- Email: [email protected]
Ewe, an animal model for corticosteroid-induced osteoporosis
134s
Abstracts The 7th International
Congress
Bone Vol. 19, No. 3, Supplement September 1996:129SSl69S
of Bone Morphometry
19
21
THE COMBINED USE OF ULTRASOUND AND DENSITOMETRY IN THE PREDICTION OF VERTEBRAL FRACTURE RISK C. Cenollaro, S. Gonnelli, D. Borracelli, S. Martini, C. Pondrelli, R. Monaco, C. Gennari. Institute of Internal Medicine, University of Siena (Italy)
GASTRECTGMY-EVOKED BONE LOSS REFLECTS IMPAIRED FORMATION AND ACCELERATED RESORPTION OF BONE. D. Chen’, R.C. Mtihlbaue?, J-S. Wang3, R.K. Schenk*, D. LehtoAxtelius’,4, P. Aspenberg3, R. Hakanson’ Departments of ‘Pharmacology, ‘Orthopedics, and 4Periodontology, Univeristy of Lund, Lund (Sweden); *Department of Pathophysiology, University of Berne, Berne (Switzerland)
Measurement of ultrasonographic parameters provides information concerning bone status, because it seems to express not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density for evaluating the probability of vertebral fracture. We studied 397 postmenopausal women (58.126.0 years) with (n=178) or without (n=219) atraumatic vertebral fracture. In all women we evaluated bone mineral density (BMD) at lumbar spine by DXA and speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness in the OS calcis by Achilles (Lunar Corp). Ultrasonographic parameters and BMD were compared by examining the magnitude of the odds ratios, to determine which produces the highest estimate of the probability of odds of fracture, and by examining widths of the respective confidence intervals (Cl) to show which estimate of odd ratio is the most precise. The relative risk of vertebral fracture after adjusting for potential confounders, was 3.5 (Cl 2.6-4.8) for BUA, 4.5 (Cl 3-2-6.2) for SOS, 5.8 (CI 4.0-8.4) for Stiffness and 7.5 (CI 4.8-11.5) for BMD. Ultrasound parameters were still significant independent predictors of vertebral fracture even after adjusting for BMD. The relative risk of fracture for a simultaneous decrease by 1 SD of BMD and by 1 SD of each of ultrasound parameters was 17.3 (CI 9.4-39.6) for BMD and SOS, 18.3 (CI 8.4-30.6) for BMD and BUA and 22.1 (CI 8.9-52.7) for BMD and Stiffness. Our data suggest that US and BMD appear to provide complementary information which can be combined to improve estimates of vertebral fracture risk.
Background: Gastrectomy causes bone loss in rat, dog and man. The present study examines the effects of gastrectomy on intact and implanted bone in mice and rats. Merhods: Mice and rats were subjected to gastrectomy or sham-operation. Rats received implants of demineralized femur diaphyses from donor rats in abdominal muscle pouches 1 week after the operations. All animals were killed after 4 weeks. Circulating concentrations of Ca*+, gastrin, parathyroid hormone (PTH) and calcitonin were measured. Femur, calvaria (mice) and sternum, tibia and bone implants (rats) were weighed and cremated. The ash weight was expressed in absolute terms and in relation to body weight and bone wet weight. The per cent bone tissue in the calvaria. the total bone area, the cortical and trabecular mineral densities, medullary cavity area, periosteal circumference and mean periosteal apposition at the metaphysis and the diaphysis of the tibia and the number of cartilage cells and the area of calcified bone in the implants were determined. Results: The serum gastrin concentration was reduced after gastrectomy and elevated in response to omeprazole; circulating concentrations of Ca*+, PTH and calcitonin were unaffected. Gastrectomy lowered the ash weight of the femur and the per cent bone tissue in the cabaria in mice and the ash weights of the sternum, tibia and bone implant in rats. The total bone area, the mean periosteal apposition and periosteal circumference of the tibia were decreased but the tibia1 medullary cavity area was increaped by gastrectomy. The number of cartilage cells and the area of calcified bone in the implants were reduced by gastrectomy. Conclusions: Gastrectomy caused bone loss in mice as well as rats. The bone loss reflects impaired formation and accelerated resorption of bone.
