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Determinants of bone mineral density in healthy elderly women
276
CE FLL’CXDE SALTS . ! . F.,*n:l.,V UC,..“.... 2RARHXtXISETfC.S Rotta Research Laborslorium, Monza. ltoly. Fluoride in plasma was assayedafter oral administration to human volunteers of different preparations used for the fluoride therapy of osteoporosis.such as capsules of plain NsF (NaF-P). monofluorophosphate (MFP-T). tablets of tablets of monofluorophosphate combined with calcium salts (MFP-Ctt), enteric coated NaF (NoF-G). NsF-P is readly absorbed from the Gl tract and fluoride in plasma peaks 30-60 min after administration, Similnr pattern of fluoride are observed after MFP-T and MFP-Ca. Conversely NaF-G is slowly absorbed and fluoride in plasma peaks after 3-5 hours. The bioavailnbility of fluoride relative to that from an aqueous solution of NaF and estimated from the AUC of fluoride in plasmrt, was 100% within the experiments1 errors for NttF-P. MFP-T and MFP-Co. Conversely the relative bioavailability of NsF-G was 20-3096. Fluoride has two effects on bone: it stimulates the osteabloststo form new bone tissue and it substitutes the hydroxylic groups of npndte to form the more stable fluoronpntite. The first effect is probably depended on the levels of fluoride in plasnrn, the second on the totnl quantity of fluoride which has become bioavniloble during the whole period of fluorotharapy. Conclusions There are convergent views that fluoroth*repy of osteoporosis should be conducted with 8-10 mg bionvailoble fluoride daily for 2-4 years. In order to assess the doses of the proprietary and nonproprietary fluoride preparations ttctually used. it is mandatory to know their pharnutcokinetic pattern. their bioovailsbility and the effects of meals tmli of calcium salts on their bioovailability. The dosage schedules must be ndjusted taking into xcount the biottvnilability of fluoride from the preparations, rather than the nominal content of fluoride.
278 BONE
277 ml-1 firr~~~.~snort 111 oor31c11trc ““I) snyc b Y,L#l.Vl-Ll”n” ” I”I.l I b.b..h.m”
I f-jrrs AT TL;IE yymm CP!NF urn_,. . “. .*._ _b.“U ,.
AND FEMORAL NECK IN QIOPATHIC GSTECPOROSIS. N. H. Bell, R& Morwessel, 1. A. Colletti. R Eastell. Ft. G. G. Russell. J. Sharv flntr. bv L. L. m. VA Med. Center ani Med. Univ. S.C., Cnarleston, SC, USA; and Univ. Sheffield Med. School, Sheffield, England Prostaglandin 4 (PG&) is produced by osteoblasts and may mediate ongoing bone resorption. Urinary calcium (Ca) is increased by PGE, and decreased by inhibition of PG synthesis. Studies were conducted to determine a) the effects of the nonsteroidal antiinflammatory drug diclofenac sodium on bone and mineral metabolism and b) whether the drug prevents bone loss in idiopathic osteoporosis. 10 normal premenopausal women, 7 normal men and 3 patients with idiopathic osteoporosis were studied. The patients had normal pituitary, thyroid, adrenal and gonadal function and no apparent cause for osteoporosis. All were hospitalized on a metabolic ward for two and a half days and were given a constant daiiy intake of Ca and phosphate before and again afler treatment with dictofenac sodium, 50 mg p.o.t.i.d. for 4 wk. Daily fasting Mood samples and two 24.hr urine samples were obtained. In the short-term studies, diclofenac sodium lowered urinary Ca from 170 f 12 to 130 f 14 mglday (k SEM, P ~0.001) in the normals and from 197 f 42 to 152 i 44 mglday (P
279
LOSSIN THE UPPER FEMUR AFTER lMMOBlLlZATION FOLLOWING UNSTABLE FRACTURES OF THE LOWER LEG. partments
of
Endocrinology,Surgery and Nuclear Medlclne, Free Unlverslty Hospltal Amsterdam, The Netherlands. Prolonged dlause followlng fracture results In bone loss, which may predispose to new fractures. We have evaluated the bone loss in 15 patients (aged 60r7.5 (SD) years, 7 men, 8 postmenopausalwomen), all suffering from a fracture of the lower leg. All fracture were unstable, necessitating l~ob~liaatlon andunloadingof the leg for 7.711.7 weeks. Bone mlneral danslty (BMDI was measured by dual X-ray absorptiometry (DXA) of the lumbar spine and both hips (femoral neck and trochanteric region). BMD was measured immediately after the fracture, after the lmmoblllzatlon period and at 6 months after the fracture. During Immobilization BMD of the trochanteric region decreased 8.5%27% (from 0.69r0.16 g/cm ’ to 0.6360.18g/cml at the side of the fracture, compared to 0.13%~7.2% at the other slde (P~O.003). After slx months the decrease was 15.6%*10% (0.57t0.16 g/cm’) at the slde of the fracture vs 2%*7.!l% In the non-fractured leg (P*O.Oll. The BMD of the femoral neck in the fractured leg decreased 7.1%*5.6% (from 0.74tO.16 g/cm’ to 0.66tO.17 glcm’l after 6 months, compared to 1.6%15.4% in the nonfractured leg (P*O.OOSl. The lumbar spine did not show significant changes during 6 months after the fracture. We conclude that immobilization and unloading of a fractured leg leads to significant bone loss In the corresponding hip, a Process that contimls for six months after the fracture. It is uncertain whether remobilization will lead to complete restoration of bone mass.
