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Milk fortified with vitamin D3 and calcium: safety and efficacy in young adults
688
Abstracts
Bone Vol. 16, No. 6 June 1 9 9 5 : 6 7 9 - 6 9 5
Mean:~em (n 12)
Normal Proliferating
Normal Hypertrophic
TD Proliferatin8
Kd (pM) Receptors/cell
29.8+3.3 1344-+186
39.5:t:3.1 1706-+201
33.6+4.9 1439-+120
TD Lesion 83.4+95.6 913_+92
N o r m a l c h o n d r o c y t e s f r o m the h y p e r t r o p h i c z o n e h a v e a h i g h e r VDR n u m b e r t h a n t h o s e f r o m the p r o l i f e r a t i n g z o n e (p<0.01, p a i r e d t-test), a l t h o u g h the affinity of 1.25 for VDR is similar. C h o n d r o c y t e s f r o m the p r o l i f e r a t i n g z o n e of TD affected birds s h o w e d n o s i g n i f i c a n t d i f f e r e n c e in e i t h e r VDR n u m b e r or affinity compared to n o r m a l b i r d s . H o w e v e r , lesion chondrocytes h a v e b o t h a r e d u c e d VDR n u m b e r a n d affinity (p<0.01, D u n n ' s test) c o m p a r e d to all o t h e r zones. Since 1,25 is k n o w n to induce its o w n receptor these results may offer one e x p l a n a t i o n of w h y t r e a t m e n t of birds with 1,25 can prevent TD. Funded by a link grant from the BBSRC
P30. M i l k f o r t i f i e d w i t h v i t a m i n D3 and calcium: safety a n d efficacy in young adults MJ M c K e n n a , R F r e a n e y , P Byrne, Y McBrinn, B M u r r a y , M Kelly, B Donne, M O'Brien
St. Vincent's Hospital, St.Michael's Hospital, Department of Physiology, University College Dublin, Department of Public Dental Health and Community Services, Dublin Dental ftospital, Department of Anatomy, Dublin University, Dublin We s t u d i e d the safety a n d efficacy of fortified milk in y o u n g a d u l t s ( m e d i a n a g e 22.6 yr; range: 18-48 yr). Fortification increased the vitamin D3 content from 0.3 , g / L to 12 , g / L , a n d elemental c a l c i u m f r o m 1270 m g / L to 1525 m g / L . Volunteers (123) w e r e recruited; 102 c o m p l e t e d the trial. A c c o r d i n g to a d o u b l e - b l i n d p r o t o c o l they w e r e assigned in a r a n d o m m a n n e r to receive e i t h e r fortified m i l k or u n f o r t i f i e d milk. Milk c o n s u m p t i o n w a s not different b e t w e e n groups: 65+40 litres in fortified g r o u p vs 64+_21 litres in non- fortified group. BlocKt was d r a w n in late a u t u m n a n d after the winter. Paired samples were m e a s u r e d in the s a m e a s s a y . S e a s o n a l d e c r e a s e in serunl 25(OH)D w a s s i g n i f i c a n t l y d i m i n i s h e d in the g r o u p d r i n k i n g fortified milk. In the fortified g r o u p , s e r u m 25(OH)D decreased b y 15 n m o l / L f r o m 77+35 to 62_+26 n m o l / L (P<0.001). In the control g r o u p , s e r u m 25(OH)D fell by 31 n m o l / L from 85-+39 to 54-+25 n m o l / L (P<0.00I). Both g r o u p s h a d a slight but significant rise in s e r u m ionised calcium, corrected for pH: fortified g r o u p (1.24_+0.04 vs 1.27-+0.06 m m o l / L ; P<.001); control g r o u p (1.23_+0.03 vs 1.26+0.03 m m o l / L ; P<.O01)). We p r o p o s e that fortification of milk with vitamin D be m a n d a t o r y in EU states.
