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Family history of hip fracture or spinal deformity as a predictor of bone density
296 EFFECTS OF OSTEOPENIA.
PAHDRONATE
IN
297 112911, A NEW
HIGH-TURNOVER
B.L.Lanadahl. L.S.Mortensen, F.F.Eriksen. P.Charles Aarhus SoneandNineral h’esearch L+-row. Vniversily Amtssygehus, OK-SD00
Department of Endocrinolcgy, Aarhus C, Denmark.
AGENT
CONTAINING STRONTIUM
IN OVARIECTOiWZED RA
Aarhus
Pamidronate is a potent inhibitor of bone resorption. Three patients with high-turnover osteoDenia was treated with Damidronate. The three patients (1 fehale(33 years), 2 males(24,49 Years)) had low BMD (QDR): below 3.4 sb far agep iiigh excretion in u-rine of liydroxyproline and calcium. One patient had elevated alkaline phosphatase in serum. All had normal values of thyroid hormones, PTH and sex hormones in serum. No history of previous medical treatment. Bone biopsies showed osteopenia, no sign of osteomalacia. Pamidronate was administrated as 0.5 mg/kg bodyweight i.v. infusion (4-6 h), followed by 300 mg p.o. per day for 112 days. Side effects: Nausea, upper abdominal pain, headaehe and fatigue during the first week of treatment. One patient had intermittent bone Dain durina the treatment. kesults: A-decrease in calcium excretion: 0.23 vs. 0.36 mmol/umol creatinine/day (38 %),max. effect after El days. A decrease in hydroxyproline excretion: 11.74 vs. 20.35 umol/u&ol creatinine/day (42 %) max effect after 112 days. An 4.3 % increase in BMD (QDR) of the lumbal spine and an 0.9 % increase in BMD (QDR) of the femoral neck. These preliminary results suggest, that highturnover osteopenia could be treated succesfully with pamidronate in a combination of i.v.infusion (0.5 mg/kg) followed by oral administrationfor 3 months (300 mg/day)
previous studies from our 1aboraLory hawe shown that stronlium adminlstration can induce stimulation of bone formation en&or decrease bone resorptfon in rats ad doe. A new egent euntainingstrontium (S 12911)has been developed end Its effects on bone have been tested In estrogen deflcientosteopenie female rats. 3 .months old female rats (15-25 pep group)were either sham-apecrated (sham) or owrieetomined end immediately treated for 2 months with l?g estradioi (OVX+E2) with 512911 at 3 different dosages (77,154 or 308 m&e) OPthe vehicle (OVX).The skeletal effects of 512911 weee evaluated by the changes in dry bone weight aod bone caicium content and by hiatomorphometricanalysis of tibial metephysis. Treatment of OVX rats with 512911 increased dose-dependently the bone mineral content wh?ebwas corrected aE the higher dcae. The trabecular bone volume in tibia was reduced by 46 %in OVXrats and was increased by 35 % (p~O.05~in OVX t 912911 (aham : 34.2&O.?% - sem- ; OVX : 12.4f0.796 ; OVXtS122P1 : 25.ljJ.l%). 812911 thus partially prevented the trabecular bone loss induced by E deficiency. 112911 decreased markediy the OVX-induced exeesaiwe eroded perimeter (-24%, p*O.O5) and osteociast ich were reduced to the normal values in sham rata t, biochemical indices (plasma alkaline phospbntase and osteoeaicin9 as well as stntic and dynamic indices of Pormationremained as eieveted as in OVX rats. There w toxic effect or mineraiizatioo defectobeerwed at my doss. ThesereauiPsahow that S 12911 is a new non toxic rpnt which IncreMesbone m by indudng a positive tal formation and resorption in oestrogen defioient ooteopenic rats through an anti-resorptive eflect combined with a maintained bone formetionon. 512911 may therefore be of potential interest In the treatment and preventionof osteop.xosis.
298
299 FAMILYHISTORYOF HIPFRACTUREOR SPlNAL DEFzqRETLyAS A PREDICTOR OF BONEDENSITY. PL Ratter, S . f er Umversltyof TexasHealthScience Center andAudie
INSUFFICIENCY FRACTURES OF THE PELVIS IN SEVERE OSTEOPOROSIS. F.Kolb,E.Morita,R.Rodvien.California-Pacific and Mount Zion-U.C.Medical Centers, San Francisco,California,LJSA. We are reporting three elderly females with severe osteoporosis who developed sudden excruciating bacl.pain without an obvious history of trauma. X-rays suggested pathologic fractures of the pelvis and the tentative diagnosis was osteoblastic tumor. A fourth patient,a younger male with mild osteopenia,developed a similar picture after strenuous exercise.Biopsy in this and one other patient showed reactive bone formation and bone scan woven bone, but no tumor.Radioisotopic in all patients showed markedly increased uptake in the sacrum extending out the iliac wings in an "H" shape (“HONDA SIGN”) .There were additional areas of increased activity in other bones ds well (femora,vertebrae,and ribs).Computed tomography ruled out a destructive process and soft tissue mdss,as seen in metastatic disease. In contrast to most patients with senile OS-
teoporosis, the serum alkaline phosphdtdse level and the serum osteoca1ci.n(Gla-Protein)levels were significantly elevated in two patients, compatible with a "high bone turnover"stdte. Conservative management with rest,pelvic SUpport,and calcium in all patients, and administration of calcitonin to two patients led to symptomatic improvement. The elevated alkaline phOSphdtdSe and osteocdlcin levels normalized, and serial bone scans showed healing of lesions. Clinicians must become aware of this syndrome which simulates osteobldstic metastdtic bone disease,.in order to avoid unnecessary diagnostic and therapeutic measures.It is probably far more common thdn previously believed.