DETERMINANTSOF BONE MINERAL DENStl’Y IN HEALTHY ELDERLY WOMEN. P. Lbs. M.E. Ooms. A. van Linaen. H.A. Valkenburq. Department of Endocrinoloav, Free Universitv Hosoital and EMGOInstitute, Free University, Am&dam, The Netherlands. Bone mineral density (BMO) and risk factors for osteoporosis were assessed In 349 women over 70 years of age (mean 2 SD 82.3 ~5.6 years), participating in a trial to investigate the effect of vimmin D supplementation on the Incidence of hip fractures. BMD was measured at both hips and the distal radius, Data were colfected on he@:, body weight, menopause, mobility (5 points SCale), d,atary ccicium intake and medlcatlon. Unear multiple regresston and .‘.iNOVA were used for statistical analysis. The best determlnants of BMD accordi;lg to stepwlse multiple regression were body weight and years since menooause (multiole F12 between 0.07 and 0.20, p~O.001). -A slgnificanuy lower BMd at the hip was observed In panicipants with fmpalred mc i-ility (-5%). users of IOOP diuretics (-5%) and users of corticosterolds ( ‘:-6< tb -17.1%). Users & thiazides dkl not have a higher BMD. Ceil;cum intake horn d&lproducts ranged from 90 to 2911 mglday (mean 921 mg(.tay). Calcium intake did not influence BMD at any site. Paniiipants with a history of Cokes’ fracture had a significantly lower Bl.9R li the other radius (-11.6%). We conclude :nat low EMD cannot be adequately be predicted. Risk factors for low BMD in the elderly are low body weight, high number of years since menopause, impaired mobility and use of loop diuretics and corticosteroids. Low calcium intake was not a risk factor In this study.
144
CE FLL’CXDE SALTS . ! . F.,*n:l.,V UC,..“.... 2RARHXtXISETfC.S Rotta Research Laborslorium, Monza. ltoly. Fluoride in plasma was assayedafter oral administration to human volunteers of different preparations used for the fluoride therapy of osteoporosis.such as capsules of plain NsF (NaF-P). monofluorophosphate (MFP-T). tablets of tablets of monofluorophosphate combined with calcium salts (MFP-Ctt), enteric coated NaF (NoF-G). NsF-P is readly absorbed from the Gl tract and fluoride in plasma peaks 30-60 min after administration, Similnr pattern of fluoride are observed after MFP-T and MFP-Ca. Conversely NaF-G is slowly absorbed and fluoride in plasma peaks after 3-5 hours. The bioavailnbility of fluoride relative to that from an aqueous solution of NaF and estimated from the AUC of fluoride in plasmrt, was 100% within the experiments1 errors for NttF-P. MFP-T and MFP-Co. Conversely the relative bioavailability of NsF-G was 20-3096. Fluoride has two effects on bone: it stimulates the osteabloststo form new bone tissue and it substitutes the hydroxylic groups of npndte to form the more stable fluoronpntite. The first effect is probably depended on the levels of fluoride in plasnrn, the second on the totnl quantity of fluoride which has become bioavniloble during the whole period of fluorotharapy. Conclusions There are convergent views that fluoroth*repy of osteoporosis should be conducted with 8-10 mg bionvailoble fluoride daily for 2-4 years. In order to assess the doses of the proprietary and nonproprietary fluoride preparations ttctually used. it is mandatory to know their pharnutcokinetic pattern. their bioovailsbility and the effects of meals tmli of calcium salts on their bioovailability. The dosage schedules must be ndjusted taking into xcount the biottvnilability of fluoride from the preparations, rather than the nominal content of fluoride.
278 BONE
277 ml-1 firr~~~.~snort 111 oor31c11trc ““I) snyc b Y,L#l.Vl-Ll”n” ” I”I.l I b.b..h.m”
I f-jrrs AT TL;IE yymm CP!NF urn_,. . “. .*._ _b.“U ,.
