- Email: [email protected]
Personal impact of osteoporotic vertebral deformity: initial results
692
Abstracts
f r a c t u r e (p=0.74). U s i n g logistic r e g r e s s i o n , t h e r e w a s no significantly g r e a t e r risk of vertebral f r a c t u r e in the presence of m o d e r a t e / s e v e r e aortic calcification (1.3, 95%C1 0.5-3.9). T h e s e r e s u l t s d o n o t s u p p o r t the h y p o t h e s i s of a d i r e c relationship between aortic calcification and vertebral osteoporosis that cannot be explained b y age.
P49. Continuous oral phosphate and intermittent intravenous clodronate in the treatment of postmenopauaal osteoporosis - a pilot study EV McCloskey, P Sirtori, K N a k a t s u k a , M N C Beneton, S Khan, J Kanis
WHO Collaborating Centre for Metabolic Bone Disease, University of Sheffield Medical School, Beech Hill Road, Sheffield $10 2RX We e v a l u a t e d the biochemical a n d h i s t o m o r p h o m e t r i c effects of a m o d i f i e d A D F R r e g i m e n in p o s t m e n o p a u s a l osteoporosis. T w e n t y w o m e n received oral p h o s p h a t e ( 1 5 0 0 m g / d a y ) for 6 m o n t h s a n d 5 s i n g l e i n f u s i o n s of c l o d r o n a t e (300mg each m o n t h ) (n=10) or 5 single infusions of c l o d r o n a t e alone (300mg each m o n t h ) (n=10). Clodronate alone significantly decreased serum alkaline p h o s p h a t a s e a c t i v i t y (-11%, p<0.05) w h e r e a s activity w a s maintained during combined treatment. Combined treatment d e c r e a s e d s e r u m c a l c i u m w i t h a slow p r o g r e s s i v e increase in PTH to 120% of p r e t r e a t m e n t values b y the fifth m o n t h (p<0.05). C l o d r o n a t e a l o n e d e c r e a s e d histological Indices of b o t h b o n e r e s o r p t i o n a n d f o r m a t i o n with significant reductions in active e r o d e d s u r f a c e (1.01_+0.63 vs 0.12_+0.10, p<0.02) a n d osteoid v o l u m e (0.35-+0.23 vs 0.19-+0.14, p<0.03). In contrast, combined t r e a t m e n t s h o w e d no significant effects on these indices. Both t r e a t m e n t s w e r e associated w i t h r e d u c t i o n s in resorption d e p t h (-18.4_+8.8, p<0.01 vs -9.5_+18.2 pm in the clodronate a n d combined t r e a t m e n t g r o u p s ) a n d n o n - s i g n i f i c a n t i n c r e a s e s in w a l l t h i c k n e s s w e r e also o b s e r v e d (+19.9_+18.7 vs +23.3-+8 p m respectively). We c o n c l u d e t h a t intermittent low dose i n t r a v e n o u s c l o d r o n a t e can s u p p r e s s b o n e t u r n o v e r at the tissue level. C o n c o m i t a n t p h o s p h a t e m a i n t a i n s b o n e t u r n o v e r but still appears to alter the b a l a n c e b e t w e e n r e s o r p t i o n a n d f o r m a t i o n within the BMU. Studies are required to confirm these findings a n d to determine h o w they translate into increments in bone mass.
