576 PROLONGED SURVIVAL OF HYPERCALCEYIC. TUMOR-BEARING NUDE MICE BY DAILY SUBCUTANEOUS INJECTIONS OF lOUSE ANTI-PTURP(l-34) I(QNoCLONAL ANTIBODY. Y. Yamakaaal. K.Sato'. K.Shizume’, R. Nahtomi’. T. Satoh', K. Yukawa’. K. Kasono’. 8. Demuraz. K.Ohsumis 1. Research Institute for Growth Science, Shinjuku -ku. Tokyo, 2. Tokyo lomen’s kledical College. 3. Ilitsubishi- Yuka BCL. Tokyo. Japan.

Previously. we reported that repeated injections of mouse q onoclonal antibody (aUoAb) agaiust human PTHrPII-34) into bypercalcemic, tuaor-bearing nude mice for 5 days decreased serum calcium concentration for a prolonged time. To eluci- date whether daily injections of the antibody could prolong the survival of hypercalcemic. cachexic, tumor-bearing nude mice, mMoAb which neutralizes PTRrPtl-34) in vitro was SC injected daily for more than 4 weeks.

SC injections of the aYoAb decreased serun cnlcium con- centration in all nude sice transplanted with human PTHrP- producing turars (EC-GI. T3Y-1, PC-S). but did not in a nude mouse transplanted with a human parathyroid carcinoma.

lhen tumor(PC-3)-bearing nude mice became hypercalcemic, 8 mice were treated with a daily injection of the mloAb (- 7D pg) for 5 weeks, Control mice received vehicle only (300 111 saline). At one weok, the scrua calcium concentra- tion dscrcused to 11.6 f 1.0 a@d! in the trented mice (n = I)(untreated mice; 16.5 k 1.9 mgidl. n = 12). Body weight increased in control mice. After 3-4 weeks of the injection. the serum calcium concentration was continuously decreased but the body weight decreaed. After 5 weeks. no treated nouse died whereas 4 untreated nice died.

These results suggest that passive immunization of PTBrP continuousty decreased serum calcium concentration and may prolong the survival of tumor-bearing nude nice. Uowever, other undetermined cytokines would be responsible for the cachexia of the tumor-bearing nude mice.

578 PAHIDRONATE TREAWNT OF P*GET*S DISEASE. R.B. Adamwn, 5-J. (iallscher* J. Gv4rs. 8-f. Bovco, s. Ra'slon' FM 1.1. eav'e*. GeDarrmSnts of

Patholaqv and MadlelnS*, G'Saaor Roval Inf'rmarv.

Hluteew$%#@trv of trans'llac bans b'opsles taken ore-tr%StmSnt and e

nwfl ot f weeks aftw treatment Sherrd a $Iqnltlc~nt fall Insan + SO) In 0 Inectlve reoorptlan Surteee (ram 18.4 t 7.5 to 1.9 t 6.0 11~~0.01', C

~cttve rasorotlan surfec~ fra 12.6 t 5.6 to 1.9 t 2.1 tDcO.Ol'. numbers

of ost%xfasts/mm2 from 1.6 t 1.8 to 0.6 f 0.7 (o<O.O5l. and mlssra'

aopas'tlon r.Sta WARI worn I.55 pmdev" * 0.17 to 0.64 t 0.12 f0~0.001)

In qrew I patients. 6GII of DatlentS Showed a COmDIete reS0anss elth

nwma"S‘St'en ot the abcvs 98rQmStarS. \I\ th0 DOt\WBt3 dOV~k.DOd 0

mild Increwe In 8Stsa'd width tram 12.3 f 5.0 to 26.1 t 9.3 pm (0'.005'

end one oatlent dovelaDed frank ostenmalacla. (Inlv 201 of qrouq II

Dat'mntS Show4 ~Inv hlSto1oqleal rePDe.nm yet In all Oat'entS the

resbrot've SUrfaCe. ostwblust numbcrrs and WI remalned elevated. Only

the OSM3fd +'dth valuas chunqed slqnltlcantlv Jncreeslnq fren I:.? f

2.2 to 19.1 ,, 2.6 pm ~O.G.OOO~l.

