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Calcium supplement and longevity in rats
268 ICTNC CA?.rFaFhrr TRY”ATk!ENT 1._,-...AVD INTERRUPTED mIDR()NATE (EHDP) FOR POSTMENOPAUSAL AND SENILE CJSTEOPOROSIS K.yoh, H.Tsuii. K.Nakano. N.Satoh, SI.Tateishi. S.Maruo of Orthopaedics , Hyoqo CdeEe of Medicine , Department Nishinomiya. Japan. The treatment effects and administration methods of etidronate (EHDP), for cases of postmenopausal and senile osteoporosis are still controversial. We conducted a prospective clinical study on treatment effects of etidronate with interrupted and coherent administration (ADFR). for 1 to 2 years. Here. the study is reported. SmmS AND METHODS: The subjects were 36 Japanese females who were clinically diagnosed as postmenoPausal and Senile osteoporosis (mean age, 69.4 2 6.8 years : mean body weight, 48.7 C 8.8 kg ; iman height, 147.3 + 5.8 cm). The patients were randomb divided into 3 groups. Group I (II patients) orally received active vitamirl D (1 (I (OH)D3) 2 fig as activator for 1 week, then Orally received etidronate ZOOme for 2 weeks, after which the administration was stopped for 10 weeks. Croup II (10 patients) orally received active vitamin D (1 CI (OH)D3) 2 clg as activator for I week, then orally received etidronate ZOOmsfor 2 weeks, and followed by no drug administration for 9 weeks. Croup m (12 patients) was control. i)ne course in each greup consisted of 12 weeks, and was repealed. Bona mineral density (SPA method), blood biochemistrv, radiography and examinations of clinical symptoms were conduclcd every 12 weeks. RESULTS: In the evaluation for variation of bone mineral density by the SPA method, group I showed increases by 11.1% after 4 courses and by 10.5% after 8 courses, and group II showed increases by 5.8% after 4 courses and by 4.1 % after 8 courses. In group Ill, the results were - 0.3 % after 4 courses and - 2.1% after 8 courses, and a significant difference was seen in the 4th course. No great variation was found in blood biochemical examinations. DISCUSSION: From the fact that groups I and Il showed a significantly higher increase of bone mineral density than that of the control group, etidronate was judged to be effective for the treatment of osteoporosis.
269
270 RESPONSEOF 7’fiE BONE OF ?HE OVARIECTOMIZED RATTO SALlION
371 REDUCED MECHANICAL COMPETENCE IN BONEBY OVARIECTOMY AND
W”..Y.\L.I
CALCITONIN.
Shih.
Institutx
of Biology and Anatomy, National
Defense China kledical
ma1 Centor, Taipei, School of Dentistry, College, Talchung, Republic of Chine. In overiectomlzed rat, a desraaae of bone mass end an ineraase of indices of bone resorption in both long bone and mandible were observed. Calcitonin (CT) is able to induce a sign!ficent diminution of bone turnover rate in
p8tients with osteoporosis. Moreover, CT is capable to bind to high effinity receptors in osteoclast, with pronounced inhibition oP activity. The purpose of this study was to BSS~SS the effects of &man celcftonin (sCT) r.! bone of the ovariaetomired rat. ‘lkcnty one female Sprague-Dawley rats, nighing were received
210 8, were divided
into
three groups.
They
sham operation (Sham), bilateral ovariectomy (OVX), or subeuraneous injection of 1.0 IU sCT per kg per day for 28 consecutive days postovariectomy (OVXtscT). respectively. Ihe proximal tibiae and the tibia1 shafts proximal to the tibiofibular junction were processed for histomorphomctris study. The trabecular bone mass of the ProximaP tibia1 metaphysis in OVXtsCTgroup was greater than OVXSroup but lesser than Sham group. The indices of trabecular
bone formation
were not statistically
signifi-
Cant among those three groups. The indices
of trabecular bone resorption of the OVX+sCTgroup were lesser than OVX group but greater than Sham group. The thickness and percent cartilage matrix OF the epiphyseal growth plate and the pcriosteal and endosteal apposition rates of the tibia1 shaft were increased dramatically in OVXtsCTand QVXgroups when compared to the Shamgraup, but no significant difference betweenOVXtsCTand OVXgroups. HOWever, cortical area was not significantly altered among those
three
groups.