P50. Trans-differentiation from hypertrophic chondrocytes to b o n e - f o r m i n g c e l l s i n v o l v e s 'unequal' cell d i v i s i o n and apoptoais - a hypothesis HI Roach, Je Erenpreisa*
Academic Orthopaedic Unit, CF86, General Hospital, Southampton and *August Kirche~tstein Institute, Riga, Latvia H y p e r t r o p h i c c h o n d r o c y t e s can switch p h e n o t y p e a n d become cells t h a t s e c r e t e a m i n e r a l i s e d b o n e m a t r i x w i t h i n intact c h o n d r o c y t i c l a c u n a e (Bone Min. 19:1-20). This p h e n o m e n o n , k n o w n as t r a n s - d i f f e r e n t i a t i o n , occurs in vivo at the g r o w t h p l a t e or d u r i n g f r a c t u r e r e p a i r , p o s s i b l y i n d u c e d b y the m i c r o m e c h a n i c a l c h a n g e s c a u s e d b y cartilage resorption. This can be r e p r o d u c e d in vitro simply by cutting t h r o u g h the region of h y p e r t r o p h i c c a r t i l a g e of e m b r y o n i c chick f e m u r s a n d culturing the pieces. By c o m b i n i n g u l t r a s t r u c t u a l observations with light microscopic i m m u n o - a n d h i s t o c h e m i s t r y w e o b t a i n e d e v i d e n c e for the following hypothesis: H y p e r t r o p h i c c h o n d r o c y t e s respond to the initial s t i m u l u s b y r e - a c t i v a t i o n of p r o t e i n s y n t h e s i s w h i c h includes " i n a p p r o p r i a t e " synthesis of t y p e 1 collagen. Then the c h o n d r o c y t e s either die by apoptosis or divide "unequally". i.e. one d a u g h t e r cell remains viable while the other is p r o g r a m m e d to die. The viable cell n o w u n d e r g o e s mitosis with the p r o g e n y being of the osteogenic p h e n o t y p e (alkaline p h o s p h a t a s e , type l c o l l a g e n , o s t e o c a l c i n a n d osteopontin). With time new b o n e matrix is secreted into the lacunae. This h i t h e r t o u n r e c o g n i s e d m e c h a n i s m offers a w a y for the direct transition from c h o n d r o c y t e s to b o n e - f o r m i n g cells, which m a y be i m p o r t a n t in the early stability of the hard fracture callus.
Bone Vol. 16, No. 6 June 1 9 9 5 : 6 7 9 - 6 9 5
1)51. Personal impact of osteoporotlc vertebral deformity: initial results BH G u r n e y , CJ T o d d , A M a r t i n , J W a l t o n , J Reeve, EV McCloskey, DRR Williams
Institute of Public Health, Robinson Way, Cambridge CB2 2SR Little is k n o w n a b o u t the r e l a t i o n s h i p b e t w e e n osteoporotic v e r t e b r a l d e f o r m i t y a n d p e r s o n impact. Studies to date h a v e been on patient or self-selected samples. A GP register based p o p u l a t i o n s t u d y of v e r t e b r a l d e f o r m i t y p r e v a l e n c e w a s c o n d u c t e d on a s a m p l e of 746 50-80 year olds stratified b y age and sex, h a l f living in s u b u r b a n H a r r o w , the o t h e r s in r u r a l C a m b r i d g e s h i r e . C a s e s w e r e identified b y s e m i - a u t o m a t e d r e a d i n g of x-rays. Personal i m p a c t data based on validated a n d r e l i a b l e p s y c h o s o c i a l i n s t r u m e r t s w e r e collected d u r i n g interview. 75 i n d i v i d u a l s w i t h one or m o r e deformities w e r e identified. Analysis w a s c o n d u c t e d using a case-control design m a t c h i n g e a c h case b y a g e a n d sex to t w o controls, one with e v i d e n c e of o s t e o a r t h r i t i s , o n e w i t h o u t . Analysis of v a r i a n c e s h o w e d no significant differences between g r o u p s on subjective health (NHP), anxiety, depression, self-rated pain, or activities of d a i l y livings. Self esteem scores differed b e t w e e n cases a n d n o r m a l con-trois (Z=-2.085, p=0.0371) but not between cases and o s t e o a r t h r i t i s c o n t r o l s or b e t w e e n the t w o control g r o u p s . G r e a t e r n u m b e r s of p e r s o n s w i t h vertebral deformities h a d b e l o w n o r m a l self esteem. M o d e r a t e deformities f o u n d in a p o p u l a t i o n s t u d y h a v e less personal impact than those found in patient p o p u l a t i o n s . The d e g r e e a n d n u m b e r of deformities that cause i n d i v i d u a l distress requires further clarification.