P31. Bone loss after the menopause: cross-sectlonal studies m a y be m i s l e a d i n g PA Mole, CR Paterson
Department of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee DDI 9SY We r e p o r t o n a s e v e n y e a r s t u d y of b o n e d e n s i t y in 67 p o s t m e n o p a u s a l w o m e n . U s i n g the s a m e M o l s g a a r d single p h o t o n a b s o r p t i o m e t e r ND1100A t h r o u g h o u t , w e m e a s u r e d the f o r e a r m b o n e m i n e r a l content (BMC). Four to ten (median 6) BMC m e a s u r e m e n t s over p e r i o d s of five to seven (median 6 9 ) years were obtained. The rate of b o n e loss calculated from the s t u d y p o p u l a t i o n as a cross-section w a s high in y o u n g e r w o m e n , one to nine years past the m e n o p a u s e , b u t m u c h lower in w o m e n more than ten years p o s t m e n o p a u s a l . H o w e v e r the m e a n l o n g i t u d i n a l rates of loss in i n d i v i d u a l s w e r e f o u n d to be no different in the t w o a g e groups. The l o n g i t u d i n a l rates of c h a n g e did not c h a n g e with a g e or m e n o p a u s a l age. A w o m a n t w e n t y years after the m e n o p a u s e could be losing b o n e at the s a m e rate as one five years after the menopause. We s u g g e s t that care should be taken in m a k i n g inferences for the future from cross-sectional data. W o m e n n o w in their sixties m i g h t a p p e a r from cross- sectional data to be losing bone more slowly t h a n is actually the case, as s h o w n by the longitudinal d a t a . H o r m o n e r e p l a c e m e n t t h e r a p y m a y well be w o r t h c o n s i d e r i n g at a n y age not just in the first few years after the menopause.
P32. Broadband ultrasound characteristics in rheumatoid arthritis and diabetes D De Lord, S P u t h r a s i n g a m , P Mulligan, K Brown, G Waiters, P Pitt
Farnborough Hospital, Orpington, Kent Introduction: B r o a d b a n d u l t r a s o u n d is currently being evaluated as a simple, n o n - i o n i s i n g investigation of bone in patients with s u s p e c t e d o s t e o p o r o s i s . R e d u c e d b r o a d b a n d ultrasorgnd at a p e r i p h e r a l site m a y be a m e a s u r e of altered b o n e structure, r e f l e c t i n g s y s t e m i c b o n e loss a n d p r e d i c t i n g f r a c t u r e risk. M e t h o d s : M e a s u r e m e n t s of b r o a d b a n d u l t r a s o u n a t t e n u a t i o n (BUA), speed of s o t m d (SOS) a n d 'stiffness', a derivative of these values, w e r e t a k e n at the os calcis in 50 w o m e n with RA, 58 d i a b e t i c s a n d a n a g e - m a t c h e d n o r m a l p o p u l a t i o n . Possible influencing factors w e r e assessed by questionnaire. Results: BUA, SOS a n d stiffness w e r e significantly lower in RA g r o u p t h a n controls: stiffness a g e - m a t c h e d z score correlated significantly w i t h H A Q score (disability index), r=-0.41, p