Eased
cating that sCT could
above results, indi1) inhibition of bone ra-
upon the
cause:
CAI,CIUM SUPPLHMIWL 1c,r;yj i_Lg,_UYrt&i.i. i ,
.
=rPtiQn, 2) a decrease in bone turnover rate and an increase in the amount of trabecular bone, 3) partial recovery from bone loss induced by OVX.and 4) no prominent effects in cortical area of the tibia1 shaft.
AXl)
LOXGBV1I’Y
IN
XA’I‘S.
It. K i t;!?!a_wa, [VI.Fukase, K_._@idL S. Motsudn. National Sanatorium Hyogo Chuo klospital,Third Div. Dept. of Med. Kobn Univ. Sch. of Med. and Shionqqi Aburahi Laboratories Hyogo and Shiga. Japan In order to test. tho efEecL of Ca supplement on li fc span and various age-associated changes, 100 mole Wistar rats wcr’c divided illto 4 group on weaning and given 1)Dasic diet containing 1% Ca, 2) Basic diet plus 1% Ca as CaCO, giving a
total of 2%. 3) Basic CaCO J and 0.5% Ca as
diet plus 0.5% Ca as oyster shell electrolysate
giving a total of 2% and 4) Basic diet plus 1% Ca as oyster shell elcctrolysate giving a total of 2%. Animals survived the longest in 41, order. followed by 3), 2) and 1) in decreasing In high Ca diet fed animal (2.3 and 4). blood hemog1ob i n concontra t ion and RBC were hi ghcr olld WBC and platelet. count lower than in normal Ca fed ones, suggesting a protection from anemia infec..ion raising WOC and blood loss increasing platelet count.Bone dc:;lsity was higher on Ca supplemen. It also maintained serum total protein , al bumin arId A/G ratio hlghcr. cholestcrol and triglyseride lower and GOT,GPT, urea, and creatinine closer to the normal range . Bone mineral density was a Iso highor in Cusupplcmcnted group, especial ly thasa given oyster shcl 1 electrolysate. Ca supplement thus appears to protect animals from age-associated progress of anemia, hypoprotei nemia. infect ion, hyperlipidemia and deterioration of renal and in audition to providing hepatic function, higher bone density. Oyster she1 1 electrolysatc seems to bc more effective than C&O 3 probably on account of a better intest ina 1 ahsnrpt,ion. Calcium supplement probably delayed the age-
bound secondary hyperparathyroidism and Ca shift from bone to soft tissue and intracellular space.
ITS PRESERVATION BY 24R,25(OH) D TREATMENT IN BEAGLES. T. Nakamura. T. Yoshiwara, M. %a$aura, K. Tsurukami and H. Orimo. Dzparment of Orthopedics, University of Occupational and Environmentzal Health, Kitakyushu, Japan. In order :a determine the changes of mechanical competence of bone by estrogen deprivation and to know the effect of 24R,25(OH)2D3 treatment, we conducted the mechanical test of bone from beagles 31 months after ovariectomy. Begles 9 to 10 kg were ovariectomized (n=ll) or shamoperated (n=3, Croup G-l). Ovarfectomized (OVX) dogs were divided into 3 groups, C-2 (n=3) received only the vehicle, G3 (n=4) and G-4 (n-4) were given the agent at doses of 2 mcglkg and 10 m&kg daily respectively. The 3rd (L3) and 4th (Lb) lumbar vertebrae were taken from each animal, and the vertebral bodies were cut up with a band saw, parralel to the end-plates to obtain rhe horizontal segments from the mid portion of the :jody. The shell of the L3 specimen was removed by using thn: saw to obtain the cancellous core. The LC specimen was left intact. Contact radiographs of AP and crania-caudal (C-1) directions were taken on each specimen after the bone miner&t determination by SPA. A compression test to Eaiiure by C-C direction was performed and the load-deformatio: curve was obtained. Structural stiffness and ultimate strength were normalized for volume and Younc’s module was calculated. Mechanical uarameters thus obtained on the L3 specimen were presenteh in Table, Group Mineral densitv Strength Stiffness Youne’s module _ (N/cmy) (N/mmocm3) (xii N/mm2) Wcm3) Gl(sham) 0.214(0.035) 1.96(0.97) 2.59(0.65) 3.46(0.18) G-2(OVX) 0.152(0.035)* 1.06(0.66)*1.35~0.21j*1,04~0.52j** G-3(low) 0.201(0.010) 1.71(0.55) 4.01(1.37) 3.57(1.24) c-4(high) 0.200(0.023) 1.74(0.41) 3.26(1.03) 2.37(0.49) * p less than 0.05, ** p less than O.Ol(Wilcoxon’s U-test) These data clearly demonstrate that Young’s module reduces most markedly in the mecanical parameters of cancellous bone in ovariectomized beagle- J, and 24R,25(OH)2D3 prevents not only the loss of bone mass but also the reduction of mechanical competence of bone when used in estrogen deficient animals.