P52. Bone density and b o d y composition in patients on long term steroids P Todd, B Bloom*, M Buxton-Thomas, C Moniz*, P Pitt** Departments of Nuclear Medicine, *Clinical Biocheistry and **Medicine, Kings College Hospital, London SE5 9RS Long-term steroid u s a g e has a deleterious effect on the skeleton. To e x a m i n e this a n d the i m p a c t of this t r e a t m e n t on b o d y c o m p o s i t i o n , d u a l X-Ray a b s o r p t i o m e t r y (DXA) w a s used to quantitate b o n e mineral density (BMD) in s t a n d a r d sites such as the spine a n d hip, b u t also the os calcis using the Norland-XR 26. In a d d i t i o n m e a s u r e m e n t s of Total Bone Mineral C o n t e n t (TBMC), Total a n d l.ean Body Mass were performed. Patients: O n e h u n d r e d a n d thirty six patients (M--48) on a daily dose of P r e d n i s o l o n e of m o r e t h a n 5 m g s / d a y (range 5-15yrs) for between 0.5-15yrs d u r a t i o n w e r e included in the study. None of the patients h a d a n u n d e r l y i n g disease k n o w n to affect b o n e m e t a b o l i s m n o r w e r e receiving treatment for osteoporosis. The clinical g r o u p s w e r e A s t h m a (n=S2, 22M), P o l y m y a l g i a Rheurnatica (n=45, 15M), Connective tissue diseases (n=30, 9M) a n d h a e m a t o l o g i c a l a n d d e r m a t o l o g i c a l conditions (n=9, 2M). Results: The p r e v a l e n c e of low b o n e m a s s a n d z scores of less than -I w a s 47.5% for the spine a n d 60.9% hip in the w h o l e g r o u p a n d at either site: 81% asthma, 76.6% collagen vascular, 48.6% P M R BMD at L2-L4, hip, trochanter, w a r d ' s and neck and os calcis s h o w e d significant correlations with each other a n d with TBMC in all s u b g r o u p s except the collagen v a s c u l a r disorders. O n l y in this g r o u p , BMDos and BMDneck a n d w a r d ' s triangle did not correlate with T B M C C o n c l u s i o n : The results d e m o n s t r a t e a g e n e r a l i s e d effect of glucocorticoids on skeletal metabolism rather than a predil~_ction for t r a b e c u l a r bone. Thus m e a s u r e m e n t s of alternative sites such as the os could be of value in osteoporosis risk assessment. The differences seen in the collagen v a s c u l a r g r o u p s u g g e s t other factors, p o s s i b l y i n f l a m m a t o y m e d i a t o r s in the a u t o i m m u n e process, m a y h a v e an additional deleterious effect on bone. P53. Effects of p o l y m y a l g l a rheumatics on bone and the consequences of steroid treatment A Dolan, C Mackintosh*, P Todd**, B D a s g u p t a , M BuxtonThomas**, C Moniz*
Departments of Rheumatology, Guy's ttospital, *Clinical Biochemistry and **Nuclear Medicine Kings College lfospital, London SE5 9RS P o l y m y a l g i a r h e u m a t i c a (PMR) is a n i n f l a m m a t o r y condition that r e s p o n d s rapidly to steroids. The effects of steroids on bone
Abstracts
f r a c t u r e (p=0.74). U s i n g logistic r e g r e s s i o n , t h e r e w a s no significantly g r e a t e r risk of vertebral f r a c t u r e in the presence of m o d e r a t e / s e v e r e aortic calcification (1.3, 95%C1 0.5-3.9). T h e s e r e s u l t s d o n o t s u p p o r t the h y p o t h e s i s of a d i r e c relationship between aortic calcification and vertebral osteoporosis that cannot be explained b y age.
P49. Continuous oral phosphate and intermittent intravenous clodronate in the treatment of postmenopauaal osteoporosis - a pilot study EV McCloskey, P Sirtori, K N a k a t s u k a , M N C Beneton, S Khan, J Kanis
WHO Collaborating Centre for Metabolic Bone Disease, University of Sheffield Medical School, Beech Hill Road, Sheffield $10 2RX We e v a l u a t e d the biochemical a n d h i s t o m o r p h o m e t r i c effects of a m o d i f i e d A D F R r e g i m e n in p o s t m e n o p a u s a l osteoporosis. T w e n t y w o m e n received oral p h o s p h a t e ( 1 5 0 0 m g / d a y ) for 6 m o n t h s a n d 5 s i n g l e i n f u s i o n s of c l o d r o n a t e (300mg each m o n t h ) (n=10) or 5 single infusions of c l o d r o n a t e alone (300mg each m o n t h ) (n=10). Clodronate alone significantly decreased serum alkaline p h o s p h a t a s e a c t i v i t y (-11%, p<0.05) w h e r e a s activity w a s maintained during combined treatment. Combined treatment d e c r e a s e d s e r u m c a l c i u m w i t h a slow p r o g r e s s i v e increase in PTH to 120% of p r e t r e a t m e n t values b y the fifth m o n t h (p<0.05). C l o d r o n a t e a l o n e d e c r e a s e d histological Indices of b o t h b o n e r e s o r p t i o n a n d f o r m a t i o n with significant reductions in active e r o d e d s u r f a c e (1.01_+0.63 vs 0.12_+0.10, p<0.02) a n d osteoid v o l u m e (0.35-+0.23 vs 0.19-+0.14, p<0.03). In contrast, combined t r e a t m e n t s h o w e d no significant effects on these indices. Both t r e a t m e n t s w e r e associated w i t h r e d u c t i o n s in resorption d e p t h (-18.4_+8.8, p<0.01 vs -9.5_+18.2 pm in the clodronate a n d combined t r e a t m e n t g r o u p s ) a n d n o n - s i g n i f i c a n t i n c r e a s e s in w a l l t h i c k n e s s w e r e also o b s e r v e d (+19.9_+18.7 vs +23.3-+8 p m respectively). We c o n c l u d e t h a t intermittent low dose i n t r a v e n o u s c l o d r o n a t e can s u p p r e s s b o n e t u r n o v e r at the tissue level. C o n c o m i t a n t p h o s p h a t e m a i n t a i n s b o n e t u r n o v e r but still appears to alter the b a l a n c e b e t w e e n r e s o r p t i o n a n d f o r m a t i o n within the BMU. Studies are required to confirm these findings a n d to determine h o w they translate into increments in bone mass.