L. MurphyMemorialVA Hospital, San Antonio. Texas. Twinstudies indicatethat-bonedensity is a heritable trait butno1
ailstudies have found an association between family history 01
fracture and bone density. The purpose of this analysis was fo examine the association between hip fractures and spinal deformity occurring in female family members and bone density of the hip and spine. A population based sample of 334 women ages 35 to79 were auestionedabout hiu fractures in their parents and grandoarents. A $cture of a woman bith thoracic spine kyphosis was shown to study participants who were asked if any female relatives had had similar deformities. Bone densitv of the hiu and lumbar snine were detemiined using a Hologic &al energy ;bsorpiiometer which has an in vivo precision of 3% at the hip cervical regio;l and 1% at the spine. 54 (16%)gave a positive family history @Ix+) of hip fractures and 94 (28%) gave a history of spinal deformity (SD+) in their mother or malemnl grandparent. Age adjusted bone density of the lumbar spine and hip cervical region were not significantly lower in study subjects with female relatives with spine deformity (spine:SD+ .98, SD- .98, p=O.93. cervical region:SD+.7§; SD- .76, p=O.73). With a positive family history of hip fracture, the hip cervical region age adjusted bone
density was significantlylower (Hx+ .72; Hx- .76, p=.O2)although the lumbarspine densitywas not lower (Hx+ .98; Hx- .98, p=.98). Age of the relativeat time of fracture(53-74 vs 75+) and study subject age group (35-49 vs 50+) had no effect on age adjusted bone densities. After adjusting for body mass inrlex (kg/m?) and age of study subjects, bone density of rhe cervical region was still significantly lower among those with a family history of hip fracture (Hx+ .76. i-lx- .73. p=.O5). Bone density of the cervical region of the hip is lower in women with matcrn;~l rchuives with a history of hip fracture although bone density is not reduced in women with a family history of spinal deformity. The effect of family history of *ractere on bonc,densify of Ihe cervical region of the hip was nor due* (0 familial simth!rities in body weight.
149
PAHDRONATE
IN
297 112911, A NEW
HIGH-TURNOVER
B.L.Lanadahl. L.S.Mortensen, F.F.Eriksen. P.Charles Aarhus SoneandNineral h’esearch L+-row. Vniversily Amtssygehus, OK-SD00
Department of Endocrinolcgy, Aarhus C, Denmark.
AGENT
CONTAINING STRONTIUM
IN OVARIECTOiWZED RA
Aarhus
Pamidronate is a potent inhibitor of bone resorption. Three patients with high-turnover osteoDenia was treated with Damidronate. The three patients (1 fehale(33 years), 2 males(24,49 Years)) had low BMD (QDR): below 3.4 sb far agep iiigh excretion in u-rine of liydroxyproline and calcium. One patient had elevated alkaline phosphatase in serum. All had normal values of thyroid hormones, PTH and sex hormones in serum. No history of previous medical treatment. Bone biopsies showed osteopenia, no sign of osteomalacia. Pamidronate was administrated as 0.5 mg/kg bodyweight i.v. infusion (4-6 h), followed by 300 mg p.o. per day for 112 days. Side effects: Nausea, upper abdominal pain, headaehe and fatigue during the first week of treatment. One patient had intermittent bone Dain durina the treatment. kesults: A-decrease in calcium excretion: 0.23 vs. 0.36 mmol/umol creatinine/day (38 %),max. effect after El days. A decrease in hydroxyproline excretion: 11.74 vs. 20.35 umol/u&ol creatinine/day (42 %) max effect after 112 days. An 4.3 % increase in BMD (QDR) of the lumbal spine and an 0.9 % increase in BMD (QDR) of the femoral neck. These preliminary results suggest, that highturnover osteopenia could be treated succesfully with pamidronate in a combination of i.v.infusion (0.5 mg/kg) followed by oral administrationfor 3 months (300 mg/day)
previous studies from our 1aboraLory hawe shown that stronlium adminlstration can induce stimulation of bone formation en&or decrease bone resorptfon in rats ad doe. A new egent euntainingstrontium (S 12911)has been developed end Its effects on bone have been tested In estrogen deflcientosteopenie female rats. 3 .months old female rats (15-25 pep group)were either sham-apecrated (sham) or owrieetomined end immediately treated for 2 months with l?g estradioi (OVX+E2) with 512911 at 3 different dosages (77,154 or 308 m&e) OPthe vehicle (OVX).The skeletal effects of 512911 weee evaluated by the changes in dry bone weight aod bone caicium content and by hiatomorphometricanalysis of tibial metephysis. Treatment of OVX rats with 512911 increased dose-dependently the bone mineral content wh?ebwas corrected aE the higher dcae. The trabecular bone volume in tibia was reduced by 46 %in OVXrats and was increased by 35 % (p~O.05~in OVX t 912911 (aham : 34.2&O.?% - sem- ; OVX : 12.4f0.796 ; OVXtS122P1 : 25.ljJ.l%). 812911 thus partially prevented the trabecular bone loss induced by E deficiency. 112911 decreased markediy the OVX-induced exeesaiwe eroded perimeter (-24%, p*O.O5) and osteociast ich were reduced to the normal values in sham rata t, biochemical indices (plasma alkaline phospbntase and osteoeaicin9 as well as stntic and dynamic indices of Pormationremained as eieveted as in OVX rats. There w toxic effect or mineraiizatioo defectobeerwed at my doss. ThesereauiPsahow that S 12911 is a new non toxic rpnt which IncreMesbone m by indudng a positive tal formation and resorption in oestrogen defioient ooteopenic rats through an anti-resorptive eflect combined with a maintained bone formetionon. 512911 may therefore be of potential interest In the treatment and preventionof osteop.xosis.