Institutes of Pathology, Erasmus University, Rotterdam, The Netherlands and *Aarhus University, Denmark, **Department of Internal Medicine III, University Hospital Dijkzigt, 3015 GD Rotterdam, The Netherlands W h e n b o n e r e m o d e l l i n g is m a r k e d l y elevated, lack of completed w a l l s p r e c l u d e s e s t i m a t i o n of s e v e r a l p a r a m e t e r s of b o n e t u r n o v e r , s u c h as d u r a t i o n of the f o r m a t i v e period (FP) a n d a c t i v a t i o n f r e q u e n c y (Ac.f), as o n e e s s e n t i a l p a r a m e t e r , c o m p l e t e d w a l l w i d t h (W.Wi) c a n n o t be assessed. Recently, Steiniche et al, p u b l i s h e d a m e t h o d to select a n d m e a s u r e walls not yet c o m p l e t e l y m i n e r a l i s e d b u t c o m p l e t e d as to their thickness (Bone 1992, 13: 147): these are f o u n d in the lowest quartile of the v a l u e s of the ratio osteoid w i d t h / m i n e r a l i z e d width. W e u s e d this criterion, p r i m a r i l y developed to s t u d y the effect of intervention, to reconstruct W.Wi (rW.Wi) in a d v a n c e d renal o s t e o d y s t r o p h y (ROD). W.Wi w a s r e c o n s t r u c t e d in c a n c e l l o u s b o n e f r o m lilac crest biopsy sections from 12 patients with predialysis ROD a n d 12 agea n d s e x - m a t c h e d controls; null hypothesis was tested b y MannW h i t n e y ' s U-test: ROD rW.Wi FP ll.Mlt Ac.f
~m days days /year
43.1 119.6 32.8 1.7
controls averages 58.9 86.6 12.5 0.9
p <0.03 < 0.03 < 0.01 < 0.005
ROD, apart from an impaired T h u s , in p r e d i a l y s i s m i n e r a l i s a t i o n ( i n c r e a s e d initial m i n e r a l i s a t i o n lag t i m e ll.Mlt), we f o u n d walls to be s u b n o r m a l l y thin. While activation f r e q u e n c y w a s f o u n d increased, a p r o t r a c t e d formative period had to be inferred.
P34. In vitro effects of methotrexate on h u m a n osteoblasts BAA Scheven*, MJ v a n d e r Veen, CA D a m e n , FPJG Lafeber, HJM v a n Rijn, JWJ Bijlsma, SA D u u r s m a
University Hospital Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands and *Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB Methotrexate l o w - d o s e t h e r a p y is considered to be a favourable a p p r o a c h for the t r e a t m e n t of r h e u m a t o i d arthritis (RA). To
Abstracts
Bone Vol. 16, No. 6 June 1 9 9 5 : 6 7 9 - 6 9 5
Mean:~em (n 12)
Normal Proliferating
Normal Hypertrophic
TD Proliferatin8
Kd (pM) Receptors/cell
29.8+3.3 1344-+186
39.5:t:3.1 1706-+201
33.6+4.9 1439-+120
TD Lesion 83.4+95.6 913_+92
N o r m a l c h o n d r o c y t e s f r o m the h y p e r t r o p h i c z o n e h a v e a h i g h e r VDR n u m b e r t h a n t h o s e f r o m the p r o l i f e r a t i n g z o n e (p<0.01, p a i r e d t-test), a l t h o u g h the affinity of 1.25 for VDR is similar. C h o n d r o c y t e s f r o m the p r o l i f e r a t i n g z o n e of TD affected birds s h o w e d n o s i g n i f i c a n t d i f f e r e n c e in e i t h e r VDR n u m b e r or affinity compared to n o r m a l b i r d s . H o w e v e r , lesion chondrocytes h a v e b o t h a r e d u c e d VDR n u m b e r a n d affinity (p<0.01, D u n n ' s test) c o m p a r e d to all o t h e r zones. Since 1,25 is k n o w n to induce its o w n receptor these results may offer one e x p l a n a t i o n of w h y t r e a t m e n t of birds with 1,25 can prevent TD. Funded by a link grant from the BBSRC
P30. M i l k f o r t i f i e d w i t h v i t a m i n D3 and calcium: safety a n d efficacy in young adults MJ M c K e n n a , R F r e a n e y , P Byrne, Y McBrinn, B M u r r a y , M Kelly, B Donne, M O'Brien