20
22
EWE, AN ANIMAL MODEL FOR CORTICOSTEROID-INDUCED OSTEOPOROSIS. P. Chavassieux, A. Buffet, P.J. Meunies. INSERM Unit& 403, Faculte Alexis Carrel, Lyon (France).
PARATHYROID HORMONE AUGMENTS THE OSTEOCYTIC RESPONSE TO MECHANICAL STIMULATION, AND POTENTIATES MECHANICALLY-INDUCED BONE FORMATION. J.W.M., S.W. Fox, C.J. Jagger, T.J. Chambers, Department of Histopathology, St George’s Hospital Medical School, London (UK)
We have previously reported that a high dose (30 mg/day) of methyl-prednisone (MP) induced in ewes a depression of bone formation, a decrease in the osteoblastic appositional rate but no effect on bone resorption parametersl. The aim of the present study was to analyze the effects of a twice lower dose of MP (16 "q/day) on bone structure and remodeling in ewes. TWO groups of 16 animals were selected (mean age : 9 * 1 yrs; mea" weight : 52 f 7 kg*). One group received a daily intramuscular injection of MP for 3 months and the other one received the vehicle. At the end of the treatment, a significant increase in eroded Perimeter (+ 77%) and a sianificant decrease of the wali width, the osteoblastic perimeter (- 47%) and the mineralizing surfaces (- 63%) were noted. As previously shown at the dose of 30 q/day, dynamic parameters reflecting the bone formation at the tissue and cell levels significantly decreased (p < 0.03) by - 65 and - 80 % for BFR/B.Pm and AjAR respectively. The augmentation of the formation period resulted only from an augmentation of the inactive one which was three fold hither than in the control CXOUD (!a < 0.02). It was associated with a decrease in the activation f;eque"cy (p < 0.02). The onset of the mineralization process was sisnificantlv delaved (D < 0.03) but in contrast to the highest dose; the &i"er&izatio" rate was unchanged. In conclusion, the effects of corticosteroid at a dose close to the therapeutic one aiven in humans (0.25 q/kg/day of MP) are-characterized by a decrease in .bo"e fornwtion and an increase in bone resorption. The mechanism of the latter could ixply a secondary hyperparathyroidism. These modifications are similar to those observed in humans after a long-term corticosteroid treatment. Thus, ewe represents a suitable animal model for the study of corticosteroid-induced osteoporosis. 1. Chavassieux P. et als. Osteoporosis Int 3:97-102, 1993
Bone has a dual role as structural support, and as a store of calcium to assist calcium homeostasis. Thus bone cells are influenced by their mechanical environment, and by fluctuating levels of calcium regulating hormones. Both mechanical stimulation and intermittent administration of parathyroid hormone(PTH) are known to increase cancellous bone formation; and both induce IGF-I and c-fos in bone cells, suggesting a shared signaling system. We tested the effect of PTH on the osteogenic response in a rat-tail model of mechanically-induced osteogenesis. Animals were given very low (Gus/kg) or low (GOug/kg) doses of hPTH i-34, either as a single dose 45 minutes before loading, or as single dose before loading and on two subsequent days, or as 6 daily doses commencing three days after mechanical stimulation. A very brief episode of loading (30 cycles, 1Hz) caused a 3-fold increase in cancellous bone formation rate compared with non-loaded vertebrae. PTH administration using 60pg/kg/day caused an increase in bone formation, regardless of the dosing regime. PTH (60ugg/kg/day) also had an additive effect on the increase in bone formation by mechanical loading when it was commenced before, but not after loading. While 300 cycles of mechanical loading has previously been found to induce substantial c-fos mRNA expression in cortical osteocytes, no osteocytic expression of c-fos mRNA was observed in the vertebrae of animals given PTH alone or subjected to 30 cycles of loading. However, in the presence of PTH, this sub-optimal loading regime resulted in detectable c-fos mRNA expression in osteocytes. Thus, our data suggests that PTH sensitizes bone cells during the early phase of their response to mechanical stimulation.