P50. Trans-differentiation from hypertrophic chondrocytes to b o n e - f o r m i n g c e l l s i n v o l v e s 'unequal' cell d i v i s i o n and apoptoais - a hypothesis HI Roach, Je Erenpreisa*
Academic Orthopaedic Unit, CF86, General Hospital, Southampton and *August Kirche~tstein Institute, Riga, Latvia H y p e r t r o p h i c c h o n d r o c y t e s can switch p h e n o t y p e a n d become cells t h a t s e c r e t e a m i n e r a l i s e d b o n e m a t r i x w i t h i n intact c h o n d r o c y t i c l a c u n a e (Bone Min. 19:1-20). This p h e n o m e n o n , k n o w n as t r a n s - d i f f e r e n t i a t i o n , occurs in vivo at the g r o w t h p l a t e or d u r i n g f r a c t u r e r e p a i r , p o s s i b l y i n d u c e d b y the m i c r o m e c h a n i c a l c h a n g e s c a u s e d b y cartilage resorption. This can be r e p r o d u c e d in vitro simply by cutting t h r o u g h the region of h y p e r t r o p h i c c a r t i l a g e of e m b r y o n i c chick f e m u r s a n d culturing the pieces. By c o m b i n i n g u l t r a s t r u c t u a l observations with light microscopic i m m u n o - a n d h i s t o c h e m i s t r y w e o b t a i n e d e v i d e n c e for the following hypothesis: H y p e r t r o p h i c c h o n d r o c y t e s respond to the initial s t i m u l u s b y r e - a c t i v a t i o n of p r o t e i n s y n t h e s i s w h i c h includes " i n a p p r o p r i a t e " synthesis of t y p e 1 collagen. Then the c h o n d r o c y t e s either die by apoptosis or divide "unequally". i.e. one d a u g h t e r cell remains viable while the other is p r o g r a m m e d to die. The viable cell n o w u n d e r g o e s mitosis with the p r o g e n y being of the osteogenic p h e n o t y p e (alkaline p h o s p h a t a s e , type l c o l l a g e n , o s t e o c a l c i n a n d osteopontin). With time new b o n e matrix is secreted into the lacunae. This h i t h e r t o u n r e c o g n i s e d m e c h a n i s m offers a w a y for the direct transition from c h o n d r o c y t e s to b o n e - f o r m i n g cells, which m a y be i m p o r t a n t in the early stability of the hard fracture callus.
