ANALYTICAL CHALLENGE Accelerator Mass Spectrometer ETH Zurich
THE ANALYTICAL CHALLENGE 1 Ca/nat. Ca in enriched samples: 10 - to 10-11 Accelerator Mass Spectrometer ETH Zurich
THE ANALYTICAL CHALLENGE SWITZERLAND ETH Zurich, Laboratory of Human Nutrition SWITZERLAND ETH Zurich, Institute of Particle Physics SWITZERLAND Paul Scherrer Institute, Villingen SWITZERLAND University Hospital Zurich, Clinical Pharmacology GERMANY University of Mainz, Institute of Physics ENGLAND Scottish Universities Environmental Research Centre East Killbride IRELAND University of Cork, Food and Nutritional Sciences EU EU Joint Research Center, Institute of Reference Materials and Measurements DENMARK The Danish Food and Veterinary Administration Institute of Food Research and Nutrition USA Lawrence Livermore National Laboratory USA Argonne National Laboratory Accelerator Mass Spectrometer ETH Zurich
EFFECT OF BISPHOSPHONATE THERAPY ON Ca- 1 SIGNAL BISPHOSPHONATES = POTENT INHIBITORS OF BONE RESORPTION LABELING PHASE single tracer dose (100 nci) 3 month bisphosphonate treatment 6 post-menopausal women with diagnosed osteopenia intervention
EFFECT OF BISPHOSPHONATE THERAPY ON Ca- 1 SIGNAL RESPONSE TO TREATMENT WITHIN WEEKS OF THERAPY IN ALL SUBJECTS evaluation by population based pharmacokinetic modelling techniques
EFFECT OF CALCIUM SUPPLEMENTATION 1 Ca/ 0 Ca isotope ratio in urine.e-10 3.E-10 2.E-10 1.E-10 ID 7 ID 8 ID 9 ID 10-100 0 100 200-100 0 100 200-100 0 100 200-100 0 100 200 5.E-10.E-10 Pla Ca 3.E-10 2.E-10 1.E-10 ID 16-100 0 100 200 7.E-10 5.E-10 Pla Pla Ca Ca 3.E-10 1.E-10 ID 17-100 0 100 200 ID 13-100 0 100 200 ID 12 Ca Ca Ca Pla Pla Pla -100 0 100 200 ID 11 Ca Ca Pla Pla -100 0 100 200 ID 1 Ca Pla -100 0 100 200 ID 20 Ca Ca Pla Pla -100 0 100 200 ID 15 Ca Pla -100 0 100 200 7.E-10 5.E-10 Pla Ca Pla Ca Pla Ca Pla Ca 3.E-10 1.E-10 ID 18-100 0 100 200 ID 19-100 0 100 200 ID 21-100 0 100 200 ID 22-100 0 100 200 Intervention period [days] 3 month blinded randomized placebo controlled supplementation trial 750 mg/d + 00 IU Vit D; 16 postmenopausal women
EFFECT OF CALCIUM SUPPLEMENTATION 1 Ca -55% p<0.001 Plasma P S B 35 mg Alendronate weekly Urine Bone Surface Deep Bone 1 Ca +27% p<0.001 +0% p<0.001 P S B 750 mg Ca daily Effect of intervention resolvable in each individual DIFFERENCES IN MECHANISMS OF ACTION CAN BE IDENTIFIED
FOCAL POINTS SINGAPORE GENETIC POLYMORPHISMS ACID BASE BALANCE ETHNIC DIFFERENCES PHYTOESTROGEN ES AND SOY OSTEOPOROSIS CALCIUM INTAKE PHYSICAL ACTIVITY TRACE ELEMENT NUTRITION VITAMIN D STATUS
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