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Urinary galactosyl hyoroxylysine excretion reflects the decrease in bone mineral content induced by ovariectomy in rats
256
A GENETIC
257 EFFECT
ON RATES OF CHANGE NG: A TWIN STUDY.
IN BONE
P Sambrook. J Eisw Garvan In Research,1 Department of Muclear Medicine, St Vincent's Hospital, Sydney, NSW, Australia and 2 Faculty of Medicine Epidemiology Unit, University of Melbourne, Melbourne. Vie. Australia Bone density and risk of fracture in later life is related to both peak bone density and subsequent bone loss with aging. Although there is evidence for a genetic effect on peak bone mass, it i is not known whether there is a genetic effect on changesin bone density with age. Data on indices of bone turnover in twins support a genetic effect on bone turnover and thus age-related changes in bone mass. We therefore examined rates of Fhange of lumbar spine and proximal femoral bone density (Lunar DP3) In a cohort of monozygotic (MZ. n = 20.3 male and 17 female pairs, age; median, range; 46,24-75 yrs) and dizygotic twins (DZ, n = 19; 43, 25-65 yrs). The median follow-up was 3 years (range 1.1-5.5 yrs) with each subject having at least two, with up to 4, bone density assessments. ElevenJwin pairs (8 MZ, 3 DZ) were postmenopausal and no twin pairs were discordant for menopausal state or years since menopause. The
intrapair correlations, r~z and ~2 for % rates of change at the lumbar spine (r = 0.94 and 0.50 respectively, p=O.O14)and Ward’s triangle (r = 60 and 0.1 I respectively, pcO.05, one-tailed) were consistent with a genetic effect on changes at these sites. The difference in m (0.49 and ~2 (0.06) for the trochanteric region was not significant however model fiittinganalysis confirmed that genetic factors contribute to changes at this site. No significant genetic effect could be demonstrated at the femoml
neck. Controlling for the effect of Possible covariates such as dietarv calcium, body weight or physical fit&s did not zher the results. These data demonstrate, for the first time. that there are strong genetic
effects on rates of change in bone density in adults, with genetic factors contributing up to 80% of the variance in bone density changes at the lumbar spine. However such an effect could not be demonstrated at the femoral neck. and this may relate to the higher proportion of cortical
OSTEOPENIA ASSOCIATED TO INSULIN-DEPENDENT DIABETES MELLITUS. M.J. Kayath. R.B. Peres, S.A. Dib, J.C.H. Vieira Division of Endocrinology, Escola Paulista de Medicina. Sio Paula, Brasil. The association of osteopenia and Insulin-Dependent Diabetes Mellitus (IDDM) has been debated in recent publications. In order to evaluate this subject in our IDDM population we measured Bone Mineral Density (BKD) in the lumbar spine (SBMD) and femoral neck (FBMD) in 40 patients using dual energy X-ray absorptidmetr; (Dexa, Lunar DPX). The results were compared to an aae and sexmatched brazilian population. The group included 14 female and 26 male patients, 19 to 57 years old with a median duration of the disease of 6.5 years. 17 patients (42.5%) were classified as having a reduced bone mineral density. 12 in both sites measured (SBMD and FBMD, median of loss: 24 and 25% respectively), 3 only FBND and 2 SB?ID. The comparison of these 17.patlents with the 23 withnormal 4MD showed that the osteopenic were younger (median 27 y vs. 34 y, pqO.05). showed a higher mean plasma glucose (15.8t6.1 vs. 11.724.1 tmnolll, meanfsd. pmO.05) and used more insulin (57219 vs 43215 U/day, mean+sd, ~~0.05). They also showed a tendency for higher HbAl values (median of 10.2% vs. 8.9X), for a higher incidence of chronic complications, mainly retinopathy (47% vs.l?X), and for a longer duration of disease (median 10 y for the osteopenic and 4 y for the patients with norinal BMD). No significant difference was foundintotal body fat (231+12%vs. .?S-+llX, mrantsd) measured by dual energy X-ray absorptiometry. Our data suggests that osteopenia can be a chronic complications of poor controlled patients with IDDM.
bone at this site and supports our previous data suggesting that environmental factors are reiiativelymoti importantat that SIG. -
258 TOTAL 24-HOUR PYRIDINIUM CROSSLINK EXCRETION CORRELATES WITH CANCELLOUS BONE RESORPTION RATE. M. A. Kotowicz. J. D. Jones. W. M. O’Fallon. E. Eriksen. R. Eastell. B. L. Rices. Mayo Clinic and Foundation, Rochester, MN 559Dl U.S.A.