142
269
270 RESPONSEOF 7’fiE BONE OF ?HE OVARIECTOMIZED RATTO SALlION
371 REDUCED MECHANICAL COMPETENCE IN BONEBY OVARIECTOMY AND
W”..Y.\L.I
CALCITONIN.
Shih.
Institutx
of Biology and Anatomy, National
Defense China kledical
ma1 Centor, Taipei, School of Dentistry, College, Talchung, Republic of Chine. In overiectomlzed rat, a desraaae of bone mass end an ineraase of indices of bone resorption in both long bone and mandible were observed. Calcitonin (CT) is able to induce a sign!ficent diminution of bone turnover rate in
p8tients with osteoporosis. Moreover, CT is capable to bind to high effinity receptors in osteoclast, with pronounced inhibition oP activity. The purpose of this study was to BSS~SS the effects of &man celcftonin (sCT) r.! bone of the ovariaetomired rat. ‘lkcnty one female Sprague-Dawley rats, nighing were received
210 8, were divided
into
three groups.
They
sham operation (Sham), bilateral ovariectomy (OVX), or subeuraneous injection of 1.0 IU sCT per kg per day for 28 consecutive days postovariectomy (OVXtscT). respectively. Ihe proximal tibiae and the tibia1 shafts proximal to the tibiofibular junction were processed for histomorphomctris study. The trabecular bone mass of the ProximaP tibia1 metaphysis in OVXtsCTgroup was greater than OVXSroup but lesser than Sham group. The indices of trabecular
bone formation
were not statistically
signifi-
Cant among those three groups. The indices
of trabecular bone resorption of the OVX+sCTgroup were lesser than OVX group but greater than Sham group. The thickness and percent cartilage matrix OF the epiphyseal growth plate and the pcriosteal and endosteal apposition rates of the tibia1 shaft were increased dramatically in OVXtsCTand QVXgroups when compared to the Shamgraup, but no significant difference betweenOVXtsCTand OVXgroups. HOWever, cortical area was not significantly altered among those
three
groups.
Eased
cating that sCT could
above results, indi1) inhibition of bone ra-
upon the
cause:
CAI,CIUM SUPPLHMIWL 1c,r;yj i_Lg,_UYrt&i.i. i ,
.
=rPtiQn, 2) a decrease in bone turnover rate and an increase in the amount of trabecular bone, 3) partial recovery from bone loss induced by OVX.and 4) no prominent effects in cortical area of the tibia1 shaft.
AXl)
LOXGBV1I’Y
IN
XA’I‘S.