298
299 FAMILYHISTORYOF HIPFRACTUREOR SPlNAL DEFzqRETLyAS A PREDICTOR OF BONEDENSITY. PL Ratter, S . f er Umversltyof TexasHealthScience Center andAudie
INSUFFICIENCY FRACTURES OF THE PELVIS IN SEVERE OSTEOPOROSIS. F.Kolb,E.Morita,R.Rodvien.California-Pacific and Mount Zion-U.C.Medical Centers, San Francisco,California,LJSA. We are reporting three elderly females with severe osteoporosis who developed sudden excruciating bacl.pain without an obvious history of trauma. X-rays suggested pathologic fractures of the pelvis and the tentative diagnosis was osteoblastic tumor. A fourth patient,a younger male with mild osteopenia,developed a similar picture after strenuous exercise.Biopsy in this and one other patient showed reactive bone formation and bone scan woven bone, but no tumor.Radioisotopic in all patients showed markedly increased uptake in the sacrum extending out the iliac wings in an "H" shape (“HONDA SIGN”) .There were additional areas of increased activity in other bones ds well (femora,vertebrae,and ribs).Computed tomography ruled out a destructive process and soft tissue mdss,as seen in metastatic disease. In contrast to most patients with senile OS-
teoporosis, the serum alkaline phosphdtdse level and the serum osteoca1ci.n(Gla-Protein)levels were significantly elevated in two patients, compatible with a "high bone turnover"stdte. Conservative management with rest,pelvic SUpport,and calcium in all patients, and administration of calcitonin to two patients led to symptomatic improvement. The elevated alkaline phOSphdtdSe and osteocdlcin levels normalized, and serial bone scans showed healing of lesions. Clinicians must become aware of this syndrome which simulates osteobldstic metastdtic bone disease,.in order to avoid unnecessary diagnostic and therapeutic measures.It is probably far more common thdn previously believed.
L. MurphyMemorialVA Hospital, San Antonio. Texas. Twinstudies indicatethat-bonedensity is a heritable trait butno1
ailstudies have found an association between family history 01
fracture and bone density. The purpose of this analysis was fo examine the association between hip fractures and spinal deformity occurring in female family members and bone density of the hip and spine. A population based sample of 334 women ages 35 to79 were auestionedabout hiu fractures in their parents and grandoarents. A $cture of a woman bith thoracic spine kyphosis was shown to study participants who were asked if any female relatives had had similar deformities. Bone densitv of the hiu and lumbar snine were detemiined using a Hologic &al energy ;bsorpiiometer which has an in vivo precision of 3% at the hip cervical regio;l and 1% at the spine. 54 (16%)gave a positive family history @Ix+) of hip fractures and 94 (28%) gave a history of spinal deformity (SD+) in their mother or malemnl grandparent. Age adjusted bone density of the lumbar spine and hip cervical region were not significantly lower in study subjects with female relatives with spine deformity (spine:SD+ .98, SD- .98, p=O.93. cervical region:SD+.7§; SD- .76, p=O.73). With a positive family history of hip fracture, the hip cervical region age adjusted bone
density was significantlylower (Hx+ .72; Hx- .76, p=.O2)although the lumbarspine densitywas not lower (Hx+ .98; Hx- .98, p=.98). Age of the relativeat time of fracture(53-74 vs 75+) and study subject age group (35-49 vs 50+) had no effect on age adjusted bone densities. After adjusting for body mass inrlex (kg/m?) and age of study subjects, bone density of rhe cervical region was still significantly lower among those with a family history of hip fracture (Hx+ .76. i-lx- .73. p=.O5). Bone density of the cervical region of the hip is lower in women with matcrn;~l rchuives with a history of hip fracture although bone density is not reduced in women with a family history of spinal deformity. The effect of family history of *ractere on bonc,densify of Ihe cervical region of the hip was nor due* (0 familial simth!rities in body weight.
149