The pyridinium crosslinks of collagen. pyridinoline (Pyr) and deoxypyridinoline (dPyd), arc released during bone degradation and are bclicved to be specific biochemical markers for bone resorption. WC cxamincd the relationship between the urinary excretion of pyridinium crosslinks of, collagen and bone turnover using dynamic histomorphometry of double tetracycline labeled transiliac biopsy samplas from 28 normal postmenopausal women (age, 65 t 6 yr, mean f SD; and 63 pos,tmenopausal osteoporotic women (age, 66 f 5 yr) with vertebral compression fractures. Free Pyd and dPyd excretion (nmol/mol crcalinine) from 24-hour urine spccimcns and total Pyd and dPyd cxcrction (nmollmol crcatinine) in acid hydrolysates were mcasurcd by HPLC aflcr CFl cellulose partition chromatography. Bone formation rate/volume referent (BFR.BV) was calculalcd from Bone resorption rate/volume tetracycline-based mcasurcmcnts. r&rent (BRsR.BV) was calculaled by the Eriksen method (Endocr Rev 7:1-30, 1986) from direct measurement ofresorpdon depth, ratios of BF/Bl? surfaces and formative data. Signilicanl correlations were found belwecn BRsR.BV and total Pyd and total dPyd, whereas BFR.BV did not correlale with total crosslink cxcrction. Corrclalions bclwccn bone histomorphomctric indices and free crosslinkexcretion were gcncrally weaker, and only the correlation bclween free dPyd and BRsR.BV rcachcd signilicancc. Neither the ratio total (Pyd:dPyd) nor free (Pyd:dPyd) corrclalcd with BRsR.BV or BFR.BV. total-dPyd free-dPyd free-Pyd total-Pyd 0.156 0.295’ 0.354‘ 0.196 BRsR.BV 0.106 0.255’ 0.095 0.191 BFR.BV For signilicnncc of corrclntion cocllicicnls: ‘fl =z0.0% ‘p c 0.01 Conclusions: 1) lolaI 24.hour urinary Pyd and dPyd arc markers of bone resorption ralhcr than bone formalion; 2) total dPyd, the bone spccilic crosslink,performs bcltcr as a marker of bone rcsorplion than to~nl Pyd; and 3) in this study. tolnl crosslinks provided a bcttcr cslimatc of bone resorption than did free crosslinks.
259 iJRiNARV GALACTGSVL HVDROXVLVSINE EXCRETiGrl REFLECTS THE DECREASE IN BONE MINERAL CONTENT INDUCED BY OWARlECTOMY IN RATS. *L. More, **P. Bertica, **P. Villani, **A. Pecile. ***A. Rubinacci, ***GL. Moro, ****N. Greco, ****!I.Specchia, ****C. Sanguinetti, *l3.de Bernard *Dep. Biochen. Trieste, **Dep. Pharnacol. Milano, ***Dep. Orthop. ililano, ****Clin. Orthop. Rona. Italy Galactosyl hydroxylysine (GHYL) was shown in human to be an index of bone resorption in physiological and paiholoqical conditions. In rhe experimental animal (e.g. rat), the validity of this urinary marker of bone resorption may be accurately studied by differet.t means including also histomorphone;ric evaluations of bone. Female Sprague Dawley rats (250 g) were subjected either to bilaLera1 ovariectomy (OVX, n=7) or co sham ol;eratior,(SH, n=8). Their urinary excre';ion of GHYL and bone mineral content (WC) of =he lef; hind lieb netaphysis were detemined every 15 days for 3 months after surgery. Tibiae and vertebrae were processed for quantizative bone norphometry at the end of ihe experinenz. 3X in OVX was found significantly lower r,hanin Sli as early as 15 days after surgery (-12.4%. p=O.O19t and furrherly decreased at 30 days (-16.7X, pCO.0001) remaining at rhese low levels until 90 days. GHYL excretion was markedly higher in OVX zhan in SH bo;h at 15 days (41.2iZ.5 vs 31.5iO.5, p=O.O48! and at 30 days after surgery (42.5k3.5 vs 33.8~1.8, p=O.O32), while it returned to similar values in bozh OVX and SH in the following times (e.g. 26.2tl.g vs 25.921.9 a< 45 days and 28.&l vs 29.45.6 at 90 days), accuraeely reflecting the changes in bone turnover thai led 'io
139
A GENETIC
257 EFFECT
ON RATES OF CHANGE NG: A TWIN STUDY.