TheSS f'ndlnqs lndlcate that a short wur%e of 160 nq ~amldrenate

q'ven OWP SIX ldl*kS Is QS rffactlvs, at raduc'nq alkal'ne ~hoSoh.tase

and wlnarv hvdrawwo'lne values ovar o year as a slmllar dose qivsn

throwwut the war but Is more Ilkte'v to be asseelstsd with slqn'tlcent

m'nwal'satlan detects et least In the Short term. Since hlSt~loqlcaI

IndIceS of Wno reswptlon rsma'nad elovatsd In .SII qraub II pa+'snts we

esw'ude th.S* e'thar a h'qhsr doss or mars fr.qwnf admln'S~,ti~ ot

45 mg thBo 0 t'mas vaar'v Is requ'red far atfactlve treatment ot p.Sqe,'S d'Se?isw. me studv a'sa warns aqatnst the sole "SO 0' blocheml~a'

markers as in~'eators et rmSwnSm to Damldranate.

577 URINARY EXCRETION OF C-TERUlNAL FRACBENTS OF PARATBYROID HORYONB-RELATED PROTEIN IN HYPERCALCEYIC PATIENTS : AN INCREASE IN A PATIENT SlITE CHRONIC VITAYIN DZ INTOXICATION. It. Sate’. K. Nohtomiz. Y,Yaaakawa'. K.Shizume2. 6. Imamurag. fl. Demura?. K.0hsumi4 1. Institute of Clinical Endocrinology. Tokyo Vomen’s redical College. Shinjuku-ku. Tokyo. 2. Research Institute for Growth Science. 3. Kagoshima City Bospital. Kagoshima. 4. Mitsubishi-Yuka BCL. Tokyo. Japan.

Urinary excretion of C-terminal fragments of parsthyroid hormone-related protein(UE-C-FTHrP) is increased in patients with malignancy-associated hypercalcemia @AH) (JBLIR.6:77. 1991). !e have improved the sensitivitv of the RIA and studied the UE-C-PTRrP in various disorders. UE-C-PTArP wasexpressed as #g PTBrP(lDS-141)/g creatinine (Cr).

UE-C-PTErP in normal subjects was 0.72 f 0.21 #g/g Cr (n -- 100, normal range 0.40 - 1.34 116/g Cr). In patients with primary hyperparathyroidism (PHP). UE-C-PTRrP was not increased. This was also the case in a patient aitb *non”- familial hypocalciuric hypercalcemia, UE-C-PTRrP was significantly increased in patients with MAH (8.2 - 89.2 ~g/g Cr). Normocalcemic patients with adult T-cell leukeoia (n =6), in whom UE-C-PTHrP was increased. developed hyper- calcemia in a few months.

UE-C-PTRrP was ulso increased in a patient with chronic vitamin Dz intoxication at the admission (4.4 pg/g Cr) but decreased to 0.39 l(g,g Cr 3 months later. In this patient. no malignancy was detected.

These findings suggest that the UE-C-PTUrP is very useful in the differential diagnosis of bypercalcemia. Particularly between PIP and YAB. Rowever, since 1.25-(OR)a-Dt stimulates PTRrP production in cultured human keratinocytes (JCL 87:884. 1991). it should be cautiously evaluated in patients with chronic vitamin D intoxication.

579 DIABETES MELLITUS AND FRACTURE RISK Thomas 14. Welchior & Ole Helmer S0rensen Steno Memorial Hospital and Dept. of Medicine Sundby Hospital, Copenhagen, Denmark. Reduced bone mass in diabetic patients has been demonstrated by various techniques leading to the hypothesis that diabetes is a risk factor for osteoporosis. Whether this has any clinical implication has only been sparsely elucidated in the literature. We evaluated the risk of hip and Colles' frac- tures in a case control study. A questionaire concerning earlier fractures and estrogen sub- stitutional treatment was sent to 838 insulin- treated diabetic females all above the age of 40. Fracture rates in the diabetic females (N=7481 was compared with those in 26.564 females, all above the age of 40,from the general population living in a similar suburban region of Copen- hagen. In diabetic females aged 40-49 Colles' fracture rate was Z/1000 years and hip fracture rate O.43/1000 years. The number of fractures in- creased with age and among BO-89 old diabetic females bath fracture rates were 31/1DOO years. Diabetic females did not have higher fracture rates as compared with the general population. Fracture rate was nog assiciated with the development of diabetic complications, long-term poor metabolic control or age of diagnosis. Our results suggest that diabetic osteopenia doas not have any clinical impact on fracture risk.

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