St. Vincent's Hospital, St.Michael's Hospital, Department of Physiology, University College Dublin, Department of Public Dental Health and Community Services, Dublin Dental ftospital, Department of Anatomy, Dublin University, Dublin We s t u d i e d the safety a n d efficacy of fortified milk in y o u n g a d u l t s ( m e d i a n a g e 22.6 yr; range: 18-48 yr). Fortification increased the vitamin D3 content from 0.3 , g / L to 12 , g / L , a n d elemental c a l c i u m f r o m 1270 m g / L to 1525 m g / L . Volunteers (123) w e r e recruited; 102 c o m p l e t e d the trial. A c c o r d i n g to a d o u b l e - b l i n d p r o t o c o l they w e r e assigned in a r a n d o m m a n n e r to receive e i t h e r fortified m i l k or u n f o r t i f i e d milk. Milk c o n s u m p t i o n w a s not different b e t w e e n groups: 65+40 litres in fortified g r o u p vs 64+_21 litres in non- fortified group. BlocKt was d r a w n in late a u t u m n a n d after the winter. Paired samples were m e a s u r e d in the s a m e a s s a y . S e a s o n a l d e c r e a s e in serunl 25(OH)D w a s s i g n i f i c a n t l y d i m i n i s h e d in the g r o u p d r i n k i n g fortified milk. In the fortified g r o u p , s e r u m 25(OH)D decreased b y 15 n m o l / L f r o m 77+35 to 62_+26 n m o l / L (P<0.001). In the control g r o u p , s e r u m 25(OH)D fell by 31 n m o l / L from 85-+39 to 54-+25 n m o l / L (P<0.00I). Both g r o u p s h a d a slight but significant rise in s e r u m ionised calcium, corrected for pH: fortified g r o u p (1.24_+0.04 vs 1.27-+0.06 m m o l / L ; P<.001); control g r o u p (1.23_+0.03 vs 1.26+0.03 m m o l / L ; P<.O01)). We p r o p o s e that fortification of milk with vitamin D be m a n d a t o r y in EU states.
P31. Bone loss after the menopause: cross-sectlonal studies m a y be m i s l e a d i n g PA Mole, CR Paterson
Department of Biochemical Medicine, Ninewells Hospital and Medical School, Dundee DDI 9SY We r e p o r t o n a s e v e n y e a r s t u d y of b o n e d e n s i t y in 67 p o s t m e n o p a u s a l w o m e n . U s i n g the s a m e M o l s g a a r d single p h o t o n a b s o r p t i o m e t e r ND1100A t h r o u g h o u t , w e m e a s u r e d the f o r e a r m b o n e m i n e r a l content (BMC). Four to ten (median 6) BMC m e a s u r e m e n t s over p e r i o d s of five to seven (median 6 9 ) years were obtained. The rate of b o n e loss calculated from the s t u d y p o p u l a t i o n as a cross-section w a s high in y o u n g e r w o m e n , one to nine years past the m e n o p a u s e , b u t m u c h lower in w o m e n more than ten years p o s t m e n o p a u s a l . H o w e v e r the m e a n l o n g i t u d i n a l rates of loss in i n d i v i d u a l s w e r e f o u n d to be no different in the t w o a g e groups. The l o n g i t u d i n a l rates of c h a n g e did not c h a n g e with a g e or m e n o p a u s a l age. A w o m a n t w e n t y years after the m e n o p a u s e could be losing b o n e at the s a m e rate as one five years after the menopause. We s u g g e s t that care should be taken in m a k i n g inferences for the future from cross-sectional data. W o m e n n o w in their sixties m i g h t a p p e a r from cross- sectional data to be losing bone more slowly t h a n is actually the case, as s h o w n by the longitudinal d a t a . H o r m o n e r e p l a c e m e n t t h e r a p y m a y well be w o r t h c o n s i d e r i n g at a n y age not just in the first few years after the menopause.