Abstracts The 7th International
Congress
Bone Vol. 19, No. 3, Supplement September 1996:129SSl69S
of Bone Morphometry
19
21
THE COMBINED USE OF ULTRASOUND AND DENSITOMETRY IN THE PREDICTION OF VERTEBRAL FRACTURE RISK C. Cenollaro, S. Gonnelli, D. Borracelli, S. Martini, C. Pondrelli, R. Monaco, C. Gennari. Institute of Internal Medicine, University of Siena (Italy)
GASTRECTGMY-EVOKED BONE LOSS REFLECTS IMPAIRED FORMATION AND ACCELERATED RESORPTION OF BONE. D. Chen’, R.C. Mtihlbaue?, J-S. Wang3, R.K. Schenk*, D. LehtoAxtelius’,4, P. Aspenberg3, R. Hakanson’ Departments of ‘Pharmacology, ‘Orthopedics, and 4Periodontology, Univeristy of Lund, Lund (Sweden); *Department of Pathophysiology, University of Berne, Berne (Switzerland)
Measurement of ultrasonographic parameters provides information concerning bone status, because it seems to express not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density for evaluating the probability of vertebral fracture. We studied 397 postmenopausal women (58.126.0 years) with (n=178) or without (n=219) atraumatic vertebral fracture. In all women we evaluated bone mineral density (BMD) at lumbar spine by DXA and speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness in the OS calcis by Achilles (Lunar Corp). Ultrasonographic parameters and BMD were compared by examining the magnitude of the odds ratios, to determine which produces the highest estimate of the probability of odds of fracture, and by examining widths of the respective confidence intervals (Cl) to show which estimate of odd ratio is the most precise. The relative risk of vertebral fracture after adjusting for potential confounders, was 3.5 (Cl 2.6-4.8) for BUA, 4.5 (Cl 3-2-6.2) for SOS, 5.8 (CI 4.0-8.4) for Stiffness and 7.5 (CI 4.8-11.5) for BMD. Ultrasound parameters were still significant independent predictors of vertebral fracture even after adjusting for BMD. The relative risk of fracture for a simultaneous decrease by 1 SD of BMD and by 1 SD of each of ultrasound parameters was 17.3 (CI 9.4-39.6) for BMD and SOS, 18.3 (CI 8.4-30.6) for BMD and BUA and 22.1 (CI 8.9-52.7) for BMD and Stiffness. Our data suggest that US and BMD appear to provide complementary information which can be combined to improve estimates of vertebral fracture risk.
Background: Gastrectomy causes bone loss in rat, dog and man. The present study examines the effects of gastrectomy on intact and implanted bone in mice and rats. Merhods: Mice and rats were subjected to gastrectomy or sham-operation. Rats received implants of demineralized femur diaphyses from donor rats in abdominal muscle pouches 1 week after the operations. All animals were killed after 4 weeks. Circulating concentrations of Ca*+, gastrin, parathyroid hormone (PTH) and calcitonin were measured. Femur, calvaria (mice) and sternum, tibia and bone implants (rats) were weighed and cremated. The ash weight was expressed in absolute terms and in relation to body weight and bone wet weight. The per cent bone tissue in the calvaria. the total bone area, the cortical and trabecular mineral densities, medullary cavity area, periosteal circumference and mean periosteal apposition at the metaphysis and the diaphysis of the tibia and the number of cartilage cells and the area of calcified bone in the implants were determined. Results: The serum gastrin concentration was reduced after gastrectomy and elevated in response to omeprazole; circulating concentrations of Ca*+, PTH and calcitonin were unaffected. Gastrectomy lowered the ash weight of the femur and the per cent bone tissue in the cabaria in mice and the ash weights of the sternum, tibia and bone implant in rats. The total bone area, the mean periosteal apposition and periosteal circumference of the tibia were decreased but the tibia1 medullary cavity area was increaped by gastrectomy. The number of cartilage cells and the area of calcified bone in the implants were reduced by gastrectomy. Conclusions: Gastrectomy caused bone loss in mice as well as rats. The bone loss reflects impaired formation and accelerated resorption of bone.