IN BONE
P Sambrook. J Eisw Garvan In Research,1 Department of Muclear Medicine, St Vincent's Hospital, Sydney, NSW, Australia and 2 Faculty of Medicine Epidemiology Unit, University of Melbourne, Melbourne. Vie. Australia Bone density and risk of fracture in later life is related to both peak bone density and subsequent bone loss with aging. Although there is evidence for a genetic effect on peak bone mass, it i is not known whether there is a genetic effect on changesin bone density with age. Data on indices of bone turnover in twins support a genetic effect on bone turnover and thus age-related changes in bone mass. We therefore examined rates of Fhange of lumbar spine and proximal femoral bone density (Lunar DP3) In a cohort of monozygotic (MZ. n = 20.3 male and 17 female pairs, age; median, range; 46,24-75 yrs) and dizygotic twins (DZ, n = 19; 43, 25-65 yrs). The median follow-up was 3 years (range 1.1-5.5 yrs) with each subject having at least two, with up to 4, bone density assessments. ElevenJwin pairs (8 MZ, 3 DZ) were postmenopausal and no twin pairs were discordant for menopausal state or years since menopause. The
intrapair correlations, r~z and ~2 for % rates of change at the lumbar spine (r = 0.94 and 0.50 respectively, p=O.O14)and Ward’s triangle (r = 60 and 0.1 I respectively, pcO.05, one-tailed) were consistent with a genetic effect on changes at these sites. The difference in m (0.49 and ~2 (0.06) for the trochanteric region was not significant however model fiittinganalysis confirmed that genetic factors contribute to changes at this site. No significant genetic effect could be demonstrated at the femoml
neck. Controlling for the effect of Possible covariates such as dietarv calcium, body weight or physical fit&s did not zher the results. These data demonstrate, for the first time. that there are strong genetic
effects on rates of change in bone density in adults, with genetic factors contributing up to 80% of the variance in bone density changes at the lumbar spine. However such an effect could not be demonstrated at the femoral neck. and this may relate to the higher proportion of cortical
OSTEOPENIA ASSOCIATED TO INSULIN-DEPENDENT DIABETES MELLITUS. M.J. Kayath. R.B. Peres, S.A. Dib, J.C.H. Vieira Division of Endocrinology, Escola Paulista de Medicina. Sio Paula, Brasil. The association of osteopenia and Insulin-Dependent Diabetes Mellitus (IDDM) has been debated in recent publications. In order to evaluate this subject in our IDDM population we measured Bone Mineral Density (BKD) in the lumbar spine (SBMD) and femoral neck (FBMD) in 40 patients using dual energy X-ray absorptidmetr; (Dexa, Lunar DPX). The results were compared to an aae and sexmatched brazilian population. The group included 14 female and 26 male patients, 19 to 57 years old with a median duration of the disease of 6.5 years. 17 patients (42.5%) were classified as having a reduced bone mineral density. 12 in both sites measured (SBMD and FBMD, median of loss: 24 and 25% respectively), 3 only FBND and 2 SB?ID. The comparison of these 17.patlents with the 23 withnormal 4MD showed that the osteopenic were younger (median 27 y vs. 34 y, pqO.05). showed a higher mean plasma glucose (15.8t6.1 vs. 11.724.1 tmnolll, meanfsd. pmO.05) and used more insulin (57219 vs 43215 U/day, mean+sd, ~~0.05). They also showed a tendency for higher HbAl values (median of 10.2% vs. 8.9X), for a higher incidence of chronic complications, mainly retinopathy (47% vs.l?X), and for a longer duration of disease (median 10 y for the osteopenic and 4 y for the patients with norinal BMD). No significant difference was foundintotal body fat (231+12%vs. .?S-+llX, mrantsd) measured by dual energy X-ray absorptiometry. Our data suggests that osteopenia can be a chronic complications of poor controlled patients with IDDM.
bone at this site and supports our previous data suggesting that environmental factors are reiiativelymoti importantat that SIG. -
258 TOTAL 24-HOUR PYRIDINIUM CROSSLINK EXCRETION CORRELATES WITH CANCELLOUS BONE RESORPTION RATE. M. A. Kotowicz. J. D. Jones. W. M. O’Fallon. E. Eriksen. R. Eastell. B. L. Rices. Mayo Clinic and Foundation, Rochester, MN 559Dl U.S.A.