P32. Broadband ultrasound characteristics in rheumatoid arthritis and diabetes D De Lord, S P u t h r a s i n g a m , P Mulligan, K Brown, G Waiters, P Pitt
Farnborough Hospital, Orpington, Kent Introduction: B r o a d b a n d u l t r a s o u n d is currently being evaluated as a simple, n o n - i o n i s i n g investigation of bone in patients with s u s p e c t e d o s t e o p o r o s i s . R e d u c e d b r o a d b a n d ultrasorgnd at a p e r i p h e r a l site m a y be a m e a s u r e of altered b o n e structure, r e f l e c t i n g s y s t e m i c b o n e loss a n d p r e d i c t i n g f r a c t u r e risk. M e t h o d s : M e a s u r e m e n t s of b r o a d b a n d u l t r a s o u n a t t e n u a t i o n (BUA), speed of s o t m d (SOS) a n d 'stiffness', a derivative of these values, w e r e t a k e n at the os calcis in 50 w o m e n with RA, 58 d i a b e t i c s a n d a n a g e - m a t c h e d n o r m a l p o p u l a t i o n . Possible influencing factors w e r e assessed by questionnaire. Results: BUA, SOS a n d stiffness w e r e significantly lower in RA g r o u p t h a n controls: stiffness a g e - m a t c h e d z score correlated significantly w i t h H A Q score (disability index), r=-0.41, p
Institutes of Pathology, Erasmus University, Rotterdam, The Netherlands and *Aarhus University, Denmark, **Department of Internal Medicine III, University Hospital Dijkzigt, 3015 GD Rotterdam, The Netherlands W h e n b o n e r e m o d e l l i n g is m a r k e d l y elevated, lack of completed w a l l s p r e c l u d e s e s t i m a t i o n of s e v e r a l p a r a m e t e r s of b o n e t u r n o v e r , s u c h as d u r a t i o n of the f o r m a t i v e period (FP) a n d a c t i v a t i o n f r e q u e n c y (Ac.f), as o n e e s s e n t i a l p a r a m e t e r , c o m p l e t e d w a l l w i d t h (W.Wi) c a n n o t be assessed. Recently, Steiniche et al, p u b l i s h e d a m e t h o d to select a n d m e a s u r e walls not yet c o m p l e t e l y m i n e r a l i s e d b u t c o m p l e t e d as to their thickness (Bone 1992, 13: 147): these are f o u n d in the lowest quartile of the v a l u e s of the ratio osteoid w i d t h / m i n e r a l i z e d width. W e u s e d this criterion, p r i m a r i l y developed to s t u d y the effect of intervention, to reconstruct W.Wi (rW.Wi) in a d v a n c e d renal o s t e o d y s t r o p h y (ROD). W.Wi w a s r e c o n s t r u c t e d in c a n c e l l o u s b o n e f r o m lilac crest biopsy sections from 12 patients with predialysis ROD a n d 12 agea n d s e x - m a t c h e d controls; null hypothesis was tested b y MannW h i t n e y ' s U-test: ROD rW.Wi FP ll.Mlt Ac.f
~m days days /year
43.1 119.6 32.8 1.7
controls averages 58.9 86.6 12.5 0.9
p <0.03 < 0.03 < 0.01 < 0.005
ROD, apart from an impaired T h u s , in p r e d i a l y s i s m i n e r a l i s a t i o n ( i n c r e a s e d initial m i n e r a l i s a t i o n lag t i m e ll.Mlt), we f o u n d walls to be s u b n o r m a l l y thin. While activation f r e q u e n c y w a s f o u n d increased, a p r o t r a c t e d formative period had to be inferred.
P34. In vitro effects of methotrexate on h u m a n osteoblasts BAA Scheven*, MJ v a n d e r Veen, CA D a m e n , FPJG Lafeber, HJM v a n Rijn, JWJ Bijlsma, SA D u u r s m a
University Hospital Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands and *Rowett Research Institute, Bucksburn, Aberdeen AB2 9SB Methotrexate l o w - d o s e t h e r a p y is considered to be a favourable a p p r o a c h for the t r e a t m e n t of r h e u m a t o i d arthritis (RA). To