20
22
EWE, AN ANIMAL MODEL FOR CORTICOSTEROID-INDUCED OSTEOPOROSIS. P. Chavassieux, A. Buffet, P.J. Meunies. INSERM Unit& 403, Faculte Alexis Carrel, Lyon (France).
PARATHYROID HORMONE AUGMENTS THE OSTEOCYTIC RESPONSE TO MECHANICAL STIMULATION, AND POTENTIATES MECHANICALLY-INDUCED BONE FORMATION. J.W.M., S.W. Fox, C.J. Jagger, T.J. Chambers, Department of Histopathology, St George’s Hospital Medical School, London (UK)
We have previously reported that a high dose (30 mg/day) of methyl-prednisone (MP) induced in ewes a depression of bone formation, a decrease in the osteoblastic appositional rate but no effect on bone resorption parametersl. The aim of the present study was to analyze the effects of a twice lower dose of MP (16 "q/day) on bone structure and remodeling in ewes. TWO groups of 16 animals were selected (mean age : 9 * 1 yrs; mea" weight : 52 f 7 kg*). One group received a daily intramuscular injection of MP for 3 months and the other one received the vehicle. At the end of the treatment, a significant increase in eroded Perimeter (+ 77%) and a sianificant decrease of the wali width, the osteoblastic perimeter (- 47%) and the mineralizing surfaces (- 63%) were noted. As previously shown at the dose of 30 q/day, dynamic parameters reflecting the bone formation at the tissue and cell levels significantly decreased (p < 0.03) by - 65 and - 80 % for BFR/B.Pm and AjAR respectively. The augmentation of the formation period resulted only from an augmentation of the inactive one which was three fold hither than in the control CXOUD (!a < 0.02). It was associated with a decrease in the activation f;eque"cy (p < 0.02). The onset of the mineralization process was sisnificantlv delaved (D < 0.03) but in contrast to the highest dose; the &i"er&izatio" rate was unchanged. In conclusion, the effects of corticosteroid at a dose close to the therapeutic one aiven in humans (0.25 q/kg/day of MP) are-characterized by a decrease in .bo"e fornwtion and an increase in bone resorption. The mechanism of the latter could ixply a secondary hyperparathyroidism. These modifications are similar to those observed in humans after a long-term corticosteroid treatment. Thus, ewe represents a suitable animal model for the study of corticosteroid-induced osteoporosis. 1. Chavassieux P. et als. Osteoporosis Int 3:97-102, 1993
Bone has a dual role as structural support, and as a store of calcium to assist calcium homeostasis. Thus bone cells are influenced by their mechanical environment, and by fluctuating levels of calcium regulating hormones. Both mechanical stimulation and intermittent administration of parathyroid hormone(PTH) are known to increase cancellous bone formation; and both induce IGF-I and c-fos in bone cells, suggesting a shared signaling system. We tested the effect of PTH on the osteogenic response in a rat-tail model of mechanically-induced osteogenesis. Animals were given very low (Gus/kg) or low (GOug/kg) doses of hPTH i-34, either as a single dose 45 minutes before loading, or as single dose before loading and on two subsequent days, or as 6 daily doses commencing three days after mechanical stimulation. A very brief episode of loading (30 cycles, 1Hz) caused a 3-fold increase in cancellous bone formation rate compared with non-loaded vertebrae. PTH administration using 60pg/kg/day caused an increase in bone formation, regardless of the dosing regime. PTH (60ugg/kg/day) also had an additive effect on the increase in bone formation by mechanical loading when it was commenced before, but not after loading. While 300 cycles of mechanical loading has previously been found to induce substantial c-fos mRNA expression in cortical osteocytes, no osteocytic expression of c-fos mRNA was observed in the vertebrae of animals given PTH alone or subjected to 30 cycles of loading. However, in the presence of PTH, this sub-optimal loading regime resulted in detectable c-fos mRNA expression in osteocytes. Thus, our data suggests that PTH sensitizes bone cells during the early phase of their response to mechanical stimulation.