AND FEMORAL NECK IN QIOPATHIC GSTECPOROSIS. N. H. Bell, R& Morwessel, 1. A. Colletti. R Eastell. Ft. G. G. Russell. J. Sharv flntr. bv L. L. m. VA Med. Center ani Med. Univ. S.C., Cnarleston, SC, USA; and Univ. Sheffield Med. School, Sheffield, England Prostaglandin 4 (PG&) is produced by osteoblasts and may mediate ongoing bone resorption. Urinary calcium (Ca) is increased by PGE, and decreased by inhibition of PG synthesis. Studies were conducted to determine a) the effects of the nonsteroidal antiinflammatory drug diclofenac sodium on bone and mineral metabolism and b) whether the drug prevents bone loss in idiopathic osteoporosis. 10 normal premenopausal women, 7 normal men and 3 patients with idiopathic osteoporosis were studied. The patients had normal pituitary, thyroid, adrenal and gonadal function and no apparent cause for osteoporosis. All were hospitalized on a metabolic ward for two and a half days and were given a constant daiiy intake of Ca and phosphate before and again afler treatment with dictofenac sodium, 50 mg p.o.t.i.d. for 4 wk. Daily fasting Mood samples and two 24.hr urine samples were obtained. In the short-term studies, diclofenac sodium lowered urinary Ca from 170 f 12 to 130 f 14 mglday (k SEM, P ~0.001) in the normals and from 197 f 42 to 152 i 44 mglday (P
279
LOSSIN THE UPPER FEMUR AFTER lMMOBlLlZATION FOLLOWING UNSTABLE FRACTURES OF THE LOWER LEG. partments
of
Endocrinology,Surgery and Nuclear Medlclne, Free Unlverslty Hospltal Amsterdam, The Netherlands. Prolonged dlause followlng fracture results In bone loss, which may predispose to new fractures. We have evaluated the bone loss in 15 patients (aged 60r7.5 (SD) years, 7 men, 8 postmenopausalwomen), all suffering from a fracture of the lower leg. All fracture were unstable, necessitating l~ob~liaatlon andunloadingof the leg for 7.711.7 weeks. Bone mlneral danslty (BMDI was measured by dual X-ray absorptiometry (DXA) of the lumbar spine and both hips (femoral neck and trochanteric region). BMD was measured immediately after the fracture, after the lmmoblllzatlon period and at 6 months after the fracture. During Immobilization BMD of the trochanteric region decreased 8.5%27% (from 0.69r0.16 g/cm ’ to 0.6360.18g/cml at the side of the fracture, compared to 0.13%~7.2% at the other slde (P~O.003). After slx months the decrease was 15.6%*10% (0.57t0.16 g/cm’) at the slde of the fracture vs 2%*7.!l% In the non-fractured leg (P*O.Oll. The BMD of the femoral neck in the fractured leg decreased 7.1%*5.6% (from 0.74tO.16 g/cm’ to 0.66tO.17 glcm’l after 6 months, compared to 1.6%15.4% in the nonfractured leg (P*O.OOSl. The lumbar spine did not show significant changes during 6 months after the fracture. We conclude that immobilization and unloading of a fractured leg leads to significant bone loss In the corresponding hip, a Process that contimls for six months after the fracture. It is uncertain whether remobilization will lead to complete restoration of bone mass.
DETERMINANTSOF BONE MINERAL DENStl’Y IN HEALTHY ELDERLY WOMEN. P. Lbs. M.E. Ooms. A. van Linaen. H.A. Valkenburq. Department of Endocrinoloav, Free Universitv Hosoital and EMGOInstitute, Free University, Am&dam, The Netherlands. Bone mineral density (BMO) and risk factors for osteoporosis were assessed In 349 women over 70 years of age (mean 2 SD 82.3 ~5.6 years), participating in a trial to investigate the effect of vimmin D supplementation on the Incidence of hip fractures. BMD was measured at both hips and the distal radius, Data were colfected on he@:, body weight, menopause, mobility (5 points SCale), d,atary ccicium intake and medlcatlon. Unear multiple regresston and .‘.iNOVA were used for statistical analysis. The best determlnants of BMD accordi;lg to stepwlse multiple regression were body weight and years since menooause (multiole F12 between 0.07 and 0.20, p~O.001). -A slgnificanuy lower BMd at the hip was observed In panicipants with fmpalred mc i-ility (-5%). users of IOOP diuretics (-5%) and users of corticosterolds ( ‘:-6< tb -17.1%). Users & thiazides dkl not have a higher BMD. Ceil;cum intake horn d&lproducts ranged from 90 to 2911 mglday (mean 921 mg(.tay). Calcium intake did not influence BMD at any site. Paniiipants with a history of Cokes’ fracture had a significantly lower Bl.9R li the other radius (-11.6%). We conclude :nat low EMD cannot be adequately be predicted. Risk factors for low BMD in the elderly are low body weight, high number of years since menopause, impaired mobility and use of loop diuretics and corticosteroids. Low calcium intake was not a risk factor In this study.
144