The pyridinium crosslinks of collagen. pyridinoline (Pyr) and deoxypyridinoline (dPyd), arc released during bone degradation and are bclicved to be specific biochemical markers for bone resorption. WC cxamincd the relationship between the urinary excretion of pyridinium crosslinks of, collagen and bone turnover using dynamic histomorphometry of double tetracycline labeled transiliac biopsy samplas from 28 normal postmenopausal women (age, 65 t 6 yr, mean f SD; and 63 pos,tmenopausal osteoporotic women (age, 66 f 5 yr) with vertebral compression fractures. Free Pyd and dPyd excretion (nmol/mol crcalinine) from 24-hour urine spccimcns and total Pyd and dPyd cxcrction (nmollmol crcatinine) in acid hydrolysates were mcasurcd by HPLC aflcr CFl cellulose partition chromatography. Bone formation rate/volume referent (BFR.BV) was calculalcd from Bone resorption rate/volume tetracycline-based mcasurcmcnts. r&rent (BRsR.BV) was calculaled by the Eriksen method (Endocr Rev 7:1-30, 1986) from direct measurement ofresorpdon depth, ratios of BF/Bl? surfaces and formative data. Signilicanl correlations were found belwecn BRsR.BV and total Pyd and total dPyd, whereas BFR.BV did not correlale with total crosslink cxcrction. Corrclalions bclwccn bone histomorphomctric indices and free crosslinkexcretion were gcncrally weaker, and only the correlation bclween free dPyd and BRsR.BV rcachcd signilicancc. Neither the ratio total (Pyd:dPyd) nor free (Pyd:dPyd) corrclalcd with BRsR.BV or BFR.BV. total-dPyd free-dPyd free-Pyd total-Pyd 0.156 0.295’ 0.354‘ 0.196 BRsR.BV 0.106 0.255’ 0.095 0.191 BFR.BV For signilicnncc of corrclntion cocllicicnls: ‘fl =z0.0% ‘p c 0.01 Conclusions: 1) lolaI 24.hour urinary Pyd and dPyd arc markers of bone resorption ralhcr than bone formalion; 2) total dPyd, the bone spccilic crosslink,performs bcltcr as a marker of bone rcsorplion than to~nl Pyd; and 3) in this study. tolnl crosslinks provided a bcttcr cslimatc of bone resorption than did free crosslinks.
259 iJRiNARV GALACTGSVL HVDROXVLVSINE EXCRETiGrl REFLECTS THE DECREASE IN BONE MINERAL CONTENT INDUCED BY OWARlECTOMY IN RATS. *L. More, **P. Bertica, **P. Villani, **A. Pecile. ***A. Rubinacci, ***GL. Moro, ****N. Greco, ****!I.Specchia, ****C. Sanguinetti, *l3.de Bernard *Dep. Biochen. Trieste, **Dep. Pharnacol. Milano, ***Dep. Orthop. ililano, ****Clin. Orthop. Rona. Italy Galactosyl hydroxylysine (GHYL) was shown in human to be an index of bone resorption in physiological and paiholoqical conditions. In rhe experimental animal (e.g. rat), the validity of this urinary marker of bone resorption may be accurately studied by differet.t means including also histomorphone;ric evaluations of bone. Female Sprague Dawley rats (250 g) were subjected either to bilaLera1 ovariectomy (OVX, n=7) or co sham ol;eratior,(SH, n=8). Their urinary excre';ion of GHYL and bone mineral content (WC) of =he lef; hind lieb netaphysis were detemined every 15 days for 3 months after surgery. Tibiae and vertebrae were processed for quantizative bone norphometry at the end of ihe experinenz. 3X in OVX was found significantly lower r,hanin Sli as early as 15 days after surgery (-12.4%. p=O.O19t and furrherly decreased at 30 days (-16.7X, pCO.0001) remaining at rhese low levels until 90 days. GHYL excretion was markedly higher in OVX zhan in SH bo;h at 15 days (41.2iZ.5 vs 31.5iO.5, p=O.O48! and at 30 days after surgery (42.5k3.5 vs 33.8~1.8, p=O.O32), while it returned to similar values in bozh OVX and SH in the following times (e.g. 26.2tl.g vs 25.921.9 a< 45 days and 28.&l vs 29.45.6 at 90 days), accuraeely reflecting the changes in bone turnover thai led 'io
139