It. K i t;!?!a_wa, [VI.Fukase, K_._@idL S. Motsudn. National Sanatorium Hyogo Chuo klospital,Third Div. Dept. of Med. Kobn Univ. Sch. of Med. and Shionqqi Aburahi Laboratories Hyogo and Shiga. Japan In order to test. tho efEecL of Ca supplement on li fc span and various age-associated changes, 100 mole Wistar rats wcr’c divided illto 4 group on weaning and given 1)Dasic diet containing 1% Ca, 2) Basic diet plus 1% Ca as CaCO, giving a
total of 2%. 3) Basic CaCO J and 0.5% Ca as
diet plus 0.5% Ca as oyster shell electrolysate
giving a total of 2% and 4) Basic diet plus 1% Ca as oyster shell elcctrolysate giving a total of 2%. Animals survived the longest in 41, order. followed by 3), 2) and 1) in decreasing In high Ca diet fed animal (2.3 and 4). blood hemog1ob i n concontra t ion and RBC were hi ghcr olld WBC and platelet. count lower than in normal Ca fed ones, suggesting a protection from anemia infec..ion raising WOC and blood loss increasing platelet count.Bone dc:;lsity was higher on Ca supplemen. It also maintained serum total protein , al bumin arId A/G ratio hlghcr. cholestcrol and triglyseride lower and GOT,GPT, urea, and creatinine closer to the normal range . Bone mineral density was a Iso highor in Cusupplcmcnted group, especial ly thasa given oyster shcl 1 electrolysate. Ca supplement thus appears to protect animals from age-associated progress of anemia, hypoprotei nemia. infect ion, hyperlipidemia and deterioration of renal and in audition to providing hepatic function, higher bone density. Oyster she1 1 electrolysatc seems to bc more effective than C&O 3 probably on account of a better intest ina 1 ahsnrpt,ion. Calcium supplement probably delayed the age-
bound secondary hyperparathyroidism and Ca shift from bone to soft tissue and intracellular space.
ITS PRESERVATION BY 24R,25(OH) D TREATMENT IN BEAGLES. T. Nakamura. T. Yoshiwara, M. %a$aura, K. Tsurukami and H. Orimo. Dzparment of Orthopedics, University of Occupational and Environmentzal Health, Kitakyushu, Japan. In order :a determine the changes of mechanical competence of bone by estrogen deprivation and to know the effect of 24R,25(OH)2D3 treatment, we conducted the mechanical test of bone from beagles 31 months after ovariectomy. Begles 9 to 10 kg were ovariectomized (n=ll) or shamoperated (n=3, Croup G-l). Ovarfectomized (OVX) dogs were divided into 3 groups, C-2 (n=3) received only the vehicle, G3 (n=4) and G-4 (n-4) were given the agent at doses of 2 mcglkg and 10 m&kg daily respectively. The 3rd (L3) and 4th (Lb) lumbar vertebrae were taken from each animal, and the vertebral bodies were cut up with a band saw, parralel to the end-plates to obtain rhe horizontal segments from the mid portion of the :jody. The shell of the L3 specimen was removed by using thn: saw to obtain the cancellous core. The LC specimen was left intact. Contact radiographs of AP and crania-caudal (C-1) directions were taken on each specimen after the bone miner&t determination by SPA. A compression test to Eaiiure by C-C direction was performed and the load-deformatio: curve was obtained. Structural stiffness and ultimate strength were normalized for volume and Younc’s module was calculated. Mechanical uarameters thus obtained on the L3 specimen were presenteh in Table, Group Mineral densitv Strength Stiffness Youne’s module _ (N/cmy) (N/mmocm3) (xii N/mm2) Wcm3) Gl(sham) 0.214(0.035) 1.96(0.97) 2.59(0.65) 3.46(0.18) G-2(OVX) 0.152(0.035)* 1.06(0.66)*1.35~0.21j*1,04~0.52j** G-3(low) 0.201(0.010) 1.71(0.55) 4.01(1.37) 3.57(1.24) c-4(high) 0.200(0.023) 1.74(0.41) 3.26(1.03) 2.37(0.49) * p less than 0.05, ** p less than O.Ol(Wilcoxon’s U-test) These data clearly demonstrate that Young’s module reduces most markedly in the mecanical parameters of cancellous bone in ovariectomized beagle- J, and 24R,25(OH)2D3 prevents not only the loss of bone mass but also the reduction of mechanical competence of bone when used in estrogen deficient animals.
142