Bone Vol. 16, No. 6 June 1 9 9 5 : 6 7 9 - 6 9 5
1)51. Personal impact of osteoporotlc vertebral deformity: initial results BH G u r n e y , CJ T o d d , A M a r t i n , J W a l t o n , J Reeve, EV McCloskey, DRR Williams
Institute of Public Health, Robinson Way, Cambridge CB2 2SR Little is k n o w n a b o u t the r e l a t i o n s h i p b e t w e e n osteoporotic v e r t e b r a l d e f o r m i t y a n d p e r s o n impact. Studies to date h a v e been on patient or self-selected samples. A GP register based p o p u l a t i o n s t u d y of v e r t e b r a l d e f o r m i t y p r e v a l e n c e w a s c o n d u c t e d on a s a m p l e of 746 50-80 year olds stratified b y age and sex, h a l f living in s u b u r b a n H a r r o w , the o t h e r s in r u r a l C a m b r i d g e s h i r e . C a s e s w e r e identified b y s e m i - a u t o m a t e d r e a d i n g of x-rays. Personal i m p a c t data based on validated a n d r e l i a b l e p s y c h o s o c i a l i n s t r u m e r t s w e r e collected d u r i n g interview. 75 i n d i v i d u a l s w i t h one or m o r e deformities w e r e identified. Analysis w a s c o n d u c t e d using a case-control design m a t c h i n g e a c h case b y a g e a n d sex to t w o controls, one with e v i d e n c e of o s t e o a r t h r i t i s , o n e w i t h o u t . Analysis of v a r i a n c e s h o w e d no significant differences between g r o u p s on subjective health (NHP), anxiety, depression, self-rated pain, or activities of d a i l y livings. Self esteem scores differed b e t w e e n cases a n d n o r m a l con-trois (Z=-2.085, p=0.0371) but not between cases and o s t e o a r t h r i t i s c o n t r o l s or b e t w e e n the t w o control g r o u p s . G r e a t e r n u m b e r s of p e r s o n s w i t h vertebral deformities h a d b e l o w n o r m a l self esteem. M o d e r a t e deformities f o u n d in a p o p u l a t i o n s t u d y h a v e less personal impact than those found in patient p o p u l a t i o n s . The d e g r e e a n d n u m b e r of deformities that cause i n d i v i d u a l distress requires further clarification.
P52. Bone density and b o d y composition in patients on long term steroids P Todd, B Bloom*, M Buxton-Thomas, C Moniz*, P Pitt** Departments of Nuclear Medicine, *Clinical Biocheistry and **Medicine, Kings College Hospital, London SE5 9RS Long-term steroid u s a g e has a deleterious effect on the skeleton. To e x a m i n e this a n d the i m p a c t of this t r e a t m e n t on b o d y c o m p o s i t i o n , d u a l X-Ray a b s o r p t i o m e t r y (DXA) w a s used to quantitate b o n e mineral density (BMD) in s t a n d a r d sites such as the spine a n d hip, b u t also the os calcis using the Norland-XR 26. In a d d i t i o n m e a s u r e m e n t s of Total Bone Mineral C o n t e n t (TBMC), Total a n d l.ean Body Mass were performed. Patients: O n e h u n d r e d a n d thirty six patients (M--48) on a daily dose of P r e d n i s o l o n e of m o r e t h a n 5 m g s / d a y (range 5-15yrs) for between 0.5-15yrs d u r a t i o n w e r e included in the study. None of the patients h a d a n u n d e r l y i n g disease k n o w n to affect b o n e m e t a b o l i s m n o r w e r e receiving treatment for osteoporosis. The clinical g r o u p s w e r e A s t h m a (n=S2, 22M), P o l y m y a l g i a Rheurnatica (n=45, 15M), Connective tissue diseases (n=30, 9M) a n d h a e m a t o l o g i c a l a n d d e r m a t o l o g i c a l conditions (n=9, 2M). Results: The p r e v a l e n c e of low b o n e m a s s a n d z scores of less than -I w a s 47.5% for the spine a n d 60.9% hip in the w h o l e g r o u p a n d at either site: 81% asthma, 76.6% collagen vascular, 48.6% P M R BMD at L2-L4, hip, trochanter, w a r d ' s and neck and os calcis s h o w e d significant correlations with each other a n d with TBMC in all s u b g r o u p s except the collagen v a s c u l a r disorders. O n l y in this g r o u p , BMDos and BMDneck a n d w a r d ' s triangle did not correlate with T B M C C o n c l u s i o n : The results d e m o n s t r a t e a g e n e r a l i s e d effect of glucocorticoids on skeletal metabolism rather than a predil~_ction for t r a b e c u l a r bone. Thus m e a s u r e m e n t s of alternative sites such as the os could be of value in osteoporosis risk assessment. The differences seen in the collagen v a s c u l a r g r o u p s u g g e s t other factors, p o s s i b l y i n f l a m m a t o y m e d i a t o r s in the a u t o i m m u n e process, m a y h a v e an additional deleterious effect on bone. P53. Effects of p o l y m y a l g l a rheumatics on bone and the consequences of steroid treatment A Dolan, C Mackintosh*, P Todd**, B D a s g u p t a , M BuxtonThomas**, C Moniz*
Departments of Rheumatology, Guy's ttospital, *Clinical Biochemistry and **Nuclear Medicine Kings College lfospital, London SE5 9RS P o l y m y a l g i a r h e u m a t i c a (PMR) is a n i n f l a m m a t o r y condition that r e s p o n d s rapidly to steroids. The effects of steroids on bone